Optogenetically modified human embryonic stem cell-derived otic neurons establish functional synaptic connection with cochlear nuclei.

Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing the functionality of derived cells within the circuit. Here, we describe a novel method for converting human embryonic stem cells (hESCs) into otic neurons (ONs) and assess their functional connectivity using an optogenetic approach with cells or an organotypic slice of rat cochlear nucleus (CN) in coculture. Embryonic stem cell-derived otic neurons (eONs) exhibited SGN marker expression and generated functional synaptic connection when cocultured with cochlear nucleus neurons (CNNs). Synapsin 1 and VGLUT expression are found in the cochlear nucleus of brain slices, where eONs projected processes during the coculture of eONs and CN brain slices. Action potential spikes and INa+/IK+ of CNNs increased in tandem with light stimulations to eONs. These findings provide further evidence that eONs may be a candidate source to treat SGN-deafness.

Case report: A case with atypical presentation oftesticular choriocarcinoma.

Testicular choriocarcinoma is a relatively rare malignancy with a highly aggressive nature. Timely diagnosis and treatment can help prolong the survival of patients and even cure them. This case reports a 29-year-old male who presented to the clinic for a month with epigastric pain. On examination, a massive mass of approximately 9*10 cm could be palpated in the upper abdomen. When asked about his previous history, the patient only described a history of a right inguinal hernia that had been repaired 12 years earlier. The admission diagnosis was considered the retroperitoneal tumor, which was found to have metastasized to the liver and lungs after the completion of relevant tests. We then performed a CT-guided lune puncture biopsy on day 8 of admission. The biopsy pathology suggested metastatic cancer was considered. As the symptoms of tumor compression gradually worsened, we performed surgical treatment (retroperitoneal tumor resection + partial duodenal resection + enteroanastomosis) on day 13 of admission. The postoperative pathology was choriocarcinoma. We subsequently conducted a detailed inquiry with the patient's family about his medical history and found a history of inguinal testicle. Through testicular ultrasound examination, it was preliminarily determined to be testicular choriocarcinoma (not yet pathologically confirmed). We wanted to start salvage chemotherapy as soon as possible after surgery. However, the patient's postoperative condition was poor, with rapid progression of hepatopulmonary metastases and gradually increased thyrotoxicosis, and we started salvage chemotherapy (EP regimen: etoposide and cisplatin) on postoperative day 12. However, the patient was forced to stop due to a severe chemotherapy reaction and died of respiratory and cardiac arrest in the hospital. For male patients with retroperitoneal mass, the possibility of germ-cell neoplasm should first be excluded. By inquiring in detail about a history of cryptorchidism and in the initial days of hospitalization, testicular exploration, ultrasounds, and serum tumor markers (AFP, ß-HCG) tests can be conducted to rule out the possibility of germ-cell neoplasm, thereby preventing misdiagnosis and treatment delays. If the clinical diagnosis is metastatic germ-cell tumor with severe symptoms of metastatic disease, surgery should never be used as the initial treatment.

Rapid detection of human cytomegalovirus by multienzyme isothermal rapid amplification and lateral flow dipsticks.

Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources. Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing. Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/µl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%. Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus.

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis: A network meta-analysis.

BACKGROUND: Currently, traditional Chinese medicine (TCM) formulas are commonly being used as adjunctive therapy for ulcerative colitis in China. Network meta-analysis, a quantitative and comprehensive analytical method, can systematically compare the effects of different adjunctive treatment options for ulcerative colitis, providing scientific evidence for clinical decision-making. AIM: To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis (UC) in clinical practice through a network meta-analysis. METHODS: Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1, 2022. Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard. The methodological quality of the studies was assessed using ReviewManager (RevMan) 5.4, and a funnel plot was constructed to test for publication bias. ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures. RESULTS: A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study. The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients. Adjuvant treatment with Baitouweng decoction (BTWT) showed a significant effect [mean difference = 36.22, 95% confidence interval (CI): 7.63 to 65.76]. For the reduction of tumor necrosis factor in patients with UC, adjunctive therapy with BTWT (mean difference = -9.55, 95%CI: -17.89 to -1.41), Shenlingbaizhu powder [SLBZS; odds ratio (OR) = 0.19, 95%CI: 0.08 to 0.39], and Shaoyao decoction (OR = -23.02, 95%CI: -33.64 to -13.14) was effective. Shaoyao decoction was more effective than BTWT (OR = 0.12, 95%CI: 0.03 to 0.39), SLBZS (OR = 0.19, 95%CI: 0.08 to 0. 39), and Xi Lei powder (OR = 0.34, 95%CI: 0.13 to 0.81) in reducing tumor necrosis factor and the recurrence rate of UC. CONCLUSION: TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

Comments and illustrations of the WFUMB CEUS liver guidelines: rare benign hematological focal liver lesions (hepatic extramedullary hematopoiesis, Hemophagocytic lymphohistiocytosis, reactive lymphoid hyperplasia).

The manifestation of benign hematological infiltration in the liver is a challenge due to their rare occurrence and therefore, limited awareness and the general need for biopsy and histological confirmation. Owing to the rarity of these lesions, there are limited data concerning their appearance on ultrasound and, specifically, contrast-enhanced ultrasound. In a series of papers, we have compiled the US and CEUS characteristics of rare FLL, where there are few reports and images available, in order to build up a library of these cases. This paper describes the US and CEUS features of benign hematological FLL which include hepatic extramedullary hematopoiesis (EMH), hemophagocytic lymphohistiocytosis (HLH) and reactive lymphoid hyperplasia (RLH). Although these lesions occur rarely in the liver, their correct identification is imperative for appropriate patient`s management.

Should patients with minor strokes be given thrombolytics?

Mild stroke symptoms are cited as the reason for not using tissue-type plasminogen activator in 29-43% of time-eligible patients. Previous studies suggested that not all of these patients had a good recovery or even survival to hospital discharge. Since then, stroke guidelines worldwide recommended thrombolysis in minor but disabling strokes.Dual antiplatelet treatment with aspirin and clopidogrel was more effective than aspirin alone for reducing subsequent events in patients with minor stroke if started within 24 hours of onset in both CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischaemic Stroke) trials. Recently, both PRISMS (The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial and TEMPO-2(The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial showed that treatment with thrombolysis versus antiplatelet did not increase the likelihood of favourable functional outcome at 90 days among patients with minor non-disabling acute ischaemic strokes. Therefore, a narrative review on thrombolysis for patients with minor strokes from published studies may help practicing clinicians.

The cold temperature associated with new-onset heart failure after incorporating dynamic status of multimorbidity: nationwide cohort, Taiwan 2012-2019.

AIMS: Cold temperatures are known to affect heart failure (HF) hospitalizations, but the dynamic status of multi-morbidity of HF was rarely incorporated. We investigated the relationship between temperature and new-onset HF by risk strata. METHODS AND RESULTS: This nationwide cohort study analysed daily data on ambient temperature, the dynamic status of risk factors (age, diabetes, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease, hypertension, myocardial infarction, and atrial fibrillation), and new-onset HF among the Taiwan population from 2012 to 2019. Poisson regression, Austin's algorithm, and classification and regression tree (CART) were used to determine risk strata and obtain the predicted HF rate. 148 708 patients developed new-onset HF over 152.52 million person-years. Three risk strata for HF were identified: Stratum 1 was predominantly those without any comorbidity (89.9%); Stratum 2 was those aged 60-69 with 2-3 comorbidities or aged 70+ with 1-2 comorbidities (9.0%), and Stratum 3 was those aged 70+ and had four or more comorbidity (1.1%). The HF incidence rates for these three strata were 25.54, 555.27, and 2315.52 per 100 000 person-years, respectively. The R2 of the Poisson regression with the three risk strata and the daily minimum temperature on the ln HF incidence rates was 77.99%. The risk of HF increased as temperatures decreased, and the slopes were 1.032, 1.040, and 1.034 for Strata 1-3, respectively. The rate ratios of HF at the winter median temperature of 17°C vs. the summer median temperature of 29°C were 1.45, 1.58, and 1.49 for Strata 1-3, respectively. Cross-validation reveals a good fit and predicted HF rates by ambient temperature for the three strata were provided. CONCLUSION: Cold temperatures are associated with an increased risk of new-onset HF. Stratum 2 (aged 60-69 with 2-3 comorbidities or aged 70+ with 1-2 comorbidities) are particularly susceptible to cold-related new-onset HF.

Cold temperatures are known to affect heart failure (HF) hospitalizations, but the dynamic status of multi-morbidity of HF was rarely incorporated. Three risk strata for HF were determined for the Taiwan population from 2012 to 2019: Stratum 1 was predominantly young or without comorbidities (89.9%); Stratum 2 was those aged 60­69 with 2­3 comorbidities or aged 70+ with 1­2 comorbidities (9.0%), and Stratum 3 was those aged 70+ and had four or more risk factors (1.1%). The HF incidence rates for these three strata were 25.54, 555.27, and 2315.52 per 100 000 person-years, respectively. The rate ratios of HF at the winter median temperature of 17°C vs. the summer median temperature of 29°C were 1.45, 1.58, and 1.49 for Strata 1­3, respectively. Other than cold temperatures are associated with an increased risk of new-onset HF, Stratum 2 (those aged 60­69 with 2­3 comorbidities or aged 70+ with 1­2 comorbidities) are particularly susceptible to cold-related new-onset HF. Predicted HF rates by ambient temperature for the three strata were provided so that individuals can find their predicted HF rate based on the risk score and the current temperature and, therefore, be amenable to primary preventive efforts.

Lens height paraments comparison according to ciliary sulcus width (CSW): a pilot study of the predictive role of CLR and STSL for vault after ICL implantation.

BACKGROUND: To assess the relationship between postoperative implantable collamer lens (ICL) vault and lens height obtained from two different measurements. METHODS: A retrospective case series study enrolled eyes with horizontally implanted ICL. Crystal lens rise (CLR) and the distance between STS plane and anterior crystalline lens surface (STSL) were measured in the horizontal and vertical directions using ultrasound biomicroscopy (UBM). We compared the differences in the parameters measured in both horizontal and vertical directions. The participants were categorized into three groups according to ciliary sulcus width (CSW) which is defined as the distance between the posterior angle of the iris and the anterior angle of the ciliary process: narrow CSW group (NSG); medium CSW group (MSG); and wide CSW group (WSG). The correlations between CLR/STSL and vault were examined in each of the three groups. Biased correlation analysis was used further to contrast the correlation between CLR/STSL and vault. RESULTS: This retrospective study included 223 myopic eyes. Vertical STSL (VSTSL) and vertical CLR (VCLR) exhibited significantly greater values compared to their horizontal counterparts (both P < 0.05). None of the indicators were statistically different between the three groups. In both NSG and MSG, STSL/CLR correlated with vault, while in WSG, only STSL correlated with vault (r=-0.316, P = 0.013). In contrast to HCLR, the correlation between HSTSL and vault remained after controlling for HCLR (r=-0.162, P = 0.015). CONCLUSIONS: STSL should deserve more attention in the preoperative evaluation of ICL compared to CLR especially when CSW is large.

Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome.

BACKGROUND: Alagille syndrome (ALGS) is a multisystem genetic disorder frequently characterized by hepatic manifestations. This study analyzed the clinical, pathological, and molecular genetic features of ALGS to improve the efficiency of clinical diagnosis. METHODS: We retrospectively analyzed the clinical manifestations, pathological examination findings, and genetic testing results of 17 children diagnosed with ALGS based on the revised criteria and hospitalized at our center from January 2012 to January 2022. RESULTS: The clinical manifestations are as follows: Cholestasis (16/17, 94%), characteristic facies (15/17, 88%), heart disease (12/16, 75%), butterfly vertebrae (12/17, 71%) and posterior embryotoxon (7/12, 58%). Among the 15 patients who underwent liver pathology examination, 13 (87%) were found to have varying degrees of bile duct paucity. Genetic testing was performed on 15 children, and pathogenic variants of the jagged canonical Notch ligand 1 (JAG1) gene were identified in 13 individuals, including 4 novel variants. No pathogenic variant in the notch homolog 2 (NOTCH2) gene were identified, and 2 children exhibited none of the aforementioned gene pathogenic variants. The median follow-up duration was 7 years. Of the remaining 15 patients (excluding 2 lost to follow-up), 11 remained stable, 4 deteriorated, and no patient died during the follow-up period. CONCLUSIONS: Among children diagnosed with ALGS, cholestasis stands as the most common feature. To minimize the risk of misdiagnosis, genetic testing should be performed on children exhibiting cholestasis, followed by the application of the revised diagnostic criteria for ALGS. While pharmacological therapy has shown effectiveness for ALGS patients, liver transplantation may be considered in instances of severe pruritus.

Silane modified Cr2O3/polyimide nanocomposite films with excellent surface insulation performance for space applications.

The exploration of deep space significantly increases the probability of spacecraft failures due to surface electrostatic discharge, which imposes higher vacuum insulation protection requirements on polyimide, the external insulation material of spacecrafts. To address this challenge, this study proposes using silane coupling agent KH550 for organic grafting treatment of Cr2O3 nanoparticles, which are then used to dope and modify polyimide to enhance the vacuum surface insulation of polyimide films. The KH550 grafting improves the interface strength between the fillers and the matrix, allowing the fillers to be uniformly dispersed in the matrix. Compared to pure polyimide films, the prepared PI-Cr2O3@KH550 composite films exhibit significantly enhanced vacuum surface flashover voltage, improved surface/volume resistivity, and dielectric properties. The results demonstrate that polyimide composite films with 0.8% by mass of Cr2O3@KH550 show the most notable performance improvement, with the DC flashover voltage and impulse flashover voltage in vacuum increasing by 20.7% and 27.8%, respectively. The doping of chromium oxide nanoparticles introduces more deep traps into the polyimide films and reduce the surface resistivity. The higher deep trap density inhibits charge migration, thereby alleviating secondary electron emission and surface electric field distortion. Simultaneously, the lower surface resistivity facilitates dissipating surface charges and improves the surface insulation. These findings are of significant reference value for promoting the enhancement of aerospace insulation performance.

Reciprocal interactions between lncRNAs and MYC in colorectal cancer: partners in crime.

Proto-oncogenic MYC is frequently dysregulated in colorectal cancer (CRC). In the past decades, long noncoding RNAs (lncRNAs) have emerged as important regulators in cancers, acting as scaffolds, molecular decoys, post-transcriptional regulators, and others. Interestingly, lncRNAs are able to control MYC expression both at transcriptional and post-transcriptional levels. It is suggested that the reciprocal interaction of MYC and lncRNAs often occurs in CRC. MYC can affect the cell fate by promoting or inhibiting the transcription of some lncRNAs. At the same time, some lncRNAs can also affect MYC expression or transcriptional activity, and in turn decide the cell fate. In this review we summarized the current knowledge about the MYC and lncRNA axis, focusing on its mutual regulation, roles in CRC, and proposed potential therapeutic prospects for CRC treatment.

Simple aneuploidy evades p53 surveillance and promotes niche factor-independent growth in human intestinal organoids.

Aneuploidy is nearly ubiquitous in tumor genomes, but the role of aneuploidy in the early stages of cancer evolution remains unclear. Here, by inducing heterogeneous aneuploidy in non-transformed human colon organoids (colonoids), we investigated how the effects of aneuploidy on cell growth and differentiation may promote malignant transformation. Previous work implicated p53 activation as a downstream response to aneuploidy induction. We found that simple aneuploidy, characterized by 1-3 gained or lost chromosomes, resulted in little or modest p53 activation and cell cycle arrest when compared with more complex aneuploid cells. Single-cell RNA sequencing analysis revealed that the degree of p53 activation was strongly correlated with karyotype complexity. Single-cell tracking showed that cells could continue to divide despite the observation of one to a few lagging chromosomes. Unexpectedly, colonoids with simple aneuploidy exhibited impaired differentiation after niche factor withdrawal. These findings demonstrate that simple aneuploid cells can escape p53 surveillance and may contribute to niche factor-independent growth of cancer-initiating colon stem cells.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study.

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen's criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

Effects of low-intensity pulsed ultrasound on the microorganisms of expressed prostatic secretion in patients with IIIB prostatitis.

To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P < 0.05 were considered statistically significant. Beta diversity analysis showed that there was a significant difference between groups (P = 0.046). LEfSe detected four kinds of characteristic microorganisms in the EPS of patients with IIIB prostatitis before and after LIPUS treatment. After multiple comparisons among groups by DESeq2 method, six different microorganisms were found. LIPUS may improve patients' clinical symptoms by changing the flora structure of EPS, stabilizing and affecting resident bacteria or opportunistic pathogens.

An [illustrative] update on pediatric emergency medicine ultrasound: part 2 - abdominal and urogenital applications.

Emergency ultrasound, or point-of-care ultrasound (POCUS), has been established into daily patient care over the last decades. The use of abdominal and pelvic ultrasound in clinical practice has the potential to improve the efficiency and safety of pediatric emergency care. This article will provide a review of current applications of pediatric emergency abdominal and urogenital ultrasound, forming the second part of the series.

Mitochondrial­associated endoplasmic reticulum membrane interference in ovarian cancer (Review).

The mitochondria­associated endoplasmic reticulum (ER) membrane (MAM), serving as a vital link between the mitochondria and ER, holds a pivotal role in maintaining the physiological function of these two organelles. Its specific functions encompass the participation in the biosynthesis and functional regulation of the mitochondria, calcium ion transport, lipid metabolism, oxidative stress and autophagy among numerous other facets. Scientific exploration has revealed that MAMs hold potential as effective therapeutic targets influencing the mitochondria and ER within the context of cancer therapy. The present review focused on elucidating the related pathways of mitochondrial autophagy and ER stress and their practical application in ovarian cancer, aiming to identify commonalities existing between MAMs and these pathways, thereby extending to related applications of MAMs in ovarian cancer treatment. This endeavor aimed at exploring new potential for MAMs in clinically managing ovarian cancer.

Controversies in endobronchial ultrasound.

Endobronchial ultrasound (EBUS) is a minimally invasive highly accurate and safe endoscopic technique for the evaluation of mediastinal lymphadenopathy and mediastinal masses including centrally located lung tumors. The combination of transbronchial and transoesophageal tissue sampling has improved lung cancer staging, reducing the need for more invasive and surgical diagnostic procedures. Despite the high level of evidence regarding EBUS use in the aforementioned situations, there are still challenges and controversial issues such as follows: Should informed consent for EBUS and flexible bronchoscopy be different? Is EBUS able to replace standard bronchoscopy in patients with suspected lung cancer? Which is the best position, screen orientation, route of intubation, and sedation/anesthesia to perform EBUS? Is it advisable to use a balloon in all procedures? How should the operator acquire skills and how should competence be ensured? This Pro-Con article aims to address these open questions.

Highly stable fiber-based photonic delay line with large and tunable delay.

A stable photonic delay line with large and tunable delay is essential for large-distance simulation, beamforming, and diverse photonic signal processing applications. Here, we demonstrate a fiber-based tunable photonic delay line (TPDL) with a maximum delay of 905 µs. Its environmental-related delay jitter is compensated for by a homodyne phase-locked loop (PLL). Precise delay tuning is realized by changing the phase of the reference with a minimum tuning step of 0.5 ps without breaking its locking state. The demonstrated delay line shows exceptional stability, as indicated by an overlapping Allan deviation (ADEV) of 2.06 × 10-17 at the averaging time of 1000 s and the delay jitter below 20 fs. Its high stability, wide delay range, wideband characteristics, and precise tunability make the TPDL an ideal photonic delay line for the above-mentioned applications.