Supplementary Material for: Blood profiles of community-dwelling people with sarcopenia: analysis based on the China Health and Retirement Longitudinal Study

Introduction Routine blood factors can be economic and easily accessible candidates for sarcopenia screening and monitoring. The associations between sarcopenia and routine blood factors remain unclear. This study aimed to examine sarcopenia and blood factor associations based on a nation-wide cohort in China. Methods 1307 participants and 17 routine blood indices were selected from two waves (Year 2011 and Year 2015) of the China Health and Retirement Longitudinal Study (CHARLS). The diagnosis of sarcopenia was based on the criteria proposed by Asian Working Group for Sarcopenia (AWGS 2019). Generalized mixed-effects models were performed for association analyses. A logistic regression (LR) model was conducted to examine the predictive power of identified significant blood factors for sarcopenia. Results A higher sarcopenia risk was cross-sectionally associated with elevated blood concentrations of high-sensitivity C-reactive protein (hsCRP) (OR = 1.030, 95%CI [1.007, 1.053]), glycated hemoglobin (HbA1c) (OR = 1.407, 95%CI [1.126, 1.758]) and blood urea nitrogen (BUN) (OR = 1.044, 95%CI [1.002, 1.089]), and a decreased level of glucose (OR = 0.988, 95%CI [0.979, 0.997]). A higher baseline hsCRP value (OR = 1.034, 95%CI [1.029, 1.039]) and a greater over time change in hsCRP within four years (OR = 1.034, 95%CI [1.029, 1.039]) were associated with a higher sarcopenia risk. A higher BUN baseline value was related to a decreased sarcopenia risk over time (OR = 0.981, 95%CI [0.976,0.986]), while a greater over time changes in BUN (OR = 1.034, 95%CI [1.029,1.040]) and a smaller over time change in glucose (OR = 0.992, 95%CI [0.984, 0.999]) within four years were also related to a higher sarcopenia risk. LR based on significant blood factors (i.e., hsCRP, HbA1c, BUN, and glucose), and sarcopenia status in Year 2015 yielded an area under the curve (AUC) of 0.859 (95% CI 0.836-0.882). Conclusion Routine blood factors involved in inflammation, protein metabolism, and glucose metabolism are significantly associated with sarcopenia. In clinical practice, plasma hsCRP, BUN, blood sugar levels, sex, age, marital status, height, and weight might be helpful for sarcopenia evaluation and monitoring

Supplementary Material for: Association of <b><i>HSD17B3</i></b> and <b><i>HSD3B1</i></b> Polymorphisms with Acne Vulgaris in Southwestern Han Chinese

Acne vulgaris is a very common skin disorder. Previous studies have indicated that genetic background factors play key roles in the onset of acne. Our previous investigation implicated several genes in the androgen metabolism pathway with acne vulgaris in the Han Chinese population. Thus, we further investigated genes and genetic variants that play important roles in this pathway for their relationship with the pathology of acne. In this study, a total of 610 subjects, including 403 acne patients and 207 healthy controls, were genotyped for 15 single-nucleotide polymorphisms in <i>HSD3B1</i> and <i>HSD17B3</i> genes. This study shows that rs6428829 in <i>HSD3B1</i> was associated with acne vulgaris in Han patients from Southwest China, even after adjusting for age and sex. The GG genotype was associated with an increased risk of acne vulgaris (p < 0.05) and G allele carriers were associated with an increased risk of acne vulgaris (p < 0.05). In addition, the haplotype AAT in <i>HSD3B1</i> significantly increased the risk of acne vulgaris in the case-control study (p < 0.05). Furthermore, for another gene in this pathway, <i>HSD17B3</i>, the haplotype H8 was significantly associated with an increased risk of acne vulgaris. Based on these analyses, our study indicates that the cutaneous androgen metabolism-regulated genes <i>HSD3B1</i> and <i>HSD17B3</i> increase the susceptibility to acne vulgaris in Han Chinese from Southwest China

Supplementary Material for: Musculoskeletal ultrasound evaluates renal injury and predicts renal outcome in patients with gout

Introduction. Kidney injury diagnosis is often delayed in patients with gout. We aimed to determine the characteristics of gout patients with CKD using musculoskeletal ultrasound (MSUS) and whether MSUS could be used as an auxiliary assessment to evaluate kidney injury and predict renal outcome in patients with gout. Methods. Clinical information, laboratory indicators and MSUS findings were collected and compared between gout-only patients (gout-CKD) and gout patients with CKD (gout+CKD). Multivariate logistic regression was applied to identify risk factors for clinical and MSUS characteristics in both groups. Correlation analysis between MSUS signs and kidney-related indicators was performed, and the effects of MSUS characteristics on renal prognosis were evaluated. Results. In total, 176 patients with gout were included, namely, 89 gout-CKD and 87 gout+CKD cases. After adjusting for confounders, the gout patients with CKD showed more frequent episodes in the previous year, higher ultrasound semiquantitative scores and more tophi than gout patients without CKD. Additionally, the number of tophi, bone erosion and synovial hypertrophy measured by MSUS were found to be negatively correlated with the eGFR. The existence of tophi was independently associated with an increased risk of a ≥10% decline in eGFR in the first-year follow-up (OR 3.56, 95% CI 1.382-9.176). Conclusions. Ultrasound-detected tophi, bone erosion and synovial hypertrophy were associated with kidney injury in gout patients. The existence of tophi was associated with faster renal function deterioration. MSUS could be a potential auxiliary diagnostic method to evaluate kidney injury and predict renal outcome in gout patients

Supplementary Material for: Depression trajectories, genetic risk, and cognitive performance in older adults: multilevel model with a 10-year longitudinal cohort

Background: Cognitive performance in older ages is strongly affected by individuals’ genetic predispositions. We investigated whether depression trajectories were associated with subsequent cognitive performance independent of participants’ genetic predispositions. Methods: Participants from the Health and Retirement Study with European ancestry and aged over 50 were included in the analysis. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale, and the 6-year trajectories were fitted using latent class linear mixed models. Linear multilevel regression was applied to model the associations between depression trajectory and subsequent cognitive performance. Stratified analyses were performed to investigate these associations in participants with different genetic predispositions of cognitive performance and APOE ε4 allelic status. Results: A total of 5942 eligible participants were included in the study. Four depression trajectories were identified. Compared with the non-depression trajectory, all other depression trajectories were associated with worse cognitive performance (β [95% CI]: mild-depression trajectory: -0.20 [-0.56, -0.06], p = 0.007; worsening-depression trajectory: -0.29 [-0.47, -0.12], p = 0.001; persistent-depression trajectory: -0.32 [-0.53, -0.13], p = 0.001). Although these associations were independent of participants' inherent genetic risk, the participants with a low polygenetic score for cognitive performance were more likely to have an enhanced association between depression trajectories and cognitive decline. Similar relationships were also found in APOE ε4 noncarriers. Conclusion: Among older participants with European ancestry, even a mild-depression trajectory was associated with worse cognitive performance. Early intervention in participants with any degree of depression might benefit regarding preventing cognitive performance decline

Supplementary Material for: Regulation of IgA Class Switch Recombination in Immunoglobulin A Nephropathy: Retinoic Acid Signaling and BATF

<p><b><i>Background:</i></b> Immunoglobulin (Ig) A nephropathy (IgAN) is the finding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Increasing evidence suggested that retinoic acid (RA) signaling selectively induces IgA isotype switching and basic leucine zipper transcription factor, ATF-like (BATF) controls the global regulators of class switch recombination (CSR) in lymphocytes. Great effort has been paid to identify whether impaired immune regulation along the ‘mucosa-bone marrow (BM) axis' play an important role in the pathogenesis of IgAN. <b><i>Methods:</i></b> The aim of the study was to investigate the expression of all-trans-RA (ATRA) and BATF, and to identify their impact on IgA CSR in IgAN patients and rat animal models. Blood samples and tonsillar tissue specimens were obtained from 22 patients with IgAN and 24 patients with chronic tonsillitis as control. <b><i>Results:</i></b> Immunohistochemical, RT-PCR and western blotting examination revealed that RA signaling and BATF productions are activated in IgAN patients compared with controls. Lipopolysaccharide and α-hemolytic streptococcus stimulation upregulated RA receptor (RAR) and BATF expression, promote IgA CSR and ATRA productions in tonsil mononuclear cells. RAR alpha (RARα) or BATF siRNA decreases IgA expression. We also built IgAN rat models and found that RARα, BATF and activation-induced cytidine deaminase were upregulated in the peripheral blood, spleen and BM. With ATRA (500 μg/kg body weight) treatment for 8 weeks, IgA deposition on glomeruli and mesangial cells proliferation increased. It also revealed that ATRA activated BATF and IgA CSR in vivo. <b><i>Conclusion:</i></b> These data point toward the role of RA signaling together with BATF in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with neoantigen results in impaired mucosal and systemic IgA responses.</p

Supplementary Material for: Prognostic Value of the Delivery Dialysis Dose on Twice-Weekly Hemodialysis Patients

<p><b><i>Background:</i></b> Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. <b><i>Methods:</i></b> This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (<i>n</i> = 98) and standard-dose groups (<i>n</i> = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). <b><i>Results:</i></b> The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (<i>p</i> < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (<i>p</i> = 0.431). No difference was found in overall survival between the 2 groups (<i>p</i> = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (<i>p</i> = 0.029). <b><i>Conclusions:</i></b> Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.</p

PowerPoint Slides for: Prognostic Value of the Delivery Dialysis Dose on Twice-Weekly Hemodialysis Patients

<p><b><i>Background:</i></b> Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. <b><i>Methods:</i></b> This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (<i>n</i> = 98) and standard-dose groups (<i>n</i> = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). <b><i>Results:</i></b> The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (<i>p</i> < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (<i>p</i> = 0.431). No difference was found in overall survival between the 2 groups (<i>p</i> = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (<i>p</i> = 0.029). <b><i>Conclusions:</i></b> Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.</p