Abstract: To explore the molecular mechanism by which long non-coding RNA Surfactant Associated 1 Pseudogene(SFTA1P) promotes the proliferation and migration of clear cell renal cell carcinoma(ccRCC) cells by regulating the microRNA-182-5p(miR-182-5p)/fibronectin 1(FN1) pathway. Methods: GEPIA2 software was utilized to analyze the expression ofSFTA1Pin ccRCC tissues from the TCGA database. Quantitative real-time PCR(qPCR) was employed to detect the expression ofSFTA1Pin ccRCC tissues, normal kidney tissues and ccRCC cell lines. A subcellular localization experiment was performed to explore the localization ofSFTA1Pwithin the human renal cell adenocarcinoma cell line(ACHN) derived from ccRCC. ACHN cells were then divided into the following groups: si-Con group, si-SFTA1P #2 group, mimic NC group, miR-182-5p mimic group, anti-miR-Con group, anti-miR-182-5p group, anti-miR-182-5p+si-FN1 group, si-Con+anti-miR-Con group, si-SFTA1P #2+anti-miR-Con group, and si-SFTA1P #2+anti-miR-182-5p group. CCK-8 and Transwell chamber experiments were conducted to assess cell proliferation and migration abilities. qPCR, Western blot, and dual-luciferase reporter assays were employed to elucidate the regulatory interactions amongSFTA1P,miR-182-5p, andFN1. Results: Analysis of The Cancer Genome Atlas(TCGA) database indicated thatSFTA1Pwas overexpressed in ccRCC tissues(P<0.05). When compared to normal kidney tissues,SFTA1Pexpression was markedly elevated in ccRCC tissues(P<0.01). Furthermore, the expression levels ofSFTA1Pin ccRCC cell lines 786-O, SN12-PM6, ACHN, and A498 were significantly higher than those in human renal proximal tubule cells(HK-2)(allP<0.01). Subcellular localization experiments revealed thatSFTA1Ppredominantly localized in the cytoplasm of ACHN cells. Compared to the si-Con group, the si-SFTA1P #2 group exhibited a significant reduction in proliferation and migration abilities of ACHN cells, accompanied by a decrease inFN1mRNA and protein expression(P<0.05). Compared to the mimic NC group, the expression ofFN1mRNA and protein in ACHN cells in the miR-182-5p mimic group reduced(P<0.01). In comparison to the anti-miR-Con group, the expression levels ofFN1mRNA and protein in ACHN cells were significantly elevated in the anti-miR-182-5p group. Additionally, there was a significant enhancement in both cell proliferation and migration capabilities(P<0.05). Conversely, the proliferation and migration abilities of ACHN cells in the anti-miR-182-5p+si-FN1 group were significantly reduced compared to the anti-miR-182-5p group(P<0.05). Furthermore, relative to the si-SFTA1P #2+anti-miR-Con group, the ACHN cells in the si-SFTA1P #2+anti-miR-182-5p group demonstrated increased proliferation and migration abilities, along with elevatedFN1mRNA and protein expression levels(P<0.05). Conclusion SFTA1Pexhibits elevated expression levels in ccRCC and facilitates the proliferation and migration of ccRCC cells through the modulation of themiR-182-5p/FN1signaling pathway.

Objective To analyze the expression of long non-coding RNA(lncRNA)ABHD11-AS1 in clear cell renal cell carcinoma(ccRCC)and renal cancer cell lines,and explore its potential functions and mechanisms of action.Methods The bioinformatics tool GEPIA2 software was used to analyze The Cancer Genome Atlas(TCGA)database and compare the expression levels of ABHD11-AS1 in ccRCC and normal kidney tissues.Real-time quantitative PCR was performed to assess ABHD11-AS1 expression in ccRCC tissues,normal kidney tissues,and renal cancer cell lines.Subcellular localization experiments were performed to determine the subcellular locali-zation of ABHD11-AS1 in renal cancer cells.The MTT assay,Transwell assay,real-time quantitative PCR,and Western blotting were used to detect the effects of ABHD11-AS1 and miR-133a-3p on the proliferation,invasion,and expression of SLC6A1 in renal cancer cells.A dual-luciferase reporter gene experiments was performed to validate the binding effect of ABHD11-AS1 to miR-133a-3p and the effect of miR-133a-3p on SLC6A1.Results GEPIA2 software and real-time quantitative PCR analyses indicated that ABHD11-AS1 was highly expressed in ccRCC tissues compared to normal kidney tissues(P＜0.05).Compared to the immortalized renal tubular epithelial cell line HK-2 cells,the expression of ABHD11-AS1 was significantly upregulated in the ACHN,786-O,and SN12-PM6 cells,with the highest expression observed in 786-O cells.The results of the subcellular localization experiments indicated that ABHD11-AS1 was primarily distributed in the cytoplasm of 786-O cells.ABHD11-AS1 knockdown reduced the proliferative and invasive abilities of 786-O cells and decreased SLC6A1 mRNA and protein expression(P＜0.05).Dual-luciferase reporter gene experiments demonstrated that ABHD11-AS1 targets and binds to miR-133a-3p,which in turn binds to SLC6A1.Overexpression of miR-133a-3p reduced the mRNA and protein levels of SLC6A1 in 786-O cells,whereas downregulation of miR-133a-3p had the opposite effect.Downregulation of miR-133a-3p enhanced the proliferation and invasion of 786-O cells,while knockdown of SLC6A1 partially reversed the promoting effect of miR-133a-3p downreg-ulation on the proliferation and invasion of 786-O cells(P＜0.05).Simultaneously,downregulation of miR-133a-3p could also partially reverse the inhibitory effects of ABHD11-AS1 knockdown on 786-O cell proliferation,invasion,and SLC6A1 expression(P＜0.05).Con-clusion ABHD11-AS1 exerts a pro-cancer effect on ccRCC by regulating the miR-133a-3p/SLC6A1 axis,which influences the prolifera-tion and invasion of renal cancer cells.

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.

Objective To analyze the expression of long non-coding RNA(lncRNA)ABHD11-AS1 in clear cell renal cell carcinoma(ccRCC)and renal cancer cell lines,and explore its potential functions and mechanisms of action.Methods The bioinformatics tool GEPIA2 software was used to analyze The Cancer Genome Atlas(TCGA)database and compare the expression levels of ABHD11-AS1 in ccRCC and normal kidney tissues.Real-time quantitative PCR was performed to assess ABHD11-AS1 expression in ccRCC tissues,normal kidney tissues,and renal cancer cell lines.Subcellular localization experiments were performed to determine the subcellular locali-zation of ABHD11-AS1 in renal cancer cells.The MTT assay,Transwell assay,real-time quantitative PCR,and Western blotting were used to detect the effects of ABHD11-AS1 and miR-133a-3p on the proliferation,invasion,and expression of SLC6A1 in renal cancer cells.A dual-luciferase reporter gene experiments was performed to validate the binding effect of ABHD11-AS1 to miR-133a-3p and the effect of miR-133a-3p on SLC6A1.Results GEPIA2 software and real-time quantitative PCR analyses indicated that ABHD11-AS1 was highly expressed in ccRCC tissues compared to normal kidney tissues(P＜0.05).Compared to the immortalized renal tubular epithelial cell line HK-2 cells,the expression of ABHD11-AS1 was significantly upregulated in the ACHN,786-O,and SN12-PM6 cells,with the highest expression observed in 786-O cells.The results of the subcellular localization experiments indicated that ABHD11-AS1 was primarily distributed in the cytoplasm of 786-O cells.ABHD11-AS1 knockdown reduced the proliferative and invasive abilities of 786-O cells and decreased SLC6A1 mRNA and protein expression(P＜0.05).Dual-luciferase reporter gene experiments demonstrated that ABHD11-AS1 targets and binds to miR-133a-3p,which in turn binds to SLC6A1.Overexpression of miR-133a-3p reduced the mRNA and protein levels of SLC6A1 in 786-O cells,whereas downregulation of miR-133a-3p had the opposite effect.Downregulation of miR-133a-3p enhanced the proliferation and invasion of 786-O cells,while knockdown of SLC6A1 partially reversed the promoting effect of miR-133a-3p downreg-ulation on the proliferation and invasion of 786-O cells(P＜0.05).Simultaneously,downregulation of miR-133a-3p could also partially reverse the inhibitory effects of ABHD11-AS1 knockdown on 786-O cell proliferation,invasion,and SLC6A1 expression(P＜0.05).Con-clusion ABHD11-AS1 exerts a pro-cancer effect on ccRCC by regulating the miR-133a-3p/SLC6A1 axis,which influences the prolifera-tion and invasion of renal cancer cells.

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.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective To investigate the impact of LncRNA FOXP4-AS1 regulating the EZH2/LATS2 axis on the proliferation and migration of bladder urothelial carcinoma(BUC)cells.Methods The Cancer Genome Atlas(TCGA)database and real-time quantitative PCR were utilized to analyze the expression of FOXP4-AS1 and LATS2 mRNA in BUC tissues.Cell proliferation was observed using MTT experiments,and migration was checked using Transwell assays.Western blot assays were performed to determine the expression of LATS2 and H3K27me3 proteins.RNA immunoprecipitation(RIP)and chromatin immunoprecipitation(ChIP)assays were employed to verify the relationship between FOXP4-AS1,EZH2 and LATS2.Results Compared with normal bladder tissues,FOXP4-AS1 expression was increased in tumor tissues,while LATS2 mRNA expression was decreased(P<0.01).Moreover,FOXP4-AS1 expression was elevated in EJ,T24,BIU-87,and 5637 cell lines compared to SV-HUC-1(P<0.01).The inhibition of FOXP4-AS1 resulted in a significant decrease in the proliferation,migration,and expression of H3K27me3 protein in BUC cells,while concurrently upregulating the expression of LATS2 mRNA and protein.Conversely,the overexpression of FOXP4-AS1 yielded contrasting effects(P<0.05).RIP and ChIP assays revealed that FOXP4-AS1 could recruit EZH2 to the promoter region of LATS2,leading to an enrich-ment of H3K27me3 in this region.Interference with LATS2 or EZH2 expression partially reversed the effects of FOXP4-AS1 silencing or overexpression on the proliferation and migration of BUC cells,with concomitant effects on LATS2 expression.Conclusion FOXP4-AS1 demonstrates a notable increase in expression in BUC,leading to a suppression of LATS2 expression through the recruitment of EZH2 to the promoter region of LATS2.This regula-tory process ultimately influences the proliferation and migration of BUC cells.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective: To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy. Materials and Methods: Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis. Results: The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = -0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = -0.582, p = 0.004) and JOA-sensory scores (ρ = -0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028). Conclusion For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.