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Triple-negative breast cancer (TNBC), which accounts for 10%–20% of breast cancer cases, is characterized by a higher metastasis rate, higher recurrence risk, and worse prognosis. Traditional treatments such as chemotherapy, surgery, and radiotherapy have limited therapeutic effects. Although immune checkpoint blockade (ICB) therapy represented by anti-programmed death 1 (aPD-1) antibody has made further progress in treating TNBC, its therapeutic effect is still not optimistic. Ataxia telangiectasia mutated (ATM) is a critical factor in the DNA damage response (DDR) pathway, which is associated with the development of tumors. Recent studies have found that it can regulate the tumor immune microenvironment, affecting ICB responsiveness. Inhibition of ATM could enhance ICB therapy by promoting mitochondrial DNA cytoplasmic leakage and activating the innate immune signaling pathway. To explore the effect of ATM siRNA(siATM) on the ICB responsiveness of TNBC, we designed and synthesized nanoparticles using 1,2-dioleoyl-glycero-3-phosphatidylcholine (DOPC) liposomes to deliver siATM. In vitro and in vivo experiments demonstrated that DOPC/siATM could enhance the ability of siRNA to enter tumor cells and effectively inhibit the expression of ATM protein. Our study found that nanoparticles carrying siATM could activate cytotoxic T lymphocytes and regulate the immunosuppressive tumor microenvironment (ITM) by activating the cGAS-STING pathway. Its combination with aPD-1 may be a potential way to improve the efficacy of TNBC.

Background: Observational studies have shown inconsistent findings of the relationships between aspirin use and the risk of Alzheimer’s disease (AD). Objective: Since residual confounding and reverse causality were challenging issues inherent in observational studies, we conducted a 2-sample Mendelian randomization analysis (MR) to investigate whether aspirin use was causally associated with the risk of AD. Methods: We conducted 2-sample MR analyses utilizing summary genetic association statistics to estimate the potential causal relationship between aspirin use and AD. Single-nucleotide variants associated with aspirin use in a genome-wide association study (GWAS) of UK Biobank were considered as genetic proxies for aspirin use. The GWAS summary-level data of AD were derived from a meta-analysis of GWAS data from the International Genomics of Alzheimer’s Project (IGAP) stage I. Results: Univariable MR analysis based on these two large GWAS data sources showed that genetically proxied aspirin use was associated with a decreased risk of AD (Odds Ratio (OR): 0.87; 95%CI: 0.77–0.99). In multivariate MR analyses, the causal estimates remained significant after adjusting for chronic pain, inflammation, heart failure (OR = 0.88, 95%CI = 0.78–0.98), or stroke (OR = 0.87, 95%CI = 0.77–0.99), but was attenuated when adjusting for coronary heart disease, blood pressure, and blood lipids. Conclusion: Findings from this MR analysis suggest a genetic protective effect of aspirin use on AD, possibly influenced by coronary heart disease, blood pressure, and lipid levels.

Yang-Hua Xiao,1,2 Mei-Fang Liu,1 Hongwen Wu,1,3 De-Rong Xu,1 Rui Zhao1 1Department of Clinical Laboratory, Medical Center for Burn and Plastic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2School of Public Health, Nanchang University, Nanchang, People’s Republic of China; 3Department of Medical Instruments, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: De-Rong Xu; Rui Zhao, Email xudr@ncu.edu.cn; zhaoruisc@163.comPurpose: Metagenomic next-generation sequencing (mNGS) is a powerful yet unbiased method to identify pathogens in suspected infections. However, little is known about its clinical effectiveness. The present study aimed to assess the efficacy of mNGS in routine clinical practice.Patients and Methods: In this single-center retrospective cohort study, 518 patients with suspected infectious diseases were assessed for inclusion. Among them, each patient had undergone mNGS testing; 407 patients had undergone both microbial culture and mNGS testing. The result of mNGS testing was compared to microbial culture performed concurrently. The diagnostic performance of mNGS was evaluated using the comprehensive clinical diagnosis as the reference standard.Results: There was a significant difference in the positive detection rates of pathogens between mNGS and culture (331/407, 81.3% vs 79/407, 19.4%, P < 0.001). The sensitivity of mNGS was much higher than the culture method (79.5% vs 21.3%, P < 0.001), especially in sample types of sputum and bronchoalveolar lavage fluid (BALF). Notably, the sensitivity of blood mNGS was relatively lower than other sample types (67.4% vs 88.9– 93.8%). Pathogen cfDNA load based on standardized stringently mapped read number at the species level of microorganisms (SDSMRN) was significantly lower in blood than in other sample types from the same patient (P = 0.0003). Importantly, mNGS directly led to a change of treatment regimen in 142 (27.4%) cases, including antibiotic escalation (15.3%), antibiotic de-escalation (9.1%), and early definitive diagnosis to initiate appropriate treatment (3.1%).Conclusion: Our in-house mNGS platform significantly improved the sensitivity for the diagnosis of infectious diseases. mNGS has the potential to improve clinical outcomes by optimizing antimicrobial therapy.Keywords: mNGS, infections, diagnostic, outcome

Objectives: Pain is one of the most common and distressing symptoms co-occurring with cancer progression and treatment, and medication adherence plays an important role in achieving good pain control. However, research on medication adherence and influential factors among individuals with cancer pain (CP) is limited in China. The present study aimed to investigate the adherence to analgesics in patients with CP in China and to identify factors that may influence adherence. Methods: A cross-sectional study was conducted from June 2020 to February 2021. Study instruments consisted of a set of validated questionnaires, 5 measurement instruments including the numerical rating scale (NRS), ID-Pain, Morisky Medication Adherence Scale-Chinese validated version (MMAS-C), Beliefs about Medicines Questionnaire (BMQ) – Specific, and the Hospital Anxiety and Depression Scale (HADS). Results: A total of 141 participants with CP including 71 males (50.4%), aged 54.5±15.5 years were surveyed in this study. Overall, 83 patients (58.9%) showed adherence, but 58 patients (41.1%) showed non-adherence to analgesics. The univariate analysis showed that analgesic adherence was associated with pain duration of>3 months, outbreaks of pain in the last 24 hours, presence of side effects, getting analgesics in time, presence of neuropathic pain, stopping analgesics or adjusting dosage by themselves, presence of anxiety and depression, and beliefs about medicines. Moreover, the multivariate logistic regression showed that getting analgesic drugs in time (odds ratio [OR]=5.218, 95% confidence interval [CI] 1.691-16.100) and high BMQ-Necessity (OR=1.907, 95% CI 1.418-2.565) were associated with high adherence, stopping analgesics or adjusting dosage by themselves (OR=7.958, 95% CI 2.443-25.926) and high BMQ-Concern (OR=0.760, 95% CI 0.600-0.964) were more likely to be associated with non-adherence. Conclusion: In view of our findings, it may be critical for individuals to have a better understanding and strong beliefs about their prescribed analgesic drugs. Pain education, counseling and follow-up of patients and their caregivers, and removal of barriers to accessing analgesic drugs could be considered in further intervention strategies.

Audio-visual tracks in video contain rich semantic information with potential in many applications and research. Since the audio-visual data have inconsistent distributions and because of the heterogeneous nature of representations, the heterogeneous gap between modalities makes them impossible to compare directly. To bridge the modality gap, a frequently adopted approach is to simultaneously project audio-visual data into a common subspace to capture the commonalities and characteristics of modalities for measurement, which has been extensively studied in relation to the issues of modality-common and modality-specific feature learning in previous research. However, it is difficult for existing methods to address the tradeoff between both issues; e.g., the modality-common feature is learned from the latent commonalities of audio-visual data or the correlated features as aligned projections, in which the modality-specific feature can be lost. To solve the tradeoff, we propose a novel end-to-end architecture, which synchronously projects audio-visual data into the explicit and the implicit dual common subspaces. The explicit subspace is used to learn modality-common features and reduce the modality gap of explicitly paired audio-visual data, where the representation-specific details are abandoned to retain the common underlying structure of audio-visual data. The implicit subspace is used to learn modality-specific features, where each modality privately pulls apart the feature distances between different categories to maintain the category-based distinctions, by minimizing the distance between audio-visual features and corresponding labels. The comprehensive experimental results on two audio-visual datasets, VEGAS and AVE, demonstrate that our proposed model for using two different common subspaces for audio-visual cross-modal learning is effective and significantly outperforms the state-of-the-art cross-modal models that learn features from a single common subspace by 4.30% and 2.30% in terms of average MAP on the VEGAS and AVE datasets, respectively.

Background: Currently there are no effective therapies to prevent or halt the development of Alzheimer’s disease (AD). Multiple risk factors are involved in AD, including ischemic stroke (IS). Aspirin is often prescribed following IS to prevent blood clot formation. Observational studies have shown inconsistent findings with respect to the relationship between aspirin use and the risk of AD. Objective: To investigate the relationship between aspirin therapy after IS and the new diagnosis of AD in elderly patients. Methods: This retrospective cohort study leveraged a large database that contains over 90 million electronic health records to compare the hazard rates of AD after IS in elderly patients prescribed aspirin versus those not prescribed aspirin after propensity-score matching for relevant confounders. Results: At 1, 3, and 5 years after first IS, elderly patients prescribed aspirin were less likely to develop AD than those not prescribed aspirin: Hazard Ratio = 0.78 [0.65,0.94], 0.81 [0.70,0.94], and 0.76 [0.70,0.92]. Conclusion: Our findings suggest that aspirin use may prevent AD in patients with IS, a subpopulation at high risk of developing the disease.

Teachers with high educational levels significantly impact the health-related knowledge and attitudes of young students and their family members. This study aimed to investigate the coronavirus disease 2019 (COVID-19) vaccine hesitancy and associated factors, and compare the differences between decision-makers and non-decision-makers among college teachers.A cross-sectional online survey was administered across mainland China from 4 to 7 August 2021. Overall, 251 college teachers were included using snowball sampling. A multivariable logistic regression model was applied to explore the association between decision-makers and hesitancy to receive a COVID-19 vaccine.Overall, 42.2% of the teachers were hesitant to being vaccinated against COVID-19. The hesitancy rate was lower among primary decision-makers than that among non-decision-makers (34.8% vs. 60.3%,Our findings indicate that a high proportion of college teachers in China are hesitant to receiving COVID-19 vaccination, and that primary decision-makers are less likely to exhibit hesitancy to being vaccinated against COVID-19 than non-decision-makers in their family. Family decision-makers among teachers can be considered a priority for COVID-19 vaccine promotion, thereby enhancing vaccine acceptance among vulnerable populations-including older adults and children-and preventing adverse outcomes.KEY MESSAGES

Nano-sized FOX-7/ZIF-8 composites are successfully prepared by a liquid-assisted mechanochemical route. They exhibited fast decomposition and reduced mechanical sensitivities.

Single-molecule fluorescence microscopy was applied to quantify photocatalytic activities and dynamics at individual structural features of g-C3N4 nanosheets at nanometer resolution.

Single-molecule fluorescence imaging was applied to in situ quantify the photo-oxidation activities and kinetics at individual structural features of g-C3N4 at the nanoscale.

Turner syndrome (TS) has an increased predisposition to ischaemic heart disease and the status of coronary microcirculation in TS is largely unknown. This study aims to evaluate myocardial microvascular function in TS using first-pass magnetic resonance perfusion imaging and determine significant risk factors contributing to microvascular dysfunction in the early stage.Perspective cohort study.The study cohort consisted of 67 children and youth with TS and 32 age- and gender-matched controls. Measurements Clinical characteristics, left ventricle (LV) volume and function and cardiovascular magnetic resonance-derived myocardial perfusion parameters were assessed. Univariable and multivariable linear regression analyses were performed to assess the potential risk factors for microvascular dysfunction.Microvascular perfusion decreased in TS in global and segmented myocardium as reflected in the lower upslopeMyocardial microvascular dysfunction can occur in children and youth patients with TS. Age and overweight/obesity were the independent risk factors of microvascular dysfunction, which imply the importance of lowering BMI for the prevention of coronary heart disease in young TS population.

This study is designed to explore the role of long non-coding RNAs (lncRNAs) NCK1-AS1 in proliferative and invasive activities of esophageal squamous cell carcinoma (ESCC) cells by binding to microRNA-133b (miR-133b) to regulate ENPEP. Differentially expressed lncRNAs, miRs, genes and their targeting relationships were screened on ESCC-related gene expression datasets GSE17351 and GSE6188. The targeting relationships among NCK1-AS1, miR-133b, and ENPEP were verified using functional assays. Loss- and gain- of function assays were carried out to examine the roles of NCK1-AS1, miR-133b, and ENPEP in ESCC cell proliferative, invasive, migrative and apoptotic abilities as well as tumorigenesis

We conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)–negative complete response/stringent complete response. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T-cell reexpansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T-cell therapy in early lines of MM treatment.Significance:CAR T cells in early lines of MM therapy could be safer and more effective than in the advanced setting, where prior studies have focused. We evaluated the safety, pharmacokinetics, and efficacy of CAR T cells in patients with low disease burden, responding to current therapy, combined with standard maintenance therapy.This article is highlighted in the In This Issue feature, p. 101

Immunothrombosis is a mechanism of defense of the organism against pathogenic microorganisms that increases their recognition, limitation, and clearance and is part of the innate immune defense. Physiological immunothrombosis is beneficial to the body against the invasion of pathogenic microorganisms, but when immunothrombosis is out of control, it is easy to cause thrombotic diseases, thus, causing unpredictable consequences to the body. Neutrophils play a pivotal role in this process. Understanding the mechanism of neutrophils in immune thrombosis and out-of-control is particularly important for the treatment of related thrombotic diseases. In this review, we studied the role of neutrophils in immune thrombosis and each link out of control (including endothelial cell dysfunction; activation of platelets; activation of coagulation factor; inhibition of the anticoagulation system; and inhibition of the fibrinolysis system).

Fusarium graminearum is an important wheat pathogen and a producer of deoxynivalenol (DON). Biosynthesis of DON is suppressed by ammonium and induced by arginine and polyamines. To better understand ammonium repression of DON biosynthesis, in this study, we functionally characterized three ammonium permease (MEP) genes in F. graminearum. All the mep deletion mutants were normal in growth on V8 agar. Whereas deletion of MEP1 had no detectable phenotypes, the mep2 and mep3 mutants had defects in hyphal growth under ammonium limiting conditions and infection of wheat heads, with the latter having less severe defects. Deletion of MEP2 but not MEP3 affected nitrogen repression of DON biosynthesis and genes involved in nitrate metabolism. The mep2 mep3 double mutant had more severe defects in nitrogen repression than the mep2 mutant and was defective in ascospore releasing. Mutant alleles of MEP2 with truncated C-terminal cytoplasmic tail (CT) failed to complement the mep2 mutant. Expression of a dominant active allele of RAS2 partially rescued the defects of mep2 in nitrogen repression. Taken together, these results suggest that Mep2 acts as the major sensor of ammonium availability in F. graminearum and its CT region functions in nitrogen repression via RAS2 and downstream signalling pathways.

Jie Yang,1 Anhui Wang,2 Lei Shang,3 Chao Sun,1 Xin Jia,1 Liming Hou,1 Rong Xu,1 Xiaoming Wang1 1Department of Geriatrics, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of China; 2Department of Epidemiology, Air Force Medical University, Xi’an, 710032, People’s Republic of China; 3Department of Health Statistics, Air Force Medical University, Xi’an, 710032, People’s Republic of ChinaCorrespondence: Xiaoming Wang, Department of Geriatrics, Xijing Hospital, Air Force Medical University, 127 Changle West Road, Xi’an, 710032, People’s Republic of China, Tel +86-29-84775543, Email xmwang@fmmu.edu.cnObjective: The purpose of this study was to explore the effects of Chinese dietary habits and patterns on frailty among elderly people in Xi’an the community. We also sought to provide dietary suggestions for prevention of frailty.Methods: A cross-sectional survey was conducted and participants were divided into three groups: non-frail group, pre-frail group, and frail group. Our sample included 100 individuals randomly selected from each group for the dietary survey. Information regarding general socio-demographic characteristics and the types and quantity of food intake in the past 3 days was collected by a questionnaire. Factor analysis was used to identify dietary patterns; multiple logistic regression analysis was used to explore the correlation between dietary pattern and frailty.Results: (1) 1693 elderly individuals were screened. The prevalence of pre-frailty and frailty was 41.0% and 16.2%, respectively. (2) Two dietary patterns were defined: ordinary dietary pattern and high-fat dietary pattern. Compared with the high-fat diet, the intake of iron, vitamin E, polyunsaturated fatty acids, and legume protein was significantly lower in the ordinary diet (P < 0.05). (3) Multivariate regression analysis showed that the ordinary dietary pattern score was positively correlated with frailty, which was consistent after adjusting for confounding factors (P < 0.05).Conclusion: The low-fat and low-protein diet was positively correlated with the risk of frailty. Appropriate increase in fat and protein intake can help improve the frailty of the elderly in China.Keywords: elderly, frailty, dietary pattern, nutrients, protein

C19H14F4O2, triclinic, P 1 ‾ $P\overline{1}$ (no. 2), a = 8.3798(6) Å, b = 9.2019(7) Å, c = 10.4504(7) Å, α = 77.941(6)°, β = 85.712(6) , γ = 79.078(6)°, V = 773.25(10) Å3, Z = 2, R gt (F) = 0.0458, wR ref (F 2) = 0.1165, T = 100 K.

OBJECTIVE: To investigate 18F-FDG PET/CT findings of tuberculous lymphadenitis and analyze the causes of misdiagnosis. METHOD: Between 2013 and 2021, a retrospective review was conducted on 22 patients at Jiangxi Provincial People’s Hospital Affiliated with Nanchang University who had lymph node tuberculosis confirmed by histology or clinical investigation. Subjective judgment and quantitative analysis were adopted. RESULTS: Out of 22 patients, 14 are male and 8 are female. The average age was 55.5 years (55.5±12.4). The most common site of lymph node tuberculosis (LNTB) is the mediastinum (41.5%), followed by the neck (24.4%) and the abdominal cavity (21.9%). Half of the patients have more than one site affected. More than half of LNTB patients (54.5%) are concurrent with other types of TB, especially PTB. Among the 41 biggest affected lymph nodes, the average maximum diameter, minimum diameter, SUVmax and the lesion SUVmax/SUVmean liver ratio are 22.04±8.39, 16.93±6.75, 9.72±5.04 and 6.72±3.60, respectively. There is a poor correlation coefficient of 0.236 between the FDG uptake and the size of the biggest affected lymph node. Patients who are concurrent with no other TB have the significantly higher FDG uptake than patients who are concurrent with other TB (12.42 vs 8.02) (p = 0.005). Among these cases, 6 cases (27.3%) are accurately diagnosed with LNTB, all of which have pulmonary tuberculosis as a complication. However, 16 cases (72.7%) are misdiagnosed as lymphoma (50%), sarcoidosis (13.6%), and lymph node metastasis (9%). CONCLUSIONS: This study demonstrates that 18F-FDG PET/CT is very useful in detecting LNTB because tuberculous granulomas show significant levels of glucose uptake. It proves to be an effective method for revealing lesion extent and discovering additional lesions that morphological imaging is missed. However, 18F-FDG PET/CT is not able to reliably distinguish LNTB from lymphoma, sarcoidosis, and metastatic lymph nodes. Nonetheless, 18F-FDG PET/CT allows for the selection of the most optimal biopsy location, and thus has potential to detect early treatment response and distinguish between active and inactive lesions.

The mechanistic relationship between amyloid-beta precursor protein (APP) processing and mitochondrial dysfunction in Alzheimer’s disease (AD) has long eluded the field. Here, we report that coiled-coil-helix-coiled-coil-helix domain containing 6 (CHCHD6), a core protein of the mammalian mitochondrial contact site and cristae organizing system, mechanistically connects these AD features through a circular feedback loop that lowers CHCHD6 and raises APP processing. In cellular and animal AD models and human AD brains, the APP intracellular domain fragment inhibits CHCHD6 transcription by binding its promoter. CHCHD6 and APP bind and stabilize one another. Reduced CHCHD6 enhances APP accumulation on mitochondria-associated ER membranes and accelerates APP processing, and induces mitochondrial dysfunction and neuronal cholesterol accumulation, promoting amyloid pathology. Compensation for CHCHD6 loss in an AD mouse model reduces AD-associated neuropathology and cognitive impairment. Thus, CHCHD6 connects APP processing and mitochondrial dysfunction in AD. This provides a potential new therapeutic target for patients.

An infectious etiology of Alzheimer’s disease has been postulated for decades. It remains unknown whether SARS-CoV-2 viral infection is associated with increased risk for Alzheimer’s disease. In this retrospective cohort study of 6,245,282 older adults (age ≥65 years) who had medical encounters between 2/2020–5/2021, we show that people with COVID-19 were at significantly increased risk for new diagnosis of Alzheimer’s disease within 360 days after the initial COVID-19 diagnosis (hazard ratio or HR:1.69, 95% CI: 1.53–1.72), especially in people age ≥85 years and in women. Our findings call for research to understand the underlying mechanisms and for continuous surveillance of long-term impacts of COVID-19 on Alzheimer’s disease.

To investigate the clinical features and surgical outcomes of pediatric congenital first branchial cleft anomalies (CFBCAs).We conducted a retrospective analysis of 100 children who were referred to Shanghai Children's Hospital from March 2014 to March 2022 for the treatment of CFBCAs.This study included 100 patients (33 males, 67 females) with an average age of 4.0 ± 2.7 years. 64 cases were type I FBCAs and 36 were type II. The main clinical manifestations included having a skin pit or discharge from it (62%), painless masses (5%), mucopurulent otorrhea (8%) and recurrent swelling with pain (90%) in the Pochet's triangle area. 92% had infection histories, 84% had incision and drainage histories, and 18% had surgical histories. 6 cases of tympanic membranous attachment were found by auricular endoscopy. Ultrasonography (US) was 55.6% (30/54) accurate and enhanced CT was 75% (75/100) accurate in diagnosing CFBCAs. We dissected the facial nerve (FN) in 46% cases. Lesions ended in the external auditory canal (EAC) wall in 86 cases. 69 exhibited close relationship with the parotid. The patients were followed up 0.25-8.2 years. 11 had postoperative temporary facial paralysis and all improved within 6 months. 3 had recurrence and they were secondarily successfully retreated. No EAC stenosis were found.CFBCAs often presented with repeated swelling and purulence in Pochet's triangle. CT, US and auricular endoscopy can assist in diagnosis and planning the surgical strategy. Complete excision in non-infection stage as soon as possible is the first choice for the treatment of CFBCAs.

Purpose. This study aims to explore the application value of the 18F-FDG PET/CT imaging in diagnosing, staging, and typing Langerhans cell histiocytosis (LCH) via the morphological and metabolic analyses of the 18F-FDG PET/CT images. Methods. We retrospectively analyzed the 18F-FDG PET/CT images and clinical data of nineteen patients with LCH. The shape, size, density, distribution, and 18F-FDG uptake of all lesions were documented. In addition, the SUVmax of the lesions, liver, and blood pool was measured prior to calculating the lesion-to-liver and lesion-to-blood pool ratios. Results. Among the 19 analyzed patients, the positive rate of the PET/CT image was 94.7% (18/19), with 1 false negative (5.3%, 1/19) case occurring in the cutaneous LCH. Among the 76 lesions, 69 were FDG-avid lesions (69/76, 90.8%). Additionally, we observed no FDG uptake in 7 lesions (7/76, 9.2%). In contrast, 59 lesions (59/76, 77.6%) were abnormal on diagnostic CT scan, but 17 lesions (17/76, 22.4%) were undetected. The 18F-FDG PET/CT image revealed additional 6 lesions in the bone, 4 in the lymph node, 3 in the spleen, and 3 occult lesions, which CT scan did not detect. Additionally, there were 6 cases with single-system LCH. The remaining 13 cases were multisystem LCH. Our 18F-FDG PET/CT image analyses altered the typing of 4 LCH patients. In the case of all lesions, the mean SUVmax of the 18F-FDG-avid lesions was 5.4 ± 5.1 (range, 0.8∼26.2), and the mean lesion-to-liver SUVmax ratio was 3.1 ± 2.52 (range, 0.7∼11.9), and the mean lesion-to-blood pool SUVmax ratio was 4.6 ± 3.4 (range 0.7∼17.5). Conclusion. The 18F-FDG PET/CT image plays an essential role in LCH diagnosis, primary staging, and typing. It can accurately evaluate the distribution, range, and metabolic information of LCH, providing a vital imaging basis for the clinical evaluation of disease conditions, selection of treatment schemes, and determining patient prognosis.

This paper expounded the important significance of the construction of vocational college social practice system to improve the employment quality of higher vocational graduates. After analyzing the problems existing in vocational college students' social practice, the "three characteristics" of vocational college social practice system, such as educative nature, professionalism, hierarchical characteristics etc, were explored. The measures to strengthen the construction of social practice system were also presented.

The second classroom in higher vocational colleges is an important channel to implement the fundamental task of moral education, improve the adaptability of vocational education and improve the quality of personnel training. Aiming at the current key problems of the second classroom education in higher vocational college, such as the fuzzy orientation of training objectives, the unidirectional supply of curriculum items, and the single implementation of training, this paper constructed the dynamic training mode of DLFL in the second classroom education, the dynamic evaluation mechanism of training objectives, the dynamic selection mechanism of curriculum items, and the multi-party collaborative dynamic education mechanism, thus forming a dynamic model of second classroom education based on the theory of trait factor. This is conducive to the development of students' commonness and individuality in the same direction, thus achieving everyone brilliant.

Continuous assessment of disease activity remains a huge challenge during the follow-ups of patients with Crohn's disease (CD). In this paper, we aimed to evaluate the performance of contrast-enhanced ultrasound (CEUS) by comparing with computed tomography enterography (CTE) in the assessment of disease activity in CD.Fifty-two patients diagnosed with CD were included in this study, using the CEUS and CTE as imaging methods for comparison. The selected parameters included the location and thickness of the thickest part of the intestinal wall, mesenteric fat proliferation, mesenteric vessels change, enhancement pattern and the presence of complications. Patients were clinically assessed using the Crohn's disease activity index (CDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Simple endoscopic score for Crohn's disease (SES-CD) was regarded as the reference standard.The location of the thickest part of the intestinal wall (κ = 0.653), bowel wall thickness (ICC = 0.795), mesenteric vessels change (κ = 0.692) and complications (κ = 0.796) displayed substantial agreement (0.61-0.80) between CEUS and CTE, while the detection of mesenteric fat proliferation (κ = 0.395) and enhancement pattern (κ = 0.288) showed fair consistency (0.21-0.40) for comparison. In CEUS, bowel wall thickness, mesenteric fat proliferation, enhancement pattern and mesenteric vessels change were statistically significant in assessing CD activity, while bowel wall thickness, mesenteric fat proliferation and mesenteric vessels change in CTE. Bowel wall thickness showed the best diagnostic performance in the assessment of CD activity at CEUS and CTE.CEUS provides a radiation-free and effective way to assess the CD activity in comparison with CTE, which also avoids frequent colonoscopy examinations, improves tolerance of patients, and reduces the cost of medical care, thereby serving as a useful tool for CD follow-up.

The pollution and adverse effects of microplastics in the marine environment have been widely reported. However, the information on the transfer of chemical additives from microplastics to the environment or organisms is quite limited. This study investigated the release of hexabromocyclododecanes (HBCDs) from expanded polystyrene (EPS) microplastics in seawater and digestive fluids. The results showed that both the particle size of EPS microplastics and environmental parameters (temperature, salinity, and pH) play crucial roles in the release of HBCDs. The release rates of ΣHBCD (sum of α-, β- and γ-HBCD) from EPS microplastics in seawater ranged from 8.64 to 33.3 ng·g-1·d-1 under different conditions. Compared with the seawater control, a slight but not significant increase in the release of HBCDs was observed in the digestive fluids. The diastereoisomer profiles of HBCDs released from EPS microplastics both in seawater and digestive fluids were similar. The proportions of α-HBCD and β-HBCD released from EPS in seawater and digestive fluids were higher than those in the original EPS microplastics, especially for β-HBCD. The diffusion model explained the release data of HBCDs from EPS microplastics apparently better than the other two models, suggesting that the diffusion within the matrix of microplastic is a rate-limiting step. Based on the mass of EPS microplastics and release rates of HBCDs, the annual release of HBCDs from EPS microplastics into the global ocean was estimated to be 9.29 to 115 kg. These HBCDs would have profound impacts on marine organisms and even endanger human health and safety. Considering the abundance of microplastics in the ocean, the release of chemical additives from microplastics deserves more attention in the future.

Carbohydrates are widely distributed in nature as an important nutritional substance and energy source. However, the utilization efficiency of carbohydrates is very poor in fish. Over consumption of carbohydrates will cause excessive inflammatory response and result in lower pathogen resistance in fish. Probiotics have been widely used to prevent inflammation, but the underlying mechanism still needs more exploration. In this study, three diets, including a control diet (CD), a high-carbohydrate diet (HD) and the HD supplemented with Bacillus amyloliquefaciens SS1 (HDB) were used to feed Nile tilapia for 10 weeks. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila (A. hydrophila) for 7 days. The data showed that the addition of Bacillus amyloliquefaciens SS1 (B. amyloliquefaciens SS1) significantly increased the survival rate and enhanced the respiratory burst activity of head kidney leukocytes in Nile tilapia. B. amyloliquefaciens SS1 treatment significantly elevated the anti-oxidative capability, which was evidenced by higher activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), and higher content of reduced glutathione (GSH) in the serum. Administration with B. amyloliquefaciens SS1 effectively suppressed inflammatory response in the liver by inhibiting nuclear factor kappa-B (NF-κB)/interleukin-1 beta (IL-1β) inflammatory signaling pathway. In vitro analysis suggested that intestinal bacteria derived-acetate has the antioxidant capability, which may account for the alleviation of inflammation. Overall, this study demonstrated that dietary supplementation with B. amyloliquefaciens SS1 protected Nile Tilapia against A. hydrophila infection and suppressed liver inflammation by enhancing antioxidant capability.

Cosmetics are widely used, but some components can be toxic at a certain dose. Thus, it is emerging to understand the toxic chemicals in cosmetics and their potential impact. This review introduces common cosmetics components with toxicity including metals, phenoxyethanol and Aloe vera. Toxic effects include some local effects, such as osteomalacia caused by metals, eye irritation, skin irritation and allergy caused by phenoxyethanol, as well as colonic mucosa caused by Aloe vera. Toxic chemicals in cosmetics are usually absorbed via the skin, and degraded in liver, then exerted through kidney and forceps. Methods to determine potential toxins includes determining heavy metals in skin-whitening cosmetics, fluorescence-based assay and the first voltametric method of phenoxyethanol determination. Future research may focus on exploring the effects of accumulation of toxic components and mechanisms of the toxicities to prevent toxic effects, as well as improving the efficiency of testing to better monitor the commercial cosmetics.

Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families.Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples.The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients.Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.

Peripheral nerve blocks are the regional techniques in orthopedic surgeries to control postoperative pain and have early discharge from hospital. However, anesthesia protocols for foot and ankle surgeries of institutes do not include multimodal analgesics including peripheral nerve blocks. The objective of the study was to compare spinal anesthesia with peripheral nerve block against general anesthesia with peripheral nerve block for elective foot and ankle surgeries. Patients have treated for elective foot and ankle surgery under general anesthesia (using propofol, 0.05 mg/kg dezocine, and 1 % sevoflurane; GA cohort, n = 112) or spinal anesthesia (using 0.5 % bupivacaine, propofol, and 0.05 mg/kg dezocine; SA cohort, n = 132) or patients have treated for elective for foot and ankle surgery under general anesthesia (GL cohort, n = 115) or spinal anesthesia (SL cohort, n = 160) with the use of peripheral nerve block (the sciatic nerve blocks and adductor canal nerve blocks using 0.25 % bupivacaine and 0.1 mg/kg dexamethasone). Propofol was administered in fewer amounts if anesthesia was used with the peripheral nerve block. Patients of the GL cohort were transferred to ward 36 min (mean) earlier than those of the SL cohort. None of the patients of the GL and the SL cohorts have received intraoperative opioid(s) for the management of pain. Patients of the GL and the SL cohorts have reported postoperative falls within 1 day after surgeries during movement. Patients of the SL cohort experienced more frequently difficulty with sleeping. Patients of the GL and the GA cohorts have reported nausea and vomiting. Only patients of the GL cohort were required usage of vasoactive drugs. The study provides information to anesthesiologists and surgeons regarding anesthesia techniques for elective foot and ankle surgeries for better surgical outcomes (Level of Evidence: 2; Technical Efficacy Stage: 4).