CD14-CD10-CD45+HLA-DR-SSC+ neutrophils may be granulocytic myeloid-derived suppressor cell-like cells and relate to disease progression in non-Hodgkin's lymphoma patients.

We explored the frequency of CD14-CD10-CD45+HLA-DR-SSC++ neutrophils (CD10- neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10- neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10- and CD10+ neutrophils were sorted, and their cytology was analyzed. CD3+ T cells were also isolated and cultured with the autologous CD10- or CD10+ neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase-1 (Arg-1) and reactive oxygen species (ROS) in CD10+ or CD10- neutrophils were examined. Few CD10- neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10- neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse-free survival and overall survival in patients with high CD10- neutrophils were shorter than those with low CD10- neutrophils. CD10- neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T-cell proliferation and facilitate T-cell death. Furthermore, a significant increase was observed in Arg-1 expression, along with an increase to a certain extent in ROS. CD10- neutrophils in patients with NHL have characteristics of myeloid-derived suppressor cells and may be related to disease progression and poor prognosis.

A multicenter, randomized, double-blinded, placebo-controlled, phase â ¢ study evaluating the efficacy and safety of Xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

DNT cells mediate resistance to CAR-T cells therapy in a pediatric patient with relapsed and refractory B-ALL.

Chimeric antigen receptor T (CAR-T) cells therapy is a milestone achievement in the immunotherapy of relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). However, some patients treated with CAR-T cells do not achieve complete remission, the mechanisms of which have not been elucidated. In the present study, we report a 9-year-old pediatric patient with refractory B-ALL received a triple infusion of autologous CD19 CAR-T cells therapy after the second relapse. CAR-T cells expanded in the peripheral blood and bone marrow. However, the patient did not achieve complete remission, indicating a lack of response to CAR-T cells therapy. Analysis of etiological factors revealed that the number of CD4 and CD8 double-negative T (DNT) cells was significantly upregulated in the peripheral blood, bone marrow, and autologous CAR-T cells products. In conclusiont, these findings indicate that DNT cells mediated resistance to CAR-T cells therapy in this pediatric patient with R/R B-ALL.

A Retrospective Cohort Study on the Comorbidity in 19,264 Chinese Patients of Different Ages with Urticaria.

To examine the prevalence of comorbidities in Chinese urticaria patients and assess medication use patterns across different ages (6-11 years, 12-17 years, above 18 years), a retrospective cohort study was performed in 192,647 urticaria patients within the Health Database. After 1:1 propensity score matching, 166,921 people were divided into the urticaria group and the control group, and the follow-up data were collected within 2 years. During the 12-month and 24-month follow-up period, significant comorbidities identified included allergic rhinitis and asthma, with distinct patterns observed across age groups. Chronic urticaria patients often have complications, such as allergic rhinitis, upper respiratory infection, oropharyngeal infection, and dental caries. The study underscores the need for age-specific treatment strategies in urticaria management.

Integrated metabolomics and proteomics analysis to understand muscle atrophy resistance in hibernating Spermophilus dauricus.

Hibernating Spermophilus dauricus experiences minor muscle atrophy, which is an attractive anti-disuse muscle atrophy model. Integrated metabolomics and proteomics analysis was performed on the hibernating S. dauricus during the pre-hibernation (PRE) stage, torpor (TOR) stage, interbout arousal (IBA) stage, and post-hibernation (POST) stage. Time course stage transition-based (TOR vs. PRE, IBA vs. TOR, POST vs. IBA) differential expression analysis was performed based on the R limma package. A total of 14 co-differential metabolites were detected. Among these, l-cystathionine, l-proline, ketoleucine, serine, and 1-Hydroxy-3,6,7-Trimethoxy-2, 8-Diprenylxanthone demonstrated the highest levels in the TOR stage; Beta-Nicotinamide adenine dinucleotide, Dihydrozeatin, Pannaric acid, and Propionylcarnitine demonstrated the highest levels in the IBA stage; Adrenosterone, PS (18:0/14,15-EpETE), S-Carboxymethylcysteine, TxB2, and 3-Phenoxybenzylalcohol demonstrated the highest levels in the POST stage. Kyoto Encyclopedia of Genes and Genomes pathways annotation analysis indicated that biosynthesis of amino acids, ATP-binding cassette transporters, and cysteine and methionine metabolism were co-differential metabolism pathways during the different stages of hibernation. The stage-specific metabolism processes and integrated enzyme-centered metabolism networks in the different stages were also deciphered. Overall, our findings suggest that (1) the periodic change of proline, ketoleucine, and serine contributes to the hindlimb lean tissue preservation; and (2) key metabolites related to the biosynthesis of amino acids, ATP-binding cassette transporters, and cysteine and methionine metabolism may be associated with muscle atrophy resistance. In conclusion, our co-differential metabolites, co-differential metabolism pathways, stage-specific metabolism pathways, and integrated enzyme-centered metabolism networks are informative for biologists to generate hypotheses for functional analyses to perturb disuse-induced muscle atrophy.

Nail psoriasis in China: A prospective multicentre study.

BACKGROUND: Data on nail psoriasis (PsO) in China are scarce. OBJECTIVES: To provide nail PsO-related data regarding epidemiologic characteristics, manifestations, fungal infections, arthritic complaints and treatments that may facilitate improved patient management globally. METHODS: From August 2021 to August 2022, patients with nail PsO were enrolled in a prospective multicentre observational study at 25 hospitals in China. We collected and analysed data concerning nail PsO demography, clinical signs, fungal detection, arthritic symptoms and treatment. RESULTS: A total of 817 patients with nail PsO were involved, with a mean body mass index of 24.13 ± 2.93. In addition, 71.41% of the patients were male. The Nail PsO Severity Index score was weakly positively correlated with body surface area. The percentage of nail involvement was 95.29% for fingernails and 57.18% for toenails, with pitting (67.11%) and subungual hyperkeratosis (60.40%) being the most prevalent manifestations, respectively. Toenails showed a significantly higher frequency of nailfold scales, subungual hyperkeratosis and nail plate crumbling and a lower frequency of splinter haemorrhages, pitting and erythema of the lunula. A total of 13.26% of the PsO patients had onychomycosis, and 77.08% were observed in the toenails. Articular symptoms were reported by 12.17% of the patients, with the peripheral type being predominant. Significant associations between articular symptoms and nailfold swelling, subungual hyperkeratosis, nailfold scales, onycholysis and longitudinal ridges were found. Only 2.30% (20 out of 871) of patients with nail PsO received treatment. The most frequently employed therapy for cutaneous PsO with nail involvement was biologic therapy (n = 366). CONCLUSIONS: PsO showed distinct manifestations in the toenails and fingernails. Additionally, toenail PsO combined with onychomycosis requires special attention. Articular symptoms in psoriatic patients are associated with specific nail changes. It is important to research and advocate for more potent treatments for nail PsO.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Targeted inhibition of biogenic amine-producing strains by spice extracts and control of biogenic amine accumulation in reduced-salt dry sausages.

This study aimed to screen spice extracts that can target the inhibition of biogenic amine (BA)-producing bacteria and reduce the BA accumulation in reduced-salt dry sausages. A total of 59 bacterial strains were isolated from reduced-salt dry sausages; among them, three isolates, namely, Staphylococcus epidermidis S1, S. saprophyticus S2, and S. edaphicus S3, had the strongest ability to produce BA. Eight spice extracts, i.e. Angelica dahurica, cinnamon, ginger, clove, fennel, Amomum, nutmeg, and orange peel, were extracted. The inhibition zone diameter and minimum inhibitory concentration indicated that A. dahurica, Amomum, and clove elicited the strongest inhibitory effect on BA-producing strains. Growth kinetics showed the strongest inhibitory effect of clove extracts, followed by Amomum and A. dahurica. In the medium system, clove extract was the most effective in controlling the total BA content by inhibiting of BA-producing strains S. epidermidis S1, S. saprophyticus S2, and S. edaphicus S3; their contents were reduced by 23.74%, 31.05% and 21.37%, respectively. In the dry sausage system, the control of BA accumulation by clove was quite prominent, and the total BA content was reduced from 373.70 mg/kg to 259.05 mg/kg on day 12.

Perceived professional preparedness and identity among senior nursing students: a latent profile Analysis.

BACKGROUND: Senior nursing students' perceptions of their professional preparedness help them for expectations of their future nursing role with more confidence, and professional identity may contribute to cultivating nursing students' perceptions of professional preparedness. In this study we applied latent profile analysis to identify the latent profiles of perceived professional preparedness among senior nursing students and to examine their identity and predictors. METHODS: This was a cross-sectional descriptive study. A total of 319 senior nursing students from five universities in China were enrolled. Data were collected using the Perceived Professional Preparedness of Senior Nursing Students' Questionnaire and the Professional Identity Scale for Nursing Students. RESULTS: Three latent profiles were identified and labeled as "low perceived professional preparedness" (n = 90, 28.2%), "low clinical competency-low EBP (Evidence-Based Practice)" (n = 190, 59.5%), and "high perceived professional preparedness" (n = 39, 12.2%). Place of residence, average clinical practicum hours per day, part-time experience, good relationships with classmates, and feeling nobility toward nursing due to COVID-19 significantly predicted profile membership. The average professional identity score was also statistically different across the three profiles (F = 54.69, p < 0.001). CONCLUSIONS: Senior nursing students' perceptions of their professional preparedness were divided into three profiles, and out results show that promoting professional identity may effectively foster their perceived professional preparedness. This study therefore highlights the importance of targeted interventions by considering their distinct perceptions of professional preparedness patterns.

Prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in acute myeloid leukemia.

Wilms tumor gene 1 (WT-1 gene) is overexpressed in most patients with acute myeloid leukemia (AML) and is an indicator for minimal residual disease (MRD) monitoring, but because the WT-1 gene has relatively low specificity, further studies of the prognostic value of a combination of the WT-1 and other genes are needed. The aim of this study was to explore the prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in AML. In AML, the transcript expression of the WT-1 gene was closely related to leukemic tumor burden and acted as an accurate molecular indicator for MRD detection. Most patients with low expression levels of the WT-1 gene after induction and consolidation therapy were significantly associated with favorable relapse-free survival (RFS) and overall survival (OS), but 17.6% of patients relapsed and died of primary disease. However, when analyzing the WT-1 gene combined with recurrent cytogenetic genes, none of the patients with low expression levels of the WT-1 gene and recurrent cytogenetic genes negative relapsed and died in the median follow-up time of 19 months (range: 3-94 months). Thus, the combination of the WT-1 gene and recurrent cytogenetic genes is a more accurate indicator for MRD monitoring and prognosis evaluation in AML patients.

Immune characteristics and prognostic implications of mucosal-associated invariant T cells in acute myeloid leukemia.

Increasing evidence suggests that mucosal-associated invariant T cells (MAITs) play a crucial role in anti-tumor responses against various cancers. In this study, we investigated the immune characteristics of MAIT cells in patients with acute myeloid leukemia (AML). Using multi-parameter flow cytometry, we performed phenotypic and functional analysis of MAITs in peripheral blood or bone marrow samples collected from 131 patients with AML including 99 newly diagnosed, 18 remission, and 14 relapsed cases, as well as 69 healthy controls. We found that MAITs exhibit signs of aging and exhaustion, particularly in CD8+ MAITs subset, at newly diagnosis. MAITs exhibit an effector memory or terminally differentiated phenotype. Frequency and number of MAITs reflect AML cell genetic features, tumor burden, disease status, and treatment responsiveness. Moreover, MAITs exhibit a highly activated or even exhausted state, as indicated by upregulation of PD-1. Furthermore, impaired production of Th1-type cytokines and increased secretion of Th17-type cytokines, granzyme B, and perforin were observed in MAITs from AML patients. Additionally, MAITs shifted toward producing cytokines that promote tumor progression, such as IL-8. Lower frequency of MAITs was associated with poorer overall survival (OS), and multivariate analysis revealed that MAITs frequency < 2.12% was an independent prognostic factor affecting OS. Collectively, our findings suggest that MAITs may play a role in immune deficiency in AML, emphasizing their potential importance in AML pathogenesis and treatment. These discoveries provide a theoretical basis for the development of novel immunotherapeutic strategies in AML.

Nucleic Acid Detection through RNA-Guided Protease Activity in Type III-E CRISPR-Cas Systems.

RNA-guided protease activity was recently discovered in the type III-E CRISPR-Cas systems (Craspase), providing a novel platform for engineering a protein probe instead of the commonly used nucleic acid probe in nucleic acid detection assays. Here, by adapting a fluorescence readout technique using the affinity- and fluorescent protein dual-tagged Csx30 protein substrate, we have established an assay monitoring Csx30 cleavage by target ssRNA-activated Craspase. Four Craspase-based nucleic acid detection systems for genes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), norovirus, and the influenza virus (IFV) were reconstituted with demonstrated specificity. The assay could reliably detect target ssRNAs at concentrations down to 25 pM, which could be further improved approximately 15 000-fold (ca. 2 fM) by incorporating a recombinase polymerase isothermal preamplification step. Importantly, the species-specific substrate cleavage specificity of Craspase enabled multiplexed diagnosis, as demonstrated by the reconstituted composite systems for simultaneous detection of two genes from the same virus (SARS-CoV-2, spike and nsp12) or two types of viruses (SARS-CoV-2 and IFV). The assay could be further expanded by diversifying the fluorescent tags in the substrate and including Craspase systems from various species, thus potentially providing an easily adaptable platform for clinical diagnosis.

Effect of a moderate CYP3A inducer efavirenz on the pharmacokinetics of fuzuloparib: An open-label, fixed sequence study in Chinese healthy male subjects.

To evaluate the potential drug-drug interaction (DDI), safety and tolerability of fuzuloparib co-administered with a moderate CYP3A inducer efavirenz in healthy male subjects. Eighteen healthy male subjects were enrolled in a single-center, single-arm, open-label, fixed-sequence study. Fuzuloparib was administered as a single oral 50 mg under a fasting state on day 1, efavirenz (600 mg once daily) was given on days 4-17 before bed time, concomitantly with fuzuloparib on day 18, and for the follow-up 3 additional days (days 19-20). Pharmacokinetic sampling was performed following each fuzuloparib dose. Safety and tolerability were assessed during the whole process via clinical laboratory tests. Ratios of least-squares means (GMRs) and 90% geometric confidence interval (90% CI) of maximum plasma concentration (Cmax), the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC0 - t) and the area under the curve of blood concentration from zero to infinity (AUC0-∞) for fuzuloparib combined with efavirenz to fuzuloparib alone were 0.473 (0.394, 0.568), 0.220 (0.185, 0.263) and 0.221 (0.185, 0.263), respectively. Co-administration with efavirenz led to 53% and 78% decreases in fuzuloparib Cmax and AUC0-∞. All 18 subjects enrolled in this study were included in the safety analysis set. A total of 16 subjects had 62 AEs during the study period. No serious adverse events (SAE) were reported. Most treatment-emergent adverse events were grade 1 or 2 based on CTCAE. Only one grade 3 adverse event was observed. Concomitant intake of fuzuloparib with the moderate CYP3A inhibitor efavirenz resulted in a decrease in fuzuloparib AUC0-∞ and Cmax of 78% and 53% respectively. The results suggested that concomitant moderate CYP3A inducers should be avoided during the administration of fuzuloparib, or else the dosage adjustments should be required. (This trial was registered at http://www.chinadrugtrials.org.cn . The registration No. is CTR20211022, and the date of registration is 2021-05-13).

Prognostic value of combined WT1 and multiparameter flow cytometry assessment for measurable residual disease after induction in non-APL acute myeloid leukemia.

The objective of this study was to investigate the expression pattern of Wilms tumor 1 (WT1) gene at diagnosis, complete remission (CR) and relapse status in non-acute promyelocytic leukemia (non-APL) acute myeloid leukemia (AML) patients, and further explore the prognostic value of measurable residual disease (MRD) assessment by WT1 gene and multiparameter flow cytometry (MFC). Our results showed that the average expression level of WT1 was 4026 ± 616.1 copies/104 ABL at diagnosis, 155.3 ± 36.03 copies/104 ABL at CR, and 1766 ± 238.8 copies/104 ABL at relapse, with statistically significant differences (p = .000). ROC analysis showed that WT1 expression levels were 118.1 copies/104 ABL and MFC-MRD was 0.155%, which had good predictive efficacy for relapse of patients during consolidation therapy. Both WT1-MRD and MFC-MRD had a significant impact on relapse-free survival (RFS) and overall survival (OS). Patients with WT1-MRD positive or MFC-MRD positive were associated with worse RFS (HR 3.840, 95% CI 1.582-9.320, p = .003), (HR 4.464, 95% CI 1.841-10.984, p = .001) and worse OS (HR 2.963, 95% CI 1.058-8.295, p = .039), (HR 3.590, 95% CI 1.254-10.280, p = .017). Besides, compared with patients who were negative for both WT1-MRD and MFC-MRD, patients who were positive both WT1-MRD and MFC-MRD were associated with worse RFS (HR 6.200, 95% CI 2.206-17.430, p = .001) and worse OS (HR 4.886, 95% CI 1.388-17.197, p = .013). This study demonstrates that combined assessment of MRD by WT1 and MFC improves relapse and prognosis prediction in non-APL AML patients, and may help guide interventions for disease relapse.

Transcriptomic and proteomic time-course analyses based on Metascape reveal mechanisms against muscle atrophy in hibernating Spermophilus dauricus.

Hibernating Spermophilus dauricus is resistant to muscle atrophy. Comprehensive transcriptome and proteome time-course analyses based on Metascape can further reveal the underlying processes (pre-hibernation stage, PRE; torpor stage, TOR; interbout arousal stage, IBA; and post-hibernation stage, POST). Transcriptome analysis showed that the cellular responses to growth factor stimulus and discrete oxygen levels continuously changed during hibernation. Proteomic analysis showed that neutrophil degranulation, sulfur compound metabolic process, and generation of precursor metabolites and energy continuously changed during hibernation. Molecular complex detection (MCODE) analysis in both transcriptome and proteome indicated that smooth muscle contraction was involved in the POST versus IBA stage, and peroxisome proliferator-activated receptor delta (Ppard), Myc proto-oncogene (Myc), Sp1 transcription factor (Sp1), and nuclear factor Kappa B subunit 1 (NFκB1) are the common TFs during the hibernation process. Integrated transcriptome and proteome analyses found 18 molecules in the TOR versus PRE stage, 1 molecule in the IBA versus TOR stage, and 16 molecules in the POST versus IBA stage. Among these molecules, carnitine palmitoyltransferase 1A (Cpt1a), SET and MYND domain containing 2 (Smyd2), four and a half LIM domains 1(Fhl1), reactive oxygen species modulator 1 (Romo1), and translocase of the inner mitochondrial membrane 50 (Timm50) were testified by Western blot. In conclusion, novel muscle atrophy resistance mechanisms can be deciphered by time-course transcriptome and proteome analyses based on Metascape.

Weakened Contractile Performance and Mitochondrial Respiratory Complex Activity in Skeletal Muscle Improve during Interbout Arousal in Hibernating Daurian Ground Squirrel, Spermophilus dauricus.

Mammalian hibernation is composed of multiple episodes of torpor bout, separated by phases of interbout arousal. During torpor, the skeletal muscles of mammals are undoubtedly inactive, but it has been proven to mitigate disuse atrophy. While interbout arousal has been implicated in the prevention of muscle atrophy, the underlying mechanisms sustaining muscle contraction remain to be explored. In the present study, Daurian ground squirrels (Spermophilus dauricus) were divided into four groups: pre-hibernation (PRE), torpor (TOR), interbout arousal (IBA), and post-hibernation (POST). The contractile performance of slow-twitch soleus muscle (SOL) and fast-twitch extensor digitorum longus muscle (EDL) was detected both in situ and in vitro. Concurrently, mitochondrial respiratory chain complex activity in these muscles was quantified. Our findings revealed that in situ contractile properties of both muscles, including force, power output, time duration, and force development/relaxation rates of twitch contraction, and force and power output of tetanic contraction declined in the TOR group compared to the PRE group, but improved in the IBA and POST groups. Fatigue resistance of muscles, determined by the power output of repetitive tetanic contractions in situ, decreased in the TOR group but recovered in the IBA and POST groups. In vitro studies demonstrated that tetanic contraction power output in isolated muscles increased with muscle temperature in both TOR and IBA groups. However, at the same temperature, power output was consistently lower in the TOR group compared to the IBA group. Moreover, the activity of the mitochondrial respiratory chain complex, especially Complexes I and II, decreased in the TOR group but showed recovery in the IBA and POST groups. These findings suggest that both the contractile performance and fatigue resistance of mammalian skeletal muscle are compromised during torpor but can be improved during interbout arousal and post-hibernation. The rebound in body temperature and rise in mitochondrial respiratory chain complex activity in skeletal muscle are involved in enhancing contractile performance and fatigue resistance. This study suggests that interbout arousal functions as a vital temporal interval during which skeletal muscles can transition from the inactivity induced by torpor to a state of restored contractile functionality. Thus, interbout arousal serves as a behavioral safeguard against disuse-induced damage to skeletal muscles during hibernation.

The mediating effects of attitude toward death and meaning of life on the relationship between perception of death and coping with death competence among Chinese nurses: a cross-sectional study.

BACKGROUND: It is important to understand how the perception of death affects the competence to cope with death. OBJECTIVES: To explore whether the perception of death has an indirect effect on competence to cope with death through the mediation of attitude toward death and meaning of life. METHODS: A total of 786 nurses from Hunan Province, China, selected by random sampling method and asked to complete an online electronic questionnaire between October and November 2021 were included in the study. RESULTS: The nurses' scored 125.39 ± 23.88 on the competence to cope with death. There was a positive correlation among perception of death, competence to cope with death, the meaning of life, and attitude toward death. There were three mediating pathways: the separate mediating effect of natural acceptance and meaning of life, and the chain mediating effect of natural acceptance and meaning of life. CONCLUSION: The nurses' competence to cope with death was moderate. Perception of death could indirectly and positively predict nurses' competence to cope with death by enhancing natural acceptance or sense of meaning in life. In addition, perception of death could improve natural acceptance and then enhance the sense of meaning in life to positively predict nurses' competence to cope with death.

Relationship between Death Coping and Death Cognition and Meaning in Life among Nurses: A Cross-Sectional Study.

To explore nurses' ability to cope with death and its relationship with death cognition and meaning in life in the context of Chinese traditional culture. 1146 nurses from six tertiary hospitals were recruited. Participants completed the Coping with Death Scale, the Meaning in Life Questionnaire, and the self-made Death Cognition Questionnaire. Multiple regression analysis revealed that the search for meaning, the understanding of "good death", receiving education related to life-and-death, cultural aspect, the presence of meaning, and the number of patient deaths experienced in career explained 20.3% of the variance in the ability to cope with death. Lacking a correct understanding of death, nurses are not sufficiently prepared to deal with death and their ability to cope with death is influenced by the unique cognition of death and the sense of the meaning in life in the context of Chinese traditional culture.

A variant rs6214 within IGF-1 confers risk for ulcerative colitis in Chinese Han populations.

Insulin growth factor-1 (IGF-1) has been found to correlate with various diseases such as cancer and cardiovascular diseases including ulcerative colitis (UC). The present study aimed to investigate the plausible association of rs6214 (C > T) within IGF-1 and UC susceptibility in Chinese Han populations. A total of 977 UC patients and 1029 healthy controls were enrolled, and rs6214 was genotyped with PCR and direct sequencing on the ABI 3730XL DNA analyzer platform. Logistic regression analysis was applied for the correlation of rs6214 and UC susceptibility via calculation of odds ratio (OR) with a 95% confidence interval (95% CI) adjusted for age and sex under different genetic models. The difference of clinical parameters between genotypes was measured by one-way analysis of variance (ANOVA). Additional functional assays were conducted to establish the probable relationship. The results indicated that the T allele of rs6214 showed roughly 37% greater risk for UC risk in the additive model (OR = 1.37, 95% CI = 1.21-1.55, P < 0.000001) when compared with C allele carriers, and the pattern was similar in other three genetic models. Further stratified analysis suggested that the association was particularly noteworthy in UC patients with extensive colitis and severe condition. Moreover, the blood level of IGF-1 was downregulated in UC patients, and the mRNA level was lower in T allele carriers in rectal tissues of UC cases. Additional luciferase assay demonstrated that rs6214 regulates IGF-1 expression via promoting miR-2053. Collectively, rs6214 increased UC susceptibility and suppresses IGF-1 expression by enhancing miR-2053 binding. The current findings provided evidence that rs6214 is a promising biomarker for UC prediction and prognosis.

Phase I study to evaluate of the gastric pH-dependent drug interaction between famitinib and the proton pump inhibitor omeprazole in healthy subjects.

To evaluate the potential gastric pH-dependent drug-drug interaction (DDI), safety and tolerability of famitinib co-administered with omeprazole in healthy subjects. Twenty healthy subjects were enrolled in a single-center, single-arm, open-label, fixed-sequence study. Famitinib was administered as a single oral 25 mg under a fasting condition on day 1, omeprazole (40 mg once daily) was given on days 10-14, concomitantly with famitinib on day 15, and for the follow-up 7 additional days (days 16-22). Blood samples were collected for the pharmacokinetic analysis of famitinib and its metabolite SHR116637 following each famitinib dose. Safety and tolerability were assessed during the whole progress via clinical laboratory tests. The least-squares geometric mean ratios (GMRs) (90% CI) of Cmax, AUC0-t and AUC0-∞ for famitinib combined with omeprazole to famitinib alone were 0.989 (0.953, 1.027), 0.956 (0.907, 1.007) and 0.953(0.905, 1.005) respectively. For the metabolite SHR116637, their GMRs (90% CI) of the above parameters were 0.851 (0.786, 0.920), 0.890 (0.838, 0.946)and 0.887 (0.835, 0.943), indicating the absence of significant differences in the parameters. During the treatment period, 9(45%) subjects reported 16 treatment emergent adverse events (TEAE), among which 6 subjects (30%) reported 9 TEAEs and 1 subject (5%) reported 1 TEAE during famitinib or omeprazole administered alone respectively, 5 subjects (25.0%) reported 6 TEAEs during in the combined administration phase. Omeprazole did not have a significant influence on the pharmacokinetics (PK) of famitinib and SHR116637, and the safety profile was good upon co-administration. ClinicalTrials.gov identifier NCT 05,041,920.