Transcriptional, post-transcriptional, and post-translational regulation of polyunsaturated fatty acid synthase genes in Aurantiochytrium limacinum strain BL10: Responses to nitrogen starvation.

Under nitrogen deficient conditions, the Aurantiochytrium limacinum strain BL10 greatly increases the production of docosahexaenoic acid (DHA) and n-6 docosapentaenoic acid. Researchers have yet to elucidate the mechanism by which BL10 promotes the activity of polyunsaturated fatty acid synthase (Pfa), which plays a key role in the synthesis of polyunsaturated fatty acid (PUFA). Analysis in the current study revealed that in nitrogen-depleted environments, BL10 boosts the transcription and synthesis of proteins by facilitating the expression of pfa genes via transcriptional regulation. It was also determined that BL10 adjusts the lengths of the 5'- and 3'-untranslated regions (suggesting post-transcriptional regulation) and modifies the ratio of two Pfa1 isoforms to favor PUFA production via post-translational regulation (ubiquitination). These findings clarify the exceptional DHA production of BL10 and provide additional insights into the regulatory mechanisms of PUFA biosynthesis in Aurantiochytrium.

Dimethyl-Dioctadecyl-Ammonium Bromide/Poly(lactic acid) Nanoadjuvant Enhances the Immunity and Cross-Protection of an NM2e-Based Universal Influenza Vaccine.

For most frequent respiratory viruses, there is an urgent need for a universal influenza vaccine to provide cross-protection against intra- and heterosubtypes. We previously developed an Escherichia coli fusion protein expressed extracellular domain of matrix 2 (M2e) and nucleoprotein, named NM2e, and then combined it with an aluminum adjuvant, forming a universal vaccine. Although NM2e has demonstrated a protective effect against the influenza virus in mice to some extent, further improvement is still needed for the induction of immune responses ensuring adequate cross-protection against influenza. Herein, we fabricated a cationic solid lipid nanoadjuvant using poly(lactic acid) (PLA) and dimethyl-dioctadecyl-ammonium bromide (DDAB) and loaded NM2e to generate an NM2e@DDAB/PLA nanovaccine (Nv). In vitro experiments suggested that bone marrow-derived dendritic cells incubated with Nv exhibited ∼4-fold higher antigen (Ag) uptake than NM2e at 16 h along with efficient activation by NM2e@DDAB/PLA Nv. In vivo experiments revealed that Ag of the Nv group stayed in lymph nodes (LNs) for more than 14 days after initial immunization and DCs in LNs were evidently activated and matured. Furthermore, the Nv primed T and B cells for robust humoral and cellular immune responses after immunization. It also induced a ratio of IgG2a/IgG1 higher than that of NM2e to a considerable extent. Moreover, NM2e@DDAB/PLA Nv quickly restored body weight and improved survival of homo- and heterosubtype influenza challenged mice, and the cross-protection efficiency was over 90%. Collectively, our study demonstrated that NM2e@DDAB/PLA Nv could offer notable protection against homo- and heterosubtype influenza virus challenges, offering the potential for the development of a universal influenza vaccine.

Application of multidisciplinary in situ simulation training in the treatment of acute ischemic stroke: a quality improvement project.

BACKGROUND: Ischemic stroke refers to a disorder in the blood supply to a local area of brain tissue for various reasons and is characterized by high morbidity, mortality, and disability. Early reperfusion of brain tissue at risk of injury is crucial for the treatment of acute ischemic stroke. The purpose of this study was to evaluate comfort levels in managing acute stroke patients with hypoxemia who required endotracheal intubation after multidisciplinary in situ simulation training and to shorten the door-to-image time. METHODS: This quality improvement project utilized a comprehensive multidisciplinary in situ simulation exercise. A total of 53 participants completed the two-day in situ simulation training. The main outcome was the self-reported comfort levels of participants in managing acute stroke patients with hypoxemia requiring endotracheal intubation before and after simulation training. A 5-point Likert scale was used to measure participant comfort. A paired-sample t-test was used to compare the mean self-reported comfort scores of participants, as well as the endotracheal intubation time and door-to-image time on the first and second days of in situ simulation training. The door-to-image time before and after the training was also recorded. RESULTS: The findings indicated that in situ simulation training could enhance participant comfort when managing acute stroke patients with hypoxemia who required endotracheal intubation and shorten door-to-image time. For the emergency management of hypoxemia or tracheal intubation, the mean post-training self-reported comfort score was significantly higher than the mean pre-training comfort score (hypoxemia: 4.53±0.64 vs. 3.62±0.69, t= -11.046, P<0.001; tracheal intubation: 3.98±0.72 vs. 3.43±0.72, t= -6.940, P<0.001). We also observed a decrease in the tracheal intubation and door-to-image time and a decreasing trend in the door-to-image time, which continued after the training. CONCLUSION: Our study demonstrates that the implementation of in situ simulation training in a clinical environment with a multidisciplinary approach may improve the ability and confidence of stroke team members, optimize the first-aid process, and effectively shorten the door-to-image time of stroke patients with emergency complications.

Combined platelet-to-lymphocyte ratio and blood-brain barrier biomarkers as indicators of disability in acute neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a complex neuroinflammatory disease characterized by severe disability. In this study, we investigated the relationship between cerebrospinal fluid (CSF)/serum albumin quotient (Qalb) and platelet to lymphocyte ratio (PLR) in assessing disease severity. METHOD: A retrospective analysis of 72 NMOSD patients and 72 healthy controls was conducted, and patients were divided into two groups based on their Expanded Disability Status Scale (EDSS) scores. RESULTS: NMOSD patients had significantly higher levels of serum PLR, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and C-reactive protein (CRP) compared to healthy controls (all P<0.01). Patients in the EDSS≥4 group exhibited significantly elevated levels of Qalb, QIgG, QIgA, QIgM, and PLR (P=0.000, P<0.0001, P=0.0019, P=0.0001, respectively). Spearman's correlation test revealed significant positive associations between Qalb, QIgG, QIgA, QIgM, PLR, and EDSS score. Specifically, Qalb (r=0.571; P<0.001), QIgG (r=0.551; P<0.001), QIgA (r=0.519; P<0.001), and QIgM (r=0.541; P<0.001) demonstrated significant positive correlations with EDSS score, while PLR exhibited a moderate positive correlation (r=0.545; P<0.001) with EDSS score and a mild positive association (r=0.387; P<0.001) with Qalb. The increase of Qalb was positively correlated with the increased EDSS score (r=0.528, P=0.001), as well as the increase of QIgG (r=0.509, P=0.001), and the increase of QIgA (r=0.4989, P=0.03). ROC analysis indicated that Qalb, QIgG, QIgA, QIgM, and PLR levels could effectively serve as indicators of NMOSD severity (all P<0.0001). Multivariate analysis confirmed the independent significance of Qalb and PLR in assessing disease severity (P=0.000). CONCLUSION: These findings provide valuable insights into the risk and pathogenesis of NMOSD and highlight the potential of Qalb and PLR as independent markers for disease severity assessment in NMOSD patients.

Strain-level structure of gut microbiome showed potential association with cognitive function in major depressive disorder: A pilot study.

BACKGROUND: Although the association between gut microbiota and the pathogenesis of major depressive disorder (MDD) has been well studied, it is unclear whether gut microbiota affects cognitive function in patients with MDD. In this study, we explored the association between gut microbiota and cognitive function in MDD and its possible mechanisms. METHODS: We enrolled 57 patients with MDD and 30 healthy controls (HCs) and used 16S rRNA gene sequencing analysis and shotgun metagenomic sequencing analysis to determine gut microbial composition. RESULTS: The richness and diversity of gut microbiota in patients with MDD were the same as those in HCs, but there were differences in the abundance of Bifidobacterium and Blautia. Compared with HCs, two strains (bin_32 and bin_55) were significantly increased, and one strain (bin_31) was significantly decreased in patients with MDD based on the strain-level meta-analysis. Time to complete the Stroop-C had significant negative correlations with bin_31 and bin_32. Bin_55 had significant negative correlations with time to complete the Stroop-C, time to complete the Stroop-CW, and repeated animal words in 60 s but significant positive correlations with correct answers in 120 s on the Stroop-CW. LIMITATIONS: This study only tested the cognitive function of MDD in a small sample, which may have caused some bias. CONCLUSIONS: Based on our strain-level analysis, we found that gut microbiota may be associated with the pathogenesis of MDD and may have potential effects on cognitive function.

Aikeqing, a kidney- and spleen-tonifying compound Chinese medicine granule, prevented ovariectomy-induced bone loss in rats via the suppression of osteoclastogenesis.

Postmenopausal women are prone to osteoporosis due to increased osteoclast activation and bone resorption caused by oestrogen deficiency. In Traditional Chinese Medicine theory, medicines with spleen- and kidney-nourishing effects are commonly used in postmenopausal osteoporosis (PMOP) treatment. Aikeqing (AKQ) is a compound Chinese medicinal granule with spleen- and kidney-nourishing effects. Herein, we investigate the in vitro and in vivo anti-osteoporotic effects of AKQ, its underlying mechanisms and pharmacodynamic basis. In vitro antiosteoporotic effects of AKQ were assessed by its ability to promote osteoblastogenesis in MC3T3-E1 and/or inhibit RANKL-induced osteoclastogenesis in murine bone marrow monocytes (BMMs). The protective effect of AKQ on bone loss induced by oestrogen deficiency was evaluated in ovariectomized rats. The underlying mechanisms were studied in BMMs by detecting the effects of AKQ on the RANKL-induced expression of genes and proteins involved in the regulation of osteoclastogenesis. The main chemical constituents of AKQ in the granule were analyzed by UPLC-QTOF-MS. Our findings show that AKQ did not affect osteoblastogenesis, but it inhibited RANKL-induced osteoclastogenesis. In the ovariectomized rats, oral administration of AKQ (4 g/kg/d) for 90 d effectively prevented oestrogen deficiency-induced bone loss. Mechanistic studies in BMMs revealed that AKQ inhibited RNAKL-induced activation of NF-κB (p65) and MAPKs (p38 and JNK) via blocking the RANK-TRAF6 interaction, subsequently suppressing the translocation and expression of NFATc1 and c-Fos. UPLC-QTOF-MS analysis quantified the 123 main components of AKQ. Taken together, AKQ was demonstrated for the first time as a novel alternative therapy for osteoclast-associated bone diseases.

4-1BB Targeting Immunotherapy: Mechanism, Antibodies, and Chimeric Antigen Receptor T.

4-1BB (CD137, TNFRSF9) is a type I transmembrane protein which binds its natural ligand, 4-1BBL. This interaction has been exploited to improve cancer immunotherapy. With ligand binding by 4-1BB, the nuclear factor-kappa B signaling pathway is activated, which results in transcription of corresponding genes such as interleukin-2 and interferon-γ, as well as the induction of T cell proliferation and antiapoptotic signals. Moreover, monoclonal antibodies that target-4-1BB, for example, Urelumab and Utomilumab, are widely used in the treatments of B cell non-Hodgkin lymphoma, lung cancer, breast cancer, soft tissue sarcoma, and other solid tumors. Furthermore, 4-1BB as a costimulatory domain, for chimeric antigen receptor T (CAR-T) cells, improves T cell proliferation and survival as well as reduces T cell exhaustion. As such, a deeper understanding of 4-1BB will contribute to improvements in cancer immunotherapy. This review provides a comprehensive analysis of current 4-1BB studies, with a focus on the use of targeting-4-1BB antibodies and 4-1BB activation domains in CAR-T cells for the treatment of cancer.

Factors associated with medication interruption among outpatients with severe mental illness exposed to COVID-19.

Many patients with severe mental illness (SMI) relapsed and deteriorated during the COVID-19 pandemic, as they experienced medication interruption. This study aimed to investigate factors affecting medication interruption in patients with SMI during the COVID-19 pandemic. A total of 2,077 patients with SMI participated in an online survey on medication interruption during the COVID-19 outbreak. The questionnaire comprised six parts: basic demographic information, COVID-19 exposure, state of disease, medication compliance before COVID-19, medication interruption during COVID-19, and the specific impact and needs. A total of 2,017 valid questionnaires were collected. Nearly 50% of patients with SMI have been affected to varying degrees of life expectancy and treatment. Among them, 74 patients stopped taking medicines for more than 14 days without a prescription. Logistic regression analysis showed that cohabitant exposure [OR = 26.629; 95% CI (3.293-215.323), p = 0.002], medication partial compliance and non-compliance pre-COVID-19 [OR = 11.109; 95% CI (6.093-20.251), p < 0.001; OR = 20.115; 95% CI (10.490-38.571), p < 0.001], and disease status [OR = 0.326; 95% CI (0.188-0.564), p < 0.001] were related to medication interruption. More than 50% of the patients wanted help in taking medications, follow-up, and receiving more financial support and protective materials. We found that the daily lives of patients with SMI were much more susceptible to impact during the pandemic. Patients with a history of partial or non-medication compliance before COVID-19 and an unstable disease state are more easily affected by pandemics and epidemics and need extra attention should similar large-scale outbreaks occur in the future.

Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells.

CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumor cell growth in vitro and in vivo. The underlying mechanism involves the suppression of the Yes-associated protein. However, the specific role of LAF in cell cycle regulation remains unknown. OBJECTIVE: This study determined the molecular mechanism by which LAF regulates cell cycle progression. MATERIALS AND METHODS: Various colon cancer cell lines (SW480, HCT15, and HCT116) were treated with LAF (25, 50, and 75 µmol/L) for 48 h. The effects of LAF on cell proliferation and cell cycle were determined using sulforhodamine B and flow cytometry assays. Differentially expressed proteins (DEPs) were identified using quantitative proteomics. Bioinformatic analysis of DEPs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Expression levels of DEPs in the cell cycle pathway were analyzed using RT-qPCR and western blotting. RESULTS: LAF suppressed the proliferation of SW480, HCT15, and HCT116 cells (IC50 47.1, 51.4, and 32.8 µmol/L, respectively) and induced cell cycle arrest at the S phase. A total of 6331 proteins were identified and quantified, of which 127 were differentially expressed between the LAF-treated and untreated groups. GO and KEGG enrichment analyses revealed that DEPs mainly participated in the cell cycle. CDKN1C/p57 showed the most significant differential expression, with the highest fold-change (3.155-fold). Knockdown of CDKN1C/p57 attenuated the S phase cell cycle arrest and proliferation inhibition induced by LAF. CONCLUSION: LAF exerts antitumor effects via S phase arrest by activating CDKN1C/p57 in colorectal cancer cells.

Plasma levels of interleukin-8 and response to paroxetine in patients with major depressive disorder.

OBJECTIVES: Immune dysregulation plays a key role in major depressive disorder (MDD). However, little is known about the complicated involvement of various interleukins in MDD. This study was performed to investigate the correlation between plasma interleukin-8 (IL-8) levels and treatment outcome of paroxetine (a selective serotonin reuptake inhibitor) in patients with MDD. METHODS: A total of 115 hospitalized patients (36 males and 79 females), aged from 18 to 72 years, were enrolled. Plasma levels of IL-8 were measured before treatment initiation (baseline) and at 8 weeks after oral paroxetine treatment. Efficacy of paroxetine was evaluated by use of the Hamilton Depression Rating Scale (HAMD-17). Baseline IL-8 levels were compared between responders and non-responders to paroxetine treatment. RESULTS: Plasma IL-8 levels decreased significantly after an 8-week antidepressant treatment in responders, in association with a dramatic decrease in HAMD-17 scores. In non-responders, plasma IL-8 levels did not change significantly at 8 weeks after antidepressant treatment. Baseline plasma IL-8 levels were found to be significantly lower in responders than in non-responders, showing a correlation between IL-8 and antidepressant response to paroxetine. CONCLUSIONS: These results indicate that plasma IL-8 levels were related to treatment outcome of paroxetine, and therefore suggest that IL-8 could be a promising predicator of treatment response in individual patients with MDD.

Neferine alleviates chronic stress-induced depression by regulating monoamine neurotransmitter secretion and gut microbiota structure.

Neferine (Nef) might possess anti-depressive properties; however, its therapeutic effects are yet to be elucidated. Therefore, in this study, we aimed to explore the anti-depressant property of Nef using a mouse model of chronic stress-induced depression. Fifteen depression-prone mice were randomly selected and divided into three groups, namely, the model, Nef, and fluoxetine (Flu) groups. We observed that in tail suspension and forced swimming tests, the Nef and Flu treatments significantly decreased the immobility time of the depressed mice, and increased their sucrose preference indices. Moreover, both Nef and Flu treatments induced significant increases in the levels of anti-depressant neurotransmitters, including dopamine (DA), serotonin (5-HT), and norepinephrine (NE), and also reduced pathological damage to the hippocampus of the depressed mice. Incidentally, Illumina MiSeq sequencing analysis demonstrated that the relative abundance of Lactobacillus in the intestinal microbiota of depressed mice was restored after Nef/Flu treatment. Moreover, colonic Lactobacillus abundance was positively correlated with the levels of DA, 5-HT, and NE in the hippocampus of the mice. In conclusion, Nef improved monoamine neurotransmitter secretion and modulated the intestinal flora structure, particularly the abundance of Lactobacillus. Hence, it showed considerable anti-depressant potential, and might be a prospective anti-depressant therapeutic agent.

Gut microbiome: A potential indicator for predicting treatment outcomes in major depressive disorder.

The therapeutic outcomes in major depressive disorder (MDD), one of the most common and heterogeneous mental illnesses, are affected by factors that remain unclear and often yield unsatisfactory results. Herein, we characterized the composition and metabolic function of the gut microbiota of patients with MDD during antidepressant treatment, based on 16S rRNA sequencing and metabolomics. The microbial signatures at baseline differed significantly between responder and non-responder groups. The gut microbiota of the non-responder group was mainly characterized by increased relative abundances of the phylum Actinobacteria, families Christensenellaceae and Eggerthellaceae, and genera Adlercreutzia and Christensenellaceae R7 group compared to that of the responder group. Additionally, the gut microbiota composition of the responder and non-responder groups differed significantly before and after treatment, especially at the genus level. Moreover, 20 differential metabolites between the responder and non-responder groups were identified that were mainly involved in lipid metabolism (cholestane steroids and steroid esters). Eggerthellaceae and Adlercreutzia displayed strong co-occurrence relationships with certain metabolites, suggesting alternations in the gut microbiome, and associated metabolites may be potential mediators of successful antidepressant treatment. Overall, our study demonstrates that alterations in gut microbiota composition and metabolic function might be relevant to the response to antidepressants, thereby providing insight into mechanisms responsible for their efficacy.

An ester derivative of tenacigenin B from Marsdenia tenacissima (Roxb.) Wight et Arn reversed paclitaxel-induced MDR in vitro and in vivo by inhibiting both P-gp and MRP2.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima is a medicinal plant, used as a raw material for cancer treatment in China. In our previous studies, 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B (MT2), the main steroid aglycone isolated from M. tenacissima, was found to significantly enhance the antitumor activity of paclitaxel (PTX) in vivo. However, it is unclear whether MT2 reverses multidrug resistance (MDR) in tumors. AIM OF THE STUDY: To determine the role and mechanism of MT2 in reversing tumor MDR. MATERIALS AND METHODS: MDR cell line HeLa/Tax was established from the human cervical carcinoma cell line HeLa by long-term exposure to subtoxic concentrations of PTX and was used to evaluate the ability of MT2 to restore chemosensitivity of cells both in vitro and in a nude mouse model. The expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) was determined using western blotting and immunohistochemistry. The substrate transport function was assessed using an MDR function assay kit. The binding modes of MT2 and P-gp were determined using the conformation-sensitive anti-P-gp antibodies. The permeability and transport properties of MT2 were analyzed in Caco-2 cell monolayers. RESULTS: Compared to parental cells, HeLa/Tax cells overexpress P-gp and MRP2 and are approximately 100-360 fold more resistant to the anticancer drugs PTX, docetaxel, and vinblastine. MT2 at 5 or 10 µmol/L significantly increased the sensitivity of HeLa/Tax to these three anticancer drugs (18-56-fold decrease in IC50 value) and suppressed the expression of P-gp and MRP2. Knockdown of P-gp with small interfering RNA partially reversed MT2-induced sensitivity to PTX in HeLa/Tax cells. Moreover, MT2 directly inhibited P-gp-mediated substrate transport while interacting with membrane P-gp in non-substrate ways. MT2 was highly permeable and could not be transported in the Caco-2 cell monolayers. In nude mice bearing HeLa/Tax xenografts, the combination treatment with MT2 and PTX exerted a synergistic inhibitory effect on the growth of tumors and the expression of P-gp and MRP2 without increasing toxicity. CONCLUSION: MT2 is a potential agent for reversing MDR. It impedes membrane drug efflux pumps by suppressing P-gp and MRP2 expression, and directly inhibiting the transport function of P-gp.

An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia.

Xiebai San (XBS) is a traditional Chinese medicine (TCM) prescription that has been widely used to treat pediatric pneumonia since the Song dynasty. To reveal its underlying working mechanism, a network pharmacology approach was used to predict the active ingredients and potential targets of XBS in treating pediatric pneumonia. As a result, 120 active ingredients of XBS and 128 potential targets were screened out. Among them, quercetin, kaempferol, naringenin, licochalcone A and isorhamnetin showed to be the most potential ingredients, while AKT1, MAPK3, VEGFA, TP53, JUN, PTGS2, CASP3, MAPK8 and NF-κB p65 showed to be the most potential targets. IL-17 signaling pathway, TNF signaling pathway and PI3K-Akt signaling pathway, which are involved in anti-inflammation processes, immune responses and apoptosis, showed to be the most probable pathways regulated by XBS. UPLC-Q/Orbitrap HRMS analysis was then performed to explore the main components of XBS, and liquiritin, quercetin, kaempferol, licochalcone A and glycyrrhetinic acid were identified. Molecular docking analysis of the compounds to inflammation-associated targets revealed good binding abilities of quercetin, kaempferol, licochalcone A and liquiritin to NF-κB p65 and of quercetin and kaempferol to Akt1 or Caspase-3. Moreover, molecular dynamics (MD) simulation for binding of quercetin or kaempferol to NF-κB p65 revealed dynamic properties of high stability, high flexibility and lowbinding free energy. In the experiment with macrophages, XBS markedly suppressed the (Lipopolysaccharides) LPS-induced expression of NF-κB p65 and the production of pro-inflammatory cytokines IL-6 and IL-1ß, supporting XBS to achieve an anti-inflammatory effect through regulating NF-κB p65. XBS also down-regulated the expression of p-Akt (Ser473)/Akt, Bax and Caspase-3 and up-regulated the expression of Bcl-2, indicating that regulating Akt1 and Caspase-3 to achieve anti-apoptotic effect is also the mechanism of XBS for treating pediatric pneumonia. Our study helped to reveal the pharmacodynamics material basis as well as the mechanism of XBS in treating pediatric pneumonia.

RURAL LEFT-BEHIND CHILDREN ARE SERIOUSLY AFFLICTED WITH INTESTINAL HELMINTH INFECTIONS IN SOUTHERN SICHUAH, CHINA.

Rural children are seriously afflicted with intestinal helminth infections in China. Of note, the term rural children includes rural left-behind children (LBC) and rural non-left-behind children (NLBC); the difference in the prevalence of intestinal helminths between the 2 groups remains unclear. In this study, Gulin and Xuyong counties in southern Sichuan were chosen for investigation in 2019. The Kato Katz thick smear method was used to detect the presence of intestinal helminth eggs in rural children. For children aged 3-6 yr, the adhesive tape perianal swab method was used to detect Enterobius vermicularis and tapeworm eggs. Statistical differences in infection rates between the 2 groups were determined by the chi-square test. In total, 1,608 rural children, 911 LBC and 697 NLBC, participated in the investigation. Six species of intestinal helminths were detected. A total of 358 (39.3%) and 130 (18.7%) intestinal helminth positives were found among LBC and NLBC, respectively; the former had a higher (P < 0.05) infection level. Moreover, an analysis of double worm infection rates among intestinal helminth positive LBC and NLBC showed a difference between the 2 groups that was also statistically significant. These surveys indicated that the risk of intestinal helminth infection was substantially higher and the severity of infection much worse in rural LBC in southern Sichuan. More attention should be paid to the parasitic infection of LBC.

Clearance of HR-HPV within one year after focused ultrasound or loop electrosurgical excision procedure in patients with HSIL under 30.

OBJECTIVE: To compare the clearance rate of high-risk human papillomavirus (HR-HPV) in patients with a high-grade squamous intraepithelial lesion (HSIL) 12 months after focused ultrasound (FUS) or loop electrosurgical excision procedure (LEEP), and analyze the influencing factors. METHODS: A retrospective cohort was established in HSIL patients with HR-HPV infection treated with FUS or LEEP from 2015 to 2019. The cohort consisted of 321 patients under 30 years of age, of which 119 patients received FUS and 202 patients received LEEP. The Cox regression model was used to identify the influencing factors for HR-HPV clearance. Kaplan-Meier method was applied to estimate the efficacy of FUS and LEEP in HR-HPV clearance, and the log-rank test was used to compare the efficacy difference between FUS and LEEP. RESULTS: Multivariate Cox regression analysis showed that both FUS and LEEP were independent influencing factors for HR-HPV clearance. HR-HPV cleared faster in the FUS group than in the LEEP group [the median time to HR-HPV clearance: 6 months in the FUS group (95% CI: 5.492-6.508) and 6 months in the LEEP group (95% CI: 5.734-6.266), p = 0.021]. The HR-HPV clearance rates at 6 and 12 months were 54.6% and 94.1% respectively in the FUS group, and 50.5% and 79. 2%, respectively in the LEEP group (p = 0.001 at 6 months, p = 0.000 at 12 months). CONCLUSIONS: For HPV-positive HSIL patients under 30, FUS had a better HR-HPV clearance effect than LEEP 1 year after treatment. FUS may be a viable modality for the treatment of young HSIL patients.

Halotherapy relieves chronic obstructive pulmonary disease by alleviating NLRP3 inflammasome-mediated pyroptosis.

Background: Airway remodeling and inflammation are considered the main characteristics of chronic obstructive pulmonary disease (COPD). Cigarette smoke promotes the occurrence of inflammation, oxidative stress, and pyroptosis. Halotherapy has been shown to dilute secretions in the airways and promote drainage, but the mechanism remains unclear. In this study, we evaluated the anti-inflammatory and antioxidant effects of halotherapy in COPD rats and investigated the underlying mechanism. Methods: A COPD rat model was constructed by cigarette smoke and lipopolysaccharide tracheal instillation. A total of 120 male Sprague-Dawley (SD) rats were randomly divided into control, model, halotherapy, terbutaline, halotherapy + terbutaline, and Ac-YVAD-CMK (Caspase-1 inhibitor) groups. After modeling and treatment, the pulmonary function of the rats was measured. Pathological changes in the lungs were measured by hematoxylin-eosin (H&E) staining. Serum interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and nitric oxide (NO) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in the lungs were determined by biochemical tests. The levels of cluster of differentiation 4 (CD4+) and CD8+ T cells in the blood were determined by flow cytometry. The expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), gasdermin-D (GSDMD), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), Caspase-1, and IL-1ß in lung tissues were detected by immunohistochemistry, Western blotting, or quantitative polymerase chain reaction (qPCR). Results: Halotherapy recovered the clinical symptoms of COPD rats, and reduced lung inflammatory cell infiltration and air wall attenuation. It also relieved oxidative stress in the lung tissue of COPD rats, reduced CD4+ and CD8+ T cell accumulation in lung tissue, and decreased inflammatory factor production in the serum of COPD rats. Furthermore, it inhibited the TLR4/NF-κB/GSDMD and NLRP3/ASC/Caspase-1 signaling pathways. Ac-YVAD-CMK could not completely inhibit the therapeutic effect of halotherapy on COPD rats. Conclusions: Halotherapy improves lung function by inhibiting the NLRP3/ASC/Caspase-1 signaling pathway to reduce inflammation and pyroptosis in COPD rats, and may be a new option for the prevention and treatment of COPD.

Ultrasound Characteristics of Cystadenofibromas: A Retrospective Multicenter Study.

ABSTRACT: Cystadenofibromas (CAFs) are relatively rare benign ovarian tumors. This study was to describe the ultrasound (US) findings of CAFs. Preoperative US information of 86 CAFs was retrospectively collected. To better illustrate their characteristic, 173 cystadenomas (CADs), 103 borderline ovarian tumors (BOTs), and 129 cystadenocarcinomas (CACs) were recruited as match groups. Besides morphology evaluation, tumors were categorized by the Ovarian-Adnexal Reporting and Data System US system. Higher-risk stratification in CAFs was more often being seen than CADs (63% of CAFs classified as Ovarian-Adnexal Reporting and Data System 4 or 5 vs 35% in CADs). Cystadenofibromas more commonly appeared as unilocular or multilocular solid than CADs. Solid components presented in 59% of CAFs and papillary projections presented in 45%. More CAFs contained solid components and papillary projections than CADs (P < 0.0001). When compared with BOTs and CACs, less CAFs contained solid components (P < 0.017 and P < 0.0001). However, no significant difference was found in CAFs versus BOTs or CACs about the presence of papillary projections. Shadowing was identified in 58% of CAFs; however, in CADs, BOTs, and CACs, the proportion was 2%, 11%, and 11%, respectively. Presence of shadowing in CAFs was noticeably more than CADs, BOTs, and CACs (P < 0.017 or P < 0.0001). Similar to CADs, most CAFs were avascular (76%) and without ascites (99%), which were significantly different from BOTs and CACs. We concluded that the sonographic markers for CAFs that differ from malignant were presence of shadowing, avascular, and absence of ascites.

Gut Microbiome: A Potential Indicator for Differential Diagnosis of Major Depressive Disorder and General Anxiety Disorder.

Background: Major depressive disorder (MDD) and general anxiety disorder (GAD) share many common features, leading to numerous challenges in their differential diagnosis. Given the importance of the microbiota-gut-brain axis, we investigated the differences in gut microbiota between representative cases of these two diseases and sought to develop a microbiome-based approach for their differential diagnosis. Methods: We enrolled 23 patients with MDD, 21 with GAD, and 10 healthy subjects (healthy crowd, HC) in the present study. We used 16S rRNA gene-sequencing analysis to determine the microbial compositions of the gut microbiome based on Illumina Miseq and according to the standard protocol. Results: GAD showed a significant difference in microbiota richness and diversity as compared with HC. Additionally, Otu24167, Otu19140, and Otu19751 were significantly decreased in MDD relative to HC, and Otu2581 and Otu10585 were significantly increased in GAD relative to MDD. At the genus level, the abundances of Sutterella and Fusicatenibacter were significantly lower in MDD relative to HC, and the abundances of Fusicatenibacter and Christensenellaceae_R7_group were significantly lower in GAD than in HC. The abundance of Sutterella was significantly higher whereas that of Faecalibacterium was significantly lower in GAD relative to MDD. Moreover, we observed that Christensenellaceae_R7_group negatively correlated with the factor score (Limited to Hopelessness) and total score of HAMD-24 (p < 0.05), whereas Fusicatenibacter negatively correlated with FT4 (p < 0.05). Furthermore, the GAD group showed significant differences at the genus level for Faecalibacterium, which negatively correlated with PTC (p < 0.05). Conclusions: This study elucidated a unique gut-microbiome signature associated with MDD and GAD that could facilitate differential diagnosis and targeted therapy.

Pharmacokinetics, plasma protein binding, and metabolism of a potential natural chemosensitizer from Marsdenia tenacissima in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima (Roxb.) Wight et Arn is a medicinal plant mainly distributed in southwest China. It is used in folk medicine for the treatment of tumors and is synergistic with chemotherapies. In our previous study, 11α-O-2-methybutyryl-12ß-O-tigloyl-tenacigenin B (MT2), a main steroid aglycone isolated from the total aglycones of M. tenacissima, significantly enhanced the in vivo antitumor effect of paclitaxel in mice bearing human tumor xenografts, showing its potential as a chemosensitizer. However, the pharmacokinetic characteristics, plasma protein binding rate, and metabolic profile of MT2 remain unclear. AIM OF THE STUDY: To elucidate the pharmacokinetic characteristics, plasma protein binding rate, and metabolic profile of MT2 in rats. MATERIALS AND METHODS: MT2 in rat plasma and phosphate-buffered saline was quantified using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, while the MT2 metabolites in rat liver microsomes were analyzed using UPLC-triple time-of-flight MS/MS. RESULTS: For intravenously administered MT2, the maximum plasma concentration and the area under the plasma concentration-time curve indicated dose dependency, while the elimination half-life time, the mean residence time, apparent volume of distribution and total apparent clearance values remained relatively unchanged in both the 5 mg/kg and 10 mg/kg groups. For orally administered MT2, the bioavailability was 1.08-1.11%. In rat plasma, MT2 exhibited a protein binding rate of 93.84-94.96%. In rat liver microsomes, MT2 was metabolized by oxidation alone or in combination with demethylation, and five MT2 metabolites were identified. CONCLUSION: MT2 has low oral bioavailability and a high plasma protein binding rate in rats. After administration, MT2 is transformed into oxidative metabolites in the liver. To achieve a high blood concentration of MT2, it should be administered intravenously. These findings would serve as a reference for further MT2-based pharmacological study and drug development.