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Linear or nonlinear interactions of multiple single-nucleotide polymorphisms (SNPs) play an important role in understanding the genetic basis of complex human diseases. However, combinatorial analytics in high-dimensional space makes it extremely challenging to detect multiorder SNP interactions. Most classic approaches can only perform one task (for detecting k-order SNP interactions) in each run. Since prior knowledge of a complex disease is usually not available, it is difficult to determine the value of k for detecting k-order SNP interactions.A novel multitasking ant colony optimization algorithm (named MTACO-DMSI) is proposed to detect multiorder SNP interactions, and it is divided into two stages: searching and testing. In the searching stage, multiple multiorder SNP interaction detection tasks (from 2nd-order to kth-order) are executed in parallel, and two subpopulations that separately adopt the Bayesian network-based K2-score and Jensen-Shannon divergence (JS-score) as evaluation criteria are generated for each task to improve the global search capability and the discrimination ability for various disease models. In the testing stage, the G test statistical test is adopted to further verify the authenticity of candidate solutions to reduce the error rate.Three multiorder simulated disease models with different interaction effects and three real age-related macular degeneration (AMD), rheumatoid arthritis (RA) and type 1 diabetes (T1D) datasets were used to investigate the performance of the proposed MTACO-DMSI. The experimental results show that the MTACO-DMSI has a faster search speed and higher discriminatory power for diverse simulation disease models than traditional single-task algorithms. The results on real AMD data and RA and T1D datasets indicate that MTACO-DMSI has the ability to detect multiorder SNP interactions at a genome-wide scale. Availability and implementation: https://github.com/shouhengtuo/MTACO-DMSI/.

OBJECTIVE: : To investigate molecular and clinical characteristics of children with permanent congenital hypothyroidism (CH) in Yunnan, China. METHODS: : The clinical data of 40 children with CH diagnosed and treated in the First People’s Hospital of Yunnan Province during January 2016 and January 2019 were retrospectively analyzed. All children were followed up to 3 years old, and Gesell intelligent score was evaluated at age of 1, 2 and 3 years, respectively. Developmental status and prognosis were evaluated. Next-generation sequencing (NGS) was used to screen all exons and exon-intron boundary sequences of the 27 known CH associated genes, and the relationship between genotypes and clinical phenotypes was analyzed. RESULTS: : Among the 40 children, the thyroid related pathogenic gene mutations were detected in 23 cases with a rate of 57.5%, and a total of 32 mutations of 8 genes were detected. Mutations in DUOX2, TPO and TSHR genes were the most common ones with mutation frequencies of 65.9%(29/44), 11.4%(5/44) and 9.1%(4/44), respectively. DUOX2 gene mutations were detected in 17 children with CH, and a total of 17 mutation types were detected. p.K530* was the most common mutation in DUOX2 gene, accounting for 20.7%(6/29). There was no significant difference in physical development and intelligence assessment between children with DUOX2 heterozygous mutation and compound heterozygous mutations. None of patients could terminate medication at 3 years of the follow-up and all of them were provisionally assessed as permanent CH. The physical and mental development assessment of children with other gene mutations were also in the normal range. CONCLUSION: : The detection rate of DUOX2, TPO and TSHR pathogenic mutations are high among children with permanent CH in Yunnan area, and no correlation is observed between gene mutation types and prognosis in children with CH.

The association between imaging features closely associated with symptomatic intracranial atherosclerotic plaques and early-onset post-stroke depression (PSD) is currently unclear.76 ischemic stroke patients who underwent high-resolution vessel wall magnetic resonance imaging (HR-VWI) were divided into PSD and non-PSD groups according to their DSM-V diagnoses and HAMD-17 scores at 14 days after onset. Clinical data and the imaging features associated with symptomatic plaques (including the enhancement index (EI), remodeling index, and plaque surface irregularity) were compared between groups. Multifactorial logistic regression analysis was used to find independent predictors of early-onset PSD. Spearman rank correlation analysis explores the association between clinical data, symptomatic plaque imaging features, and HAMD-17 in patients.The sample comprised 36 patients with early-onset PSD. The symptomatic plaque EI and infarct volume were significantly higher in depressed patients than in patients without depression (P 0.05). Multivariate logistic regression showed that symptomatic plaque EI could be used as an independent predictor of early-onset PSD after correcting for the confounding factor of infarct volume (OR = 1.034, 95% CI:1.014-1.055, P = 0.001). In the total sample, symptomatic plaque EI, infarct volume, and HAMD-17 had a significant positive correlation with each other (P 0.05).This study focused only on the patients' symptomatic plaques and did not monitor patients' systemic inflammation levels at the time of HR-VWI.The degree of symptomatic plaque enhancement is an independent predictive imaging marker of early-onset PSD and can be used the early diagnosis of early-onset PSD.

Recent studies have noted the role of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in developing neuropathic pain, but the underlying mechanisms are obscure. We found that PTEN was mainly expressed in astrocytes in the rat spinal cord and dramatically downregulated after chronic constriction injury (CCI). Intrathecal injection of a PTEN inhibitor induced pain-related behaviors in naive rats. By contrast, administration of a PTEN protector effectively mitigated CCI-induced pain. Adeno-associated virus-mediated overexpression of astrocytic PTEN in the spinal cord reduced glial activation and neuroinflammation and subsequently alleviated pain-related behaviors. Importantly, astrocyte-specific PTEN knockout ( Pten conditional knockout , Pten CKO) mice showed nociceptive sensitization and glial activation. Proteomic analysis revealed that PTEN overexpression upregulated at least 7 enzymes in the cholesterol biosynthesis pathway and the total cholesterol level in the spinal cord of CCI rats. Furthermore, PTEN directly interacted with enzymes, including 3-hydroxy-3-methylglutaryl-CoA reductase, in the cholesterol biosynthesis pathway. Astrocytic 3-hydroxy-3-methylglutaryl-CoA reductase overexpression alleviated both CCI-induced pain and mechanical allodynia in Pten CKO mice. Finally, cholesterol replenishment attenuated CCI-induced pain and suppressed spinal glial activation. Taken together, these findings imply that spinal astrocytic PTEN plays a beneficial role in CCI-induced pain by regulating cholesterol biosynthesis, and an increased level of PTEN may accelerate cholesterol biosynthesis and reduce glial activation, thereby alleviating neuropathic pain. Recovery of PTEN or cholesterol might be an effective therapeutic strategy for neuropathic pain.

Attempts to determine why some patients respond to electroconvulsive therapy (ECT) are valuable in schizophrenia. Schizophrenia is associated with aberrant dynamic functional architecture, which might impact the efficacy of ECT. We aimed to explore the relationship between pre-treatment temporal variability and ECT acute efficacy. Forty-eight patients with schizophrenia and 30 healthy controls underwent functional magnetic resonance imaging to examine whether patterns of temporary variability of functional architecture differ between high responders (HR) and low responders (LR) at baseline. Compared with LR, HR exhibited significantly abnormal temporal variability in right inferior front gyrus (IFGtriang.R), left temporal pole (TPOsup.L) and right middle temporal gyrus (MTG.R). In the pooled patient group, ∆PANSS was correlated with the temporal variability of these regions. Patients with schizophrenia with a distinct dynamic functional architecture appear to reveal differential response to ECT. Our findings provide not only an understanding of the neural functional architecture patterns that are found in schizophrenia but also the possibility of using these measures as moderators for ECT selection.

Cross-linking mass spectrometry (XL-MS) is a powerful method for the investigation of protein-protein interactions (PPI) from highly complex samples. XL-MS combined with tandem mass tag (TMT) labeling holds the promise of large-scale PPI quantification. However, a robust and efficient TMT-based XL-MS quantification method has not yet been established due to the lack of a benchmarking dataset and thorough evaluation of various MS parameters. To tackle these limitations, we generate a two-interactome dataset by spiking in TMT-labeled cross-linked

The utilization rate of respite care in Taiwan is low, and past studies that evaluated the effects of in-home respite care on caregiver burden are few. This two-wave panel study used Taiwan’s long-term care plan 1.0 database and included 2342 care recipient–caregiver dyads who used home services to examine the impact of in-home respite care on caregiver burden. Propensity score matching was used to select 323 in-home respite service users matched with 646 nonusers as control groups (1:2 matching). The mixed effect model was applied to estimate the effects of receiving in-home respite care on caregiver burden. Results showed that compared with those of nonusers, caregiver burden scores of service users decreased significantly after receiving in-home respite care for more than 14 days (adjusted B = −0.14, SE = 0.05). The government should prioritize increasing the number of days of in-home respite care for those in need to reduce the caregiver burden.

s: Chronic wounds have always been a tough fight in clinical practice, which can not only make patients suffer from pain physically and mentally but also impose a heavy burden on the society. More than one factor is relevant to each step of the development of chronic wounds. Along with the in-depth research, we have realized that figuring out the pathophysiological mechanism of chronic wounds is the foundation of treatment, while wound infection is the key point concerned. The cause of infection should be identified and prevented promptly once diagnosed. This paper mainly describes the mechanism, diagnosis and therapeutic strategies of chronic wound infection, and will put an emphasis on the principle of debridement.

The global "myopia boom" has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies (GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent (SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou (631 -6.00D and 574 0.00D) and Wenzhou (593 -6.00D and 54 -1.75D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1q25.2 FAM163A, 10p11.22 NRP1/PRAD3, and 10p11.21 ANKRD30A/MTRNR2L7, together explaining 3.34% of SE variance. 10p11.21 is successfully replicated. The allele frequencies of all three loci show significant differences between major continental groups (P 0.001). The SE reducing (more myopic) allele of rs10913877 (1q25.2 FAM163A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans (EAS = 0.60, EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities.

Introduction: This study was conducted to investigate the underlying associations between urine macrophages polarization and renal function recovery after nephron-sparing surgery (NSS) in patients with renal cell carcinoma (RCC) and to explore the potential application values of urine macrophages polarization in predicting the severity of renal ischemia/reperfusion injury (RIRI). Methods: Sixty-two patients with unilateral RCC who underwent NSS in our departments were prospectively recorded and followed up for long-term renal function to assess the onset of acute kidney injury (AKI) and chronic kidney disease (CKD). Urine samples of patients were collected 72 h after surgery for analyzing pro-inflammatory (classically activated/M1) and pro-reparative (alternatively activated/M2) macrophages polarization by flow cytometry. The detailed correlations between urine macrophages polarization and renal function recovery after NSS were explored by statistical analyses. Results: The cumulative incidence of postoperative AKI was 27.4% (17/62), and 47.0% (8/17) of those eventually developed to CKD during the follow-up. The mean urine M1/M2 ratio was 10.54 ± 8.13 in the AKI group and 3.93 ± 3.10 in the non-AKI group, presenting a significant statistical difference (p < 0.0001). Meanwhile, the urine M1/M2 ratio presented amazing potential in predicting postoperative CKD as well, with a mean ratio of 12.54 ± 9.41 in the CKD group and 4.28 ± 3.21 in the non-CKD group (p < 0.0001). Though univariate analysis implied that urine M1/M2 ratio was a relevant factor of both postoperative AKI and CKD in NSS surgical patients, multivariate analysis did not show satisfying predicting potential in postoperative CKD, mainly due to the very limited candidates enrolled in this study. Conclusion: Urine macrophages polarization could predict renal function recovery after NSS in patients with RCC. The urine M1/M2 ratio might a potential biomarker of RIRI but needs to be further verified in clinical settings.

IntroductionNon-pharmacological treatments for postpartum depression have been investigated in various systematic reviews, and their efficacy has been evaluated. However, the quality of the evidence as a whole has not been quantified. The quality of this evidence may influence the choice of interventions and even cause misleading clinical decisions. This study aims to provide an objective presentation of the methodological bias and identify treatments supported by solid evidence.Methods and analysisFor the purpose of conducting systematic reviews and meta-analyses, a comprehensive search of the relevant published literature will be conducted in English databases such as PubMed, Embase, Cochrane Library, PsycINFO and Scopus, as well as in four Chinese databases: the Chinese Biomedical Databases (CBM), Wan fang database, China National Knowledge Infrastructure and VIP Database (VIP). The time of publication will be limited from their inception to 31 May 2022. We will extract the following data from the included literature: title, first author, journal type of included literature, number and sample size, intervention/control measures, outcome indicators and main study outcomes. The Assessment of Multiple Systematic Reviews-2 will be used to measure the quality of the methods. In addition, we will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to evaluate the quality of the reporting, as well as the Grading of Recommendations Assessment, Development and Evaluation to evaluate the quality of the evidence.PROSPERO registration numberCRD42021285470.

Standard genome-wide association studies (GWASs) rely on analyzing a single trait at a time. However, many human phenotypes are complex and composed by multiple correlated traits. Here we introduce C-GWAS, a method for combining GWAS summary statistics of multiple potentially correlated traits. Extensive computer simulations demonstrated increased statistical power of C-GWAS compared to the minimal p-values of multiple single-trait GWASs (MinGWAS) and the current state-of-the-art method for combining single-trait GWASs (MTAG). Applying C-GWAS to a meta-analysis dataset of 78 single trait facial GWASs from 10,115 Europeans identified 56 study-wide suggestively significant loci with multi-trait effects on facial morphology of which 17 are novel loci. Using data from additional 13,622 European and Asian samples, 46 (82%) loci, including 9 (53%) novel loci, were replicated at nominal significance with consistent allele effects. Functional analyses further strengthen the reliability of our C-GWAS findings. Our study introduces the C-GWAS method and makes it available as computationally efficient open-source R package for widespread future use. Our work also provides insights into the genetic architecture of human facial appearance.

Cells respond to fluctuating nutrient supply by adaptive changes in organelle dynamics and in metabolism. How such changes are orchestrated on a cell-wide scale is unknown. We show that endosomal signaling lipid turnover by MTM1, a phosphatidylinositol 3-phosphate [PI(3)P] 3-phosphatase mutated in X-linked centronuclear myopathy in humans, controls mitochondrial morphology and function by reshaping the endoplasmic reticulum (ER). Starvation-induced endosomal recruitment of MTM1 impairs PI(3)P-dependent contact formation between tubular ER membranes and early endosomes, resulting in the conversion of ER tubules into sheets, the inhibition of mitochondrial fission, and sustained oxidative metabolism. Our results unravel an important role for early endosomal lipid signaling in controlling ER shape and, thereby, mitochondrial form and function to enable cells to adapt to fluctuating nutrient environments.

It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

ObjectiveThe objective of this study was to investigate occupational blood-borne pathogen exposure among dental nurses and their attitudes toward infected patients, as well as the effectiveness of the training course, to provide a scientific basis for improving the quality of safety management in the dental hospital.Materials and methodsThe study was conducted using questionnaires administered from November 2019 to December 2019 in three hospitals in Sichuan Province, China. Frequencies for answers were calculated and presented as percentages.ResultsIn total, 257 valid questionnaires were returned. Most (61.9%) nurses stated that they were involved in occupational exposure. Among them, 154 had experienced sharp injuries, and the syringe needle was the most common instrument for injuries (45.8%). Twenty-two individuals had mucosal exposure, and the proportion of eye exposure was the highest (90.9%). Only associations between training and mucosal membrane exposure were found; however, the relevance was weak (r = 0.141). Of the participants, 86.4% felt morally responsible for taking care of patients with infectious diseases, and most (92.6%) said they would continue with this career.ConclusionOccupational exposure, particularly to sharp injuries, was common in medical care among dental nurses; however, vocational training had little effect on their incidence. As dental nurses still have positive attitudes toward patients with infectious diseases, more effective training should be conducted.

Electroporation (EP) is an effective and widely accepted intracellular delivery method for fundamental research and medical applications. Existing electroporation methods usually require a commercially available EP system or tailor-made high-voltage (HV, up to kV) power source and are complicated, expensive, harmful to the cells, and even dangerous to the operators. A triboelectric nanogenerator (TENG) is a highly studied device that can generate HV output with limited charges and ultrahigh internal impedance. Here, we developed a Bulk Electroporation System based on TENG (BEST). To maximize the load voltage of the TENG, a flowing EP unit with a capillary was designed as a resistive load to realize impedance matching. A low conductivity buffer was used to further match and assist cell electroporation. Besides, the electrical model and experiments on cells transfected with the BEST showed that the bulk electric field of the cell medium could reach up to 1 kV/cm, therefore resulting in a nearly 30 times increase of trans-membrane potential, thus largely improving transfection efficiency. Finally, using 40 kDa FITC-dextran, we showed that a delivery efficiency above 50% with a cell viability maintained over 90% can be achieved in HeLa cells. This work demonstrated the potential of TENG in the biomedical field as a naturally safe HV power source. It also provided a simple, alternative, and low-cost solution for EP research and related biomedicine applications.

Background and aimsAlong with an aging population, exploring the impact of oral health on holistic health and determining exact outcomes in elderly individuals are important in both scientific research and clinical practice. Significant increase in the number of systematic reviews shows that oral health can directly or indirectly affect the overall health of elderly people physically, mentally and socially. To systematically collate, appraise, and synthesize the current evidence, we carried out an umbrella review of the impacts of oral health on holistic health in elderly individuals.MethodsA systematic reviews and meta-analyses search was performed in the major databases PubMed, MEDLINE, Web of Science and the Cochrane Library from inception to February 1, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The JBI (Joanna Briggs Institute) Critical Appraisal Checklist for Systematic Reviews and Research Syntheses was referred to assess methodological quality, and the GRADE (Grading of Recommendations, assessment, Development, and Evaluation working group classification) was used to assess the quality of evidence for each outcome included in the umbrella review.ResultsOut of 1,067 records, a total of 35 systematic reviews were included. Respiratory diseases, malnutrition, age-related oral changes, frailty, cognitive impairment, depression and poor quality of life were identified as seven key outcomes that affect the physical, mental and social health of elderly individuals. Meanwhile, three intervention measures of oral health were summarized as (i) more rigorous and universal scales, (ii) dental cleaning and denture installation, and (iii) improving self-awareness regarding oral care.ConclusionsEvidence showed that oral health can significantly affect holistic health, and the diverse oral diseases directly lead to multiple health outcomes in elderly individuals. Clear high-quality evidence revealed that oral health is strongly associated with seven health outcomes covering physical, mental, and social levels, which directly corresponds to holistic health, and impacts the quality of life of elderly individuals. Such the results remind the importance of oral care in public health, and further studies need to be conducted to verity more specific association between oral health and other chronic diseases.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42022315315.

BackgroundAcupuncture is a widely practiced, convenient, and safe treatment modality within complementary and integrative medicine. Increasing studies have revealed the efficacy of acupuncture for the treatment of osteoporosis in both human and non-human subjects. The aim of the present study was to assess the improvement of osteoporosis after overall adjustment acupuncture (OA) as well as its endocrine-modulating effect in an ovariectomized rat model.MethodsIn total, 32 female Sprague–Dawley (SD) rats were randomly divided into the sham, model, ovariectomy+estrogen (OVX+E), and OVX+OA (OVX+A) groups with eight rats in each group. The postmenopausal osteoporosis (PMOP) rat model was induced by bilateral ovariectomy. At 12 weeks after surgery, rats in the OVX+E group received estradiol (0.2 mg/kg/i.g./qod) for 12 weeks, and rats in the OVX+A group were treated with acupuncture at Zusanli (ST36), Shenshu (BL23), and Dazhu (BL11) points (qod) for 12 weeks. At the end of the treatment, all rats were sacrificed, and the body weight, uterus index, bone mineral density (BMD), bone mineral content (BMC), bone trabeculae structural parameters, femoral biomechanical properties, femoral histomorphology, and several hormone levels were examined.ResultsIn OVX rats, OA abrogated the body weight gain and improved osteoporosis in terms of BMD, BMC, bone trabeculae structural parameters, bone strength, and bone tissue histomorphology. Moreover, OA modulated the serum levels of estradiol, corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT).ConclusionsOA improves osteoporosis and exerts an endocrine-modulating effect in ovariectomized rats.

Studies suggest that the scaffolding protein, postsynaptic density protein-95 (PSD-95), is involved in multiple neurological dysfunctions. However, the role of PSD-95 in the anterior cingulate cortex (ACC) in neuropathic pain (NP) has not been investigated. The current study addressed the role of PSD-95 in the ACC in NP and its modulating profile with NMDA receptor subunit 2B (NR2B). The NP model was established by chronic constriction injury (CCI) of the sciatic nerve, and mechanical and thermal tests were used to evaluate behavioral hyperalgesia. Protein expression and distribution were evaluated using immunohistochemistry and western blotting. The results showed that PSD-95 and NR2B were co-localized in neurons in the ACC. After CCI, both PSD-95 and NR2B were upregulated in the ACC. Inhibiting NR2B with Ro 25-6981 attenuated pain hypersensitivity and decreased the over-expression of PSD-95 induced by CCI. Furthermore, intra-ACC administration of PSD-95 antisense oligonucleotide not only attenuated pain hypersensitivity but also downregulated the NR2B level and the phosphorylation of cyclic AMP response element-binding protein. These results demonstrated that PSD-95 in the ACC contributes to NP by interdependent activation of NR2B.

Fluorescent imaging has been expanded, as a non-invasive diagnostic modality for cancers, in recent years. Fluorescent probes in the near-infrared window can provide high sensitivity, resolution, and signal-to-noise ratio, without the use of ionizing radiation. Some fluorescent compounds with low molecular weight, such as rhodamine B (RhB) and indocyanine green (ICG), have been used in fluorescent imaging to improve imaging contrast and sensitivity; however, since these probes are excreted from the body quickly, they possess significant restrictions for imaging. To find a potential solution to this, this work investigated the synthesis and properties of novel macromolecular fluorescent compounds. Herein, water-soluble dextran fluorescent compounds (SD-Dextran-RhB) were prepared by the attachment of RhB and sulfadiazine (SD) derivatives to dextran carrier. These fluorescent compounds were then characterized through IR, 1H NMR, 13C NMR, UV, GPC, and other methods. Assays of their cellular uptake and cell cytotoxicity and fluorescent imaging were also performed. Through this study, it was found that SD-Dextran-RhB is sensitive to acidic conditions and possesses low cell cytotoxicities compared to normal 293 cells and HepG2 and HeLa tumor cells. Moreover, SD-Dextran-RhB demonstrated good fluorescent imaging in HepG2 and HeLa cells. Therefore, SD-Dextran-RhB is suitable to be potentially applied as a probe in the fluorescent imaging of tumors.

Background Pylorus-preserving gastrectomy (PPG) is a function-preserving surgery for the treatment of early gastric cancer (EGC) in the middle third of the stomach. According to the literature reports, PPG decreases the incidence of dumping syndrome, bile reflux, gallstone formation, and nutritional deficit compared with conventional distal gastrectomy (CDG). However, the debates about PPG have been dominated by the incomplete lymphadenectomy and oncological safety. We carried out a systematic review and meta-analysis to evaluate the pathological and oncological outcomes of PPG. Methods The protocol was registered in PROSPERO under number CRD42022304677. Databases including PubMed, Embase, Web of Science, and the Cochrane Register of Controlled Trials were searched before February 21, 2022. The outcomes included the pooled odds ratios (ORs) for dichotomous variables and weighted mean differences (WMDs) for continuous variables. For all outcomes, 95% confidence intervals (CIs) were calculated. Meta-analysis was performed using STATA software (Stata 14, Stata Corporation, Texas) and Review Manager 5.4. Results A total of 4500 patients from 16 studies were included. Compared with the CDG group, the PPG group had fewer lymph nodes harvested (WMD= −3.09; 95% CI −4.75 to −1.43; P < 0.001). Differences in the number of resected lymph nodes were observed at stations No. 5, No. 6, No. 9, and No. 11p. There were no differences in lymph node metastasis at each station. Shorter proximal resection margins (WMD = −0.554; 95% CI −0.999 to −0.108; P = 0.015) and distal resection margins (WMD = −1.569; 95% CI −3.132 to −0.007; P = 0.049) were observed in the PPG group. There were no significant differences in pathological T1a stage (OR = 0.99; 95% CI 0.80 to 1.23; P = 0.88), T1b stage (OR = 1.01; 95% CI 0.81 to 1.26; P = 0.88), N0 stage (OR = 0.97; 95% CI 0.63 to 1.48; P = 0.88), tumor size (WMD = −0.10; 95% CI −0.25 to 0.05; P = 0.187), differentiated carcinoma (OR = 1.04; 95% CI 0.74 to 1.47; P = 0.812) or signet ring cell carcinoma (OR = 1.22; 95% CI 0.90 to 1.64; P = 0.198). No significant differences were observed between the groups in terms of overall survival (HR = 0.63; 95% CI 0.24 to 1.67; P = 0.852) or recurrence-free survival (HR = 0.29; 95% CI 0.03 to 2.67; P = 0.900). Conclusions The meta-analysis of existing evidence demonstrated that the survival outcomes of PPG may be comparable to those of CDG. However, fewer lymph nodes at stations in No. 5, No. 6, No. 9, and No. 11p were harvested with PPG. We also found shorter proximal resection margins and distal resection margins for PPG, meaning more remnant stomachs would be preserved in PPG.

Funder: AIR@InnoHK Programme, We analysed the effectiveness of various non-pharmaceutical interventions in containing the 2022 Omicron outbreak in China. The results show that the Rapid Antigen Test contributed to containing the outbreak, reducing the reproduction number by 0.788 (95% CI:−0.306, 1.880) in studied cities.

Uro-originated epidermoid cysts, especially located in the upper urinary tract are rare and only 4 cases of epidermoid cyst occurring in the upper urinary tract have been reported worldwide so far. In the previous cases, the cysts were diagnosed as tumors and organs were removed.We report a case of epidermoid cyst in ureter in a 48-year-old female patient admitted to the local hospital suffering from paroxysmal pain in the right hypochondriac for 8 years.She underwent right ureteroscopy in order to rule out the possibility of urinary epithelial carcinoma. The tumor was pathological diagnosed as a benign ureterocyst epidermoid. Postoperatively, the patient showed good recovery. During the 24-month follow-up period, the patient remained well and free of complications.This case illustrates that benign epidermoid cysts can appear in the ureter, although it is extremely rare. It also indicates that perioperative examinations must be exhaustive to avoid the further injury to the patients.

Periostin is a critical extracellular regulator in the pathogenesis of liver disorders such as hepatosteatosis, non-alcoholic steatohepatitis, inflammation, and fibrosis. Periostin is also involved in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms of periostin in hepatic stellate cell (HSC) activation and tumor cell proliferation in the pathogenesis of HCC remain largely unknown. We demonstrate that periostin is markedly upregulated in diethylnitrosamine (DEN)-induced mouse HCC tissues and that periostin knockout impairs DEN-induced HCC development. Periostin is predominantly derived from activated HSCs and periostin deficiency in HSCs impairs HSC activation and inhibits HSC-promoted HCC cell proliferation in vitro and tumor growth in vivo. Mechanistically, periostin promotes HSC activation through the integrin-FAK-STAT3-periostin pathway and augments HCC cell proliferation by activating ERK. There are positive correlations between periostin and HSC activation and cell proliferation in HCC clinical samples. Collectively, our findings demonstrate that HSC-derived periostin promotes HCC development by enhancing HSC activation through an autocrine periostin-integrin-FAK-STAT3-periostin circuit and by augmenting HCC cell proliferation via the ERK pathway in a paracrine manner. Thus, periostin is a multifaceted extracellular regulator in the development of HCC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Objectives Myocardial infarction (MI) is the leading cause of death worldwide. Histone deacetylases (HDACs) collectively participate in the initiation and progression of heart diseases, including MI. This study aimed to investigate the roles of histone deacetylase 9 (HDAC9) in the development of MI. Methods In vivo and in vitro assays were conducted to determine the effects of HDAC9 on heart function and MI. qRT-PCR was applied to determine the mRNA level. Western blot was performed for protein expression. Immunofluorescence was applied to detect the fluorescence tensity of Myog and Myod. CCK-8, flow cytometry and transwell assays were carried out for function analysis. Key findings HDAC9 was upregulated in MI models in vivo and in vitro. Downregulated HDAC9 modulated the changes in left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS) and left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD). Moreover, HDAC9 knockdown activated NFE2-related factor 2 (Nrf2)/Keap1/HO-1 pathways. Additionally, HDAC9/Nrf2 axis modulated the proliferation, apoptosis and myogenesis of cardiomyocytes. Conclusions Taken together, HDAC9 knockout induced the activation of Nrf2 and protected heart from MI injury. Thus, the HDAC9/Nrf2 axis can be a novel marker for the treatment of MI.

Lung cancer is the leading cause of cancer-related deaths worldwide. Identifying genetic risk factors and understanding their mechanisms will help reduce lung cancer incidence. The p53 apoptosis effect is related to PMP-22 (PERP), a tetraspan membrane protein, and an apoptotic effector protein downstream of p53. Although historically considered a tumor suppressor, PERP is highly expressed in lung cancers. Stable knockdown of PERP expression induces CL1-5 and A549 lung cancer cell death, but transient knockdown has no effect. Interestingly, relative to the PERP-428GG genotype, PERP-428CC was associated with the highest lung cancer risk (OR = 5.38; 95% CI = 2.12-13.65, p 0.001), followed by the PERP-428CG genotype (OR = 2.34; 95% CI = 1.55-3.55, p 0.001). Ectopic expression of PERP-428G, but not PERP-428C, protects lung cancer cells against ROS-induced DNA damage. Mechanistically, PERP-428 SNPs differentially regulate p53 protein stability. p53 negatively regulates the expression of the antioxidant enzymes catalase (CAT) and glutathione reductase (GR), thereby modulating redox status. p53 protein stability is higher in PERP-428C-expressing cells than in PERP-428G-expressing cells because MDM2 expression is decreased and p53 Ser20 phosphorylation is enhanced in PERP-428C-expressing cells. The MDM2 mRNA level is decreased in PERP-428C-expressing cells via PTEN-mediated downregulation of the MDM2 constitutive p1 promoter. This study reveals that in individuals with PERP-428CC, CAT/GR expression is decreased via the PTEN/MDM2/p53 pathway. These individuals have an increased lung cancer risk. Preventive antioxidants and avoidance of ROS stressors are recommended to prevent lung cancer or other ROS-related chronic diseases.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) can differentiate into all blood lineages to maintain hematopoiesis, wound healing, and immune functions. Recently, cobalt-chromium alloy casting implants have been used extensively in total hip replacements; however, cobalt nanoparticles (CoNPs) released from the alloy were toxic to HSCs and HPCs. We aimed to investigate the mechanism underlying the toxic effect of CoNPs on HSCs/HPCs and to determine the protective effect of selenomethionine (SeMet) against CoNPs in vitro and in vivo. Human and rat CD34+ HSCs/HPCs were isolated from cord blood and bone marrow, respectively. CoNPs decreased the viability of CD34+ HSCs/HPCs and increased apoptosis. SeMet attenuated the toxicity of CoNPs by enhancing the antioxidant ability of cells. The protective effect of SeMet was not completely abolished after adding H2O2 to abrogate the improvement of the antioxidant capacity by SeMet. SeMet and CoNPs stimulated ATM/ATR DNA damage response signals and inhibited cell proliferation. Unlike CoNPs, SeMet did not damage the DNA, and cell proliferation recovered after removing SeMet. SeMet inhibited the CoNP-induced upregulation of hypoxia inducible factor (HIF)-1α, thereby disrupting the inhibitory effect of HIF-1α on breast cancer type 1 susceptibility protein (BRCA1). Moreover, SeMet promoted BRCA1-mediated ubiquitination of cyclin B by upregulating UBE2K. Thus, SeMet enhanced cell cycle arrest and DNA repair post-CoNP exposure. Overall, SeMet protected CD34+ HSCs/HPCs against CoNPs by stimulating antioxidant activity and DNA repair.

Human milk oligosaccharides (HMOs) play key roles in shaping infant fecal microbiota, and HMOs profiles have been reported to vary according to the mother's glycosyltransferase phenotype. In this study, the profiles of HMOs in human milk from secretor or non-secretor mothers collected at 2 months postpartum were analyzed by liquid chromatography quadrupole time-of-flight tandem mass spectrometry. 16S rRNA sequencing was used to characterize the fecal microbiota of breastfed infants. The amount of total and fucosylated HMOs were higher in secretor than non-secretor mothers, while Bifidobacterium genus were highly enriched in infants fed by non-secretor mothers. Associations between HMOs and infant fecal microbiota showed that the relative abundance of Bifidobacterium-OTU158 was positively associated with 2'-fucosyllactose and 3-fucosyllactose, and Bifidobacterium-OTU90 was negatively associated with lacto-N-difucohexaose. The present study provides the HMO profiles from Chinese mothers and their associations with infant fecal microbiota composition, suggesting that HMO compositions are associated with different Bifidobacterium strains in species-specific manner.

In recent years, G-quadruplexes (G4s), types of noncanonical four-stranded nucleic acid structures, have been identified in many viruses that threaten human health, such as HIV and Epstein-Barr virus. In this context, G4 ligands were designed to target the G4 structures, among which some have shown promising antiviral effects. In this Perspective, we first summarize the diversified roles of RNA G4s in different viruses. Next, we introduce small-molecule ligands developed as G4 modulators and highlight their applications in antiviral studies. In addition to G4s, we comprehensively review the medical intervention of G4-interacting proteins from both the virus (N protein, viral-encoded helicases, severe acute respiratory syndrome-unique domain, and Epstein-Barr nuclear antigen 1) and the host (heterogeneous nuclear ribonucleoproteins, RNA helicases, zinc-finger cellular nucelic acid-binding protein, and nucleolin) by inhibitors as an alternative way to disturb the normal functions of G4s. Finally, we discuss the challenges and opportunities in G4-based antiviral therapy.

BackgroundMounting evidence strongly uncovered that peripheral immuno-inflammatory response induced by acute stroke is associated with the appearance of post-stroke depression (PSD), but the mechanism remains unclear.Methods103 stroke patients were assessed at 2 weeks after onset using Diagnostic and Statistical Manual of Mental Disorders, 5th edition and then divided into PSD and non-PSD groups. Polymorphisms of inflammatory molecules (interleukin [IL]-1β, IL-6, IL-10, IL-18, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ] and C-reactive protein [CRP]), complete blood count parameters, splenic attenuation (SA) and splenic volume (SV) on unenhanced chest computed tomography, demographic and other clinical characteristics were obtained. Binary logistic regression model was used to analyze the associations between inflammation-related factors and the occurrence of PSD at 2 weeks after stroke.Results49 patients were diagnosed with PSD at 2 weeks after onset (early-onset PSD). The C/T genotypes of CRP rs2794520 and rs1205 were less in PSD group than non-PSD group (both adjusted odds ratio = 3.364; 95%CI: 1.039-10.898; p = 0.043). For CRP rs3091244, the frequency of G allele was higher (80.61% vs. 13.89%) while the frequency of A allele was lower (6.12% vs. 71.30%) in PSD patients than non-PSD patients (χ2 = 104.380; pp = 0.039). Peripheral monocyte count was less in PSD group than non-PSD group (adjusted odds ratio = 0.057; 95%CI: 0.005-0.686; p = 0.024).ConclusionsCRP polymorphisms, SA based on CRP genotype, and peripheral monocytes are associated with the risk of early-onset PSD, suggesting peripheral immuno-inflammatory activities elicited by stroke in its aetiology.

Background Dexamethasone is widely used in the prevention of postoperative complications in oral surgery and strengthening the analgesic effect after anesthesia, but the efficacy is controversial, and the relationship between postoperative complications and pain is still unclear. The purpose of this study was to evaluate the analgesic effect of dexamethasone in the treatment of jaw cyst and to explore the relationship between postoperative complications and pain. Methods We conducted a prospective, randomized, double-blind clinical trial. 120 patients were divided into two groups, dexamethasone group ( group D) and control group (Group C). All patients were given 0.02 mg·kg−1 of hydromorphone to relieve pain in advance at 10 min before the beginning of operation. Meanwhile, dexamethasone was injected 0.2 mg·kg−1 intravenously in group D and normal saline was injected in group C. The primary endpoint was pain intensity at 2 h, 6 h, 12 h, 24 h and 48 h after surgery. The secondary endpoints were the incidence and extent of complications after surgery, including facial swelling and trismus. Results Compared with group C, the visual analogue scale (VAS) scores and occurrence of painful event postoperatively in group D were significantly lower both at rest (P P = 0.0014) and during mobilization (P P P = 0.00022) and 48 h (P P = 0.00015) after surgery, but there was no difference at 6 h and 12 h (P = 0.137 and P = 0.083) after surgery. The C-reactive protein (CRP) level at 24 h after operation in group D was lower than group C (P = 0.012), but there was no significant difference in blood glucose concentration between the two groups (P = 0.608). Conclusion Dexamethasone can reduce the degree of facial swelling and trismus after jaw cyst surgery by inhibiting the production of inflammation, which alleviated the postoperative pain of patients significantly. In addition, it did not increase the risk of hyperglycemia. Trial registration This study was registered with the Chinese Clinical Trial Registry on May 07, 2020 (URL: http://www.chictr.org.cn/showproj.aspx?proj=53344. Registry number: ChiCTR2000032693). Registered on 07/05/2020.

Hepatocellular carcinoma (HCC) is a highly malignant, fatal disease with a complex tumor microenvironment (TME) characterized by severe immunosuppression and malformed vascular structures, thus most advanced HCC patients do not respond well to current mainstream pharmacotherapy and T-cell-related immunotherapy. Therefore, an efficient immunovascular crosstalk modulation strategy may help combat HCC by reversing immunosuppression and vessel normalization, especially by reprogramming tumor associated macrophages (TAMs). In this study, tyrosine kinase inhibitor lenvatinib (Len) was loaded into mesoporous Fe

Hepatocellular carcinoma (HCC) accounts for 85%-90% of primary liver cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'UTR of mRNA. Abnormal expression and regulation of miRNAs are involved in the occurrence and progression of HCC, and miRNAs can also play a role in the diagnosis and treatment of HCC as oncogenes or tumor suppressors.In the past decades, a large number of studies have shown that miRNAs play an essential regulatory role in HCC and have potential as biomarkers for HCC. We reviewed the literature to summarize these studies.By reviewing the literature, we retrospected the roles of miRNAs in the development, diagnosis, treatment, and prognosis of HCC, and put forward prospects for the further research on miRNAs in the precision treatment of HCC.MicroRNAs are important regulators and biomarkers in the occurrence, progression, outcome, and treatment of HCC, and can provide new targets and strategies for improving the therapeutic effect of HCC.

Particulate matter (PM) pollution and the coronavirus (COVID-19) pandemic have increased demand for protective masks. However, typical protective masks only intercept particles and produce peculiar odors if worn for extended periods owing to bacterial growth. Therefore, new protective materials with good filtration and antibacterial capabilities are required.In this study, we prepared multi-scale polyvinylidene fluoride (PVDF) nanofibrous membranes for efficient filtration and durable antibacterial properties via N-halamine modification.The N-halamine-modified nanofibrous membrane (PVDF-PAA-TMP-Cl) had sufficient active chlorine content (800 ppm), and the tensile stress and strain were improved compared with the original membrane, from 6.282 to 9.435 MPa and from 51.3 % to 56.4 %, respectively. To further improve the interception efficiency, ultrafine nanofibers (20-35 nm) were spun on PVDF-PAA-TMP-Cl nanofibrous membranes, and multi-scale PVDF-PAA-TMP-Cl nanofibrous membranes were prepared. These membranes exhibited good PM

The effective components of mulberry leaf polyphenols (MLPs) should be absorbed and transported by the intestinal cells before regulating lipid metabolism. The Caco-2 intestinal epithelial cell and 3 T3-L1 adipocytes were coupled to screen the effective components of MLPs that are being absorbed and transported by intestinal cells. The regulation and molecular mechanism by which the effective components affect adipogenesis were analyzed in this study. Among the 12 main components identified, five main compounds were well absorbed with Papp in the order of benzoic acidchlorogenic acidastragalosidehyperosiderutin. Chlorogenic acid and benzoic acid were mainly absorbed through passive diffusion, while rutin, astragaloside, and hyperoside were mainly by active transport, of which chlorogenic and rutin absorption were mediated by the efflux protein, P-glycoprotein (P-pg). Based on the transport volume of 2 mg/ml MLPs within 2 h, 25% of the maximum transported MLPs (TMLPs) was a safe concentration for 3 T3-L1 preadipocytes. Except for astragaloside, the other four components showed a significant inhibitory effect on lipid droplets, TG and TC, and chlorogenic acid and benzoic acid had the strongest effect. Additionally, we observed a synergistic effect as TMLPs were the most effective. We hypothesized that TMLPs, chlorogenic acid and benzoic acid suppressed adipogenesis and regulated lipid metabolism by inhibiting PPAR-γ, C/EBP-α, and FAS mRNA while promoting ADIPO and Leptin mRNA expression. PRACTICAL APPLICATIONS: The absorption and adipogenesis inhibition effect of mulberry leaf phenolics were evaluated in this study. The results provided guideline for the development of functional foods in regulating lipid metabolism.

Self-reference effect has been widely discussed. Previous scholars believed that self-related information can be processed faster is due to the positive attribute of self-concept which speeds up self-related information processing. When self-related information is given negative attributes, the self-reference effect will be weakened. In this study, fat and sick, two kinds of stimuli associated with disgust characteristics, were added to self- and other-faces. We found that disease stimuli, which are closely related to survival threats, eliminated the self-reference effect while the obesity stimuli only weakened the self-reference effect to a certain extent. Event-related potential (ERP) analysis demonstrated that sick-faces have a greater amplitude than standard-faces in the EPN and LPP components. We believe that this may be due to the urgency of the disease threat, which leads to the selective attention to the disease threat in the early perception stage and the allocation of more attention resources for rapid response in the later stage. In addition, we found that disgust sensitivity specifically maintains individuals' self-referential effects by dissociating individuals from others in disease contexts. These results further support the behavioral immune function of disgust as a gatekeeper of the self in potentially contaminated environments. In conclusion, our study showed that in the face of survival threat, the self-reference effect is eliminated, and disgust tried to slow down this elimination effect to protect self. This study extends the behavioral immunity theory to some extent and further deepens the understanding of the relationship between disgust and self.

National Cheng Kung University (NCKU) promotes university social responsibility and strives to ensure that all of its teaching staff and students engage in academics in a manner that incorporates both social awareness and social practice. The NCKU team has launched a series of social practice and research projects focused on accompanying and caring for older adults who live in the community, looking to establish a social practice model that bridges university teaching and research to practical community needs. The objective of this initiative is to develop an innovative model of social support and a new model for younger generations to work with older adults living in the community. The results of this survey project show better well-being in older adults to be associated with the following sets of traits: exercising regularly and lacking dental problems; engaging in daily laughter and holding positive aging perceptions; and having a higher subjective social status, more family support, and a sense of community attachment. The study results imply that multiple factors affect well-being in the context of caring for community-dwelling older adults and social development, especially during the current COVID-19 pandemic.社區創新與地方永續—國立成功大學高齡社會調查應用案例分享.國立成功大學推動大學社會責任計畫致力於讓全校師生成為具有社會意識與社會實踐力的入世學術人。國立成功大學團隊開啟一系列社會實踐與高齡研究，期待建立發展大學教學研究與在地社群間的社會實踐模式，同時也嘗試發展人才培育與支援機制。本計畫之社區調查研究顯示，有運動習慣和沒有牙齒問題的高齡者有較好的幸福感；每天歡笑的老年人、有正向老化態度的老年人幸福感較佳；有較高主觀社會地位、更多家庭社會支持，以及有社區依存感的老年人亦有較高的幸福感。本計畫結果提醒在新冠疫情時期針對中高齡者社區照顧的多面向意涵及對未來社區發展之啟示。.

Long-distance walking with heavy loads is often needed when going hiking or for field rescue, which is prone to cumulative fatigue. There is also a great need for labor-saving and biomechanical energy harvesting in daily life for extended security and communication needs. Here, we report a load-suspended backpack for harvesting the wasted energy of human motion based on a triboelectric nanogenerator (TENG). Two elastomers are incorporated into the backpack to decouple the synchronous movement of the load and the human body, which results in little or no extra accelerative force. With such a design, through theoretical analysis and field experiments, the backpack can realize a reduction of 28.75 % in the vertical oscillation of the load and 21.08 % in the vertical force on the wearer, respectively. Meanwhile, the mechanical-to-electric energy conversion efficiency is modeled and calculated to be 14.02 % under normal walking conditions. The designed backpack has the merits of labor-saving and shock absorption as well as electricity generation, which has the promising potential to be a power source for small-scale wearable and portable electronics, GPS systems, and other self-powered health care sensors.

Introduction: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a recently described chronic inflammatory disease of the central nervous system. There are few reports of CLIPPERS in the Chinese population to date. We summarized the clinical characteristics of 6 CLIPPERS patients to deepen the understanding of this disease. Methods: The clinical manifestations and treatment of 6 CLIPPERS patients confirmed by pathology or clinical diagnosis in our hospital were retrospectively analyzed. Results: The common clinical manifestations included ataxia, dysarthria, diplopia, dysphagia, dizziness, cognitive impairment, facial paresthesia, and paralysis. Most of the lesions showed typical symmetric “pepper powder”-like dot and nodular enhancement centered in the pontine and cerebellum except 1 patient with unilateral nodular enhancement. The brain histopathological examination of the 5 biopsied patients indicated that, with the exception of patient 4 with no lymphocyte infiltration, a large amount of perivascular lymphocytic infiltration was found in the other 4 patients, among whom only 1 patient was dominated by CD3+ T cell infiltration and the other 3 patients were dominated by CD20+ B cell infiltration. After treatment with intravenous methylprednisolone, all patients had significant clinical recovery associated with complete or significant MRI recovery, but they were prone to relapse after withdrawal or reduction of the corticosteroid. Conclusion: Our reports highlight the importance of neuropathological examinations when encountering atypical imaging manifestations, such as unilateral and large nodular Gd+ lesions, in order to establish a final diagnosis of CLIPPERS. In addition, the lymphocytic infiltration in the lesions of CLIPPERS may be dominated by CD20+ B cells instead of CD3+ T cells.

Background: The aim of this study is to systematically review the literature to summarize the evidence surrounding the clinical utility of artificial intelligence (AI) in the field of mammography. Databases from PubMed, IEEE Xplore, and Scopus were searched for relevant literature. Studies evaluating AI models in the context of prediction and diagnosis of breast malignancies that also reported conventional performance metrics were deemed suitable for inclusion. From 90 unique citations, 21 studies were considered suitable for our examination. Data was not pooled due to heterogeneity in study evaluation methods. Summary: Three studies showed the applicability of AI in reducing workload. Six studies demonstrated that AI can aid in diagnosis, with up to 69% reduction in false positives and an increase in sensitivity ranging from 84 to 91%. Five studies show how AI models can independently mark and classify suspicious findings on conventional scans, with abilities comparable with radiologists. Seven studies examined AI predictive potential for breast cancer and risk score calculation. Key Messages: Despite limitations in the current evidence base and technical obstacles, this review suggests AI has marked potential for extensive use in mammography. Additional works, including large-scale prospective studies, are warranted to elucidate the clinical utility of AI.

Objectives: This study aimed to examine how intrinsic and extrinsic factors of job satisfaction affect home care workers’ intention to stay and determine whether ageist behaviors moderate the relation between job satisfaction and intention to stay. Method: We recruited 380 participants to complete measures of job satisfaction, ageist behaviors, and intention to stay. Results: Monthly wages, extrinsic and intrinsic factors, and positive and negative ageist behaviors were significantly related to home care workers’ retention. Both positive and negative ageist behaviors negatively moderated the relation between job satisfaction and retention. Conclusion: Home care workers’ retention may be increased by providing reasonable extrinsic rewards and enhancing the intrinsic nature of the job itself. Reducing negative ageist behaviors and increasing positive ones for those with low job satisfaction could be related to higher retention. The harmful effects of positive behaviors should be addressed. These findings could contribute to workforce retention in long-term care.

As a main element in the hard metal industry, cobalt is one of the major components of human metal implants. Cobalt-containing implants, especially joint prostheses used for artificial joint replacement, can be corroded due to the complex physiological environment in vivo, producing a large number of nanoscale cobalt particles (Cobalt Nanoparticles, CoNPs). These CoNPs can be first accumulated around the implant to cause adverse local reactions and then enter into the blood vessels followed by reaching to the liver, heart, brain, kidney, and other organs through systematic circulation, which leads to multi-system toxicity symptoms. To ensure the long-term existence of cobalt-containing implants in the body, it is urgently required to find out a safe and effective detoxification drug. Herein, we have demonstrated that CoNPs could induce the ferroptosis-like cell death through the enhancement of intracellular reactive oxygen species (ROS) level, cytoplasmic Fe2+ level, lipid peroxidation and consumption of reduced glutathione (GSH) as well as inhibition of glutathione peroxidase 4 (GPX4) activity. Importantly, α-lipoic acid (ALA), a natural antioxidant with the capability to scavenge free radicals and chelate toxic metals, was found to efficiently alleviate the adverse effects of CoNPs. The present study illustrates a new mechanism of CoNPs mediated by ferroptosis-like cytotoxicity and discloses an effective method for the detoxification of CoNPs by employing the natural antioxidant of ALA, providing a basis for further in vivo detoxification study.

In cross-linking mass spectrometry (XL-MS), the depth and sensitivity of cross-link detection is often limited by the low abundance of cross-links compared to non-cross-linked peptides in the digestion mixture. To improve the identification efficiency of cross-links, here, we present a gas-phase separation strategy using high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to the Orbitrap Tribrid mass spectrometers. By enabling an additional peptide separation step in the gas phase using the FAIMS device, we increase the number of cross-link identifications by 22% for a medium complex sample and 59% for strong cation exchange-fractionated HEK293T cell lysate in XL-MS experiments using disuccinimidyl sulfoxide (DSSO) cross-linker. When disuccinimidyl suberate (DSS) cross-linker is in use, we are able to boost cross-link identification by 89% for the medium and 100% for the high complex sample compared to the analyses without FAIMS. Furthermore, we show that, for medium complex samples, FAIMS enables the collection of single-shot XL-MS data with a comparable depth to the corresponding sample fractionated by chromatography-based approaches. Altogether, we demonstrate FAIMS is highly beneficial for XL-MS studies by expanding the proteome coverage of cross-links while improving the efficiency and confidence of cross-link identification.

With the aim of developing a fast algorithm for high-quality MRI reconstruction from undersampled k-space data, we propose a novel deep neural Network, which is inspired by Iterative Shrinkage Thresholding Algorithm with Data consistency (NISTAD). NISTAD consists of three consecutive blocks: an encoding block, which models the flow graph of ISTA, a classical iteration-based compressed sensing magnetic resonance imaging (CS-MRI) method; a decoding block, which recovers the image from sparse representation; a data consistency block, which adaptively enforces consistency with the acquired raw data according to learned noise level. The ISTA method is thereby mapped to an end-to-end deep neural network, which greatly reduces the reconstruction time and simplifies the tuning of hyper-parameters, compared to conventional model-based CS-MRI methods. On the other hand, compared to general deep learning-based MRI reconstruction methods, the proposed method uses a simpler network architecture with fewer parameters. NISTAD has been validated on retrospectively undersampled diencephalon standard challenge data using different acceleration factors, and compared with DAGAN and Cascade CNN, two state-of-the-art deep neural network-based methods which outperformed many other state-of-the-art model-based and deep learning-based methods. Experimental results demonstrated that NISTAD reconstruction achieved comparable image quality with DAGAN and Cascade CNN reconstruction in terms of both PSNR and SSIM metrics, and subjective assessment, though with a simpler network structure.

BackgroundKnowledge on the epidemiological features and transmission patterns of novel coronavirus disease (COVID-19) is accumulating. Detailed line-list data with household settings can advance the understanding of COVID-19 transmission dynamics.MethodsA unique database with detailed demographic characteristics, travel history, social relationships, and epidemiological timelines for 1407 transmission pairs that formed 643 transmission clusters in mainland China was reconstructed from 9120 COVID-19 confirmed cases reported during 15 January–29 February 2020. Statistical model fittings were used to identify the superspreading events and estimate serial interval distributions. Age- and sex-stratified hazards of infection were estimated for household vs nonhousehold transmissions.ResultsThere were 34 primary cases identified as superspreaders, with 5 superspreading events occurred within households. Mean and standard deviation of serial intervals were estimated as 5.0 (95% credible interval [CrI], 4.4–5.5) days and 5.2 (95% CrI, 4.9–5.7) days for household transmissions and 5.2 (95% CrI, 4.6–5.8) and 5.3 (95% CrI, 4.9–5.7) days for nonhousehold transmissions, respectively. The hazard of being infected outside of households is higher for people aged 18–64 years, whereas hazard of being infected within households is higher for young and old people.ConclusionsNonnegligible frequency of superspreading events, short serial intervals, and a higher risk of being infected outside of households for male people of working age indicate a significant barrier to the identification and management of COVID-19 cases, which requires enhanced nonpharmaceutical interventions to mitigate this pandemic.

The endogenous non-coding microRNA (miRNA) let-7b-5p is highly expressed in the blood of patients with acute pulmonary embolism (PE). However, the mechanism underlying the involvement of let-7b-5p in acute PE remains unclear. To address this, we investigated the role of let-7b-5p in acute PE in both in vitro and in vivo experimental models. The results showed that let-7b-5p upregulated the expression of stress-associated endoplasmic reticulum protein 1 (SERP1) at the post-transcriptional level. SERP1 activation leads to modulation of its chaperone protein SEC61B in the response of endoplasmic reticulum (ER) stress. Furthermore, our data show that the unfolded protein response was triggered and activation of unfolded proteins GRP78, PERK, RNF121, and CHOP occurred through the PERK-CHOP pathway, resulting in an inflammatory response and apoptosis of lung epithelial cells. These characteristics were promoted by the in vitro expression of a let-7b-5p mimic; conversely, transfection with a let-7b-5p inhibitor decreased the response of ER stress in acute PE. The results from this study thus provide evidence that let-7b-5p promotes protein processing during ER stress response by upregulating SERP1 expression, ultimately resulting in an inflammatory response and apoptosis of lung cells, cumulatively playing a critical role in the pathogenesis of acute PE.

Objective To evaluate the feasibility of arthroplasty with varisized three‐dimensional(3D) printing lunate prosthesis for the treatment of advanced Kienböck's disease (KD). Methods From 2016 November to 2018 September, a retrospective study was performed for the patients of KD in our hospital. Five patients (two males, three females) were included in this study. The mean age of the patients at the time of surgery was 51.6 years (range, 37–64 years). Varisized prosthesis identical to the live model in a ratio of 1:0.85, 1:1, and 1:1.1 were fabricated by 3D printing. All patients (one in Lichtman IIIA stage, two in Lichtman IIIB stage, one in Lichtman IIIC stage, and one in Lichtman IV stage) were treated with lunate excision and 3D printing prosthetic arthroplasty. Visual analog scale score (VAS), the active movement of wrist (extension, flexion) and strength were assessed preoperatively and postoperatively. The Mayo Modified Wrist Score (MMWS), Disabilities of the Arm, Shoulder and Hand (DASH) Score, and patient's satisfaction were evaluated during the follow‐up. Results Prosthesis identical to the live model in a ratio of 1:0.85 or 1:1 were chosen for arthroplasty. The mean operation time (range, 45 to 56 min) was 51.8 ± 4.44 min. Follow‐up time ranged from 11 months to 33 months with the mean value of 19.4 months. The mean extension range of the wrist significantly increased from preoperative 44° ± 9.6° to postoperative 60° ± 3.5° (P

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play critical roles in female reproduction, while the underlying genetic basis is poorly understood. Genome-wide association studies (GWASs) of FSH and LH levels were conducted in 2590 Chinese females including 1882 polycystic ovary syndrome (PCOS) cases and 708 controls. GWAS for FSH level identified multiple variants at FSHR showing genome-wide significance with the top variant (rs2300441) located in the intron of FSHR. The A allele of rs2300441 led to a reduced level of FSH in the PCOS group (β = −.43, P = 6.70 × 10−14) as well as in the control group (β = −.35, P = 6.52 × 10−4). In the combined sample, this association was enhanced after adjusting for the PCOS status (before: β = −.38, P = 1.77 × 10−13; after: β = −.42, P = 3.33 × 10−16), suggesting the genetic effect is independent of the PCOS status. The rs2300441 explained sevenfold higher proportion of the FSH variance than the total variance explained by the two previously reported FSHR missense variants (rs2300441 R2 = 1.40% vs rs6166 R2 = 0.17%, rs6165 R2 = 0.03%). GWAS for LH did not identify any genome-wide significant associations. In conclusion, we identified genome-wide significant association between variants in FSHR and circulating FSH first, with the top associated variant rs2300441 might be a primary contributor at the population level.