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Objective: To explore the related factors of anxiety and anxiety tendency in patients with tinnitus. Methods: A cross-sectional study was carried out. Basic information, tinnitus characteristics, and psychological status of patients who complained of tinnitus in the Outpatient Department of Eye & ENT Hospital, Fudan University between January 2020 and December 2023 were collected. All patients filled out the self-rating anxiety scale (SAS) and underwent pure tone audiometry testing. According to the SAS scores, patients were divided into three groups: non-anxiety group (SAS<40), anxiety tendency group (40≤SAS<50), and anxiety group (SAS≥50). The related factors of anxiety and anxiety tendency were analyzed using multivariate ordered logistic regression analysis. Results: A total of 176 patients (57 males and 119 females) aged (49.4±10.7) years (range: 13-76 years)were included, with the onset time of 3 days-37 years. There were 78 cases (44.3%), 65 cases (36.9%) and 33 cases (18.8%) in the non-anxiety group, the anxiety tendency group and the anxiety group, respectively. The duration of disease in the anxiety group [(43.4±15.1) months] was significantly longer than that in the anxiety tendency group [(27.2±5.3) months] and the non-anxiety group [(19.6±3.5) months], with statistically significant differences (both P <0.05). The proportion of female patients in the anxiety group [81.8% (27/33)] and anxiety tendency group [75.4% (47/65)] was significantly higher than that in the non-anxiety group [57.7% (45/78)], and the differences were statistically significant (both P <0.05). The proportion of patients with emotional disorders [12.1% (4/33) vs 2.6% (2/78)], stress [15.1% (5/33) vs 3.9% (3/78)], and sleep disorders [48.5% (16/33) vs 23.1% (18/78)] in the anxiety group was significantly higher than that in the non-anxiety group (all P <0.05). The proportion of patients only had sleep disorders in the anxiety tendency group [38.5% (25/65) vs 23.1% (18/78)] was higher than that in the non-anxiety group, with a statistically significant difference ( P <0.05). The results of multivariate ordered logistic regression analysis showed that sleep disorders werethe most significant factor affecting anxiety and anxiety tendency in tinnitus patients ( OR =2.667, 95% CI : 1.451-4.909, P =0.002). Conclusion: A significant proportion of tinnitus patients exhibit anxiety and anxiety tendency, and sleep disorders play a major role in the development of anxiety and anxiety tendencies in tinnitus patients.

PAMP-triggered immunity (PTI) is the first layer of plant defense response that occurs on the plant plasma membrane. Recently, the application of a rhizobacterium, Bacillus amyloliquefaciens strain PMB05, has been demonstrated to enhance flg22 Pst - or harpin-triggered PTI response such as callose deposition. This PTI intensification by PMB05 further contributes to plant disease resistance to different bacterial diseases. Under the demand for rapid and large-scale screening, it has become critical to establish a non-staining technology to identify microbial strains that can enhance PTI responses. Firstly, we confirmed that the expression of the GSL5 gene, which is required for callose synthesis, can be enhanced by PMB05 during PTI activation triggered by flg22 or PopW (a harpin from Ralstonia solanacearum ). The promoter region of the GSL5 gene was further cloned and fused to the coding sequence of gfp . The constructed fragments were used to generate transgenic Arabidopsis plants through a plant transformation vector. The transgenic lines of At GSL5 -GFP were obtained. The analysis was performed by infiltrating flg22 Pst or PopW in one homozygous line, and the results exhibited that the green fluorescent signals were observed until after 8 h. In addition, the PopW-induced fluorescent signal was significantly enhanced in the co-treatment with PMB05 at 4 h after inoculation. Furthermore, by using At GSL5 -GFP to analyze 13 Bacillus spp. strains, the regulation of PopW-induced fluorescent signal was observed. And, the regulation of these fluorescent signals was similar to that performed by callose staining. More importantly, the Bacillus strains that enhance PopW-induced fluorescent signals would be more effective in reducing the occurrence of bacterial wilt. Taken together, the technique by using At GSL5 -GFP would be a promising platform to screen plant immunity-intensifying microbes to control bacterial wilt.

Scope: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits., Methods and Results: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels., Conclusion: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments. On this basis, researchers have conducted various clinical studies to evaluate the potential of selective and pan-HDACis in clinical settings. In our work, we extensively summarized and organized current clinical trials, providing a comprehensive overview of the current clinical advancements in targeting HDAC therapy. Furthermore, we engaged in discussions about several clinical trials that did not yield positive outcomes, analyzing the factors that led to their lack of anticipated therapeutic effectiveness. Apart from the experimental design factors, issues such as toxicological side effects, tumor heterogeneity, and unexpected off-target effects also contributed to these less-than-expected results. These challenges have naturally become significant barriers to the application of HDACis. Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors., (© 2024. The Author(s).)

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1β), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1β, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1β, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1β, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.

Introduction: Bacterial pneumonia poses a significant global public health challenge, where unaddressed pathogens and inflammation can exacerbate acute lung injury and prompt cytokine storms, increasing mortality rates. Alveolar macrophages are pivotal in preserving lung equilibrium. Excessive inflammation can trigger necrosis in these cells, disrupting the delicate interplay between inflammation and tissue repair. Methods: We obtained extracellular vesicle from aloe and tested the biosafety by cell viability and hemolysis assays. Confocal microscopy and flow cytometry were used to detect the uptake and internalization of extracellular vesicle by macrophages and the ability of extracellular vesicle to affect the phenotypic reprogramming of macrophages in vitro . Finally, we conducted a clinical feasibility study employing clinical bronchoalveolar lavage fluid as a representative model to assess the effective repolarization of macrophages influenced by extracellular vesicle. Results: In our study, we discovered the potential of extracellular vesicle nanovesicles derived from aloe in reprograming macrophage phenotypes. Pro-inflammatory macrophages undergo a transition toward an anti-inflammatory immune phenotype through phagocytosing and internalizing these aloe vera-derived extracellular vesicle nanovesicles. This transition results in the release of anti-inflammatory IL-10, effectively curbing inflammation and fostering lung tissue repair. Discussion: These findings firmly establish the immunomodulatory impact of aloe-derived extracellular vesicle nanovesicles on macrophages, proposing their potential as a therapeutic strategy to modulate macrophage immunity in bacterial pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that they were editorial board members of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Zhou, Peng, Wang, Wang, Wang, Sun, Shi, Chen, Ji and Wang.)

Background: Continuous glucose monitoring (CGM) has shown potential in improving maternal and neonatal outcomes in individuals with type 1/2 diabetes, but data in gestational diabetes mellitus (GDM) is limited. We aimed to explore the relationship between CGM-derived metrics during pregnancy and pregnancy outcomes among women with GDM., Methods: We recruited 1302 pregnant women with GDM at a mean gestational age of 26.0 weeks and followed them until delivery. Participants underwent a 14-day CGM measurement upon recruitment. The primary outcome was any adverse pregnancy outcome, defined as having at least one of the outcomes: preterm birth, large-for-gestational-age (LGA) birth, fetal distress, premature rupture of membranes, and neonatal intensive care unit (NICU) admission. The individual outcomes included in the primary outcome were considered as secondary outcomes. We conducted multivariable logistic regression to evaluate the association of CGM-derived metrics with these outcomes., Findings: Per 1-SD difference in time above range (TAR), glucose area under the curve (AUC), nighttime mean blood glucose (MBG), daytime MBG, and daily MBG was associated with higher risk of any adverse pregnancy outcome, with odds ratio: 1.22 (95% CI 1.08-1.36), 1.22 (95% CI 1.09-1.37), 1.18 (95% CI 1.05-1.32), 1.21 (95% CI 1.07-1.35), and 1.22 (95% CI 1.09-1.37), respectively. Time in range, TAR, AUC, nighttime MBG, daytime MBG, daily MBG, and mean amplitude of glucose excursions were positively associated, while time blow range was inversely associated with the risk of LGA. Additionally, higher value for TAR was associated with higher risk of NICU admission. We further summarized the potential thresholds of TAR (2.5%) and daily MBG (4.8 mmol/L) to distinguish individuals with and without any adverse pregnancy outcome., Interpretation: The CGM-derived metrics may help identify individuals at higher risk of adverse pregnancy outcomes. These CGM biomarkers could serve as potential new intervention targets to maintain a healthy pregnancy status among women with GDM., Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Westlake Laboratory of Life Sciences and Biomedicine., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© 2023 The Author(s).)

Objectives: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at both urogenital and extragenital sites has been recommended in many countries. Testing of the infections using pooled specimens from urogenital and extragenital sites offer the opportunity to shorten the testing time and reduce the testing cost. Ex-ante pooling is placing the original single-site specimens in a tube with transport media, while ex-post pooling is making a pool of the transport media from both anorectal and oropharyngeal specimens and the urine. This study aimed to conduct a multisite performance evaluation of two pool-specimen approaches (ex-ante and ex-post) in detection of CT and NG using the Cobas 4800 platform among men who have sex with men (MSM) in China., Design: Diagnostic accuracy study., Setting, Participants and Outcome Measures: Participants were recruited from MSM communities at six cities in China. Two oropharyngeal and anorectal swabs collected by clinical staff and 20 mL first-void urine collected by the participant himself were used for evaluating sensitivity and specificity., Results: A total of 1311 specimens were collected from 437 participants in six cities. The sensitivities of ex-ante pooling approach as compared with single-specimen approach (reference standard) were 98.7% (95% CI, 92.7% to 100.0%) for detection of CT and 89.7% (95% CI, 75.8% to 97.1%) for NG, and the specificities were 99.5% (95% CI, 98.0% to 99.9%) and 98.7% (95% CI, 97.1% to 99.6%), respectively. The sensitivities of ex-post pooling approach were 98.7% (95% CI, 92.7% to 100.0%) for CT and 100.0% (95% CI, 91.0% to 100.0%) for NG, and the specificities were 100.0% (95% CI, 99.0% to 100.0%) and 100.0% (95% CI, 99.1% to 100.0%), respectively., Conclusions: The ex-ante and ex-post pooling approaches show good sensitivity and specificity in detecting urogenital and extragenital CT and/or NG, indicating that these approaches can be used in epidemiological surveillance and clinical management of CT and NG infections, particularly among MSM population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Chlamydia trachomatis (CT) causes the most prevalent bacterial sexually transmitted infection in the world, and men who have sex with men (MSM) are considered as a high-risk population for this infection. Data regarding the prevalence of CT infection in China are limited and fragmented. In this study, we aim to determine at the national level the anatomically specific CT prevalence and genotype distribution of CT strains among MSM, recruiting from the venues where MSM commonly seek sexual partners., Methods and Analysis: The study will be a nationwide cross-sectional survey to estimate the prevalence of chlamydial infections among MSM who meet the inclusion criteria over a period of 6 months (May-October 2022). A total of 2429 participants will be recruited from the venues where MSM most often seek sex partners in 14 cities of the 7 geographical regions in China. A mobile phone app-based anonymous self-administered questionnaire will be used to collect sociodemographic and behavioural data, and specimens of urine, anorectal and pharyngeal swabs will be collected for identifying the infections of CT and Neisseria gonorrhoeae and genotypes of CT. The data will be analysed using the IBM SPSS program V.20 ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethics Committee of the Chinese Academy of Medical Sciences Institute of Dermatology and the National Center for STD Control on 9 October 2021 (approval number 2021-KY-037). The study is based on voluntary participation and a written informed consent process. The study results will be submitted for publication in peer-reviewed journals and reported in conferences. The relevant data will be made available to development of control programmes and used as health education materials to disseminate to the community. The dataset will be deposited in a public repository., Trial Registration Number: ChiCTR2100052869., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to evaluate the clinical performance of the GeneXpert ® (Xpert) CT/NG assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using urine and cervical swabs collected from patients in China., Methods: This study was conducted from September 2016 to September 2018 in three Chinese urban hospitals. The results from the Xpert CT/NG test were compared to those from the Roche cobas ® 4800 CT/NG test. Discordant results were confirmed by DNA sequence analysis., Results: In this study, 619 first void urine (FVU) specimens and 1,042 cervical swab specimens were included in the final dataset. There were no statistical differences between the results of the two tests for the detection of CT/NG in urine samples ( p  > 0.05), while a statistical difference was found in cervical swabs ( p  < 0.05). For CT detection, the sensitivity and specificity of the Xpert test were 100.0% (95%CI = 96.8-99.9) and 98.3% (95%CI = 96.6-99.2) for urine samples and 99.4% (95%CI = 96.5-100.0) and 98.6% (95%CI 97.5-99.2) for cervical swabs, respectively. For NG detection, the sensitivity and specificity of the Xpert test were 99.2% (95%CI = 94.9-100.0) and 100.0% (95%CI = 99.0-100.0) for urine and 100% (95%CI = 92.8-100.0) and 99.7% (95%CI = 99.0-99.9) for cervical swabs, respectively., Conclusion: The Xpert CT/NG test exhibited high sensitivity and specificity in the detection of CT and NG in both urine and cervical samples when compared to the reference results. The 90-min turnaround time for CT and NG detection at the point of care using Xpert may enable patients to receive treatment promptly., Competing Interests: FT and YT are employees of Cepheid, the commercial manufacturer of the Xpert® CT/NG test. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Shi, Jiang, Le, Qin, Xiong, Zheng, Tenover, Tang and Yin.)

Background: Little is known about rectal Chlamydia trachomatis (CT) infection in outpatients attending sexually transmitted disease (STD) clinics in China. In this study, we aimed to explore the clinical and epidemiologic features of rectal CT infection in this population., Methods: A cross-sectional study was conducted among patients attending STD clinics in Tianjin and Guangxi provinces of China from June 2018 to August 2020. Bivariate and multivariate logistic regression analysis were developed to explore the association of different risk factors for urogenital and rectal CT infection., Results: The prevalence of urogenital and rectal CT was 11.2% (154/1374) and 4.9% (68/1377), respectively. The rectal CT prevalence among female and male patients was 7.8% (60/767) and 1.3% (8/610), respectively. The most common genotype in urogenital CT-positive samples was genotype E (29.9%), while the most common genotype among rectal CT-positive samples was genotype J (23.4%). More than 85% (52/60) of women infected with rectal CT were co-infected with urogenital CT. About 90.0% (36/40) of women shared similar genotypes between rectal and urogenital samples. Females and patients infected with urogenital CT were deemed to be at an increased risk for rectal CT infection. A high proportion of rectal CT infection had concurrent urogenital CT infection, especially in women, and most of the co-infections were shared among the same genotypes., Conclusions: It would be prudent to encourage awareness and introduce detection tests and treatment strategies for rectal CT infection particularly in female patients visiting STD clinics in China., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)