Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive fibroblast growth factor 23 (FGF23) secretion. However, TIO lesions located in the neurocranium (NC) and intracranial (IC) structures remain poorly characterized. To characterize the clinical features of TIO lesions in NC and IC structures and to compare them with those located in the sinuses. This retrospective study included patients diagnosed with TIO who underwent tumor resection at Peking Union Medical College Hospital between January 2016 and December 2023. Patients with lesions in NC and IC structures were defined as the study group, while those with sinus lesions served as the control group. Clinical characteristics, biochemical parameters, and surgical outcomes were systematically analyzed and compared between groups. TIO lesions in NC and IC structures were distributed across the skull base, temporal region, sellar region, frontal lobe, and occipital region. Compared with sinus lesions, patients with NC and IC lesions showed comparable clinical and biochemical profiles but exhibited significantly worse outcomes, including higher rates of non-remission and tumor recurrence. These findings suggest increased difficulty in complete tumor resection and disease control in this subgroup. TIO lesions in NC and IC structures are associated with poorer surgical outcomes and higher recurrence rates despite similar baseline characteristics. These results highlight the need for improved localization strategies and tailored management approaches for this challenging subgroup.

ContextFibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare skeletal disorder frequently manifesting in childhood, often leading to progressive bone lesions, pain and functional impairment. Denosumab as a monoclonal antibody targeting RANKL has emerged as a potential therapeutic option, while its safety and efficacy in pediatric population remains poorly defined.ObjectiveInvestigate the efficacy and safety of denosumab in pediatric FD/MAS population.Design12-month single-arm study.SettingSingle center study at Peking Union Medical College Hospital.PatientsFD/MAS patients under 18.InterventionsDenosumab 1mg/kg with a maximum dosage of 60mg every 3 months for 12-month follow-up.Main outcome measuresFD-related bone pain, bone turnover markers, 99mTc-MDP bone scintigraphy, bone mineral density.ResultsIn 5 pediatric FD/MAS patients treated with denosumab, significant clinical improvements were observed, including alleviation of FD-associated bone pain, reductions in bone turnover markers, and regression of FD lesions. Alkaline phosphatase levels dropped to an average of 41.8% of baseline, accompanied by concurrent reductions in C-terminal telopeptide and type 1 N-terminal pro-peptide levels. Adverse events particularly hypercalcemia following treatment cessation occurred in 2 of the 5 patients, indicating a relatively high incidence of rebound hypercalcemia and highlighting the need for careful monitoring and cautious use of denosumab in pediatric patients.ConclusionsDenosumab appears to be effective in pediatric FD/MAS patients, however safety concerns remain. Comprehensive pre-treatment evaluation and close monitoring throughout the treatment course are essential. Further prospective studies and randomized controlled trials are needed to determine optimal dosing strategies and establish long-term safety in this population.

This study systematically analyzed 72 adults with genetically confirmed hypophosphatasia and compared them with 36 individuals with persistent hypophosphatasemia but negative ALPL variants. Using four routinely available indicators, a simplified diagnostic tool was developed and externally validated to facilitate the early identification of adult hypophosphatasia in clinical practice. Hypophosphatasia (HPP), an underdiagnosed inborn error of disorder caused by ALPL mutations, poses diagnostic challenges in adults due to phenotypic heterogeneity. This study aimed to establish a large adult HPP cohort in China and develop a practical diagnostic tool using routine clinical parameters. Clinical and genetic characteristics were systematically analyzed in 72 genetically confirmed adult HPP patients and 36 individuals with persistent hypophosphatasemia and negative ALPL genetic testing. Two models were developed to predict HPP: Model 0 (alkaline phosphatase (ALP)+pyridoxal-5′-phosphate (PLP)) and Model 1 (ALP+height Z-score+family history+chronic musculoskeletal pain). Model performance was evaluated by tenfold cross-validation, decision curve analysis (DCA) and external validation (n = 40, including 28 HPP). HPP patients exhibited lower ALP (27.0 (21.8, 33.3) U/L vs. 36.00 (32.0, 38.0) U/L; P < 0.001), elevated PLP (214.3 (121.3, 457.7) nmol/L vs. 42.6 (31.9, 63.5) nmol/L; P < 0.001), growth impairment, and higher prevalence of chronic musculoskeletal pain and family history. Optimal ALP and PLP cutoffs were 28.2 U/L and 114.9 nmol/L, respectively. Compound heterozygotes and crown domain variants in ALPL gene showed lower ALP and higher PLP levels. Model 1 performed comparably to Model 0 (AUC 0.918 vs. 0.896; P = 0.513), remained robust in the age-stratified sensitivity analysis (<50 years), and achieved an AUC of 0.833 in external validation. A nomogram based on Model 1 was constructed. This study provides the largest clinical-genetic characterization of adult HPP in China and proposes a simple four-variable nomogram that enables accurate recognition of HPP without PLP testing, facilitating earlier diagnosis in routine practice.

Purpose Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder characterized by both skin and skeletal abnormalities and is classified into two subtypes: PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2). Cyclooxygenase-2 (COX-2) inhibitor Etoricoxib is first-line medication for PHO which could alleviate digital clubbing and pachydermia. However, its effects on the skeletal abnormalities associated with PHO remain unclear. This study aims to comprehensively investigate changes in bone microarchitecture at the distal radius, tibia and interphalangeal bones in PHO patients after 12-month Etoricoxib treatment. Methods A total of 20 PHO patients were enrolled, including 9 PHOAR1 patients and 11 PHOAR2 patients. Bone microstructure was investigated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results After 12 months' treatment, periosteosis in long bones and osteolysis at the 3rd interphalangeal joint of PHO were visually reduced. HR-pQCT parameters revealed improvements in total volumetric bone mineral density (Tot.vBMD), cortical vBMD (Ct.vBMD) at distal radius and tibia, accompanied with decreased cortical porosity. Trabecular bone showed no significant improvement. Besides, bone stiffness and failure load were significantly enhanced at radius site. In subgroup analysis, PHOAR2 patients experienced decline in trabecular number at the distal tibia, a change not observed in PHOAR1 patients. Correlation analysis revealed inverse associations between disease duration and changes in vBMD and bone strength in PHOAR2 patients, whereas no significant associations were found in PHOAR1 patients. Conclusions Our findings indicated that 12 months of Etoricoxib treatment improved bone microstructure in PHO patients and highlighted differential treatment responses between different genotypes, which might optimize treatment strategies for PHO patients.

Purpose:Neural EGF-like 1 (Nell-1), originally implicated in craniosynostosis, has been identified as a key regulator in osteogenic processes. While preclinical data were encouraging, clinical studies correlating serum Nell-1 levels with osteoporosis remain scarce. This study aims to investigate the relationship between circulation Nell-1 level and bone turnover markers, bone mineral density (BMD), bone microstructure, muscle strength, fall risk, and fractures in Chinese postmenopausal women. Methods:Serum Nell-1 levels were measured in 123 Chinese postmenopausal women. Muscle function was evaluated through grip strength tests, the Short Physical Performance Battery (SPPB), and the Timed Up and Go (TUG) test. Dual-energy X-ray absorptiometry was used to assess areal bone mineral density (aBMD), lumbar trabecular bone score (TBS), and muscle mass. High-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to determine volumetric bone mineral density (vBMD), analyze bone microarchitecture, and estimate bone strength. Result:Postmenopausal women with higher serum Nell-1 levels had higher aBMD and total volumetric bone mineral density (Tot.vBMD) at the distal tibia, larger cortical area (Ct.Ar) and thicker cortical thickness (Ct.Th) at the distal tibia, and higher bone strength. There was a significant negative association between serum Nell-1 levels and C-terminal cross-linking telopeptide of type I collagen (β-CTX), while no significant correlations were observed between serum Nell-1 levels and muscle mass or function. Conclusion:Postmenopausal women with higher serum Nell-1 levels exhibited higher BMD and bone strength, indicating its potential as a therapeutic invention for osteoporosis.

This study estimated FRAX®-based intervention thresholds for initiating osteoporosis treatment in Chinese postmenopausal women, using real-world data from the largest nationally representative osteoporosis survey in China and a validated Markov microsimulation model. Denosumab became cost-effective at a 10-year major osteoporotic fracture probability of 7

PurposeHigh serum periostin is linked to an increased risk of osteoporotic fractures in postmenopausal women. However, the relationships between serum periostin and bone microarchitecture, particularly muscle mass, and muscle function remain unclear. This study aims to investigate the relationships between serum periostin and bone mineral density, bone microarchitecture, muscle mass and function, falls, and fractures in community-dwelling Chinese postmenopausal women.MethodSerum periostin levels were measured in 135 Chinese postmenopausal women. Dual-energy X-ray absorptiometry assessed areal bone mineral density (aBMD), lumbar trabecular bone score (TBS), and muscle mass. High-resolution peripheral quantitative computed tomography (HR-pQCT) evaluated bone microarchitecture. Muscle function and fall risk were assessed using handgrip strength, the Short Physical Performance Battery (SPPB), the Timed Up and Go (TUG) test, and the Falls Risk for Older People in the Community (FROP-Com) screening tool.ResultThe mean serum periostin was 1770.3 ± 440.4 pmol/L. Serum periostin was negatively correlated with bone microarchitecture parameters, total area (Tot.Ar), cortical perimeter (Ct.Pm), trabecular area (Tb.Ar), estimated bone strength stiffness, and failure load. Negative correlations were also found with appendicular skeletal muscle mass (ASM), balance test scores, and gait speed. Conversely, serum periostin was positively correlated with TUG time and FROP-Com scores.ConclusionHigher serum periostin is associated with smaller bone cross-sectional area, lower estimated bone strength, reduced muscle mass, and higher fall risk, indicating its potential as a predictor for assessing skeletal and muscular health in postmenopausal women.

Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic disorders characterized by fibro-osseous skeletal lesions and hyperfunctioning endocrinopathies. Large-scale pediatric cohort data from China remain scarce. We aimed to characterize the phenotypic spectrum of Chinese children with FD/MAS and examine cross-sectional associations between skeletal distribution and endocrine phenotypes. Methods: We conducted a nationally representative retrospective cross-sectional study at Peking Union Medical College Hospital. Patients aged ≤18 years diagnosed with FD/MAS between January 1st 2015 and December 31st 2024, with complete baseline data were included. Main outcomes include demographic features, clinical manifestations, skeletal manifestations, endocrine manifestations, and serum profile. Skeletal involvement was categorized by anatomical region and quantified using the Skeletal Burden Score. Associations between skeletal lesion distribution and endocrinopathies were evaluated using odds ratios. Unsupervised hierarchical clustering assessed symptom patterns at onset. Random forest classification models identified baseline features associated with pituitary adenoma and peripheral precocious puberty in girls. Findings: Of 137 screened pediatric patients, 90 were included (56·7% female). Median age at symptom onset was 5·0 years, with a median diagnostic delay of 2·0 years; 21·1% experienced delays exceeding five years. MAS was present in 76·7% of patients, polyostotic FD in 94·4%, and craniofacial involvement in 76·7%. Among MAS cases, peripheral precocious puberty occurred in 52·2%, hyperthyroidism in 29·0%, pituitary adenoma in 21·7%, and hypophosphatemia in 5·8%. Two phenotype clusters were identified at disease onset. Craniofacial involvement was associated with pituitary adenoma (OR 10·71, 95%CI 2·34-49·08), while pelvic involvement in girls was associated with peripheral precocious puberty (OR 20·94, 95% CI 4·52-96·97). Random forest models yielded AUCs of 0·799 (95%CI 0·625-0·973) for pituitary adenoma and 0·917 (95%CI 0·782-1·000) for peripheral precocious puberty. Interpretation​: This national pediatric cohort demonstrates substantial diagnostic delay, high skeletal, and endocrine burden. Anatomical skeletal distribution is cross-sectionally associated with specific endocrinopathies, supporting anatomy-informed surveillance strategies that warrant prospective validation.

OBJECTIVE:This study aimed to analyze the temporal trends in cancer mortality in China from 2013-2021 and project the future trends through 2030. METHODS:This study was based on the China Causes of Death Surveillance Dataset, which covers 2.37 billion person-years. Age-standardized mortality rates (ASMRs) were calculated using Segi's world standard population and the trends were evaluated via Joinpoint regression. Bayesian age-period-cohort models were used for mortality projections. Contributions of demographic changes (population size and age structure) and risk factors to the mortality burden were quantified using the decomposition analysis. RESULTS:The combined ASMRs for all cancers decreased annually by 2.3%, driven by significant declines in esophageal (4.8%), stomach (4.5%), and liver cancers (2.7%). In contrast, the pancreatic and prostate cancer ASMRs increased by 2.0% and 3.4% annually, respectively. Urban areas demonstrated a more rapid decline in the combined ASMRs for all cancers [average annual percent change (AAPC) = -3.0% in urban areas vs. -2.0% in rural areas], highlighting persistent disparities. Population aging contributed 20%-50% to death increases between 2013 and 2021. The combined ASMRs for all cancers, like the findings of temporal trend analyses, will continue to decrease and the regional (urban and rural) difference is projected to simulate that of the temporal trend through 2030. In fact, cancer deaths are projected to reach 2.4 million by 2030. CONCLUSIONS:The cancer burden in China is facing the dual challenges of population aging and urban-rural disparities. It is necessary to prioritize rural screening, control risk factors, such as smoking and diet, and integrate more efficacious cancer prevention and control programmes into the policy to reduce mortality in the future.

RATIONALE:Primary ectopic meningiomas (PEMs) are extremely rare, with limited literature available on the subject. Understanding their clinical and radiological characteristics is crucial for accurate diagnosis and treatment. PATIENT CONCERNS:This study presents a case of a multicentric PEM involving the lungs and cranial bone barrier, aiming to provide new insights into its clinical and diagnostic features. DIAGNOSES:A 46-year-old woman with no prior history of intracranial meningiomas or other tumors was found to have multiple lobulated nodules in the lungs during a routine physical examination. Computed tomography scans revealed well-defined lesions with mild to moderate heterogeneous enhancement. Magnetic resonance imaging showed a lesion at the cranial bone barrier, which presented as a high-signal area on T2-weighted FLAIR images and mild to moderate enhancement on T1-weighted images. The magnetic resonance spectroscopy displayed a broad Lip peak but lacked N-acetylaspartate or creatine peaks. Histopathological and immunohistochemical analyses confirmed the diagnosis of multicentric PEMs. INTERVENTIONS:We performed surgical resection of the lesion on the cranial bone plate and conducted follow-up examinations for the multiple lesions in the lungs. OUTCOMES:This case highlights the diagnostic challenges of multicentric PEMs involving the lungs and cranial bone barrier. Due to their extremely low incidence and nonspecific clinical manifestations, a comprehensive evaluation combining radiological, pathological, and immunophenotypic data is essential for accurate diagnosis. LESSONS:This case underscores the importance of a thorough, multidisciplinary approach to diagnosis and treatment and provides valuable insights for managing similar rare cases.

This study presents a preoperative prediction model for tumor-induced osteomalacia (TIO) surgery outcomes on the basis of patient characteristics. The model, which was validated in 309 patients, identifies key risk factors and aids in clinical decision-making to optimize treatment strategies, reduce the number of unnecessary surgeries, and improve patient care. Tumor-induced osteomalacia (TIO) should be curable by complete removal of the causative tumor. Knowledge of the prognosis of surgery is lacking. This study aimed to establish a prediction model that uses the preoperative characteristics of patients to predict the surgical treatment outcomes of patients with TIO. This was a single-center, retrospective, case-control study. The main outcome was the surgical outcomes of patients with TIO. Patients with TIO who underwent surgical treatment were divided into a training set and a validation set. A nomogram was established in the training set, and the model was evaluated by the C-index, calibration curve, and clinical impact curve and verified in the validation set. A total of 309 patients with TIO were included, with 222 in the training set and 87 in the validation set. The C-index of the nomogram was 0.864 (p < 0.001). The model had high goodness of fit—which is suggested by the calibration curve, and clinical benefit is indicated by the decision curve analysis and clinical impact curve. In the validation set, the area under the curve of the prediction model was 0.782 (p < 0.001), and decision curve analysis and clinical impact curve also suggested the existence of clinical benefit. This study established a prognostic model for the preoperative prediction of surgical outcomes for TIO. This model can be used as a reference in clinical practice for the development of individualized treatment strategies.

Context Osteopetrosis (OPT) is a rare skeletal disease characterized by high bone mass that has 2 major inheritance patterns: autosomal dominant osteopetrosis and autosomal recessive osteopetrosis (ARO). However, comprehensive descriptions of bone microarchitecture in OPT patients are limited.Objectives The aim of this study was to comprehensively investigate the bone microarchitecture of OPT patients, explore age-related bone alterations, and describe the skeletal heterogeneity among different genotypes.Methods Nine OPT patients, including 7 with autosomal dominant osteopetrosis and CLCN7 mutations, 1 ARO patient with CAII mutation, and 1 ARO patient with TCIRG1 mutation, were retrospectively enrolled in this study. Clinical and biochemical examinations were performed. Bone microstructure was investigated by high-resolution peripheral quantitative computed tomography.Results Compared with age- and sex-matched healthy controls, OPT patients had greater total volumetric bone mineral density. In addition, trabecular bone was denser, with greater trabecular volumetric bone mineral density, increased trabecular number, and decreased trabecular separation. However, the cortical bone in OPT patients was weaker, characterized by increased cortical thickness and porosity. OPT patients exhibited characteristic patterns, including bone islets and uneven dense structures, on the representative reconstruction high-resolution peripheral quantitative computed tomography images. Skeletal heterogeneity across different genotypes was observed, with looser cortical bone in 1 OPT patient with CAII mutation and thicker cortical bone in 1 OPT patient with TCIRG1 mutation.Conclusion Compared with healthy controls, OPT patients presented with denser trabecular bone, thicker but looser cortical bone, unique bone patterns, and skeletal heterogeneity. These results provide new insights into bone alterations in OPT patients.

Human papillomavirus (HPV) infection and osteoporosis (OP) are global health concerns, with higher prevalence observed in women compared to men. However, the impact of HPV infection on bone health remains uncertain. This case–control study utilized data from the National Health and Nutrition Examination Survey (NHANES). Comparable datasets were created using nearest neighbor propensity score matching (PSM) at a ratio of 1:1. The association between HPV infection and bone mineral density (BMD) was analyzed using the Welch two-sample t-test. Furthermore, linear mixed models were employed for validation purposes. Restricted cubic spline (RCS) analysis and Kendall’s tau-b tests were performed to explore the effect of different types of HPV infection on BMD. Individuals with HPV infection (mean age 38.11 ± 11.32 years) had lower BMD in the femur and lumbar spine compared to uninfected individuals (mean age 37.92 ± 11.42 years). RCS analysis revealed that an increasing number of cooccurring HPV types in women was associated with lower BMD. Specifically, four HPV types were negatively associated with femur BMD, while 14 HPV types were negatively associated with lumbar spine BMD. Additionally, HPV types 53, 59, and 89 exhibited effects on both femur and lumbar spine BMD. HPV infection is associated with a decrease in BMD, and co-infection with multiple types of HPV implies even lower BMD. Appropriately designed trials are needed to determine if interventions targeted at preventing HPV infection can have a protective effect on BMD.

X-linked hypophosphatemia (XLH) is the most common type of hereditary hypophosphatemic rickets caused by elevated fibroblast growth factor 23 (FGF23). Multiple cases have reported XLH had Fanconi syndrome (FS) with unidentified mechanism. We investigated the association between genetic polymorphisms of phosphate transporters in renal proximal tubules and XLH with FS for the first time. 25 Chinese XLH patients with FS (XLH-FS) and 33 patients without any urine abnormalities (XLH-nonFS) were included. We collected their clinical manifestations and laboratory results, screened the single-nucleotide polymorphisms (SNPs) of XPR1, SLC34A1 and SLC34A3 by a next generation sequencing-based method, and analyzed the correlation between SNPs and XLH with FS. Computational predictions identified microRNAs (miRNAs) targeting SNPs that influenced susceptibility of FS, and confirmed their interaction and impact on gene expression by a dual-luciferase reporter system. XLH-FS group had a higher proportion of trouble walking (88.0

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (β-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100

Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.

Context: X-linked hypophosphatemia (XLH) is a rare metabolic bone disease caused by inactivation mutations in the PHEX gene. Despite the extensive number of reported PHEX variants, only a few cases of chromosomal abnormalities have been documented. Objective: We aimed to identify the pathogenic variants in 6 unrelated families with a clinical diagnosis of XLH and to propose a genetic workflow for hypophosphatemia patients suspected of having XLH. Methods: Multiple genetic testing assays were used to analyze the 6 families' genetic profiles, including whole exome sequencing, multiplex ligation-dependent probe amplification, whole genome sequencing, reverse transcript polymerase chain reaction, Sanger sequencing, and karyotyping. Results: The study identified 6 novel pathogenic variants, including 1 mosaic variant (exon 16-22 deletion), 3 chromosomal abnormalities (46, XN, inv[X][pter -> p22.11::q21.31 -> p22.11::q21.31 -> qter], 46, XN, inv[X][p22.11p22.11], and XXY), a nonclassical intron variant (NM_000444.6, c.1701_31A > G), and a deletion variant (NM_000444.6, c.64_5464-186 del5215) of PHEX. Additionally, a genetic testing workflow was proposed to aid in diagnosing patients suspected of XLH. Conclusion: Our research expands the mutation spectrum of PHEX and highlights the significance of using multiple genetic testing methods to diagnose XLH.

The progression of high-grade squamous intraepithelial lesion (HSIL) to invasive cervical cancer (ICC) is a complex process involving persistent human papillomavirus (HPV) infection and changes in signal transduction regulation, energy and material metabolism, cell proliferation, autoimmune, and other biological process in vaginal microenvironment and immune microenviroment. Signaling pathways are a series of interacting molecules in cells that regulate various physiological functions of cells, such as growth, differentiation, metabolism, and death. In the progression of HSIL to ICC, abnormal activation or inhibition in signaling pathways plays an essensial role. This review presented some signaling pathways related to the malignant progression of HSIL to ICC, including p53, Rb, PI3K/AKT/mTOR, Wnt/β-catenin, Notch, NF-κB, MAPK, TGF-β, JAK-STAT, Hippo, and Hedgehog. The molecular mechanisms involved in the biological process of pathway regulation were also analyzed, in order to illustrate the molecular pathway of HSIL progression to ICC and provide references for the development of more effective prevention and treatment methods.