Efficacy of acupuncture in animal models of various ovarian dysfunctions: a systematic review and meta-analysis.

Objective: This study aims to assess the comprehensive and integrated modulatory effects of acupuncture and electroacupuncture on various ovarian dysfunctions. Methods: We systematically searched for articles on animal experiments related to polycystic ovary syndrome (PCOS), premature ovarian failure (POF), premature ovarian insufficiency (POI), and perimenopausal syndrome (PMS) across multiple databases, including PubMed, Web of Science, Cochrane Library, Embase, and four Chinese language databases. The search covered the period from inception to November 2023. We conducted a comparative analysis between the acupuncture group and the model group (untreated) based on eligible literature. Our primary outcomes encompassed serum sex hormones (Luteinizing hormone, Follicle-stimulating hormone, Testosterone, Estradiol, Progesterone, and Anti-Müllerian hormone) and ovarian weight. Dichotomous data were synthesized to establish the relative risk (RR) of notable post-treatment improvement, while continuous data were pooled to determine the standardized mean difference (SMD) in post-treatment scores between the groups. Statistical analyses, including sensitivity analysis, Egger's test, and the trim-and-fill method, were executed using Stata 15.0 software. Results: The meta-analysis encompassed 29 articles involving a total of 623 rats. In comparison to rat models of PCOS, the experimental group exhibited a reduction in serum levels of LH, T and LH/FSH ratio. However, no statistically significant differences were observed in AMH, FSH, E2 levels, and ovarian weight between the two groups. In the ovarian hypoplasia model rats, both acupuncture and electroacupuncture interventions were associated with an increase in E2 levels. However, the levels of LH and FSH did not exhibit a significant difference between the two groups. Conclusions: Acupuncture or electroacupuncture facilitates the restoration of ovarian function primarily through the modulation of serum sex hormones, exerting regulatory effects across various types of ovarian dysfunction disorders. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316279.

Assessing the diagnostic value of left ventricular synchrony indices derived from phase analysis by D-SPECT in identifying obstructive coronary artery disease.

This study aimed to assess the diagnostic efficacy of left ventricular synchrony (LVS) for detecting coronary artery disease (CAD). We explored whether the LVS index derived from phase analysis of D-SPECT provides superior diagnostic value compared to conventional perfusion analysis in identifying obstructive CAD. Patients with suspected or confirmed CAD underwent drug-stress/rest gated D-SPECT myocardial perfusion imaging (MPI) and coronary angiography (CAG). A 50% stenosis was set as the threshold for obstructive CAD. 110 participants were enrolled in this analysis. There were significant differences in phase standard deviation (PSD), phase histogram bandwidth (PHB) and entropy among the four groups. Patients without cardiac disease and those with mild-moderate stenosis exhibited no noticeable contraction asynchrony. However, LVS indices demonstrated a gradual increase with the progression of coronary stenosis when compared to NC (P < 0.001). Obstructive CAD was identified in 43 out of 110 participants (39%). Optimal cutoff values for diagnosing obstructive CAD during stress were determined as 7.6° for PSD, 24° for PHB, and 37% for entropy, respectively. Notably, PSD, PHB, and entropy indices exhibited higher sensitivity compared to MPI. The integration of the stress-induced LVS indices into routine MPI analysis resulted in a significantly greater area under the curve (AUC), leading to improved diagnostic performance and enhanced differential capacity. Stress-induced LVS indices increase with the severity of coronary artery stenosis by D-SPECT phase analysis. Further, the indices-derived phase analysis exhibits superior sensitivity and discriminatory ability compared to MPI in detecting obstructive CAD.

[Effect of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on PI3K/AKT/FOXO3a pathway in mice with poor ovarian response].

OBJECTIVE: To observe the protective effect of acupuncture at "Zhibian" (BL 54) through "Shuidao (ST 28)" based on the PI3K/AKT/FOXO3a pathway in mice with poor ovarian response (POR), and to explore the possible mechanism of acupuncture in inhibiting ovarian granulosa cells apoptosis in POR. METHODS: A total of 45 mice with regular estrous cycles were randomly divided into a blank group, a model group and an acupuncture group, with 15 mice in each group. Mice in the model group and the acupuncture group were given triptolide suspension (50 mg•kg-1•d-1) by gavage for 2 weeks to establish POR model. After successful modeling, mice in the acupuncture group were given acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) for 2 weeks, once a day, 20 min each time. Ovulation induction was started the day after the intervention ended, and samples were taken from each group after ovulation induction. Vaginal smears were used to observe changes in the estrous cycle of mice. The number of oocytes retrieved, ovarian wet weight, final body weight, and ovarian index were measured. The levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) in serum were detected by ELISA. The morphology of ovarian tissue was observed by HE staining. The apoptosis of ovarian granulosa cells was detected by TUNEL staining. The mRNA expression of PI3K, AKT, and FOXO3a in ovarian tissue was detected by real-time fluorescence quantitative PCR. The protein expression of Bcl-2 associated X protein (BAX), caspase-3, phosphorylated phosphatidylinositol 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) in ovarian tissue was detected by Western blot. RESULTS: Compared with the blank group, the rate of estrous cycle disorder in the model group was increased (P<0.01); compared with the model group, the rate of estrous cycle disorder in the acupuncture group was decreased (P<0.01). Compared with the blank group, the number of oocytes retrieved, ovarian wet weight, ovarian index, and final body weight in the model group were decreased (P<0.01); compared with the model group, the number of oocytes retrieved, ovarian index, and ovarian wet weight were increased (P<0.01, P<0.05), and there was no significant difference in final body weight (P>0.05) in the acupuncture group. Compared with the blank group, the serum levels of FSH and LH were increased (P<0.01), and the serum levels of AMH and E2 were decreased (P<0.01) in the model group; compared with the model group, the serum levels of FSH and LH were decreased (P<0.01, P<0.05), and the serum levels of AMH and E2 were increased (P<0.01, P<0.05) in the acupuncture group. Compared with the blank group, the number of normal developing follicles in ovarian tissue in the model group was decreased and the morphology was poor, while the number of atretic follicles increased; compared with the model group, the number, morphology, and granulosa cell structure of follicles in the acupuncture group improved to varying degrees, and the number of atretic follicles decreased. Compared with the blank group, the apoptosis rate of ovarian granulosa cells in the model group was increased (P<0.01); compared with the model group, the apoptosis rate of ovarian granulosa cells in the acupuncture group was decreased (P<0.01). Compared with the blank group, the FOXO3a mRNA expression and caspase-3 and BAX protein expression in ovarian tissue in the model group were increased (P<0.01), and the mRNA expression of PI3K and AKT and the protein expression of p-PI3K, p-AKT, and p-FOXO3a in ovarian tissue were decreased (P<0.01); compared with the model group, the mRNA expression of FOXO3a and protein expression of caspase-3 and BAX in ovarian tissue in the acupuncture group were decreased (P<0.05, P<0.01), and the mRNA expression of PI3K and AKT and the protein expression of p-PI3K, p-AKT, and p-FOXO3a in ovarian tissue were increased (P<0.01, P<0.05). CONCLUSION: Acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) could inhibit ovarian cell apoptosis, and improve ovarian function in POR mice, and its mechanism may be related to the regulation of key factors in the PI3K/AKT/FOXO3a pathway.

A fluorescence aptamer sensor utilizing WS2 nanosheets for sensitive detection of patulin: enhanced specificity and wide applicability.

A tungsten disulfide (WS2) nanosheet-based aptamer sensor was developed to detect patulin (PAT). The 5'-end of the PAT aptamer was modified with a cyanine 3 (Cy3) fluorophore, which self-assembled on WS2 nanosheets. The interaction between the Cy3 fluorophore at the 5'-end of the PAT aptamer and the WS2 nanosheets resulted in reduced fluorescence (FL) intensity due to fluorescence resonance energy transfer (FRET). The introduction of PAT into this sensing system led to hybridization with the PAT aptamer, forming a G-quadruplex/PAT complex with low affinity for the WS2 nanosheet surface. This hybridization increased the distance between the Cy3 fluorophore and the WS2 nanosheets, inhibiting FRET and producing a strong FL signal. Under optimal experimental conditions, the FL intensity of the sensing system demonstrated an excellent linear correlation with PAT concentrations ranging from 0.5 to 40.0 ng mL-1, and it achieved a detection limit (S/N = 3) of 0.23 ng mL-1. This sensing system offers enhanced specificity for PAT detection and has the potential for broad application in detecting other toxins by substituting the sequence of the recognition aptamer.

Association of early-term birth and breastfeeding practices with nutritional outcomes in singleton term infants: a multicenter cross-sectional study.

BACKGROUND: Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants. METHODS: This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5-4.0 kg). RESULTS: Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: ß = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: ß = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (ß=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (ß=-0.15, 95%CI -0.30, 0.00 and ß=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings. CONCLUSIONS: The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.

Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells.

This work investigated the high-throughput classification performance of microscopic images of mesenchymal stem cells (MSCs) using a hyperspectral imaging-based separable convolutional neural network (CNN) (H-SCNN) model. Human bone marrow mesenchymal stem cells (hBMSCs) were cultured, and microscopic images were acquired using a fully automated microscope. Flow cytometry (FCT) was employed for functional classification. Subsequently, the H-SCNN model was established. The hyperspectral microscopic (HSM) images were created, and the spatial-spectral combined distance (SSCD) was employed to derive the spatial-spectral neighbors (SSNs) for each pixel in the training set to determine the optimal parameters. Then, a separable CNN (SCNN) was adopted instead of the classic convolutional layer. Additionally, cultured cells were seeded into 96-well plates, and high-functioning hBMSCs were screened using both manual visual inspection (MV group) and the H-SCNN model (H-SCNN group), with each group consisting of 96 samples. FCT served as the benchmark to compare the area under the curve (AUC), F1 score, accuracy (Acc), sensitivity (Sen), specificity (Spe), positive predictive value (PPV), and negative predictive value (NPV) between the manual and model groups. The best classification Acc was 0.862 when using window size of 9 and 12 SSNs. The classification Acc of the SCNN model, ResNet model, and VGGNet model gradually increased with the increase in sample size, reaching 89.56 ± 3.09, 80.61 ± 2.83, and 80.06 ± 3.01%, respectively at the sample size of 100. The corresponding training time for the SCNN model was significantly shorter at 21.32 ± 1.09 min compared to ResNet (36.09 ± 3.11 min) and VGGNet models (34.73 ± 3.72 min) (P < 0.05). Furthermore, the classification AUC, F1 score, Acc, Sen, Spe, PPV, and NPV were all higher in the H-SCNN group, with significantly less time required (P < 0.05). Microscopic images based on the H-SCNN model proved to be effective for the classification assessment of hBMSCs, demonstrating excellent performance in classification Acc and efficiency, enabling its potential to be a powerful tool in future MSCs research.

Electrochemiluminescence of Ultrasmall Silica Nanoparticles from Size Modulation and Multipath Surface State Adjustment for Ultrasensitive HIV-DNA Fragment Detection.

Here, ultrasmall SiO2 nanoparticles (u-SiO2 NPs, <5 nm) with obvious electrochemiluminescence (ECL) phenomenon, which was absent for conventional silica nanoparticles (c-SiO2 NPs), were reported. In a finite ultrasmall volume, the u-SiO2 NPs exhibited increasing ground state energy and higher optical absorption strength due to the electron-hole confinement model and favored catalyzing the reaction through the rapid diffusion of bulk charge, resulting in apparent ECL emission. Then, Zn2+-induced u-SiO2 nanoaggregates (Zn/u-SiO2-Ov nAGG) were synthesized and exhibited improved ECL performance via multipath surface state adjustment of u-SiO2 from several aspects, including aggregation-induced ECL, the generation of oxygen vacancy (Ov), and more positive surface charge. In addition, an ECL biosensor was constructed for ultrasensitive human immunodeficiency virus-related deoxyribonucleic acid detection from 100 aM to 1 nM with a low limit of 50.48 aM, combining the ECL luminescence of Zn/u-SiO2-Ov nAGG with three-dimensional DNA nanomachine-mediated multioutput amplification for enhanced accuracy and sensitivity compared to the single-output method. Therefore, exploring the ECL of ultrasmall nanoparticles via the adjustment of size and surface state provided a valuable indication to a wider investigation and application of novel ECL materials for clinical diagnostic.

Epidemiological and clinical characteristics of hospitalized unintentional injuries among children in central China from 2017-2023.

Objectives: To examine the epidemiological and clinical characteristics of hospitalized unintentional injuries among children in Central China and theoretically propose preventive and control measures. Methods: We conducted a retrospective study of children aged 0-18 years with unintentional injuries who were admitted to a tertiary hospital in Central China from January 2017 to December 2023. We examined various aspects of the unintentional injuries, including age, gender, urban-rural distribution, external causes, trends, location of injury, cost, and length of stay. Results: A total of 20,166 children with hospitalized unintentional injuries were enrolled. The median age with IQR was 2.8 (1.6, 5.1) years, with majority of the patients (57.0%) were aged 1-3 years, while the fewest were aged 11-18 years. The male-to-female ratio was 1.8:1, and the urban-to-rural ratio was 1.1:1. The most common external causes were foreign bodies (41.7%), exposure to inanimate mechanical forces (25.1%), and falls (22.1%). The most frequently injured body parts were head (72.5%). The total number of unintentional injuries exhibited an increasing trend from 2017-2022, and a decreasing trend from 2022-2023. The urban-rural distribution reversed after 2020. The overall hospitalization cost was 20,810,870.4 USD, with an median cost of 758.7 (556.4, 1,186.2) USD per person. Conclusion: Unintentional injuries imposed a heavy burden on society and families. However, the number of cases and the urban-rural distribution showed significant trend changes from 2017-2023. The external causes varied by age group, gender, and region, while prevention and control measures should be developed accordingly.

Low-dose-rate induces more severe cognitive impairment than high-dose-rate in rats exposed to chronic low-dose γ-radiation.

Background: Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR). Methods: The rats were exposed to γ-irradiation at a LDR of 6 mGy/h and a HDR of 20 mGy/h for 30 days (5 h/day). Functional imaging was performed to assess the brain inflammation and blood-brain barrier (BBB) destruction of rats. Histological and immunofluorescence analyses were used to reveal the neuron damage and the activation of microglia and astrocytes in the hippocampus. RNA sequencing was conducted to investigate changes in gene expression in hippocampus. Results: The rats in the LDR group exhibited more persistent cognitive impairment than those in the HDR group. Furthermore, irradiated rats showed brain inflammation and a compromised BBB. Histologically, the number of hippocampal neurons were comparable in the LDR group but were markedly decreased in the HDR. Additionally, activated M1-like microglia and A1-like astrocytes were observed in the hippocampus of rats in the LDR group; however, only M1-like microglia were activated in the HDR group. Mechanistically, the PI3K-Akt signaling pathway contributed to the different cognitive function change between the LDR group and HDR group. Conclusion: Compared with chronic low-dose γ-irradiation at HDR, LDR induced more severe cognitive impairment which might involve PI3K/Akt signaling pathway.

Clinician-to-clinician connectedness and access to gastric cancer surgery at National Cancer Institute-designated cancer centers.

BACKGROUND: For patients with gastric cancer, the pathway from primary care (PC) clinician to gastroenterologist to cancer specialist (medical oncologist or surgeons) is referral dependent. The impact of clinician connectedness on disparities in quality gastric cancer care, such as at National Cancer Institute-designated cancer centers (NCI-CC), remains underexplored. This study evaluated how clinician connectedness influences access to gastrectomy at NCI-CC. METHODS: Maryland's All-Payer Claims Database was used to evaluate 667 patients who underwent gastrectomy for cancer from 2013 to 2018. Two separate referral linkages, defined as ≥9 shared patients, were examined: (1) PC clinicians to gastroenterologists at NCI-CC and (2) gastroenterologists to cancer specialists at NCI-CC. Multiple logistic regression models determined associations between referral linkages and odds of undergoing gastrectomy at NCI-CC. RESULTS: Only 15% of gastrectomies were performed at NCI-CC. Patients of gastroenterologists with referral links to cancer specialists at NCI-CC were more likely to be <65 years, male, White, and privately insured. Every additional referral link between PC clinician and gastroenterologist at NCI-CC and between gastroenterologist and cancer specialist at NCI-CC increased the odds of gastrectomy at NCI-CC by 71% and 26%, respectively. Black patients had half the odds as White patients in receiving gastrectomy at NCI-CC; however, adjusting for covariates including clinician-to-clinician connectedness attenuated this observation. CONCLUSION: Patients of clinicians with low connectedness and Black patients are less likely to receive gastrectomy at NCI-CC. Enhancing clinician connectedness is necessary to address disparities in cancer care. These results are relevant to policy makers, clinicians, and patient advocates striving for health equity.

Comprehensive analysis of signaling lymphocyte activation molecule family as a prognostic biomarker and correlation with immune infiltration in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common type of kidney cancer and accounts for 2-3% of all cancer cases. Furthermore, a growing number of immunotherapy approaches are being used in antitumor treatment. Signaling lymphocyte activation molecule family (SLAMF) members have been well studied in several cancers, whereas their roles in ccRCC have not been investigated. The present study comprehensively assessed the molecular mechanisms of SLAMF members in ccRCC, performed using The Cancer Genome Atlas database, with analysis of gene transcription, prognosis, biological function, clinical features, tumor-associated immune cells and the correlation with programmed cell death protein 1/programmed death-ligand 1 immune checkpoints. Simultaneously, the Tumor Immune Dysfunction and Exclusion algorithm was used to predict the efficacy of immune checkpoint blockade (ICB) therapy in patients with high and low SLAMF expression levels. The results demonstrated that all SLAMF members were highly expressed in ccRCC, and patients with high expression levels of SLAMF1, 4, 7 and 8 had a worse prognosis that those with low expression. SLAMF members were not only highly associated with immune activation but also with immunosuppressive agents. The level of immune cell infiltration was associated with the prognosis of patients with ccRCC with high SLAMF expression. Moreover, high ICB response rates were observed in patients with high expression levels of SMALF1 and 4. In summary, SLAMF members may serve as future potential biomarkers for predicting the prognosis of ccRCC and emerge as a novel immunotherapy target.

Dynamic analysis and optimal control of knowledge diffusion model in regional innovation ecosystem under digitalization.

Knowledge diffusion in regional innovation ecosystems is an important factor that influences the regional innovation efficiency. In regional innovation ecosystems under digital empowerment, the knowledge diffusion enables the optimal allocation of innovation resources and promotes the sustainable development and ecological evolution of regional innovation ecosystems. In this paper, a SEIR (Susceptible-Exposed-Infected-Recovered) model is proposed for knowledge diffusion in regional innovation ecosystems under digitization. The basic reproduction number of the proposed model is calculated and its stability is validated. Finally, the expressions for the optimal control system and the optimal control parameters are presented. According to the research conclusions of this paper, the knowledge-diffusion ability of innovation agents in an innovation ecosystem affects the knowledge diffusion in a system; the contact rate between innovation agents affects the efficiency of knowledge diffusion in the system and the structure of the system; the digital transmission ability of innovation agents affects the breadth of knowledge diffusion in the system; and the self-learning ability of innovation agents affects the efficiency of knowledge diffusion in the system.The digital technologies help heterogeneous innovation agents in regional innovation ecosystems to break down the knowledge silos. At the same time, the digital technologies enhance the ability of innovation agents to absorb and learn knowledge in regional innovation ecosystems under digitization, thereby increasing the infection rate of knowledge diffusion in such systems.These conclusions extend the theoretical boundaries of innovation ecosystems and knowledge diffusion and offer management implications for enterprises and governments in decision-making.

Immune-related adverse events of immune checkpoint inhibitors combined with angiogenesis inhibitors: A real-world pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database (2014-2022).

INTRODUCTION: Although immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) has become increasingly used for cancers, the impact of combination therapy on immune-related adverse events (irAEs) in real-world settings has not been well elucidated to date. METHODS: The FDA Adverse Event Reporting System (FAERS) database from 2014 to 2022 was retrospectively queried to extract reports of irAEs referred as standardized MedDRA queries (SMQs), preferred terms (PTs) and system organ classes (SOCs). To perform disproportionality analysis, information component (IC) and reporting odds ratio (ROR) were calculated and lower limit of 95 % confidence interval (CI) for IC (IC025) > 0 or ROR (ROR025) > 1 with at least 3 reports was considered statistically significant. RESULTS: Compared to ICIs alone, ICIs + AGIs demonstrated a lower IC025/ROR025 for irAEs-SMQ (2.343/5.082 vs. 1.826/3.563). Regarding irAEs-PTs, there were fewer irAEs-PTs of significant value in ICIs + AGIs than ICIs alone (57 vs. 150 PTs) and lower signal value for most PTs (88 %) in ICIs + AGIs. Moreover, lower IC025 for most of irAEs-SOCs in ICIs + AGIs (11/13) compared with ICIs alone was observed. As for outcomes of irAEs, ICIs + AGIs showed a lower frequency of "fatal" for irAEs-SMQ than ICIs alone (4.88 % vs. 7.83 %), so as in cardiac disorder (SOC) (15.45 % vs. 26.37 %), and respiratory, thoracic and mediastinal disorders (SOC) (13.74 % vs. 20.06 %). Similarly, there were lower occurrence and fewer fatality of irAEs in ICIs + AGIs + chemotherapy (CT) than ICIs + CT. CONCLUSION: ICIs combined with AGIs may reduce incidence and mortality for most of irAEs compared to ICIs alone whether or not with CT.

Association of different doses of antenatal corticosteroids exposure with early major outcomes and early weight loss percentage in extremely preterm infants or extremely low birthweight infants: a multicentre cohort study.

OBJECTIVES: To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI) or extremely low birthweight infants (ELBWI). METHODS: A multicentre, retrospective cohort study of EPI or ELBWI born between 2017 and 2018 was conducted. Infants were classified into no ANS, partial ANS and complete ANS exposure group; three subgroups were generated by gestational age and birth weight. Multiple logistic regression and multiple linear regression were performed. RESULTS: There were 725 infants included from 32 centres. Among no ANS, partial ANS and complete ANS exposure, there were significant differences in the proportions of bronchopulmonary dysplasia (BPD) (24.5%, 25.4% and 16.1%), necrotising enterocolitis (NEC) (6.7%, 2.0% and 2.0%) and death (29.6%, 18.5% and 13.5%), and insignificant differences in the proportions of intraventricular haemorrhage (IVH) (12.5%, 13.2% and 12.2%), and extrauterine growth restriction (EUGR) (50.0%, 56.6% and 59.5%). In the logistic regression, compared with no ANS exposure, complete ANS reduced the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91), NEC (OR 0.21, 95% CI 0.08 to 0.57) and death (OR 0.36, 95% CI 0.23 to 0.56), and partial ANS reduced the risk of NEC (OR 0.23, 95% CI 0.07 to 0.72) and death (OR 0.54, 95% CI 0.34 to 0.87). Compared with partial ANS exposure, complete ANS decreased the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91). There were insignificant associations between ANS exposure and IVH, EUGR. In the multiple linear regression, partial and complete ANS exposure increased EWLP only in the ≥28 weeks (w) and <1000 g subgroup (p<0.05). CONCLUSIONS: Different doses of ANS (dexamethasone) exposure were protectively associated with BPD, NEC, death in hospital, but not EUGR at discharge among EPI or ELBWI. Beneficial dose-dependent associations between ANS (dexamethasone) exposure and BPD existed. ANS exposure increased EWLP only in the ≥28 w and<1000 g subgroup. ANS administration, especially complete ANS, is encouraged before preterm birth. TRIAL REGISTRATION NUMBER: NCT06082414.

A Computational Approach to Understanding and Predicting the Edulcorant Profile of Glucosyl Steviol Glycosides.

Understanding the edulcorant profile of synthetic glucosyl steviol glycosides (GSGs) and rare natural steviol glycosides (SGs) is challenging due to their numerous species and rareness. This study developed a computational model based on the interactions of SG molecules with human sweet and bitter taste receptors (hSTR/hBTR). The models demonstrated a high correlation between the cumulative interaction energies and the perceived sweetness of SGs (R2 = 0.97), elucidating the mechanism of the diverse sweetness of SGs. It also revealed that more (within three) glucose residues at the C-13 position of the SG molecule yield stronger sweetness and weaker bitterness. Furthermore, the computational prediction was consistently validated with the known sweetness of GSG and also aligned well with that of several natural mogrosides. Thus, this model possesses a potential to predict the sweetness of SGs, GSGs, and mogrosides, facilitating the application or targeted synthesis of GSGs with desired sensory profiles.

[A prospective cohort study of association between early childhood body mass index trajectories and the risk of overweight].

OBJECTIVE: To compare the association between body mass index (BMI) trajectories determined by different methods and the risk of overweight in early childhood in a prospective cohort study, and to identify children with higher risk of obesity during critical growth windows of early childhood. METHODS: A total of 1 330 children from Peking University Birth Cohort in Tongzhou (PKUBC-T) were included in this study. The children were followed up at birth, 1, 3, 6, 9, 12, 18, and 24 months and 3 years of age to obtain their height/length and weight data, and calculate BMI Z-score. Latent class growth mixture modeling (GMM) and longitudinal data-based k-means clustering algorithm (KML) were used to determine the grouping of early childhood BMI trajectories from birth to 24 mouths. Linear regression was used to compare the association between early childhood BMI trajectories determined by different methods and BMI Z-score at 3 years of age. The predictive performance of early childhood BMI trajectories determined by different methods in predicting the risk of overweight (BMI Z-score > 1) at 3 years was compared using the average area under the curve (AUC) of 5-fold cross-validation in Logistic regression models. RESULTS: In the study population included in this research, the three-category trajectories determined using GMM were classified as low, medium, and high, accounting for 39.7%, 54.1%, and 6.2% of the participants, respectively. The two-category trajectories determined using the KML method were classified as low and high, representing 50. 3% and 49. 7% of the participants, respectively. The three-category trajectories determined using the KML method were classified as low, medium, and high, accounting for 31.1%, 47.4%, and 21.5% of the participants, respectively. There were certain differences in the growth patterns reflected by the early childhood BMI trajectories determined using different methods. Linear regression analysis found that after adjusting for maternal ethnicity, educational level, delivery mode, parity, maternal age at delivery, gestational week at delivery, children' s gender, and breastfeeding at 1 month of age, the association between the high trajectory group in the three-category trajectories determined by the KML method (manifested by a slightly higher BMI at birth, followed by rapid growth during infancy and a stable-high BMI until 24 months) and BMI Z-scores at 3 years was the strongest. Logistic regression analysis revealed that the three-category trajectory grouping determined by the KML method had the best predictive performance for the risk of overweight at 3 years. The results were basically consistent after additional adjustment for the high bound score of the child' s diet balanced index, average daily physical activity time, and screen time. CONCLUSION: This study used different methods to identify early childhood BMI trajectories with varying characteristics, and found that the high trajectory group determined by the KML method was better able to identify children with a higher risk of overweight in early childhood. This provides scientific evidence for selecting appropriate methods to define early childhood BMI trajectories.

Calpain 8 as a potential biomarker regulates the progression of pancreatic cancer via EMT and AKT/ERK pathway.

Calpain is a non-lysozyme, calcium-dependent intracellular cysteine protease that has been shown to play a role in tumor proliferation, survival, migration, invasion, and apoptosis. Dysregulation of calpain expression is closely related to tumorigenesis. However, the role of calpain-8 (CAPN8), as a member of the calpain family, in pancreatic cancer (PC) is remains unclear. In elucidating the mechanism of CAPN8 in PC, a comprehensive bioinformatics analysis and in vitro experiments were conducted. The TCGA database was used to explore the expression level of CAPN8, and the results in PC tissues and cell lines were verified. Then, the correlation between CAPN8 and clinicopathological features was analyzed. Additionaly, promoter methylation, immune infiltration, and GO/KEGG enrichment analyses were performed. Lastly, the molecular mechanism of CAPN8 in PC was investigated by using cell counting kit (CCK) 8, transwell, wound healing, Western blot assays, and so on. Results indicate that CAPN8 was highly expressed in PC and correlated with poor prognosis and advanced TNM stage. In addition, a low level of immune infiltration was closely associated with the high expression level of CAPN8. Based on these findings, we hypothesized that CAPN8 is a potential biomarker that regulates progression of PC via EMT and the AKT/ERK pathway. SIGNIFICANCE: Through comprehensive biological information and in vitro experiments, CAPN8 has been confirmed to play an important role in regulating pancreatic cancer (PC) proliferation, migration and invasion. CAPN8 is found to be closely related to the diagnosis, survival and prognosis of PC. Above all, CAPN8 may be a potential biomarker for the diagnosis and prognosis of PC.

Potential drug targets for tumors identified through Mendelian randomization analysis.

According to the latest cancer research data, there are a significant number of new cancer cases and a substantial mortality rate each year. Although a substantial number of clinical patients are treated with existing cancer drugs each year, the efficacy is unsatisfactory. The incidence is still high and the effectiveness of most cancer drugs remains unsatisfactory. Therefore, we evaluated the human proteins for their causal relationship to for cancer risk and therefore also their potential as drug targets. We used summary tumors data from the FinnGen and cis protein quantitative trait loci (cis-pQTL) data from a genome-wide association study, and employed Mendelian randomization (MR) to explore the association between potential drug targets and nine tumors, including breast, colorectal, lung, liver, bladder, prostate, kidney, head and neck, pancreatic caners. Furthermore, we conducted MR analysis on external cohort. Moreover, Bidirectional MR, Steiger filtering, and colocalization were employed to validate the main results. The DrugBank database was used to discover potential drugs of tumors. Under the threshold of False discovery rate (FDR) < 0.05, results showed that S100A16 was protective protein and S100A14 was risk protein for human epidermal growth factor receptor 2-positive (HER-positive) breast cancer, phosphodiesterase 5A (PDE5A) was risk protein for colorectal cancer, and melanoma inhibitory activity (MIA) was protective protein for non-small cell lung carcinoma (NSCLC). And there was no reverse causal association between them. Colocalization analysis showed that S100A14 (PP.H4.abf = 0.920) and S100A16 (PP.H4.abf = 0.932) shared causal variation with HER-positive breast cancer, and PDE5A (PP.H4.abf = 0.857) shared causal variation with colorectal cancer (CRC). The MR results of all pQTL of PDE5A and MIA were consistent with main results. In addition, the MR results of MIA and external outcome cohort were consistent with main results. In this study, genetic predictions indicate that circulating S100 calcium binding protein A14 (S100A14) and S100 calcium binding protein A16 (S100A16) are associated with increase and decrease in the risk of HER-positive breast cancer, respectively. Circulating PDE5A is associated with increased risk of CRC, while circulating MIA is associated with decreased risk of NSCLC. These findings suggest that four proteins may serve as biomarkers for cancer prevention and as potential drug targets that could be expected for approval.

Cardiorespiratory fitness attenuates the association between fatness and cardiometabolic risk in Chinese children.

Background: Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences. Methods: We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF. Results: Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What's more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% (P < 0.001). Conclusion: In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children.

Solvent Regulation Induced Cathode Aggregation-Induced Electrochemiluminescence of Tetraphenylethylene Nanoaggregates for Ultrasensitive Zearalenone Analysis.

Zearalenone (ZEN) is an extremely hazardous chemical widely existing in cereals, and its high-sensitivity detection possesses significant significance to human health. Here, the cathodic aggregation-induced electrochemiluminescence (AIECL) performance of tetraphenylethylene nanoaggregates (TPE NAs) was modulated by solvent regulation, based on which an electrochemiluminescence (ECL) aptasensor was constructed for sensitive detection of ZEN. The aggregation state and AIECL of TPE NAs were directly and simply controlled by adjusting the type of organic solvent and the fraction of water, which solved the current shortcomings of low strength and weak stability of the cathode ECL signal for TPE. Impressively, in a tetrahydrofuran-water mixed solution (volume ratio, 6:4), the relative ECL efficiency of TPE NAs reached 16.03%, which was 9.2 times that in pure water conditions, and the maximum ECL spectral wavelength was obviously red-shifted to 617 nm. In addition, "H"-shape DNA structure-mediated dual-catalyzed hairpin self-assembly (H-D-CHA) with higher efficiency by the synergistic effect between the two CHA reactions was utilized to construct a sensitive ECL aptasensor for ZEN analysis with a low detection limit of 0.362 fg/mL. In conclusion, solvent regulation was a simple and efficient method for improving the performance of AIECL materials, and the proposed ECL aptasensor had great potential for ZEN monitoring in food safety.