bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of endothelial NO synthase and P2X7 receptor modification mediates the cholinergic control of ATP-induced interleukin-1β release by mononuclear phagocytes
Authors: Richter Katrin , Asci Nilay , Singh Vijay K. , Yakoob Sanaria Hawro , Meixner Marion , Zakrzewicz Anna , Liese Juliane , Hecker Andreas , Wilker Sigrid , Stumpf Sabine , Schlüter Klaus-Dieter , Rohde Marius , Gödecke Axel , Padberg Winfried , Manzini Ivan , Schmalzing Günther , Grau Veronika
Published: March 2023

Objective

The pro-inflammatory cytokine interleukin-1β (IL-1β) plays a central role in host defense against infections. High systemic IL-1β levels, however, promote the pathogenesis of inflammatory disorders. Therefore, mechanisms controlling IL-1β release are of substantial clinical interest. Recently, we identified a cholinergic mechanism inhibiting the ATP-mediated IL-1β release by human monocytes via nicotinic acetylcholine receptor (nAChR) subunits α7, α9 and/or α10. We also discovered novel nAChR agonists that trigger this inhibitory function in monocytic cells without eliciting ionotropic functions at conventional nAChRs. Here, we investigate the ion flux-independent signaling pathway that links nAChR activation to the inhibition of the ATP-sensitive P2X7 receptor (P2X7R).

Methods

Different human and murine mononuclear phagocytes were primed with lipopolysaccharide and stimulated with the P2X7R agonist BzATP in the presence or absence of nAChR agonists, endothelial NO synthase (eNOS) inhibitors, and NO donors. IL-1β was measured in cell culture supernatants. Patch-clamp and intracellular Ca2+ imaging experiments were performed on HEK cells overexpressing human P2X7R or P2X7R with point mutations at cysteine residues in the cytoplasmic C-terminal domain.

Results

The inhibitory effect of nAChR agonists on the BzATP-induced IL-1β release was reversed in the presence of eNOS inhibitors (L-NIO, L-NAME) as well as in U937 cells after silencing of eNOS expression. In peripheral blood mononuclear leukocytes from eNOS gene-deficient mice, the inhibitory effect of nAChR agonists was absent, suggesting that nAChRs signal via eNOS to inhibit the BzATP-induced IL-1β release. Moreover, NO donors (SNAP, S-nitroso-N-acetyl-DL-penicillamine; SIN-1) inhibited the BzATP-induced IL-1β release by mononuclear phagocytes. The BzATP-induced ionotropic activity of the P2X7R was abolished in the presence of SIN-1 in both, Xenopus laevis oocytes and HEK cells over-expressing the human P2X7R. This inhibitory effect of SIN-1 was absent in HEK cells expressing P2X7R, in which C377 was mutated to alanine, indicating the importance of C377 for the regulation of the P2X7R function by protein modification.

Conclusion

We provide first evidence that ion flux-independent, metabotropic signaling of monocytic nAChRs involves eNOS activation and P2X7R modification, resulting in an inhibition of ATP signaling and ATP-mediated IL-1β release. This signaling pathway might be an interesting target for the treatment of inflammatory disorders.
Extensive prokaryotic maintenance respiration in the sea influenced by osmoregulation
Authors: Wikner Johan , Vikström Kevin
Published: March 2023

Microbial respiration is the major process consuming oxygen in the biosphere. The relative energy demand from growth of biomass or maintenance activities determines the regulation of respiration with impact on how the development of hypoxia and CO2 emissions is controlled. This coupling is crucial for understanding the life history and associated ecological interactions of microorganisms. However, the knowledge of rate and regulating factors of maintenance respiration in the biosphere is limited. In this study, we demonstrated significant relationships in marine field samples where the prokaryotic specific growth rate predicts cell-specific respiration, in accordance with theory from culture models, over a 10-fold salinity range. This enables the first reported direct estimates of maintenance respiration in nature to show a 6-fold variation between 0.12-0.62 fmol O2 cell-1 d-1, comprising 29-72% of prokaryotic specific respiration. The lowest maintenance respiration occurred at salinity close to physiological osmolarity, suggesting osmoregulation as one of the more energy-consuming maintenance activities. A conservative global estimate of maintenance respiration accounted for 66% of the total prokaryotic respiration in the ocean´s mixed layer. This means that maintenance activities dominate the use of the energy generated by prokaryotic respiration in the sea, where osmoregulation is one significant energy consumer. Consequently, maintenance respiration and its regulation must be included in ecological and biogeochemical models to accurately project and manage the development of hypoxia and CO2 emissions from the ocean.
Protective effects of intrathecal injection of AAV9-RabGGTB-GFP+ in SOD1G93A mice
Authors: Gao Tianchu , Huo Jia , Xin Cheng , Yang Jing , Liu Qi , Dong Hui , Li Rui , Liu Yaling
Published: March 2023

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that widely affects motor neurons of the CNS. About 20% of patients with ALS have familial ALS (fALS). One of the classic models of ALS are SOD1G93A mice. Misfolded SOD1 protein can be overexpressed in motor neurons, which results in progressive paralysis of the limbs of mice. There is still no effective treatment for ALS. In recent years, the treatment of ALS by regulating autophagy has become a research hotspot. Autophagy obstacles have been confirmed to be one of the early pathological events of ALS. Rab7 is a member of the Ras superfamily and plays a key role in the late stage of autophagy. In our previous studies, we found that prenoylation of Rab7 was inhibited in the ALS model. Prenylation is a post-translational modification in which farnesyl or geranylgeranyl groups are covalently linked to target proteins. Based on these findings, we proposed the novel idea that the regulation of RabGGTB (the β-subunit of RabGGTase) mediated prenylation modification of Rab7, and that this can be used as a prevention and treatment of ALS associated with abnormal protein accumulation.

Methods

In the present study, RabGGTB was overexpressed in mouse spinal cord motoneurons by using adeno-associated virus as vector. Then immunofluorescence quantitative analysis was used for pathological study. The body weight, footprint analysis, the accelerating rotarod test, and neurological deficits score were used to evaluate animal behavior.

Results

Our results show that the protein level of RabGGTB was significantly increased in the lumbar and thoracic regions of spinal cord motoneurons of injected mice. Furthermore, the onset time and survival time of SOD1G93A mice injected with AAV9-RabGGTB-GFP+ were delayed compared with those of mice without overexpression. At the same time, we also observed a decrease in SOD1 misfolded and glial overactivation in the lumbar spinal cord of these SOD1G93A mice.

Conclusion

The findings reported here show that RabGGTB plays a significant role in the pathogenesis of SOD1G93A mice and with great therapeutic potential for reducing abnormal aggregation of SOD1 in ALS.
Characteristics of fatigue in Parkinson’s disease: A longitudinal cohort study
Authors: Zhou Xiaoxia , Xiang Yaqin , Song Tingwei , Zhao Yuwen , Pan Hongxu , Xu Qian , Chen Yase , Sun Qiying , Wu Xinyin , Yan Xinxiang , Guo Jifeng , Tang Beisha , Lei Lifang , Liu Zhenhua ,   for Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC)
Published: March 2023

Objective

To assess the prevalence, evolution, clinical characteristics, correlates and predictors of fatigue as well as to investigate the influence of comorbid fatigue on the longitudinal changes in motor and non-motor symptoms over a 2-year longitudinal follow-up period in a large cohort of patients with Parkinson’s disease (PD).

Materials and methods

A total of 2,100 PD patients were enrolled from the Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC), and their motor and non-motor symptoms were assessed biennially using comprehensive scales, including the 16-item Parkinson Fatigue Scale (PFS-16). Each PD patient was categorized as PD with or without fatigue on the basis of a cut-off mean PFS-16 score of 3.3.

Results

The prevalence of fatigue in our cohort was 36.8%. Compared to PD patients without fatigue, PD patients with fatigue were more likely to be older, have a longer disease duration, and higher baseline levodopa equivalent daily dose (all p < 0.05). Moreover, PD patients with fatigue showed more severe motor and non-motor phenotypes than those without fatigue. Overall, high total Unified Parkinson’s Disease Rating Scale (UPDRS) score (odds ratio [OR] = 1.016, 95% confidence interval [CI]: 1.009–1.024), Non-Motor Symptoms Scale score (OR = 1.022, 95% CI: 1.015–1.029), postural instability and gait difficulty (PIGD) subtype (OR = 1.586, 95% CI: 1.211–2.079), presence of excessive daytime sleepiness (EDS; OR = 1.343, 95% CI: 1.083–1.666), and wearing-off (OR = 1.282, 95% CI: 1.023–1.607) were significantly associated with fatigue in PD patients (all p < 0.05). High total UPDRS score at baseline (OR = 1.014, 95% CI: 1.002–1.027, p = 0.028) increased the risk of developing fatigue during follow-up. Although significant, the odds ratios were low and confidence intervals were narrow. Analysis of disease progression showed significant group differences in motor and non-motor symptoms. In comparison with the never-fatigue group, the persistent-fatigue group showed significantly greater progression in motor, autonomic dysfunction, sleep, depression and cognitive symptoms (all p < 0.05).

Conclusion

Increased disease severity, presence of the PIGD subtype, EDS, and wearing-off were associated with fatigue in PD patients. Significant subgroup-level differences were observed in the progression of motor and non-motor symptoms across different fatigue subgroups of PD patients.
Advances in biotechnology and clinical therapy in the field of peripheral nerve regeneration based on magnetism
Authors: Fan Zheyuan , Wen Xinggui , Ding Xiangdong , Wang Qianqian , Wang Shoushuai , Yu Wei
Published: March 2023

Peripheral nerve injury (PNI) is one of the most common neurological diseases. Recent studies on nerve cells have provided new ideas for the regeneration of peripheral nerves and treatment of physical trauma or degenerative disease-induced loss of sensory and motor neuron functions. Accumulating evidence suggested that magnetic fields might have a significant impact on the growth of nerve cells. Studies have investigated different magnetic field properties (static or pulsed magnetic field) and intensities, various magnetic nanoparticle-encapsulating cytokines based on superparamagnetism, magnetically functionalized nanofibers, and their relevant mechanisms and clinical applications. This review provides an overview of these aspects as well as their future developmental prospects in related fields.
Research progress of endogenous hematoma absorption after intracerebral hemorrhage
Authors: Fu Peijie , Zhang Manqing , Wu Moxin , Zhou Weixin , Yin Xiaoping , Chen Zhiying , Dan Chuanjun
Published: March 2023

Non-traumatic intraparenchymal brain hemorrhage is referred to as intracerebral hemorrhage (ICH). Although ICH is associated with a high rate of disability and case fatality, active intervention can significantly lower the rate of severe disability. Studies have shown that the speed of hematoma clearance after ICH determines the patient's prognosis. Following ICH, depending on the hematoma volume and mass effect, either surgical- or medication-only conservative treatment is chosen. The goal of promoting endogenous hematoma absorption is more relevant because surgery is only appropriate for a small percentage of patients, and open surgery can cause additional trauma to patients. The primary method of removing hematoma after ICH in the future will involve understanding how to produce and manage macrophage/microglial endogenous phagocytic hematomas. Therefore, it is necessary to elucidate the regulatory mechanisms and key targets for clinical purposes.
Machine learning approaches and non-linear processing of extracted components in frontal region to predict rTMS treatment response in major depressive disorder
Authors: Ebrahimzadeh Elias , Fayaz Farahnaz , Rajabion Lila , Seraji Masoud , Aflaki Fatemeh , Hammoud Ahmad , Taghizadeh Zahra , Asgarinejad Mostafa , Soltanian-Zadeh Hamid
Published: March 2023

Predicting the therapeutic result of repetitive transcranial magnetic stimulation (rTMS) treatment could save time and costs as ineffective treatment can be avoided. To this end, we presented a machine-learning-based strategy for classifying patients with major depression disorder (MDD) into responders (R) and nonresponders (NR) to rTMS treatment. Resting state EEG data were recorded using 32 electrodes from 88 MDD patients before treatment. Then, patients underwent 7 weeks of rTMS, and 46 of them responded to treatment. By applying Independent Component Analysis (ICA) on EEG, we identified the relevant brain sources as possible indicators of neural activity in the dorsolateral prefrontal cortex (DLPFC). This was served through estimating the generators of activity in the sensor domain. Subsequently, we added physiological information and placed certain terms and conditions to offer a far more realistic estimation than the classic EEG. Ultimately, those components mapped in accordance with the region of the DLPFC in the sensor domain were chosen. Features extracted from the relevant ICs time series included permutation entropy (PE), fractal dimension (FD), Lempel-Ziv Complexity (LZC), power spectral density, correlation dimension (CD), features based on bispectrum, frontal and prefrontal cordance, and a combination of them. The most relevant features were selected by a Genetic Algorithm (GA). For classifying two groups of R and NR, K-Nearest Neighbor (KNN), Support Vector Machine (SVM), and Multilayer Perceptron (MLP) were applied to predict rTMS treatment response. To evaluate the performance of classifiers, a 10-fold cross-validation method was employed. A statistical test was used to assess the capability of features in differentiating R and NR for further research. EEG characteristics that can predict rTMS treatment response were discovered. The strongest discriminative indicators were EEG beta power, the sum of bispectrum diagonal elements in delta and beta bands, and CD. The Combined feature vector classified R and NR with a high performance of 94.31% accuracy, 92.85% specificity, 95.65% sensitivity, and 92.85% precision using SVM. This result indicates that our proposed method with power and nonlinear and bispectral features from relevant ICs time-series can predict the treatment outcome of rTMS for MDD patients only by one session pretreatment EEG recording. The obtained results show that the proposed method outperforms previous methods.
Anemia in pregnancy and sleep of 6-month-old infants: A prospective cohort study
Authors: Zhang Lei , Ma Shuangshuang , Dai Feicai , Li Qiong , Wu Lin , Yu Lijun , Xie Tianqin , Zhu Dao-min , Zhu Peng
Published: March 2023

Objective

Anemia has been reported to adversely influence sleep in infants. However, the association between anemia in pregnancy and infant sleep remains unclear. We aimed to examine the association between maternal anemia in pregnancy and sleep parameters of 6-month-old infants.

Methods

We enrolled 2,410 mother-infant pairs between 2018 and 2021 in Hefei. Data on maternal hemoglobin concentration were collected at 24–28 gestational weeks from the electronic medical records of the hospitals. Nocturnal and daytime sleep duration, number of night awakenings, nocturnal wakefulness, and sleep latency of infants aged 6 months were measured using the Brief Infant Sleep Questionnaire with five items. A restricted cubic spline model was used to examine the relationship between maternal hemoglobin concentration and infant nocturnal sleep duration after adjusting for potential confounders.

Results

In our study, 807 (33.5%) mothers had anemia during pregnancy. Compared to infants born to mothers without anemia, infants born to mothers with anemia in pregnancy had shorter nocturnal sleep duration [mean (SD), 560.29 (79.57) mins vs. 574.27 (75.36) mins] at the age of 6 months. Subgroup analysis showed consistent significant differences in nocturnal sleep duration between infant born to anemic and non-anemic mothers, except in case of stratification by preterm birth [mean difference (mins), 2.03 (95% CI, −20.01, −24.07)] and pre-pregnancy obesity [mean difference (mins), −0.85 (95% CI, −16.86, −15.16)]. A J-shaped nonlinear correlation curve was observed between maternal hemoglobin concentration and infant nocturnal sleep duration. Compared with mothers without daily iron supplementation, mothers who had daily iron supplementation had higher hemoglobin concentrations [mean (SD), 112.39 (11.33) g/L vs. 110.66 (10.65) g/L] at delivery and their infants had longer nocturnal sleep duration [mean (SD), 565.99 (82.46) mins vs. 553.66 (76.03) mins].

Conclusion

Anemia in pregnancy may have an adverse influence on the sleep of 6-mon-old infants, and the relationship between maternal hemoglobin concentration and nocturnal sleep duration is nonlinear.
The association between visceral adiposity index and decreased renal function: A population-based study
Authors: Qin Zheng , Chen Xinyang , Sun Jiantong , Jiang Luojia
Published: March 2023

Aims

We aimed to investigate the association of visceral adiposity index (VAI) with decreased renal function in US adults.

Design and methods

Cross-sectional data were analyzed for 35,018 adults in the National Health and Nutrition Examination Survey (NHANES) 2005–2018. VAI was determined using waist circumference, body mass index (BMI), triglycerides (TGs) and high-density lipoprotein-cholesterol. Albuminuria was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g. A low estimated-glomerular filtration rate (eGFR) was defined as an eGFR lower than 60 ml/min/1.73 m2. Chronic kidney disease (CKD) was defined as either albuminuria or low-eGFR. A multivariable logistic regression analysis was utilized to explore the relationship of VAI with albuminuria, low-eGFR and CKD. Subgroup analysis and interaction tests were also conducted.

Results

A total of 35,018 participants were enrolled with albuminuria, low-eGFR, and CKD prevalence rates of 5.18, 6.42, and 10.62%, respectively, which increased with the higher VAI tertiles. After full adjustment, a positive association of VAI with albuminuria (OR = 1.03, 95% CI: 1.00, 1.06) and CKD (OR = 1.04, 95% CI: 1.02, 1.06) was observed. Participants in the highest VAI tertile had a significantly 30% increased risk for albuminuria (OR = 1.30, 95% CI: 1.07, 1.58) and a 27% increased risk for CKD (OR = 1.27, 95% CI: 1.08, 1.49) compared with those in the lowest VAI tertile. No statistically significant association between VAI and low-eGFR was detected. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications.

Conclusion

Visceral adiposity accumulation evaluating by VAI was associated with increased likelihood of the decline in renal function.
Deep learning for the detection of anatomical tissue structures and neoplasms of the skin on scanned histopathological tissue sections
Authors: Kriegsmann Katharina , Lobers Frithjof , Zgorzelski Christiane , Kriegsmann Jörg , Janßen Charlotte , Meliß Rolf Rüdinger , Muley Thomas , Sack Ulrich , Steinbuss Georg , Kriegsmann Mark
Published: March 2023

Basal cell carcinoma (BCC), squamous cell carcinoma (SqCC) and melanoma are among the most common cancer types. Correct diagnosis based on histological evaluation after biopsy or excision is paramount for adequate therapy stratification. Deep learning on histological slides has been suggested to complement and improve routine diagnostics, but publicly available curated and annotated data and usable models trained to distinguish common skin tumors are rare and often lack heterogeneous non-tumor categories. A total of 16 classes from 386 cases were manually annotated on scanned histological slides, 129,364 100 x 100 µm (~395 x 395 px) image tiles were extracted and split into a training, validation and test set. An EfficientV2 neuronal network was trained and optimized to classify image categories. Cross entropy loss, balanced accuracy and Matthews correlation coefficient were used for model evaluation. Image and patient data were assessed with confusion matrices. Application of the model to an external set of whole slides facilitated localization of melanoma and non-tumor tissue. Automated differentiation of BCC, SqCC, melanoma, naevi and non-tumor tissue structures was possible, and a high diagnostic accuracy was achieved in the validation (98%) and test (97%) set. In summary, we provide a curated dataset including the most common neoplasms of the skin and various anatomical compartments to enable researchers to train, validate and improve deep learning models. Automated classification of skin tumors by deep learning techniques is possible with high accuracy, facilitates tumor localization and has the potential to support and improve routine diagnostics.
Loss of liver kinase B1 in human seminoma
Authors: Kumar Manish , Sahoo Subhransu S. , Jamaluddin M. Fairuz B. , Tanwar Pradeep S.
Published: March 2023

Testicular cancer is a common malignancy of young males and is believed to be originated from defective embryonic or adult germ cells. Liver kinase B1 (LKB1) is a serine/threonine kinase and a tumor suppressor gene. LKB1 is a negative regulator of the mammalian target of rapamycin (mTOR) pathway, often inactivated in many human cancer types. In this study, we investigated the involvement of LKB1 in the pathogenesis of testicular germ cell cancer. We performed immunodetection of LKB1 protein in human seminoma samples. A 3D culture model of human seminoma was developed from TCam-2 cells, and two mTOR inhibitors were tested for their efficacy against these cancer cells. Western blot and mTOR protein arrays were used to show that these inhibitors specifically target the mTOR pathway. Examination of LKB1 showed reduced expression in germ cell neoplasia in situ lesions and seminoma compared to adjacent normal-appearing seminiferous tubules where the expression of this protein was present in the majority of germ cell types. We developed a 3D culture model of seminoma using TCam-2 cells, which also showed reduced levels of LKB1 protein. Treatment of TCam-2 cells in 3D with two well-known mTOR inhibitors resulted in reduced proliferation and survival of TCam-2 cells. Overall, our results support that downregulation or loss of LKB1 marks the early stages of the pathogenesis of seminoma, and the suppression of downstream signaling to LKB1 might be an effective therapeutic strategy against this cancer type.
FES null mice demonstrate a reduction in neutrophil dependent pancreatic cancer metastatic burden
Authors: Strøbech Jan E. , Giuriatti Pietro , Stagaard Rikke , De Sepulveda Paulo , Nielsen Sebastian R. , Erler Janine T.
Published: March 2023

Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5-year survival rate of less than 10%, predominantly due to delayed diagnosis and a lack of effective treatment options. In the PDAC tumor microenvironment (TME), neutrophils are among the immune cell types that are most prevalent and are linked to a poor clinical prognosis. However, treatments that target tumor-associated neutrophils are limited despite recent developments in our understanding of neutrophil function in cancer. The feline sarcoma oncogene (FES) is a nonreceptor tyrosine kinase previously associated with leukemia and hematopoietic homeostasis. Here we describe a newly derived FES null mouse with no distinct phenotype and no defects in hematopoietic homeostasis including neutrophil viability. The immune cell composition and neutrophil population were analyzed with flow cytometry, colony-forming unit (CFU) assay, and a neutrophil viability assay, while the response to PDAC was examined with an in vivo cancer model. In an experimental metastasis model, the FES null model displayed a reduced PDAC hepatic metastatic burden and a reduction in neutrophils granulocytes. Accordingly, our results indicate FES as a potential target for PDAC TME modulation.
Development and validation of nomograms for predicting axillary non-SLN metastases in breast cancer patients: A retrospective analysis
Authors: Lei Huizi , Yuan Pei , Guo Changyuan , Ying Jianming
Published: March 2023

Purpose

The aim of this study was to develop a nomogram for predicting positive non-sentinel lymph nodes (non-SLNs) in positive SLN breast cancer patients and validate the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram for non-SLN metastasis in Chinese patients.

Methods

The pathological features of 2,561 breast cancer patients were retrospectively reviewed, and the patients were divided into training and validation cohorts. Positive non-SLN predictors were identified using univariate and multivariate analyses and used to construct the nomogram. In patients with positive SLNs, the MSKCC nomogram was used to calculate the probability of non-SLN metastasis. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of this model and the MSKCC nomogram.

Results

According to multivariate logistic regression analysis, the number of positive and negative SLNs, tumor stage, lymphovascular invasion, perineural invasion, and extracapsular extension were independent predictive factors for non-SLN metastasis and were selected to establish the nomogram for predicting positive non-SLNs. This nomogram performed favorably in predicting positive non-SLNs, with AUCs of 0.765 and 0.741 for the training and validation cohorts, respectively. The MSKCC nomogram predicted non-SLN metastasis with an AUC of 0.755.

Conclusion

A nomogram was developed and validated to assist clinicians in evaluating the likelihood of positive non-SLN. For Chinese patients with a known ER status before surgery, the MSKCC nomogram can be used to predict non-SLN metastases.
Severe hyperlipidemia pancreatitis induced by taking tamoxifen after breast cancer surgery—Case report
Authors: Zhai Chao , Li Xiang , Xiao Dong , Chen Liang , Wang Chaoyang , Zheng MingHua
Published: March 2023

Introduction

The research investigates the mechanism, diagnosis, treatment, and subsequent endocrine therapy of severe pancreatitis induced by tamoxifen treatment in patients who have undergone breast cancer surgery.

Case presentation

We studied two cases of breast cancer in whom severe acute pancreatitis developed after taking tamoxifen for endocrine therapy in our hospital. A brief literature review was provided to analyze the causes, clinical manifestations, treatment process, and prognosis of severe acute pancreatitis. Both cases involved patients with severe hyperlipidemic pancreatitis. After conservative treatment, none of them died. Pancreatitis did not recur after changing endocrine therapy drugs.

Discussion/conclusion

Endocrine therapy with tamoxifen in breast cancer patients can induce hyperlipidemia, which can subsequently cause severe pancreatitis. The treatment of severe pancreatitis should strengthen the regulation of blood lipids. The application of low-molecular-weight heparin combined with insulin therapy can rapidly lower blood lipids. Involved treatments, including acid suppression, enzyme suppression, and peritoneal dialysis, can accelerate the recovery of pancreatitis and reduce the occurrence of serious complications. Patients with severe pancreatitis should not continue to use tamoxifen for endocrine therapy. To complete follow-up endocrine therapy, switching to a steroidal aromatase inhibitor is better if the situation allows it.
Can angiogenesis inhibitor therapy cause changes in imaging features of hepatic hemangioma- Initial study
Authors: Liu Tang , Pan Wenxue , Lai Shengyuan , Luo Jiawen
Published: March 2023

Background

To observe whether anti-angiogenesis therapy can induce changes in size and enhancement characteristics of hepatic hemangioma.

Method

133 patients with hepatic hemangioma lesions were analyzed and classified into a Bevacizumab group (n=65) and the control group (n=68). The parameters (Volume, CT enhancement ratio, enhancement patterns) of pre-and post-treatment in the bevacizumab and control groups independently calculated and compared by two radiologists. Correlation among the systolic blood pressure, diastolic blood pressure, heart rate with the hemangioma volume was evaluated using Pearson’s correlation analysis.

Results

The hepatic hemangioma volume was significantly decreased after treatment in the Bevacizumab group (8.6 ± 18.7mL vs.7.3 ± 16.3mL, P<0.05), and there was no significant change in the control group (15.1 ± 19.8mL vs.15.4 ± 20.7mL, P = 0.504). A significant difference in enhancement patterns of hepatic hemangiomas was observed after treatment with Bevacizumab (P<0.01). There was no significant difference in arterial phase (AP)enhancement rate and arterial phase-portal venous phase (AP-PVP) enhancement ratios after treatment in the Bevacizumab and control groups (Ps>0.05).The Pearson correlation results showed that blood pressure, heart rate, and hemangioma volume were unrelated or weakly related before and after bevacizumab treatment under the control of factors including weight, contrast injection scheme and CT scanning scheme.

Conclusions

Anti-angiogenesis therapy can cause changes in enhancement pattern and volume of hepatic hemangioma. Radiologists should pay more attention to the reexamination of tumor patients treated with anti-angiogenesis therapy.
LSD1 inhibition modulates transcription factor networks in myeloid malignancies
Authors: Hartung Emily E. , Singh Kanwaldeep , Berg Tobias
Published: March 2023

Acute Myeloid Leukemia (AML) is a type of cancer of the blood system that is characterized by an accumulation of immature hematopoietic cells in the bone marrow and blood. Its pathogenesis is characterized by an increase in self-renewal and block in differentiation in hematopoietic stem and progenitor cells. Underlying its pathogenesis is the acquisition of mutations in these cells. As there are many different mutations found in AML that can occur in different combinations the disease is very heterogeneous. There has been some progress in the treatment of AML through the introduction of targeted therapies and a broader application of the stem cell transplantation in its treatment. However, many mutations found in AML are still lacking defined interventions. These are in particular mutations and dysregulation in important myeloid transcription factors and epigenetic regulators that also play a crucial role in normal hematopoietic differentiation. While a direct targeting of the partial loss-of-function or change in function observed in these factors is very difficult to imagine, recent data suggests that the inhibition of LSD1, an important epigenetic regulator, can modulate interactions in the network of myeloid transcription factors and restore differentiation in AML. Interestingly, the impact of LSD1 inhibition in this regard is quite different between normal and malignant hematopoiesis. The effect of LSD1 inhibition involves transcription factors that directly interact with LSD1 such as GFI1 and GFI1B, but also transcription factors that bind to enhancers that are modulated by LSD1 such as PU.1 and C/EBPα as well as transcription factors that are regulated downstream of LSD1 such as IRF8. In this review, we are summarizing the current literature on the impact of LSD1 modulation in normal and malignant hematopoietic cells and the current knowledge how the involved transcription factor networks are altered. We are also exploring how these modulation of transcription factors play into the rational selection of combination partners with LSD1 inhibitors, which is an intense area of clinical investigation.
The abnormal umbilical venous–arterial index in the second half of pregnancy is associated with fetal outcome: A retrospective cross-sectional study
Authors: Wang Ling , Zhou Dan , Long Baiguo , Wang Jiqing , Li Lingling , Peng Yang , Zhou Qichang , Zeng Shi
Published: March 2023

Objective

This study aims to observe the changes of the umbilical venous–arterial index (VAI) and investigate its predictive power for fetal outcome during the second half of pregnancy.

Methods

Fetuses with gestational age (GA) at 24–39 weeks were collected. According to the outcome score, neonates with outcome scores of 0, 1, or 2 were assigned to the control group, whereas those with scores of 3–12 were assigned to the compromised group. VAI was calculated as the ratio of normalized umbilical vein blood flow volume and umbilical artery pulsatility index. Regression analysis was performed to obtain the best-fitting curves between VAI and GA in the controls. Doppler parameters and perinatal outcomes were compared in both groups. Receiver operating characteristic analysis was used to assess the diagnostic performance of the VAI.

Results

A total of 833 (95%) fetuses had Doppler parameters and pregnancy outcomes documented. Compared with the controls, the VAI was significantly lower in the compromised group (83.2 vs. 184.8 ml/min/kg, p < 0.001). The sensitivity and specificity of VAI to predict compromised neonates were 95.15% (95% Cl, 89.14 to 97.91%) and 99.04% (95% CI: 98.03 to 99.53%), respectively at a cutoff value of 120 ml/min/kg.

Conclusions

VAI presents better diagnostic performance than umbilical vein blood flow volume and umbilical artery pulsatility index. A cutoff value of 120 ml/min/kg might be used as the warning value for predicting the fetal outcome.
The emerging role of long non-coding RNAs in renal cell carcinoma progression and clinical therapy via targeting metabolic regulation
Authors: Gao Xingyu , Zhang Haiying , Zhang Chang , Li Minghe , Yu Xiao , Sun Yanan , Shi Yingai , Zhang Hongxia , He Xu
Published: March 2023

Graphical Abstract

This review mainly describes that lncRNAs interact with miRNA-mRNA axis, or directly binds to mRNAs and proteins, to influence RCC progression via metabolic regulation, mainly including glucose metabolism, lipid metabolism, amino acid metabolism and mitochondrial dynamics (Created with biorender.com).
Pharmacological activities and effective substances of the component-based Chinese medicine of Ginkgo biloba leaves based on serum pharmacochemistry, metabonomics and network pharmacology
Authors: Liang Hongbao , Yao Jingchun , Miao Yu , Sun Ying , Gao Yanbing , Sun Chenghong , Li Rui , Xiao He , Feng Qun , Qin Guofei , Lu Xiaoyan , Liu Zhong , Zhang Guimin , Li Feng , Shao Mingguo
Published: March 2023

As a potential drug candidate for the treatment of hypertension and complications, it is speculated that the component-based Chinese medicine of Ginkgo biloba leaves (GBCCM) which mainly composed of flavonoid aglycones (FAs) and terpene lactones (TLs) may have different pharmacological effects at different doses or ratios. Taking the normal mice as the study object, metabonomics was conducted by giving different doses of GBCCM. Based on the components of GBCCM absorbed into the blood, the network pharmacological prediction was carried out. By integrating the results of metabonomics and network pharmacology, predict the possible pharmacological effects of GBCCM and conduct experimental verification. It was found that eight of the 19 compounds in GBCCM could be absorbed into the blood. GBCCM mainly affected the signal pathways of unsaturated fatty acid, pyruvate, bile acid, melanin and stem cells. It was speculated that GBCCM might have activities such as lowering blood pressure, regulating stem cell proliferation and melanogenesis. By establishing the models of mushroom tyrosinase, rat bone marrow mesenchymal stem cells (BMSCs) and spontaneously hypertensive rats (SHRs), we found that FAs and TLs showed synergistic effect in hypertension and tyrosinase models, and the optimal ratio was 3:2 (4.4 mg/kg) and 1:1 (0.4 mg/ml), respectively. As effective substances, FAs significantly promoted the proliferation of rat BMSCs on the third and fifth days at the concentration of 0.2 μg/ml (p < 0.05). GBCCM showed a variety of pharmacological effects at different doses and ratios, which provided an important reference for the druggability of GBCCM.
Effects of running-based versus body-weight-based high-intensity interval training on physical fitness in healthy adolescents
Authors: Li Zhen , Liu Yang , Han Xiaowei , Zhou Zhixiong
Published: March 2023

Objectives: High-intensity interval training improves aerobic endurance, but the effectiveness of different training protocols is unclear. This study compared the effects of running-based high-intensity interval training (R-HIIT) and body weight-based high-intensity interval training (B-HIIT) on physical fitness in adolescents.

Methods: This was a pre-and post-test quasi-experimental design in which a seventh-grade natural class was randomly selected from three homogeneous middle schools, and then the three natural classes were randomly divided into three groups: the R-HIIT group (n = 54), the B-HIIT group (n = 55), and the control group (Con, n = 57). Both intervention groups exercised twice a week for 12 weeks with a 2:1 (1 min:30 s) load-interval ratio and exercise intensity controlled at 70%–85% maximum heart rate. R-HIIT was in the form of running, and B-HIIT was in the form of resistance exercises using the participants’ body weight. The control group was instructed to continue their normal behavior. cardiorespiratory fitness, muscle strength and endurance, and speed were measured before and after the intervention. Statistical differences between and within groups were determined using repeated measures analysis of variance.

Results: Compared to the baseline, both the R-HIIT and B-HIIT intervention groups significantly improved CRF, muscle strength, and speed (p < 0.05). The B-HIIT group was significantly better than R-HIIT in improving CRF (4.48 mL/kg/min vs 3.34 mL/kg/min, p < 0.05), and only the B-HIIT improved sit-up muscle endurance (ηp2 = 0.30, p < 0.05).

Conclusion: The B-HIIT protocol was significantly more effective than the R-HIIT protocol in developing CRF and improving muscle health indicators.
Effects of high resistance muscle training on corticospinal output during motor fatigue assessed by transcranial magnetic stimulation
Authors: Dietmann Anelia , Blanquet Marisa , Rösler Kai Michael , Scheidegger Olivier
Published: March 2023

Introduction: Central fatigue refers to a reduced drive of motor cortical output during exercise, and performance can be enhanced after training. However, the effects of training on central fatigue remain unclear. Changes in cortical output can be addressed non-invasively using transcranial magnetic stimulation (TMS). The aim of the study was to compare responses to TMS during a fatiguing exercise before and after a 3 weeks lasting resistance training, in healthy subjects.

Methods: The triple stimulation technique (TST) was used to quantify a central conduction index (CCI = amplitude ratio of central conduction response and peripheral nerve response) to the abductor digiti minimi muscle (ADM) in 15 subjects. The training consisted of repetitive isometric maximal voluntary contractions (MVC) of ADM for 2 min twice a day. Before and after this training, TST recordings were obtained every 15 s during an 2 min exercise of MVC of the ADM, where subjects performed repetitive contractions of the ADM, and repeatedly during a recovery period of 7 min.

Results: There was a consistent decrease of force to approximately 40% of MVC in all experiments and in all subjects, both before and after training. In all subjects, CCI decreased during exercise. While before training, theCCI decreased to 49% (SD 23.7%) after 2 min of exercise, it decreased after training onlyto 79% (SD 26.4%) after exercise (p < 0.01).

Discussion: The training regimen increased the proportion of target motor units that could be activated by TMS during a fatiguing exercise. The results point to a reduced intracortical inhibition, which may be a transient physiological response to facilitate the motor task. Possible underlying mechanisms at spinal and supraspinal sites are discussed.
A compact multi-functional model of the rabbit atrioventricular node with dual pathways
Authors: Ryzhii Maxim , Ryzhii Elena
Published: March 2023

The atrioventricular node (AVN) is considered a “black box”, and the functioning of its dual pathways remains controversial and not fully understood. In contrast to numerous clinical studies, there are only a few mathematical models of the node. In this paper, we present a compact, computationally lightweight multi-functional rabbit AVN model based on the Aliev-Panfilov two-variable cardiac cell model. The one-dimensional AVN model includes fast (FP) and slow (SP) pathways, primary pacemaking in the sinoatrial node, and subsidiary pacemaking in the SP. To obtain the direction-dependent conduction properties of the AVN, together with gradients of intercellular coupling and cell refractoriness, we implemented the asymmetry of coupling between model cells. We hypothesized that the asymmetry can reflect some effects related to the complexity of the real 3D structure of AVN. In addition, the model is accompanied by a visualization of electrical conduction in the AVN, revealing the interaction between SP and FP in the form of ladder diagrams. The AVN model demonstrates broad functionality, including normal sinus rhythm, AVN automaticity, filtering of high-rate atrial rhythms during atrial fibrillation and atrial flutter with Wenckebach periodicity, direction-dependent properties, and realistic anterograde and retrograde conduction curves in the control case and the cases of FP and SP ablation. To show the validity of the proposed model, we compare the simulation results with the available experimental data. Despite its simplicity, the proposed model can be used both as a stand-alone module and as a part of complex three-dimensional atrial or whole heart simulation systems, and can help to understand some puzzling functions of AVN.
Ultrasonic optic disc height combined with the optic nerve sheath diameter as a promising non-invasive marker of elevated intracranial pressure
Authors: Yu Ze-yang , Xing Ying-qi , Li Cong , Wang Si-bo , Song Xiao-nan , Wang Cui-cui , Wang Li-juan
Published: March 2023

Background/aim: Patients with elevated intracranial pressure (ICP) tend to have optic disc edema and a thicker optic nerve sheath diameter (ONSD). However, the cut-off value of the optic disc height (ODH) for evaluating elevated ICP is not clear. This study was conducted to evaluate ultrasonic ODH and to investigate the reliability of ODH and ONSD for elevated ICP.

Methods: Patients suspected of having increased ICP and who underwent a lumbar puncture were recruited. ODH and ONSD were measured before lumbar puncture. Patients were divided according to elevated and normal ICP. We analyzed the correlations between ODH, ONSD, and ICP. ODH and ONSD cut-off points for the identification of elevated ICP were determined and compared.

Results: There were a total of 107 patients recruited for this study, 55 patients with elevated ICP and 52 with normal ICP. Both ODH and ONSD in the elevated ICP group were higher than in the normal group [ODH: median 0.81 (range 0.60–1.06) mm vs. 0.40 [0–0.60] mm, p < 0.001; ONSD: 5.01 ± 0.37 mm vs. 4.20 ± 0.38 mm, p < 0.001]. ICP was positively correlated with ODH (r = 0.613; p < 0.001) and ONSD (r = 0.792; p < 0.001). The cut-off values of ODH and ONSD for evaluating elevated ICP were 0.63 mm and 4.68 mm, respectively, with 73% and 84% sensitivity and 83% and 94% specificity, respectively. ODH combined with ONSD showed the highest value under the receiver operating characteristic curve of 0.965 with a sensitivity of 93% and a specificity of 92%.

Conclusion: Ultrasonic ODH combined with ONSD may help monitor elevated ICP non-invasively.
The importance of plant growth-promoting rhizobacteria to increase air pollution tolerance index (APTI) in the plants of green belt to control dust hazards
Authors: Najafi Zilaie Mahmood , Mosleh Arani Asghar , Etesami Hassan
Published: March 2023

Dust causes adverse effects on the physiological and biochemical characteristics of plants and limits their use in the development of the green belt. Air Pollution Tolerance Index (APTI) is an important tool to screen out plants, based on their tolerance or sensitivity level to different air pollutants. The aim of this study was to investigate the effect of two plant growth-promoting bacterial strains (Zhihengliuella halotolerans SB and Bacillus pumilus HR) and their combination as a biological solution on APTI of three desert plant species of Seidlitzia rosmarinus, Haloxylon aphyllum and Nitraria schoberi under dust stress (0 and 1.5 g m-2 30 days-1). Dust caused a significant decrease of 21% and 19%, respectively, in the total chlorophyll of N. schoberi and S. rosmarinus, an 8% decrease in leaf relative water content, a 7% decrease in the APTI of N. schoberi, and a decrease of 26 and 17% in protein content of H. aphyllum and N. schoberi, respectively. However, Z. halotolerans SB increased the amount of total chlorophyll in H. aphyllum and S. rosmarinus by 236% and 21%, respectively, and the amount of ascorbic acid by 75% and 67% in H. aphyllum and N. schoberi, respectively. B. pumilus HR also increased the leaf relative water content in H. aphyllum and N. schoberi by 10% and 15%, respectively. The inoculation with B. pumilus HR, Z. halotolerans SB and the combination of these two isolates decreased the activity of peroxidase by 70%, 51%, and 36%, respectively, in N. schoberi, and 62%, 89%, and 25% in S. rosmarinus, respectively. These bacterial strains also increased the concentration of protein in all three desert plants. Under dust stress, H. aphyllum had a higher APTI than the other two species. Z. halotolerans SB, which had been isolated from S. rosmarinus, was more effective than B. pumilus HR in alleviating the effects of dust stress on this plant. Therefore, it was concluded that plant growth-promoting rhizobacteria can be effective at improving the mechanisms of plant tolerance to air pollution in the green belt.
Transcriptional and metabolic responses of apple to different potassium environments
Authors: Sun Tingting , Zhang Junke , Zhang Qiang , Li Xingliang , Li Minji , Yang Yuzhang , Zhou Jia , Wei Qinping , Zhou Beibei
Published: March 2023

Potassium (K) is one of the most important macronutrients for plant development and growth. The influence mechanism of different potassium stresses on the molecular regulation and metabolites of apple remains largely unknown. In this research, physiological, transcriptome, and metabolite analyses were compared under different K conditions in apple seedlings. The results showed that K deficiency and excess conditions influenced apple phenotypic characteristics, soil plant analytical development (SPAD) values, and photosynthesis. Hydrogen peroxide (H2O2) content, peroxidase (POD) activity, catalase (CAT) activity, abscisic acid (ABA) content, and indoleacetic acid (IAA) content were regulated by different K stresses. Transcriptome analysis indicated that there were 2,409 and 778 differentially expressed genes (DEGs) in apple leaves and roots under K deficiency conditions in addition to 1,393 and 1,205 DEGs in apple leaves and roots under potassium excess conditions, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that the DEGs were involved in flavonoid biosynthesis, photosynthesis, and plant hormone signal transduction metabolite biosynthetic processes in response to different K conditions. There were 527 and 166 differential metabolites (DMAs) in leaves and roots under low-K stress as well as 228 and 150 DMAs in apple leaves and roots under high-K stress, respectively. Apple plants regulate carbon metabolism and the flavonoid pathway to respond to low-K and high-K stresses. This study provides a basis for understanding the metabolic processes underlying different K responses and provides a foundation to improve the utilization efficiency of K in apples.