Multiple transcriptome analyses reveal mouse testis developmental dynamics.

The testes are the organs of gamete production and testosterone synthesis. Up to date, no model system is available for mammalian testicular development, and only few studies have characterized the mouse testis transcriptome from no more than three postnatal ages. To describe the transcriptome landscape of the developing mouse testis and identify the potential molecular mechanisms underlying testis maturation, we examined multiple RNA-seq data of mouse testes from 3-week-old (puberty) to 11-week-old (adult). Sperm cells appeared as expected in 5-week-old mouse testis, suggesting the proper sample collection. The principal components analysis revealed the genes from 3w to 4w clustered away from other timepoints, indicating they may be the important nodes for testicular development. The pairwise comparisons at two adjacent timepoints identified 7,612 differentially expressed genes (DEGs), resulting in 58 unique mRNA expression patterns. Enrichment analysis identified functions in tissue morphogenesis (3-4w), regulation of peptidase activity (4-5w), spermatogenesis (7-8w), and antigen processing (10-11w), suggesting distinct functions in different developmental periods. 50 hub genes and 10 gene cluster modules were identified in the testis maturation process by protein-protein interaction (PPI) network analysis, and the miRNA-lncRNA-mRNA, miRNA-circRNA-mRNA and miRNA-circRNA-lncRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed. The results suggest that testis maturation is a complex developmental process modulated by various molecules, and that some potential RNA-RNA interactions may be involved in specific developmental stages. In summary, this study provides an update on the molecular basis of testis development, which may help to understand the molecular mechanisms of mouse testis development and provide guidance for mouse reproduction.

Y-STR analysis of highly degraded DNA from skeletal remains over 70 years old.

The goal of the following study is to clarify whether the skeletal remains over 70 years old from missing persons and their alleged relatives shared identical Y-STR loci. Nowadays, advances in ancient DNA extraction techniques and approaches of using multiple different Y-STRs have significantly increased the possibility of obtaining DNA profiles from highly degraded skeletal remains. Given the ages and conditions of the skeletal remains, ancient DNA extraction methods can be used to maximize the probability of DNA recovery. Considering that information about distant relatives is more relevant for long-term missing persons and alleged family members are male, Y-STR loci analysis is considered the most appropriate and informative approach for determining paternal lineage relationship. In this study, Y-STR genotypes obtained from these alleged relatives were identical to each other and to the alleles of missing persons' consensus profiles at more than 22 loci examined, whilst not being found in Y-STR population database from Y-Chromosome STR Haplotype Reference Database. Therefore, Missing Person No.7 and Missing Person No.18 have a patrilineal relationship with reference samples from Family1 and Family2, respectively. In addition, the fact that Y-STR haplotypes obtained from skeletal remains of missing persons and reference samples are not found in the Han Chinese people from East Asian demonstrates its rarity and further supports a paternal lineage relationship amongst them.

Machine learning based biomarker discovery for chronic kidney disease-mineral and bone disorder (CKD-MBD).

INTRODUCTION: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by bone abnormalities, vascular calcification, and some other complications. Although there are diagnostic criteria for CKD-MBD, in situations when conducting target feature examining are unavailable, there is a need to investigate and discover alternative biochemical criteria that are easy to obtain. Moreover, studying the correlations between the newly discovered biomarkers and the existing ones may provide insights into the underlying molecular mechanisms of CKD-MBD. METHODS: We collected a cohort of 116 individuals, consisting of three subtypes of CKD-MBD: calcium abnormality, phosphorus abnormality, and PTH abnormality. To identify the best biomarker panel for discrimination, we conducted six machine learning prediction methods and employed a sequential forward feature selection approach for each subtype. Additionally, we collected a separate prospective cohort of 114 samples to validate the discriminative power of the trained prediction models. RESULTS: Using machine learning under cross validation setting, the feature selection method selected a concise biomarker panel for each CKD-MBD subtype as well as for the general one. Using the consensus of these features, best area under ROC curve reached up to 0.95 for the training dataset and 0.74 for the perspective dataset, respectively. DISCUSSION/CONCLUSION: For the first time, we utilized machine learning methods to analyze biochemical criteria associated with CKD-MBD. Our aim was to identify alternative biomarkers that could serve not only as early detection indicators for CKD-MBD, but also as potential candidates for studying the underlying molecular mechanisms of the condition.

Population genetic analyses of Eastern Chinese Han nationality using ForenSeq™ DNA Signature Prep Kit.

Currently, the most commonly used method for human identification and kinship analysis in forensic genetics is the detection of length polymorphism in short tandem repeats (STRs) using polymerase chain reaction (PCR) and capillary electrophoresis (CE). However, numerous studies have shown that considerable sequence variations exist in the repeat and flanking regions of the STR loci, which cannot be identified by CE detection. Comparatively, massively parallel sequencing (MPS) technology can capture these sequence differences, thereby enhancing the identification capability of certain STRs. In this study, we used the ForenSeq™ DNA Signature Prep Kit to sequence 58 STRs and 94 individual identification SNPs (iiSNPs) in a sample of 220 unrelated individuals from the Eastern Chinese Han population. Our aim is to obtain MPS-based STR and SNP data, providing further evidence for the study of population genetics and forensic applications. The results showed that the MPS method, utilizing sequence information, identified a total of 486 alleles on autosomal STRs (A-STRs), 97 alleles on X-chromosome STRs (X-STRs), and 218 alleles on Y-chromosome STRs (Y-STRs). Compared with length polymorphism, we observed an increase of 260 alleles (157, 31, and 72 alleles on A-STRs, X-STRs, and Y-STRs, respectively) across 36 STRs. The most substantial increments were observed in DYF387S1 and DYS389II, with increases of 287.5% and 250%, respectively. The most increment in the number of alleles was found at DYF387S1 and DYS389II (287.5% and 250%, respectively). The length-based (LB) and sequence-based (SB) combined random match probability (RMP) of 27 A-STRs were 6.05E-31 and 1.53E-34, respectively. Furthermore, other forensic parameters such as total discrimination power (TDP), cumulative probability of exclusion of trios (CPEtrio), and duos (CPEduo) were significantly improved when using the SB data, and informative data were obtained for the 94 iiSNPs. Collectively, these findings highlight the advantages of MPS technology in forensic genetics, and the Eastern Chinese Han genetic data generated in this study could be used as a valuable reference for future research in this field.

Construction of recombinant Lactococcus expressing thymosin and interferon fusion protein and its application as an immune adjuvant.

BACKGROUND: In recent years, biosafety and green food safety standards have increased the demand for immune enhancers and adjuvants. In the present study, recombinant food-grade Lactococcus lactis (r-L. lactis-Tα1-IFN) expressing thymosin Tα1 and chicken interferon fusion protein was constructed. RESULTS: The in vitro interactions with macrophages revealed a mixture of recombinant r-L. lactis-Tα1-IFN could significantly activate both macrophage J774-Dual™ NF-κB and interferon regulator (IRF) signaling pathways. In vitro interactions with chicken peripheral blood mononuclear cells (PBMCs) demonstrated that a mixture of recombinant r-L. lactis-Tα1-IFN significantly enhanced the expression levels of interferon (IFN)-γ, interleukin (IL)-10, CD80, and CD86 proteins in chicken PBMCs. Animal experiments displayed that injecting a lysis mixture of recombinant r-L. lactis-Tα1-IFN could significantly activate the proliferation of T cells and antigen-presenting cells in chicken PBMCs. Moreover, 16S analysis of intestinal microbiota demonstrated that injection of the lysis mixture of recombinant r-L. lactis-Tα1-IFN could significantly improve the structure and composition of chicken intestinal microbiota, with a significant increase in probiotic genera, such as Lactobacillus spp. Results of animal experiments using the lysis mixture of recombinant r-L. lactis-Tα1-IFN as an immune adjuvant for inactivated chicken Newcastle disease vaccine showed that the serum antibody titers of the experimental group were significantly higher than those of the vaccine control group, and the expression levels of cytokines IFN-γ and IL-2 were significantly higher than those of the vaccine control group. CONCLUSION: These results indicate that food-safe recombinant r-L. lactis-Tα1-IFN has potential as a vaccine immune booster and immune adjuvant. This study lays the foundation for the development of natural green novel animal immune booster or immune adjuvant.

Association between hearing loss and physical performance in patients on maintenance hemodialysis.

Background: The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = -0.356, p < 0.001 and r = -0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73-1.81), 1.69 (1.07-2.70), and 2.87 (1.69-4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Genetic Variations Within METTL16 and Susceptibility to Sudden Cardiac Death in Chinese Populations With Coronary Artery Disease.

Despite recent advances in the prevention of coronary heart disease, the mortality rate of sudden cardiac death (SCD) remains high, which has become a substantial public health issue. Methyltransferase-like protein 16 (METTL16), as a newly discovered m6A methyltransferase, may be related to cardiovascular diseases. In the present study, a 6-base-pair insertion/deletion (del) polymorphism (rs58928048) in the METTL16 3'untranslated region (3'UTR) region was chosen as a candidate variant based on the findings of systematic screening. Then, the association between rs58928048 and susceptibility to SCD originating from coronary artery disease (SCD-CAD) in the Chinese population was investigated by conducting a case-control study that included 210 SCD-CAD cases and 644 matched healthy controls. Logistic regression analysis showed that the del allele of rs58928048 significantly reduced the SCD risk (odds ratio 0.69, 95% confidence interval 0.55 to 0.87, p = 0.00177). Genotype-phenotype correlation studies in human cardiac tissue samples demonstrated that the lower messenger RNA and protein expression levels of METTL16 were associated with the del allele of rs58928048. In the dual-luciferase activity assay, the del/del genotype exhibited lower transcriptional competence. Further bioinformatic analysis showed that the rs58928048 del variant may create transcription factor binding sites. Finally, pyrosequencing showed that the genotype of rs58928048 was related to the methylation status of the 3'UTR region of METTL16. Taken together, our findings provide evidence that rs58928048 may affect the methylation status of the 3'UTR region of METTL16 and subsequently affect its transcriptional activity thus as a potential genetic risk marker for SCD-CAD.

Pheochromocytoma crisis with refractory Acute Respiratory Distress Syndrome (ARDS), Takotsubo syndrome, emergency adrenalectomy, and need for Extracorporeal Membrane Oxygenation (ECMO) in a previously undiagnosed and asymptomatic patient, due to the use of metoclopramide.

BACKGROUND: Pheochromocytoma (PCC) crisis is a rare life-threatening endocrine emergency. The diagnosis and treatment of PCC crisis, with acute respiratory distress syndrome (ARDS) as the first manifestation, is highly challenging, and traditional PCC management strategies are no longer suitable for these patients. CASE PRESENTATION: A 46-year-old female patient was admitted to the Intensive Care Unit (ICU) following sudden-onset acute respiratory distress and subsequent initiation of mechanical ventilation via endotracheal intubation. She was initially suspected of having a PCC crisis through the bedside critical care ultrasonic examination protocol. The computed tomography examination revealed a left adrenal neoplasm of 6.5cm × 5.9cm. The plasma-free metanephrine level was 100 times higher than the reference value. These findings were compatible with her PCC diagnosis. Alpha-blockers and fluid intake were started immediately. The endotracheal intubation was removed on the 11th day after admission to the ICU. The patient progressed to severe ARDS again, and invasive ventilation and continuous renal replacement therapy were needed. Despite aggressive therapy, her condition deteriorated. Therefore, she underwent veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-assisted emergency adrenalectomy after multidisciplinary discussion. Postoperatively, the patient was supported by VA-ECMO for 7days. She was discharged from the hospital on day 30 after tumor resection. CONCLUSIONS: This case highlighted the challenges in diagnosing and managing ARDS associated with PCC crisis. The traditional preoperative preparation protocol and optimal operation timing for patients with PCC are not suitable for patients with PCC crisis. Patients with life-threatening PCC crisis may benefit from early tumor removal, and VA-ECMO could maintain hemodynamic stability during and after surgery.

Internal validation of an improved system for forensic application: a 41-plex Y-STR panel.

Y-chromosome short tandem repeats (Y-STRs) have a unique role in forensic investigation. However, low-medium mutating Y-STRs cannot meet the requirements for male lineage differentiation in inbred populations, whereas rapidly mutating (RM) high-resolution Y-STRs might cause unexpected exclusion of paternal lineages. Thus, combining Y-STRs with low and high mutation rates helps to distinguish male individuals and lineages in family screening and analysis of genetic relationships. In this study, a novel 6-dye, 41-plex Y-STR panel was developed and validated, which included 17 loci from the Yfiler kit, nine RM Y-STR loci, 15 low-medium mutating Y-STR loci, and three Y-InDels. Developmental validation was performed for this panel, including size precision testing, stutter analysis, species specificity analysis, male specificity testing, sensitivity testing, concordance evaluation, polymerase chain reaction inhibitors analysis, and DNA mixture examination. The results demonstrated that the novel 41-plex Y-STR panel, developed in-house, was time efficient, accurate, and reliable. It showed good adaptability to directly amplify a variety of case-type samples. Furthermore, adding multiple Y-STR loci significantly improved the system's ability to distinguish related males, making it highly informative for forensic applications. In addition, the data obtained were compatible with the widely used Y-STR kits, facilitating the search and construction of population databases. Moreover, the addition of Y-Indels with short amplicons improves the analyses of degraded samples. Key Points: A novel multiplex comprising 41 Y-STR and 3 Y-InDel was developed for forensic application.The multiplex included rapidly mutating Y-STRs and low-medium mutating Y-STRs, which is compatible with many commonly used Y-STR kits.The multiplex is a powerful tool for distinguishing related males, familial searching, and constructing DNA databases.

Changes of dysfunctional lens index before and after implantable collamer lens V4c implantation in patients with moderate-to-high myopia.

BACKGROUND: Dysfunctional lens index (DLI) changing is rarely reported after implantable collamer lens (ICL) implantation. In the current research, we hope to investigate the changes of DLI by ray-tracing aberrometry before and after implantation of the posterior chamber phakic implantable collamer lens with a central artificial hole for patients with moderate-to-high myopia. METHODS: This retrospective, observational case series included 206 eyes of 104 patients with moderate-to-high myopia who underwent ICL V4c implantation. Data were collected on ocular indicators preoperatively and at 1 day, 1, 3, and 6 months postoperatively. The i-Trace Visual Functional Analyzer was used to assess the DLI measurement. RESULTS: The overall values of safety index and efficacy index were both more than 1. Preoperatively, the mean spherical equivalent (SE) of included 206 eyes was - 10.77 ± 3.46 diopter (D). Then at 1-day postoperation, the mean SE was - 0.22 ± 0.55 D, and barely changed from 1 day to 6 months postoperatively. Although the endothelial parameters had no significant differences between preoperation and postoperation, the mean loss of endothelial cells was 0.74 ± 0.98% at 6 months. Regarding the vault, there was a significant difference between each time of follow-up (P < 0.001). The mean of the vault decreased 109.6 ± 13.5 µm from 1-day post-op to 6 months post-op. The DLI values were 3.70, 9.26, 10.00, and 9.68 at baseline, 1, 3, and 6 months, respectively (P < 0.001), but no significant differences were found between 1, 3, and 6 months postoperatively (P > 0.05). The preoperative lnDLI showed a significant positive linear correlation (r = 0.621, P < 0.001) with the preoperative spherical equivalent (SE). The lnDLI was negatively correlated with the axial length (r = - 0.462, P < 0.001), corneal thickness (r = - 0.207, P = 0.003), preoperative LogMAR UDVA (r = - 0.189, P = 0.006), and preoperative LogMAR CDVA (r = - 0.306, P < 0.001). CONCLUSIONS: The postoperative refractive parameters were confirmed excellent in efficacy, predictability, and stability in half a year. The DLI was significantly improved after the ICL V4c implantation in patients with moderate-to-high myopia and showed good stability during the follow-up periods. The DLI deserves a more comprehensive understanding and application in clinical services.

Exploring the effect of industrial agglomeration on income inequality in China.

Income inequality is a good indicator reflecting the quality of people's livelihood. There are many studies on the determinants of income inequality. However, few studies have been conducted on the impacts of industrial agglomeration on income inequality and their spatial correlation. The goal of this paper is to investigate the impact of China's industrial agglomeration on income inequality from a spatial perspective. Using data on China's 31 provinces from 2003 to 2020 and the spatial panel Durbin model, our results show that industrial agglomeration and income inequality present an inverted "U-shape" relationship, proving that they are the non-linear change. As the degree of industrial agglomeration increases, income inequality will rise, after it reaches a certain value, income inequality will drop. Therefore, Chinese government and enterprises had better pay attention to the spatial distribution of industrial agglomeration, thereby reducing China's regional income inequality.

SFI, a sex hormone binding globulin based nomogram for predicting non-alcoholic fatty liver disease in the Chinese population.

Background: The purpose of this study is to establish a novel nomogram model for accurate detection of non-alcoholic fatty liver disease (NAFLD) in the Chinese population based on sex hormone binding globulin (SHBG) and other routine laboratory tests. Methods: A total of 1417 participants (1003 testing and 414 validations) were enrolled into the study. Risk factors independently associated with NAFLD were identified and incorporated in the new nomogram, SFI. The performance of nomogram was assessed by analysis of receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results: We formulated a new nomogram incorporating four independent factors: SHBG, body mass index (BMI), ALT/AST, and triglycerides (TG). The nomogram achieved good indexes of area under ROC 0.898 (95% confidence interval 0.865-0.926) in predicting NAFLD, which was significantly superior to previously reported models of FLI, HSI, LFS, and LAP. The calibration curve and decision curve demonstrated high performance and clinical utility of the nomogram in predicting NAFLD. Conclusion: The nomogram SFI has high performance in predicting NAFLD in Chinese population and may be used as a cost-effective screening model to assess NAFLD in the general population.

Salidroside attenuates LPS-induced inflammatory activation in young rats with acute lung injury via PI3K/Akt signaling pathway.

This experiment aimed to analyze the salidroside effect on lipopolysaccharide (LPS)-induced inflammatory activation in young rats with acute lung injury (ALI) via PI3K/Akt signaling pathway. In this study, sixty SD young rats were divided into 5 groups (control, model, salidroside low-dose, salidroside medium-dose and salidroside high-dose), with 12 rats in each group. ALI rat model was established. In the control and model group, rats were intraperitoneally injected with normal saline, while the salidroside low-, medium-, and high-dose groups were intraperitoneally injected with 5, 20, and 40 mg/kg salidroside, then the pathological changes of lung tissue, lung injury score, wet/dry lung weight ratio, neutrophils and TNF-α, MPO, MDA, NO, p-PI3K and p-AKT were detached and compared between these groups. Results showed that the ALI rat model was successfully established. The lung injury score, wet/dry lung weight ratio, neutrophils and TNF-α in alveolar lavage fluid, MPO, MDA, NO, p-PI3K and p-AKT in the lung tissue of the model group were increased than the control group. With the increase of salidroside dose, lung injury score, wet lung weight/dry lung weight ratio, neutrophils and TNF-α in alveolar lavage fluid, and the levels of MPO, MDA, NO, p-PI3K and p-AKT in lung tissues of the salidroside group were decreased then model group (P < 0.05). In conclusion, salidroside may reduce the activation of inflammatory cells in the lung tissue of young rats with LPS-induced ALI by activating PI3K/AKT signaling pathway, thereby exerting a certain protective effect on the lung tissue with LPS-induced ALI.

Different multi-scale structural features of oat resistant starch prepared by ultrasound combined enzymatic hydrolysis affect its digestive properties.

In this research, oat resistant starch (ORS) was prepared by autoclaving-retrogradation cycle (ORS-A), enzymatic hydrolysis (ORS-B), and ultrasound combined enzymatic hydrolysis (ORS-C). Differences in their structural features, physicochemical properties and digestive properties were studied. Results of particle size distribution, XRD, DSC, FTIR, SEM and in vitro digestion showed that ORS-C was a B + C-crystal, and ORS-C had a larger particle size, the smallest span value, the highest relative crystallinity, the most ordered and stable double helix structure, the roughest surface shape and strongest digestion resistance compared to ORS-A and ORS-B. Correlation analysis revealed that the digestion resistance of ORS-C was strongly positively correlated with RS content, amylose content, relative crystallinity and absorption peak intensity ratio of 1047/1022 cm-1 (R1047/1022), and weakly positively correlated with average particle size. These results provided theoretical support for the application of ORS-C with strong digestion resistance prepared by ultrasound combined enzymatic hydrolysis in the low GI food application.

Mitogenome evidence shows two radiation events and dispersals of matrilineal ancestry from northern coastal China to the Americas and Japan.

Although it is widely recognized that the ancestors of Native Americans (NAs) primarily came from Siberia, the link between mitochondrial DNA (mtDNA) lineage D4h3a (typical of NAs) and D4h3b (found so far only in East China and Thailand) raises the possibility that the ancestral sources for early NAs were more variegated than hypothesized. Here, we analyze 216 contemporary (including 106 newly sequenced) D4h mitogenomes and 39 previously reported ancient D4h data. The results reveal two radiation events of D4h in northern coastal China, one during the Last Glacial Maximum and the other within the last deglaciation, which facilitated the dispersals of D4h sub-branches to different areas including the Americas and the Japanese archipelago. The coastal distributions of the NA (D4h3a) and Japanese lineages (D4h1a and D4h2), in combination with the Paleolithic archaeological similarities among Northern China, the Americas, and Japan, lend support to the coastal dispersal scenario of early NAs.

Blau syndrome with NOD2 mutation in a 54-year-old man: A case report.

Blau syndrome (BS) is a rare genetic immune disease which commonly presents in childhood. Currently, the miss-rate of BS diagnosis is very high, and an effective clinical management of BS has not been well established. This case report depicts a 54-year-old male Chinese patient presenting with hand malformation, fever, skin rash and joint pain. His diagnosis was ultimately confirmed according to typical medical history and genetic analysis. This case report will further help clinicians to be aware of this rare clinical entity for correct diagnosis and proper treatment.

Androgen receptor (CAG)n repeat polymorphism contributes to risk of sudden cardiac death originated from coronary artery disease with sex discrepancy.

Sudden cardiac death (SCD) is the leading cause of natural death worldwide which is responsible for almost half of all heart disease deaths, making it a substantial public health problem. Previous epidemiological studies from different countries have demonstrated the significant SCD incident difference rate between males and females. Besides environmental and social effects, differential genetic architecture also underlines the SCD incidence discrepancy. To this end, the functional (CAG)n repeat polymorphism within Androgen Receptor (AR) gene was analyzed to evaluate its associations with SCD originated from coronary artery disease (SCD-CAD) susceptibility in Chinese populations using 182 SCD-CAD cases and 564 healthy controls. At allelic level, the (CAG)26 allele conferred a lower SCD-CAD risk in males (adjusted odds ratio [OR] = 0.428; 95% confidence interval [CI] = 0.254, 0.915; P = 0.023). On the contrary, the (CAG)26 allele was reversely associated with a higher SCD-CAD risk in females (OR = 2.581; 95% CI = 0.944, 7.056; P = 0.057). Further cutoff strategy analysis revealed that those male subjects carrying shorter allele (≤26 repeats) had significantly lower SCD-CAD risk (OR = 0.343; 95% CI = 0.221, 0.531; P = 8.1653e-7). Additionally, an allele-dependent SCD risk tendency was observed in male subjects. Specifically, compared with males carrying allele longer than 26 repeats, the SCD-CAD risk (OR value) for male subjects carrying shorter alleles (from 25 to 21) gradually increased from 0.437 to 0.533, indicating the (CAG)26 allele of the repeat polymorphism may be the watershed in male SCD etiology. Lastly, the length variations associated with multiple phenotypes were also summarized. Collectively, our results revealed for the first time that the (CAG)n repeat polymorphism within the AR gene was associated with SCD-CAD risk in Chinese populations with sex discrepancy, proposing a new candidate genetic marker for molecular diagnosis of SCD-CAD. Furthermore, a sex-dependent SCD-CAD risk stratification and prevention approach was encouraged. Further studies with more female samples were warranted to validate our findings.

Development and validation of a diagnostic nomogram for sarcopenia in Chinese hemodialysis patients.

BACKGROUND: Sarcopenia is a clinical condition that is common in patients with chronic kidney disease (CKD), especially in those on dialysis. However, the relatively complicated diagnostic procedure limits its use in clinical situations. In this study we aimed to establish a simplified tool for the diagnosis of sarcopenia in patients on hemodialysis (HD). METHODS: Overall, 757 eligible patients from seven HD centers in Shanghai and Suzhou, China, were recruited from 2020 to 2021. The cross-sectional data were analyzed. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria. Among them, 511 consecutive patients (77 with and 434 without sarcopenia) from five centers were included in the training set for the establishment of a diagnostic nomogram. Ten investigative parameters including clinical characteristics, body measurements and physical performance were used to derive the diagnostic nomogram. A total of 246 consecutive patients (47 with and 199 without sarcopenia) were included for validation of the diagnostic model. RESULTS: The average age of the enrolled patients was 60.4 ± 12.1 years, 59.8% were males and 90.5% received dialysis using an arteriovenous fistula. Overall, the sarcopenia rate was 16.4%. The training and validation sets showed no significant differences in sarcopenia rate (15.1% and 19.1%, respectively; P = .160). The nomogram derived from the training set for sarcopenia, which was based on only four features-age, sex, body weight and grip strength-achieved high C-indexes of 0.929 [95% confidence interval (CI) 0.904-0.953] and 0.955 (95% CI 0.931-0.979) in the training and external sets, respectively, and had a well-fitted calibration curve. The cut-off value was 0.725, with a sensitivity of 0.909 and a specificity of 0.816. The nomogram accurately diagnosed sarcopenia with fewer variables and more simplified diagnostic procedures. CONCLUSIONS: The nomogram had a good diagnostic capability for sarcopenia in patients on HD and may be a convenient tool for clinical use.

Mediating effect of gait speed on the relationship between ankle-brachial index and mild cognitive impairment in hemodialysis patients.

BACKGROUND: Patients undergoing hemodialysis are highly predisposed to arterial disease, poor physical performance, and cognitive impairment. However, the connection between them is not yet known. We aimed to investigate the mediating effect of physical performance on the relationship between arterial stiffness and mild cognitive impairment (MCI). METHODS: We conducted a multicenter cross-sectional study. The final analyzed hemodialysis patients comprised 616 subjects (men 391, women 225) from seven dialysis units in Shanghai, China. MCI was assessed by Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale. Arterial function was measured by ankle-brachial index (ABI) and branchial-ankle pulse-wave velocity (baPWV). Physical function was assessed by the Short Physical Performance Battery (SPPB). Logistic regression and mediation model were used to analysis. RESULTS: The mean age of the final analysis sample (n = 616) was 59.0 ± 12.0 years. Hemodialysis patients with MCI were more likely to have lower ABI (p < 0.001) and higher baPWV (p < 0.01). After adjusting for covariates, lower ABI (abnormal ≤0.9 and borderline 0.91-0.99) were positively associated with MCI (OR = 4.43, 95% CI = 1.89-10.39; OR = 4.83, 95% CI = 1.61-14.46). SPPB total score and its components standing balance, gait speed score were negatively associated with MCI. In the mediational model, gait speed played a mediating role (indirect effect ab = -0.21; 95% CI = -0.58 to -0.03) in the association of ABI (≤0.9) and MMSE, while standing balance and chair stands did not. CONCLUSIONS: Lower gait speed mediates a positive association between ABI and MCI in hemodialysis patients. Suitable interventions for physical performance, especially gait speed, may reduce the risk of MCI in hemodialysis patients.

Developmental validation of a 381 Y-chromosome SNP panel for haplogroup analysis in the Chinese populations.

Y-chromosome single nucleotide polymorphism (Y-SNP) shows great variation in geographical distribution and population heterogeneity and can be used to map population genetics around the world. Massive parallel sequencing (MPS) methodology enables high-resolution Y-SNP haplogrouping for a certain male and is widely used in forensic genetics and evolutionary studies. In this present study, we used MPS to develop a customized 381 Y-SNP panel (SifaMPS 381 Y-SNP panel) to investigate the basic structure and subbranches of the haplogroup tree of the Chinese populations. The SifaMPS 381 Y-SNP panel covers all the Y-SNPs from our previously designed 183 Y-SNP panel and additional SNPs under the predominant haplogroups in the Chinese populations based on certain criteria. We also evaluated the sequencing matrix, concordance, sensitivity, repeatability of this panel and the ability to analyze mixed and case-type samples based on the Illumina MiSeq System. The results demonstrated that the novel MPS Y-SNP panel possessed good sequencing performance and generated accurate Y-SNP genotyping results. Although the recommended DNA input was greater than 1.25 ng, we observed that a lower DNA amount could still be used to analyze haplogroups correctly. In addition, this panel could handle mixed samples and common case-type samples and had higher resolution among Chinese Han males than previously reported. In conclusion, the SifaMPS 381 Y-SNP panel showed an overall good performance and offers a better choice for Y-SNP haplogrouping of the Chinese population, thereby facilitating paternal lineage classification, familial searching and other forensic applications.