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To construct a therapeutic play program for children undergoing preparation for kidney biopsy under local anesthesia and explore the feasibility of the program from stakeholders' perspectives.The program was constructed by a multidisciplinary team and the feasibility and acceptability of the program were explored by a descriptive qualitative study.Based on LazarusFolkman's stress-coping model and Piaget's theory of play, and using on-site participatory field observation, a multidisciplinary team constructed a therapeutic play program for children undergoing kidney biopsy under local anesthesia. The feasibility and acceptability of the program were evaluated by interviewing children, their caregivers, and physicians.The main tools constructed for the intervention were a 15-page picture book titled Kidney Biopsy Treasure Hunt and a homemade kidney biopsy play package. The therapeutic play intervention for kidney biopsy under local anesthesia was led by nurses and followed the steps of kidney biopsy, using the picture book, and group play simulation. Through informed in-depth interviews with 10 children and their caregivers, we showed that the therapeutic play program materials were accessible, clinically feasible, and necessary for kidney biopsy under local anesthesia in children. The children and their caregivers had high acceptance of the content of the picture book, the format of the play, and high satisfaction with the overall program.The therapeutic play program we constructed for children undergoing kidney biopsy with local anesthesia was simple, feasible, and well accepted in the clinical setting.

Dental biofilm is the initiating factor of oral diseases, such as periodontitis and caries. Orthodontic treatment could alter the microbiome structure balance, and increase the risk of such diseases. Furthermore, fixed appliances can induce temporary changes in the microbiome community, and the changes that clear aligners bring are smaller by comparison. Temporary anchorage devices (TADs) are skeletal anchorages that are widely used in orthodontic treatment. Microorganisms affect the occurrence and development of inflammation surrounding TADs. At present, existing researches have verified the existence of plaque biofilm on the surface of TADs, but the formation of plaque biofilm and plaque composition under different stable conditions have not been fully understood. The development of high-throughput sequencing, molecular biology experiments, and metabonomics have provided new research ideas to solve this problem. They can become an effective means to explore the microbiome surrounding TADs.

Purpose:Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Nucleosome assembly protein 1-like 5 (NAP1L5) is a protein-coding gene that encodes a protein similar to nucleosome assembly protein 1 (NAP1). It is a histone chaperone that plays an important role in gene transcription in organisms. However, the role of NAP1L5 in the pathogenesis of hepatocellular carcinoma remains to be elucidated.Method：We used QRT-PCR, immunohistochemistry and westernbolting to detect the expression of NAP1L5 in tissues and cell lines, and analyzed the relationship between its expression and clinicopathological features and prognosis. after up-regulating and down-regulating NAP1L5 in cell lines, we used a variety of methods to verify its regulatory effect on HCC, and verified it again in animal experiments, mass spectrometry analysis to find the possible binding protein (MYH9) and downstream signaling pathway (PI3K/AK/mTOR). And verify the relationship between them.Results: In this study, low expression of NAP1L5 was found in hepatocellular carcinoma, and the downregulation of NAP1L5 was related to shorter survival and disease-free survival. In addition, its expression is also related to the tumor size and recurrence of hepatocellular carcinoma. The overexpression and knockdown of NAP1L5 by plasmid and siRNA showed that NAP1L5 inhibited the proliferation, migration and invasion and induced apoptosis of hepatoma cells. In vivo experiments confirmed that NAP1L5 can inhibit the growth and metastasis of hepatocellular carcinoma cells. In the mechanistic study, we found that NAP1L5 affects the occurrence and development of hepatocellular carcinoma by regulating MYH9 to inhibit the PI3K/AKT/mTOR signaling pathway. Conclusion: As a functional tumor suppressor, NAP1L5 is expressed at low levels in HCC. NAP1L5 inhibits the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma by regulating MYH9.It may be a new potential target for liver cancer treatment.

Background: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. Methods: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target

Adrenomedullin (ADM) is thought to play a significant role in regulating insulin secretion and glucose metabolism. However, studies on the relationship between ADM and gestational diabetes mellitus (GDM) are limited. We hypothesized that a higher serum ADM concentration would be associated with an increased risk of GDM. Therefore, a nested case-control study of 65 GDM cases and 130 prepregnancy body mass index, age, parity, and gestational age of blood collection-matched controls was conducted to prospectively evaluate the association between circulating ADM concentrations in early pregnancy and the risk of GDM in pregnant women based on the Tongji Birth Cohort. Serum ADM concentrations in the GDM group were higher than those in the control group (2125.04 ± 644.97 vs 1880.76 ± 581.13 pg/mL) (P = .008). Serum ADM concentration was positively associated with the risk of developing GDM (P

Background: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are two commonly used cognitive screening and diagnostic tools. Objective: Our goal was to assess their efficacy for monitoring cognitive changes, as well as the correlation between the two tests. Methods: At baseline, participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were divided into four groups based on their cognitive diagnoses: healthy control (HC), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and Alzheimer’s disease (AD). MMSE or MoCA scores were compared among the four groups using an analysis of variance (ANOVA) model with repeated measures with post-hoc Bonferroni correction. For those participants who had both MMSE and MoCA assessments done, a Pearson correlation analysis was performed between the two assessments for each visit. Results: The MMSE scores were significantly different among the four groups at baseline, which was true for each of the three annual follow-up visits. By contrast, the MoCA scores were not significantly different between HC and EMCI groups at either baseline or any of the follow-up visits. For participants with a diagnosis of LMCI, the cognitive performance deteriorated in a linear manner 12 months after the baseline, which was independent of MMSE or MoCA. At last, the MMSE scores were moderately related to MoCA scores, which got stronger along with the time of follow-up. Conclusion: MMSE and MoCA are comparable as cognitive assessment tools to monitor cognitive changes. In addition, the measurements of MMSE and MoCA are moderately correlated for the follow-up visits.

Diffuse intrinsic pontine gliomas (DIPGs) are prone to high surgical risks, and they could even lead to death due to their specific sites. To determine the value of frameless robot-assisted stereotactic biopsies of DIPGs, when compared it with microsurgical biopsies.We conducted a retrospective study of 71 pediatric patients who underwent biopsies from January 2016 to January 2021. (i) group 1: microsurgical biopsies, and (ii) group 2: frameless robot-assisted stereotactic biopsies. Demographic information, neuroimaging characteristics, pathological diagnoses, operation time, postoperative intensive care unit (ICU) stay time, postoperative hospitalization time, complications, cost, and perioperative mortality rate (POMR) were collected for analyses.32 Cases underwent microsurgical biopsies (group 1) and 39 cases underwent frameless robot-assisted stereotactic biopsies (group 2). All cases were accurately diagnosed after surgery. There was no significant difference in gender, age, symptom times and tumor volumes between the two groups (p 0.05); operation time, postoperative ICU, stay time and postoperative hospitalization time were longer in group 1 than in group 2 (p 0.001); the intraoperative bleeding volumes and cost were higher in group 1 than in group 2 (p 0.001). Group 1 patients required more perioperative blood transfusion than group 2 (p = 0.001), and the new neurological impairments were more frequent in group 1 than in group 2 (p = 0.003). The POMR was 9.38% (3/32) in group 1 and 0 in group 2 (p = 0.087).Frameless robot-assisted stereotactic biopsy was an effective and minimally invasive technique for pediatric DIPGs.

China is a major producer of copper concentrate as its smelting capacity continues to expand dramatically. The present study analyzes the life cycle environmental impact of copper concentrate production, along with selection of a typical copper sulphate mine in China. Life cycle assessment (LCA) was conducted using SimaPro with ReCiPe 2016 method. The midpoint and endpoint results were performed with uncertainty information based on Monte Carlo calculation. Normalization of midpoint results revealed that impact from the marine ecotoxicity category was the largest contributor to the total environmental impact, followed by freshwater ecotoxicity, human carcinogenic toxicity, human non-carcinogenic and terrestrial ecotoxicity. The mining activity, backfilling activity and electricity generation were proved to be the dominant factors. In addition, main processes and substances to the identified key categories were also classified. Specifically, the cement production in the backfilling process, blasting activity, on-site emission and electricity generation were regarded as the critical processes. Copper to air and zinc emission to water were considered as the critical substances. The sensitivity analysis indicated that controlling on-site emissions and reducing pollution from cement production were the most effective measure to solve the environmental problems caused by the concentrate production process. Finally, the corresponding technical and management measures were proposed to facilitate the development of cleaner metal industry.

Acute thrombotic thrombocytopenic purpura (TTP) is a life-threatening emergency and plasma exchange (PEX) is the initial treatment shown to reduce acute mortality.To compare current practice in the United Kingdom (UK) against the standards set out in the 2012 British Society of Haematology guideline, and to better understand the issues affecting prompt initiation of PEX.The trainee research network HaemSTAR conducted a retrospective nationwide review of adults presenting to UK hospitals with a first episode of acute TTP.Data on 148 patients treated at 80 UK hospitals between 2014 and 2019 demonstrated that 64.8% of patients received PEX within 24 h. Diagnostic uncertainty was the most commonly cited reason for delayed treatment. Conversely, a shorter time to PEX occurred in patients who had red cell fragments or severe thrombocytopenia identified on their first complete blood count. Availability of on-site PEX was associated with a greater proportion of patients receiving PEX within 8 h compared to patients transferred, but by 24 h there was no difference between the two groups and two-thirds of all patients had received their first PEX. The mortality rate for patients that received PEX was 9.2%, with 27.8% of deaths linked to delayed treatment initiation.This is the first multi-center evaluation of treatment delays in acute TTP and it will inform targeted pathways to improve prompt access to life-saving intervention.

To evaluate the health risks of drinking water in Hanyuan County, 96 samples of peripheral drinking water were collected from 30 sites in the area. The samples were then analysed for physicochemical properties including Fe, Mn, NH 3 -N, , F-, Pb, Hg, As, Cr 6+ , Cd, and so on. The health risks of ten trace elements in drinking water were probabilistically assessed using the health risk assessment model and Monte Carlo simulation. On this basis, sequential indicator simulations were used to classify the health risk levels of drinking water in the region, to conduct hierarchical management and control. The results showed that except for , all other indicators met World Health Organisation standards and China’s drinking water sanitation standards. Drinking water presents a specific carcinogenic risk to adults, and the cumulative contribution of As and Cr 6+ exceeds 95%, and has a specific non-carcinogenic risk to children if the cumulative contribution of F - , , and As exceeds 90%. Grade I, II, and III non-carcinogenic risk areas accounted for 0.89%, 24.72%, and 74.39% of the total area of Hanyuan County, respectively, while grade I, II, and III carcinogenic risk areas accounted for 27.71%, 45.56%, and 26.73% of the total Hanyuan County area, respectively. Finally, according to the health risk characteristics of each control area, corresponding zoning control suggestions were proposed.

Melanotic nerve sheath tumor (MNST) is a rare variant of schwannoma. Here, we report an unusual case of multiple MNST lesions located in the upper limb nerves. The patient presented with a mass on the left wrist in 2016 and another mass on the left thumb in 2017. In both instances, magnetic resonance imaging scans confirmed multiple giant-cell tumors of the tendon sheath. Persistent pain in the left upper limb and numbness in the ring finger and little finger recurred in 2021. High-frequency ultrasound (HFUS) showed that the left brachial plexus nerves (C5-8) were widened compared with those on the contralateral side; the neuroma formed at the lateral cord, and the median nerve was markedly thickened. The surgical findings were consistent with the ultrasound results. Pathology confirmed that the tumors were malignant MNSTs. HFUS is important for preoperative diagnosis and lesion localization, even identifying some lesions that are unrecognized on magnetic resonance imaging; thus, HFUS is crucial for improving surgical strategy and decision-making.

Posterior cerebral artery (PCA) aneurysms are rare. This study is to evaluate the preliminary experience of braided stents applied in PCA aneurysms treatment.Angiographic and clinical data of 28 PCA patients treated with braided stents from July 2016 and September 2020 were retrospectively analyzed.A total of 28 PCA aneurysms were enrolled. 22 (78.6%) aneurysms were dissecting aneurysms, while 6 (21.4%) aneurysms were saccular aneurysms. Thirty-five braided stents were implanted with dual stents implanted in 7 cases. Immediate angiographic results show that Raymond class I was obtained in 13 patients (46.4%), Raymond class II was obtained in 4 patients (14.3%), and Raymond class III was obtained in 11 patients (39.3%). Perioperative hemorrhagic events occurred in 1 patient (3.6%). Twenty-four patients (85.7%) received angiographic follow-up, and the mean follow-up time was 11.2 ± 4.9 months. Two patients (8.3%) were confirmed with IA neck recurrence, and 3 patients (12.5%) were confirmed asymptomatic parent artery occlusion (PAO). The other 19 patients were confirmed promoted occlusion with 18 Raymond class I (75%) and 1 Raymond class II (4.2%). Twenty-seven patients (96.4%) received clinical follow-up, and the mean follow-up time was 32.2 ± 13.5 months. One patient (3.7%) confirmed the death event 2 weeks after discharge. The other 27 patients (96.3%) got favorable clinical outcomes with an mRS score of 0-2.Braided stent-assisted coiling with a high occlusion rate and relatively low complication rate provides an alternative strategy in treating PCA aneurysms. Long-term outcomes need further randomized study with larger case numbers.

SARS-CoV-2 cellular infection is mediated by the heavily glycosylated spike protein. Recombinant versions of the spike protein and the receptor-binding domain (RBD) are necessary for seropositivity assays and can potentially serve as vaccines against viral infection. RBD plays key roles in the spike protein's structure and function, and thus, comprehensive characterization of recombinant RBD is critically important for biopharmaceutical applications. Liquid chromatography coupled to mass spectrometry has been widely used to characterize post-translational modifications in proteins, including glycosylation. Most studies of RBDs were performed at the proteolytic peptide (bottom-up proteomics) or released glycan level because of the technical challenges in resolving highly heterogeneous glycans at the intact protein level. Herein, we evaluated several online separation techniques: (1) C2 reverse-phase liquid chromatography (RPLC), (2) capillary zone electrophoresis (CZE), and (3) acrylamide-based monolithic hydrophilic interaction chromatography (HILIC) to separate intact recombinant RBDs with varying combinations of glycosylations (glycoforms) for top-down mass spectrometry (MS). Within the conditions we explored, the HILIC method was superior to RPLC and CZE at separating RBD glycoforms, which differ significantly in neutral glycan groups. In addition, our top-down analysis readily captured unexpected modifications (e.g., cysteinylation and N-terminal sequence variation) and low abundance, heavily glycosylated proteoforms that may be missed by using glycopeptide data alone. The HILIC top-down MS platform holds great potential in resolving heterogeneous glycoproteins for facile comparison of biosimilars in quality control applications.

We aimed to compare the prognosis of laryngeal squamous cell carcinoma (LSCC) and nSCCs of the larynx.Then we established a nomogram for nSCCs of the larynx.Prognosis between the 529 pairs nSCCs of the larynx patients and LSCC patients were compared after propensity score matching (PSM). 591 nSCCs of the larynx patients were divided into the modeling and validation groups. Univariate and multivariate Cox analyses obtain independent prognostic factors, which were then included in the nomogram to predict the 3 and 5 year survival. Prognostic accuracy of the nomogram was evaluated using the consistency index (C-index) and the calibration curve.Prognosis of nSCCs of the larynx was poorer than LSCC. Age, race, tumor location, tumor-node-metastasis stage, and method were independent prognostic factors of nSCCs of the larynx (P0.05). Internal and external validation proves the nomogram reliable CONCLUSION: The nomogram showed good prognostic accuracy and would assist clinicians in making more accurate evaluations for patients.

Accumulating evidence suggests that vitamin D deficiency increases the risk of adverse perinatal outcomes. However, the dose-response relationship between maternal vitamin D status and adverse birth outcomes remains unclear. Focusing on prospective observational studies, we aimed to explore the dose-response relationship of vitamin D status with the risk of low birth weight (LBW), macrosomia (MA), preterm birth (PTB), small for gestational age (SGA), and intrauterine growth restriction (IUGR).Databases including PubMed, Embase, Scopus, and Web of Science were used up to 19 January 2021 to search for observational studies that fulfilled criteria as follows: cohort studies, case-cohort studies, or nested case-control studies. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs) in the observational studies.A total of 72 publications were included in this systematic review and 71 in the meta-analysis. Maternal 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with the risk of LBW (RR: 0.65; 95% CI 0.48-0.86), PTB (RR: 0.67; 95% CI 0.57-0.79), and SGA (RR: 0.61; 95% CI 0.49-0.76) in the highest versus lowest meta-analysis, but not associated with MA and IUGR. Linear dose-response analysis showed that each 25 nmol/L increase in 25(OH)D was associated with a 6% and 10% reduction in the risk of PTB (RR: 0.94; 95% CI 0.90-0.98) and SGA (RR: 0.90; 95% CI 0.84-0.97), respectively.Our study suggests that a sufficient vitamin D status during pregnancy is protective against the risk of LBW, PTB, and SGA.

BackgroundThe inflammatory response caused by microglia in the central nervous system plays an important role in Alzheimer's disease. Neuregulin-1 (NRG1) is a member of the neuregulin family and has been demonstrated to have anti-inflammatory properties. The relationship between NRG1, microglia phenotype and neuroinflammation remains unclear.Materials and MethodsBV2 cells were used to examine the mechanism of NRG1 in regulating microglia polarization. Neuronal apoptosis, inflammatory factors TNF-α and iNOS, microglia polarization, ErbB4 and NF-κB p65 expression were assessed.ResultsWe found that exogenous NRG1 treatment or overexpression improved microglial activity and reduced the secretion of the inflammatory factors TNF-α and iNOS in vitro. The expression of Bax in SH-SY5Y neuron cells incubated with medium collected from the NRG1 treatment group decreased. Additionally, our study showed that NRG1 treatment reduced the levels of the M1 microglia markers CD120 and iNOS and increased the levels of the M2 microglia markers CD206 and Arg-1. Furthermore, we observed that NRG1 treatment attenuated Aβ-induced NF-κB activation and promoted the expression of p-ErbB4 and that knockdown of ErbB4 abrogated the effects of NRG1 on NF-κB, Bax levels and M2 microglial polarization. Conclusion NRG1 inhibits the release of inflammatory factors in microglia and regulates the switching of the M1/M2 microglia phenotype, most likely via ErbB4-dependent inhibition of the NF-κB pathway.

Gremlin has been reported to regulate inflammation and osteogenesis. Periodontitis is a destructive disease degenerating periodontal tissues, therefore leads to alveolar bone resorption and tooth loss. Based on the importance of Gremlin's bio-activity, the aim of this study is to, in vivo and in vitro, unveil the function of Gremlin in regulating the development of periodontitis and its consequent effects on alveolar bone loss.Clinical specimens were used to determine the expression of Gremlin in periodontal tissues by immunohistochemical staining and western blot. Then utilizing the rat periodontitis model to investigate the function of gremlin-regulated nuclear factor-kappa B (NF-κB) pathway during the development of periodontal inflammation and the alveolar bone loss. Last, the regulation of the osteogenesis of human periodontal ligament stem cells (hPDLSCs) by Gremlin under inflamed condition was analyzed by alkaline phosphatase (ALP) and alizarin red staining (ARS).We found clinically and experimentally that the expression of Gremlin is markedly increased in periodontitis tissues. Interestingly, we revealed that Gremlin regulated the progress of periodontitis via regulating the activities of NF-κB pathway and interleukin-1β (IL-1β). Notably, we observed that Gremlin influenced the osteogenesis of hPDLSCs. Thus, our present study identified Gremlin as a new key regulator for development of periodontitis.Our current study illustrated that Gremlin acts as a crucial mediator and possibly serves as a potential diagnostic marker for periodontitis. Discovery of new factors involved in the pathophysiology of periodontitis could contribute to the development of novel therapeutic treatment for the disease.

Functional rhinoplasty (FRP) is used to improve nasal ventilation by correcting problems with the nasal valves. It has not been systematically reviewed on a large scale.A comprehensive literature search was conducted in the PubMed, EMBASE, and Cochrane Library databases to identify studies evaluating nasal obstruction before and after functional rhinoplasty in patients with nasal valve problems.A total of 57 cohorts from 43 studies involving 2024 patients were included in the current meta-analysis. The Nasal Obstruction Symptom Evaluation (NOSE) scores indicated significant improvement in nasal obstruction at the 1-month follow-up (WMD = 38.12; 95% CI, 29.15-47.10; IFRP may have a positive effect on nasal obstruction caused by nasal valve problems. Broader and well-designed studies are needed to shed more light on the relationships in this area.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

By November 30, 2021, approximately 130,781 COVID-19-associated deaths, one in six of all U.S. deaths from COVID-19, had occurred in California and New York.* COVID-19 vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19), associated severe illness, and death (1,2); among those who survive, previous SARS-CoV-2 infection also confers protection against severe outcomes in the event of reinfection (3,4). The relative magnitude and duration of infection- and vaccine-derived protection, alone and together, can guide public health planning and epidemic forecasting. To examine the impact of primary COVID-19 vaccination and previous SARS-CoV-2 infection on COVID-19 incidence and hospitalization rates, statewide testing, surveillance, and COVID-19 immunization data from California and New York (which account for 18% of the U.S. population) were analyzed. Four cohorts of adults aged ≥18 years were considered: persons who were 1) unvaccinated with no previous laboratory-confirmed COVID-19 diagnosis, 2) vaccinated (14 days after completion of a primary COVID-19 vaccination series) with no previous COVID-19 diagnosis, 3) unvaccinated with a previous COVID-19 diagnosis, and 4) vaccinated with a previous COVID-19 diagnosis. Age-adjusted hazard rates of incident laboratory-confirmed COVID-19 cases in both states were compared among cohorts, and in California, hospitalizations during May 30-November 20, 2021, were also compared. During the study period, COVID-19 incidence in both states was highest among unvaccinated persons without a previous COVID-19 diagnosis compared with that among the other three groups. During the week beginning May 30, 2021, compared with COVID-19 case rates among unvaccinated persons without a previous COVID-19 diagnosis, COVID-19 case rates were 19.9-fold (California) and 18.4-fold (New York) lower among vaccinated persons without a previous diagnosis; 7.2-fold (California) and 9.9-fold lower (New York) among unvaccinated persons with a previous COVID-19 diagnosis; and 9.6-fold (California) and 8.5-fold lower (New York) among vaccinated persons with a previous COVID-19 diagnosis. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These relationships changed after the SARS-CoV-2 Delta variant became predominant (i.e., accounted for50% of sequenced isolates) in late June and July. By the week beginning October 3, compared with COVID-19 cases rates among unvaccinated persons without a previous COVID-19 diagnosis, case rates among vaccinated persons without a previous COVID-19 diagnosis were 6.2-fold (California) and 4.5-fold (New York) lower; rates were substantially lower among both groups with previous COVID-19 diagnoses, including 29.0-fold (California) and 14.7-fold lower (New York) among unvaccinated persons with a previous diagnosis, and 32.5-fold (California) and 19.8-fold lower (New York) among vaccinated persons with a previous diagnosis of COVID-19. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These results demonstrate that vaccination protects against COVID-19 and related hospitalization, and that surviving a previous infection protects against a reinfection and related hospitalization. Importantly, infection-derived protection was higher after the Delta variant became predominant, a time when vaccine-induced immunity for many persons declined because of immune evasion and immunologic waning (2,5,6). Similar cohort data accounting for booster doses needs to be assessed, as new variants, including Omicron, circulate. Although the epidemiology of COVID-19 might change with the emergence of new variants, vaccination remains the safest strategy to prevent SARS-CoV-2 infections and associated complications; all eligible persons should be up to date with COVID-19 vaccination. Additional recommendations for vaccine doses might be warranted in the future as the virus and immunity levels change.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome involved in many organ systems. At the same time, epilepsy is the most common manifestation and more than 50% of TSC patients present with intractable epilepsy. This study investigated the efficacy and safety of optimized and high-density stereoelectroencephalography (SEEG) guided radiofrequency thermocoagulation (RF-TC) in treating TSC-related epilepsy.Nine TSC children with refractory epilepsy were treated with first-stage SEEG-Guided RF-TC, and four underwent second-stage-optimized high-density array of SEEG-Guided RF-TC. Patients' clinical data and postoperative outcomes were analyzed retrospectively.The patients' median age at surgery was 4 years and 2 month (range from 3 years and 5 month to 16 years and 7 month). The mean age at surgery was 6.7 years old. Eight in 9 (88.9%) patients achieved complete remission after the final operation at half-year follow-up. Of seven patients with final postoperative time beyond 1 year, 6 (85.7%) reached completely seizure-free. No severe or long-term neurologic impairment existed in all nine patients.Optimized high-density array of SEEG-guided RF-TC is a safe and highly effective approach and can be an alternative application applied for TSC patients with refractory epilepsy.

Acute kidney injury (AKI) with maladaptive tubular repair leads to renal fibrosis and progresses to chronic kidney disease (CKD). At present, there is no curative drug to interrupt AKI-to-CKD progression. The nuclear factor of the activated T cell (NFAT) family was initially identified as a transcription factor expressed in most immune cells and involved in the transcription of cytokine genes and other genes critical for the immune response. NFAT2 is also expressed in renal tubular epithelial cells (RTECs) and podocytes and plays an important regulatory role in the kidney. In this study, we investigated the renoprotective effect of 11R-VIVIT, a peptide inhibitor of NFAT, on renal fibrosis in the AKI-to-CKD transition and the underlying mechanisms. We first examined human renal biopsy tissues and found that the expression of NFAT2 was significantly increased in RTECs in patients with severe renal fibrosis. We then established a mouse model of AKI-to-CKD transition using bilateral ischemia-reperfusion injury (Bi-IRI). The mice were treated with 11R-VIVIT (5 mg/kg, i.p.) on Days 1, 3, 10, 17 and 24 after Bi-IRI. We showed that the expression of NFAT2 was markedly increased in RTECs in the AKI-to-CKD transition. 11R-VIVIT administration significantly inhibited the nuclear translocation of NFAT2 in RTECs, decreased the levels of serum creatinine and blood urea nitrogen, and attenuated renal tubulointerstitial fibrosis but had no toxic side effects on the heart and liver. In addition, we showed that 11R-VIVIT administration alleviated RTEC apoptosis after Bi-IRI. Consistently, preapplication of 11R-VIVIT (100 nM) and transfection with NFAT2-targeted siRNA markedly suppressed TGFβ-induced HK-2 cell apoptosis in vitro. In conclusion, 11R-VIVIT administration inhibits IRI-induced NFAT2 activation and prevents AKI-to-CKD progression. Inhibiting NFAT2 may be a promising new therapeutic strategy for preventing renal fibrosis after IR-AKI.

Background Recurrence of nasopharyngeal carcinoma (NPC) after chemoradiotherapy is common, but submucosal recurrence of NPC is rare. The final pathological results determine the optimal therapeutic schedule for treatment of NPC recurrence, but tissue retrieval from submucosal lesions is usually difficult. The present study aimed to assess the safety and efficacy of a novel approach of endonasopharyngeal ultrasound-guided transnasopharyngeal needle aspiration (ENUS-TNNA) for submucosal neoplasms in patients with suspected NPC recurrence. Methods Between March 2017 and June 2021, 11 post-chemoradiotherapy patients with suspected magnetic resonance imaging (MRI) findings of submucosal recurrence of NPC underwent ENUS-TNNA. The safety and effectiveness of using ENUS-TNNA to sample submucosal neoplasms were evaluated. Results Needle aspiration biopsies were performed without any incidences in all cases. Out of the 11 patients, nine were diagnosed with submucosal recurrence of NPC via histopathological or cytological evaluations. Of the two puncture-negative cases, one patient had atypical imaging findings and clinical manifestations and was therefore followed-up using MRI. After follow-up for 3 years, this patient was still considered to be cancer-free due to the shrinking diameters of the submucosal lesions. For the other puncture-negative patient, submucosal biopsy samples were obtained using a surgical method. Pathological examination of these biopsies revealed that an angiosarcoma had developed after radiotherapy. There were no severe complications that occurred during the ENUS-TNNA procedure. Conclusion ENUS-TNNA is a safe, effective, and minimally invasive approach to obtain tissue samples from the submucosal region of the nasopharynx for patients with suspected NPC recurrence.

A major challenge to the treatment of advanced prostate cancer (PCa) is the development of resistance to androgen-deprivation therapy (ADT) and chemotherapy. It is imperative to discover effective therapies to overcome drug resistance and improve clinical outcomes. We have developed a novel class of silicon-containing compounds and evaluated the anticancer activities and mechanism of action using cellular and animal models of drug-resistant PCa. Five organosilicon compounds were evaluated for their anticancer activities in the NCI-60 panel and established drug-resistant PCa cell lines. GH1504 exhibited potent in vitro cytotoxicity in a broad spectrum of human cancer cells, including PCa cells refractory to ADT and chemotherapy. Molecular studies identified several potential targets of GH1504, most notably androgen receptor (AR), AR variant 7 (AR-v7) and survivin. Mechanistically, GH1504 may promote the protein turnover of AR, AR-v7 and survivin, thereby inducing apoptosis in ADT-resistant and chemoresistant PCa cells. Animal studies demonstrated that GH1504 effectively inhibited the in vivo growth of ADT-resistant CWR22Rv1 and chemoresistant C4-2B-TaxR xenografts in subcutaneous and intraosseous models. These preclinical results indicated that GH1504 is a promising lead that can be further developed as a novel therapy for drug-resistant PCa.

Background Scrub typhus is caused by O. tsutsugamushi and spreads through mite larvae biting the skin. Classic symptoms of the disease are eschar and lymphadenopathy. Previous reports have revealed clinical manifestations of scrub typhus, including gastrointestinal symptoms, meningoencephalitis, ocular flutter, pneumonitis, acute respiratory distress syndrome, and acute kidney injury. However, cases of scrub typhus presenting as a urinary tract infection (UTI) with high D-dimer levels could be easily misdiagnosed when clinical attention is insufficient, resulting in difficulty in making a timely diagnosis of the infection. Metagenomics next-generation sequencing (mNGS) is a revolutionary and highly sensitive method that may help in diagnosing atypical cases, even when trace amounts of pathogens are present. Case presentation A 52-year-old female presented with a 10-day history of fever, chills, headache and myalgia. She was initially diagnosed with influenza at a local clinic. Various antibacterials were used on the 2nd–12th day onwards; however, her symptoms persisted and were followed by increased urination duration, frequency, urgency and dysuria for 2 days. Orientia tsutsugamushi was confirmed as the pathogen responsible for the infection through mNGS analysis of her blood samples from Day 13 onwards. The patient’s temperature changed remarkably 24 h after the initiation of doxycycline. Over the next 48 h (i.e., Day 15 onwards), the patient showed clinical improvement. She recovered and was discharged from the hospital. Conclusions Scrub typhus can present atypical clinical symptoms, such as UTIs, in a febrile patient. mNGS may be a useful method for identifying O. tsutsugamushi infection in patients with atypical clinical manifestations.

Laryngeal squamous cell cancer (LSCC) is the second most prevalent malignancy occurring in the head and neck with a high incidence and mortality rate. Immunotherapy has recently become an emerging treatment for cancer. It is therefore essential to explore the role of tumour immunity in laryngeal cancer. Our study first delineated and evaluated the comprehensive immune infiltration landscapes of the tumour microenvironment in LSCC. A hierarchical clustering method was applied to classify the LSCC samples into two groups (high- and low-infiltration groups). We found that individuals with low immune infiltration characteristics had significantly better survival than those in the high-infiltration group, possibly because of the elevated infiltration of immune suppressive cells, such as regulatory T cells and myeloid-derived suppressor cells, in the high-infiltration group. Differentially expressed genes between two groups were involved in some immune-related terms, such as antigen processing and presentation. A univariate Cox analysis and least absolute shrinkage and selection operator analysis were performed to identify an immune gene-set-based prognostic signature (IBPS) to assess the risk of LSCC. The prognostic model comprising six IBPSs was successfully verified to be robust in different cohorts. The expression of the six IBPSs was detected by immunohistochemistry in 110 cases of LSCC. In addition, different inflammatory profiles and immune checkpoint landscape of LSCC were found between two groups. Hence, our model could serve as a candidate immunotherapeutic biomarker and potential therapeutic target for laryngeal cancer.

Background Thoracoscopic segmentectomy is a common surgical procedure in thoracic surgery today. However, identifying the intersegmental plane is difficult in the surgical process. Therefore, we evaluated the feasibility of the arterial ligation method for determining the intersegmental plane and compared the demarcation status with the intravenous indocyanine green (ICG). Methods We retrospectively reviewed the records of 35 patients with peripheral small lung nodules who underwent thoracoscopic segmentectomy between May and December 2020. First, the preoperative three-dimensional reconstruction was performed to distinguish the location of lung nodules and the anatomical structures of targeted segmental arteries, veins, and bronchi. Second, the targeted segmental arteries were ligated, and the intersegmental plane was determined by the inflation-deflation technique. The waiting time for the appearance of the inflation-deflation line was recorded. Thirdly, the intersegmental plane was identified again using the ICG fluorescence method. Finally, the consistency of the two intersegmental planes was evaluated. Results The intersegmental planes were successfully observed in all patients using the arterial ligation method. Thirty-four patients underwent segmentectomy as planned, and one patient finally underwent lobectomy due to insufficient surgical margin. The waiting time for the appearance of the intersegmental plane by arterial ligation method was 13.7 ± 3.2 min (6–19 min). The intersegmental planes determined by the arterial ligation method and the ICG fluorescence method were comparable, with a maximum distance of no more than 5 mm between the two planes. The mean operative duration was 119.1 ± 34.9 min, and the mean blood loss was 76.9 ± 70.3 ml. No evident air leakage was found during the operation. Only one patient experienced a prolonged air leak (≥ 5 days) during the postoperative recovery. No atelectasis occurred in all cases. The chest tube duration was 3.1 ± 0.9 days. Conclusion The arterial ligation method can efficiently and accurately identify the intersegmental plane, comparable to the ICG fluorescence method.

Background The vital-sign monitoring strategy of patients with acute aortic dissection in the emergency department is mainly based on traditional experience. This study attempts to explore the significance of the national early warning score (NEWS) in monitoring the condition of patients with acute aortic dissection during emergency observation and to provide evidence for emergency nurses in optimal and scientific monitoring of patients. Methods The case-control method was used to continuously enrol patients with acute aortic dissection who had been in the emergency department; the STROBE checklist was used in this process. Based on patients' clinical deterioration, they were divided into two groups: clinical deterioration and non-clinical deterioration. The NEWS at each time point was compared by independent-samples t-test, and the predictive power of NEWS was evaluated according to the area under the receiver operating characteristic curve. Results A total of 290 patients with acute aortic dissection were included: 46 patients showed clinical deterioration and 244 did not. There were significant differences in the NEW scores of the two groups at admission time and at 12, 8, 4 and 0.5 h before clinical deterioration. The NEW scores of the clinical deterioration group showed an upward trend, while the non-clinical deterioration group showed a relatively stable trend. The NEWS can be used to predict the occurrence of clinical deterioration earlier at 4 h before clinical deterioration. Simultaneously, the patient's respiration rate and SpO2 had better predictive performance than other vital signs. Conclusion The NEWS can be used to triage patients with acute aortic dissection admitted to the emergency department. Continuous use of the NEWS for monitoring can play a vital role in early warning of clinical deterioration in patients with acute aortic dissection. In clinical care, attention should also be paid when patients with acute aortic dissection have abnormal respiration rate and SpO2 .

The functions of the brain and heart, which are the two main supporting organs of human life, are closely linked. Numerous studies have expounded the mechanisms of the brain-heart axis and its related clinical applications. However, the effect of heart disease on brain function, defined as the heart-brain axis, is less studied even though cognitive dysfunction after heart disease is one of its most frequently reported manifestations. Hypoperfusion caused by heart failure appears to be an important risk factor for cognitive decline. Blood perfusion, the immune response, and oxidative stress are the possible main mechanisms of cognitive dysfunction, indicating that the blood-brain barrier, glial cells, and amyloid-β may play active roles in these mechanisms. Clinicians should pay more attention to the cognitive function of patients with heart disease, especially those with heart failure. In addition, further research elucidating the associated mechanisms would help discover new therapeutic targets to intervene in the process of cognitive dysfunction after heart disease. This review discusses cognitive dysfunction in relation to heart disease and its potential mechanisms.

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: The present study aimed to investigate the prevalence of peri-implant disease and identify potential disease risk factors in western China. Methods: The present retrospective study was conducted in 131 consecutive patients receiving 248 dental implants treated with implant-supported prostheses with a mean follow-up of 2.52 years. Several patient-related, implant-related, and oral hygiene maintenance factors were analyzed. Results: Peri-implant disease developed in 68 (51.91%) patients and 110 (44.35%) implants. The prevalence of peri-implant mucositis and peri-implantitis were 45.80% and 7.63%, respectively, at the subject level, and 36.69% and 7.66%, respectively, at the implant level. Multivariate analysis exhibited that male [odds ratio (OR) = 1.91; 95% confidence interval (CI): 1.02–3.57; p = 0.04], implant length < 10mm (OR = 7.87; 95% CI:1.62–38.46; p = 0.01), poor proximal contact of the prosthesis (OR = 1.90; 95% CI: 1.06–3.42; p = 0.03), tooth brushing once a day (OR = 3.11; 95% CI: 1.26–7.68; p = 0.04) and moderate periodontitis (OR = 13.00; 95% CI: 4.38–38.60; p < 0.01) were independent risk factors for peri-implant disease.

Rhythmical oscillations of neural populations can reflect working memory performance. However, whether neuronal oscillations of the cerebral cortex change in extreme environments, especially in a space station, remains unclear. Here, we recorded electroencephalography (EEG) signals when volunteers and astronauts were executing a memory task in extreme working conditions. Our experiments showed that two extreme conditions affect neuronal oscillations of the cerebral cortex and manifest in different ways. Lengthy periods of mental work impairs the gating mechanism formed by theta-gamma phase-amplitude coupling of two cortical areas, and sleep deprivation disrupts synaptic homeostasis, as reflected by the substantial increase in theta wave activity in the cortical frontal-central area. In addition, we excluded the possibility that nutritional supply or psychological situations caused decoupled theta-gamma phase-amplitude coupling or an imbalance in theta wave activity increase. Therefore, we speculate that the decoupled theta-gamma phase-amplitude coupling detected in astronauts results from their lengthy periods of mental work in the China Space Station. Furthermore, comparing preflight and inflight experiments, we find that long-term spaceflight and other hazards in the space station could worsen this decoupling evolution. This particular neuronal oscillation mechanism in the cerebral cortex could guide countermeasures for the inadaptability of humans working in spaceflight.

Dilated cardiomyopathy (DCM) is a common heart disease that can lead to heart failure and sudden cardiac death. Mutations in the TTN gene are the most frequent cause of DCM. Here, we generated two human induced pluripotent stem cell (iPSC) lines from the peripheral blood mononuclear cells (PBMCs) of two DCM patients carrying c.94816CT and c.104188AG mutations in TTN, respectively. The two lines exhibited a normal morphology, full expression of pluripotency markers, a normal karyotype and the ability of trilineage differentiation. The two lines can serve as useful tools for drug screening and mechanism studies on DCM.

Background A significant proportion of women with preeclampsia (PE) exhibit persistent postpartum hypertension (PHTN) at 3 months postpartum associated with cardiovascular morbidity. This study aimed to screen patients with PE to identify the high-risk population with persistent PHTN. Methods This retrospective cohort study enrolled 1,000 PE patients with complete parturient and postpartum blood pressure (BP) profiles at 3 months postpartum. The enrolled patients exhibited new-onset hypertension after 20 weeks of pregnancy, while those with PE superimposed upon chronic hypertension were excluded. Latent class cluster analysis (LCCA), a method of unsupervised learning in machine learning, was performed to ascertain maternal exposure clusters from eight variables and 35 subordinate risk factors. Logistic regression was applied to calculate odds ratios (OR) indicating the association between clusters and PHTN. Results The 1,000 participants were classified into three exposure clusters (subpopulations with similar characteristics) according to persistent PHTN development: high-risk cluster (31.2%), medium-risk cluster (36.8%), and low-risk cluster (32.0%). Among the 1,000 PE patients, a total of 134 (13.4%) were diagnosed with persistent PHTN, while the percentages of persistent PHTN were24.68%, 10.05%, and 6.25% in the high-, medium-, and low-risk clusters, respectively. Persistent PHTN in the high-risk cluster was nearly five times higher (OR, 4.915; 95% confidence interval (CI), 2.92–8.27) and three times (OR, 2.931; 95% CI, 1.91–4.49) than in the low- and medium-risk clusters, respectively. Persistent PHTN did not differ between the medium- and low-risk clusters. Subjects in the high-risk cluster were older and showed higher BP, poorer prenatal organ function, more adverse pregnancy events, and greater medication requirement than the other two groups. Conclusion Patients with PE can be classified into high-, medium-, and low-risk clusters according to persistent PHTN severity; each cluster has cognizable clinical features. This study’s findings stress the importance of controlling persistent PHTN to prevent future cardiovascular disease.

BackgroundHIV services were inevitably disrupted and affected due to COVID-19. There are many challenges in implementing appropriate HIV services, particularly in the provision of health care and the link between people living with HIV/AIDS and retention in care. The study investigated the impact of COVID-19 on HIV services and the anticipated benefit of the COVID-19 vaccination on HIV service restoration in North Shewa, Oromia, Ethiopia.MethodsA qualitative descriptive study approach was used to explore how healthcare delivery evolved during the outbreak of COVID-19 in Ethiopia. Sixteen antiretroviral therapy (ART) clinics were selected from 13 districts and one administrative town in Ethiopia. From them, 32 ART providers were purposively selected based on their experience in ART provision. Data were collected from June to July 2021 using in-depth interviews. A thematic analysis approach was used to analyze the data, based on themes and subthemes emerging from the data. ATLAS.ti software was used for coding.ResultsHealthcare for people living with HIV was interrupted due to the COVID-19 pandemic. Medical appointments, HIV testing and counseling services, opportunistic infection treatment, medicine supply, and routine viral load and CD4 T-cell count tests were interrupted. Due to a shortage of healthcare staff, outreach testing services and home index testing were discontinued and HIV testing was limited only to hospitals and health centers. This has substantially affected accessibility to HIV testing and reduced the quality of HIV service delivery. Telehealth and less frequent visits to health facilities were used as alternative ways of delivering HIV services. The COVID-19 vaccination campaign is expected to restore healthcare services. Vaccination may also increase the confidence of healthcare providers by changing their attitudes toward COVID-19.ConclusionsThe COVID-19 pandemic has substantially impacted HIV services and reduced the quality of HIV care in Ethiopia. Health facilities could not provide routine HIV services as they prioritize the fight against COVID-19, leading to an increase in service discontinuation and poor adherence.

Drug-induced cardiotoxicity is the leading cause of drug attrition and withdrawal from the market. Therefore, using appropriate preclinical cardiac safety assessment models is a critical step during drug development. Currently, cardiac safety assessment is still highly dependent on animal studies. However, animal models are plagued by poor translational specificity to humans due to species-specific differences, particularly in terms of cardiac electrophysiological characteristics. Thus, there is an urgent need to develop a reliable, efficient, and human-based model for preclinical cardiac safety assessment. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as an invaluable in vitro model for drug-induced cardiotoxicity screening and disease modeling. hiPSC-CMs can be obtained from individuals with diverse genetic backgrounds and various diseased conditions, making them an ideal surrogate to assess drug-induced cardiotoxicity individually. Therefore, methodologies to comprehensively investigate the functional characteristics of hiPSC-CMs need to be established. In this protocol, we detail various functional assays that can be assessed on hiPSC-CMs, including the measurement of contractility, field potential, action potential, and calcium handling. Overall, the incorporation of hiPSC-CMs into preclinical cardiac safety assessment has the potential to revolutionize drug development.

Adzuki beans are grown in several countries around the world and are widely popular in Asia, where they are often prepared in various food forms. Adzuki beans are rich in starch, and their proteins contain a balanced variety of amino acids with high lysine content, making up for the lack of protein content of cereals in the daily diet. Therefore, the research on adzuki beans and the development of their products have broad prospects for development. The starch, protein, fat, polysaccharide, and polyphenol contents and compositions of adzuki beans vary greatly among different varieties. The processing characteristic components of adzuki beans, such as starch, isolated protein, and heated flavor, are reported with a view to further promote the processing and development of adzuki bean foods. In addition to favorable edibility, the human health benefits of adzuki beans include antioxidant, antibacterial, and anti-inflammatory properties. Furtherly, adzuki beans and extracts have positive effects on the prevention and treatment of diseases, including diabetes, diabetes-induced kidney disease or kidney damage, obesity, and high-fat-induced cognitive decline. This also makes a case for the dual use of adzuki beans for food and medicine and contributes to the promotion of adzuki beans as a healthy, edible legume.

Background and Aim Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes. Methods Meta-analyses of observational studies that examined the associations between inflammatory bowel disease and the risk of adverse health outcomes in PubMed, EMBASE, and Web of Science were screened. Results This umbrella review identified 25 meta-analyses, which yielded 123 effect estimates for 60 unique putative health outcomes. Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes, including multiple cancers, cardiovascular disease, adverse pregnancy outcomes, adverse oral outcomes, and other adverse events. Moreover, inflammatory bowel diseases caused greater harm to health based on the presented evidence. However, none of the evidence was classified as “high” quality, only 15% was classified as “moderate,” and 65% of outcomes were rated as “very low.” Conclusion Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes and further studies should be conducted to draw firmer conclusions.

Signal transducer and activator 5a (STAT5A) is a classical transcription factor that plays pivotal roles in various biological processes, including tumor initiation and progression. A fraction of STAT5A is localized in the mitochondria, but the biological functions of mitochondrial STAT5A remain obscure. Here, we show that STAT5A interacts with pyruvate dehydrogenase complex (PDC), a mitochondrial gatekeeper enzyme connecting two key metabolic pathways, glycolysis and the tricarboxylic acid cycle. Mitochondrial STAT5A disrupts PDC integrity, thereby inhibiting PDC activity and remodeling cellular glycolysis and oxidative phosphorylation. Mitochondrial translocation of STAT5A is increased under hypoxic conditions. This strengthens the Warburg effect in cancer cells and promotes in vitro cell growth under hypoxia and in vivo tumor growth. Our findings indicate distinct pro-oncogenic roles of STAT5A in energy metabolism, which is different from its classical function as a transcription factor.

Background Anatomical knowledge of the zygomatico-orbital artery and its most relevant clinical applications is essential for ensuring the safety of filler injection into the temporal region. The purpose of this study was to provide the precise position, detailed course, and relationship with surrounding structures of the zygomatico-orbital artery. Methods Fifty-eight patients who underwent head contrast-enhanced three-dimensional computed tomography and 10 fresh frozen cadavers were investigated. Results The zygomatico-orbital artery was identified in 93 percent of the samples in this work. Ninety-four percent of the zygomatico-orbital arteries derived directly from the superficial temporal artery, and the remaining arteries started from the frontal branch of the superficial temporal artery. According to the origin of the zygomatico-orbital artery, it was classified into type I and type II. Type I arteries were then classified into three subtypes. The trunk of the zygomatico-orbital artery was located between the deep temporal fascia and the superficial temporal fascia. Deep branches of the zygomatico-orbital artery pierced the superficial layer of the deep temporal fascia. The zygomatico-orbital artery originated from 11.3 mm in front of the midpoint of the apex of the tragus, and most of its trunks were located less than 20.0 mm above the zygomatic arch. The mean diameter of the zygomatico-orbital artery was 1.2 ± 0.2 mm. There were extensive anastomoses between the zygomatico-orbital artery and various periorbital arteries at the lateral orbital rim. Conclusion The precise anatomical knowledge of the zygomatico-orbital artery described in this study could be helpful for cosmetic physicians for improving the safety of temporal augmentation.

To evaluate the utility of a contact-free device in screening for obstructive sleep apnea.Three hundred fifty-nine participants (mean age 46 ± 13 years, body mass index 26.1 ± 4.2 kg/m², 67.7% male) underwent overnight monitoring using a contact-free device, the OrbSense, and polysomnography (PSG) in the sleep laboratory simultaneously. The OrbSense recordings were analyzed automatically, and PSG was scored based on recommended guidelines.The respiratory event index from the OrbSense was lower than the apnea-hypopnea index (AHI) from PSG (25.5 ± 20.7 vs 27.0 ± 25.2 events/h; P = .007) and was significantly correlated with AHI (Pearson coefficient, 0.92; P.0001). Bland-Altman analysis showed a mean difference of 1.5 events/h, and the limit of agreement was -18.6 to 21.5 events/h. Use of the OrbSense resulted in larger underestimates of AHI and lower negative predictive values at higher AHI values (especially when AHI ≥ 30 events/h). When we used a PSG diagnostic criterion of AHI5 events/h, the optimal diagnostic cutoff value from the OrbSense was 8 events/h, with a sensitivity of 90.4%, a specificity of 77.6%, a 94.6% positive predictive value, and a 65% negative predictive value. For patients with moderate to severe obstructive sleep apnea whose AHI was15 events/h, the OrbSense cutoff was 16.6 events/h, with a sensitivity of 87.1% and a specificity of 89.7%. Among the 359 participants, 250 patients (69.6%) had the same obstructive sleep apnea severity division classified by both PSG and the OrbSense.The contact-free device OrbSense can detect respiratory events during sleep and has close agreement with in-laboratory PSG in screening for obstructive sleep apnea. Further studies are warranted to test its utility in community-based settings and at home.

The malar augmentation injection has gained popularity in recent years, but the exact location of each injection site has not been clearly identified.To discover ideal injection sites by comprehensively considering the distributions of ligaments, muscles, and vessels.Eighteen cadaver heads were dissected to investigate the zygomatic ligamentous system and to measure the position of muscles. Sixty-six cadaver heads were subjected to computed tomographic scanning and three-dimensional vessel reconstruction. Radiological evaluation of the fillers was performed before and after experimental injection in one hemiface and dissected to confirm safe delivery. Five patients were enrolled in a prospective clinical study. 2D and 3D photographs were taken before and after the injections for comparison.Site 1 was defined along the zygomatic arch, except the first 1/4 length and the midline of the arch. Site 2 was on the body of the zygoma, superior to the level of the infraorbital foramen and medial to the jugale. Site 3 was defined in the anteromedial midface approximately 30 mm below the lateral canthus.Injections at these 3 sites can be performed within the range of the ligaments to achieve effective lifting effects and minimize potential complications.

BackgroundAlthough the Chinese promotion of labor analgesia began in 2018 to improve maternal health, high-quality medical care is difficult to provide to pregnant women when medical staff cannot implement standard labor analgesia procedures. This study aims to examine medical personnel's adherence to labor analgesia protocols and to explore the relationships among adherence, satisfaction, and other factors.MethodsThe data were from a national cross-sectional dataset (N = 13,944) of the 2020 Chinese Labor Analgesia Pilot Evaluation Project. Mediating and moderating effects analyses were used to examine the role of satisfaction as a mediator between support measures and adherence.ResultsThere were differences in adherence between different types of medical personnel. Support measures and satisfaction had a positive association with adherence to labor analgesia protocols. Satisfaction had a significant mediating and moderating effect on the relationship between support measures and adherence to labor analgesia standards. Moderating effects of professional titles and attitudes were also observed.ConclusionPrimary health care policies worth considering include comprehensive incentives for medical institutions to improve the use of labor analgesia by medical personnel. It is also worth considering providing more training opportunities for the staff in anesthesiology departments.

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic β-catenin destruction complex (GSK-3β and Axin), promotes the ubiquitination degradation of β-catenin, and inhibits its nuclear transfer, thus, decreasing c-Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

Hearing aids are effective at improving listening ability and health-related quality of life. Recently, we observed that there are many hearing aids-related videos published on TikTok. However, the quality of the information they offer remains unstudied. This study aimed to evaluate the information quality of hearing aids videos on TikTok. We collected a sample of 155 hearing aids-related videos in Chinese and extracted the basic information. First, we identified the source of each video. Two independent raters assessed the quality of the information in the videos, using the PEMAT-A/V tool and DISCERN instrument. Regarding content, the results showed that the video contents on TikTok mainly about features, functionalities, and suggestions of purchase or fitting of hearing aids, while the information about the disadvantages and complications of hearing aids was limited. The overall quality of the hearing aids-related videos was acceptable on average, although the quality varies greatly depending on the type of source. Patients should be cautious in obtaining information about hearing aids on TikTok.

Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing treatment costs, reducing chemotherapy effectiveness and affecting prognosis. Based on real-world data, this study analyzed the safety, efficacy, and economic of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of CIT in hematological tumors from the perspective of the health care system.We retrospectively collected the data of hematological tumor patients treated with rhTPO and rhIL-11 due to thrombocytopenia caused by chemotherapy. The propensity score matching (PSM) method was used to balance the baseline information of the two groups and they were further stratified according to the degree of thrombocytopenia (grade I-II and grade III-IV). The platelet compliance rate at 2 weeks of treatment was used as the efficacy evaluation index, and the cost-effectiveness method was used to evaluate the economic value of the two drugs in the treatment of thrombocytopenia based on drug effectiveness. Univariate and probabilistic sensitivity analyses were performed.A total of 1,571 patients met the inclusion and exclusion criteria, and 476 patients were included after 1:1 PSM. For patients with grade I-II thrombocytopenia, no significant difference in the platelet compliance rate was found between the two groups after 1 and 2 weeks of treatment. The platelet compliance rate in the rhTPO group was higher than that in the rhIL-11 group for patients with grade III-IV thrombocytopenia. Cost-effectiveness analysis (CEA) showed that the incremental cost-effectiveness ratio (ICER) for the rhTPO and rhIL-11 groups was 226,615.8. The ICER value was sensitive to the platelet compliance rate of the two groups, the cost of rhTPO, the cost of platelet transfusion in the rhTPO group. Probabilistic sensitivity analysis showed that when willingness to pay was less than approximately 220,000 yuan, rhIL-11 economy presented 100% better than that of rhTPO.In CIT treatment for hematological tumors, rhTPO yielded a higher platelet compliance rate than rhIL-11 treatment, especially for patients with grade III-IV thrombocytopenia. However, whether rhTPO has economic advantages still requires further exploration.

The development of hydrazone bond-oriented epitope imprinting strategy is reported to synthesize the polymeric binders for the selective recognition of a protein-β

The present study aimed to explore latent markers for identifying primary Sjogren's syndrome (pSS), as well as their expression and molecular mechanism. Hub inducible T cell co‑stimulator genes were retrieved from the Gene Expression Omnibus. A total of 95 patients with pSS and 68 healthy individuals from Affiliated Hospital of Nantong University (Nantong, China) were included in the study. The expression of inducible T cell co‑stimulator (ICOS) in whole blood and saliva was evaluated using ELISA. Western blotting was performed to investigate aquaporin 5 (AQP5) protein expression, as well as the inflammatory effects of ICOS in patients with pSS compared with healthy individuals. Differentially expressed mRNAs were analyzed in whole blood (GSE84844) and salivary gland (GSE40611) of patients with pSS. In total, 15 hub genes were identified, among which ICOS was indicated to serve a role in the most pivotal immunity pathways. pSS was markedly associated with inflammatory pathways. Results from the present study found that ICOS was upregulated in the salivary gland, whole blood and saliva of patients with pSS. Salivary weight was negatively correlated with the levels of ICOS in the saliva of patients with pSS. The expression of AQP5 was markedly lower in patients with pSS. The expression of AQP5 was negatively associated with ICOS. Compared with that of healthy individuals, the expression of ICOS and inflammatory factors was higher and the expression of AQP5 was lower in pSS patients as assessed by western blotting. These data demonstrated that ICOS may affect AQP5 expression by promoting inflammation in the salivary glands of patients with pSS.

BackgroundMyasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. Cytokines play important roles in facilitating the immune response and augmenting the pathogenic antibody production. The current study aims to sensitively characterize the serum levels of cytokines with very low concentration in generalized MG (gMG).MethodsUsing ultrasensitive single-molecule arrays (SIMOA), we measured serum IL-2, IL-4, IL-5 and IL-12p70 in 228 participants including 152 immunotherapy-naïve anti-acetylcholine receptor (AChR) subtype gMG from Huashan MG registry and 76 age-matched healthy controls. Subgroup analysis was then performed by stratifying patients according to the onset ages, MGFA classification, disease duration at baseline.ResultsSerum IL-2, IL-4, IL-5 and IL-12p70 levels were significantly elevated in gMG compared to controls (0.179 pg/mL versus 0.011 pg/mL,P P = 0.0259; 0.215 pg/mL versus 0.143 pg/mL,P = 0.0007; 0.132 pg/mL versus 0.118 pg/mL,P = 0.0401). Subgroup analysis revealed that IL-2 levels were slightly elevated in gMG with MGFA II compared to MGFA III/IV (0.195 pg/mL versus 0.160 pg/mL,P = 0.022), as well as elevated levels of IL-2 (0.220 pg/mL versus 0.159 pg/mL,P = 0.0002) and IL-5 (0.251 pg/mL versus 0.181 pg/mL,P = 0.004) in late-onset gMG compared with the early-onset gMG. gMG patients with a long duration had a significant increased serum IL-12p70 than those with a short duration (0.163 pg/mL versus 0.120 pg/mL,P = 0.011).ConclusionSerum IL-2, IL-4, IL-5 and IL-12p70 levels were increased in AChR subtype gMG using ultrasensitive measurement. Serum cytokines with very low concentrations may provide as potential biomarkers in stratifying gMG patients in future prospective cohort studies.

Improvement in an individuals’ cognition is the key to promote garbage classification. This study takes university students as the research subjects, through three educational interventions, including the self-learning, heuristic learning, and interactive learning ways, to seek the most effective intervention based upon event-related potentials (ERPs) that is beneficial to enhance cognition of garbage classification. The results show that the experimental subjects induced P300 and LPP components, representing attentional changes and cognitive conflicts in classification judgments. There are differences in the amplitudes and peak latency of the two components corresponding to different interventions, indicating that the three educational interventions are able to improve the individual’s cognition level of garbage classification within a certain period of time. The interactive-learning intervention triggers the largest amplitudes of P300 and LPP, as well as the smallest peak latency, indicating its effect is the best. Such results provide insight into the design for an appropriate strategy in garbage classification education. The study also shows that an EEG signal can be used as the endogenous neural indicator to measure the performance of garbage classification under different educational interventions.

ObjectiveTo investigate the association between the structural deformity and foot pain in hallux valgus (HV) patients using a multi-variate pattern analysis (MVPA) approach.MethodsPlain radiographic metrics were calculated from 36 painful and 36 pain-free HV feet. In analysis 1, univariate analyses were performed to investigate the clinical and radiographic differences between painful and pain-free HV. In analysis 2, we investigated the pattern differences for radiographic metrics between these two groups using a MVPA approach utilizing a support vector machine. In analysis 3, sequential backward selection and exhaustive search were performed as a feature-selection procedure to identify an optimal feature subtype. In analysis 4, hierarchical clustering analysis was used to identify the optimal radiographic HV subtype associated with pain in HV.ResultsWe found that: (1) relative to feet with pain-free HV, the painful ones exhibited a higher hallux valgus angle, i.e., the magnitude of distal metatarsal and phalangeal deviation; (2) painful HV could be accurately differentiated from pain-free HV via MVPA. Using sequential backward selection and exhaustive search, a 5-feature subset was identified with optimal performance for classifying HV as either painful or pain-free; and (3) by applying hierarchical clustering analysis, a radiographic subtype with an 80% pain incidence was identified.ConclusionThe pain in HV is multifactorial and associated with a radiographic pattern measured by various angles on plain radiographs. The combination of hallux valgus angle, inter-phalangeal angle, distal metatarsal articular angle, metatarsal cuneiform angle and metatarsal protrusion distance showed the optimal classification performance between painful and pain-free HV.