Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis ...(EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin−) Sca‐1+ c‐Kit+ haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY‐treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY‐treated mice. Moreover, the number of c‐Kit+ HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c‐Kit+ HSPCs was only up‐regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY‐treated mice. We also found that a fraction of c‐Kit+/CD45+ HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY‐treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow.
Subjective cognitive decline (SCD) may be the early screening signal to distinguish susceptible population with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Subjective cognitive ...complaints (SCCs) have been proved strongly associated with SCD. This study aimed to explore the association between sleep duration and SCCs in the Chinese elderly.
We conducted a cross-sectional study involving 688 participants aged 60 years and older in Guangdong Province, China. SCCs were assessed by the Subjective Cognitive Decline questionnaire 9 (SCD-Q9), which contained 9 items with two dimensions, including the overall memory function and time comparison (OMTC) and daily activity ability (DAA). Restricted cubic splines and generalized additive model (GAM) were used to fit the association between sleep duration and SCD-Q9 score.
There were significant U-shaped associations between sleep duration and overall score of SCD-Q9 (EDF = 3.842, P < 0.001), as well as the OMTC dimension (EDF = 4.471, P < 0.001) in the age- and gender-adjusted GAM. The lowest points on the overall score of SCD-Q9 and OMTC score were observed in those sleeping 8 h per night. After further adjusting for other demographic characteristics, lifestyle behaviors, hypertension and diabetes, the U-shaped associations between sleep duration and the overall score of SCD-Q9 (EDF = 3.575, P = 0.004), sleep duration and the OMTC score (EDF = 4.478, P = 0.010) were still found. The daily activity ability (DAA) score was also non-linear associated with sleep duration both in the age- and gender-adjusted GAM (EDF = 2.314, P < 0.001) and further adjusted GAM (EDF = 2.080, P = 0.010).
Both longer sleep duration (> 8 h) and shorter duration (< 8 h) were linked to worse SCCs. Future studies should explore the protective effect of managing sleep duration on SCD and its progression to dementia.
The activation of dinitrogen (N2) and direct incorporation of its N atom into C–H bonds to create aliphatic C–N compounds remains unresolved. Incompatible conditions between dinitrogen reduction and ...C–H functionalization make this process extremely challenging. Herein, we report the first example of dinitrogen insertion into an aliphatic Csp 3–H bond on the ligand scaffold of a 1,3-propane-bridged N2N2–-type dititanium complex. Mechanistic investigations on the behaviors of dinuclear and mononuclear Ti complexes indicated the intramolecular synergistic effect of two Ti centers at a C–N bond-forming step. Computational studies revealed the critical isomerization between the inactive side-on N2 complex and the active nitridyl complex, which is responsible for the Csp 3–H amination. This strategy maps an efficient route toward the future synthesis of aliphatic amines directly from N2.
The purpose of this study was to explore the prognostic value of imaging features and related models in nasopharyngeal carcinoma (NPC) patients that received neoadjuvant chemotherapy.
We ...systematically reviewed the data of 110 NPC patients who received radiotherapy and neoadjuvant chemotherapy. The patients were randomly divided into the training cohort (n = 88) and the verification cohort (n = 22). The imaging data collected in this study were screened via Pyramidics and used to construct prediction models based on histology and clinical nomographs. The models' accuracy was evaluated via calibration curves and the consistency index (C-index). In addition, we also explored the correlation between radiomics expression patterns, quantitative histological characteristics, and clinical data and then constructed a model to predict the prognosis of NPC.
The models that integrated radiomics contours with all the clinical data were superior to those based on the clinical data alone (C-index 0.746 vs. C-index 0.814, respectively) and the calibration curves showed good consistency. The heat map showed that the radiomics expression pattern and selected histological characteristics were correlated with the clinical stage, T stage, and N stage (p < 0.05), and no radiomics feature was associated with lactate dehydrogenase expression, lymphocyte count, or mononuclear cell count.
MRI-based radiomics can significantly improve the efficacy of traditional TNM staging and clinical data in predicting the progression-free survival (PFS) of patients with advanced NPC, which may provide an opportunity for precision medicine.
This paper proposes an approach called block scaling quality (BSQ) for estimating the prediction accuracy of a deep network model. The basic operation perturbs the input spectrogram by multiplying ...all values within a block by , where is equal to 0 in the experiments. The ratio of perturbed spectrograms that have different prediction labels than the original spectrogram to the total number of perturbed spectrograms indicates how much of the spectrogram is crucial for the prediction. Thus, this ratio is inversely correlated with the accuracy of the dataset. The BSQ approach demonstrates satisfactory estimation accuracy in experiments when compared with various other approaches. When using only the Jamendo and FMA datasets, the estimation accuracy experiences an average error of 4.9% and 1.8%, respectively. Moreover, the BSQ approach holds advantages over some of the comparison counterparts. Overall, it presents a promising approach for estimating the accuracy of a deep network model.
Psoriasis is a chronic inflammatory skin disease that can significantly impact the quality of human life. Various drug treatments are available; however, due to their long-term severe side effects ...the usage of these drugs is limited. Photodynamic therapy (PDT) has been clinically approved for skin diseases due to its non-invasive nature. We present novel NNO-tridentate vanadium(
iv
) complexes used in PDT for anti-inflammatory effects in an imiquimod-induced psoriasis-like skin disease mouse model. The vanadium(
iv
) complexes (
1-4
) were synthesized using the NNO-tridentate ligand with a benzo
i
dipyrido3,2-
a
;2′,3′-
c
phenazine (dppn) moiety, and were characterized by UV/Visible spectroscopy, EPR spectroscopy, NMR (
1
H, and
13
C) spectroscopy, electrospray ionization mass (ESI-MS) spectrometry and cyclic voltammetry (CV) studies. The photocytotoxicity of vanadium(
iv
) complexes (
1-4
) was low under dark conditions and complex (
4
) showed remarkable photocytotoxicity under blue light (430 nm, 8 W cm
−2
, 30 min) irradiation. Moreover, VO(
t
-butylL)(dppn) (
4
)-mediated PDT down-regulated inflammatory cytokines IL-17A and IL-22 in the psoriasis-like mouse model, which could evidence the significant relieving of the psoriatic-like symptoms in the mouse model. Overall, these results suggested that VO(
t
-butylL)(dppn) (
4
) could be a potential candidate for the treatment of psoriasis both
in vitro
and
in vivo
.
In a psoriasis-like mice model, NNO-tridentate vanadium(
iv
) complexes were synthesized for photodynamic therapy.
Aberrant NLRP3 activation has been implicated in the pathogenesis of numerous inflammation-associated diseases. However, no small molecular inhibitor that directly targets NLRP3 inflammasome has been ...approved so far. In this study, we show that Atranorin (C
H
O
), the secondary metabolites of lichen family, effectively prevents NLRP3 inflammasome activation in macrophages and dendritic cells. Mechanistically, Atranorin inhibits NLRP3 activation induced cytokine secretion and cell pyroptosis through binding to ASC protein directly and therefore restraining ASC oligomerization. The pharmacological effect of Atranorin is evaluated in NLRP3 inflammasome-driven disease models. Atranorin lowers serum IL-1β and IL-18 levels in LPS induced mice acute inflammation model. Also, Atranorin protects against MSU crystal induced mice gouty arthritis model and lowers ankle IL-1β level. Moreover, Atranorin ameliorates intestinal inflammation and epithelial barrier dysfunction in DSS induced mice ulcerative colitis and inhibits NLRP3 inflammasome activation in colon. Altogether, our study identifies Atranorin as a novel NLRP3 inhibitor that targets ASC protein and highlights the potential therapeutic effects of Atranorin in NLRP3 inflammasome-driven diseases including acute inflammation, gouty arthritis and ulcerative colitis.
Few large-scale studies have demonstrated the efficacy of tobramycin nebulization in bronchiectasis. We evaluated the efficacy and safety of nebulized tobramycin inhalation solution (TIS) in adults ...with bronchiectasis with Pseudomonas aeruginosa infection.
Can TIS effectively reduce sputum P aeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with P aeruginosa infection?
This was a phase 3, 16-week, multicenter, randomized, double-blind, placebo-controlled trial. Eligible adults with bronchiectasis were recruited from October 2018 to July 2021. On the basis of usual care, patients nebulized TIS (300 mg/5 mL twice daily) or normal saline (5 mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28 days on-treatment and 28 days off-treatment. The coprimary end points included changes from baseline in P aeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day 29.
The modified intention-to-treat population consisted of 167 patients in the tobramycin group and 172 patients in the placebo group. Compared with placebo, TIS resulted in a significantly greater reduction in P aeruginosa density (adjusted mean difference, 1.74 log10 colony-forming units/g; 95% CI, 1.12-2.35; P < .001) and greater improvement in Quality-of-Life Bronchiectasis Respiratory Symptoms score (adjusted mean difference, 7.91; 95% CI, 5.72-10.11; P < .001) on day 29. Similar findings were observed on day 85. TIS resulted in a significant reduction in 24-h sputum volume and sputum purulence score on days 29, 57, and 85. More patients became culture negative for P aeruginosa in the tobramycin group than in the placebo group on day 29 (29.3% vs 10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups.
TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with P aeruginosa infection.
ClinicalTrials.gov; No. NCT03715322; URL: www.clinicaltrials.gov
Display omitted
Background
Mental health literacy (MHL) is rarely reported in the Chinese elderly. This study explored the pattern of MHL in the Chinese elderly in relation to depression, anxiety and poor sleep ...quality.
Methods
A cross‐sectional study was conducted among older adults in Guangzhou, south China. Participants were investigated face‐to‐face using the Chinese National Mental Health Literacy Scale, the Patient Health Questionnaire‐9 item (PHQ‐9), the 7‐item Generalized Anxiety Disorder (GAD‐7) and the Pittsburgh Sleep Quality Index (PSQI). Mental Health Literacy Scale contains three dimensions: mental health knowledge, mental health skills (such as social support, cognitive reappraisal and attentional distraction) and mental health awareness. Multivariate logistic regression was used for examining the association between MHL and mental health.
Results
A total of 506 older adults were recruited. The percentage of depression, anxiety, and poor sleep quality were 16.6%, 7.9% and 40.9%, respectively. MHL dimensions independently associated with depression included cognitive reappraisal (OR = 1.95, p < .001), attentional distraction (OR = 0.61, p = 0.044) and awareness (OR = 0.56, p = 0.027). MHL dimensions independently associated with anxiety symptoms included cognitive reappraisal (OR = 1.90, p = 0.011) and attentional distraction (OR = 0.44, p = 0.016). MHL dimensions independently associated with poor sleep quality included social support (OR = 0.75, p = 0.022), cognitive reappraisal (OR = 1.55, p = 0.003) and attentional distraction (OR = 0.65, p = 0.016).
Conclusion
Given the low MHL and its association with poor mental health in the Chinese elderly, policymakers and health professionals should improve the older adults' MHL, which could be conducive to the prevention and control of their mental health problems.
Depression and insomnia are highly related-insomnia is a common symptom among depression patients, and insomnia can result in depression. Although depression patients and insomnia patients should be ...treated with different approaches, the lack of practical biological markers makes it difficult to discriminate between depression and insomnia effectively.
This study aimed to disclose critical vocal features for discriminating between depression and insomnia.
Four groups of patients, comprising six severe-depression patients, four moderate-depression patients, ten insomnia patients, and four patients with chronic pain disorder (CPD) participated in this preliminary study, which aimed to record their speaking voices. An open-source software, openSMILE, was applied to extract 384 voice features. Analysis of variance was used to analyze the effects of the four patient statuses on these voice features.
statistical analyses showed significant relationships between patient status and voice features. Patients with severe depression, moderate depression, insomnia, and CPD reacted differently to certain voice features. Critical voice features were reported based on these statistical relationships.
This preliminary study shows the potential in developing discriminating models of depression and insomnia using voice features. Future studies should recruit an adequate number of patients to confirm these voice features and increase the number of data for developing a quantitative method.
PDF
