The Hedgehog (Hh) signaling pathway is a critical transduction system regulating cell proliferation, differentiation, and tissue homeostasis during embryonic development. Its aberrant activation is closely associated with the pathogenesis of malignancies such as basal cell carcinoma and medulloblastoma. Although Smoothened (SMO)-targeting inhibitors have received clinical approval, their therapeutic efficacy is limited by acquired resistance mutation and compensatory pathway activation. Glioma-associated oncogene homolog 1 (GLI1), the terminal effector transcription factor of the Hh pathway, has emerged as a promising therapeutic target due to its tumor-specific overexpression and lower propensity for resistance induction. However, GLI1 is classified as an "undruggable" target due to the absence of well-defined ligand-binding pockets, low inhibitory activity, and poor drug-like properties. Currently, no GLI1 inhibitor has entered clinical trials. This review systematically analyzes multidimensional modulation strategies (e.g., allosteric modulation, protein-protein interaction disruption, targeted protein degradation) for targeting transcription factors, based on the structural and functional features of GLI1-DNA interaction combined with recent advances in structural biology and chemical biology, offering new paradigms to overcome therapeutic barriers against undruggable targets.

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.

AIM: To compare the effectiveness of foldable capsular body(FCB)with traditional scleral buckling(SB)in the treatment of experimental retinal detachment animal models.METHODS: After successfully establishing rhegmatogenous retinal detachment(RRD)animal models, 24 New Zealand white rabbits were randomly divided into three groups(RRD models group, SB group, and FCB group), with 8 rabbits in each group. The FCB and SB groups underwent SB and FCB surgeries for the RRD animal models, while the RRD models group only consists of RRD models without any surgical intervention during the follow-up period. The follow-up duration was 3 mo. Wide-field neonatal fundus imaging system and ophthalmic B-ultrasound were used to assess the fundus conditions before and after surgery. The Icare® TONOVET Plus tonometer was utilized to evaluate intraocular pressure changes before and after surgery. The Eaton and Draize scoring systems were selected to monitor postoperative inflammatory reactions.RESULTS: The retinal reattachment rates in the FCB and SB groups were 87.5% and 75.0%, respectively, with no statistically significant difference between the groups(P>0.05). The intraocular pressure in both the FCB and SB groups increased postoperatively compared to preoperative levels(P<0.01), and there were no significant differences in intraocular pressure at any time points during the follow-up period between the groups(P>0.05). The intraocular pressure in the RRD models group remained at a low level throughout the follow-up period. The average surgical time for the FCB group was 16.87±2.29 min, which was shorter than 46.25±4.74 min in the SB group(t=-15.166, P<0.001). According to the Eaton and Draize scoring systems, the FCB group had lower grades of conjunctival hyperemia and edema in the early postoperative period compared to the SB group, indicating milder inflammatory reactions(P<0.05).CONCLUSION: Both FCB and SB are effective in treating experimental RRD. Compared to SB, FCB is simpler to operate, and also has a shorter surgical time and milder postoperative inflammatory reactions.

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.

China now has the largest number of people living with diabetes worldwide. To address such a burden, the Healthy China 2030 initiative and subsequent Healthy China Initiative-Diabetes Prevention and Treatment Action Plan(2024-2030)were launched. A shift from " disease-centred" approach to " health-centred" approach and from treatment to prevention is the core of diabetes management in China. Various regions have formed some characteristic prevention and control models with local features in their long-term diabetes prevention and control work, such as the " Community Three-in-One" management model, hospital-community integrated prevention and control model, " Three Doctors Shared Management" model, and family doctor model. Based on the description of the current situation of diabetes prevention and control in China, this article elaborates on the diabetes prevention and control model, key measures, and practical effects in Bao′an District, Shenzhen. It aims to introduce the practices and reflections on diabetes prevention and control in Bao′an, Shenzhen, and provide experiential reference for diabetes prevention and control in other areas.

China now has the largest number of people living with diabetes worldwide. To address such a burden, the Healthy China 2030 initiative and subsequent Healthy China Initiative-Diabetes Prevention and Treatment Action Plan(2024-2030)were launched. A shift from " disease-centred" approach to " health-centred" approach and from treatment to prevention is the core of diabetes management in China. Various regions have formed some characteristic prevention and control models with local features in their long-term diabetes prevention and control work, such as the " Community Three-in-One" management model, hospital-community integrated prevention and control model, " Three Doctors Shared Management" model, and family doctor model. Based on the description of the current situation of diabetes prevention and control in China, this article elaborates on the diabetes prevention and control model, key measures, and practical effects in Bao′an District, Shenzhen. It aims to introduce the practices and reflections on diabetes prevention and control in Bao′an, Shenzhen, and provide experiential reference for diabetes prevention and control in other areas.

ObjectiveTo systematically evaluate the distribution of traditional Chinese medicine（TCM） syndromes of primary osteoporosis（POP） in China by using evidence-based medicine methods， and to understand the distribution law of the syndromes. MethodChina National Knowledge Infrastructure（CNKI）， VIP Chinese Science and Technology Journal Database（VIP）， WanFang Data Knowledge Service Platform（WanFang） and China Biology Medicine（CBM） were searched to obtain representative literature， and each database was searched from the 1994 World Health Organization defined diagnostic criteria for osteoporosis until May 1， 2023. Two researchers independently screened literature according to the criteria， extracted data， and cross-checked them. Meta analysis was conducted using R4.1.3， and subgroup analysis was performed. ResultA total of 56 Chinese papers were included， involving 14 415 patients. After standardized classification of syndromes， 11 articles were excluded， and Meta analysis results of the ultimately included 45 Chinese articles showed that the distribution frequencies of liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome in 12 723 patients were 27%［95% confidence interval（CI） 0.24-0.31］， 32%（95% CI 0.29-0.36）， 36%（95% CI 0.30-0.42）. Subgroup analysis showed that there was a statistically significant difference in the distribution of the three TCM syndromes in the north and south（P<0.05）. In addition， the incidence of TCM syndrome fractures in different types of POP was 15%（95% CI 0.09-0.24） for liver-kidney Yin deficiency syndrome， 20%（95% CI 0.12-0.30） for spleen-kidney Yang deficiency syndrome， and 31%（95% CI 0.25-0.39） for kidney deficiency and blood stasis syndrome. ConclusionThe distribution of syndromes in POP patients is mainly kidney deficiency， accompanied by liver and spleen dysfunction. Liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome are all the main syndromes of POP and osteoporotic fractures， and kidney deficiency and blood stasis syndrome is most closely related to the development of osteoporotic fractures. The reference standards for syndrome determination among the included studies are inconsistent， and in the future， it is necessary to focus on their determination standards to obtain consensus research results， at the same time， conduct large-scale syndrome research to obtain representative research results， providing a basis for clinical practice and research.

Objective To analyze the prevalence and genetic characteristics of influenza A(H3N2) viruses in the city of Xiangyang in 2022-2023, and to provide a scientific basis for predicting the epidemic and mutation of influenza virus. Methods Throat swab specimens of the influenza like cases were collected from national influenza monitoring sentinel hospitals in Xiangyang every week. RNA was extracted from the specimens for influenza diagnosing using real-time RT-PCR．Viruses were isolated from H3N2 positive specimens, and HA and NA genes were amplified and sequenced．3D modeling analyses were conducted. Results The gene phylogenetic tree showed that the H3N2 isolates in 2022-2023 belonged to 3C.2a1b.2a1 and 3C.2a1b.2a2 branches, respectively. The A(H3N2) influenza virus strains all had amino acid point mutation sites on important antigenic determinants of HA protein. The epitope mutations of the 2022 A(H3N2) strain mainly occurred in regions B, C, and D. The epitope mutations of the A(H3N2) strain in 2023 mainly occurred in regions C and D. Different glycosylation sites of HA gene were found in 2022-2023 strains. No variation was found in key amino acid sites associated with neuraminidase inhibitor resistance. The difference of overall structure was not obvious in the three-dimensional simulation structure diagram. Conclusion The A(H3N2) influenza strains isolated in this study have shown antigenic drift, especially the mutation of HA, which may affect the protective effect of the vaccine on the local population and lead to influenza epidemic. The variations of HA and NA suggest that close attention should be paid to the epidemic and genetic variation of H3N2 subtype influenza virus, to provide a scientific basis for the selection of influenza virus vaccine strains and the prevention and control of influenza.

BACKGROUND:The addition of traditional rod-rod fixation for atlantoaxial joint disease to C1-C2 pedicle screw-rod fixation(C1-C2 PSR)can provide stronger anti-rotation stability for screw/rod fixation,but there is a risk of installation difficulties,impact on bone graft bed,and spinal cord injury.The new horizontal screw-screw crosslink(hS-S CL)designed by the authors can effectively overcome the above shortcomings,but its biomechanical properties are unclear. OBJECTIVE:To analyze biomechanical properties of new horizontal screw-screw crosslink in C1-C2 PSR by three-dimensional finite element analysis. METHODS:CT thin layer scanning data were collected from the occipital base to the axis(C0-2)of one adult healthy male volunteer.The atlantoaxial finite element models were established respectively:the normal group,the unstable group,the non-crosslink group(unstable+C1-C2 PSR),and the crosslink group(C1-C2 PSR+hS-S CL).Range of motion and Von Miss Stresses in flexion and extension,lateral flexion and rotation of the four groups were calculated by applying 1.5 Nm torque to each finite element model,and the stress cloud was extracted. RESULTS AND CONCLUSION:(1)Range of motion of the unstable group was increased by 43.8%-78.7%compared with the normal group,and the range of motion of the internal fixation groups was 90.2%-98.7%lower than that of the unstable group under six conditions.The range of motion of the crosslink group and the non-crosslink group was basically the same in flexion and extension states,but in lateral flexion and rotation states,the range of motion of the crosslink group decreased 34.3%-43.8%and 78.6%-79.1%,respectively,compared with the non-crosslink group,and range of motion decreased most obviously in rotation state.(2)The stress peak of the internal plant model:The maximum stress of the crosslink group was generally smaller than that of the non-crosslink group,and the stress peak value of all the internal fixation groups was the lowest when the extension was carried out.(3)The stress cloud of internal plants showed that there was no obvious stress concentration phenomenon in the internal fixation,and the main stress distribution areas were the screw root and bone joint,and the crosslink ends were the screw tail groove or the joint rod joint.(4)The new horizontal screw-screw crosslink can obviously improve the anti-rotation stability of internal fixation and it can share part of the pressure in the three-dimensional motion direction of the internal fixation system and reduce the maximum stress of the internal plants.However,the stress distribution is obvious at both ends of the crosslink,and this part may be prone to fracture of the crosslink.

BACKGROUND:Posterior atlantoaxial pedicle screw rod internal fixation is the main method for treating atlantoaxial dislocation,and the horizontal crosslink plays an important role in the antirotation ability of the internal fixation system.The new horizontal screw-screw crosslink can effectively overcome the disadvantages of traditional horizontal crosslink,such as inconvenient installation,impact on bone grafting bed,and potential spinal cord injury.However,the biomechanical properties of the new horizontal screw-screw crosslink with different installation modes are still unclear. OBJECTIVE:To investigate the biomechanical characteristics of new different installation modes of horizontal screw-screw crosslink in the C1-C2 pedicle screw-rod fixation and to provide a theoretical basis for optimal installation mode. METHODS:Six fresh human occipitocervical specimens were divided into the intact state group(group A),and the atlantoaxial instability model of type Ⅱ odontoid fracture was established based on the intact state group as the instability group(group B).The C1-C2 pedicle screw-rod fixation was performed on each specimen based on the instability group(group C).In group C,different installation modes of horizontal screw-screw crosslink were successively installed in each specimen,including upper transverse connection(two atlas screw tails)as group D,lower transverse connection(two axis screw tails)as group E,diagonal transverse connection(upper left and lower right for group F,lower left and upper right for group G),and cross transverse connection as group H.The specimen models were tested in order of flexion,extension,lateral flexion and lateral rotation on a three-dimensional motion machine,and the atlantoaxial range of motion of each group of specimens was obtained.Repeated measure analysis of variance was used to evaluate the biomechanical properties of each group. RESULTS AND CONCLUSION:(1)Under six states,the range of motion of groups A,C,D,E,F,G and H was smaller than that of group B,and there were statistically significant differences(P＜0.05).(2)In the flexion and extension states,there was no significant difference among the five types of horizontal screw-screw crosslink groups(P＞0.05).(3)In the left and right rotation directions,there were significant differences in D and E groups compared with F,G and H groups(P＜0.05);there were no significant differences between D and E groups,and F and G groups(P＞0.05),and there were no significant differences in F and G groups compared with H group(P＞0.05).(4)In conclusion,under flexion-extension states,the biomechanical stability of five types of horizontal screw-screw crosslink groups was similar,but under the rotation state,the stability of diagonal horizontal screw-screw crosslink group and cross horizontal screw-screw crosslink group was obviously better than that of transverse horizontal screw-screw crosslink group;however,the stability of diagonal horizontal screw-screw crosslink group is similar to the cross horizontal screw-screw crosslink group,so the former is more worthy of clinical recommendation.