Introduction: 45,X/46,XY mosaicism is a rare disorder of sex development characterized by marked phenotypic variability, ranging from typical male or female genitalia to significant genital ambiguity. Data describing long-term clinical outcomes in affected patients remain limited. This study aimed to characterize the phenotypic spectrum and longitudinal outcomes of patients with 45,X/46,XY mosaicism, focusing on growth, associated comorbidities, and gonadal pathology. Methodology: We conducted a retrospective longitudinal study at a tertiary paediatric endocrine referral centre between January 2006 and January 2025. Patients with cytogenetically confirmed 45,X/46,XY mosaicism or related variants were included. Clinical presentation, karyotype, anthropometry, hormonal profiles, imaging findings, and gonadal histology were reviewed. External genital phenotype was quantified using the External Masculinization Score (EMS). Height was expressed as standard deviation scores (SDS) relative to population norms and compared with genetic potential. Results: Fourteen patients (10 males, 4 females) with 45,X/46,XY mosaicism were identified. Ambiguous genitalia was the predominant presenting feature, observed in 11 of 12 patients with available phenotype data. Growth impairment was common; median height SDS was −2.62 (range −3.26 to −2.00) in females and −0.46 (range 0.13 to −1.70) in males, both below expected genetic potential. Associated congenital anomalies were present in 25% of patients, including cardiac and renal abnormalities. Male patients demonstrated variable degrees of undervirilization with a median EMS of 4.5 (3.75–7.25). Müllerian duct remnants were identified in 66% of patients on imaging. Testicular microlithiasis was observed in two males. During follow-up, two patients underwent gender reassignment. Histological analysis of 14 gonads obtained via gonadectomy or biopsy revealed abnormal gonadal architecture in all cases. All intra-abdominal gonads demonstrated streak gonads or dysgenetic testicular tissue. Conclusion 45,X/46,XY mosaicism demonstrates a broad phenotypic spectrum with frequent genital ambiguity, growth impairment, and abnormal gonadal development. The high prevalence of gonadal dysgenesis underscores the importance of careful surveillance and individualized multidisciplinary management guided by clinical, endocrine, and histopathological findings.
Child ; Longitudinal Studies ; Mosaicism

PURPOSE: Ultrasonography has been used increasingly in orthopaedic practice credited to its low cost, easy accessibility, non-invasiveness, reproducibility, and safety from radiation. The purpose of this study was to test the validity and efficacy of ultrasonography as an adjunct in the assessment of fracture healing in long bones treated with intramedullary interlocking devices and its predictive value in determining the need for a secondary surgical procedure. METHODS: This was a descriptive longitudinal study of 40 skeletally mature patients from November 2016 to February 2019, who sustained long bone fractures of the tibia or femur treated using intramedullary interlocking nails. Patients with comminuted and segmental fracture patterns were excluded from the study. Each patient was evaluated at 6- and 12-week post-surgery using standard orthogonal radiographs and ultrasonography to assess fracture healing. Patients were then followed up until fracture union. Quantitative data was analyzed using frequency statistics and descriptive data with inferential statistics. RESULTS: Ultrasonography predicted 87.5% union and 12.5% delayed or non-union as early as 6 weeks after surgery, while radiographs predicted 22.5% union as late as 3 months of follow-up. The sensitivity and specificity of ultrasonography in assessing fracture healing were 100% and 97.2%, respectively, with a positive predictive value of 80.0%. Vascular resistance index was less than 0.5 in all patients who developed delayed or non-union. CONCLUSION Ultrasonography is able to predict fracture outcomes much earlier than standardized radiographs with comparable sensitivity and specificity. Vascular resistance index is an objective parameter in assessing callus quality and predicting fracture outcomes.
Humans ; Fracture Fixation, Intramedullary/methods* ; Male ; Female ; Ultrasonography/methods* ; Adult ; Fracture Healing ; Tibial Fractures/diagnostic imaging* ; Middle Aged ; Femoral Fractures/diagnostic imaging* ; Longitudinal Studies ; Bone Nails ; Young Adult ; Predictive Value of Tests ; Aged ; Treatment Outcome ; Adolescent

PURPOSE: To evaluate the diagnostic accuracy of the observational chart for traumatic limb swelling (OCTLS) for osteofascial compartment syndrome (OCS). METHODS: This was a descriptive-longitudinal study. Data of 316 patients who underwent surgical treatment for tibial fractures in our department from January 2015 to December 2023 were collected. Patients with Gustilo type II or higher open fractures, vascular injury, or bilateral fractures were excluded from the study. Two groups of double-blinded investigators independently assessed patients for the presence of OCS using 2 distinct diagnostic methods. Three senior orthopedic trauma surgeons evaluated patients with post-fracture calf swelling for OCS and the need for fasciotomy based on clinical signs and their extensive clinical experience. Subsequently, fasciotomy was performed according to their judgment, followed by postoperative examination of muscle and soft tissue conditions. Additionally, a follow-up evaluation was conducted to assess for complications such as ischemic muscle contracture. Another 3 trained researchers used OCTLS to grade swelling severity and determine the need for fasciotomy. The final diagnostic gold standard of OCS was determined by referring to whether there was escape of muscles at fasciotomy and/or color change in the muscles or muscle necrosis intraoperatively, and neurological abnormality or contracture at the last follow-up. The results of the 2 diagnostic methods were compared with the final diagnostic result. Kappa consistency test, paired χ² test (McNemar test), and receiver operating characteristic curve were used to evaluate the diagnostic efficacy of the 2 diagnostic methods. RESULTS: Of the 316 patients, 211 were finally included in the study, including 160 males and 51 females, with an average follow-up time of (14.5 ± 2.7) months. Among the 211 patients with tibial fracture-associated swelling, 42 were definitively diagnosed with OCS. Based on clinical symptoms and signs judgment, among the 65 fasciotomy patients, 38 were confirmed as correct, while among the 146 non-fasciotomy patients, 4 developed ischemic muscle contractures. Based on the OCTLS for assessment, fasciotomy was correctly recommended in 36 out of 43 cases, while 6 out of 168 non-fasciotomy patients developed OCS. Compared to the use of the gold standard, clinical signs judgment showed moderate consistency (McNemar's test p < 0.001, Kappa = 0.618, p < 0.001), whereas OCTLS demonstrated strong agreement (McNemar's test p = 1.000, Kappa = 0.808, p < 0.001). Receiver operating characteristic analysis revealed higher diagnostic accuracy for OCTLS (area under curve = 0.908, 95% CI: 0.843 - 0.972) compared to clinical signs judgment (area under curve = 0.872, 95% CI: 0.812 - 0.933). OCTLS achieved superior accuracy (93.8% vs. 85.3%, χ² = 8.221, p < 0.001) and a lower fasciotomy rate (20.4% vs. 30.8%, χ² = 6.023, p = 0.014). CONCLUSION Compared to clinical signs judgment, OCTLS significantly reduces unnecessary fasciotomy, improves diagnostic accuracy for OCS, and enables non-invasive, dynamic, and quantitative assessment, making it a valuable tool for clinical practice.
Humans ; Compartment Syndromes/etiology* ; Male ; Female ; Adult ; Tibial Fractures/surgery* ; Middle Aged ; Fasciotomy ; Edema/etiology* ; Longitudinal Studies ; Aged ; Young Adult

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

This study was to survey the relationship between semen values and demographics, comorbidities, and recreational substance use in a large cohort of adult men at the University of Chicago Medical Center Department of Urology (Chicago, IL, USA). We performed an analysis from January 2013 to December 2023 of semen samples obtained from adult patients at our institution and collected their demographics, comorbid medical conditions, and recreational substance use information. Patients were divided into categories of normozoospermia, oligozoospermia, and azoospermia on the basis of the 5 th version of the World Health Organization (WHO) guidelines. Data were analyzed by univariate linear and logistic regression models, after which statistically significant variables were placed into multivariable models. Azoospermia and oligozoospermia were both associated with Caucasian or Black, Indigenous, and People of Color (BIPOC) race (both P < 0.001), increasing age ( P = 0.005 and P < 0.001, respectively), anemia ( P < 0.001 and P = 0.02, respectively), lifetime tobacco use (both P < 0.001), lifetime alcohol use ( P = 0.02 and P < 0.001, respectively), and lifetime use of at least two recreational substances ( P < 0.001 and P = 0.003, respectively) in multivariable models. Oligospermia was additionally associated with benign prostatic hyperplasia (BPH; P = 0.003) in multivariable models. This study suggests that at-risk populations may benefit from additional early screening and workup for infertility.
Humans ; Male ; Adult ; Longitudinal Studies ; Middle Aged ; Semen Analysis ; Life Style ; Oligospermia/epidemiology* ; Azoospermia/epidemiology* ; Comorbidity ; Midwestern United States/epidemiology* ; Young Adult

BACKGROUND: Studies have shown that married couples often share similar lifestyles, as well as lifestyle-associated conditions such as diabetes, hypertension, and hyperlipidemia. This study aims to prospectively investigate the association between an individual's development of a non-communicable disease and the subsequent development of the same condition in their spouse. METHODS: This population-based cohort study utilized 12 waves of annual prospective surveys from 2005 onwards in Japan, with a discrete-time design. A total of 9,417 middle-aged couples (18,834 participants; discrete-time observations = 118,876) were included. Each participant whose spouse had developed one of six conditions was propensity score-matched with five controls whose spouses had not been diagnosed with the condition: diabetes [n = 1374 vs n = 6870], hypertension [n = 2657 vs n = 13285], hypercholesterolemia [n = 3321 vs n = 16605], stroke [n = 567 vs n = 2835], coronary heart disease (CHD) [n = 1093 vs n = 5465] or cancer [n = 923 vs n = 4615]. Using conditional logistic regression, we assessed participants' development of the same condition within three years following their spouse's diagnosis. RESULTS: Participants whose spouses had developed diabetes, hypertension, hypercholesterolemia, or CHD were more likely to develop the same condition within three years. The odds ratios (ORs) and 95% confidence intervals (CIs) were: 1.96 (1.53-2.50), 1.20 (1.06-1.36), 1.63 (1.47-1.81) and 1.43 (1.05-1.95), respectively. No significant associations were observed in stroke [1.69 (0.80-3.58)] or cancer [1.08 (0.75-1.54)]. CONCLUSION Spouses of individuals recently diagnosed with certain metabolic conditions are at a higher risk of developing those conditions themselves. These findings may provide valuable guidance for targeting and personalizing chronic disease screening and prevention efforts.
Humans ; Spouses/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Japan/epidemiology* ; Longitudinal Studies ; Noncommunicable Diseases/epidemiology* ; Prospective Studies ; Neoplasms/epidemiology* ; Diabetes Mellitus/epidemiology* ; Risk Factors ; Aged, 80 and over ; Adult ; Hypertension/epidemiology*

BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

BACKGROUND: Cancer is a major public health concern, particularly among middle-aged and elderly populations, who are disproportionately affected by rising cancer incidence. Environmental pollution has been identified as a significant risk factor for cancer development. China's Carbon Emission Trading Policy (CETP), implemented in pilot regions since 2013, aims to reduce carbon emissions and improve air quality. This study evaluates the impact of CETP on pan-cancer incidence, with a focus on its effects on specific cancer types and vulnerable populations. METHODS: This quasi-natural experiment utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and environmental data from the China National Environmental Monitoring Center (2011-2018). A staggered difference-in-differences (DID) model was employed to estimate the impact of CETP on cancer incidence. Robustness tests, including parallel trend tests, placebo analysis, and entropy balancing, validated the findings. Subgroup analyses were performed to assess the policy's heterogeneous effects based on gender, Body Mass Index (BMI), and smoking status. RESULTS: CETP implementation significantly reduced the incidence of six cancer types: endometrial, cervical, gastric, esophageal, breast, and lung cancers. Overall, pan-cancer incidence significantly declined post-policy implementation (CETP × POST: -47.200, 95% CI: [-61.103, -33.296], p < 0.001). The policy demonstrated stronger effects in highly polluted areas and among individuals with poorer mental health. Subgroup analysis revealed that females, individuals with lower BMI, and non-smokers experienced more substantial benefits. CONCLUSIONS CETP significantly reduces cancer incidence by improving environmental quality and influencing mental health, with particularly strong effects observed among high-risk populations. This study highlights the important role of environmental economic policies in mitigating cancer burden and promoting public health. Future research should further explore the long-term impacts of this policy and its applicability across different national and regional contexts.
Humans ; Incidence ; Neoplasms/epidemiology* ; China/epidemiology* ; Middle Aged ; Female ; Male ; Aged ; Air Pollution/legislation & jurisprudence* ; Carbon/analysis* ; Longitudinal Studies ; Air Pollutants/analysis* ; Environmental Exposure

BACKGROUND: Cardiovascular disease (CVD) is the predominant cause of mortality in China. However, the mechanisms linking sarcopenia to CVD remain poorly understood, particularly in normal-weight populations. Individuals with the absence of overweight or obesity may tend to experience missed opportunities for timely intervention. This study aimed to investigate the longitudinal association between sarcopenia and incidence of new-onset CVD in a normal-weight population, and to examine the mediating effect of functional limitation in this relationship. METHODS: We conducted a closed-cohort analysis using a nationwide sample of 4,147 middle-aged and older adults with normal weight in China. We performed Cox proportional hazards regression analysis to explore the associations of baseline sarcopenia with incident CVD. The difference method was applied to estimate the mediation proportion of functional limitation in this association. RESULTS: Over a mean follow-up period of 7.62 years, CVD occurred in 835 participants. In the multivariable-adjusted Cox model, individuals with sarcopenia exhibited a significantly higher likelihood of developing incident CVD compared to those without sarcopenia (adjusted hazard ratio [aHR] = 1.45, 95% confidence interval [CI]: 1.21-1.73, P < 0.001). Similar associations were observed for the incidence of heart disease and stroke. Functional limitation accounted for approximately 15.0% of the total effect of sarcopenia on incident CVD (P < 0.001). CONCLUSIONS Sarcopenia exerts both direct and indirect effects on incident CVD among middle-aged and older adults who are normal weight, with functional limitation serving as a significant mediator. Interventions targeting both sarcopenia and functional limitation may offer a promising strategy for enhancing cardiovascular health in this population.
Humans ; Sarcopenia/complications* ; China/epidemiology* ; Male ; Female ; Middle Aged ; Cardiovascular Diseases/etiology* ; Aged ; Incidence ; Cohort Studies ; Proportional Hazards Models ; Risk Factors ; Aged, 80 and over ; Longitudinal Studies

BACKGROUND: Depression among older adults is an important public health issue, and air and noise pollution have been found to contribute to exacerbation of depressive symptoms. This study examined the association of exposure to air and noise pollutants with clinically-newly-diagnosed depressive disorder. The mediating role of individual pro-inflammatory markers was explored. METHODS: We linked National Health Insurance claim data with 2998 healthy community-dwellers aged 55 and above who participated in the Healthy Aging Longitudinal Study between 2009 and 2013. Newly diagnosed depressive disorder was identified using diagnostic codes from the medical claim data. Pollutants were estimated using nationwide land use regression, including PM_2.5 and PM₁₀, carbon monoxide, ozone, nitrogen dioxide, sulfur dioxide, and road traffic noise. Cox proportional hazard models were employed to examine the association between pollutants and newly developed depressive disorders. The mediating effect of serum pro-inflammatory biomarkers on the relationship was examined. RESULTS: Among the 2998 participants, 209 had newly diagnosed depressive disorders. In adjusted Cox proportional hazard models, one interquartile range increase in PM_2.5 (8.53 µg/m³) was associated with a 17.5% increased hazard of developing depressive disorders. Other air pollutants and road traffic noise were not linearly associated with depressive disorder incidence. Levels of serum tumor necrosis factor receptor 1 mediated the relationship between PM_2.5 and survival time to newly onset depressive disorder. CONCLUSION PM_2.5 is related to an increased risk of newly developed depressive disorder among middle-aged and older adults, and the association is partially mediated by the pro-inflammatory marker TNF-R1.
Humans ; Particulate Matter/analysis* ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Aged ; Incidence ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Taiwan/epidemiology* ; Receptors, Tumor Necrosis Factor, Type I/blood* ; Proportional Hazards Models ; Biomarkers/blood* ; Depression/epidemiology* ; Aged, 80 and over ; Depressive Disorder/chemically induced* ; Risk Factors ; Air Pollution/adverse effects*