Targeted treatment of chondrosarcoma with a bacteriophage-based particle delivering a secreted tumor necrosis factor-related apoptosis-inducing ligand.

Chondrosarcoma (CS) is a malignant cartilage-forming bone tumor that is inherently resistant to chemotherapy and radiotherapy, leaving surgery as the only treatment option. We have designed a tumor-targeted bacteriophage (phage)-derived particle (PDP), for targeted systemic delivery of cytokine-encoding transgenes to solid tumors. Phage has no intrinsic tropism for mammalian cells; therefore, it was engineered to display a double cyclic RGD4C ligand on the capsid to target tumors. To induce cancer cell death, we constructed a transgene cassette expressing a secreted form of the cytokine tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). We detected high expression of αvß3 and αvß5 integrin receptors of the RGD4C ligand, and of the TRAIL receptor-2 in human CS cells (SW1353), but not in primary normal chondrocytes. The RGD4C.PDP-Luc particle carrying a luciferase reporter gene, Luc, effectively and selectively mediated gene delivery to SW1353 cells, but not primary chondrocytes. Transduction of SW1353 cells with RGD4C.PDP-sTRAIL encoding a human sTRAIL, resulted in the expression of TRAIL and subsequent cell death without harming the normal chondrocytes. Intravenous administration of RGD4C.PDP-sTRAIL to mice with established human CS resulted in a decrease in tumor size and tumor viability. Altogether, RGD4C.PDP-sTRAIL can be used to target systemic treatment of CS with the sTRAIL.

Navigate biopsy with ultrasound under augmented reality device: Towards higher system performance.

PURPOSE: Biopsies play a crucial role in determining the classification and staging of tumors. Ultrasound is frequently used in this procedure to provide real-time anatomical information. Using augmented reality (AR), surgeons can visualize ultrasound data and spatial navigation information seamlessly integrated with real tissues. This innovation facilitates faster and more precise biopsy operations. METHODS: We have developed an augmented reality biopsy navigation system characterized by low display latency and high accuracy. Ultrasound data is initially read by an image capture card and streamed to Unity via net communication. In Unity, navigation information is rendered and transmitted to the HoloLens 2 device using holographic remoting. Concurrently, a retro-reflective tool tracking method is implemented on the HoloLens 2, enabling the simultaneous tracking of the ultrasound probe and biopsy needle. Distinct navigation information is provided during in-plane and out-of-plane punctuation. To evaluate the effectiveness of our system, we conducted a study involving ten participants, assessing puncture accuracy and biopsy time in comparison to traditional methods. RESULTS: Ultrasound image was streamed from the ultrasound device to augmented reality headset with 122.49±11.61ms latency, while only 16.22±11.25ms was taken after data acquisition from image capture card. Navigation accuracy reached 1.23±0.68mm in the image plane and 0.95±0.70mm outside the image plane, within a depth range of 200 millimeters. Remarkably, the utilization of our system led to 98% and 95% success rate in out-of-plane and in-plane biopsy, among ten participants with little ultrasound experience. CONCLUSION: To sum up, this paper introduces an AR-based ultrasound biopsy navigation system characterized by high navigation accuracy and minimal latency. The system provides distinct visualization contents during in-plane and out-of-plane operations according to their different characteristics. Use case study in this paper proved that our system can help young surgeons perform biopsy faster and more accurately.

Comprehensive analysis of sesame LRR-RLKs: structure, evolution and dynamic expression profiles under Macrophomina phaseolina stress.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) can participate in the regulation of plant growth and development, immunity and signal transduction. Sesamum indicum, one of the most important oil crops, has a significant role in promoting human health. In this study, 175 SiLRR-RLK genes were identified in S. indicum, and they were subdivided into 12 subfamilies by phylogenetic analysis. Gene duplication analysis showed that the expansion of the SiLRR-RLK family members in the sesame was mainly due to segmental duplication. Moreover, the gene expansion of subfamilies IV and III contributed to the perception of stimuli under M. phaseolina stress in the sesame. The collinearity analysis with other plant species revealed that the duplication of SiLRR-RLK genes occurred after the differentiation of dicotyledons and monocotyledons. The expression profile analysis and functional annotation of SiLRR-RLK genes indicated that they play a vital role in biotic stress. Furthermore, the protein-protein interaction and coexpression networks suggested that SiLRR-RLKs contributed to sesame resistance to Macrophomina phaseolina by acting alone or as a polymer with other SiLRR-RLKs. In conclusion, the comprehensive analysis of the SiLRR-RLK gene family provided a framework for further functional studies on SiLRR-RLK genes.

Sunlight-Activated Hour-Long Afterglow from Transparent and Flexible Polymers.

Afterglow materials featuring long emission durations ranging from milliseconds to hours have garnered increasing interest owing to their potential applications in sensing, bioimaging, and anti-counterfeiting. Unfortunately, polymeric materials rarely exhibit afterglow properties under ambient conditions because of the rapid nonradiative decay rate of triplet excitons. In this study, hour-long afterglow (HLA) polymer films are fabricated using a facile molecular doping strategy. Flexible and transparent polymer films emitted a bright afterglow lasting over 11 h at room temperature in air, which is one of the best performances among the organic afterglow materials reported to date. Intriguingly, HLA polymer films can be activated by sunlight, and their cyan afterglow in air can be readily observed by the naked eye. Moreover, the HLA color of the polymer films could be tuned from cyan to red through the Förster resonance energy transfer mechanism. Their application in flexible displays and information storage has also been demonstrated. With remarkable advantages, including an hour-long and bright afterglow, tunable afterglow colors, superior flexibility and transparency, and ease of fabrication, the HLA polymer paves the way for the practical application of afterglow materials in the engineering sector.

Effect of methylene blue on outcomes in patients with distributive shock: a meta-analysis of randomised controlled trials.

OBJECTIVE: This meta-analysis aimed to demonstrate the effect of methylene blue (MB) in patients with distributive shock. DESIGN: Meta-analysis. METHODS: According to the Prospective International Register of Systematic Reviews (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched the relevant randomised controlled trials (RCTs) via PubMed, Embase and Cochrane Library from the date of database inception to 19 April 2023. The primary outcome was mortality during follow-up, and secondary outcomes included mean arterial pressure (mm Hg), mechanical ventilation time (hours), intensive care unit (ICU) length of stay (LOS) (days), hospital LOS (days) and heart rate (times/min). RESULTS: This study included six RCTs with 265 participants. The study showed no significant difference in mortality between the MB and placebo groups (ORs: 0.59; 95% CI 0.32 to -1.06). However, MB reduced the duration of mechanical ventilation (mean difference (MD): -0.68; 95% CI -1.23 to -0.14), ICU LOS (MD: -1.54; 95% CI -2.61 to -0.48) and hospital LOS (MD: -1.97; 95% CI -3.92 to -0.11). CONCLUSIONS: The use of MB may not reduce mortality in patients with distributive shock, but may shorten the duration of mechanical ventilation, ICU LOS and hospital LOS. More clinical studies are needed to confirm these findings in the future. TRIAL REGISTRATION NUMBER: CRD42023415938.

Full-length transcriptome and RNA-Seq analyses reveal the resistance mechanism of sesame in response to Corynespora cassiicola.

BACKGROUND: Corynespora leaf spot is a common leaf disease occurring in sesame, and the disease causes leaf yellowing and even shedding, which affects the growth quality of sesame. At present, the mechanism of sesame resistance to this disease is still unclear. Understanding the resistance mechanism of sesame to Corynespora leaf spot is highly important for the control of infection. In this study, the leaves of the sesame resistant variety (R) and the sesame susceptible variety (S) were collected at 0-48 hpi for transcriptome sequencing, and used a combined third-generation long-read and next-generation short-read technology approach to identify some key genes and main pathways related to resistance. RESULTS: The gene expression levels of the two sesame varieties were significantly different at 0, 6, 12, 24, 36 and 48 hpi, indicating that the up-regulation of differentially expressed genes in the R might enhanced the resistance. Moreover, combined with the phenotypic observations of sesame leaves inoculated at different time points, we found that 12 hpi was the key time point leading to the resistance difference between the two sesame varieties at the molecular level. The WGCNA identified two modules significantly associated with disease resistance, and screened out 10 key genes that were highly expressed in R but low expressed in S, which belonged to transcription factors (WRKY, AP2/ERF-ERF, and NAC types) and protein kinases (RLK-Pelle_DLSV, RLK-Pelle_SD-2b, and RLK-Pelle_WAK types). These genes could be the key response factors in the response of sesame to infection by Corynespora cassiicola. GO and KEGG enrichment analysis showed that specific modules could be enriched, which manifested as enrichment in biologically important pathways, such as plant signalling hormone transduction, plant-pathogen interaction, carbon metabolism, phenylpropanoid biosynthesis, glutathione metabolism, MAPK and other stress-related pathways. CONCLUSIONS: This study provides an important resource of genes contributing to disease resistance and will deepen our understanding of the regulation of disease resistance, paving the way for further molecular breeding of sesame.

Genome-wide characterization of the wall-associated kinase-like (WAKL) family in sesame (Sesamum indicum) identifies a SiWAKL6 gene involved in resistance to Macrophomina Phaseolina.

BACKGROUND: Sesame charcoal rot caused by Macrophomina phaseolina is one of the most serious fungal diseases in sesame production, and threatens the yield and quality of sesame. WAKL genes are important in the plant response to biotic stresses by sensing and transmitting external signals to the intracellular receptor. However, there is still a lack about the WAKL gene family and its function in sesame resistance to M. phaseolina. The aim of this study was to interpret the roles of WAKL genes in sesame resistance to M. phaseolina. RESULTS: In this study, a comprehensive study of the WAKL gene family was conducted and 31 WAKL genes were identified in the sesame genome. Tandem duplication events were the main factor in expansion of the SiWAKL gene family. Phylogenetic analysis showed that the sesame SiWAKL gene family was divided into 4 groups. SiWAKL genes exhibited different expression patterns in diverse tissues. Under M. phaseolina stress, most SiWAKL genes were significantly induced. Notably, SiWAKL6 was strongly induced in the resistant variety "Zhengzhi 13". Functional analysis showed that SiWAKL6 was induced by salicylic acid but not methyl jasmonate in sesame. Overexpression of SiWAKL6 in transgenic Arabidopsis thaliana plants enhanced their resistance to M. phaseolina by inducing the expression of genes involved in the salicylic acid signaling pathway and reconstructing reactive oxygen species homeostasis. CONCLUSIONS: Taken together, the results provide a better understanding of functions about SiWAKL gene family and suggest that manipulation of these SiWAKL genes can improve plant resistance to M. phaseolina. The findings contributed to further understanding of functions of SiWAKL genes in plant immunity.

[SWI/SNF Complex Gene Mutations Promote the Liver Metastasis 
of Non-small Cell Lung Cancer Cells in NSI Mice].

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS: This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.

Prolonged Tracheal Intubation in the ICU as a Possible Risk Factor for Arytenoid Dislocation After Liver Transplant Surgery: A Retrospective Case-Control Study.

BACKGROUND Arytenoid dislocation (AD) is a rare complication of general anesthesia with tracheal intubation, with a published incidence of 0.009-0.097%. This retrospective case-control study aimed to identify risk factors associated with AD in patients who underwent liver transplantation. MATERIAL AND METHODS This study included 476 patients who underwent liver transplantation between January 2013 and December 2022. Patients with AD who underwent surgery were included in the AD group. For each case of AD, 4 patients matched by anesthesia type and anesthetist were randomly selected as the non-AD group. Data on patient characteristics, anesthetic factors, and surgical factors were collected and compared between patients with and without AD. Logistic regression analysis was performed to determine the risk factors for AD after liver transplantation. RESULTS Of the 476 patients who underwent liver transplantation, 17 (3.57%) had AD. AD occurred on the left side in 13 patients and on the right side in 4 patients. The 17 patients who experienced AD and 68 matched non-AD patients were enrolled. Patients in the AD group had a greater intubation depth (24 [23-24] vs 24 [24-24], P=0.043), a higher level of hemoglobin (134.5 [118-147.5] vs 112 [96.25-125], P=0.014), and prolonged tracheal intubation in the ICU (19.75 [15.87-31.87] vs 13 [10.62-15], P<0.001) compared to those in the non-dislocation group. Multivariate logistic regression analysis showed that prolonged tracheal intubation in the ICU was independently associated with the occurrence of AD in patients who underwent liver transplantation (P=0.013). CONCLUSIONS This study showed that the incidence of AD was 3.57% in patients undergoing liver transplant surgery and that prolonged tracheal intubation in the ICU was a possible risk factor for AD.

Anisotropic wood-hydrogel composites: Extending mechanical properties of wood towards soft materials' applications.

Delignified wood (DW) offers a versatile platform for the manufacturing of composites, with material properties ranging from stiff to soft and flexible by preserving the preferential fiber directionality of natural wood through a structure-retaining production process. This study presents a facile method for fabricating anisotropic and mechanically tunable DW-hydrogel composites. These composites were produced by infiltrating delignified spruce wood with an aqueous gelatin solution followed by chemical crosslinking. The mechanical properties could be modulated across a broad strength and stiffness range (1.2-18.3 MPa and 170-1455 MPa, respectively) by varying the crosslinking time. The diffusion-led crosslinking further allowed to manufacture mechanically graded structures. The resulting uniaxial, tubular structure of the anisotropic DW-hydrogel composite enabled the alignment of murine fibroblasts in vitro, which could be utilized in future studies on potential applications in tissue engineering.

High prevalence of postoperative arytenoid dislocation in patients undergoing liver transplantation: A case-control study.

Arytenoid dislocation (AD) is a rare complication of surgery under general anesthesia. The potential factors for AD remain poorly defined, and the identification of risk factors is beneficial for reducing its incidence. We found that patients undergoing liver transplantation appeared to be more susceptible to postoperative AD at our hospital. The present study was designed to clarify this issue. A retrospective hospital-based case-control study was conducted in patients undergoing surgery under general anesthesia between 2017 and 2021. Recorded data for all patients were age, sex, body weight, height, body mass index, position of patients during surgery, duration of surgery, emergency status of surgery, and liver transplantation. Logistic regression analysis was performed to determine risk factors for AD. Thirty thousand one hundred fifty-four patients who underwent general anesthesia between 2017 and 2021 were included. Sixteen (0.05%) patients were diagnosed with AD, including 10 (3.9%) patients among 259 patients who underwent liver transplantation and 6 patients had complications among the 29,895 patients who underwent other operations (P < .0001). Postoperative AD incidence was significantly elevated in patients undergoing liver transplantation. This finding should be clinically relevant and alarming for anesthesiologists and clinicians to help avoid arytenoid dislocation and improve patient outcomes. Further studies that incorporate detailed data are needed to determine risk factors for AD.

Comparison of accuracy for hip-knee-ankle (HKA) angle by X-ray and knee motion analysis system and the relationships between HKA and gait posture.

BACKGROUND: The lower limb mechanical axis was used to assess the severity of knee osteoarthritis (KOA) with varus/valgus deformity and the accuracy of targeted lower limb alignment correction after operation by conventional X-rays. There are lots of parameters to assess the gait in elder patients such as velocity, stride length, step width and swing/stance ratio by knee joint movement analysis system. However, the correlation between the lower limb mechanical axis and gait parameters is not clear. This study is aimed at obtaining the accuracy of the lower limb mechanical axis by the knee joint movement analysis system and the correlation between the lower limb mechanical axis and gait parameters. METHODS: We analysed 3D knee kinematics during ground gait of 99 patients with KOA and 80 patients 6 months after the operations with the vivo infrared navigation 3D portable knee joint movement analysis system (Opti-Knee®, Innomotion Inc, Shanghai, China). The HKA (Hip-Knee-Ankle) value was calculated and compared to X-ray findings. RESULTS: HKA absolute variation after the operation was 0.83 ± 3.76°, which is lower than that before the operation (5.41 ± 6.20°, p = 0.001) and also lower than the entire cohort (3.36 ± 5.72). Throughout the cohort, a significant correlation with low coefficients (r = -0.19, p = 0.01) between HKA value and anterior-posterior displacement was found. In comparing the HKA values measured on the full-length alignment radiographs and 3D knee joint movement analysis system (Opti-Knee), there was a significant correlation with moderate to high coefficients (r = 0.784 to 0.976). The linear correlation analysis showed that there was a significant correlation between the values of HKA measured by X-ray and movement analysis system (R2 = 0.90, p < 0.01). CONCLUSIONS: Data with equivalent results as HKA, the 6DOF of the knee and ground gait data could be provided by infrared navigation based 3D portable knee joint movement analysis system comparing with the conventional X-rays. There is no significant effect of HKA on the kinematics of the partial knee joint.

Foreign Body Granuloma Originating From the Lateral Process of Malleus: A Case Series of 19 Children.

OBJECTIVE: A special presentation of foreign body granuloma originating from the lateral process of the malleus (FBGLP) was noted in the absence of a history of foreign body entry into the external auditory canal (EAC). This study reported the clinical features, pathology, and prognosis of patients with FBGLP. DESIGN: Retrospective study. SETTING: Shandong Provincial ENT Hospital. PATIENTS: Nineteen pediatric patients (age, 1-10 yr) with FBGLP. INTERVENTIONS: Clinical data were collected from January 2018 to January 2022. MAIN OUTCOME MEASURES: Clinicopathologic characteristics of the patients were analyzed. RESULTS: All patients had an acute course, and were within 3 months of ineffective medical treatment. The most common symptoms were suppurative (57.9%) and hemorrhagic (42.1%) otorrhea. FBGLP imaging examinations demonstrated a soft mass blocking the EAC without bone destruction and occasionally concomitant effusion in the middle ear. The most common pathologic findings were foreign body granuloma (94.7%,18/19), granulation tissue (73.7%, 14/19), keratotic precipitate (73.7%, 14/19), calcium deposition (63.2%, 12/19), hair shafts (47.4%, 9/19), cholesterol crystals (5, 26.3%), and hemosiderin (15.8%, 3/19). Foreign body granuloma and granulation tissue showed higher expression levels of CD68 and cleaved caspase-3 than did the normal tympanic mucosa, whereas Ki-67 levels were similarly low in all tissues. The patients were followed up for 3 months to 4 years without recurrence. CONCLUSION: FBGLP is caused by endogenous foreign particles in the ear. We recommend the trans-external auditory meatus approach for FBGLP surgical excision, as this shows promising outcomes.

Therapeutic effects of vasopressin on cardiac arrest: a systematic review and meta-analysis.

OBJECTIVE: To demonstrate the therapeutic effect of vasopressin as an alternative treatment for cardiac arrest. DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, the Cochrane Library and Web of Science were searched for randomised controlled trials. The intervention included administration of vasopressin alone or vasopressin combined with epinephrine or vasopressin, steroids and epinephrine (VSE) versus epinephrine combined with placebo as control group. The primary outcome was the return of spontaneous circulation (ROSC). The secondary outcomes included mid-term survival and mid-term good neurological outcome. We conducted subgroup analyses of the primary outcome based on different settings, different study drug strategies and different types of initial rhythm. RESULTS: Twelve studies (n=6718) were included, of which eight trials (n=5638) reported the data on patients with out-of-hospital cardiac arrest and four trials (n=1080) on patients with in-hospital cardiac arrest (IHCA). There were no significant differences between intravenous vasopressin and placebo in the outcomes of ROSC (relative risk (RR): 1.11; 95% CI: 0.99 to 1.26), mid-term survival (RR: 1.23; 95% CI: 0.90 to 1.66) and mid-term good neurological outcome (RR: 1.20; 95% CI: 0.77 to 1.87). However, in the subgroup analysis, intravenous vasopressin as part of VSE can significantly improve the rate of ROSC (RR: 1.32; 95% CI: 1.18 to 1.47) but not the rate of mid-term survival (RR: 2.15; 95% CI: 0.75 to 6.16) and mid-term good neurological outcome (RR: 1.80; 95% CI: 0.81 to 4.01) for patients with IHCA. CONCLUSIONS: Our study failed to demonstrate increased benefit from vasopressin with or without epinephrine compared with the standard of care. However, vasopressin as a part of VSE is associated with the improvement of ROSC in patients with IHCA, and the benefit on mid-term survival or mid-term good neurological outcome is uncertain. Larger trials should be conducted in the future to address the effect of vasopressin only, vasopressin plus epinephrine or VSE on cardiac arrest. PROSPERO REGISTRATION NUMBER: CRD42021293347.

Assessment of the Iodine Status of Lactating Women and Infants in Shanghai, China.

There is a risk of iodine deficiency among pregnant women in China. However, research on the iodine status of lactating women and infants is scarce. In this study, we aimed to evaluate the iodine status of lactating women and their infants and explore the relationship between breast milk iodine concentrations (BMICs) and urinary iodine concentrations (UICs). In total, 257 lactating women and their infants were recruited from the Shanghai Sixth People's Hospital East campus between May 2018 and May 2019. The BMIC and UIC were measured by inductively coupled plasma‒mass spectrometry (ICP‒MS). One-day 24-h dietary recall was used to determine the dietary intake of iodine. The mean dietary intake of iodine among the lactating women was 145.1 µg/day, and 97.83% (n = 225) of the lactating women had a dietary iodine intake below 240 µg/day. The median BMIC and UIC of the lactating women was 150.7 µg/L (interquartile range, IQR 102.9, 205.5) and 110.0 µg/L (IQR 65.8, 171.4), respectively, and the median UIC of the infants was 212.7 µg/L (IQR 142.1, 320.6). The BMIC of lactating women who consumed iodized salt was significantly higher than that of lactating women who did not consume iodized salt (p = 0.015). The infants' UIC values were significantly correlated with the BMIC values (r = 0.597**, p < 0.001). The iodine nutritional status of lactating women and infants in Shanghai was generally sufficient according to the WHO's iodine nutritional status recommendation. The use of iodized salt was related to increasing dietary iodine intake and the BMIC. Improvements in BMICs have positive effects on the nutritional levels of iodine in infants.

Longitudinal variation of endolymphatic hydrops in patients with Ménière's disease.

Background: The relationships of endolymphatic hydrops (EH) and perilymphatic enhancement (PE) with Ménière's disease (MD) remains unclear. This study aimed to describe the dynamic variation of EH and PE for MD patients over 2 hospitalizations by applying magnetic resonance imaging (MRI) to further clarify the relationships of EH and PE with MD. Methods: A total of 77 MD patients who underwent inner ear MRI after intravenous administration of gadolinium and pure-tone average (PTA) testing during a first and second hospitalization were included. The degree of EH and PE were evaluated via MRI, and the duration and frequency of vertigo attacks and PTA were collected and recorded. The PTA, EH, and PE for the 2 hospitalizations were compared, and the relationships of EH and cochlear PE with the MD stage were investigated. Results: There was no difference between the 2 hospitalizations for duration of vertigo attacks or frequency of vertigo attacks. However, there were significant differences in PTA (Z=-3.02, P=0.003). Additionally, the cochlear and vestibular EH in the asymptomatic ear at the second hospitalization was significantly worse than that of the first hospitalization (Z=-2.33 and -2.49, P=0.020 and 0.013, respectively), while there were no differences in EH and PE in the affected ear (all P>0.05). Moreover, the degree of cochlear and vestibular EH was correlated with MD stage (both P<0.01). Conclusions: Although EH and PE in the affected ear were unchanged over 2 hospitalizations, an underlying EH in the asymptomatic ear and hearing loss in the affected ear for MD patients developed longitudinally with the duration of disease, and EH varied with the natural course of MD whereas PE did not. Therefore, EH instead of PE is necessary but insufficient to cause the clinical symptoms of MD.

Surfactant Protein A can Affect the Surface Tension of the Eustachian Tube and Macrophage Migration.

OBJECTIVE: To assess the role and possible mechanism of surfactant protein A (SPA) in the pathogenesis of otitis media with effusion (OME). METHODS: This was a multi-part study with both an in vivo mouse model study as well as an in vitro study. The control and study groups (OME group) received phosphate-buffered saline and inactivated Streptococcus pneumoniae, respectively, via external auditory meatus injections. Changes in the surface tension of secretions from the eustachian tube (ET) and SPA expression were measured in both groups. A transwell assay was performed to observe the effect of different concentrations of SPA on the migration ability of macrophages. We examined the differentially expressed genes related to SPA-treated macrophages using RNA-seq analysis. RESULTS: On Day 3, the surface tension of the OME group was higher than that of the control group (p = 0.014). The variation intensity of SPA in the ET of the OME group was significantly lower than that of the control group (p < 0.001). Surface tension was correlated with SPA (r = -0.525, p = 0.037). The expression of SPA and macrophages in the ET was different between the two groups. In vitro experiments revealed that macrophages showed different migration abilities with SPA concentration changes (p < 0.05). RNA-seq and western blotting were performed after macrophages were treated with SPA. The results showed that RhoA and Rac1/2/3 were differentially expressed. CONCLUSIONS: SPA can change the surface tension of secretions from the ET and affect macrophage migration to alter the function of the ET. Although research in this field of OME is nascent, initial work suggests that SPA likely plays an important role in OME progression. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1726-1733, 2023.

Regulation of rhizospheric microbial network to enhance plant growth and resist pollutants: Unignorable weak electric field.

The union of Plant Growth-Promoting Bacteria (PGPB) and rhizosphere confers a series of functions beneficial to plant. However, the lack of an opearable in situ method limits the further understanding on the mechanism. In this study, a weak electric field was designed to regulate rhizospheric microflora in a constructed root-splitting reactor. Compared with the control, the aboveground and underground biomass of rice seedling increased by 17 % and 18 % (p < 0.05) respectively under the exist of weak electric field of 0.14 V/cm. The joint action of rhizosphere and PGPB displayed the detoxification ability in the condition of soluble petroleum hydrocarbons, where the height, stem diameter, biomass and root vigor of the plant was increased by 58 %, 32 %, 43 % and 48 % respectively than the control. The selective reproduction of endophytes and ectophytes (denitrifying, auxin-producing, hydrocarbon-degrading and electroactive bacteria) was observed under applied weak electric field, which enhanced the nitrogen utilization, cellular metabolic activity and resistance to toxic organics of plant. This was further confirmed by the up-regulated OTUs related to the hydrocarbon degradation function, tryptophan metabolism and metabolism of nicotinate and nicotinamide. Moreover, the weak electric field also enhanced the transfer ability of partial endophytes grown in the root to improve plant stress resistance. The results in this work inspired an exercisable method for in situ enrichment of PGPB in the rhizosphere to cope with food crisis and provided a new way to deal with sudden environmental events.

Clinical Significance of High Expression of tRF-Glu-TTC-2 in Prostate Carcinoma and its Effect on Growth.

The tRNA-derived fragments (tRFs) are a new class of regulatory noncoding RNAs and have different biological functions in cancer. This article investigated the expression and clinicopathological significance of tRF-Glu-TTC-2 in prostate carcinoma (PCa), and its effect on tumor growth. Expression profiles of tRFs and tiRNAs were analyzed by tRF and tiRNAs microarray in PCa samples, and then the expression was confirmed by qRT-PCR; RNA in situ hybridization was used to detect the positive expression of tRF-Glu-TTC-2 and to analyze the correlation between the expression level of tRF-Glu-TTC-2 and clinicopathological parameters. CCK-8 experiment was used to detect the effect of tRF-Glu-TTC-2 on the proliferation of PCa cells, and nude mice subcutaneous tumor model was used to detect the effect of tRF-Glu-TTC-2 on the growth of PCa cells. The results showed that tRF-Glu-TTC-2 was mainly positive and its expression level increased in PCa. The high expression was closely related to the tumor size (p < .05). Overexpression of tRF-Glu-TTC-2 promoted the proliferation of PCa cells, and decreased expression of tRF-Glu-TTC-2 inhibited the proliferation of PCa cells (p < .05). The results of subcutaneous tumor transplantation in nude mice showed that the tumor volume and weight of the knockdown group were smaller than those of the control group(all ps < .05). Ki-67 staining showed that the proportion of Ki-67-positive cells in the reduced tRF-Glu-TTC-2 group was lower than that in the control group (p < .05). The tRF-Glu-TTC-2 may be a new oncogene that can promote growth and proliferation of PCa. It provides a new idea for the treatment of PCa.

Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Up to 80% of patients in the intensive care unit (ICU) suffer from delirium. Studies on the preventative use of melatonin in the ICU have produced mixed results. We performed a systematic review and meta-analysis to evaluate whether early administration of melatonin reduces the prevalence of delirium in critically ill patients. METHODS: We searched Medline, Embase, and the Cochrane Library for randomized controlled trials comparing melatonin or melatonin agonists to placebo in ICU setting. The population included adult patients in the ICU. The primary outcome was the prevalence of delirium. Secondary outcomes included duration of delirium, delirium-free day, serum melatonin concentration, need for sedation, duration of mechanical ventilation, hospital and ICU length of stay (LOS), all-cause mortality, sleep quality, and adverse events. Trial sequential analysis (TSA) was performed on the primary outcome to prevent the risk of random error and multiplicity phenomenon as a result of repeated significance testing across all the included trials. RESULTS: Twelve trials with a total of 2538 patients were analyzed. When all trials were pooled, the incidence of delirium in ICU patients who received melatonin was significantly lower than in those who received placebo (risk ratio, 0.77; 95% confidence interval: 0.61-0.96; I2 = 56%). There were no significant differences in secondary outcomes including duration of delirium, duration of mechanical ventilation, ICU LOS, hospital LOS, and mortality. TSA indicated that Z-curve crossed the traditional boundary, but did not cross the monitoring boundary for benefit, which indicated that it is still inconclusive that melatonin affects the incidence of delirium. CONCLUSIONS: This meta-analysis found that early administration of melatonin may result in a decreased delirium prevalence in critically ill patients. However, the sensitivity analysis of high-quality studies did not support this finding. In addition, TSA demonstrated that the result may have false-positive error. Therefore, this finding should be interpreted with caution. Further studies are needed to examine the effectiveness of prophylactic melatonin on the prevalence and duration of ICU delirium in the future.