The objective of this study was to explore the clinical utility of the implementation of expanded carrier screening (ECS) in Chinese population of childbearing age.
Based on capillary ...electrophoresis, a first-generation sequencing technology, a prospective screening study of carriers of 15 single-gene diseases was carried out in 327 subjects in Anhui Province, including 84 couples and 159 women of childbearing age, the disease carrier rate, types of screened pathogenic genes, and incidence of both partners carrying the same pathogenic genes were summarized and analyzed.
In 320 people with normal phenotypes who underwent ECS for 15 genetic diseases and 7 spouses who underwent targeted gene sequencing, 65 carriers of at least one disease were detected, with a total carrier rate of 20.31% (65/320). Among the 65 carriers, 81.54% (53/65) carried one genetic variant, 16.92% (11/65) carried two genetic variants, and 1.54% (1/65) carried three genetic variants. In this study, the three diseases with the highest carrier rates were hereditary deafness (8.13%, 26/320), Wilson's disease (4.06%, 13/320), and phenylketonuria (3.13%, 10/320). One high-risk couple (1.19%, 1/84) was detected.
It has certain clinical application value to implement ECS in the population of childbearing age in China.
Abstract
Background
Many clinical studies based on spontaneous pregnancies (SPs) have demonstrated the superiority of non-invasive prenatal testing (NIPT), and the question of whether this technology ...is suitable for offspring conceived by assisted reproductive technology has attracted attention. This study aimed to evaluate the application value of NIPT in screening for trisomy (T)21, T18, T13 and sex chromosome aneuploidy (SCA) in pregnant women who conceived by in vitro fertilization (IVF).
Results
In total, there were 804 high-risk cases 0.88% (804/91280), singleton = 795, twin = 9 in the SP group. Among the 558 invasive prenatal diagnosis (IPD) cases (singleton = 556, twin = 2), 343 (singleton = 342, twin = 1) were true positive, including 213 cases of T21, 28 of T18, 5 of T13 and 97 (singleton = 96, twin = 1) of SCA. The positive predictive values (PPVs) of T21, T18, T13, SCA and T21/T18/T13 combined in singleton pregnancy were 89.12% (213/239), 51.85% (28/54), 21.74% (5/23), 40.00% (96/240), and 77.85% (246/316), respectively, and the PPV of SCA in twin pregnancy was 100.00%. In the IVF group, IPD was performed in 19 (singleton = 16, twin = 3) of the 27 high-risk cases 0.78% (27/3477), singleton = 16, twin = 3, of which 9 (singleton = 8, twin = 1) were true positive, including 5 cases (singleton = 4, twin = 1) of T21 and 4 of SCA. The PPVs of singleton T21, SCA and T21/T18/T13 combined were 66.67% (4/6), 50.00% (4/8) and 57.14% (4/7), respectively, and the PPV of twin T21 was 100.00% (1/1). There were no significant differences in PPV among T21, SCA and T21/T18/T13 combined in singletons between the groups (89.12% vs. 66.67%,
p
= 0.09; 40.00% vs. 50.00%,
p
= 0.57; 77.85% vs. 57.14%,
p
= 0.20). The sensitivity and specificity were higher for singleton and twin pregnancies in the two groups. Based on follow-up results, 1 case of false negative T21 was found in the singleton SP group. Additionally, the mean foetal fraction (FF) of the IVF group was lower than that of the SP group (11.23% vs. 10.51%,
p
< 0.05).
Conclusion
NIPT has high sensitivity and specificity in screening chromosomal aneuploidies in both IVF pregnancy and spontaneous pregnancy, so it is an ideal screening method for IVF pregnancy.
Osteoarthritis (OA) is a chronic and degenerative condition that persists and progresses over time. Sipeimine (Sip), a steroidal alkaloid derived from Fritillariae Cirrhosae Bulbus, has attracted ...considerable attention due to its exceptional anti-inflammatory, analgesic, antioxidant, and anti-cancer characteristics. However, Sip's effects on OA and its mechanism still need further research.
This study utilized network pharmacology to identify initial targets for Sip. Functional associations of Sip in OA were clarified through Gene Ontology (GO) enrichment analysis, bioinformatically analyzing a list of targets. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis assessed pathways linked to Sip's therapeutic efficacy in OA. Molecular docking techniques explored Sip's binding affinity with key targets. In vitro experiments assessed Sip's impact on lipopolysaccharide (LPS)-induced pro-inflammatory factors and its protective effects on collagen-II and aggrecan degradation within the extracellular matrix (ECM). Western blotting and fluorescence analyses were conducted to determine Sip-mediated signaling pathways. Moreover, in vivo experiments using a mouse OA model validated Sip's therapeutic efficacy.
The results from network pharmacology revealed a total of 57 candidate targets for Sip in OA treatment. GO enrichment analysis demonstrated a robust correlation between Sip and inflammatory response, response to LPS and NF-κB-inducing kinase activity in OA. KEGG enrichment analysis highlighted the significance of NF-κB and PI3K-AKT pathways in Sip's therapeutic potential for OA. Furthermore, molecular docking results demonstrated Sip's robust binding affinity with p65 and PI3K. In vitro experiments demonstrated Sip's effectively suppressed the expression of pro-inflammatory factors induced by LPS, such as COX-2, iNOS, IL-1β, and IL-18. Besides, Sip counteracted the degradation of collagen-II and aggrecan within the ECM and the expression of MMP-13 and ADAMTS-5 mediated by LPS. The safeguarding effects of Sip were ascribed to its inhibition of PI3K/AKT/NF-κB pathway and NLRP3 inflammasome mediated pyroptosis. Additionally, in vivo experiments revealed that Sip could alleviate the subchondral remodeling, cartilage degeneration, synovitis as well as ECM degradation a mouse model of OA.
Sip exhibited potential in attenuating OA progression by suppressing the PI3K/AKT/NF-κB pathway, consequently inhibiting the activation of NLRP3 inflammasome and pyroptosis.
The translational potential of this articleThis study provides a biological rationale for the use of Sip as a potential candidate for OA treatment, provide a new concept for the cartilage targeted application of natural compounds.
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The translational potential of this article: This study provides a biological rationale for the use of Sip as a potential candidate for OA treatment, provide a new concept for the cartilage targeted application of natural compounds.
To evaluate the value of noninvasive prenatal testing (NIPT) in the screening of rare autosomal abnormalities and provide further support for the clinical application of NIPT.
A total of 81,518 ...pregnant women who underwent NIPT at the Anhui Maternal and Child Health Hospital between May 2018 and March 2022 were selected. The high-risk samples were analyzed using amniotic fluid karyotype and chromosome microarray analysis (CMA), and the pregnancy outcomes were followed up.
NIPT detected 292 cases (0.36%) with rare autosomal abnormalities among the 81,518 cases sampled. Of these, 140 (0.17%) showed rare autosomal trisomies (RATs), and 102 of these patients agreed to undergo invasive testing. Five cases were true positives, with a positive predictive value (PPV) of 4.90%. Copy number variants (CNV) were detected in 152 samples of the total cases (0.19%), and 95 of the patients involved agreed to the use of CMA. Twenty-nine of these cases were confirmed to be true positive, with a PPV of 30.53%. Detailed follow-up information was obtained in 81 cases from 97 patients with false-positive results for RATs. Thirty-seven of these cases (45.68%) had adverse perinatal outcomes, with a higher incidence of small for gestational age (SGA), intrauterine growth retardation (IUGR), and preterm birth (PTB).
NIPT is not recommended for screening for RATs. However, considering that positive results are associated with an increased risk of IUGR and PTB, additional fetal ultrasound examination should be performed to monitor fetal growth. In addition, NIPT has a reference value in screening for CNVs, especially pathogenic CNVs, but a comprehensive analysis of prenatal diagnosis combined with ultrasound and family history is still needed.
Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes joint destruction. Cucurbitacin B (CuB) is a naturally occurring triterpenoid compound derived from ...plants in the Cucurbitaceae family. The aim of this study is to investigate the potential role and mechanisms of CuB in a mouse model of OA. This study identified the key targets and potential pathways of CuB through network pharmacology analysis. In vivo and in vitro studies confirmed the potential mechanisms of CuB in OA. Through network pharmacology, 54 potential targets for CuB in treating OA were identified. The therapeutic potential of CuB is associated with the nod‐like receptor pyrin domain 3 (NLRP3) inflammasome and pyroptosis. Molecular docking results indicate a strong binding affinity of CuB to nuclear factor erythroid 2‐related factor 2 (Nrf2) and p65. In vitro experiments demonstrate that CuB effectively inhibits the expression of pro‐inflammatory factors induced by interleukin‐1β (IL‐1β), including cyclooxygenase‐2, inducible nitric oxide synthase, IL‐1β, and IL‐18. CuB inhibits the degradation of type II collagen and aggrecan in the extracellular matrix (ECM), as well as the expression of matrix metalloproteinase‐13 and a disintegrin and metalloproteinase with thrombospondin motifs‐5. CuB protects cells by activating the Nrf2/hemeoxygenase‐1 (HO‐1) pathway and inhibiting nuclear factor‐κB (NF‐κB)/NLRP3 inflammasome‐mediated pyroptosis. Moreover, in vivo experiments show that CuB can slow down cartilage degradation in an OA mouse model. CuB effectively prevents the progression of OA by inhibiting inflammation in chondrocytes and ECM degradation. This action is further mediated through the activation of the Nrf2/HO‐1 pathway to inhibit NF‐κB/NLRP3 inflammasome activation. Thus, CuB is a potential therapeutic agent for OA.
Background Mild cognitive impairment (MCI) is an age-related chronic noncommunicable disease facing a certain caregiving burden. At present, most studies focus on the caregiving burden and social ...support of caregivers of patients with moderate-to-severe cognitive impairment, but there are few studies on the social support and related factors of caregivers of MCI patients. Objective To explore the social support and related factors of caregivers of MCI patients, and provide evidence for feasible social support for caregivers of MCI patients. Methods A total of 102 family caregivers of patients initially diagnosed as MCI in Weifang Community Health Service Center, Pudong New Area, Shanghai from April 2020 to August 2021 were recruited. A cognitive impairment management group was established to investigate basic information, social support rate score (SSRS), positive aspects of caregiver (PAC) score and Zarit Caregiver Burden Questionnaire (ZBI) score of the caregivers of patients with MCI. The related factors o
Schematic diagram of Lycium berry phenolic composition, potential health benefits, and industrial applications.
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•Lycium berries of different species contain a total of 186 phenolic ...compounds.•Lycium berries have potent antioxidant activities and other health benefits due to their rich phenolics content.•More attention should be given to lignanamides and phenolic acids amides present in Lycium berries.•Phenolics content in dried Lycium berry is influenced by the processing method.•An increasing trend to incorporate Lycium berry into other food products as functional component.
This review provides a comprehensive summary of phenolic compounds in Lycium berry, focusing on their composition, functionalities, potential health benefits, industrial applications and their incorporation into different food products. This review summarizes 186 phenolic compounds in the Lycium berry, featuring the most abundant classes of flavonoids, phenolic acids and their derivatives. According to in vivo and in vitro studies, these phenolic compounds display potent antioxidant activities, anti-diabetic, anti-inflammatory, neuroprotective, anti-cancer effects and gut microbiota modulating effect. In the food industry, dried Lycium berry is the most common commodity, where different pretreatments and drying methods are implemented to preserve the fruit, in the meantime, play an important role to modify the phenolics composition and product quality. Recent industrial advances include incorporating Lycium berry into other food products, which could enhance the nutritional value, improve the sensory properties and attract consumers by meeting their health and organoleptic demands.
Anti-CD19 chimeric antigen receptor (CAR) T cell therapies can cause severe cytokine-release syndrome (CRS) and neurotoxicity, impeding their therapeutic application. Here we generated a new ...anti-CD19 CAR molecule (CD19-BBz(86)) derived from the CD19-BBz prototype bearing co-stimulatory 4-1BB and CD3ζ domains. We found that CD19-BBz(86) CAR T cells produced lower levels of cytokines, expressed higher levels of antiapoptotic molecules and proliferated more slowly than the prototype CD19-BBz CAR T cells, although they retained potent cytolytic activity. We performed a phase 1 trial of CD19-BBz(86) CAR T cell therapy in patients with B cell lymphoma (ClinicalTrials.gov identifier NCT02842138 ). Complete remission occurred in 6 of 11 patients (54.5%) who each received a dose of 2 × 10
-4 × 10
CD19-BBz(86) CAR T cells. Notably, no neurological toxicity or CRS (greater than grade 1) occurred in any of the 25 patients treated. No significant elevation in serum cytokine levels after CAR T cell infusion was detected in the patients treated, including in those who achieved complete remission. CD19-BBz(86) CAR T cells persistently proliferated and differentiated into memory cells in vivo. Thus, therapy with the new CD19-BBz(86) CAR T cells produces a potent and durable antilymphoma response without causing neurotoxicity or severe CRS, representing a safe and potent anti-CD19 CAR T cell therapy.
To investigate the chemical properties of PM2.5 and put forward reasonable control measures, daily samples of PM2.5 were collected at an urban site in Beijing from August 4 to September 3 of 2012 ...using two 2-channel samplers. Chemical analysis was conducted for eight water soluble inorganic ions (WSII, including Na+, NH4+, K+, Mg2+, Ca2+, Cl−, NO3−, and SO42−), organic carbon (OC) and elementary carbon (EC). PM2.5 concentrations ranged from 8.8 to 218.6μgm−3, with an average concentration of 80.6±57.3μgm−3. WSII, the most dominant PM2.5 constituents contributing 60±18% of its mass, ranged from 3.1 to 172.2μgm−3. SO42−, NO3−, and NH4+ dominated WSII (90±28%) and their concentrations were 1.3–105.7μgm−3, 0.5–52.7μgm−3 and 0.3–33.5μgm−3, respectively. The concentrations of OC and EC were 3.0–28.8 μgC m−3 and 0.8–7.4 μgC m−3, constituting 17.6% and 4.9% of PM2.5, respectively. Three serious pollution episodes (haze days) occurred during the campaign. PM2.5 and its chemical species showed substantial increases during haze episodes. The greater enhancement factors for SO42− (4.5), NO3− (4.0), and NH4+ (4.2) during haze days compared to non-haze days were obtained, suggesting that these secondary inorganic ions play important roles in the formation of haze. The average ratio of NO3−/SO42− was 0.52. Ion balance calculations showed that PM2.5 samples were acidic during haze periods and close to neutral during non-haze days. Correlation analysis between the major ions was conducted and the results suggested that the main forms of NH4+ might be (NH4)2SO4. In addition, the variations between haze days and non-haze days for OC, EC, and the ratio of OC/EC were discussed.
•Daily samples of PM2.5 were collected at Beijing from August 4 to September 3 of 2012.•Three serious pollution episodes (haze days) occurred.•Secondary inorganic ions play important roles in the formation of haze.•The variations during haze and non-haze days for WSII, OC, EC, and their ratios and sources were discussed.
•A high prevalence of probable PTSD (20.87%) was found about six months after the first local outbreak of COVID-19 among healthcare workers at the Central Hospital of Wuhan.•Healthcare workers with ...negative COVID-19 tests, those with high Social Support Self-Rating Scale (SSRS) scores, and HCWs whose family members tested negative were less likely to have probable PTSD.•High levels of psychiatric and somatic illness and insomnia were associated with probable PTSD.
This study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms and assessed mental illness via an online survey among healthcare workers (HCWs) at the Central Hospital of Wuhan after the peak of the COVID-19 outbreak. PTSD symptoms were measured using the PTSD Checklist Civilian Version (PCL-C), with a cutoff score of 50. Among the 642 HCWs, the prevalence of probable PTSD was 20.87%. Additionally, 88.88%, 82.09%, 100%, and 95.52% of HCWs with probable PTSD reported varying degrees of anxiety, depression, somatic symptoms, and insomnia, respectively. HCWs with probable PTSD scored higher on the Hospital Anxiety and Depression Scale (HADS), Patient Health questionnaire-15 (PHQ-15), and Insomnia Severity Index (ISI) than non-PTSD HCWs (all p < 0.05). Multivariate regression analysis revealed that HCWs with negative COVID-19 tests (OR, 0.35; 95% CI, 0.21–0.58; p < 0.00), those with high Social Support Self-Rating Scale (SSRS) scores (OR, 0.30; 95% CI, 0.17–0.52; p < 0.00), and HCWs whose family members tested negative (OR, 0.64; 95% CI, 0.42–0.96; p = 0.03) were less likely to have probable PTSD. This study found a high prevalence of probable PTSD and severe mental illness among local HCWs. Our finding emphasizes the need to provide mental health support for HCWs.
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