The magnetic resonance imaging-based vertebral bone quality scoring system: A novel method to evaluate endplate changes in patients with primary single-level disk herniation and Modic changes.

OBJECTIVES: This study aimed to investigate differences in vertebral fat distribution and bone density between patients with and without Modic changes (MCs) using a magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) scoring system. PATIENTS AND METHODS: In this retrospective study, 189 patients (95 males, 94 females; mean age: 54±2.2 years; range, 18 to 82 years) with primary single-level disk herniation were reviewed between June 2021 and June 2022. The patients were divided into the MC group (n=99) and the non-MC (NMC) group (n=90). The subcutaneous fat tissue thickness and bone mineral density were determined. The system consisted of two scores: the VBQ score, which reflected the fatty infiltration within the vertebral body, and the endplate bone quality (EBQ) score, which reflected the signal intensity (SI) of the upper and lower endplates. The EBQ score is a novel measurement that we introduced in this study. The VBQ and EBQ were measured and scored using MRI scans. The mean SI of the upper and lower endplates (endplate SI)/the bone marrow SI (marrow SI) was measured. RESULTS: There was a considerable difference in subcutaneous fat tissue thickness between the MC and NMC groups (1.40 vs. 1.16 cm, p=0.01). The EBQ scores of the L4 and L5 vertebrae and endplate SI/marrow SI of all vertebral body levels were significantly higher in the MC group. CONCLUSION: The occurrence of MCs in the lumbar spine may be associated with abnormal fat distribution. The distribution of vertebral fat in patients with MCs is distributed earlier in the upper and lower endplates of the vertebral body, and this trend is not observed in patients without MC. The thickness of subcutaneous fat tissue is a key factor in the occurrence of MCs.

Simultaneous Regulation of the Mechanical/Osteogenic Capacity of Brushite Calcium Phosphate Cement by Incorporating with Poly(ethylene glycol) Dicarboxylic Acid.

Brushite calcium phosphate cement (brushite CPC) is a prospective bone repair material due to its ideal resorption rates in vivo. However, the undesirable mechanical property and bioactivity limited its availability in clinic application. To address this issue, incorporating polymeric additives has emerged as a viable solution. In this study, poly(ethylene glycol) dicarboxylic acid, PEG(COOH), was synthesized and employed as the polymeric additive. The setting behavior, anti-washout ability, mechanical property, degradation rate, and osteogenic capacity of brushite CPC were regulated by incorporating PEG(COOH). The incorporation of PEG(COOH) with carboxylic acid groups demonstrated a positive effect on both mechanical properties and osteogenic activity in bone repair. This study offers valuable insights and suggests a promising strategy for the development of materials in bone tissue engineering.

Osteoporosis prediction in lumbar spine X-ray images using the multi-scale weighted fusion contextual transformer network.

Osteoporosis is a bone-related disease characterized by decreased bone density and mass, leading to brittle fractures. Osteoporosis assessment from radiographs using a deep learning algorithm has proven a low-cost alternative to the golden standard DXA. Due to the considerable noise and low contrast, automated diagnosis of osteoporosis in X-ray images still poses a significant challenge for traditional diagnostic methods. In this paper, an end-to-end transformer-style network was proposed, termed FCoTNet, to overcome the shortcoming of insufficient fusion of texture information and local features in the traditional CoTNet. To extract complementary geometric representations at each scale of the transformer module, we integrated parallel multi-scale feature extraction architectures in each unit layer of FCoTNet to utilize convolution to aggregate features from different receptive fields. Moreover, in order to extract small-scale texture features which were more critical to the diagnosis of osteoporosis in radiographs, larger fusion weights were assigned to the feature maps with small-size receptive fields. Afterward, the multi-scale global modeling was conducted by self-attention mechanism. The proposed model was first investigated on a private lumbar spine X-ray dataset with the 5-fold cross-validation strategy, obtaining an average accuracy of 78.29 ± 0.93 %, an average sensitivity of 69.72 ± 2.35 %, and an average specificity of 88.92 ± 0.67 % for the multi-classification of normal, osteopenia, and osteoporosis categories. We then conducted a controlled trial with five orthopedic clinicians to evaluate the clinical value of the model. The average clinician's accuracy improved from 61.50 ± 10.79 % unaided to 80.00 ± 5.92 % aided (18.50 % improvement), sensitivity improved from 64.38 ± 8.07 % unaided to 83.31 ± 5.43 % aided (18.93 % improvement), and specificity improved from 80.11 ± 4.72 % unaided to 89.94 ± 3.82 % aided (9.83 % improvement). Meanwhile, the prediction consistency among clinicians significantly improved with the assistance of FCoTNet. Furthermore, the proposed model showed good robustness on an external test dataset. These investigations indicate that the proposed deep learning model achieves state-of-the-art performance for osteoporosis prediction, which substantially improves osteoporosis screening and reduced osteoporosis fractures.

Glucose-Responsive Antioxidant Hydrogel Accelerates Diabetic Wound Healing.

Diabetic complications can be ameliorated by inhibiting excessive oxidative stress with antioxidants. To enhance therapeutic intervention, it is crucial to develop intelligent scaffolds for efficient delivery of antioxidants to diabetic wounds. This study introduces reversible boronic bonds to create an intelligent antioxidant hydrogel scaffold. This study modifies gelatin methacryloyl (GelMA) with 4-carboxyphenyboronic acid (CPBA) to synthesize a derivative of GelMA (GelMA-CPBA), and then photo cross-links GelMA-CPBA with (-)-epigallocatechin-3-gallate (EGCG) to form GelMA-CPBA/EGCG (GMPE) hydrogel. The GMPE hydrogel responds to changes in glucose levels, and more EGCG is released as glucose level increases due to the dissociation of boronic ester bonds. The GMPE hydrogel shows good biocompatibility and biodegradability, and its mechanical property is similar to that of the skin tissue. Both in vitro and in vivo results demonstrate that the GMPE hydrogel scaffolds effectively eliminate reactive oxygen species (ROS), reduce the inflammation, and promote angiogenesis, thereby improve collagen deposition and tissue remodeling during diabetic wound healing. This strategy offers new insight into glucose-responsive scaffolds, and this responsive antioxidan hydrogel scaffold holds great potential for the treatment of chronic diabetic wounds.

In Vitro and In Vivo Antitumor Assay of Mitochondrially Targeted Fluorescent Half-Sandwich Iridium(III) Pyridine Complexes.

Half-sandwich iridium(III) complexes show potential value in the anticancer field. However, complexes with favorable luminescence performance are rare, which limits further investigation of the anticancer mechanism. In this paper, 10 triphenylamine-modified fluorescent half-sandwich iridium(III) pyridine complexes {[(η5-Cpx)Ir(L)Cl2]} (Ir1-Ir10) were prepared and showed potential antiproliferative activity, effectively inhibiting the migration of A549 cells. Ir6, showing the best activity among these complexes, exhibited excellent fluorescence performance (absolute fluorescence quantum yield of 15.17%) in solution. Laser confocal detection showed that Ir6 followed an energy-dependent cellular uptake mechanism, specifically accumulating in mitochondria (Pearson co-localization coefficient of 0.95). A Western blot assay further confirmed the existence of a mitochondrial apoptotic channel. Additionally, Ir6 could arrest the cell cycle at the G2/M phase, catalyze NADH oxidation, reduce the mitochondrial membrane potential, induce an increase in the level of intracellular reactive oxygen species, and exhibit a mechanism of oxidation. An in vivo antitumor assay confirmed that Ir6 can effectively inhibit tumor growth and is safer than cisplatin.

Ambient temperature exposure and risk of outpatient visits for dermatologic diseases in Xinxiang, China: a time-series analysis.

The effect of ambient temperature on dermatologic diseases has received widespread attention. Previous studies have shown that ambient temperature might affect specific dermatologic diseases, but results were inconsistent. This study aims to assess the short-term effect of ambient temperature on outpatient visits due to dermatologic diseases (DMs) in Xinxiang, China. Daily DMs outpatient visits, mean temperature, mean relative humidity, and air pollution data of Xinxiang were retrieved from January 1, 2015, to December 31, 2018. A distributed lag nonlinear model (DLNM) was applied to analyze the effect of ambient temperature on DMs outpatients. We controlled several potential confounding factors such as the long-term trend, public holiday, day of the week, humidity, and air pollutants (NO2, PM2.5). Finally, two more stratification analysis was conducted by age and gender. A total of 164,270 outpatients of DMs were enrolled during our study, and the daily mean visits were 113. The estimated effect of temperature on DMs was nonlinear. Heat temperature would exacerbate outpatients of dermatologic diseases. With a reference median temperature (17 °C), the effect of temperature on DMs was most pronounced at lag0-14; exposure to heat (32 °C, 99th) was associated with 1.565 (95% CI: 1.266-1.934) increased risk of outpatients for DMs. Stratification analysis showed that citizens of young ages were susceptive to heat; both genders had a similar relationship between temperature and DMs risk. This study highlights that ambient temperature was associated with DMs outpatients; heat temperature might aggravate DMs risk. The health hazards of heat temperature required more attention, and more effective prevention measurements should be designed and implemented to curb global warming.

Proteome-wide identification of palmitoylated proteins in mouse testis.

The reversible lipid modification, S-palmitoylation, plays regulatory roles in various physiological processes, e.g., neuronal plasticity and organs development; however, the roles of palmitoylation engaged in testis have yet remained unexplored. Here, we used combined approaches of palm-proteomics, informatics and quantitative PCR to systematically analyze the expression of key enzymes related to protein palmitoylation and identify proteome-wide palmitoylated proteins during the processes of spermatogenesis. Specifically, different timepoints were chosen to collect samples to cover the initiation of meiosis (postnatal, P12), the appearance of the first batch of sperm (P36) and fully fertile status (P60) in mouse. Interestingly, our results showed that only a few enzymes related to protein palmitoylation are highly expressed at later stages (from P36 to P60), rather than in the earlier phase of testis development (P12). To focus on the molecular event of spermatogenesis, we examined the palm-proteomics of testes in P36 and P60 mouse. In total, we identified 4,883 palmitoylated proteins, among which 3,310 proteins match the published palmitoyl-proteome datasets and 1,573 proteins were firstly identified as palmitoylated proteins in this study. Informatics analysis suggested that palmitoylation is involved in events of protein transport, metabolic process, protein folding and cell adhesion, etc. Importantly, further analysis revealed that several networks of palmitoylated proteins are closely associated with sperm morphology and motility. Together, our study laid a solid ground for understanding the roles of protein palmitoylation in spermatogenesis for future studies.

A study of three-dimensional reconstruction and printing models in two cases of soft tissue sarcoma of the thigh.

PURPOSE: The aim of our study was to demonstrate the value of three-dimensional (3D) reconstruction and three-dimensional printing (3DP) models in two cases of soft tissue sarcoma (STS) of the thigh. MATERIALS AND METHODS: Two patients with STS were recruited and underwent enhanced CT and MRI scans. Then, the 3D models were reconstructed and printed using the obtained data, and five experts were invited to assess the segmentation quality. In addition, 34 junior, intermediate and senior general surgeons were recruited to demonstrate the value of 3D models in preoperative planning and invited five surgeons to complete the assessment of 3D models-assisted intraoperative navigation. Finally, 32 interns were enrolled to explore the significance of 3D models in medical education. RESULTS: All experts agree with the accuracy of the 3D models. The application of 3D models in preoperative planning improved the understanding of general surgeons (P = 0.000, P = 0.000, P = 0.000). After the planning tools were exchanged between the two groups, senior surgeons in group A showed more significant improvements in performance than junior and intermediate surgeons in group A (P = 0.001, P = 0.006). Surgeons unanimously agree on the value of 3D models in intraoperative navigation. When applied for the education of medical interns, these models could enhance their understanding of pathologic anatomies (P = 0.036). CONCLUSION: In two operations for STS of the thigh with complex adjacencies, our study demonstrates that 3D models are of great value for preoperative planning, intraoperative navigation and medical education. More importantly, these models were more helpful to senior general surgeons.

MiR-502 Suppresses TNF-α-Induced Nucleus Pulposus Cell Apoptosis by Targeting TARF2.

Intervertebral disc degeneration (IVDD) is a common cause of low back pain. This study is aimed at investigating the role of microRNAs (miRNAs) in regulating human nucleus pulposus (NP) cell injury induced by tumor necrosis factor- (TNF-) α in IVDD. In this study, we induced NP cells with 20 ng/mL TNF-α in vitro, which promoted the obvious apoptosis of NP cells and the activation of nuclear transcription factor (NF)-κB. In contrast, using the specific NF-κB inhibitor BAY 11-7082 to treat cells greatly impaired the activation of NF-κB and increased the sensitivity of NP cells to TNF-α-induced apoptosis. Moreover, both TNF-α and BAY 11-7082 treatments were associated with marked miRNA dysregulation, with miR-502 being upregulated by TNF-α treatment and downregulated by BAY 11-7082 treatment, respectively. And the overexpression of miR-502 enhanced NF-κB activation and suppressed apoptosis of human NP cells induced by TNF-α, whereas the opposite was observed following miR-502 inhibition. Last, through bioinformatic analyses and luciferase reporter gene experiments, we identified TRAF2, an important activator of NF-κB, as a miR-502 target gene. Similarly, siRNA-mediated knockdown of the TRAF2 expression also suppressed TNF-α-induced apoptosis and enhanced NF-κB activation. Our findings provide evidence indicating that miR-502 is a key regulator of apoptosis of human NP cells induced by TNF-α by targeting TRAF2 and activating NF-κB.

Association of dyslipidaemia with osteoporosis in postmenopausal women.

OBJECTIVE: To assess the association of dyslipidaemia with osteoporosis in postmenopausal women. METHODS: Data from 160 postmenopausal women with newly diagnosed osteoporosis (osteoporosis group) and 156 healthy controls (control group) were retrospectively reviewed from 2016 to 2020. The primary outcomes were laboratory values assessed by a multivariate binary logistic regression model. RESULTS: Factors that greatly increased the risk of being in the osteoporosis group included high low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) levels. The osteoporosis group had lower HDL and higher LDL levels than the control group. A multivariate binary logistic regression model showed that lower HDL and higher LDL levels were the only variables that were significantly associated with osteoporosis (odds ratio 1.86, 95% confidence interval: 3.66-4.25 and odds ratio 1.47, 95% confidence interval: 1.25-2.74, respectively). CONCLUSION: Low HDL and high LDL levels may be associated with the occurrence of osteoporosis in postmenopausal women.

Risk factors of cage nonunion after anterior cervical discectomy and fusion.

The aim of our study was to explore risk factors of cage nonunion after anterior cervical discectomy and fusion (ACDF).295 patients underwent ACDF in our hospital between Jan. 2014 and Jan. 2017. Of them, 277 patients suffered cage union (union group, UG) after 6-month follow-up and 18 did not (nonunion group, NG). We collected possible factors including gender, history of smoking, alcohol, hypertension, heart disease, diabetes, body mass index, diagnose, and preoperative visual analog scale -neck, visual analog scale-arm, neck disability index (NDI) and Japanese Orthorpaedic Association, surgical duration, blood loss, fusion levels, superior fusion segment, angle of C2-C7, range of motion for C2-C7, C2-C7 sagittal vertical axis and T1 slope. We performed univariable and multivariable analysis to compare data in 2 groups.The rate of cage nonunion after ACDF was 6.1% (18 of 295) in our study. The outcome of univariable analysis showed that age (63.5 ±â€Š10.1), angle of C2-C7 (18.0 ±â€Š4.6), range of motion of C2-C7 (32.5 ±â€Š7.7), C2-C7 sagittal vertical axis (17.9 ±â€Š4.3) and T1 slope (22.1 ±â€Š5.3) were higher in NG than these (59.4 ±â€Š9.2, 16.2 ±â€Š4.5, 30.2 ±â€Š6.9,16.1 ±â€Š4.0, 20.9 ±â€Š4.9) in UG. Additionally, patients with osteoporosis had markedly higher rate of cage nonunion after ACDF than those without. What's more, the multivariable analysis implied the same results with univariable analysis.Many factors could predict cage nonunion after ACDF. Cervical sagittal parameters play an important role in cage nonunion after ACDF. We hope that we can provide some guidance for spine surgeon before performing ACDF.

Genome-wide scan identified genetic variants associated with skin aging in a Chinese female population.

BACKGROUND: The progression of human skin aging has a strong genetic basis. However, recent studies have mainly focused on Caucasian populations and we have thus performed a genetic association study on skin aging signs in Han Chinese population. OBJECTIVE: To investigate genetic risk factors in skin aging in Han Chinese female, we performed a genome-wide association study. METHODS: We collected genotype data from 1534 Han Chinese female from Taizhou cohort and evaluated 15 skin aging phenotypes by using the validated skin aging SCINEXA™ score. Genetic associations were tested by linear and logistic regression analyses and adjusted for potential confounders. RESULTS: Six genomic regions significantly associated with a risk for skin aging were revealed : 6q24.2 (rs3804540, P=4.6×10-9, additive model) with size of pigmented spots on forehead, 10q26.13 (rs4962295, P=1.9 ×10-8, additive model) with wrinkles under eyes, 15q21.1 (rs28392847, P=1.6×10-8, additive model) with crow's feet, 2p25.1 (rs191497052, P=5.5×10-9, dominant model) with telangiectasia, 13q34 (rs3825460, P=3.7×10-8, dominant model) with size of pigmented spots on cheeks and 16p13.11(rs76053540, P=5.0×10-9, dominant model) with nasolabialfold. The signal on 15q21.1 was replicated in the meta-analysis with two independent Caucasian cohorts (P=8.6×10-10). We have also successfully replicated in our cohort an association between SNP rs1048943 of gene CYP1A1 (P=7.1 × 10-4) and pigmented spots on cheeks previously described in Caucasian cohort. CONCLUSIONS: Our study has identified new genetic risk factors for signs of skin aging in the Han Chinese. This study suggests there are differences in genetic susceptibility to skin aging between Caucasians and the Han Chinese.

Lateral ventriculo-peritoneal shunt treating delayed cerebrospinal fluid leak after cervical laminoplasty: Case report.

RATIONALE: Delayed cerebrospinal fluid (CSF) leak is a rare and terrible complication after cervical surgery, potentially causing morbidity or even threatening life. PATIENT CONCERNS: A 55-year-old Chinese male, with a history of hypertension for 8 years, complained of numbness and weakness of both upper limbs for 10 years. Strength of right upper limb triceps and wrist extensor muscle was slight weakness. Bilateral Hoffman sign was positive. Cervical magnetic resonance imaging (MRI) indicated multilevel cervical spondylotic myelopathy. We performed cervical laminoplasty for that patient on August 23, 2018. Nevertheless, he abruptly complained of dizziness and vision, but the wound condition was good. Cervical MRI showed delayed cerebrospinal fluid leak on October 15, 2018. DIAGNOSES: He was diagnosed with delayed CSF leak after cervical laminoplasty. INTERVENTIONS: We performed lateral ventriculo-peritoneal shunt (LVPS) for that patient on October 17, 2018. OUTCOMES: At 3-month follow-up, the treatment has a good outcome and there is no recurrence of clinical symptoms. LESSONS: Delayed CSF leak after cervical laminoplasty is rare. Once diagnosed, surgery is needed as soon as possible. LVPS has been proven an effective treatment for this server disease.

Infection of finger caused by Morganella morganii leading to digital amputation: A case report.

RATIONALE: Digital infection is a common disease in clinic, featured by pain and swelling of digits. As far as we know, no article has reported a case of digital infected by Morganella morganii. PATIENT CONCERNS: A 58-year-old Chinese female complains about whitlow with pain and swelling for 2 weeks. She has a history of diabetes for 10 years. She received incision and drainage before coming to our hospital and preoperative X-ray of left ring finger presented no bone eroded. DIAGNOSIS: She is diagnosed with infection of ring finger caused by M morganii in our hospital. INTERVENTIONS: We perform aggressive operative debridement and drainage firstly. Meanwhile, we provide tissue samples for diagnosis and the result indicates M morganii infection. Then, she is treated with anti-infection therapy and regulation of diabetes. However, 1 week after first surgery, her condition deteriorate presenting bone erosion in distal phalanx of ring finger from X-ray. Considering severity of illness, we decide to perform digital amputation. OUTCOMES: At 3-month follow-up, the patient has a satisfactory result and X-ray shows no bone eroded. LESSONS: Clinicians should consider M morganii, which is rare in hand infection, as a cause of digital infection. This case reminds us that some whitlow is dangerous, amputation should be considered if necessary.

Factors predicting adjacent segment disease after anterior cervical discectomy and fusion treating cervical spondylotic myelopathy: A retrospective study with 5-year follow-up.

The purpose of this study is to explore perioperative factors predicting symptomatic adjacent segment disease (ASD) after anterior cervical discectomy and fusion (ACDF) for patients with cervical spondylotic myelopathy (CSM) at 5-year follow-up.This study included 356 patients who underwent ACDF for CSM from Jan.2011 to Jan.2013. Up to Jan. 2018, 39 patients suffered from ASD and 317 did not. Assessments include: age, sex, body mass index (BMI), diabetes, smoking, alcohol, duration of symptoms, preoperative Cobb angle of C2 to 7, T1 slope, C2 to 7 range of motion (C2-7 range of motion [ROM]), C2 to 7 sagittal vertical axis (C2-7 SVA), fusion level involved, superior fusion segment, high signal intensity on T2-WI of magnetic resonance imaging (MRI), preoperative visual analogue scale (VAS)-neck, VAS-Arm, Neck Disability Index (NDI) and Japanese Orthopaedic Association (JOA). Factors were processed by univariate analysis and multivariate linear regression.Data analyzed by univariate and multivariate analysis shows that age (68.9 years old), duration of symptoms (18.8 months), superior fusion segment, more fusion level involved (2.7), high signal intensity on T2-WI (17 of 39 patients), Cobb angle of C2 to C7 (18.7°), C2 to C7 SVA (31.0 mm), T1 slope (28.4°), preoperative VAS-neck (5.2), VAS-Arm (5.6) and NDI (36.7) in ASD group are significantly higher than those in non-ASD group, however, preoperative JOA (8.2 vs 11.2, P < .001) has an opposite trend in 2 groups.The rate of ASD after ACDF is 10.9% in 5-year follow up. Patients with cervical sagittal imbalance, advanced age and sever state of CSM, which have a positive relation with ASD before surgery should be paid attention for surgeons.

Indoor PM2.5 exposure affects skin aging manifestation in a Chinese population.

Traffic-related air pollution is known to be associated with skin aging manifestations. We previously found that the use of fossil fuels was associated with skin aging, but no direct link between indoor air pollutants and skin aging manifestations has ever been shown. Here we directly measured the indoor PM2.5 exposure in 30 households in Taizhou, China. Based on the directly measured PM2.5 exposure and questionnaire data of indoor pollution sources, we built a regression model to predict the PM2.5 exposure in larger datasets including an initial examination group (N = 874) and a second examination group (N = 1003). We then estimated the association between the PM2.5 exposure and skin aging manifestations by linear regression. In the initial examination group, we showed that the indoor PM2.5 exposure levels were positively associated with skin aging manifestation, including score of pigment spots on forehead (12.5% more spots per increase of IQR, P-value 0.0371), and wrinkle on upper lip (7.7% more wrinkle on upper lip per increase of IQR, P-value 0.0218). The results were replicated in the second examination group as well as in the pooled dataset. Our study provided evidence that the indoor PM2.5 exposure is associated with skin aging manifestation in a Chinese population.

Genetic variants associated with skin aging in the Chinese Han population.

BACKGROUND: The progression and manifestation of human skin aging has a strong genetic basis; however, most of the supporting evidence has been gathered in Caucasian populations. The genetic contribution to the variation in skin aging in non-Caucasian populations is poorly understood. OBJECTIVE: To investigate the genetic risk factors of relevance for skin aging in East Asians, we conducted the first candidate gene study for signs of skin aging in Han Chinese. METHODS: We collected skin aging and genotype data in 502 female Han Chinese from the Taizhou cohort. We evaluated skin aging by the validated skin aging score SCINEXA™. Confounding factors were assessed through a questionnaire. We obtained the genotype data for 21 candidate SNPs and for a further 509 SNPs from 16 related candidate genes. Associations were tested by linear and logistic regression analyses and adjusted for potential confounders. RESULTS: Our candidate study found a significant association between SNP rs2066853 in exon 10 of the aryl hydrocarbon receptor gene AHR and crow's feet. In addition, we found a significant association between SNP rs10733310 in intron 5 of BNC2 and pigment spots on the arms, and between SNP rs11979919, 3kb downstream of COL1A2, and laxity of eyelids. CONCLUSIONS: Our results identified genetic risk factors for signs of skin aging (pigmentation, wrinkles or laxity) in Han Chinese. We also found that the manifestation of skin aging is further modified by anatomical site. Together with previous work, our results also suggest that different genetic variants could be responsible for distinct skin aging signs characteristic of Caucasians compared to East Asians.