Effects of vitamin D3 supplementation on strength of lower and upper extremities in athletes: an updated systematic review and meta-analysis of randomized controlled trials.

Background: Coaches and athletes are increasingly interested in understanding athletes' serum vitamin D levels, their impact on strength, physical performance, and athletic outcomes. Previous meta-analyses were reported with limited sample size and no significant overall effect was found. Hence, it is crucial to conduct a thorough and up-to-date systematic examination and meta-analysis to elucidate the potential advantages of supplementing with vitamin D3 in enhancing muscle strength for athletes. Methods: We performed a thorough investigation, spanning three databases (PubMed, EBSCO, and Cochrane Library), seeking randomized controlled trials (RCTs) in all languages. These trials delved into the influence of vitamin D3 supplementation on the changes of pre- and post-intervention muscle strength in healthy athletes. Our systematic examination and meta-analysis took into account serum 25(OH)D levels exceeding 30 ng/mL as a marker of adequacy. Results: Ten RCTs, comprising 354 athletes (185 in the vitamin D3 group and 169 in the placebo group), fulfilled the inclusion criteria. During the study, 36 athletes were lost to follow-up, leaving 318 athletes (166 in the vitamin D3 group and 152 in the placebo group) with documented complete results. In comparison with the placebo group, there is a significant increase between the changes of pre- and post-intervention serum 25(OH)D levels among athletes following a period of vitamin D3 supplementation (MD 14.76, 95% CI: 8.74 to 20.77, p < 0.0001). Overall effect of four strength measurements including handgrip, one repetition maximum Bench Press (1-RM BP), vertical jump, and quadriceps contraction was not significantly improved (SMD 0.18, 95% CI: -0.02 to 0.37, p = 0.08), but there was a significant increase in quadriceps contraction (SMD 0.57, 95% CI: 0.04 to 1.11, p = 0.04). Conclusion: This updated meta-analysis indicates the potential benefits of vitamin D supplementation for enhancing muscle strength in athletes when analyzing its quantitatively synthesized effects. With limited available studies for the quantitative synthesis, it cannot warrant significant overall enhancements in muscle strength when athletes attain adequate serum 25(OH)D levels through supplementation.

Fungal vaccines and adjuvants: a tool to reveal the interaction between host and fungi.

Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated life-threatening diseases (such as invasive pulmonary aspergillosis and cryptococcal meningitis) and becoming a global health problem in especially immunodeficient population. The major obstacle to conquer fungal harassment lies in the presence of increasing resistance to conventional antifungal agents used in newly clinically isolated strains. Although recombinant cytokines and mono-/poly-clonal antibodies are added into antifungal armamentarium, more effective antimycotic drugs are exceedingly demanded. It is comforting that the development of fungal vaccines and adjuvants opens up a window to brighten the prospective way in the diagnosis, prevention and treatment of fungal assaults. In this review, we focus on the progression of several major fungal vaccines devised for the control of Candida spp., Aspergillus spp., Cryptococcus spp., Coccidioides spp., Paracoccidioides spp., Blastomyces spp., Histoplasma spp., Pneumocystis spp. as well as the adjuvants adopted. We then expound the interaction between fungal vaccines/adjuvants and host innate (macrophages, dendritic cells, neutrophils), humoral (IgG, IgM and IgA) and cellular (Th1, Th2, Th17 and Tc17) immune responses which generally experience immune recognition of pattern recognition receptors, activation of immune cells, and clearance of invaded fungi. Furthermore, we anticipate an in-depth understanding of immunomodulatory properties of univalent and multivalent vaccines against diverse opportunistic fungi, providing helpful information in the design of novel fungal vaccines and adjuvants.

Fast-BEV: A Fast and Strong Bird's-Eye View Perception Baseline.

Recently, perception task based on Bird's-Eye View (BEV) representation has drawn more and more attention, and BEV representation is promising as the foundation for next-generation Autonomous Vehicle (AV) perception. However, most existing BEV solutions either require considerable resources to execute on-vehicle inference or suffer from modest performance. This paper proposes a simple yet effective framework, termed Fast-BEV, which is capable of performing faster BEV perception on the on-vehicle chips. Towards this goal, we first empirically find that the BEV representation can be sufficiently powerful without expensive transformer based transformation nor depth representation. Our Fast-BEV consists of five parts, We innovatively propose (1) a lightweight deploymentfriendly view transformation which fast transfers 2D image feature to 3D voxel space, (2) an multi-scale image encoder which leverages multi-scale information for better performance, (3) an efficient BEV encoder which is particularly designed to speed up on-vehicle inference. We further introduce (4) a strong data augmentation strategy for both image and BEV space to avoid over-fitting, (5) a multiframe feature fusion mechanism to leverage the temporal information. Among them, (1) and (3) enable Fast-BEV to be fast inference and deployment friendly on the on-vehicle chips, (2), (4) and (5) ensure that Fast-BEV has competitive performance. All these make Fast-BEV a solution with high performance, fast inference speed, and deployment-friendly on the on-vehicle chips of autonomous driving. Through experiments, on 2080Ti platform, our R50 model can run 52.6 FPS with 47.3% NDS on the nuScenes validation set, exceeding the 41.3 FPS and 47.5% NDS of the BEVDepth-R50 model [1] and 30.2 FPS and 45.7% NDS of the BEVDet4D-R50 model [2]. Our largest model (R101@900x1600) establishes a competitive 53.5% NDS on the nuScenes validation set. We further develop a benchmark with considerable accuracy and efficiency on current popular on-vehicle chips. The code is released at: https://github.com/Sense-GVT/FastBEV.

Effects of nanoplastic exposure routes on leaf decomposition in streams.

Polystyrene nanoparticles (PS NPs) released from plastic products have been demonstrated to pose a threat to leaf litter decomposition in streams. Given the multitrophic systems of species interactions, the effects of PS NPs through different exposure routes on ecosystem functioning remain unclear. Especially dietary exposure, a frequently overlooked pathway leading to toxicity, deserves more attention. A microcosm experiment was conducted in this study to assess the effects of waterborne and dietary exposure to PS NPs on the litter-based food chain involving leaves, microbial decomposers, and detritivores (river snails). Compared to waterborne contamination, dietary contamination resulted in lower microbial enzyme activities and a significantly higher decrease in the lipid content of leaves. For river snails, their antioxidant activity was significantly increased by 20.21%-69.93%, and their leaf consumption rate was significantly reduced by 16.60% through the dietary route due to the lower lipid content of leaves. Besides, the significantly decreased nutritional quality of river snails would negatively influence their palatability to predators. The findings of this study indicate that dietary exposure to PS NPs significantly impacts microbial and detritivore activities, thus affecting their functions in the detritus food chain as well as nutrient cycling.

Menopausal hormone therapy decreases the likelihood of diabetes development in peri­menopausal individuals with prediabetes.

BACKGROUND: The influence of menopausal hormone therapy (MHT) on the probability of developing diabetes mellitus in individuals with prediabetes remains uncertain. METHODS: This retrospective cohort study, utilizing the TriNetX U.S. Collaborative Network, investigated cohorts, implemented propensity score matching, and analyzed outcomes associated with diabetes mellitus. The study focused on individuals aged 46-60 with prediabetes prior to menopause, categorizing them into MHT and non-MHT groups. Further stratified analyses, including variables such as age and race, were conducted to thoroughly examine potential variations in outcomes. RESULTS: The study involved 6566 individuals (MHT and non-MHT), with propensity score matching ensuring balanced cohorts. Over a 20-year follow-up, the MHT group demonstrated a lower incidence of diabetes mellitus compared to the non- MHT group, with a Hazard Ratio of 0.693 (95 % CI: 0.577, 0.832). Stratified analyses revealed age-specific nuances, with significant protective effects in individuals aged 46-50 and 55-60. Additionally, ethnicity played a role, with MHT demonstrating significant benefits in White individuals but not in the Black or Asian populations. BMI analysis indicated a significant risk reduction with MHT in individuals with BMI less than or equal to 24.9 and 25-29.9 kg/m 2, but not in those with BMI greater than or equal to 30 kg/m 2. CONCLUSION: In our study, we demonstrate a sustained 20-year decrease in the risk of diabetes among premenopausal individuals with prediabetes who undergo menopausal hormone therapy.

Decitabine as epigenetic priming with CLAG induce improved outcome of relapsed or refractory acute myeloid leukemia in children.

BACKGROUND: Decitabine (DAC), a DNA methyltransferase inhibitor, has shown efficacy combined with chemotherapy for relapsed or refractory (R/R) acute myeloid leukemia (AML) in adults, but less is known about its efficacy in children. Accordingly, we conducted a study which involved a priming regimen consisting of DAC with cladribine, cytarabine, and granulocyte-stimulating factor (DAC-CLAG) and compared the efficacy and safety of this regimen with CLAG alone. METHODS: A total of 39 R/R AML children who received the CLAG or DAC-CLAG regimen in Shanghai Children's Hospital were retrospectively enrolled in this non-randomized study. These regimens were studied sequentially over time. Twenty-two patients received CLAG from 2015, while 17 patients were administered epigenetic priming with DAC before CLAG from 2020. Patients were subsequently bridged to stem cell transplantation (SCT) or consolidation chemotherapy. Complete remission (CR) and adverse effects were analyzed by Fisher's exact test, and survival was analyzed by the Kaplan-Meier method. RESULTS: DAC-CLAG conferred a numerically higher CR compared to CLAG (70.59% vs 63.64%; P = 0.740). High CR rates occurred in patients with good cytogenetics (P = 0.029) and prior induction without cladribine (P = 0.099). The 1-year event-free survival (EFS) was 64.71% ± 11.59% and 63.31% ± 10.35% in the DAC-CLAG and CLAG group (P = 0.595), and 1-year overall survival (OS) was 81.45% ± 9.72% and 77.01% ± 9.04%, respectively (P = 0.265). The 1-year OS and EFS after SCT were higher in the DAC-CLAG than in the CLAG cohort (100% vs 92.31% ± 7.39%, P = 0.072; 92.31% ± 7.39% vs 85.71% ± 9.35%, P = 0.158). Univariate analysis revealed that a good prognosis included good cytogenetics (P = 0.002), non-complex karyotype (P = 0.056), CR on reinduction (P < 0.0001), and bridging to SCT (P = 0.0007). Use of a hypomethylating agent (P = 0.049) and bridging to SCT (P = 0.011) were independent prognostic factors. Grade 3/4 hematologic toxicity and infection were the main adverse events. CONCLUSIONS: DAC prior to the CLAG regimen improved remission in pediatric R/R AML, and was feasible and well tolerated. CLAG ± DAC as a salvage therapy prior to SCT induced improved survival.

Transcriptomics Reveals Effect of Pulsatilla Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling.

The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced by heparan sulfate (HS), do not successfully engulf Candida albicans (C. albicans). Instead, they release many inflammatory factors that cause damage to the vaginal mucosa. This study aims to understand the molecular mechanism by which the n-butanol extract of Pulsatilla decoction (BEPD) treats VVC through transcriptomics. High-performance liquid chromatography was used to identify the primary active components of BEPD. A VVC mouse model was induced using an estrogen-dependent method and the mice were treated daily with BEPD (20 mg/kg, 40 mg/kg, and 80 mg/kg) for seven days. The vaginal lavage fluid of the mice was analyzed for various experimental indices, including fungal morphology, fungal burden, degree of neutrophil infiltration, and cytokines. Various assessments were then performed on mouse vaginal tissues, including pathological assessment, immunohistochemistry, immunofluorescence, Western blot (WB), quantitative real-time PCR, and transcriptome assays. Our results showed that BEPD reduced vaginal redness and swelling, decreased white discharge, inhibited C. albicans hyphae formation, reduced neutrophil infiltration and fungal burden, and attenuated vaginal tissue damage compared with the VVC model group. The high-dose BEPD group even restored the damaged vaginal tissue to normal levels. The medium- and high-dose groups of BEPD also significantly reduced the levels of IL-1ß, IL-6, TNF-α, and LDH. Additionally, transcriptomic results showed that BEPD regulated several chemokine (CXCL1, CXCL3, and CXCL5) and S100 alarmin (S100A8 and S100A9) genes, suggesting that BEPD may treat VVC by affecting chemokine- and alarmin-mediated neutrophil chemotaxis. Finally, we verified that BEPD protects the vaginal mucosa of VVC mice by inhibiting neutrophil recruitment and chemotaxis in an animal model of VVC via the TLR4/MyD88/NF-κB pathway. This study provides further evidence to elucidate the mechanism of BEPD treatment of VVC.

Prenatal 1-Nitropyrene Exposure Causes Autism-Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1-nitropyrene (1-NP), a key component of motor vehicle exhaust, on autism-like behaviors in a mouse model. Three-chamber test finds that prenatal 1-NP exposure causes autism-like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1-NP-exposed weaning pups. Immunofluorescence finds that prenatal 1-NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1-NP exposure retards tangential migration of GAD67-positive interneurons and downregulates interneuron migration-related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1-NP exposure reduces hydroxymethylation of interneuron migration-related genes through inhibiting ten-eleven translocation (TET) activity in fetal forebrain. Supplement with alpha-ketoglutarate (α-KG), a cofactor of TET enzyme, reverses 1-NP-induced hypohydroxymethylation at specific sites of interneuron migration-related genes. Moreover, α-KG supplement alleviates 1-NP-induced migration retardation of interneurons in fetal forebrain. Finally, maternal α-KG supplement improves 1-NP-induced autism-like behaviors in weaning offspring. In conclusion, prenatal 1-NP exposure causes autism-like behavior partially by altering DNA hydroxymethylation of interneuron migration-related genes in developing brain.

Regulatory mechanisms used by ZmMYB39 to enhance drought tolerance in maize (Zea mays) seedlings.

Drought is a significant abiotic stressor that limits maize (Zea mays L.) growth and development. Thus, enhancing drought tolerance is critical for promoting maize production. Our findings demonstrated that ZmMYB39 is an MYB transcription factor with transcriptional activation activity. Drought stress experiments involving ZmMYB39 overexpression and knockout lines indicated that ZmMYB39 positively regulated drought stress tolerance in maize. DAP-Seq, EMSA, dual-LUC, and RT-qPCR provided initial insights into the molecular regulatory mechanisms by which ZmMYB39 enhances drought tolerance in maize. ZmMYB39 directly promoted the expression of ZmP5CS1, ZmPOX1, ZmSOD2, ZmRD22, ZmNAC49, and ZmDREB2A, which are involved in stress resistance. ZmMYB39 enhanced drought tolerance by interacting with and promoting the expression of ZmFNR1, ZmHSP20, and ZmDOF6. Our study offers a theoretical basis for understanding the molecular regulatory networks involved in maize drought stress response. Furthermore, ZmMYB39 serves as a valuable genetic resource for breeding drought-resistant maize.

[Mechanism of n-butanol extract of Pulsatilla Decoction in treating ulcerative colitis by activating BMP signaling pathway].

The study aimed to investigate the therapeutic effects of the n-butanol extract of Pulsatilla Decoction(BEPD) on ulcerative colitis(UC) via the bone morphogenetic protein(BMP) signaling pathway. C57BL/6 mice were divided into six groups: control, model, mesalazine, and BEPD low-, medium-, and high-dose groups. Except for the control group, the rest groups were treated with 3% dextran sulfate sodium(DSS) freely for seven consecutive days to establish the UC mouse model, followed by treatment with different concentrations of BEPD and mesalazine by gavage. The murine body weight and disease activity index(DAI) were recorded. After the mice were sacrificed, their colon tissues were collected for histological analysis. Alcian blue/periodic acid-Schiff(AB/PAS) staining was used to detect the number and mucus secretion status of goblet cells; immunohistochemistry was performed to measure the expression of ki67, cleaved caspase-3, mucin 2(Muc2), and matrix metalloproteinase-9(MMP9) in colon tissues; and immunofluorescence was used to analyze the expression of tight junction proteins in colon tissues, and enzyme linked immunosorbent assay(ELISA) was employed to quantify the levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1ß, and IL-6. Western blot was conducted to evaluate the expression of BMP pathway-related proteins in mouse colon tissues. Quantitative real-time PCR(qRT-PCR) was performed to measure the expression of genes related to goblet cell differentiation in mouse colon tissues. In addition, this study also examined the protective effect and underlying mechanism of BEPD-containing serum on lipopolysaccharide(LPS)-induced barrier damages in LS174T goblet cells in vitro. The results showed that BEPD significantly alleviated UC symptoms in mice, restored goblet cell diffe-rentiation function, promoted Muc2 secretion and tight junction protein expression, and suppressed inflammatory factor secretion while activating the BMP signaling pathway. Therefore, BEPD may exert its therapeutic effects on UC by activating the BMP signaling pathway, providing a new strategy for drug intervention in UC.

Nurses' Personality Traits and Perceived Work Environments During Public Health Emergencies: Implications for Nursing Workforce Planning.

Background: The nursing workforce faces substantial challenges, particularly in the aftermath of the COVID-19 era. Developing an effective strategy for workforce maintenance and the strategic deployment of nurses is crucial. Purpose: This study aimed to explore and categorize nurses' personality traits, with a focus on analyzing differences in their perceptions of the nursing work environment. Participants and Methods: Between January 2023 and February 2023, a multi-center cross-sectional study was carried out involving nurses from 12 tertiary hospitals actively engaged in frontline COVID-19 response duties. Through cluster sampling, surveys were distributed among eligible nursing staff, comprising a general information questionnaire, the Chinese Big Five Personality Questionnaire-Short Form, subjective evaluations of emergency nursing management, and the Chinese Nursing Work Environment Scale for Public Health Emergencies. Various statistical analyses, such as descriptive analysis, cluster analysis, non-parametric tests, and general linear model analysis, were employed to investigate the correlation between personality types and the perception of nursing work environments. Results: The analysis encompassed 1059 valid questionnaires, reflecting the experiences of frontline nurses. The majority of these nurses possessed 1-5 years of experience, held junior professional titles, volunteered for their roles, and served as attending nurses. Categorization based on personality traits revealed three groups: resilient (35.60%), ordinary (16.15%), and distressed (48.25%) types. Significantly distinct perceptions of nursing work environments emerged among these categories, with resilient and ordinary types expressing notably higher satisfaction compared to the distressed group (H value = 256.487, p < 0.001). Conclusion: This study illustrates the connection between nurses' perceived working environment and their personality traits. Nursing managers should factor in nurses' personality traits when choosing and deploying frontline responders during public health emergencies. Prioritizing resilient-type nurses and crafting a supportive work environment that aligns with nurses' characteristics is indispensable for an effective emergency response.

Prognostic significance of systemic immune inflammatory index in NSCLC: a meta-analysis.

Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients. PROSPERO registration number: CRD42022336270.

Prenatal exposure to fenvalerate causes depressive-like behavior in adulthood by inhibiting brain-derived 5-HT synthesis.

The developmental toxicity of fenvalerate, a representative pyrethroid insecticide, is well documented. The present study aimed to explore whether prenatal exposure to fenvalerate causes depression-like behavior in adulthood. Pregnant mice were orally administrated with either corn oil or fenvalerate (2 or 20 mg/kg) during pregnancy. Depressive-like behaviors were assessed by tail suspension test (TST), forced swim test (FST) and sucrose preference test (SPT). Immobility times in TST and FST were increased in offspring whose mothers were exposed to fenvalerate throughout pregnancy. By contrast, sugar preference index, as determined by SPT, was decreased in fenvalerate-exposed offspring. Prefrontal PSD95, a postsynaptic membrane marker, was downregulated in fenvalerate-exposed adulthood offspring. Fenvalerate-induced reduction of prefrontal PSD95 began at GD18 fetal period. Accordingly, prefrontal 5-HT, a neurotransmitter for synaptogenesis, was also reduced in fenvalerate-exposed GD18 fetuses. Tryptophan hydroxylase 2 (TPH2), a key enzyme for 5-HT synthesis, was downregulated in the midbrain of fenvalerate-exposed GD18 fetuses. Additional experiment showed that GRP78 and p-eIF2α, two endoplasmic reticulum stress-related proteins, were increased in the midbrain of fenvalerate-exposed fetal mice. The present results suggest that prenatal exposure to fenvalerate causes depressive-like behavior in adulthood, partially by inhibiting brain-derived 5-HT synthesis.

[Prognostic analysis of childhood T-lymphoblastic lymphoma treated with leukemia regimen]. / 儿童Tæ·‹å·´æ¯ç»†èƒžæ·‹å·´ç˜¤é‡‡ç”¨ç™½è¡€ç— æ–¹æ¡ˆæ²»ç–—çš„é¢„åŽåˆ†æž.

OBJECTIVES: To investigate the prognosis of childhood T-lymphoblastic lymphoma (T-LBL) treated with acute lymphoblastic leukemia (ALL) regimen and related influencing factors. METHODS: A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen (ALL-2009 or CCCG-ALL-2015 regimen) from May 2010 to May 2022. RESULTS: The 29 children with T-LBL had a 5-year overall survival (OS) rate of 84%±7% and an event-free survival (EFS) rate of 81%±8%. The children with B systemic symptoms (unexplained fever >38°C for more than 3 days; night sweats; weight loss >10% within 6 months) at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms (P<0.05). The children with platelet count >400×109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates (P<0.05). There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen (P>0.05). Compared with the ALL-2009 regimen, the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections (P<0.05). CONCLUSIONS: The ALL regimen is safe and effective in children with T-LBL. Children with B systemic symptoms, platelet count >400×109/L, and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis. Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections, but it does not affect prognosis.

Immunophenotype of lymphocytes and real-world outcome of COVID-19 infection in children with hematology and oncology.

BACKGROUND: Patients with immunocompromise were suspected to encounter a high risk for severe coronavirus disease 2019 (COVID-19) infection on early period; however, data is lacking nowadays and immune response remain unclear. METHODS: In this retrospective study, internet questionnaire survey and medical records were acquired in pediatric hematology oncology patients. Clinical severity, immunological characteristics, and outcomes were analyzed from December 1, 2022 to January 31, 2023 at the 3rd year of pandemic in China. RESULTS: A total of 306 patients were included, with 21 patients (6.9%) asymptomatic, 262 (85.6%) mild severity, 17 (5.6%) moderate severity, 5 (1.6%) severe severity, and 1 (0.3%) critical severity. Seventy-eight (25.5%) patients were on intensive chemotherapy, and 32.0% children were on maintenance chemotherapy. Delays in cancer therapy occurred in 86.7% patients. Univariable analysis revealed active chemotherapy (P < 0.0001), long duration of symptom (P < 0.0001), low lymphocytes count (P = 0.095), low CD3 + and CD8 + T cell count (P = 0.013, P = 0.022), high percentage of CD4 + TCM (P = 0.016), and low percentage of transitional B cells (P = 0.045) were high risk factors for severe COVID-19 infection. Cox regression model showed that the absolute lymphocytes count (P = 0.027) and long duration of symptom (P = 0.002) were the independent factors for severity. Patients with CD8 + dominant and B cell depletion subtype wasn't related with severity, but had higher percentage of CD8 + effector memory T cells (TEM) and terminally differentiated effector memory T cells (TEMRA) (P < 0.001, P < 0.001), and a longer COVID-19 duration (P = 0.045). CONCLUSION: The severity was relatively mild in children with immunodeficiencies in the third year of COVID-19 pandemic. Low lymphocyte count and long duration of symptom were the independent risk factors with COVID-19 severity. Delays in cancer care remain a major concern and the long outcome is pending.

Risk factors of Carbapenem-resistant Enterobacterales intestinal colonization for subsequent infections in hematological patients: a retrospective case-control study.

Objective: Infections caused by Carbapenem-resistant Enterobacterales (CRE) have high treatment costs, high mortality and few effective therapeutic agents. This study aimed to determine the risk factors for progression from intestinal colonization to infection in hematological patients and the risk factors for 30-day mortality in infected patients. Methods: A retrospective case-control study was conducted in the Department of Hematology at Shandong Provincial Hospital affiliated to Shandong First Medical University from April 2018 to April 2022. Patients who developed subsequent infections were identified as the case group by electronic medical record query of patients with a positive rectal screen for CRE colonization, and patients who did not develop subsequent infections were identified as the control group by stratified random sampling. Univariate analysis and logistic regression analysis determined risk factors for developing CRE infection and risk factors for mortality in CRE-infected patients. Results: Eleven hematological patients in the study developed subsequent infections. The overall 30-day mortality rate for the 44 hematological patients in the case-control study was 11.4% (5/44). Mortality was higher in the case group than in the control group (36.5 vs. 3.0%, P = 0.0026), and septic shock was an independent risk factor for death (P = 0.024). Univariate analysis showed that risk factors for developing infections were non-steroidal immunosuppressants, serum albumin levels, and days of hospitalization. In multivariable logistic regression analysis, immunosuppressants [odds ratio (OR), 19.132; 95% confidence interval (CI), 1.349-271.420; P = 0.029] and serum albumin levels (OR, 0.817; 95% CI, 0.668-0.999; P = 0.049) were independent risk factors for developing infections. Conclusion: Our findings suggest that septic shock increases mortality in CRE-infected hematological patients. Hematological patients with CRE colonization using immunosuppressive agents and reduced serum albumin are more likely to progress to CRE infection. This study may help clinicians prevent the onset of infection early and take measures to reduce mortality rates.

Advancements in the synthesis of carbon dots and their application in biomedicine.

As a sort of fluorescent carbon nanomaterial with a particle size of less than 10 nm, carbon dots (CDs) have their own merits of good dispersibility in water, stable optical properties, strong chemical inertness, stable optical properties, and good biosecurity. These excellent peculiarities facilitated them like sensing, imaging, medicine, catalysis, and optoelectronics, making them a new star in the field of nanotechnology. In particular, the development of CDs in the fields of chemical probes, imaging, cancer therapy, antibacterial and drug delivery has become a hot topic in current research. Although the biomedical applications in CDs have been demonstrated in many research articles, a systematic summary of their role in biomedical applications is scarce. In this review, we introduced the basic information of CDs in detail, including synthesis approaches of CDs as well as their favorable properties including photoluminescence and low cytotoxicity. Subsequently, the application of CDs in the field of biomedicine was emphasized. Finally, the main challenges and research prospects of CDs in this field were proposed, which might provide some detailed information in designing new CDs in this promising biomedical field.

Detection of SARS-CoV-2 virus in middle ear effusions and its association with otitis media with effusion.

A large-scale outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) occurred in Shanghai, China, in early December 2022. To study the incidence and characteristics of otitis media with effusion (OME) complicating SARS-CoV-2, we collected 267 middle ear effusion (MEE) samples and 172 nasopharyngeal (NP) swabs from patients. The SARS-CoV-2 virus was detected by RT-PCR targeting. The SARS-CoV-2 virus, angiotensin-converting enzyme 2 (ACE2), and transmembrane serine protease 2 (TMPRSS2) expression in human samples was examined via immunofluorescence. During the COVID-19 epidemic in 2022, the incidence of OME (3%) significantly increased compared to the same period from 2020 to 2022. Ear symptoms in patients with SARS-CoV-2 complicated by OME generally appeared late, even after a negative NP swab, an average of 9.33 ± 6.272 days after COVID-19 infection. The SARS-CoV-2 virus was detected in MEE, which had a higher viral load than NP swabs. The insertion rate of tympanostomy tubes was not significantly higher than in OME patients in 2019-2022. Virus migration led to high viral loads in MEE despite negative NP swabs, indicating that OME lagged behind respiratory infections but had a favorable prognosis. Furthermore, middle ear tissue from adult humans coexpressed the ACE2 receptor for the SARS-CoV-2 virus and the TMPRSS2 cofactors required for virus entry.

Explore the active ingredients and potential mechanism of action on Actinidia arguta leaves against T2DM by integration of serum pharmacochemistry and network pharmacology.

BACKGROUND: Actinidia arguta leaves (AAL) are traditionally consumed as a vegetable and as tea in folk China and Korea. Previous studies have reported the anti-diabetic effect of AAL, but its bioactive components and mechanism of action are still unclear. AIM OF THE STUDY: This study aims to identify the hypoglycemic active components of AAL by combining serum pharmacochemistry and network pharmacology and to elucidate its possible mechanism of action. METHODS: Firstly, the effective components in mice serum samples were characterized by UPLC-Q/TOF-MSE. Furthermore, based on these active ingredients, network pharmacology analysis was performed to establish an "H-C-T-P-D" interaction network and reveal possible biological mechanisms. Finally, the affinity between serum AAL components and the main proteins in the important pathways above was investigated through molecular docking analysis. RESULTS: Serum pharmacochemistry analysis showed that 69 compounds in the serum samples were identified, including 23 prototypes and 46 metabolites. The metabolic reactions mainly included deglycosylation, dehydration, hydrogenation, methylation, acetylation, glucuronidation, and sulfation. Network pharmacology analysis showed that the key components quercetin, pinoresinol diglucoside, and 5-O-trans-p-coumaroyl quinic acid butyl ester mainly acted on the core targets PTGS2, HRAS, RELA, PRKCA, and BCL2 targets and through the PI3K-Akt signaling pathway, endocrine resistance, and MAPK signaling pathway to exert a hypoglycemic effect. Likewise, molecular docking results showed that the three potential active ingredients had good binding effects on the five key targets. CONCLUSION: This study provides a basis for elucidating the pharmacodynamic substance basis of AA against T2DM and further exploring the mechanism of action.