Single-cell transcriptomic analysis reveals that the APP-CD74 axis promotes immunosuppression and progression of testicular tumors.

Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Prevalence and Genotype Distribution of Human Papillomavirus Infection Among Women in Wuhan, China: A Retrospective Study.

Purpose: Human papillomavirus (HPV) infection is a prevalent sexually transmitted infection worldwide, with its persistence being a significant factor in the development of cervical cancer and precancerous lesions. Understanding the prevalence and genotypes distribution of HPV can aid in the implementation of more focused strategies for cervical cancer prevention and treatment. This study aimed to investigate the prevalence and genotype distribution of HPV infection among outpatient-based populations in Wuhan, China. Methods: Our study retrospectively analyzed the results of cervical HPV screening in 14,492 outpatient women. The cervicovaginal infection of 18 high-risk genotypes and 10 low-risk genotypes were analyzed by PCR and reverse dot hybridization techniques. Results: The overall prevalence of HPV infection in the outpatient female population was 15.33%, with a predominance of single infection and a predominance of dual infection among multiple infections. The top five genotypes in terms of prevalence of HR-HPV and LR-HPV were HPV-52 (3.77%), 53 (1.46%), 16 (1.31%), 58 (1.19%), 39 (1.18%) for HR-HPV, and HPV-54 (1.23%), 61 (1.08%), 81 (1.04%), 42 (0.87%), 44 (0.70%) for LR-HPV. Two peaks of HPV infection prevalence were observed among women under 25 years (22.88%) and over 56 years (24.26%). The prevalence and genotype distribution of HPV infection varied among different outpatient populations, with higher rates of HPV single infection, multiple infections, and infection across all ages observed in the gynecology outpatient population compared to the health check-up population. Conclusion: This study revealed the HPV prevalence and genotype distribution among different outpatient populations in Wuhan city, which may provide guidance for HPV vaccination and cervical cancer prevention strategies in the region.

Analysis of nasopharyngeal microbiota revealing microbial disturbance associated with ovine respiratory complex.

The ovine respiratory complex (ORC) is a complex respiratory disease process in ovine causing a significant health concern with substantial morbidity and mortality. It poses a significant threat of impacting animal health, leading to severe health consequences and considerable economic loss. Research on the upper respiratory tract (URT) microbiota is critical for offering insights into pathogenesis, prevention, and treatment strategies of ORC. The goal of this study is to compare the nasopharyngeal microbiota of clinically healthy Hu sheep (Group H) and sheep with ORC (Group P). The 16S rDNA gene amplicon high-throughput sequencing technique was applied to identify the microbial composition in the nasopharyngeal samples. The results showed that there was no significant difference in the microbiota diversity and richness between ORC and healthy sheep. However, there were significant differences in microbial composition, such as the relative abundance of Enterobacteriaceae, Moraxellaceae, Pasteurellaceae, and Streptococcaceae between the two groups. The abundance of aerobes in sheep with ORC increased significantly, while the abundance of anaerobes and facultative anaerobes decreased significantly. There were also differences in the taxa phenotypes associated with biofilm forming, mobile element-containing, oxidative stress-tolerance, and potential pathogens between the two groups. Our study showed the nasopharyngeal microbiota composition and its associated shifts between clinically healthy sheep and ORC sheep in China. These findings suggest that shifts in the nasopharyngeal microbiota could be a contributing factor to the pathogenesis of ORC, offering a potential avenue for the development of targeted interventions and treatments for this condition in sheep.

Activation of CD14+ Monocytes via the IFN-γ Signaling Pathway Is Associated with Immune-Related Adverse Events in Hepatocellular Carcinoma Patients Receiving PD-1 Inhibition Combination Therapy.

(1) Background: Immune-related adverse events (irAEs) are a series of unique organ-specific inflammatory toxicities observed in patients with hepatocellular carcinoma (HCC) undergoing PD-1 inhibition combination therapy. The specific underlying mechanisms remain unclear. (2) Methods: We recruited 71 patients with HCC undergoing PD-1 inhibition combination therapy. These patients were then divided into two groups based on irAE occurrence: 34 had irAEs and 37 did not. Using Olink proteomics, we analyzed the aberrant inflammation-related proteins (IRPs) in these patient groups. For single-cell RNA sequencing (scRNA-seq) analysis, we collected peripheral blood mononuclear cells (PBMCs) from two representative patients at the pretreatment, irAE occurrence, and resolution stages. (3) Results: Our study revealed distinct plasma protein signatures in HCC patients experiencing irAEs after PD-1 inhibition combination therapy. We clarified the relationship between monocyte activation and irAEs, identified a strongly associated CD14-MC-CCL3 monocyte subset, and explored the role of the IFN-γ signaling pathway in monocyte activation during irAEs. (4) Conclusions: The activation of monocytes induced by the IFN-γ signaling pathway is an important mechanism underlying the occurrence of irAEs in HCC patients receiving PD-1 inhibition combination therapy.

Anti-tumor activity of niclosamide-mediated oxidative stress against acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a heterogeneous clonal disease originated from B- or T-cell lymphoid precursor cells. ALL is often refractory or relapses after treatment. Novel treatments are anxiously needed in order to achieve a better response and prolonged overall survival in ALL patients. In the present study, we aimed at examining the anti-tumor effect of niclosamide on ALL. We investigated the effects of niclosamide on the proliferation and apoptosis in vitro, the growth of ALL cells in xenografted NCG mice. The results showed that niclosamide treatment potently inhibited the growth of ALL cells and induced apoptosis via elevating the levels of reactive oxygen species (ROS) and activating TP53. These findings suggest that niclosamide may be a promisingly potential agent for ALL therapy.

In vitro and in vivo study of antibacterial and anti-encrustation coating on ureteric stents.

OBJECTIVES: To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. MATERIALS AND METHODS: Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. RESULTS: The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. CONCLUSIONS: Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.

Case report: remedial microdissection testicular sperm extraction after onco-microdissection testicular sperm extraction failure.

BACKGROUND: Testicular cancer (TC) mostly occurs in men aged 14 to 44. Studies have shown that TC seriously damages male fertility, and 6% to 24% of patients with TC were even found to suffer from azoospermia when they are diagnosed. At present, some studies have pointed out that onco-microdissection testicular sperm extraction (mTESE) can extract sperm from tumor testicles. However, there are almost no reports on remedial measures after onco-mTESE failure. Given the valuable opportunity for fertility preservation in patients with TC and azoospermia, it is necessary to provide effective remedial methods for patients with failed onco-mTESE. METHODS: Two young men, who were diagnosed with TC and also found to have azoospermia, tried onco-mTESE while undergoing radical orchiectomy for fertility preservation. However, sperm extraction failed in both patients. Subsequently, the isolated testicular tissue of the patient in case 1 suffered from TC again, and the patient in case 2 was scheduled to receive multiple cycles of gonadotoxic chemotherapy. Because both had a plan to have a birth in the future, we performed remedial mTESE. RESULTS: Sperm was successfully extracted from both patients. The patient recovered well, without complications. The patient couple in case 1 underwent 1 intracytoplasmic sperm injection (ICSI) cycle but did not achieve clinical pregnancy. CONCLUSIONS: There is still an opportunity to extract sperm successfully using onco-mTESE, despite the difficulty of fertility preservation in TC patients with azoospermia. If sperm extraction from the tumor testis fails, implementing remedial mTESE as early as possible would likely preserve the last chance of fertility for these patients.

The Microbiota Architecture of the Chinchilla Gastrointestinal Tract.

The gastrointestinal microbiota develop alongside the host and play a vital role in the health of cecal fermenters such as chinchillas. However, little is known about the microbiota architecture in healthy chinchillas. Illumine-based 16S rRNA gene amplicon sequencing was used to investigate the microbiota present in six different gastrointestinal tract regions of three healthy adult chinchillas. The findings revealed significantly more abundant microbiota in the large intestine compared with the proximal segments. In addition, the cecum exhibited better evenness compared to the colon. The core microbiota are Firmicutes, Bacteroidota, Actinobacteriota, and Proteobacteria at the phylum level. The signature microbiota of each segment were identified. The cecum had 10 signature microbiota, which had the widest coverage and overlapped with that of the cecum. The stomach had five signature microbiota, exhibiting the second widest coverage and overlapping with the duodenum. No signature microbiota were detected in the jejunum and ileum. While similarities exist with the microbiota of other cecal fermenters, chinchillas exhibit distinct microbiota closely related to their unique digestive mechanisms. This study is a preliminary study of the gastrointestinal microbiota architecture and distribution in healthy chinchillas. Further study is needed in order to better understand the effect of gastrointestinal microbiota on the health of the chinchilla.

A systematic review and meta-analysis of the efficacy of platelet-rich plasma products for treatment of equine joint disease.

BACKGROUND: Equine joint disease including septic arthritis (SA) and osteoarthritis (OA) is a critical cause of equine lameness. Platelet-rich plasma (PRP) is one of the most popular regenerative therapies to treat equine OA, even SA, but the evidence in support of the treatment is conflicting. OBJECTIVES: The aim of the study was to systematically review the current evidence on PRP products used for SA and OA, as well as the efficacy of PRP products as treatment for OA on the basis of a meta-analysis of the available literature. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic search of relevant databases (PubMed, Web of Science, Scopus) was performed to identify studies published from 2013 to 2023, in accordance with the PRISMA guidelines. Randomised controlled trials, non-randomised trials and controlled laboratory studies that used at least one type of PRP products were included. Dichotomous outcomes were presented using odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 21 publications were identified in the systematic review and 5 of them in the meta-analysis. These publications involved various types of PRP products and reported different outcomes. Although most of the studies were associated with a high risk of bias, the overall estimated effect was consistent with a significant improvement in the PRP products treatment group compared with the control group (OR: 15.32; 95% CI: 3.00-78.15; p < 0.05). There was a significant improvement in clinical performance outcomes between the groups (OR: 36.64; 95% CI: 3.69-364.30; p < 0.05). CONCLUSION: PRP products as intra-articular treatment are likely efficacious for treatment of equine OA and have potential for treating SA. These conclusions might be affected by the limited number of randomised controlled studies and high variability of different types of PRP products. To better evaluate the efficacy of PRP, a widely recognised classification system and the utilisation of randomised, blinded, equivalency or non-inferiority trials are required.

Whole-Exome Sequencing Analysis of Idiopathic Hypogonadotropic Hypogonadism: Comparison of Varicocele and Nonobstructive Azoospermia.

As a rare disease leading to male infertility, idiopathic hypogonadotropic hypogonadism (IHH) has strong heterogeneity of clinical phenotype and gene mutation. At present, there is no effective diagnosis and treatment method for this disease. This study is to explore the possible new pathogenic gene of idiopathic hypogonadotrophic hypogonadism and the pathological mechanism affecting its occurrence. We performed a whole-exome sequencing on 9 patients with normosmic idiopathic hypogonadotropic hypogonadism (nIHH), 19 varicocele patients with asthenospermia, oligospermia, or azoospermia, 5 patients with simple nonobstructive azoospermia, and 13 normal healthy adult males and carried out comparative analysis, channel analysis, etc. After preliminary sequencing screening, 309-431 genes harbouring variants, including SNPs and indels, were predicted to be harmful per single patient in each group. In genetic variations of nIHH patients' analysis, variants were detected in 10 loci and nine genes in nine patients. And in co-analysis of the three patient groups, nine nIHH patients, 19 VC patients, and five SN patients shared 116 variants, with 28 variant-harbouring genes detected in five or more patients. We found that the NEFH, CCDC177, and PCLO genes and the Gene Ontology pathways GO:0051301: cell division and GO:0090066: regulation of anatomical structure size may be key factors in the pathogenic mechanism of IHH. Our results suggest that the pathogenic mechanism of IHH is not limited to the central nervous system effects of GnRH but may involve other heterogeneous pathogenic genetic variants that affect peripheral organs.

Development of Digital Polymerase Chain Reaction Technology and Its Progress in Disease Detection / 分析化学

Digital polymerase chain reaction(dPCR)is a PCR technology that realizes accurate quantification of single-copy nucleic acid molecules by dividing the reaction system into tens of thousands of independent PCR reaction units for single-molecule-level amplification and integrating Poisson distribution.Due to its single-copy sensitivity and accurate quantification without the need of standard curves,dPCR has been widely used in disease diagnosis.By introducing technologies such as stepped emulsification and three-dimensional imaging,dPCR has been greatly improved in terms of accuracy,multiplexability and turnaround time,significantly enhancing its performance in clinical disease diagnosis.Based on this,this paper traced the technological development history of dPCR,gave an overview of its application in detection of tumors,infections and other diseases,and further discussed the challenges and opportunities of the development of dPCR,with the aim of providing a reference for the development and utilization of dPCR in the future,and promoting the high-quality development of molecular technology in clinical testing.

Correlation between geriatric nutritional risk index and adverse events in elderly hemodialysis patients / 中华老年心脑血管病杂志

Objective To explore the relationship between geriatric nutritional risk index(GNRI)and adverse outcomes in elderly patients undergoing maintenance hemodialysis(MHD).Methods A prospective cohort trial was conducted on 337 MHD patients aged ≥60 years in hemodialysis centers of 11 hospitals in Beijing from April to June 2017.Their baseline data were collected,and they were divided into non-malnutrition(GNRI≥98,226 cases),mild malnutrition(92≤GNRI＜98,81 cases),and major malnutrition groups(GNRI＜92,30 cases).All of them were followed up until June 2018.The endpoint events were all-cause mortality and cardiovascular disease(CVD)mortality.Kaplan-Meier survival analysis was used to compare the cumulative survival rate among the 3 groups.Multivariate Cox regression model was employed to analyze the relationship of GNRI with all-cause and CVD mortality.Results The mild and major malnutrition groups had significantly lower BMI,serum albumin level and GNRI(P＜0.01).During the median follow-up of 52(4.4-52.0)weeks,56(16.6％)patients died of all-cause death and 25(44.6％)of CVD death.Kaplan-Meier survival curve showed significant differences in all-cause mortality(x2=30.484,P＜0.01)and CVD mortality(x2=22.398,P＜0.01)in the 3 groups.Multivariate Cox regression analysis indicated that,as a continuous variable,elevated GNRI was a protective factor for all-cause mortality(HR=0.910,95％CI:0.870-0.952,P=0.000)and CVD mortality(HR=0.895,95％CI:0.852-0.940,P=0.000),and as a categorical variable,mild and major malnutri-tion were independently correlated with all-cause and CVD mortality(P＜0.05).Conclusion GNRI is an independent risk factor for all-cause and CVD mortality in elderly MHD patients.Mo-nitoring the nutritional status using GNRI can predict the risk of adverse prognosis.

Mechanical Performance of Porous Titanium Alloy Scaffolds with Different Cell Structures / 医用生物力学

Objective To investigate the influence of different cell structures on the static and dynamic mechanical performance of porous titanium alloy scaffolds,and to provide a theoretical mechanical basis for the application of scaffolds in the repair of mandibular bone defects.Methods Porous titanium alloy scaffolds with diamond,cubic,and cross-sectional cubic cell structures were manufactured using three-dimensional printing technology.Uniaxial compression tests and ratcheting fatigue with compression load tests were conducted to analyze the static and dynamic mechanical performances of scaffolds with different cell structures.Results The elastic moduli of the diamond cell,cross-sectional cubic cell,and cubic cell scaffolds were 1.17,0.566,and 0.322 GPa,respectively,and the yield strengths were 71.8,65.1,and 31.8 MPa,respectively.After reaching the stable stage,the ratcheting strains of the cross-sectional cubic,diamond,and cubic cell scaffolds were 3.3%,4.0%,and 4.5%,respectively.The ratcheting strain increased with increasing average stress,stress amplitude,and peak holding time,and decreased with increasing loading rate.Conclusions The evaluation results of the static mechanical performance showed that the diamond cell scaffold was the best,followed by the cross-sectional cubic cell scaffold and the cubic cell scaffold.The evaluation results of the dynamic mechanical performance showed that the cross-sectional cubic cell scaffold performed the best,followed by the diamond cell scaffold,whereas the cubic cell scaffold performed the worst.The fatigue performance of the scaffold is affected by the loading conditions.These results provide new insights for scaffold construction for the repair of mandibular bone defects and provide an experimental basis for further clinical applications of this scaffold technology.

Evaluation of Mechanical Properties of Three-Dimensional-Printed Metal Vertebral Body Substitutes / 医用生物力学

Objective To study the mechanical properties of titanium mesh and three-dimensional(3D)-printed metal vertebral body substitutes(VBS)to provide guidance for the selection and structural optimization of artificial vertebral implants in clinical practice.Methods The equivalent elastic modulus,equivalent yield strength,and structural failure mode of titanium mesh and 3D-printed porous,truss,and topologically optimized VBS were systematically investigated using compression tests.Results The elastic modulus of the titanium mesh(2 908.73±287.39 MPa)was only lower than that of the topologically optimized VBS.However,their structural strengths and stabilities were inadequate.The yield strength of the titanium mesh(46.61±4.85 MPa)was only higher than that of the porous VBS and it was the first to yield during compression.The porous VBS was insufficient for use as the vertebral implant owing to its poor mechanical strength(18.14±0.17 MPa-25.79±0.40 MPa).The truss VBS had good elastic modulus(2 477.86±55.19 MPa-2 620.08±194.36 MPa)and strength(77.61±0.50 MPa-88.42±1.07 MPa).However,the structural stability of the truss VBS was insufficient,and instability occurred easily during compression.The topologically optimized VBS had the highest elastic modulus(3 746.28±183.80 MPa)and yield strength(177.43±3.82 MPa)among all the tested VBS types,which could provide improved security and stability for artificial vertebral implant in vivo services.Conclusions Topology optimization results in a high strength and high stability VBS design.Moreover,it provides a large design space and great safety margin to provide increased possibilities for lightweight and new material design of future artificial vertebral implants.

Efficacy,metabolic characteristics,safety and immunogenicity of AK-HER2 compared with reference trastuzumab in patients with metastatic HER2-positive breast cancer:a multicenter,randomized,double-blind phase Ⅲ equivalence trial / 中国癌症杂志

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Application and Prospect of Pre-transfusion Detection Technology / 生物化学与生物物理进展

Blood transfusion accuracy is crucial for disease treatment and emergency rescue. Prior to a blood transfusion, it is essential to perform a number of tests to assure proper clinical treatment and reduce the risk of complications. Pre-transfusion testing refers primarily to the blood group, coagulation, and infection to assure transfusion safety and prevent cross-infection. Blood type, cross-matching blood, fibrinogen, viral hepatitis, human immunodeficiency virus, and syphilis are routine pre-transfusion tests. Immunoassay is the traditional clinical pretransfusion detection method. With the expansion of clinical treatment requirements from hospital to on-site treatment, new technologies, such as electrochemical sensing, microfluidics, and spectroscopy technology, are being developed gradually for rapid detection prior to blood transfusion. The development of technologies including colloidal gold immunity and biochips has facilitated the shift from large-scale laboratory equipment to portable testing for pre-transfusion screening. Further, the introduction of artificial intelligence technologies such as machine learning, biometric technology, and computer vision has contributed to the advancement of intelligent pre-transfusion testing. This article reviews the various application scenarios, benefits, and drawbacks of different pre-transfusion detection technologies, analyzes the application of a series of new technologies in pre-transfusion detection and its future development trend, and provides a reference for promoting the development of pre-transfusion detection and even rapid disease marker detection.

A novel splicing mutation identified in a DMD patient: a case report.

Background: Duchenne muscular dystrophy (DMD, ORPHA:98896) is a lethal X-linked recessive disease that manifests as progressive muscular weakness and wasting. Mutations in the dystrophy gene (DMD) are the main cause of Duchenne muscular dystrophy. Case presentation: This study aims to determine novel mutations of DMD and help preimplantation genetic diagnosis (PGD) for family planning. Here present a 4-year-old Chinses boy with DMD, whole-exome sequencing (WES) was performed to identify the molecular basis of the disease. It was confirmed that the boy carried a novel hemizygous mutation of NC_000023.11(NM_004006.3): c.5912_5922 + 19delinsATGTATG in DMD which inherited from his mother. This led to the aberrant splicing of DMD which demonstrated by a minigene splicing assay and further resulted in the impairment of the dystrophy protein. Conclusions: Our study discovered a novel splicing mutation of DMD in a DMD patient, which expands the variant spectrum of this gene and provide precise genetic diagnosis of DMD for timely therapy. Meanwhile, this finding will supply valuable information for preimplantation genetic diagnosis.

Limited clinical role of blood eosinophil levels in early life atopic disease: A mother-child cohort study.

BACKGROUND: Blood eosinophil count is a well-established biomarker of atopic diseases in older children and adults. However, its predictive role for atopic diseases in preschool children is not well established. OBJECTIVE: To investigate the association between blood eosinophil count in children and development of atopic diseases up to age 6 years. METHODS: We investigated blood eosinophil count at age 18 months and 6 years in relation to recurrent wheeze/asthma, atopic dermatitis, allergic rhinitis, and allergic sensitization during the first 6 years of life in the two Copenhagen Prospective Studies on Asthma in Childhood cohorts (n = 1111). Blood eosinophil count was investigated in association with remission of existing atopic disease, current atopic disease, and later development of atopic disease. RESULTS: Blood eosinophil count at 18 months was not associated with current wheezing/asthma or atopic dermatitis, while blood eosinophil count at age 6 years was associated with increased occurrence of current wheezing/asthma (OR = 1.1; 1.04-1.16, p = .0005), atopic dermatitis (OR = 1.06; 1.01-1.1, p = .02), and allergic rhinitis (OR = 1.11; 1.05-1.18, p = .0002). Blood eosinophil count at 18 months did not predict persistence or development of recurrent wheeze/asthma or atopic dermatitis at age 6 years. CONCLUSION: Blood eosinophil count at 18 months was not associated with current wheezing/asthma or atopic dermatitis and did not predict persistence or development of disease. This implies a limited clinical role of blood eosinophil levels in early-life atopic disease and questions the clinical value of blood eosinophil counts measured in toddlers as a predictive biomarker for subsequent atopic disease in early childhood.

Migraine, chronic kidney disease and kidney function: observational and genetic analyses.

Epidemiological studies demonstrate an association between migraine and chronic kidney disease (CKD), while the genetic basis underlying the phenotypic association has not been investigated. We aimed to help avoid unnecessary interventions in individuals with migraine through the investigation of phenotypic and genetic relationships underlying migraine, CKD, and kidney function. We first evaluated phenotypic associations using observational data from UK Biobank (N = 255,896). We then investigated genetic relationships leveraging genomic data in European ancestry for migraine (Ncase/Ncontrol = 48,975/540,381), CKD (Ncase/Ncontrol = 41,395/439,303), and two traits of kidney function (estimated glomerular filtration rate [eGFR, N = 567,460] and urinary albumin-to-creatinine ratio [UACR, N = 547,361]). Observational analyses suggested no significant association of migraine with the risk of CKD (HR = 1.13, 95% CI = 0.85-1.50). While we did not find any global genetic correlation in general, we identified four specific genomic regions showing significant for migraine with eGFR. Cross-trait meta-analysis identified one candidate causal variant (rs1047891) underlying migraine, CKD, and kidney function. Transcriptome-wide association study detected 28 shared expression-trait associations between migraine and kidney function. Mendelian randomization analysis suggested no causal effect of migraine on CKD (OR = 1.03, 95% CI = 0.98-1.09; P = 0.28). Despite a putative causal effect of migraine on an increased level of UACR (log-scale-beta = 0.02, 95% CI = 0.01-0.04; P = 1.92 × 10-3), it attenuated to null when accounting for both correlated and uncorrelated pleiotropy. Our work does not find evidence supporting a causal association between migraine and CKD. However, our study highlights significant biological pleiotropy between migraine and kidney function. The value of a migraine prophylactic treatment for reducing future CKD in people with migraine is likely limited.

D-A-D-T-type four-component radical dual-difunctionalization and acylative azidation of two different alkenes.

From a single alkene to two different alkenes! An iron-catalyzed four-component reaction involving an aldehyde, two different alkenes and TMSN3 is developed to assemble these four reactants in an orderly fashion based on the inherent nucleophilic/electrophilic reaction activity of the radicals and alkenes via a double radical addition, providing various multifunctional compounds containing an azido group and two carbonyl groups.