Reconstruction of a robust bacterial replication module.

Chromosomal DNA replication is a fundamental process of life, involving the assembly of complex machinery and dynamic regulation. In this study, we reconstructed a bacterial replication module (pRC) by artificially clustering 23 genes involved in DNA replication and sequentially deleting these genes from their naturally scattered loci on the chromosome of Escherichia coli. The integration of pRC into the chromosome, moving from positions farther away to close to the replication origin, leads to an enhanced efficiency in DNA synthesis, varying from lower to higher. Strains containing replication modules exhibited increased DNA replication by accelerating the replication fork movement and initiating chromosomal replication earlier in the replication cycle. The minimized module pRC16, containing only replisome and elongation encoding genes, exhibited chromosomal DNA replication efficiency comparable to that of pRC. The replication module demonstrated robust and rapid DNA replication, regardless of growth conditions. Moreover, the replication module is plug-and-play, and integrating it into Mb-sized extrachromosomal plasmids improves their genetic stability. Our findings indicate that DNA replication, being a fundamental life process, can be artificially reconstructed into replication functional modules. This suggests potential applications in DNA replication and the construction of synthetic modular genomes.

Epigenetic regulation of DNA repair gene program by Hippo/YAP1-TET1 axis mediates sorafenib resistance in HCC.

Hepatocellular carcinoma (HCC) is a malignancy that occurs worldwide and is generally associated with poor prognosis. The development of resistance to targeted therapies such as sorafenib is a major challenge in clinical cancer treatment. In the present study, Ten-eleven translocation protein 1 (TET1) was found to be highly expressed in sorafenib-resistant HCC cells and knockdown of TET1 can substantially improve the therapeutic effect of sorafenib on HCC, indicating the potential important roles of TET1 in sorafenib resistance in HCC. Mechanistic studies determined that TET1 and Yes-associated protein 1 (YAP1) synergistically regulate the promoter methylation and gene expression of DNA repair-related genes in sorafenib-resistant HCC cells. RNA sequencing indicated the activation of DNA damage repair signaling was extensively suppressed by the TET1 inhibitor Bobcat339. We also identified TET1 as a direct transcriptional target of YAP1 by promoter analysis and chromatin-immunoprecipitation assays in sorafenib-resistant HCC cells. Furthermore, we showed that Bobcat339 can overcome sorafenib resistance and synergized with sorafenib to induce tumor eradication in HCC cells and mouse models. Finally, immunostaining showed a positive correlation between TET1 and YAP1 in clinical samples. Our findings have identified a previously unrecognized molecular pathway underlying HCC sorafenib resistance, thus revealing a promising strategy for cancer therapy.

Children's oppositional defiant disorder symptoms and neural synchrony in mother-child interactions: An fNIRS study.

Interpersonal neural synchrony (INS) between mothers and children responds to the temporal similarity of brain signals in joint behavior between dyadic partners and is considered an important neural indicator of the formation of adaptive social interaction bonds. Parent-child interactions are particularly important for the development and maintenance of oppositional defiant disorder (ODD) in children, but the underlying neurocognitive mechanisms are unknown. Therefore, in the current study we measured INS between mothers and children in interactions by using simultaneous functional Near-infrared Spectroscopy (fNIRS), and explored its association with ODD symptoms in children. Seventy-two mother-child dyads were recruited to participate in the study, including 35 children with ODD and 37 healthy children to be used as a control. Each mother-child dyad was measured for neural activity in frontal, parietal, and temporal lobe regions while completing free-play as well as positive, and negative topic discussion tasks. We used Phase-locked value to calculate the synchrony strength and then used the K-means algorithm and k-space based alignment tests to confirm the specific patterns of parent-child synchrony in different brain areas. The results showed that, in free-play (right MFG and bilateral SFG), positive (left TPJ and bilateral SFGdor), and negative (bilateral SFGmed, right ANG, and left MFG) topic discussions, the mother-child pairs showed different patterns of INS. These specific INS patterns were significantly lower in the ODD group compared to the control group and were negatively associated with ODD symptoms in children. Network analyses showed that these INS patterns were connected to different nodes in the ODD symptom network. Our findings suggest that ODD mother-child dyads exhibit lower neural synchrony across a wide range of parent-child interactions. Neural synchrony in the context of interpersonal interactions provides new insights into understanding the neural mechanisms of ODD and can be used as an indicator of neural and socio-environmental factors in the network of psychological disorder symptoms.

Immune repertoire profiling in myasthenia gravis.

Myasthenia gravis (MG) is the most frequent immune-mediated neurological disorder, characterized by fluctuating muscle weakness. Specific recognition of self-antigens by T-cell receptors (TCRs) and B-cell receptors (BCRs), coupled with T-B cell interactions, activates B cells to produce autoantibodies, which are critical for the initiation and perpetuation of MG. The immune repertoire comprises all functionally diverse T and B cells at a specific time point in an individual, reflecting the essence of immune selectivity. By sequencing the nucleotide sequences of TCRs and BCRs, it is possible to track individual T- and B-cell clones. This review delves into the generation of autoreactive TCRs and BCRs in MG and comprehensively examines the applications of immune repertoire sequencing in understanding disease pathogenesis, developing diagnostic and prognostic markers and informing targeted therapies. We also discuss the current limitations and future potential of this approach.

Identification and characterization of a novel type II toxin-antitoxin system in Aeromonas veronii.

The bacterial type II toxin-antitoxin (TA) system is a rich genetic element that participates in various physiological processes. Aeromonas veronii is the main bacterial pathogen threatening the freshwater aquaculture industry. However, the distribution of type II TA system in A. veronii was seldom documented and its roles in the life activities of A. veronii were still unexplored. In this study, a novel type II TA system AvtA-AvtT was predicted in a fish pathogen Aeromonas veronii biovar sobria with multi-drug resistance using TADB 2.0. Through an Escherichia coli host killing and rescue assay, we demonstrated that AvtA and AvtT worked as a genuine TA system, and the predicted toxin AvtT actually functioned as an antitoxin while the predicted antitoxin AvtA actually functioned as a toxin. The binding ability of AvtA with AvtT proteins were confirmed by dot blotting analysis and co-immunoprecipitation assay. Furthermore, we found that the toxin and antitoxin labelled with fluorescent proteins were co-localized. In addition, it was found that the transcription of AvtAT bicistronic operon was repressed by the AvtAT protein complex. Deletion of avtA gene and avtT gene had no obvious effect on the drug susceptibility. This study provides first characterization of type II TA system AvtA-AvtT in aquatic pathogen A. veronii.

Comparing ultrasound-derived fat fraction and MRI-PDFF for quantifying hepatic steatosis: a real-world prospective study.

OBJECTIVE: To compare the agreement between ultrasound-derived fat fraction (UDFF) with magnetic resonance proton density fat fraction (MRI-PDFF) for quantification of hepatic steatosis and verify its reliability and diagnostic performance by comparing with MRI-PDFF as the reference standard. METHODS: This prospective study included a primary analysis of 191 patients who underwent MRI-PDFF and UDFF from February 2023 to February 2024. MRI-PDFF were derived from three liver segment measurements with calculation of an overall median PDFF. UDFF was performed by two different sonographers for each of the six measurements, and the median was taken. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to assess agreement. Receiver operating characteristics (ROC) curves were used to evaluate the diagnostic performance of UDFF in detecting different degrees of hepatic steatosis. RESULTS: A total of 176 participants were enrolled in the final cohort of this study (median age, 36.0 years; 82 men, 94 women). The median MRI-PDFF value was 11.3% (interquartile range (IQR) 7.5-18.9); 84.7% patients had a median MRI-PDFF value ≥ 6.4%. The median UDFF measured by different sonographers were 9.5% (IQR: 5.0-18.0) and 9.0% (IQR: 5.0-18.0), respectively. The interobserver agreement of UDFF measurement was excellent agreement (ICC = 0.951 [95% CI: 0.934-0.964], p < 0.001). UDFF was positively strongly correlated with MRI-PDFF with ICC of 0.899 (95% CI: 0.852-0.930). The Bland-Altman analysis showed high agreement between UDFF and MRI-PDFF measurements, with a mean bias of 1.7% (95% LOA, -8.7 to 12.2%). The optimal UDFF cutoff values were 5.5%, 15.5% and 17.5% for detecting MRI-PDFF at historic thresholds of 6.4%, 17.4%, and 22.1%, with AUC of 0.851, 0.952, and 0.948, respectively. The sensitivity was 79.2%, 87.5%, 88.9%, and specificity was 81.5%, 90.6%, 90.0%, respectively. CONCLUSIONS: UDFF is a reliable and accurate method for quantification and classification of hepatic steatosis, with strong agreement to MRI-PDFF. The UDFF cutoff values of 5.5%, 15.5%, and 17.5% provide high sensitivity and specificity for the detection of mild, moderate, and severe hepatic steatosis, respectively. KEY POINTS: Question Is ultrasound-derived fat fraction (UDFF) reliable for the quantitative detection of hepatic steatosis compared to MRI proton density fat fraction (MRI-PDFF)? Findings UDFF cutoff values of 5.5%, 15.5%, and 17.5% provided high sensitivity and specificity for the detection of mild, moderate, and severe hepatic steatosis, respectively. Clinical relevance UDFF is a reliable and accurate method for quantification and classification of hepatic steatosis, with strong agreement to MRI-PDFF and high reproducibility of liver fat content by different sonographers.

Effects of Antibiotics on the DAMO Process and Microbes in Cattle Manure.

Denitrifying anaerobic methane oxidation (DAMO) can mitigate methane emissions; however, this process has not been studied in cattle manure, an important source of methane emissions in animal agriculture. The objective of this study was to investigate the occurrence of DAMO microbes in cattle manure and examine the impacts of veterinary antibiotics on the DAMO process in cattle manure. Results show that DAMO archaea and bacteria consistently occur at high concentrations in beef cattle manure. During the long-term operation of a sequencing batch reactor seeded with beef cattle manure, the DAMO activities intensified, and DAMO microbial biomass increased. Exposure to chlortetracycline at initial concentrations up to 5000 µg L-1 did not inhibit DAMO activities or affect the concentrations of the 16S rRNA gene and functional genes of DAMO microbes. In contrast, exposure to tylosin at initial concentrations of 50 and 500 µg L-1 increased the activities of the DAMO microbes. An initial concentration of 5000 µg L-1 TYL almost entirely halted DAMO activities and reduced the concentrations of DAMO microbes. These results show the occurrence of DAMO microbes in cattle manure and reveal that elevated concentrations of dissolved antibiotics could inhibit the DAMO process, potentially affecting net methane emissions from cattle manure.

Caffeine and neonatal acute kidney injury.

Acute kidney injury is one of the most threatening diseases in neonates, with complex pathogenesis and limited treatment options. Caffeine is a commonly used central nervous system stimulant for treating apnea in preterm infants. There is compelling evidence that caffeine may have potential benefits for preventing neonatal acute kidney injury, but comprehensive reports are lacking in this area. Hence, this review aims to provide a summary of clinical data on the potential benefits of caffeine in improving neonatal acute kidney injury. Additionally, it delves into the molecular mechanisms underlying caffeine's effects on acute kidney injury, with a focus on various aspects such as oxidative stress, adenosine receptors, mitochondrial dysfunction, endoplasmic reticulum stress, inflammasome, autophagy, p53, and gut microbiota. The ultimate goal of this review is to provide information for healthcare professionals regarding the link between caffeine and neonatal acute kidney injury and to identify gaps in our current understanding.

Risk of incident venous thromboembolism in patients with atopic dermatitis: systematic analysis of the literature and meta-analysis.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. While various inflammatory conditions have been linked to venous thromboembolism (VTE), the risk of VTE among patients with AD remains unclear. We sought to systematically review and meta-analyze population-based studies to determine the association between AD and incident VTE. A systematic review was performed of published studies in PubMed, Web of Science, Embase and Cochrane library from their inception to 27 May 2024. At least two reviewers conducted title/abstract, full-text review and data extraction. Cohort studies examining the association of AD with incident VTE were included. Quality of evidence was assessed using the Newcastle-Ottawa Scale. Six cohort studies, encompassing a total of 10,186,861 participants, were included. The meta-analysis revealed a significantly increased risk for incident VTE among AD patients (pooled hazard ratio (HR), 1.10; 95% CI, 1.00-1.21), with an incidence rate of VTE at 3.35 events per 1000 patient-years. Individual outcome analyses suggested that AD was associated with higher risks of deep vein thrombosis (pooled HR, 1.15; 95% CI, 1.04-1.27) but not pulmonary embolism (pooled HR, 0.99; 95% CI, 0.87-1.13). This systematic review and meta-analysis indicated an increased risk of incident VTE among patients with AD. Future studies are necessary to elucidate the underlying pathophysiology of the association between AD and VTE.

Hedgehog signaling regulates bone homeostasis through orchestrating osteoclast differentiation and osteoclast-osteoblast coupling.

Imbalance of bone homeostasis induces bone degenerative diseases such as osteoporosis. Hedgehog (Hh) signaling plays critical roles in regulating the development of limb and joint. However, its unique role in bone homeostasis remained largely unknown. Here, we found that canonical Hh signaling pathway was gradually augmented during osteoclast differentiation. Genetic inactivation of Hh signaling in osteoclasts, using Ctsk-Cre;Smof/f conditional knockout mice, disrupted both osteoclast formation and subsequent osteoclast-osteoblast coupling. Concordantly, either Hh signaling inhibitors or Smo/Gli2 knockdown stunted in vitro osteoclast formation. Mechanistically, Hh signaling positively regulated osteoclast differentiation via transactivation of Traf6 and stabilization of TRAF6 protein. Then, we identified connective tissue growth factor (CTGF) as an Hh-regulatory bone formation-stimulating factor derived from osteoclasts, whose loss played a causative role in osteopenia seen in CKO mice. In line with this, recombinant CTGF exerted mitigating effects against ovariectomy induced bone loss, supporting a potential extension of local rCTGF treatment to osteoporotic diseases. Collectively, our findings firstly demonstrate that Hh signaling, which dictates osteoclast differentiation and osteoclast-osteoblast coupling by regulating TRAF6 and CTGF, is crucial for maintaining bone homeostasis, shedding mechanistic and therapeutic insights into the realm of osteoporosis.

The ICF2 gene Zbtb24 specifically regulates the differentiation of B1 cells via promoting heme synthesis.

BACKGROUND: Loss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype-phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells. METHODS: We used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms. RESULTS: Zbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. CONCLUSIONS: Zbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.

Unveiling Gambogenic Acid as a Promising Antitumor Compound: A Review.

Gambogenic acid is a derivative of gambogic acid, a polyprenylated xanthone isolated from Garcinia hanburyi. Compared with the more widely studied gambogic acid, gambogenic acid has demonstrated advantages such as a more potent antitumor effect and less systemic toxicity than gambogic acid according to early investigations. Therefore, the present review summarizes the effectiveness and mechanisms of gambogenic acid in different cancers and highlights the mechanisms of action. In addition, drug delivery systems to improve the bioavailability of gambogenic acid and its pharmacokinetic profile are included. Gambogenic acid has been applied to treat a wide range of cancers, such as lung, liver, colorectal, breast, gastric, bladder, and prostate cancers. Gambogenic acid exerts its antitumor effects as a novel class of enhancer of zeste homolog 2 inhibitors. It prevents cancer cell proliferation by inducing apoptosis, ferroptosis, and necroptosis and controlling the cell cycle as well as autophagy. Gambogenic acid also hinders tumor cell invasion and metastasis by downregulating metastasis-related proteins. Moreover, gambogenic acid increases the sensitivity of cancer cells to chemotherapy and has shown effects on multidrug resistance in malignancy. This review adds insights for the prevention and treatment of cancers using gambogenic acid.

Coagulation Risk Predicting in Anticoagulant-Free Continuous Renal Replacement Therapy.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is a prolonged continuous extracorporeal blood purification therapy to replace impaired renal function. Typically, CRRT therapy requires routine anticoagulation, but for patients at risk of bleeding and with contraindications to sodium citrate, anticoagulant-free dialysis therapy is necessary. However, this approach increases the risk of CRRT circuit coagulation, leading to treatment interruption and increased resource consumption. In this study, we utilized artificial intelligence machine learning methods to predict the risk of CRRT circuit coagulation based on pre-CRRT treatment metrics. METHODS: We retrospectively analyzed 212 patients who underwent anticoagulant-free CRRT from October 2022 to October 2023. Patients were categorized into high-risk and low-risk groups based on CRRT circuit coagulation within 24 h. We employed eight machine learning methods to predict the risk of circuit coagulation. The performance of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic. 5-fold cross-validation was used to validate the machine learning models. Feature importance and SHAP plots were used to interpret the model's performance and key drivers. RESULTS: We identified 88 patients (41.51%) at high risk of circuit coagulation within 24 h of CRRT. Our machine learning models showed excellent predictive performance, with ensemble learning achieving an AUC of 0.863 (95% CI: 0.860-0.868), outperforming individual algorithms. Random forest was the best single-algorithm model, with an AUC of 0.819 (95% CI: 0.814-0.823). The top three features identified as most important by the SHAP summary plot and feature importance graph are platelet, filtration fraction (FF), and triglycerides. CONCLUSION: We created a model using machine learning to predict the risk of circuit coagulation during anticoagulant-free CRRT therapy. Our model performs well (AUC 0.863) and identifies key factors like platelets, FF, and triglycerides. This facilitates the development of personalized treatment strategies by clinicians aimed at reducing circuit coagulation risk, thereby enhancing patient outcomes and reducing healthcare expenses.

Survey on pattern of myopia in school children in Hangzhou after the COVID-19 pandemic: a school-based vision screening study.

BACKGROUND: Myopia is a major health issue around the world. Myopia in children has increased significantly during the COVID-19 pandemic in China, but reports are scarce on the prevalence of myopia following the pandemic. This study collected vision screening data of school children in China for five consecutive years to observe the changes in myopia after the pandemic and compare the observed prevalence of myopia before and after the pandemic. METHODS: A school-based vision screening study used stratified samplings to collect the vision screening data in school children aged 6-13 from 45 primary schools in Hangzhou. Vision screening data including uncorrected visual acuity(UCVA) and spherical equivalent refraction(SER). Calculating the mean of SER and the prevalence of myopia and hyperopia from 2019 to 2023. RESULTS: A total of 79,068 screening results (158,136 eyes) were included in the analysis. A substantial myopic shift (approximately -0.30 diopters [D] on average) was found in 2020 and 2021 compared with 2019 in all age groups and a substantial myopic shift (approximately 0.4 D on average) was found in 2022 compared with 2021. A slight myopic shift (approximately -0.14 D on average) was found in 2023 compared with 2022. The prevalence of myopia in all age groups was the highest for five years in 2020 or 2021, which was 31.3% for 6-year-olds, 43.0% for 7-year-olds, and 53.7% for 8-year-olds. A positive change in the prevalence rate of myopia was found at 6 years old (0.59%, 0.12%, 0.36%, 0.25%, p < 0.001). The change in prevalence rate in myopia was shifted slightly in children aged 10-13 years. Children aged 8 to 13 years had a slight increase in myopia prevalence from 2022 to 2023. The prevalence of hyperopia was low and stable in all grade groups, ranging from 0.7% to 2.2% over five years. CONCLUSION: Myopia in children has increased rapidly during the COVID-19 pandemic. After the pandemic, the prevalence of myopia in children gradually decreased temporarily and then rebounded. Myopic shift was more apparent in younger children. Myopic shift in children may be related to the reduction of outdoor time, less light, and near work habits, and further research is needed.

Assessment of Fetal Ventricular Size and Shape in Women With Intrahepatic Cholestasis of Pregnancy Using Speckle Tracking.

OBJECTIVE: To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology. METHODS: This case-control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24-segment spherical indices (SIs) were measured and compared between groups. RESULTS: The routine fetal cardiac parameters, global and right-ventricular SIs did not differ between the ICP and control groups. The left-ventricular apical (segments 16-24) SIs were lower in the ICP group than in the control group (P < .05), with no significant difference in the other left-ventricular segments. CONCLUSIONS: Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty-four-segment SIs can be used to effectively evaluate these changes.

Grandmother-grandchild physiological synchrony in Chinese three-generation families: Links with child emotion regulation.

The current study examined the characteristics of physiological synchrony between grandmothers and grandchildren in Chinese three-generation families, and the associations between physiological synchrony and child emotion regulation. The participants included 92 children (age 8-10-year old) and their grandmothers. Respiratory sinus arrhythmia (RSA) was collected from both grandmothers and their grandchildren throughout a collaborative drawing task and a conflict discussion task. Child emotion regulation was measured using the Children's Emotional Management Scale. We found no evidence for an overall pattern of concordant or discordant synchrony within dyads. Instead, there was great variability in patterns of synchrony across dyads. During the collaborative drawing task, concordance in grandmother's RSA and grandchildren's subsequent RSA was linked with better emotion regulation. During the conflict discussion, concordance in grandmother's RSA and grandchildren's simultaneous RSA was linked with poorer emotion regulation. These results suggest that grandmother-grandchild synchrony in different directions, time lags, and contexts has different influences on children's emotion regulation. The findings of this study highlight the importance of contextual physiological co-regulation between Chinese children and their grandmothers for children's social-emotional development.

Effects of biological agents on glycogen metabolism in psoriasis patients: A systematic review and meta-analysis.

The effectiveness and safety of biological agents for treating psoriasis have been confirmed; however, their effects on glucose metabolism biomarkers in psoriasis patients remain unclear. A systematic review and meta-analysis were performed according to PRISMA guidelines. The final analysis enrolled 12 studies, including eight randomized controlled trial (RCT) (n = 5628 patients) and four observational cohort studies (OBSs) (n = 393 patients). The meta-analysis comprising nine studies (six RCTs and three OBSs) revealed a slight reduction in the levels of HOMA-IR associated with the use of biological therapies in OBS (biological therapies vs. traditional therapies: WMD = -0.2, CI = -0.10 to 0.50, p = 0.02). Although a considerable number of studies were analysed, our review did not show a significant alteration in HOMA-IR levels among patients treated with biological therapies such as IL-17 inhibitors and IL-12/23 inhibitors at weeks 12-16 in RCTs. We also did not observe remarkable alterations in the fasting plasma glucose levels of patients in both OBS and RCT. Additional RCT on a larger scale and duration is required to provide more conclusive evidence regarding the effect of biological agents on glycogen metabolism in psoriasis.

Transmission of depressive symptoms in the nuclear family: a cross-sectional and cross-lagged network perspective.

Children are more likely to develop depressive symptoms in families where parents have depressive symptoms. By conceptualizing the individual depressive symptom network of each family member as a whole, this study proposes a family symptom network model, and explored the mechanisms of transmission of depression within nuclear families at the symptom level. This study used four waves (2012, 2016, 2018, 2020) of data from the China Family Panel Studies (CFPS), which in wave one contained a representative sample of 1963 children (1038 boys; age = 12.60), 4763 mothers and 4614 fathers from China. Children with their parents completed the Center for Epidemiology Studies Depression Scale at each wave. Individual depressive symptom networks among children, fathers, and mothers were highly similar and stable across time. When considering depressive symptoms of all family members as a whole, there was a wide range of associations between child, father, and mother depressive symptom networks. The results of the cross-lagged network model suggest the bidirectional relationships between couples and parent-child depression. The current study provides preliminary validation of the family symptom network model. The model represents a further integration and extension of network theory of mental disorders and family systems theory, and points out the limitations of studying the intergenerational transmission of depression from a latent variable perspective. Thus, the family symptom network model proposed in this study could provide valuable new insights into understanding the intergenerational transmission of depression.

Longitudinal relationship between oppositional defiant disorder symptoms and attention-deficit/hyperactivity disorder symptoms in Chinese children: insights from cross-lagged panel network analyses.

Oppositional defiant disorder (ODD) and attention-deficit/hyperactivity disorder (ADHD) are two of the most common childhood mental disorders, and they have substantial comorbidity. The developmental precursor model has long been widely used to explain the mechanisms of comorbidity between ODD and ADHD, however whether it is equally effective at the symptomatic level is unclear. Therefore, this study aimed to (a) examine the stability of the ODD and ADHD comorbidity network in a longitudinal sample of high-risk children in China; and (b) examine the longitudinal relationship between the ODD and ADHD symptom networks based on a developmental precursor model. Two hundred sixty-three Chinese children aged 6 to 13 years with ODD and/or ADHD were assessed for symptoms of ODD and ADHD in two surveys conducted 1 year apart. We used data from these two time points to construct two cross-sectional networks and a cross-lagged panel network (CLPN) to explore the symptom network for comorbidity of ODD and ADHD. The analysis shows that: (1) the two cross-sectional networks are highly similar in terms of structure, existence of edges, centrality estimates, and the invariance test shows that there is no significant difference between them. The symptoms "follow through", "interrupts/intrudes", "difficulty playing quietly" and "concentration" had the highest expected influence centrality at both time points. (2) Combined with the results of the cross-sectional and cross-lagged networks, we found that "annoy" and "blame" are potential bridge symptoms between the ODD and ADHD symptom networks. The symptom "annoy" forms a reciprocal predictive relationship with "interrupts/intrudes", while "blame" unidirectionally predicts "close attention". In addition, we found that "vindictive" predicted numerous ADHD symptoms, whereas "angry" was predicted by numerous ADHD symptoms. The findings emphasize the broad predictive relationship between ODD and ADHD symptoms with each other, and that ODD symptoms may lead to activation of the ADHD symptom network and vice versa. These findings suggest that the developmental precursor model at the symptom level may partially explain the comorbidity mechanisms of ODD and ADHD, and future studies should further investigate the underlying multiple mechanisms.

Effect of remimazolam on intra-operative hypotension: Systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hypotension is common during anaesthesia. Increasing number of studies have reported that remimazolam may be associated with lower incidence of intra-operative hypotension compared with other anaesthetics. However, the results remain controversial. OBJECTIVE: This study aimed to evaluate the influence of remimazolam on intra-operative hypotension and its related outcomes (hypoxaemia, bradycardia and time to awake). DESIGN: A systematic review of randomised controlled trials (RCTs) with meta-analyses. DATA SOURCES: PubMed, Cocharane and Embase databases were searched to identify eligible RCTs published up to June 2024. ELIGIBILITY CRITERIA: RCTs published in English were eligible for inclusion. The study patients were 18 years or older who were administered with remimazolam and other positive control agents in either the pre-operative or intra-operative period. The incidence of intra-operative hypotension was identified in these studies. RESULTS: This study evaluated 34 trials including 4847 individuals. Basing on moderate-certainty evidence, we found that remimazolam administration reduced the incidence of intra-operative hypotension [risk ratio (RR) = 0.48, 95% confidence interval (95% CI): 0.41 to 0.57] and bradycardia (16 studies, n  = 2869, RR = 0.40, 95% CI: 0.29 to 0.54). No difference was observed in the incidence of hypoxaemia (RR = 0.70, 95% CI: 0.48 to 1.01) and time to awake (MD = -0.91, 95% CI: -2.42 to 0.60). The remarkable association between remimazolam and hypotension remained robust and significant, regardless of general anaesthesia or procedural sedation ( P  < 0.01, I2  = 82%). No significant difference was found between different control drugs ( P  = 0.97, I2  = 82%). CONCLUSION: Moderate-quality evidence shows that remimazolam administration to patients undergoing general anaesthesia or procedural sedation decreases the incidence of intra-operative hypotension and bradycardia.