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Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs. From July 2019 to June 2020, we performed a case-control study among children aged 3–24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs. 304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44–36.58, P = 0.0165). Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.

Networks-or graphs-are universal descriptors of systems of interacting elements. In biomedicine and healthcare, they can represent, for example, molecular interactions, signalling pathways, disease co-morbidities or healthcare systems. In this Perspective, we posit that representation learning can realize principles of network medicine, discuss successes and current limitations of the use of representation learning on graphs in biomedicine and healthcare, and outline algorithmic strategies that leverage the topology of graphs to embed them into compact vectorial spaces. We argue that graph representation learning will keep pushing forward machine learning for biomedicine and healthcare applications, including the identification of genetic variants underlying complex traits, the disentanglement of single-cell behaviours and their effects on health, the assistance of patients in diagnosis and treatment, and the development of safe and effective medicines.

Parents provide motivational and cognitive support within the same interaction, yet researchers have investigated these separately. We examined two key aspects of parental support, praise (motivational support) and spatial language (cognitive support), from fathers and mothers during three tasks with their first-grade children (6-7-year-olds

To evaluate the effects of different interventions on Internet addiction (IA), a meta-analysis and network meta-analyses were performed.We searched PubMed, Cochrane, Embase, Web of Science, PsycINFO, ProQuest, CNKI, WanFang, VIP database, and CBM from their inception to August 2021 to identify randomized controlled trials (RCTs) where the effects of interventions on IA were assessed. The risk of bias was evaluated according to the Revised Cochrane risk-of-bias tool for randomized trials (RoB2). The R studio Software and Stata 14.0 were used to perform traditional meta-analysis and network meta-analyses.A total of 59 RCTs including 3832 participants were incorporated into meta-analysis. The results of the traditional meta-analysis of 24 studies showed that CBT, group counseling, sports intervention, and Internet-based intervention could significantly reduce IA levels (SMD = -1.90, 95%CI: -2.26 to -1.55, P 0.01, IMost interventions have significant effects on the treatment of IA. Compared with single interventions, combined interventions showed a more pronounced improvement in Internet addiction symptoms.

Automatic detection of cervical lesion cells or cell clumps using cervical cytology images is critical to computer-aided diagnosis (CAD) for accurate, objective, and efficient cervical cancer screening. Recently, many methods based on modern object detectors were proposed and showed great potential for automatic cervical lesion detection. Although effective, several issues still hinder further performance improvement of such known methods, such as large appearance variances between single-cell and multi-cell lesion regions, neglecting normal cells, and visual similarity among abnormal cells. To tackle these issues, we propose a new task decomposing and cell comparing network, called TDCC-Net, for cervical lesion cell detection. Specifically, our task decomposing scheme decomposes the original detection task into two subtasks and models them separately, which aims to learn more efficient and useful feature representations for specific cell structures and then improve the detection performance of the original task. Our cell comparing scheme imitates clinical diagnosis of experts and performs cell comparison with a dynamic comparing module (normal-abnormal cells comparing) and an instance contrastive loss (abnormal-abnormal cells comparing). Comprehensive experiments on a large cervical cytology image dataset confirm the superiority of our method over state-of-the-art methods.

Background The aging brain is typically associated with aberrant interactions of large-scale intrinsic networks. However, the dynamic variation of these networks' coactivation or deactivation across the adult lifespan remains unclear. Purpose To promote the interpretation of dynamic brain network variations underlying the complex aging process by quantifying activation levels and obtaining a clear definition of coactivation patterns (CAPs) with resting-state functional MRI (rsfMRI). Materials and Methods In a retrospective study (October 2010 to September 2013), rsfMRI data from healthy participants in the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data repository were used to generate CAPs by applying single-volume temporal clustering analysis. Spatial clustering analysis was then performed to capture dynamic coactivation and deactivation within or between primary sensory networks and high-order cognitive networks (including the default mode network [DMN], attentional network [AN], and frontoparietal network [FPN]). Linear relationships between dynamic metrics and age were revealed with Spearman partial correlations. Results A total of 614 participants (mean age, 54 years ± 18 [SD]; 311 women) ranging in age from 18 to 88 years were evaluated. There was a negative correlation of the CAPs (Spearman correlations

Design of chemical probes with high specificity and responses are particularly intriguing. In this work, a fluorescent probe (

BACKGROUND: Rewriting the genomes of living organisms has been a long-standing aim in the biological sciences. The revelation of the CRISPR/Cas9 technology has revolutionized the entire biological field. Since its emergence, this technology has been widely applied to induce gene knockouts, insertions, deletions, and base substitutions. However, the classical version of this system was imperfect for inducing or correcting desired mutations. A subsequent development generated more advanced classes, including cytosine and adenine base editors, which can be used to achieve single nucleotide substitutions. Nevertheless, these advanced systems still suffer from several limitations, such as the inability to edit loci without a suitable PAM sequence and to induce base transversions. On the other hand, the recently emerged prime editors (PEs) can achieve all possible single nucleotide substitutions as well as targeted insertions and deletions, which show promising potential to alter and correct the genomes of various organisms. Of note, the application of PE to edit livestock genomes has not been reported yet.RESULTS: In this study, using PE, we successfully generated sheep with two agriculturally significant mutations, including the fecundity-related FecBB p.Q249R and the tail length-related TBXT p.G112W. Additionally, we applied PE to generate porcine blastocysts with a biomedically relevant point mutation (KCNJ5 p.G151R) as a porcine model of human primary aldosteronism.CONCLUSIONS: Our study demonstrates the potential of the PE system to edit the genomes of large animals for the induction of economically desired mutations and for modeling human diseases. Although prime-edited sheep and porcine blastocysts could be generated, the editing frequencies are still unsatisfactory, highlighting the need for optimizations in the PE system for efficient generation of large animals with customized traits.

To identify magnetic resonance imaging (MRI) features associated with injury type, severity, and liver transplantation (LT)/liver-related death (LRD) in drug-induced liver injury (DILI).The eligible DILI patients (2016 to 2020) who underwent contrast abdominal MRI within 3 months of onset were retrospectively analysed at Beijing Friendship Hospital, Capital Medical University. The MRI features independently associated with severity and prognosis were identified by backwards logistic regression. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) are given.The median age of 180 patients was 55.5 years, with 126 (70.0%) women. The injury types included hepatocellular (135 cases, 75.0%), mixed (23, 12.8%), and cholestatic (22, 12.2%). The proportion of periportal oedema in patients with hepatocellular and mixed injury was significantly higher than that in cholestatic injury (62.2%, 47.8% vs. 18.2%, p0.001). For severity, 157 (87.2%) patients had mild to moderate injury, and 23 (12.8%) had severe to fatal/LT. Irregularity of the liver surface (6.56 (95% CI, 1.27-22.84)), transient hepatic attenuation difference (THAD) (3.27 (95% CI, 1.14-9.36)), and splenomegaly (5.86 (95% CI, 1.96-17.53)) were independently associated with severity. Eight (4.4%) patients died/underwent LT. THAD (8.89 (95% CI, 1.35-58.43)), and ascites (64.63 (95% CI, 6.93-602.40)) were independently associated with LT/LRD. The prediction of the new model employing THAD and ascites for LT/LRD within 1 year was 0.959 (95% CI, 0.917-1.000).Periportal oedema was associated with the type of injury. Irregularity of the liver surface, THAD, and splenomegaly were associated with severity. THAD and ascites may have potential clinical utility in predicting LT/LRD outcomes within 1 year.• Contrast abdominal magnetic resonance imaging features can help clinicians evaluate the type of injury, severity, and poor prognosis of drug-induced liver injury. • Transient hepatic attenuation difference and ascites have potential clinical utility in the prediction of the poor prognosis of liver transplantation/liver-related death. • The new model predicting poor prognosis has a relatively high sensitivity of 0.875 and a high specificity of 0.919.

Objectives: The aim is to evaluate the efficacy of cognitive behavioral therapy for insomnia (CBT-I) in older adults. We searched six databases to identify articles published in English or Chinese until January 30th, 2022. Methods: The two authors of the review independently selected the studies, assessed the risk of bias, and extracted the data. Fourteen studies were included. Results: Based on the results from sleep logs, a significant pooled effect size was observed for sleep efficiency (SE%) (MD = 8.36; 95% CI, 5.96–10.76; I 2 = 77%; p < .00001), sleep onset latency (SOL) (MD = −9.29; 95% CI, −13.62 to −4.96; I 2 = 64%; p < 0.0001), wake after sleep onset (WASO) (MD = −23.44; 95% CI, −32.41 to −14.47; I 2 = 85%; p < .00001), and total sleep time (TST) (MD = −12.35; 95% CI, −21.27 to −3.42; I 2 = 63%; p = 0.007). Conclusions: Our study suggests that CBT-I may be a safe and effective approach for improving insomnia in older adults.

Dynamic changes of the paired heavy and light chain B cell receptor (BCR) repertoire provide an essential insight into understanding the humoral immune response post-SARS-CoV-2 infection and vaccination. However, differences between the endogenous paired BCR repertoire kinetics in SARS-CoV-2 infection and previously recovered/naïve subjects treated with the inactivated vaccine remain largely unknown. We performed single-cell V(D)J sequencing of B cells from six healthy donors with three shots of inactivated SARS-CoV-2 vaccine (BBIBP-CorV), five people who received the BBIBP-CorV vaccine after having recovered from COVID-19, five unvaccinated COVID-19 recovered patients and then integrated with public data of B cells from four SARS-CoV-2-infected subjects. We discovered that BCR variable (V) genes were more prominently used in the SARS-CoV-2 exposed groups (both in the group with active infection and in the group that had recovered) than in the vaccinated groups. The VH gene that expanded the most after SARS-CoV-2 infection was IGHV3-33, while IGHV3-23 in the vaccinated groups. SARS-CoV-2-infected group enhanced more BCR clonal expansion and somatic hypermutation than the vaccinated healthy group. A small proportion of public clonotypes were shared between the SARS-CoV-2 infected, vaccinated healthy, and recovered groups. Moreover, several public antibodies had been identified against SARS-CoV-2 spike protein. We comprehensively characterize the paired heavy and light chain BCR repertoire from SARS-CoV-2 infection to vaccination, providing further guidance for the development of the next-generation precision vaccine.

Background: In recent years, many naphthoquinone compounds with anticancer activity have been identified in Arnebiae Radix, and some of them have the potential to be developed into anticancer drugs. Objective: This article aimed to provide a comprehensive overview of the anticancer effects of naphthoquinone compounds through a detailed review of literature and Chinese patents, and discuss their potential to be developed as anticancer drugs for clinical application. Methods: Research papers were collected through the databases of PubMed, Cnki and SciDirect using keyword searches “naphthoquinone compounds” and “anticancer”. The keywords of “shikonin” and “shikonin derivatives” were also used in PubMed, Cnki and SciDirect databases to collect research articles. The Chinese patents were collected using the Cnki patent database. Results: Naphthoquinone compounds have been found to possess anti-cancer activity, and their modes of action are associated with inducing apoptosis, inhibiting cancer cell proliferation, promoting autophagy in cancer cells, anti-cancer angiogenesis and inhibition of cell adhesion, invasion and metastasis, inhibiting glycolysis and inhibiting DNA topoisomerase activity. Conclusion: Most of the naphthoquinone compounds show effective anti-cancer activity in vitro. The structure modification of naphthoquinone aims to develop anti-cancer drugs with high efficacy and low toxicity.

BACKGROUND: Evidence about moxibustion and abdominal massage for treating constipation in older hospitalized patients is limited. PURPOSE: To investigate the safety and effectiveness of moxibustion and abdominal massage in hospitalized older patients with constipation. METHODS: Hospitalized older patients (age ≥60 years) with constipation were retrospectively categorized as 2 cohorts according to whether the patients received moxibustion and abdominal massage in addition to routine nursing care. Gastrointestinal symptoms, Constipation Assessment Scale (CAS) scores, and Geriatric Depression Scale (GDS) scores were compared before and after treatment between cohorts. RESULTS: The 2 cohorts (n = 100 for each) had similar baseline characteristics and gastrointestinal symptoms; the control cohort and the additional intervention cohort also had similar CAS scores (7.14 ± 3.67 vs 7.48 ± 2.96, respectively), and GDS scores (>17: 31% vs 29%, respectively). Improvement in the 2 scores from baseline was observed after 2 weeks in both the control cohort and the additional intervention cohort (CAS, 5.37 ± 5.34 and 3.80 ± 4.47, respectively; GDS, >17: 28% and 15%, respectively). The cohort with additional interventions had a lower ineffective rate (defined as persistent symptoms or absence of decrease in CAS, 49% vs 32%; P = .028) but had more diarrhea (9% vs 21%; P = .017). CONCLUSION: Moxibustion and abdominal massage may help relieve constipation in hospitalized elderly patients, but attention should be paid to the increased occurrence of diarrhea. More study is needed.

Objective. To observe the effects of core stabilization training on the Cobb angle, respiratory muscle strength (maximum inspiratory pressure, MIP; maximal expiratory pressure, MEP), and pulmonary function (forced vital capacity, FVC; forced expiratory volume, FEV1.0; FEV1.0/FVC%) in adolescent patients with idiopathic scoliosis (AIS) and offer practical-based evidence for the rehabilitation treatment for AIS patients. Methods. 36 AIS patients were assigned to the core stability training (CST) group (n = 18) and control group (n = 18); the CST group participated in three sessions of core stabilization exercise per week for 12 weeks and the control group did not perform regular physical training during 12 weeks of study. Then, the Cobb angle, respiratory muscle strength (MIP and MEP), and pulmonary function (FVC, FEV1.0, and FEV1.0/FVC%) were measured before and after core stabilization training. Results. After 12 weeks of core stabilization training, compared with the pretest, the Cobb angle showed a significant decrease, FVC, FEV1, MIP, and MEP a significant increase ( P < 0.01 respectively), and there was no statistical difference in FEV1/FVC in the CST group; there was no significant difference ( P > 0.05 respectively) before and after an experiment in the control group except MEP decreased significantly ( P < 0.01 , P < 0.05 ). After 12 weeks of core stabilization training, compared with the control group, the Cobb angle significantly decreased ( P < 0.01 ), FVC, FEV1, MIP, and MEP significantly increased ( P < 0.05 respectively) in the CST group, but there was no significant difference ( P > 0.05 , respectively) in FEV1/FVC between the control group and CST group. Conclusions. Core stabilization exercise can be considered to have a positive effect on the normal physiological curvature of the spine in AIS patients, as it decreases the Cobb angle and strengthens respiratory muscle strength and pulmonary function.

Glioblastoma (GBM) is a complex ecosystem that includes a heterogeneous tumor population and the tumor-immune microenvironment (TIME), prominently containing tumor-associated macrophages (TAM) and microglia. Here, we demonstrated that β2-microglobulin (B2M), a subunit of the class I major histocompatibility complex (MHC-I), promotes the maintenance of stem-like neoplastic populations and reprograms the TIME to an anti-inflammatory, tumor-promoting state. B2M activated PI3K/AKT/mTOR signaling by interacting with PIP5K1A in GBM stem cells (GSC) and promoting MYC-induced secretion of transforming growth factor-β1 (TGFβ1). Inhibition of B2M attenuated GSC survival, self-renewal, and tumor growth. B2M-induced TGFβ1 secretion activated paracrine SMAD and PI3K/AKT signaling in TAMs and promoted an M2-like macrophage phenotype. These findings reveal tumor-promoting functions of B2M and suggest that targeting B2M or its downstream axis may provide an effective approach for treating GBM. Significance: β2-microglobulin signaling in glioblastoma cells activates a PI3K/AKT/MYC/TGFβ1 axis that maintains stem cells and induces M2-like macrophage polarization, highlighting potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment in glioblastoma.

Technology-enhanced teaching and learning, including Artificial Intelligence (AI) applications, has started to evolve in surgical education. Hence, the purpose of this scoping review is to explore the current and future roles of AI in surgical education.Nine bibliographic databases were searched from January 2010 to January 2021. Full-text articles were included if they focused on AI in surgical education.Out of 14,008 unique sources of evidence, 93 were included. Out of 93, 84 were conducted in the simulation setting, and 89 targeted technical skills. Fifty-six studies focused on skills assessment/classification, and 36 used multiple AI techniques. Also, increasing sample size, having balanced data, and using AI to provide feedback were major future directions mentioned by authors.AI can help optimize the education of trainees and our results can help educators and researchers identify areas that need further investigation.

RNA translation is the rate-limiting step when cells synthesize proteins. Elevating translation efficiency (TE) is intuitively beneficial. Particularly, when viruses invade host cells, how to compete with endogenous RNAs for efficient translation is a major issue to be resolved. We collected millions of worldwide SARS-CoV-2 sequences during the past year and traced the dynamics of allele frequency of every mutation. We defined adaptive and deleterious mutations according to the rise and fall of their frequencies along time. For 5'UTR and synonymous mutations in SARS-CoV-2, the selection on TE is evident near start codons. Adaptive mutations generally decrease GC content while deleterious mutations increase GC content. This trend fades away with increasing distance to start codons. Mutations decreasing GC content near start codons would unravel the complex RNA structure and facilitate translation initiation, which are beneficial to SARS-CoV-2, and vice versa. During this evolutionary arms race between human and virus, SARS-CoV-2 tries to improve its

Adolescents may have educational aspirations that are different from their parents' educational aspirations for them, and such discrepancy may affect adolescents' psychological adjustment. This longitudinal study examined how parent-child discrepancy in educational aspirations relate to depressive symptoms in early adolescents, both concurrently and prospectively, when controlling for parents' depressive symptoms. Moreover, parent and child gender differences in the effects were explored. Data were collected from 3799 students (52.0% boys; M

In optical noninvasive glucose detection, how to detect the glucose-caused signals from the constant human variations and disturbed probing conditions is always the biggest challenge. Developing effective measurement strategies is essential to realize the detection. A near-infrared (NIR) spectroscopy-based strategy is studied to effectively solve the in vivo measurement issues, obtaining clean blood glucose-caused signals. Two solutions composing our strategy are applied to the NIR spectroscopy-based measurement system to acquire clean raw signals in the data collection, which are a customized high signal-to-noise ratio multi-ring InGaAs detector to reduce the influence of human variations, and a fixing and aiming method to reproduce a consistent measurement condition. Seventeen cases of glucose tolerance test (GTT) on healthy and diabetic volunteers were conducted to validate the strategy. The human experiment results clearly show that the expected blood glucose changes have been detected at 1550 nm. The average correlation coefficient of the 17 cases of GTT between light signal and glucose reference reaches 0.84. The proposed measurement strategy is verified feasible for the glucose detecting in vivo. The strategy provides references to further studies and product developments for the NIR spectroscopy-based glucose measurement and references to other optical measurements in vivo.

To conduct a meta-analysis to quantitatively assess the association between mobile phone addiction (MPA) and sleep disorder (SD) by reviewing current evidence from observational studies.The meta-analysis was conducted by searching Pubmed, Embase, Scopus, and Web of science using a retrieval strategy related to MPA and SD. Pooled Odds ratios and Pearson's correlation coefficients were calculated by R software using a random effects model.29 studies including a total of 20041 participants were identified. We found that MPA was significantly associated with an increased risk of adolescents having SD (OR = 2.25, 95%CI= 1.72-2.94). Additionally, the findings also demonstrated that weak-to-moderate positive correlations were found between MPA and SD (summary r = 0.30, 95%CI= 0.25-0.34). The meta-regression analysis and subgroup analysis suggested that the geographic location and the measurement of MPA might be the sources of heterogeneity, and the robustness of the findings was confirmed by sensitivity analysis.The information collected was self-reported, and the recall bias was inevitable.This study updated the findings of the association between MPA and SD from the previous reviews and was also the first meta-analysis to assess the association between MPA and SD using Odds Radios and correlation coefficients concurrently. The result of this study re-emphasized that paying more attention to the public health concerns of MPA and SD is needed in the future, whether implementation more relevant researches or developing targeted policies.

BackgroundHigh levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We studied the effect of E2 concentration on breast cancer survival among pre- menopausal and post- menopausal patients in China.MethodsWe evaluated this association among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints.ResultsA total of 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR=1.79, 95% CI: 1.17-2.75, P=0.008) and OS in post-menopausal women (HR=1.35, 95% CI: 1.04-1.74, P=0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation (“L-shaped” and “U-shaped”, respectively) with E2 levels. However, there was a linear relationship in post-menopausal women, among whom increasing E2 was associated with escalating risks of death and progression. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a “U-shaped” relationship with OS and PFS in pre-menopausal women.ConclusionsPre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.

Background: Postoperative hypoxemia is a high-risk complication after acute type A aortic dissection (TAAD) surgery. Prone position (PP) is an effective treatment for acute respiratory failure, which may improve the gas exchange of the injured lung and the patient’s survival. PP is reported to improve the respiratory condition after cardiac surgery. However, limited data exist on the effect of PP in patients who underwent acute TAAD surgery. Methods: We retrospectively analyzed the clinical outcomes of seven patients with severe hypoxemia who underwent PP after acute TAAD surgery. The results of arterial blood gas, chest X-ray, and survival were collected. Results: Seven patients (3 female, mean age 48.3±11.7 years) were recruited in this study. All patients received total arch replacement and frozen elephant trunk implantation procedure. The PaO2 at day 1 after PP was higher than before PP (126.3±49.3 vs. 77.8±15.5 mmHg). The oxygenation index rose sharply from 83.0 (80.0, 87.0) to 188.3±56.5 at day 3 after PP. There was no significant difference in heart rate between before and after PP procedure. Chest X-ray showed the diffuse shadow was significantly improved after PP. All patients responded well to PP, and all patients were discharged except for one patient, who died perioperatively due to multiple organ failure. Conclusions: PP is a safe and feasible option for severe hypoxemia patients after TAAD surgery.

Hemoglobin (HGB), a potent spasmogen, may cause irreversible damage to the brain after aneurysm rupture. However, there is no clinical evidence to reveal the relationship between blood HGB concentrations on admission and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively reviewed all aSAH patients admitted to our institution between January 2015 and December 2020. Functional outcome was assessed at 90 days after discharge using the modified Rankin scale (mRS). Independent risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cutoff value of HGB to discriminate 90-day unfavorable outcomes. Then, patients were divided into two groups according to the cutoff value of HGB, and to account for imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of HGB on in-hospital complications. A total of 800 aSAH patients without anemia on admission were retrospectively enrolled in this study. Elevated blood HGB (OR = 1.02, 95% CI = 1.00-1.03, p = 0.018) on admission was identified as an independent risk factor associated with 90-day unfavorable outcomes, and the cutoff value was 149.5 g/L. After PSM, patients with an HGB 149.5 g/L had a higher incidence of in-hospital delayed cerebral ischemia (DCI) (33.9% vs. 22.0%, p = 0.013) and deep vein thrombosis (DVT) (11.9% vs. 4.0%, p = 0.006). Patients with a blood HGB 149.5 g/L on admission might develop more DCI and DVT during hospitalization, leading to 90-day unfavorable outcomes in aSAH patients. ClinicalTrials.gov Identifier: NCT04785976. 2021/03/05, retrospectively registered.

Endogenous nitric oxide (NO) is an important effector molecule and signal transduction molecule, which participates in the regulation of multiple functions in organisms, involving a variety of physiological and pathological processes, especially playing a very important role in the cardiovascular, immune, and nervous systems. NO is a gaseous substance with a short half-life in the body and is unstable in aqueous solutions. Therefore, many researchers focus on the release and activity of NO donors and their derivatives. However, NO donors can release free NO or NO analogues under physiological conditions to meet the human need. NO donors can be coupled with the corresponding active basic nucleus, so that they have the biological activity derived from both the basic nucleus and the NO donors, thus performing better bioactivity. This paper reviewed the routes of synthesis and advance activities of NO donor derivatives.

Background: Papillary thyroid carcinoma (PTC) is a subtype of thyroid cancer with increasing incidence over time. Objective: This study aimed to build a risk score (RS) system for PTC patients. Methods: PTC microRNA (miRNA) and messenger RNA (mRNA) expression data were extracted from The Cancer Genome Atlas (TCGA) database. The 491 PTC samples were randomly divided into training and validation sets. Using the limma software package, differentially expressed mRNAs (DEGs) and miRNAs (DEMs) between the tumor and control groups were screened. In order to construct an RS system, a survival package was used to select independent miRNAs related to prognosis. Enrichment analysis was performed, and a miRNA-mRNA co-expression network was constructed. High-throughput sequencing was also used to verify the prognostic miRNAs in exosomes. Results: We found 1363 DEGs and 171 DEMs between the tumor and control groups. After identifying 26 DEMs that were significantly related to prognosis, 6 independent prognosis-associated miRNAs were selected to build an RS system. The areas under the curves of the overall survival rates of the training, validation, and entire sets were 0.847, 0.772, and 0.819, respectively. By conducting pathway analysis using the miRNA-mRNA co-expression network, one overlapping factor and five overlapping pathways were obtained. In addition, high-throughput sequencing revealed that the hsa-miR-129-2, hsa-miR-548j, hsa-miR-6734, and hsa-miR-889 expression levels in TCGA tumor tissues and exosomes were consistent, and those of hsa-miR-129-2 and hsa-miR-889 between patients and controls were significantly different in exosomes. Conclusion: The six-miRNA RS system in exosomes may comprise independent signatures for predicting PTC patient prognosis.

OBJECTIVE: : To analyze the clinical features of hemophagocytic syndrome (HLH) following B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy in patients with relapsed/refractory multiple myeloma. METHODS: : Ninety-nine patients with relapsed/refractory multiple myeloma (including 3 cases of plasma cell leukemia) undergoing BCMA CAR-T cell therapy (monocentric phaseⅠclinical trial, ChiCTR1800017404) in the First Affiliated Hospital, Zhejiang University School of Medicine from July 2018 to December 2021 were enrolled in the study. The baseline features, laboratory findings, treatment, and clinical response of these patients were analyzed. RESULTS: : CAR-T cell associated HLH (carHLH) occurred in 20 patients (20.20%), and the median onset time was 7(0–19) d after cytokine release syndrome (CRS). Patients with carHLH were maily male patients, and manifested as high percentage of abnormal plasma cells, higher incidence of severe CRS (grade 3–4), and robust expansion of CAR-T cells in the peripheral blood (all P0.05]. CONCLUSIONS: The incidence of carHLH is relatively high in BCMA CAR-T cell treated patients, which is closely related to pretreatment tumor cell percentage in bone marrow, expansion of CAR-T cells and the secretion of cytokines. Medication based on tocilizumab and steroids can achieve considerable therapeutic effects in patient with carHLH.

A novel low molecular mass ginkgo biloba trypsin inhibitor (GBTI) was isolated from ginkgo fruits (GF) by trypsin inhibitory activity-guided fractionation by using ammonium sulphate precipitation, followed by ultra-filtration, affinity chromatography and RP-HPLC. The molecular mass and amino acid sequence of GBTI was determined using ESI-MS and ESI-MS/MS, respectively. The structure of GBTI was identified as MKNLTVIPPICLKFPN, with a molecular mass of 1826 Da. GBTI was stable in the pH range of 4–8 and in the temperature range of 0–80 °C for 30 min. However, the inhibitory activity of the GBTI reduced when incubated with various metalions (K+, Na+, Fe2+, Mg2+ and Ca2+) . Finally, GBTI exhibited significant antiproliferative effect in human MDA-MB-231 and mouse 4 T-1 triple-negative breast cancer cells and without toxicity to MCF-10A normal breast cells. Our results suggest that GBTI could be exploited as a natural and hyperstable anticancer agent for triple-negative breast cancer patients.

Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure (ICP) that predominantly affects young obese women. IIH is a diagnosis of exclusion. That is, if increased ICP is suspected, magnetic resonance imaging and magnetic resonance venography of the brain are recommended to exclude secondary causes. Imaging findings, such as empty sella, orbital findings, meningocele, and encephalocele, are not diagnostic of ICP, nor does their absence exclude ICP either. Therefore, venous manometry is recommended as the gold standard for evaluation, regardless of previous anatomic imaging results. Venous manometry is an invasive examination that is frequently applied to derive physiologic information concerning the nature of the pressure gradient. However, the pathogenesis of IIH has not been fully elucidated. The presence of venous sinus stenosis in a subset of patients has provided some support for the potential mechanisms underlying this condition. Hence, this review provides an up-to-date discussion on the potential pathogenic mechanisms of IIH with a special focus on venous sinus stenosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Epidermolysis bullosa (EB) is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation. Here, we investigated five Chinese families with EB, and eight variants including a novel nonsense variant (c.47GA, p.W16*) in LAMA3, a known recurrent variant (c.74CT, p.P25L) in KRT5, 2 novel (c.2531TA, p.V844E; c.6811_6814del, p.R2271fs) and 4 known (c.6187CT, p.R2063W; c.7097GA, p.G2366D; c.8569GT, p.E2857*; c.3625_3635del, p.S1209fs) variants in COL7A1 were detected. Notably, this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay. Our study expands the mutation spectra of Chinese patients with EB.

Objectives Our objective was to assess the effects of mental health interventions for children, adolescents, and adults not quarantined or undergoing treatment due to COVID-19 infection. Methods We searched 9 databases (2 Chinese-language) from December 31, 2019, to March 22, 2021. We included randomised controlled trials of interventions to address COVID-19 mental health challenges among people not hospitalised or quarantined due to COVID-19 infection. We synthesized results descriptively due to substantial heterogeneity of populations and interventions and risk of bias concerns. Results We identified 9 eligible trials, including 3 well-conducted, well-reported trials that tested interventions designed specifically for COVID-19 mental health challenges, plus 6 other trials with high risk of bias and reporting concerns, all of which tested standard interventions (e.g., individual or group therapy, expressive writing, mindfulness recordings) minimally adapted or not specifically adapted for COVID-19. Among the 3 well-conducted and reported trials, 1 ( N = 670) found that a self-guided, internet-based cognitive-behavioural intervention targeting dysfunctional COVID-19 worry significantly reduced COVID-19 anxiety (standardized mean difference [SMD] 0.74, 95% confidence interval [CI], 0.58 to 0.90) and depression symptoms (SMD 0.38, 95% CI, 0.22 to 0.55) in Swedish general population participants. A lay-delivered telephone intervention for homebound older adults in the United States ( N = 240) and a peer-moderated education and support intervention for people with a rare autoimmune condition from 12 countries ( N = 172) significantly improved anxiety (SMD 0.35, 95% CI, 0.09 to 0.60; SMD 0.31, 95% CI, 0.03 to 0.58) and depressive symptoms (SMD 0.31, 95% CI, 0.05 to 0.56; SMD 0.31, 95% CI, 0.07 to 0.55) 6-week post-intervention, but these were not significant immediately post-intervention. No trials in children or adolescents were identified. Conclusions Interventions that adapt evidence-based strategies for feasible delivery may be effective to address mental health in COVID-19. More well-conducted trials, including for children and adolescents, are needed.