Glucose Sensing by Skeletal Myocytes Couples Nutrient Signaling to Systemic Homeostasis.

Skeletal muscle is a major site of postprandial glucose disposal. Inadequate insulin action in skeletal myocytes contributes to hyperglycemia in diabetes. Although glucose is known to stimulate insulin secretion by ß cells, whether it directly engages nutrient signaling pathways in skeletal muscle to maintain systemic glucose homeostasis remains largely unexplored. Here we identified the Baf60c-Deptor-AKT pathway as a target of muscle glucose sensing that augments insulin action in skeletal myocytes. Genetic activation of this pathway improved postprandial glucose disposal in mice, whereas its muscle-specific ablation impaired insulin action and led to postprandial glucose intolerance. Mechanistically, glucose triggers KATP channel-dependent calcium signaling, which promotes HDAC5 phosphorylation and nuclear exclusion, leading to Baf60c induction and insulin-independent AKT activation. This pathway is engaged by the anti-diabetic sulfonylurea drugs to exert their full glucose-lowering effects. These findings uncover an unexpected mechanism of glucose sensing in skeletal myocytes that contributes to homeostasis and therapeutic action.

Development of a coding SNP panel for tracking the origin of whole-exome sequencing samples.

Whole-exome sequencing (WES) is widely used to diagnose complex genetic diseases and rare conditions. The implementation of a robust and effective quality control system for sample identification and tracking throughout the WES process is essential. We established a multiplex panel that included 22 coding single-nucleotide polymorphism (cSNP) loci. The personal identification and paternity identification abilities of the panel were evaluated, and a preliminary validation of the practical feasibility of the panel was conducted in a clinical WES case. These results indicate that the cSNP panel could be a useful tool for sample tracking in WES.

Improving DNA mixtures analysis using compound markers composed of InDels and SNPs screened from the whole genome with next-generation sequencing.

Next-generation sequencing (NGS) allows for better identification of insertion and deletion polymorphisms (InDels) and their combination with adjacent single nucleotide polymorphisms (SNPs) to form compound markers. These markers can improve the polymorphism of microhaplotypes (MHs) within the same length range, and thus, boost the efficiency of DNA mixture analysis. In this study, we screened InDels and SNPs across the whole genome and selected highly polymorphic markers composed of InDels and/or SNPs within 300 bp. Further, we successfully developed and evaluated an NGS-based panel comprising 55 loci, of which 24 were composed of both SNPs and InDels. Analysis of 124 unrelated Southern Han Chinese revealed an average effective number of alleles (Ae ) of 7.52 for this panel. The cumulative power of discrimination and cumulative probability of exclusion values of the 55 loci were 1-2.37 × 10-73 and 1-1.19 × 10-28 , respectively. Additionally, this panel exhibited high allele detection rates of over 97% in each of the 21 artificial mixtures involving from two to six contributors at different mixing ratios. We used EuroForMix to calculate the likelihood ratio (LR) and evaluate the evidence strength provided by this panel, and it could assess evidence strength with LR, distinguishing real and noncontributors. In conclusion, our panel holds great potential for detecting and analyzing DNA mixtures in forensic applications, with the capability to enhance routine mixture analysis.

Effects of vaginal microbiota on human papillomavirus infection and its related diseases.

With the knowledge of female reproductive tract microbiota gradually increasing, the connection between vaginal microbiota (VMB) and its related diseases is increasingly highlighted. Manifestation of VMB keeps changing with various dominated bacteria, which can affect the immune response of mucosal barrier and the entrance of pathogens. Human papillomavirus (HPV), as an oncogenic virus, is closely related to viral-associated cancer, such as cervical cancer. According to HPV infection status, VMB can transform into different types, and result in accelerating or restraining the progression of diseases, which have exposed the inner link between VMB and HPV. Therefore, probiotics therapy promises to be a new complementary therapy to rebuild a healthy VMB for patients, but there's still a long way to go before its ready for the clinic. This review focuses on composition, immune response, and application of VMB in HPV and its associated diseases and aims to provide the new ideas and directions for the research on VMB.

Characterization of posterior circulation blood perfusion in patients with different degrees of basilar artery tortuosity.

OBJECTIVE: The morphology of basilar artery (BA) may affect posterior circulation blood perfusion. We aimed to investigate whether different degrees of BA tortuosity could lead to the alterations of posterior circulation perfusion. METHODS: We collected 138 subjects with different BA tortuosity scores, including 32 cases of score 0, 45 cases of score 1, 43 cases of score 2, and 18 cases of score 3. A higher score represented a higher degree of BA tortuosity. Ordered logistic regression analysis was performed to investigate the risk factors for BA tortuosity. We quantitatively measured the cerebral blood flow (CBF) in eight posterior circulation brain regions using arterial spin labeling. SPSS 25.0 was used for statistical analysis. The correlation between the CBF and BA tortuosity was corrected by the Bonferroni method. The significance level was set at 0.006 (0.05/8). RESULTS: Hypertension (HR: 2.39; 95%CI: 1.23-4.71; P = 0.01) and vertebral artery dominance (HR: 2.38; 95%CI: 1.10-4.67; P = 0.03) were risk factors for BA tortuosity. CBF in occipital gray matter (R = -0.383, P < 0.001), occipital white matter (R = -0.377, P < 0.001), temporal gray matter (R = -0.292, P = 0.001), temporal white matter (R = -0.297, P < 0.001), and cerebellum (R = -0.328, P < 0.001) were negatively correlated with BA tortuosity degree. No significant correlation was found between the BA tortuosity degree and CBF in hippocampus (R = -0.208, P = 0.014), thalamus (R = -0.001, P = 0.988) and brainstem (R = -0.204, P = 0.016). CONCLUSIONS: BA tortuosity could affect posterior circulation blood perfusion. CBF was negatively correlated with BA tortuosity degree. The morphology of BA may serve as a biomarker for posterior circulation and the severity of posterior circulation ischemia.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Social poverty indicators with school bullying victimization: evidence from the global school-based student health survey (GSHS).

BACKGROUND: School bullying is prevalent in children and adolescents. Bullying victims are seen higher risk of negative psychological outcomes. Previously published studies suggested that social indicators may pose significant influence on bullying victimization. However, the association between social poverty and bullying victimization has not been exclusively discussed. METHODS: In this cross-sectional study, we analyzed the association between 6 commonly used social poverty indicators (Poverty Headcount Ratio, PHR; Poverty Gap, PG; Squared Poverty Gap, SPG; monthly household per capita income, PCI; Watts' Poverty Index, WPI; the Gini Index, Gini) and the prevalence of school bullying at country level by using the Global school-based Student Health Survey (GSHS) database. RESULTS: Altogether 16 countries were included into the final analysis, with school bullying victimization prevalence ranged from 12.9 to 47.5%. Bubble plots revealed statistically significant associations between the three indicators measuring absolute poverty level (PHR, PCI, WPI) and bullying victimization. Subsequently performed principal component regression indicated that, for all types of bullying victimization, the increase of absolute poverty level was related to elevated prevalence rates, and the association was particularly strong for verbal bullying victimization. CONCLUSIONS: Our study results may suggest that absolute social poverty is an important parameter for constructing and implementing school bullying victimization intervention strategies and measures.

Analysis of cantharidin-induced kidney injury and the protective mechanism of resveratrol in mice determined by liquid chromatography/mass spectrometry-based metabonomics.

Cantharidin (CTD) is the main active component in the traditional Chinese medicine Mylabris and an effective anti-tumor agent. However, it is relatively toxic and exhibits nephrotoxicity, which limits its clinical use. However, its toxic mechanism is not clear. The toxic effects of CTD exposure on the kidney and the protective effect of resveratrol (RES) were studied in a mouse model, by determination of serum biochemical and renal antioxidant indicators, histopathological and ultrastructural observation, and metabonomics. After CTD exposure, serum uric acid, creatinine, and tissue oxidative stress indicators increased, and the renal glomerular and tubular epithelial cells showed clear pathological damage. Ultrastructure observation revealed marked mitochondrial swelling, endoplasmic reticulum dilation, and the presence of autophagy lysosomes in glomerular epithelial cells. RES ameliorated the renal injury induced by CTD. Metabonomics analysis indicated that CTD can induce apoptosis and oxidative damage in kidney cells, mainly by disrupting sphingolipid and glutathione metabolism, increasing sphingosine and sphingomyelin levels, and decreasing glutathione levels. RES counteracts these effects by regulating renal cell proliferation, the inflammatory response, oxidative stress, and apoptosis, by improving the levels of phosphatidylcholine (PC), LysoPC, and lysophosphatidyl glycerol in the glycerophospholipid metabolism pathway, thereby reducing CTD-induced nephrotoxicity. The mechanisms of CTD-induced renal injury and the protective effect of RES were revealed by metabonomics, providing a basis for evaluating clinical treatment regimens to reduce CTD-induced nephrotoxicity.

Anisodamine Hydrobromide ameliorates acute lung injury via inhibiting pyroptosis in murine sepsis model.

OBJECTIVE: Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered acute lung injury (ALI) and elucidate the fundamental mechanisms involved. MATERIALS AND METHOD: The protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. RESULTS: Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1ß in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines. CONCLUSION: These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.

Transcriptomic profiling and differential analysis reveal the renal toxicity mechanisms of mice under cantharidin exposure.

Cantharidin (CTD), extracted from the traditional Chinese medicine mylabris, has shown significant curative effects against a variety of tumors, but its clinical application is limited by its high toxicity. Studies have revealed that CTD can cause toxicity in the kidneys; however, the underlying molecular mechanisms remain unclear. In this study, we investigated the toxic effects in mouse kidneys following CTD treatment by pathological and ultrastructure observations, biochemical index detection, and transcriptomics, and explored the underlying molecular mechanisms by RNA sequencing (RNA-seq). The results showed that after CTD exposure, the kidneys had different degrees of pathological damage, altered uric acid and creatinine levels in serum, and the antioxidant indexes in tissues were significantly increased. These changes were more pronounced at medium and high doses of CTD. RNA-seq analysis revealed 674 differentially expressed genes compared with the control group, of which 131 were upregulated and 543 were downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that many differentially expressed genes were closely related to the stress response, the CIDE protein family, and the transporter superfamily, as well as the MAPK, AMPK, and HIF-1 pathways. The reliability of the RNA-seq results was verified by qRT-PCR of the six target genes. These findings offer insight into the molecular mechanisms of renal toxicity caused by CTD and provide an important theoretical basis for the clinical treatment of CTD-induced nephrotoxicity.

Prognostic value of tertiary lymphoid structures (TLS) in digestive system cancers: a systematic review and meta-analysis.

BACKGROUND: Existing literature suggests that tertiary lymphatic structure (TLS) is associated with the progression of cancer. However, the prognostic role of TLS in digestive system cancers remains controversial. This meta-analysis aims to synthesize currently available evidence in the association between TLS and the survival of digestive system cancers. METHODS: We systematically searched three digital databases (PubMed, Embase, Web of Science) for articles published from database inception to December 23, 2022. Study selection criteria are based on PECO framework: P (population: patients with digestive system cancers), E (exposure: presence of TLS), C (comparator: absence of TLS), O (outcome: overall survival, OS; recurrence-free survival, RFS; disease-free survival, DFS). The Quality in Prognostic Studies (QUIPS) tool was used to assess risk of bias for included studies. The study protocol was registered with PROSPERO (CRD42023416307). RESULTS: A total of 25 studies with 6910 patients were included into the final meta-analysis. Random-effects models revealed that the absence of TLS was associated with compromised OS, RFS, and DFS of digestive system cancers, with pooled hazard ratios (HRs) of 1.74 (95% CI: 1.50-2.03), 1.96 (95% CI: 1.58-2.44), and 1.81 (95% CI: 1.49-2.19), respectively. Subgroup analyses disclosed a stronger TLS-survival association for pancreatic cancer, compared with other digestive system cancers. CONCLUSION: TLS may be of prognostic significance for digestive system cancers. More original studies are needed to further corroborate this finding.

Effect of intestinal microbiota on liver disease and its related future prospection: From the perspective of intestinal barrier damage and microbial metabolites.

Liver diseases contribute notably to the global concern of mortality and disease. Emerging evidence has demonstrated that intestinal microbiota can regulate intestinal barrier function and produce bioactive metabolites. Failure of any aspect of this barrier can result in the translocation of microbes into the blood and a sustained inflammatory response that promotes liver injury, fibrosis, and cirrhosis. Here, we review the mechanisms by that intestinal microbiota regulate the intestinal barrier. The multiple underlying mechanisms of intestinal microbiota in liver disease are elaborated in detail, emphasizing them as the bridge linking the liver with gut microbiota. Thus, we highlight the feasibility of targeting the gut-liver axis for treating liver diseases.

Spectral-domain optical coherence tomography biomarkers in vitreoretinal lymphoma.

BACKGROUND: Although early detection is critical, diagnosing vitreoretinal lymphoma (VRL) remains difficult. We sought to assess the potential diagnostic value of spectral-domain optical coherence tomography (SD-OCT) in VRL. METHODS: We reviewed the clinical records and pre-treatment SD-OCT images of biopsy-confirmed VRL and uveitis patients, with primary involvement of the sub-retinal pigment epithelium (RPE) and the outer retina, including acute syphilitic posterior placoid chorioretinitis (ASPPC), chronic stage sympathetic ophthalmitis (SO), and idiopathic multifocal choroiditis (MFC). RESULTS: We included 45 eyes of 45 VRL patients and 40 eyes of 40 uveitis patients (17 ASPPC eyes, eight chronic SO eyes, and 15 MFC eyes). On SD-OCT, lymphoma cell infiltration was observed in various retinal layers, most commonly in the sub-RPE (80%) and sub-retinal space (62%). Highly sensitive features for VRL as compared to uveitis included vitreous cells (93%), focal hyper-reflective sub-retinal infiltration (51%), and diffuse RPE elevations (56%). The features strongly specific for VRL included preretinal deposits (92.5%), intra-retinal infiltration (except the incomplete vertical hyper-reflective type, 100%), banded hyper-reflective sub-retinal infiltration (90%), and confluent RPE detachments (100%). We identified an approach to VRL diagnosis based on these SD-OCT findings: (1) two highly sensitive features plus one strongly specific feature; or (2) one highly sensitive feature plus two strongly specific features, demonstrated a sensitivity of 80% and specificity of 95% for VRL. CONCLUSIONS: The SD-OCT may enable the detection of detailed lymphoma infiltration characteristics and provide significant supplemental value for VRL diagnosis, particularly when combining highly sensitive and specific VRL-associated SD-OCT features.

Therapeutic Efficacy of Intravitreal Conbercept Injections with or without Focal Macular Photocoagulation for Diabetic Macular Edema.

Objective: This study aimed to investigate the effectiveness and safety of intravitreal conbercept injections with or without focal macular photocoagulation in the treatment of diabetic macular edema (DME). Methods: This retrospective study included 60 DME patients (60 eyes) divided into two treatment groups. The conbercept group received monthly intravitreal injections for 5 consecutive sessions, while the combination therapy group received intravitreal injections and focal macular photocoagulation. Changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were observed before and at months 1, 3, 6, 9, and 12 after treatment in both groups, along with the number of intravitreal conbercept injections administered. Results: At 1, 3, 6, 9, and 12 months after treatment, both the conbercept and combined treatment groups showed improvement in best-corrected visual acuity (BCVA) and decrease in central macular thickness (CMT) compared to before treatment, with statistical significant differences (P < .05). However, the differences in BCVA and CMT between the two groups at each time point after treatment were not significant (P > .05). During the 1-year follow-up period, the mean number of injections in the combined treatment group was 6.3±0.8, which was less than that in the conbercept treatment group (7.6 ± 0.9), with a significant difference (t = 5.556, P < .001). The incidence of subconjunctival hemorrhage was 10.9% and 10.5% in the two groups, respectively, with no significant inter-group difference (χ² = 0.013, P = .908). None of the patients exhibited serious treatment-related ocular and systemic complications during the treatment period. Conclusions: Treatment of DME with intravitreal conbercept injections, whether with or without focal macular photocoagulation, is safe and effective in improving the patients' visual acuity and retinal anatomy. However, patients who receive combined treatment require fewer intravitreal injections than those who receive conbercept treatment alone.

NGS-based targeted sequencing identified two novel variants in Southwestern Chinese families with oculocutaneous albinism.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of heterogeneous genetic diseases characterized by a reduction or complete lack of pigmentation in the hair, skin, and eyes. It is associated with reduced visual acuity, nystagmus, photophobia, and strabismus. OCA type 1 (OCA1) and type 2 (OCA2) are caused by mutations in the tyrosinase (TYR) and OCA2 genes, which are responsible for most cases of OCA. The present study aimed to identify the mutational spectra of 18 southwest Chinese probands with OCA. RESULTS: We used a skin disease-targeted panel to sequence more than 400 genes, including 23 genes (TYR, OCA2, AP3B1, BLOC1S3, BLOC1S6, C10orf11, DTNBP1, FRMD7, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, LYST, MC1R, MITF, MLPH, MYO5A, RAB27A, SLC24A5, SLC45A2, TYRP1) associated with syndromic and non-syndromic albinism. The targeted panel was applied to 18 patients from southwest China, nine (50%) patients were diagnosed with OCA1, and nine (50%) were diagnosed with OCA2. Our data indicate that OCA1 and OCA2, the most common subtypes, probably have the same prevalence in southwest China. In total, we identified 26 variants in TYR and OCA2 from 18 OCA cases using the NGS technology, including 24 variants presented in the Human Gene Mutation Database Professional (HGMD) and two novel variants, c.559_560insCATTATTATGTGTCAAATTATCCCC in TYR and c.1514 T > C in OCA2, which have not been previously reported. According to the American College of Medical Genetics and Genomics (ACMG) classification, c.559_560insCATTATTATGTGTCAAATTATCCCC (p.G190Cfs*12) is classified as a pathogenic variant, and c.1514 T > C (p.F505S) is evaluated as a likely pathogenic variant. CONCLUSIONS: Two novel variants were identified which will expand the mutational spectra of TYR and OCA2. The results of the present study may have implications for genetic counseling, carrier screening, and clinical management of the disease.

Serum cholinesterase may independently predict prognosis in non-small-cell lung cancer.

BACKGROUND: Serum cholinesterase (ChE) was found to be involved in cancer initiation and progression. However, the survival association between serum ChE and non-small cell lung cancer (NSCLC) has not been extensively discussed. In the present study, we aim to elevate the role of ChE in overall survival (OS) of NSCLC patients. METHODS: A total of 961 histologically confirmed NSCLC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant information, such as histological type, clinical stage, chemotherapy, smoking status, body mass index (BMI), important serum indicators (albumin, neutrophil-to-lymphocyte ratio, ChE), date of death of the patients was extracted from the computerized hospital information system. Univariate and multivariate Cox proportional hazards models were used to determine the association between baseline serum ChE measured at the diagnosis and the OS of NSCLC patients. RESULTS: The median of baseline ChE (7700 units/liter) was used as a cut-off to dichotomize NSCLC patients. After controlling for possible confounding factors, serum ChE at diagnosis was significantly associated with OS of NSCLC: patients with higher level of ChE were observed a better prognosis (hazard ratio, HR: 0.77, 95% CI: 0.67-0.93, p = 0.006). Subgroup analysis revealed significant ChE-OS association for NSCLC patients: with lower systemic inflammation level (baseline NLR < 2.95, HR: 0.71, 95% CI: 0.56-0.89, p = 0.003), of adenocarcinoma (HR: 0.66, 95% CI: 0.54-0.80, p < 0.001), in advanced stage (HR: 0.77, 95% CI: 0.66-0.92, p < 0.01), and received chemotherapy (HR: 0.75, 95% CI: 0.59-0.96, p < 0.02). CONCLUSION: Baseline ChE may have independent prognostic value for NSCLC patients. Longitudinal studies should be performed to corroborate this finding.

An overview of SNP-SNP microhaplotypes in the 26 populations of the 1000 Genomes Project.

Microhaplotypes (MHs) are a promising new type of forensic markers that are defined by the combinations of two- or more single-nucleotide polymorphisms (SNPs) within 200 bp. Their advantages, such as low mutation rates, lack of stutter artifacts, and short amplicons, have improved human identification, kinship analysis, ancestry prediction, and mixture deconvolution capabilities. Information on published MHs, e.g., allele frequencies, is available in widely used public databases, ALlele FREquency Database, and MicroHapDB. However, there are abundant non-published MHs spread over the whole genome, and those databases do not incorporate other databases (e.g., the SNP Database) to provide users with more integrated information. Therefore, it is essential to establish a robust, responsive, and comprehensive MHs database. In this study, we thoroughly screened for SNP-SNP MHs among 26 populations from the 1000 Genomes Project (Phase 3). All genotype data of SNPs in each MH were converted to PHASE input files, and allele frequencies were estimated using PHASE. We compiled a detailed summary of SNP-SNPs at the global, continental, and population levels focused on haplotypes and the Ae value and supplemented our database using dbSNP data (last updated in 2015). We have successfully established a dual-SNP MH database (D-SNPsDB) of MHs within 50 bp for 26 populations in the integration of basic data such as physical positions in the human genome, mapping of variant identifiers (rsIDs), allele frequencies, and basic variant information. For public database queries, the D-SNPsDB web app was developed with the R Shiny package to get integrated information.

Establishment of a co-analysis system for personal identification and body fluid identification: a preliminary report.

Analysis of genetic markers can provide clues for case investigation. Short tandem repeat (STR) detection and analysis are widely used for both personal identification and parentage testing. However, DNA analysis currently cannot provide sufficient information for body fluid identification. Tissue or cell sources of samples can be identified by detecting body fluid-specific mRNA markers, which have been studied thoroughly. Integrating STR profiling and mRNA expression patterns can provide more information than conventional methods for investigations and the reconstruction of crime scenes; this can be achieved by DNA/RNA co-extraction technology, which is economical, efficient, and suitable for low-template samples. Here, we propose a co-analysis system based on the PowerPlex 16 kit. This system can simultaneously amplify 25 markers, including 15 STRs, one non-STR amelogenin, and nine mRNA markers (three blood-specific, two saliva-specific, two semen-specific, and two housekeeping gene markers). The specificity and sensitivity of the co-analysis system were determined and aged and degraded samples were used to validate the stability of the co-analysis system. Finally, different DNA/RNA ratios and various carriers were evaluated. The results showed that the DNA/RNA co-analysis system correctly identified different types of body fluid stains. The STR profiles obtained using the co-analysis system were identical to those obtained using the PP16 kit, which demonstrates that the mRNA primers used did not affect STR profiling. Complete STR and mRNA profiles could be obtained from 1/8 portions of buccal swabs, 1/16 portions of swabs of blood and semen samples, 0.1 cm2 of blood samples, 0.25 cm2 of semen samples, and 1.0 cm2 saliva samples. Additionally, our findings indicate that complete STR and mRNA profiles can be obtained with this system from blood and semen samples when the DNA/RNA ratio is 1:1/32. This study suggests that the co-analysis system could be used for simultaneous personal identification and body fluid identification.

Childhood maltreatment and suicidal ideation in Chinese children and adolescents: the mediating role of mindfulness.

BACKGROUND: Childhood maltreatment (CM) has been associated with suicidal ideation (SI) in children and adolescents, yet the mediating role of mindfulness in this association remains unclear. This study aims to test the mediation of mindfulness in CM-SI association among a large sample of Chinese children and adolescents. METHODS: A population-based cross-sectional study of 3455 children and adolescents aged 10-17 years from southwest China Yunnan province was conducted. Information from the participants was collected by using a comprehensive self-administered questionnaire. The Chinese version of the Childhood Trauma Questionnaire (CTQ), Five Facet Mindfulness Questionnaire (FFMQ), and the Beck Scale for Suicidal Ideation (BSSI) were used to measure CM, mindfulness and SI. Univariate and multivariate binary logistic regression models were used to estimate the crude and adjusted associations between CM, mindfulness and SI (one-week, one-year, lifetime). Pathway analysis was subsequently performed to test the mediation of mindfulness in CM-SI association. RESULTS: The findings showed that mindfulness, CM and SI were significantly correlated with each other (p < 0.05). Mindfulness is a significant mediator in CM-SI association, accounted for 7.5, 11.4, and 17.6% of the total associations for one-week SI, one-year SI, and lifetime SI, respectively. For the five types of CM, the highest level of mediation via mindfulness had been found for physical neglect (PN) and one-year SI (34.3%), followed by emotional neglect (EN) and one-year SI (30.2%), sexual abuse (SA) and one-year SI (25.4%). CONCLUSIONS: Our study findings highlight the intervention potential of mindfulness in preventing CM associated suicidal risk. Future longitudinal studies are warranted to corroborate the effectiveness of mindfulness-based intervention for Chinese children and adolescents.

CLINICAL CHARACTERISTICS OF STREAKY MULTIFOCAL CHOROIDITIS: A Subtype of Multifocal Choroiditis.

PURPOSE: To describe and analyze clinical characteristics of multifocal choroiditis with linear streaks (LSs). METHODS: Eight cases of multifocal choroiditis with LSs were retrospectively studied. Multimodal imaging was performed. Demographic data and spherical equivalent were collected. Axial length was measured. RESULTS: All cases are young myopic women with a mean age of 17.13 ± 3.64 years (range, 13-23 years), presenting with vision loss and distortion. Nine eyes with LSs were high myopia of -8.97 ± 2.69 D (range, -6.00 to 12.5 D; growing by 1.88 ± 0.61 D annually since wearing glasses), with mean axial length of 26.36 ± 1.71 mm. Vitreous cells were noted in seven eyes. LSs were located in the equator (eight eyes), around the optic disk (three eyes), and at the edge of the posterior pole (one eye). Angio-optical coherence tomography showed choroidal neovascularization in eight eyes, especially 2 to 3 choroidal neovascularizations in three eyes. The location of choroidal neovascularization were in subfovea (three eyes), parafovea (six eyes), and perifovea (two eyes). Swept source optical coherence tomography showed punched-out disruption of retinal pigment epithelium‒Bruch's membrane‒choriocapillaris complex at the LSs' sites. LSs showed fluorescence staining on late FA but hypofluorescence throughout all phases on ICGA. CONCLUSION: Multifocal choroiditis with LSs mostly occurs in young women with high myopia, especially occurring in eyes with rapid progression of myopia. LSs are mainly located in the midperiphery near the equator, being prone to concur with choroidal neovascularization. Based on our findings, we propose a new term called "streaky multifocal choroiditis" as a subtype of multifocal choroiditis.