A comparative study on the dose-effect of low-dose radiation based on microdosimetric analysis and single-cell sequencing technology.

The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation.

A ZBP1 isoform blocks ZBP1-mediated cell death.

ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA) to promote cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here, we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppressor of the inflammatory signaling mediated by full-length ZBP1. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Ripk1D325A/D325A) with cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-dependent cell death. Intriguingly, Ripk1D325A/D325A cells die spontaneously when ZBP1-S is deleted, indicating that cell death driven by ZBP1 is under the control of ZBP1-S. Thus, our findings reveal that alternative splicing of Zbp1 represents autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against autoinflammations.

Focal length switchable metalens based on vanadium dioxide.

A metalens is a flat lens that can control the phase of light so that dispersed light can be reconcentrated. This study devised a tunable metalens with a switchable focal length based on the phase transition properties of vanadium dioxide (V O 2). The unit structure comprises three layers from bottom to top: gold, polyimide, and two square resonant rings. The metalens can not only transform incident x-polarized waves into y-polarized waves but also achieve beam focusing simultaneously. The designed metalens achieves polarization conversion efficiency at an operating frequency of 0.8 THz. In the insulating state of V O 2, the beam focal point is at L=1914µm; in the metallic state, the wave converges at L=982µm, closely aligning with the predetermined focal length. By controlling external temperature, focal point switching can be achieved, making it highly versatile in practical applications.

Feature selection and risk prediction for diabetic patients with ketoacidosis based on MIMIC-IV.

Background: Diabetic ketoacidosis (DKA) is a frequent acute complication of diabetes mellitus (DM). It develops quickly, produces severe symptoms, and greatly affects the lives and health of individuals with DM.This article utilizes machine learning methods to examine the baseline characteristics that significantly contribute to the development of DKA. Its goal is to identify and prevent DKA in a targeted and early manner. Methods: This study selected 2382 eligible diabetic patients from the MIMIC-IV dataset, including 1193 DM patients with ketoacidosis and 1186 DM patients without ketoacidosis. A total of 42 baseline characteristics were included in this research. The research process was as follows: Firstly, important features were selected through Pearson correlation analysis and random forest to identify the relevant physiological indicators associated with DKA. Next, logistic regression was used to individually predict DKA based on the 42 baseline characteristics, analyzing the impact of different physiological indicators on the experimental results. Finally, the prediction of ketoacidosis was performed by combining feature selection with machine learning models include logistic regression, XGBoost, decision tree, random forest, support vector machine, and k-nearest neighbors classifier. Results: Based on the importance analysis conducted using different feature selection methods, the top five features in terms of importance were identified as mean hematocrit (haematocrit_mean), mean hemoglobin (haemoglobin_mean), mean anion gap (aniongap_mean), age, and Charlson comorbidity index (charlson_comorbidity_index). These features were found to have significant relevance in predicting DKA. In the individual prediction using logistic regression, these five features have been proven to be effective, with F1 scores of 1.000 for hematocrit mean, 0.978 for haemoglobin_mean, 0.747 for age, 0.692 for aniongap_mean and 0.666 for charlson_comorbidity_index. These F1 scores indicate the effectiveness of each feature in predicting DKA, with the highest score achieved by mean hematocrit. In the prediction of DKA using machine learning models, including logistic regression, XGBoost, decision tree, and random forest demonstrated excellent results, achieving an F1 score of 1.000. Additionally, by applying feature selection techniques, noticeable improvements were observed in the experimental performance of the support vector machine and k-nearest neighbors classifier. Conclusion: The study found that hematocrit, hemoglobin, anion gap, age, and Charlson comorbidity index are closely associated with ketoacidosis. In clinical practice, these five baseline characteristics should be given with the special attention to achieve early detection and treatment, thus reducing the incidence of the disease.

Clinicopathological role of Cyclin A2 in uterine corpus endometrial carcinoma: Integration of tissue microarrays and ScRNA-Seq.

BACKGROUND: The comprehensive expression level and potential molecular role of Cyclin A2 (CCNA2) in uterine corpus endometrial carcinoma (UCEC) remains undiscovered. METHODS: UCEC and normal endometrium tissues from in-house and public databases were collected for investigating protein and messenger RNA expression of CCNA2. The transcription factors of CCNA2 were identified by the Cistrome database. The prognostic significance of CCNA2 in UCEC was evaluated through univariate and multivariate Cox regression as well as Kaplan-Meier curve analysis. Single-cell RNA-sequencing (scRNA-seq) analysis was performed to explore cell types in UCEC, and the AUCell algorithm was used to investigate the activity of CCNA2 in different cell types. RESULTS: A total of 32 in-house UCEC and 30 normal endometrial tissues as well as 720 UCEC and 165 control samples from public databases were eligible and collected. Integrated calculation showed that the CCNA2 expression was up-regulated in the UCEC tissues (SMD = 2.43, 95% confidence interval 2.23∼2.64). E2F1 and FOXM1 were identified as transcription factors due to the presence of binding peaks on transcription site of CCNA2. CCNA2 predicted worse prognosis in UCEC. However, CCNA2 was not an independent prognostic factor in UCEC. The scRNA-seq analysis disclosed five cell types: B cells, T cells, monocytes, natural killer cells, and epithelial cells in UCEC. The expression of CCNA2 was mainly located in B cells and T cells. Moreover, CCNA2 was active in T cells and B cells using the AUCell algorithm. CONCLUSION: CCNA2 was up-regulated and mainly located in T cells and B cells in UCEC. Overexpression of CCNA2 predicted unfavorable prognosis of UCEC.

Tetrahydrobiopterin metabolism attenuates ROS generation and radiosensitivity through LDHA S-nitrosylation: novel insight into radiogenic lung injury.

Genotoxic therapy triggers reactive oxygen species (ROS) production and oxidative tissue injury. S-nitrosylation is a selective and reversible posttranslational modification of protein thiols by nitric oxide (NO), and 5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. However, the mechanism by which BH4 affects protein S-nitrosylation and ROS generation has not been determined. Here, we showed that ionizing radiation disrupted the structural integrity of BH4 and downregulated GTP cyclohydrolase I (GCH1), which is the rate-limiting enzyme in BH4 biosynthesis, resulting in deficiency in overall protein S-nitrosylation. GCH1-mediated BH4 synthesis significantly reduced radiation-induced ROS production and fueled the global protein S-nitrosylation that was disrupted by radiation. Likewise, GCH1 overexpression or the administration of exogenous BH4 protected against radiation-induced oxidative injury in vitro and in vivo. Conditional pulmonary Gch1 knockout in mice (Gch1fl/fl; Sftpa1-Cre+/- mice) aggravated lung injury following irradiation, whereas Gch1 knock-in mice (Gch1lsl/lsl; Sftpa1-Cre+/- mice) exhibited attenuated radiation-induced pulmonary toxicity. Mechanistically, lactate dehydrogenase (LDHA) mediated ROS generation downstream of the BH4/NO axis, as determined by iodoacetyl tandem mass tag (iodoTMT)-based protein quantification. Notably, S-nitrosylation of LDHA at Cys163 and Cys293 was regulated by BH4 availability and could restrict ROS generation. The loss of S-nitrosylation in LDHA after irradiation increased radiosensitivity. Overall, the results of the present study showed that GCH1-mediated BH4 biosynthesis played a key role in the ROS cascade and radiosensitivity through LDHA S-nitrosylation, identifying novel therapeutic strategies for the treatment of radiation-induced lung injury.

Dual ensemble system for polyp segmentation with submodels adaptive selection ensemble.

Colonoscopy is one of the main methods to detect colon polyps, and its detection is widely used to prevent and diagnose colon cancer. With the rapid development of computer vision, deep learning-based semantic segmentation methods for colon polyps have been widely researched. However, the accuracy and stability of some methods in colon polyp segmentation tasks show potential for further improvement. In addition, the issue of selecting appropriate sub-models in ensemble learning for the colon polyp segmentation task still needs to be explored. In order to solve the above problems, we first implement the utilization of multi-complementary high-level semantic features through the Multi-Head Control Ensemble. Then, to solve the sub-model selection problem in training, we propose SDBH-PSO Ensemble for sub-model selection and optimization of ensemble weights for different datasets. The experiments were conducted on the public datasets CVC-ClinicDB, Kvasir, CVC-ColonDB, ETIS-LaribPolypDB and PolypGen. The results show that the DET-Former, constructed based on the Multi-Head Control Ensemble and the SDBH-PSO Ensemble, consistently provides improved accuracy across different datasets. Among them, the Multi-Head Control Ensemble demonstrated superior feature fusion capability in the experiments, and the SDBH-PSO Ensemble demonstrated excellent sub-model selection capability. The sub-model selection capabilities of the SDBH-PSO Ensemble will continue to have significant reference value and practical utility as deep learning networks evolve.

A dual functional tunable terahertz metamaterial absorber based on vanadium dioxide.

A dual-functional switchable metamaterial absorber (MMA) based on vanadium dioxide (VO2), which achieves flexible switching between broadband absorption and four-band absorption by adjusting the VO2 conductivity, was proposed. The device has a broadband absorption function when VO2 is in the metal phase, and the conductivity is 3 × 105 S m-1. Numerical simulation shows that the absorption rate of the device reaches over 90% in the frequency range of 3.36-6.98 THz. The absorber exhibits polarization insensitivity and wide-angle absorption to transverse electric (TE) and transverse magnetic (TM) waves. When VO2 is in the insulator phase, and the conductivity is 3 × 102 S m-1, the device switches to a narrowband absorber with a band-efficient absorption function. Numerical simulation shows that the device has an absorption rate of 99.7% at 2.39 THz, 98.3% at 2.83 THz, 95.6% at 3.84 THz, and 96.1% at 4.61 THz. It can be used as a sensor with high sensitivity. In addition, to verify the absorption mechanism of the absorber, we introduced impedance matching theory to analyze the device. Finally, the influence of structural parameters on the performance of resonators was investigated. Through the joint action of multi-layer structures, the proposed MMA concentrates broadband and narrowband absorption functions on one device, achieving flexible switching between tasks without changing the structure. The switchable metamaterial absorber designed through simple tuning methods has broad application prospects in stealth technology and thermal emitters. It provides a wide range of ideas for the design of terahertz functional devices.

Research progress in spasmodic torticollis rehabilitation treatment.

Spasmodic torticollis (ST) is a focal dystonia that affects adults, causing limited muscle control and impacting daily activities and quality of life. The etiology and curative methods for ST remain unclear. Botulinum toxin is widely used as a first-line treatment, but long-term usage can result in reduced tolerance and adverse effects. Rehabilitation therapy, with its minimal side effects and low potential for harm, holds significant clinical value. This article explores the effectiveness of adjunctive therapies, including exercise therapy, transcranial magnetic stimulation, shockwave therapy, neuromuscular electrical stimulation, vibration therapy, electromyographic biofeedback, and acupuncture, in the treatment of ST. The aim is to provide clinicians with additional treatment options and to discuss the efficacy of rehabilitation therapy for ST.

Cardiotoxicity induced by fluoropyrimidine drugs in the treatment of gastrointestinal tumors.

In this editorial, we review the article published in World J Gastrointest Oncol 2019, 11: 1031-1042. We specifically focus on the occurrence, clinical characteristics, and risk factors of fluoropyrimidine drug-related cardiotoxicity in patients with gastrointestinal tumors. Despite significant advancements in diagnostic and therapeutic techniques that have reduced mortality rates associated with digestive system tumors, the incidence and mortality rates of treatment-related cardiotoxicity have been increasing, severely impacting the survival and prognosis of cancer patients. Fluoropyrimidine drugs are widely used as antimetabolites in the treatment of malignant tumors, including gastrointestinal tumors, and they represent the second largest class of drugs associated with cardiotoxicity. However, there is often a lack of awareness or understanding regarding their cardiotoxic effects and associated risks.

Tri-branch feature pyramid network based on federated particle swarm optimization for polyp segmentation.

Deep learning technology has shown considerable potential in various domains. However, due to privacy issues associated with medical data, legal and ethical constraints often result in smaller datasets. The limitations of smaller datasets hinder the applicability of deep learning technology in the field of medical image processing. To address this challenge, we proposed the Federated Particle Swarm Optimization algorithm, which is designed to increase the efficiency of decentralized data utilization in federated learning and to protect privacy in model training. To stabilize the federated learning process, we introduced Tri-branch feature pyramid network (TFPNet), a multi-branch structure model. TFPNet mitigates instability during the aggregation model deployment and ensures fast convergence through its multi-branch structure. We conducted experiments on four different public datasets：CVC-ClinicDB, Kvasir, CVC-ColonDB and ETIS-LaribPolypDB. The experimental results show that the Federated Particle Swarm Optimization algorithm outperforms single dataset training and the Federated Averaging algorithm when using independent scattered data, and TFPNet converges faster and achieves superior segmentation accuracy compared to other models.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Nucleoporin Seh1 controls murine neocortical development via transcriptional repression of p21 in neural stem cells.

Mutations or dysregulation of nucleoporins (Nups) are strongly associated with neural developmental diseases, yet the underlying mechanisms remain poorly understood. Here, we show that depletion of Nup Seh1 in radial glial progenitors results in defective neural progenitor proliferation and differentiation that ultimately manifests in impaired neurogenesis and microcephaly. This loss of stem cell proliferation is not associated with defects in the nucleocytoplasmic transport. Rather, transcriptome analysis showed that ablation of Seh1 in neural stem cells derepresses the expression of p21, and knockdown of p21 partially restored self-renewal capacity. Mechanistically, Seh1 cooperates with the NuRD transcription repressor complex at the nuclear periphery to regulate p21 expression. Together, these findings identified that Nups regulate brain development by exerting a chromatin-associated role and affecting neural stem cell proliferation.

Congenital trans-sellar trans-sphenoidal encephalocele: a systematic review of diagnosis, treatment, and prognosis.

PURPOSE: Clinical presentations encompass respiratory, feeding issues, nasopharyngeal mass, meningitis, CSF leakage, craniofacial anomalies, and endocrine problems. Surgery is the primary treatment, transitioning from frontal craniotomy to endoscopic methods, offering improved outcomes. Yet, more studies are needed. A comprehensive review on trans-sellar trans-sphenoidal encephalocele (TSTSE) is missing. Our study aims to fill this gap, offering a comprehensive perspective for physicians. METHODS: This review adhered to the PRISMA guideline. Eligible studies focused on human subjects, specifically trans-sellar encephaloceles, and provided comprehensive treatment details. English language articles published up to April 11th, 2023, were considered. Two trained researchers conducted article screening using consistent criteria. Data extraction covered various aspects, including clinical presentation, surgical methods, and outcomes, with results presented descriptively in two tables. Due to the rarity of this congenital anomaly, meta-analysis and publication bias assessment were not feasible. Data extraction was independently conducted by two reviewers, with subsequent cross-verification. RESULTS: A total of 36 patients were identified from 14 studies, the most frequently observed clinical presentation was dyspnea (41.67%) and the most frequently observed accompanying anomaly was cleft lip/palate (55.56%). CT and MRI were adopted in nearly all the cases, and trans-nasal approach was the most often used surgical approach (57.14%) with the 'soft material combination' the most commonly used method for cranial base repairment (35.71%). A total of two deaths occurred and diabetes insipidus was the most common perioperative complication which occurred in six surgery patients (21.43%). CONCLUSION: TSTSE predominantly affects males and presents with dyspnea, visual deficits, pituitary insufficiency, and cranial base-related symptoms. Early diagnosis is critical, with advanced imaging playing a key role. Endocrine assessment is vital for hormone management. Surgery offers symptom relief but entails risks, including reported fatalities and complications. The choice between surgery and conservative management requires careful deliberation. The trans-nasal approach is favored for its reduced trauma, yet further research is necessary to validate this preference.

Associations of Serum Testosterone and Sex Hormone-binding Globulin With Incident Arrhythmias in Men From UK Biobank.

CONTEXT: Sex hormones have been identified as cardiovascular risk factors, whereas the relationship between sex hormones and the risk of arrhythmias in men has not yet been well studied in the prospective cohort study. OBJECTIVE: To analyze associations of serum testosterone and SHBG concentrations and calculate free testosterone (cFT) with arrhythmias in men. METHODS: Sex hormones were measured at baseline from UK Biobank. Main outcomes were incidence of atrial fibrillation/flutter (AF), ventricular arrhythmia (VA), and bradyarrhythmia (BA). RESULTS: Of 173 498 men (aged 37-73 years, followed for 11 years), 11 368 had incident AF, 1646 had incident VA, and 4788 had incident BA. Compared with the third quartiles, the lowest category of serum testosterone was associated with increased risks of AF (hazard ratio [HR], 1.06; 95% CI, 1.00-1.12) and BA (HR, 1.11; 95% CI, 1.02-1.20) after multivariable adjustment, but no VA. Likewise, similar associations were found between cFT values and AF and BA events. Furthermore, higher levels of cFT were associated with increased risks of AF (HR, 1.07; 95% CI, 1.02-1.13) and VA (HR, 1.18; 95% CI, 1.01-1.37). Higher SHBG concentrations were associated with increased risks of AF (HR, 1.44; 95% CI, 1.34-1.54), VA (HR, 1.27; 95% CI, 1.07-1.52), and BA (HR, 1.17; 95% CI ,1.05-1.29). CONCLUSIONS: Lower levels of testosterone and cFT were associated with increased risk of AF and BA. Higher cFT levels were associated with increased risk of AF and VA. Higher SHBG levels were associated with increased risk of AF, VA, and BA.

Altered bile acid metabolism in skin tissues in response to ionizing radiation: deoxycholic acid (DCA) as a novel treatment for radiogenic skin injury.

OBJECTIVE: Radiogenic skin injury (RSI) is a common complication during cancer radiotherapy or accidental exposure to radiation. The aim of this study is to investigate the metabolism of bile acids (BAs) and their derivatives during RSI. METHODS: Rat skin tissues were irradiated by an X-ray linear accelerator. The quantification of BAs and their derivatives were performed by liquid chromatography-mass spectrometry (LC-MS)-based quantitative analysis. Key enzymes in BA biosynthesis were analyzed from single-cell RNA sequencing (scRNA-Seq) data of RSI in the human patient and animal models. The in vivo radioprotective effect of deoxycholic acid (DCA) was detected in irradiated SD rats. RESULTS: Twelve BA metabolites showed significant differences during the progression of RSI. Among them, the levels of cholic acid (CA), DCA, muricholic acid (MCA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), glycohyodeoxycholic acid (GHCA), 12-ketolithocholic acid (12-ketoLCA) and ursodeoxycholic acid (UDCA) were significantly elevated in irradiated skin, whereas lithocholic acid (LCA), tauro-ß-muricholic acid (Tß-MCA) and taurocholic acid (TCA) were significantly decreased. Additionally, the results of scRNA-Seq indicated that genes involved in 7a-hydroxylation process, the first step in BA synthesis, showed pronounced alterations in skin fibroblasts or keratinocytes. The alternative pathway of BA synthesis is more actively altered than the classical pathway after ionizing radiation. In the model of rat radiogenic skin damage, DCA promoted wound healing and attenuated epidermal hyperplasia. CONCLUSIONS: Ionizing radiation modulates the metabolism of BAs. DCA is a prospective therapeutic agent for the treatment of RSI.

Supraglottic Jet Oxygenation and Ventilation to Minimize Hypoxia in Patients Receiving Flexible Bronchoscopy Under Deep Sedation: A 3-Arm Randomized Controlled Trial.

BACKGROUND: Hypoxia often occurs due to shared airway and anesthetic sedation-induced hypoventilation in patients receiving flexible bronchoscopy (FB) under deep sedation. Previous evidence has shown that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) reduces the incidence of hypoxia during FB. This study aimed to investigate the extent to which SJOV via WNJ could decrease the incidence of hypoxia in patients under deep sedation as compared to oxygen supplementation via WNJ alone or nasal catheter (NC) for oxygen supplementation during FB. METHODS: This was a single-center 3-arm randomized controlled trial (RCT). Adult patients scheduled to undergo FB were randomly assigned to 3 groups: NC (oxygen supplementation via NC), low-pressure low-flow (LPLF) (low-pressure oxygen supplementation via WNJ alone), or SJOV (high-pressure oxygen supplementation via WNJ). The primary outcome was hypoxia (defined as peripheral saturation of oxygen [Sp o2 ] <90% lasting more than 5 seconds) during FB. Secondary outcomes included subclinical respiratory depression or severe hypoxia, and rescue interventions specifically performed for hypoxia treatment. Other evaluated outcomes were sore throat, xerostomia, nasal bleeding, and SJOV-related barotraumatic events. RESULTS: One hundred and thirty-two randomized patients were included in 3 interventions (n = 44 in each), and all were included in the final analysis under intention to treat. Hypoxia occurred in 4 of 44 patients (9.1%) allocated to SJOV, compared to 38 of 44 patients (86%) allocated to NC, with a relative risk (RR) for hypoxia, 0.11; 98% confidence interval (CI), 0.02-0.51; P < .001; or to 27 of 44 patients (61%) allocated to LPLF, with RR for hypoxia, 0.15; 95% CI, 0.04-0.61; P < .001, respectively. The percentage of subclinical respiratory depression was also significantly diminished in patients with SJOV (39%) compared with patients with NC (100%) or patients with LPLF (96%), both P < .001. In SJOV, no severe hypoxia event occurred. More remedial interventions for hypoxia were needed in the patients with NC. Higher risk of xerostomia was observed in patients with SJOV. No severe adverse event was observed throughout the study. CONCLUSIONS: SJOV via WNJ effectively reduces the incidence of hypoxia during FB under deep sedation.

Down syndrome child with multiple heart diseases: A case report.

BACKGROUND: Down syndrome, also known as trisomy 21 syndrome, is commonly associated with congenital heart disease, and can often result in early formation of pulmonary hypertension. The development of pulmonary hypertension can result from factors such as intracardiac and macrovascular shunts, and upper airway obstruction or hypoplasia of lung tissue. Individuals with Down syndrome and congenital heart disease have a significantly lower average life expectancy, with surgical intervention being the most viable treatment option to improve longevity. CASE SUMMARY: We report the case of a 13-year-old boy with Down syndrome presenting with atrial septal defect and patent ductus arteriosus along with severe pulmonary hypertension. The electrocardiogram shows sinus rhythm and right ventricular hypertrophy. The echocardiogram shows an atrial septal defect with interrupted echo in the interatrial septum, measuring 0.813 cm in length. The patient was initially refused to be offered surgical treatment by many hospitals due to the high surgical risk and pulmonary artery resistance. After discussing the patient's diagnosis and treatment options, we ultimately recommended surgical treatment. However, the patient and their family declined this recommendation and chose to be discharged. During the follow-up period of 6 mo, there were no significant improvements or deteriorations in the patient's condition. CONCLUSION: In conclusion, this case highlights the challenges faced by individuals with Down syndrome and congenital heart disease complicated by severe pulmonary hypertension. Timely intervention and a multidisciplinary approach are crucial for improving prognosis and life expectancy. Further research is needed to enhance our understanding and develop effective interventions for this population.

Related mechanisms and research progress in straight back syndrome.

Despite the high prevalence of straight back syndrome (SBS), there is still limited research on this condition, posing challenges for effective diagnosis and treatment. The disease has been known for a long time, but there have been few related studies, which mostly consist of case reports. These studies have not been systematically summarized, making it difficult to meet the current needs of diagnosis and treatment. This article summarized the existing literature and comprehensively reviewed the diagnosis, pathogenesis, treatment, and research status of mitral valve prolapse related to SBS. We specifically emphasized the mechanisms and prognosis of SBS combined with mitral valve prolapse and discussed the latest research progress in this disease.

Nuclear import carrier Hikeshi cooperates with HSP70 to promote murine oligodendrocyte differentiation and CNS myelination.

Dysregulation of factors in nucleocytoplasmic transport is closely linked to neural developmental diseases. Mutation in Hikeshi, encoding a nonconventional nuclear import carrier of heat shock protein 70 family (HSP70s), leads to inherited leukodystrophy; however, the pathological mechanisms remain elusive. Here, we showed that Hikeshi is essential for central nervous system (CNS) myelination. Deficiency of Hikeshi, which is observed in inherited leukodystrophy patients, resulted in murine oligodendrocyte maturation arrest. Hikeshi is required for nuclear translocation of HSP70s upon differentiation. Nuclear-localized HSP70 promotes murine oligodendrocyte differentiation and remyelination after white matter injury. Mechanistically, HSP70s interacted with SOX10 in the nucleus and protected it from E3 ligase FBXW7-mediated ubiquitination degradation. Importantly, we discovered that Hikeshi-dependent hyperthermia therapy, which induces nuclear import of HSP70s, promoted oligodendrocyte differentiation and remyelination following in vivo demyelinating injury. Overall, these findings demonstrate that Hikeshi-mediated nuclear translocation of HSP70s is essential for myelinogenesis and provide insights into pathological mechanisms of Hikeshi-related leukodystrophy.