bluuebunny/crossref_metadata_2025 huggingface dataset:
A review on the research progress on non-pharmacological therapy of Helicobacter pylori
Authors: Luo Qian , Liu Na , Pu Sugui , Zhuang Ze , Gong Hang , Zhang Dekui
Published: March 2023

Helicobacter pylori is a pathogenic microorganism that mainly resides in the human stomach and is the major cause of chronic gastritis, peptic ulcer and gastric cancer. Up to now, the treatment of Helicobacter pylori has been predominantly based on a combination of antibiotics and proton pump inhibitors. However, the increasing antibiotic resistance greatly limits the efficacy of anti-Helicobacter pylori treatment. Turning to non-antibiotic or non-pharmacological treatment is expected to solve this problem and may become a new strategy for treating Helicobacter pylori. In this review, we outline Helicobacter pylori’s colonization and virulence mechanisms. Moreover, a series of non-pharmacological treatment methods for Helicobacter pylori and their mechanisms are carefully summarized, including probiotics, oxygen-rich environment or hyperbaric oxygen therapy, antibacterial photodynamic therapy, nanomaterials, antimicrobial peptide therapy, phage therapy and modified lysins. Finally, we provide a comprehensive overview of the challenges and perspectives in developing new medical technologies for treating Helicobacter pylori without drugs.
Identification of dynamic gene expression profiles during sequential vaccination with ChAdOx1/BNT162b2 using machine learning methods
Authors: Li Jing , Ren JingXin , Liao HuiPing , Guo Wei , Feng KaiYan , Huang Tao , Cai Yu-Dong
Published: March 2023

To date, COVID-19 remains a serious global public health problem. Vaccination against SARS-CoV-2 has been adopted by many countries as an effective coping strategy. The strength of the body’s immune response in the face of viral infection correlates with the number of vaccinations and the duration of vaccination. In this study, we aimed to identify specific genes that may trigger and control the immune response to COVID-19 under different vaccination scenarios. A machine learning-based approach was designed to analyze the blood transcriptomes of 161 individuals who were classified into six groups according to the dose and timing of inoculations, including I-D0, I-D2-4, I-D7 (day 0, days 2–4, and day 7 after the first dose of ChAdOx1, respectively) and II-D0, II-D1-4, II-D7-10 (day 0, days 1–4, and days 7–10 after the second dose of BNT162b2, respectively). Each sample was represented by the expression levels of 26,364 genes. The first dose was ChAdOx1, whereas the second dose was mainly BNT162b2 (Only four individuals received a second dose of ChAdOx1). The groups were deemed as labels and genes were considered as features. Several machine learning algorithms were employed to analyze such classification problem. In detail, five feature ranking algorithms (Lasso, LightGBM, MCFS, mRMR, and PFI) were first applied to evaluate the importance of each gene feature, resulting in five feature lists. Then, the lists were put into incremental feature selection method with four classification algorithms to extract essential genes, classification rules and build optimal classifiers. The essential genes, namely, NRF2, RPRD1B, NEU3, SMC5, and TPX2, have been previously associated with immune response. This study also summarized expression rules that describe different vaccination scenarios to help determine the molecular mechanism of vaccine-induced antiviral immunity.
ALASCA: An R package for longitudinal and cross-sectional analysis of multivariate data by ASCA-based methods
Authors: Jarmund Anders Hagen , Madssen Torfinn Støve , Giskeødegård Guro F.
Published: March 2023

The increasing availability of multivariate data within biomedical research calls for appropriate statistical methods that can describe and model complex relationships between variables. The extended ANOVA simultaneous component analysis (ASCA+) framework combines general linear models and principal component analysis (PCA) to decompose and visualize the separate effects of experimental factors. It has recently been demonstrated how linear mixed models can be included in the framework to analyze data from longitudinal experimental designs with repeated measurements (RM-ASCA+). The ALASCA package for R makes the ASCA+ framework accessible for general use and includes multiple methods for validation and visualization. The package is especially useful for longitudinal data and the ability to easily adjust for covariates is an important strength. This paper demonstrates how the ALASCA package can be applied to gain insights into multivariate data from interventional as well as observational designs. Publicly available data sets from four studies are used to demonstrate the methods available (proteomics, metabolomics, and transcriptomics).
Comprehensive overview of the role of PBX1 in mammalian kidneys
Authors: Zou Fei , Liu Mingsheng , Sui Yutong , Liu Jinyu
Published: March 2023

Pre-B-cell leukemia homeobox transcription factor 1 (PBX1) is a member of the TALE (three-amino acid loop extension) family and functions as a homeodomain transcription factor (TF). When dimerized with other TALE proteins, it can act as a pioneer factor and provide regulatory sequences via interaction with partners. In vertebrates, PBX1 is expressed during the blastula stage, and its germline variations in humans are interrelated with syndromic anomalies of the kidney, which plays an important role in hematopoiesis and immunity among vertebrates. Herein, we summarize the existing data on PBX1 functions and the impact of PBX1 on renal tumors, PBX1-deficient animal models, and blood vessels in mammalian kidneys. The data indicated that the interaction of PBX1 with different partners such as the HOX genes is responsible for abnormal proliferation and variation of the embryonic mesenchyme, while truncating variants were shown to cause milder phenotypes (mostly cryptorchidism and deafness). Although such interactions have been identified to be the cause of many defects in mammals, some phenotypic variations are yet to be understood. Thus, further research on the TALE family is required.
Functional metagenomics uncovers nitrile-hydrolysing enzymes in a coal metagenome
Authors: Achudhan Arunmozhi Bharathi , Kannan Priya , Saleena Lilly M.
Published: March 2023

Introduction: Nitriles are the most toxic compounds that can lead to serious human illness through inhalation and consumption due to environmental pollution. Nitrilases can highly degrade nitriles isolated from the natural ecosystem. In the current study, we focused on the discovery of novel nitrilases from a coal metagenome using in silico mining.

Methods: Coal metagenomic DNA was isolated and sequenced on the Illumina platform. Quality reads were assembled using MEGAHIT, and statistics were checked using QUAST. Annotation was performed using the automated tool SqueezeMeta. The annotated amino acid sequences were mined for nitrilase from the unclassified organism. Sequence alignment and phylogenetic analyses were carried out using ClustalW and MEGA11. Conserved regions of the amino acid sequences were identified using InterProScan and NCBI-CDD servers. The physicochemical properties of the amino acids were measured using ExPASy’s ProtParam. Furthermore, NetSurfP was used for 2D structure prediction, while AlphaFold2 in Chimera X 1.4 was used for 3D structure prediction. To check the solvation of the predicted protein, a dynamic simulation was conducted on the WebGRO server. Ligands were extracted from the Protein Data Bank (PDB) for molecular docking upon active site prediction using the CASTp server.

Results and discussion:In silico mining of annotated metagenomic data revealed nitrilase from unclassified Alphaproteobacteria. By using the artificial intelligence program AlphaFold2, the 3D structure was predicted with a per-residue confidence statistic score of about 95.8%, and the stability of the predicted model was verified with molecular dynamics for a 100-ns simulation. Molecular docking analysis determined the binding affinity of a novel nitrilase with nitriles. The binding scores produced by the novel nitrilase were approximately similar to those of the other prokaryotic nitrilase crystal structures, with a deviation of ±0.5.
Ion channels as molecular targets of glioblastoma electrotherapy
Authors: Abed Tayeb , Ganser Katrin , Eckert Franziska , Stransky Nicolai , Huber Stephan M.
Published: March 2023

Therapies with weak, non-ionizing electromagnetic fields comprise FDA-approved treatments such as Tumor Treating Fields (TTFields) that are used for adjuvant therapy of glioblastoma. In vitro data and animal models suggest a variety of biological TTFields effects. In particular, effects ranging from direct tumoricidal, radio- or chemotherapy-sensitizing, metastatic spread-inhibiting, up to immunostimulation have been described. Diverse underlying molecular mechanisms, such as dielectrophoresis of cellular compounds during cytokinesis, disturbing the formation of the spindle apparatus during mitosis, and perforating the plasma membrane have been proposed. Little attention, however, has been paid to molecular structures that are predestinated to percept electromagnetic fields—the voltage sensors of voltage-gated ion channels. The present review article briefly summarizes the mode of action of voltage sensing by ion channels. Moreover, it introduces into the perception of ultra-weak electric fields by specific organs of fishes with voltage-gated ion channels as key functional units therein. Finally, this article provides an overview of the published data on modulation of ion channel function by diverse external electromagnetic field protocols. Combined, these data strongly point to a function of voltage-gated ion channels as transducers between electricity and biology and, hence, to voltage-gated ion channels as primary targets of electrotherapy.
An enhanced ant colony optimizer with Cauchy-Gaussian fusion and novel movement strategy for multi-threshold COVID-19 X-ray image segmentation
Authors: Zhao Xiuzhi , Liu Lei , Heidari Ali Asghar , Chen Yi , Ma Benedict Jun , Chen Huiling , Quan Shichao
Published: March 2023

The novel coronavirus pneumonia (COVID-19) is a respiratory disease of great concern in terms of its dissemination and severity, for which X-ray imaging-based diagnosis is one of the effective complementary diagnostic methods. It is essential to be able to separate and identify lesions from their pathology images regardless of the computer-aided diagnosis techniques. Therefore, image segmentation in the pre-processing stage of COVID-19 pathology images would be more helpful for effective analysis. In this paper, to achieve highly effective pre-processing of COVID-19 pathological images by using multi-threshold image segmentation (MIS), an enhanced version of ant colony optimization for continuous domains (MGACO) is first proposed. In MGACO, not only a new move strategy is introduced, but also the Cauchy-Gaussian fusion strategy is incorporated. It has been accelerated in terms of convergence speed and has significantly enhanced its ability to jump out of the local optimum. Furthermore, an MIS method (MGACO-MIS) based on MGACO is developed, where it applies the non-local means, 2D histogram as the basis, and employs 2D Kapur’s entropy as the fitness function. To demonstrate the performance of MGACO, we qualitatively analyze it in detail and compare it with other peers on 30 benchmark functions from IEEE CEC2014, which proves that it has a stronger capability of solving problems over the original ant colony optimization for continuous domains. To verify the segmentation effect of MGACO-MIS, we conducted a comparison experiment with eight other similar segmentation methods based on real pathology images of COVID-19 at different threshold levels. The final evaluation and analysis results fully demonstrate that the developed MGACO-MIS is sufficient to obtain high-quality segmentation results in the COVID-19 image segmentation and has stronger adaptability to different threshold levels than other methods. Therefore, it has been well-proven that MGACO is an excellent swarm intelligence optimization algorithm, and MGACO-MIS is also an excellent segmentation method.
Drug repurposing using meta-analysis of gene expression in Alzheimer’s disease
Authors: Jang Ha Young , Oh Jung Mi , Kim In-Wha
Published: March 2023

Introduction

Alzheimer’s disease and other forms of dementia are disease that bring an increased global burden. However, the medicine developed to date remains limited. The purpose of this study is to predict drug repositioning candidates using a computational method that integrates gene expression profiles on Alzheimer’s disease and compound-induced changes in gene expression levels.

Methods

Gene expression data on Alzheimer’s disease were obtained from the Gene Expression Omnibus (GEO) and we conducted a meta-analysis of their gene expression levels. The reverse scores of compound-induced gene expressions were computed based on the reversal relationship between disease and drug gene expression profiles.

Results

Reversal genes and the candidate compounds were identified by the leave-one-out cross-validation procedure. Additionally, the half-maximal inhibitory concentration (IC50) values and the blood-brain barrier (BBB) permeability of candidate compounds were obtained from ChEMBL and PubChem, respectively.

Conclusion

New therapeutic target genes and drug candidates against Alzheimer’s disease were identified by means of drug repositioning.
1400 W, a selective inducible nitric oxide synthase inhibitor, mitigates early neuroinflammation and nitrooxidative stress in diisopropylfluorophosphate-induced short-term neurotoxicity rat model
Authors: Massey Nyzil , Vasanthi Suraj Sundara , Samidurai Manikandan , Gage Meghan , Rao Nikhil , Meyer Christina , Thippeswamy Thimmasettappa
Published: March 2023

Organophosphate nerve agent (OPNA) exposure induces acute and long-term neurological deficits. OPNA exposure at sub-lethal concentrations induces irreversible inhibition of acetylcholinesterase and cholinergic toxidrome and develops status epilepticus (SE). Persistent seizures have been associated with increased production of ROS/RNS, neuroinflammation, and neurodegeneration. A total of 1400W is a novel small molecule, which irreversibly inhibits inducible nitric oxide synthase (iNOS) and has been shown to effectively reduce ROS/RNS generation. In this study, we investigated the effects of 1400W treatment for a week or two weeks at 10 mg/kg or 15 mg/kg per day in the rat diisopropylfluorophosphate (DFP) model. 1400W significantly reduced the number of microglia, astroglia, and NeuN+FJB positive cells compared to the vehicle in different regions of the brain. 1400W also significantly reduced nitrooxidative stress markers and proinflammatory cytokines in the serum. However, neither of the two concentrations of 1400W for two weeks of treatment had any significant effect on epileptiform spike rate and spontaneous seizures during the treatment period in mixed sex cohorts, males, or females. No significant sex differences were found in response to DFP exposure or 1400W treatment. In conclusion, 1400W treatment at 15 mg/kg per day for two weeks was more effective in significantly reducing DFP-induced nitrooxidative stress, neuroinflammatory and neurodegenerative changes.
Culinary strategies to manage glycemic response in people with type 2 diabetes: A narrative review
Authors: Murillo Serafin , Mallol Ariadna , Adot Alba , Juárez Fabiola , Coll Alba , Gastaldo Isabella , Roura Elena
Published: March 2023

Diet plays a critical role in the management of many chronic diseases. It is well known that individuals with type 2 diabetes (T2D) need to pay close attention to foods rich in carbohydrates to better manage their blood sugar. Usually, individuals are told to increase their dietary fiber intake which is associated with better glycemic control and limit their overall carbohydrate consumption. However, there are many other cooking strategies available to reduce the glycemic response to meals rich in carbohydrates and with a high glycemic index, such as adding fats, proteins, or vinegar, modifying the cooking or preparation processes, and even the selection and storage of foods consumed. The aim of the present narrative review is to summarize some of these existing strategies applied to the cooking process and their ability to modulate glycemic response to meals in individuals with T2D.
Formation and characterization of solid fat mimetic based on pea protein isolate/polysaccharide emulsion gels
Authors: Hou Wenbo , Long Jie , Hua Yufei , Chen Yeming , Kong Xiangzhen , Zhang Caimeng , Li Xingfei
Published: March 2023

The emulsion gels that can be used as solid fat replacers were produced with different polysaccharides (κ-carrageenan, κC; high-acyl gellan, HA; konjac glucomannanon, and KGM), pea protein isolate (PPI) and sunflower seed oil. The effect of polysaccharide concentration on the texture, rheological property, microstructure, and water holding capacity of the mixed emulsion gels were investigated. Rheological results showed that the presence of polysaccharides enhanced the hardness, storage modulus and resistance against deformation of emulsion gel, where PPI/κC system exhibited superior hardness with a similar level of pig back fat, due to the self-gelation behavior of κC. CLSM and SEM results showed that the presence of κC, HA, and KGM broke the uniform structure of gel network and formed irregular, threadlike, and oval shaped inclusions respectively, resulting in the broken and coalescence of oil droplets. The α-helix content of emulsion gels decreased, while β-sheet, β-turn and random coils slightly increased due to the unfolding of protein during gel formation. This study may offer a valuable strategy for the development of solid fat mimetic with the characteristics closing to the pig back fat.
Effects of different heat treatments on Maillard reaction products and volatile substances of camel milk
Authors: Zhao Xiaoxuan , Guo Yinping , Zhang Yumeng , Pang Xiaoyang , Wang Yunna , Lv Jiaping , Zhang Shuwen
Published: March 2023

Camel milk has unique compositional, functional and therapeutic properties compared to cow's milk and also contains many protective proteins with anti-cancer, anti-diabetic and anti-bacterial properties. In this experiment, fresh camel milk was heat-treated at different temperatures and times, and the changes in Millard reaction products were analyzed. Meanwhile, headspace-gas chromatography-ion migration spectrometry (HS-GC-IMS), electronic nose and electronic tongue were used to analyze the changes of volatile components in camel milk after different heat treatments. The results showed that the Maillard reaction was more severe with the increase of heat treatment, and the contents of furosine and 5-hydroxymethylfurfural increased significantly when the heat treatment temperature was higher than 120°C. HS-GC-IMS results showed that the contents of aldehydes and ketones increased obviously with the increase of heat treatment degree. The study clarifies the effects of different heat treatment degrees on Maillard reaction degree and flavor of camel milk, which has practical production guidance significance for the research and industrialization of liquid camel milk products.
Valorization of Adhatoda vasica leaves: Extraction, in vitro analyses and in silico approaches
Authors: Rudrapal Mithun , Vallinayagam Sugumari , Aldosari Sahar , Khan Johra , Albadrani Hind , Al-Shareeda Alaa , Kamal Mehnaz
Published: March 2023

Adhatoda vasica(also called Vasaka) is a traditional medicinal herb used traditionally for the relief of cough, asthma, nasal congestion, bronchial inflammation, upper respiratory infections, bleeding disorders, skin diseases, leprosy, tuberculosis, diabetes, allergic conditions, rheumatism, tumor, and many more diseases. The present study aims to investigate the biological activities of vasicine, a potent alkaloid from A. vasica with different biological/ pharmacological assays andin silicotechniques. Vasicine showed antimicrobial activity as evidenced fromthe colony-forming unit assay. It showed antioxidant activity in ABTS scavenging assay (IC50= 11.5 μg/ml), ferric reducing power assay (IC50= 15 μg/ml), DPPH radical scavenging assay (IC50= 18.2 μg/ml), hydroxyl radical scavenging assay (IC50= 22 μg/ml), and hydrogen peroxide assay (IC50= 27.8 μg/ml). It also showed anti-inflammatory activity in proteinase inhibitory assay (IC50= 76 μg/ml), BSA method (IC50= 51.7 μg/ml), egg albumin method (IC50= 53.2 μg/ml), and lipooxygenase inhibition assay (IC50= 76 μg/ml). Vasicine showed antidiabetic activity in α-amylase inhibition assay (IC50= 47.6 μg/ml), α-glucosidase inhibition assay (IC50= 49.68 μg/ml), and non-enzymatic glycosylation of hemoglobin assay. It showed antiviral activity against HIV-protease (IC50= 38.5 μg/ml). Vasicine also showed anticancer activity against lung cancer cells (IC50= 46.5 μg/ml) and human fibroblast cells (IC50= 82.5 μg/ml).In silicostudies revealed that similar to the native ligands, vasicine also showed a low binding energy, i.e., good binding affinity for the active binding sites and interacted with α-amylase (-6.7 kcal/mol), α-glucosidase (-7.6 kcal/mol), cyclooxygenase (-7.4 kcal/mol), epidermal growth factor receptor (-6.4 kcal/mol), lipooxygenase (-6.9 kcal/mol), and HIV-protease (-6.4 kcal/mol). The present study ascertains the potential of vasicine as a bioactive compound isolated from A. vasica having therapeutic usefulness in many human diseases.
A phase I dose-escalation study of neoantigen-activated haploidentical T cell therapy for the treatment of relapsed or refractory peripheral T-cell lymphoma
Authors: Chen Yuan , Zhao Hu , Luo Jing , Liao Youping , Dan Xu , Hu Guoyu , Gu Weiyue
Published: March 2023

Peripheral T-cell lymphoma (PTCL) is a type of highly heterogeneous non-Hodgkin lymphoma with a poor prognosis and lack of effective targeted therapies. Adoptive T-cell therapy has been successfully used in the treatment of B-cell malignancies. We first used adoptive transfer of haploidentical T cells activated by patient-specific neoantigens in vitro to treat an elderly patient with refractory angioimmunoblastic T-cell lymphoma (AITL) in 2017, and the patient achieved long-term complete remission (CR). Here we report on early results from this first-in-human phase 1 clinical trial that aims to assess the safety and tolerability of neoantigen-activated haploidentical T cell therapy (NAHTC) for relapsed/refractory PTCL.

Clinical trial registration

http://www.chictr.org.cn/index.aspx, identifier [ChiCTR1800017440].
Immunotherapy or targeted therapy: What will be the future treatment for anaplastic thyroid carcinoma?
Authors: Gao Xiaoni , Hong Chengcheng , Xie Yang , Zeng Xiangtai
Published: March 2023

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive form of thyroid carcinoma (TC). Currently, there are no effective treatments for this condition. In the past few years, targeted therapy and immunotherapy have made significant progress in ATC treatment. Several common genetic mutations have been found in ATC cells, involving different molecular pathways related to tumor progression, and new therapies that act on these molecular pathways have been studied to improve the quality of life of these patients. In 2018, the FDA approved dabrafenib combined with trametinib to treat BRAF-positive ATC, confirming its therapeutic potential. At the same time, the recent emergence of immunotherapy has also attracted wide attention from researchers. While immunotherapy for ATC is still in the experimental stage, numerous studies have shown that immunotherapy is a potential therapy for ATC. In addition, it has also been found that the combination of immunotherapy and targeted therapy may enhance the anti-tumor effect of targeted therapy. In recent years, there has been some progress in the study of targeted therapy or immunotherapy combined with radiotherapy or chemotherapy, showing the prospect of combined therapy in ATC. In this review, we analyze the response mechanism and potential effects of targeted therapy, immunotherapy, and combination therapy in ATC treatment and explore the future of treatment for ATC.
Adjuvant therapy for cholangiocarcinoma after surgery and prognosis factors for cholangiocarcinoma: A single-center retrospective cohort study
Authors: Sun Zhongquan , Han Xin , You Wanlu , Tang Jinlong , Xu Juehua , Ye Binglin , Li Tengfei , Zhang Yixin , Chen Kai , Ding Yuan , Wang Weilin
Published: March 2023

Background

Cholangiocarcinoma (CCA) is a highly heterogeneous malignant tumor, and more than 60% of patients have recurrence and metastasis after surgery. The efficacy of postoperative adjuvant therapy for CCA remains unclear. This study aimed to explore whether adjuvant therapy benefits patients with CCA and examine the independent prognostic factors for overall survival (OS) and progression-free survival (PFS).

Methods

Patients with CCA undergoing surgery were retrospectively enrolled in this study from June 2016 to June 2022. The chi-square test or Fisher exact test was used to analyze the correlation between clinicopathologic characteristics. Survival curves were plotted using the Kaplan-Meier method, and the Cox regression model was used for univariate and multivariate analysis to search for independent prognostic factors.

Results

Of the 215 eligible patients, 119 patients received adjuvant therapy, and the other 96 patients did not. The median follow-up was 37.5 months. The median OS of CCA patients with and without adjuvant therapy was 45 and 18 months (P < 0.001), respectively. The median PFS of CCA patients with and without adjuvant therapy was 34 and 8 months (P < 0.001), respectively. The Cox univariate and multivariate regression analysis showed that preoperative aspartate transaminase and carbohydrate antigen 19-9, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for OS (all P values < 0.05). Preoperative carbohydrate antigen 125, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for PFS (all P values < 0.05). The stratified analysis by TMN stage detected significant differences in the early stages (median OS [mOS]: P = 0.0128; median PFS [mPFS]: P = 0.0209) and advanced stages (mOS and mPFS: both P values < 0.001). Adjuvant therapy was also identified as a significantly favorable prognostic factor for OS and PFS in the early stages and advanced stages.

Conclusion

Postoperative adjuvant therapy can improve the prognosis of patients with CCA, even in the early stages and advanced stages. All data suggest that adjuvant therapy should be incorporated into the treatment of CCA in all cases, where appropriate.
SMC4, a novel tumor prognostic marker and potential tumor therapeutic target
Authors: Zhao Zonglei , Wang Xixiu , Ding Yan , Cao Xuefeng , Zhang Xingyuan
Published: March 2023

The structural maintenance of chromosome 4 (SMC4) is a member of the ATPase family of chromosomes. The most widely reported function of SMC4, as well as the remaining subunits of whole condensin complexes, is compression and dissociation of sister chromatids, DNA damage repair, DNA recombination, and pervasive transcription of the genome. Studies have also shown that SMC4 plays an exceedingly essential role in the division cycle of embryonic cells, such as RNA splicing, DNA metabolic process, cell adhesion, and extracellular matrix. On the other hand, SMC4 is also a positive regulator of the inflammatory innate immune response, while excessive innate immune responses not only disrupt immune homeostasis and may lead to autoimmune diseases, but even cancer. To further understand the expression and prognostic value of SMC4 in tumors, we provide an in-depth review of the literature and several bioinformatic databases, for example, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), The Human Protein Atlas and Kaplan Meier plotter tools, illustrating that SMC4 plays a vital role in the occurrence and development of tumors, and high expression of SMC4 seems to consistently predict worse overall survival. In conclusion, we present this review which introduces the structure, biological function of SMC4, and its correlation with the tumor in detail; it might provide new insight into a novel tumor prognostic marker and potential tumor therapeutic target.
Emergency department use by patients who received chimeric antigen receptor T cell infusion therapy
Authors: Lipe Demis N. , Qdaisat Aiham , Chaftari Patrick , Wattana Monica K. , Krishnamani Pavitra P. , Reyes-Gibby Cielito , Yeung Sai-Ching J.
Published: March 2023

Background

Chimeric antigen receptor T cell infusion (CAR T) therapy has revolutionized the treatment of hematologic malignancies, but treatment-related toxicities are of concern. Understanding the timing and reasons for which patients present to the emergency department (ED) after CAR T therapy can assist with the early recognition and management of toxicities.

Methods

A retrospective observational cohort study was conducted for patients who had undergone CAR T therapy in the past 6 months and visited the ED of The University of Texas MD Anderson Cancer Center between 04/01/2018 and 08/01/2022. The timing of presentation after CAR T product infusion, patient characteristics, and outcomes of the ED visit were examined. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates.

Results

During the period studied, there were 276 ED visits by 168 unique patients. Most patients had diffuse large B-cell lymphoma (103/168; 61.3%), multiple myeloma (21/168; 12.5%), or mantle cell lymphoma (16/168; 9.5%). Almost all 276 visits required urgent (60.5%) or emergent (37.7%) care, and 73.5% of visits led to admission to the hospital or observation unit. Fever was the most frequent presenting complaint, reported in 19.6% of the visits. The 30-day and 90-day mortality rates after the index ED visits were 17.0% and 32.2%, respectively. Patients who had their first ED visit >14 days after CAR T product infusion had significantly worse overall survival (multivariable hazard ratio 3.27; 95% confidence interval 1.29–8.27; P=0.012) than patients who first visited the ED within 14 days of CAR T product infusion.

Conclusion

Cancer patients who receive CAR T therapy commonly visit the ED, and most are admitted and/or require urgent or emergent care. During early ED visits patients mainly present with constitutional symptoms such as fever and fatigue, and these early visits are associated with better overall survival.
Diagnosis of benign and malignant thyroid nodules by a dual-layer spectral detector CT-based nomogram
Authors: Yi Rongqi , Li Ting , Xie Gang , Li Kang
Published: March 2023

Introduction

Preoperative diagnosis of benign and malignant thyroid nodules is crucial for appropriate clinical treatment and individual patient management. In this study, a double-layer spectral detector computed tomography (DLCT)-based nomogram for the preoperative classification of benign and malignant thyroid nodules was developed and tested.

Methods

A total of 405 patients with pathological findings of thyroid nodules who underwent DLCT preoperatively were retrospectively recruited. They were randomized into a training cohort (n=283) and a test cohort (n=122). Information on clinical features, qualitative imaging features and quantitative DLCT parameters was collected. Univariate and multifactorial logistic regression analyses were used to screen independent predictors of benign and malignant nodules. A nomogram model based on the independent predictors was developed to make individualized predictions of benign and malignant thyroid nodules. Model performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis(DCA).

Results

Standardized iodine concentration in the arterial phase, the slope of the spectral hounsfield unit(HU) curves in the arterial phase, and cystic degeneration were identified as independent predictors of benign and malignant thyroid nodules. After combining these three metrics, the proposed nomogram was diagnostically effective, with AUC values of 0.880 for the training cohort and 0.884 for the test cohort. The nomogram showed a better fit (all p > 0.05 by Hosmer−Lemeshow test) and provided a greater net benefit than the simple standard strategy within a large range of threshold probabilities in both cohorts.

Discussion

The DLCT-based nomogram has great potential for the preoperative prediction of benign and malignant thyroid nodules. This nomogram can be used as a simple, noninvasive, and effective tool for the individualized risk assessment of benign and malignant thyroid nodules, helping clinicians make appropriate treatment decisions.
Robotic natural orifice specimen extraction surgery versus conventional robotic resection for patients with colorectal neoplasms
Authors: Li Linye , Liu Kuijie , Li Tiegang , Zhou Jiangjiao , Xu Shu , Yu Nanhui , Guo Zhushu , Yao Hongliang
Published: March 2023

Background

Laparoscopic natural orifice specimen extraction surgery (NOSES) has been widely used in colorectal neoplasms. However, only a few studies have focused on robotic NOSES. This study compared the short-term clinical outcomes and long-term survival outcomes between robotic NOSES and conventional robotic resection (CRR) groups.

Methods

From March 2016 to October 2018, a consecutive of 143 patients who underwent robotic sigmoid and rectal resection at the Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, were considered for inclusion in this study. Propensity-score matching (PSM) was conducted to account for differences in the baseline characteristics. After PSM, 39 patients were included in the robotic NOSES group, and 39 patients in the CRR group. The baseline characteristics between the two groups were all balanced and comparable.

Results

Patients in the NOSES group experienced less intraoperative blood loss (p=0.001), lower requirements for additional analgesia (p=0.020), shorter time to first flatus (p=0.010), and a shorter time to first liquid diet (p=0.003) than the CRR group. The 3-year overall survival rates (NOSES: 92.3% vs. CRR: 89.7% p=1.000) and 3-year disease-free survival rates (NOSES: 82.1% vs. CRR: 84.6% p=0.761) between the two groups were comparable.

Conclusion

Robotic natural orifice specimen extraction surgery is a safe and feasible surgery for patients with colorectal neoplasms. Robotic NOSES is associated with better short-term clinical outcomes and similar long-term survival outcomes to conventional robotic resection.
Case report: Prader–Willi syndrome and inflammatory arthritis—An important consideration
Authors: Marelli Luca , Dallos Tomáš , Miserocchi Elisabetta , Nucci Paolo , Tombolini Beatrice , De Lucia Orazio , Gattinara Maurizio , Caporali Roberto , Marino Achille
Published: March 2023

Background

Prader–Willi syndrome (PWS) is a multisystemic genetically determined disorder. Musculoskeletal manifestations are common in most patients. We report the cases of two children with PWS who developed inflammatory arthritis, complicated with chronic anterior bilateral uveitis in one case. To our knowledge, no previous reports of such an association exist.

Case presentation

Case 1 was of a 3-year-old girl diagnosed with PWS who developed arthritis of the right knee with morning stiffness, joint swelling, and limited range of motion. Other causes of arthritis were ruled out. Increased inflammatory markers, antinuclear antibody (ANA) positivity, and hypertrophic synovitis on ultrasound confirmed the diagnosis of inflammatory arthritis compatible with juvenile idiopathic arthritis (JIA). Despite the treatment with methotrexate, arthritis progressed, and etanercept was added. The patient reached and maintained articular remission while on combined MTX and etanercept treatment during 9 years of follow-up. Case 2 was of a 6-year-old boy diagnosed with PWS who developed arthritis of the right knee. Laboratory investigations showed mildly increased acute phase reactants, microcytic anemia, and ANA positivity at high titer (titer 1:1,280). Infectious and other causes of arthritis were excluded. Ultrasound confirmed the presence of joint effusion and synovial thickening, and synovial fluid analysis was consistent with inflammatory arthrosynovitis (white blood cell count of 14,200/µl) compatible with JIA. Shortly after the diagnosis, the ophthalmologic evaluation revealed the presence of bilateral anterior uveitis. Despite MTX and topical corticosteroid, ocular inflammation persisted and adalimumab was added. At the last follow-up, 9 months later, the child experienced inactivity of arthritis and uveitis with normal growth.

Conclusions

We aim to raise awareness of this possible association among pediatricians since arthritis might be underestimated due to high pain tolerance, behavioral disturbances, and other musculoskeletal abnormalities in PWS patients.
Retroperitoneal kaposiform hemangioendothelioma with kasabach-merritt phenomenon in children: A case report and review of the literature
Authors: Huo Junming , Chen Song , Li Jing , Liu Chengjun
Published: March 2023

Objective

To investigate the clinical features, diagnosis and treatment methods and prognosis of retroperitoneal Kaposiform hemangioendothelioma (R-KHE) in children.

Methods

The clinical data of an infant with R-KHE was retrospectively analyzed. Literature on R-KHE in pediatrics were retrieved in databases including Wanfang, CNKI and PubMed as of April 2022.

Results

A 1 month and 6 days female infant with R-KHE was reported. After the diagnosis was confirmed by biopsy and pathological examination, the patient was treated by interventional embolization, and a combined therapy with glucocorticoid, vincristine, sirolimus and propranolol. The patient has been followed up for 1 year and 2 months, and is still alive with tumor. Through literature search, a total of 15 children, together with the case in our report, were included. The main manifestations were diversity among those patients. 14 cases have combined Kasabach-Merritt phenomenon (KMP). 6 cases accepted surgery plus drug therapy. 4 cases accepted only surgery, and 4 cases only accepted drug therapy. While drug therapy plus radiotherapy were employed to 1 case. Improvement was observed in 11 cases, with significantly reduced tumor and survival with tumor. Tumor disappeared completely in 2 cases. While 2 cases suffered death.

Conclusion

R-KHE has diverse clinical presentations and non-specificity in symptoms and imaging examinations, and most cases accompanied with KMP. Methods for R-KHE treatment include surgical resection, interventional embolization and drug therapy. Close attention needs to be paid to the adverse reactions of the drug during the course of treatment.
Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway
Authors: Chen Yuru , Wang Yanyan , Zhai Yu , Yuan Ye , Wang Junhong , Jin Yajing , Dang Lingling , Song Liming , Chen Changbao , Wang Yu
Published: March 2023

Cinobufacini injection (CI), an aqueous extract of Cutis Bufonis, is clinically used for cancer therapy in China, but its molecular mechanism for the treatment of osteosarcoma (OS) remains unclear. We constructed U2OS ectopic subcutaneous tumor model to verify the anti-OS effect of CI in vivo. Meanwhile, cell proliferation of U2OS and MG63 cells was monitored in vitro using the CCK-8 assay, colony formation and morphological changes. Cell cycle arrest and apoptosis were detected by flow cytometry and western blot, which showed that CI significantly inhibited proliferation, induced cell cycle arrest and apoptosis in human OS cells. The further RNA-seq results identified that the Hippo signaling pathway was involved in the anti-OS effect of CI. YAP/TAZ are two major components of the Hippo pathway in breast cancer and are positively regulated by prolyl isomerase PIN1, we assessed their role in OS using both clinicopathological sections and western blots. CI also inhibited PIN1 enzyme activity in a dose-dependent manner, which resulted in impaired PIN1, YAP, and TAZ expression in vitro and in vivo. Additionally, 15 potential compounds of CI were found to occupy the PIN1 kinase domain and inhibit its activity. In summary, CI plays an anti-OS role by down-regulating the PIN1-YAP/TAZ pathway.
Cinnamomi ramulus inhibits cancer cells growth by inducing G2/M arrest
Authors: Li Jing , Huang Hsi-Yuan , Lin Yang-Chi-Dung , Zuo Huali , Tang Yun , Huang Hsien-Da
Published: March 2023

Introduction:Cinnamomi ramulus (CR) is one of the most widely used traditional Chinese medicine (TCM) with anti-cancer effects. Analyzing transcriptomic responses of different human cell lines to TCM treatment is a promising approach to understand the unbiased mechanism of TCM.

Methods: This study treated ten cancer cell lines with different CR concentrations, followed by mRNA sequencing. Differential expression (DE) analysis and gene set enrichment analysis (GSEA) were utilized to analyze transcriptomic data. Finally, the in silico screening results were verified by in vitro experiments.

Results: Both DE and GSEA analysis suggested the Cell cycle pathway was the most perturbated pathway by CR across these cell lines. By analyzing the clinical significance and prognosis of G2/M related genes (PLK1, CDK1, CCNB1, and CCNB2) in various cancer tissues, we found that they were up-regulated in most cancer types, and their down-regulation showed better overall survival rates in cancer patients. Finally, in vitro experiments validation on A549, Hep G2, and HeLa cells suggested that CR can inhibit cell growth by suppressing the PLK1/CDK1/ Cyclin B axis.

Discussion: This is the first study to apply transcriptomic analysis to investigate the cancer cell growth inhibition of CR on various human cancer cell lines. The core effect of CR on ten cancer cell lines is to induce G2/M arrest by inhibiting the PLK1/CDK1/Cyclin B axis.
Network pharmacology, molecular docking, and experimental validation to explore the potential mechanism of Long Mu Qing Xin mixture for the treatment of attention deficit hyperactivity disorder
Authors: Li Xuejun , Xiao Zhen , Pu Wenyan , Jiang Zhiyan , Wang Shumin , Zhang Yixing
Published: March 2023

Background: Long Mu Qing Xin Mixture (LMQXM) has shown potentially positive effects in alleviating attention deficit hyperactivity disorder (ADHD); however, the action mechanism is still not fully understood. This study aimed to predict the potential mechanism of LMQXM for ADHD using network pharmacology and molecular docking, which were then validated using animal experiments.

Methods: Network pharmacology and molecular docking techniques were used to predict the core targets and potential pathways of LMQXMQ for ADHD, and KEGG pathway enrichment analysis revealed the potential significance of dopamine (DA) and cyclic adenosine monophosphate (cAMP) signaling pathways. To verify the hypothesis, we conducted an animal experiment. In the animal experiment, the young spontaneously hypertensive rats (SHRs) were randomly divided into the model group (SHR), the methylphenidate hydrochloride group (MPH, 4.22 mg/kg), and 3 LMQXM groups (low-dose (LD) group, 5.28 ml/kg; medium-dose (MD) group, 10.56 ml/kg; and high-dose (HD) group, 21.12 ml/kg), and administered by gavage for 4 weeks; the WKY rats were set as the control group. The open field test and Morris water maze test were used to evaluate the behavioral performance of rats, high performance liquid chromatography mass spectrometry (LC-MS) was used to analyze DA levels in the prefrontal cortex (PFC) and striatum of rats, ELISA was used to detect cAMP concentrations in the PFC and striatum, and immunohistochemistry and qPCR were used to analyze positive cell expression and mRNA expression for indicators related to DA and cAMP pathways.

Results: The results showed that beta-sitosterol, stigmasterol, rhynchophylline, baicalein, and formononetin might be key components of LMQXM for ADHD and that these components bind well to the core targets, DA receptors (DRD1 and DRD2). Furthermore, LMQXM might act through the DA and cAMP signaling pathways. In the animal experiment, we found that MPH and LMQXM-MD controlled hyperactivity and improved learning and memory in SHRs, while LMQXM-HD only controlled hyperactivity in SHRs; meanwhile, MPH and LMQXM-MD upregulated DA and cAMP levels, mean optical density (MOD) of cAMP, and MOD and mRNA expression of DRD1 and PKA in the prefrontal cortex (PFC) and striatum of SHRs, while LMQXM-LD and LMQXM-HD upregulated DA and cAMP levels in the striatum, MOD of cAMP in the PFC, and mRNA expression of PKA in the PFC. However, we did not find a significant regulatory effect of LMQXM on DRD2.

Conclusion: To sum up, this study demonstrated that LMQXM may increase DA levels mainly by activating the cAMP/PKA signaling pathway through DRD1, thereby controlling the behavioral disorders of SHRs, which is most effective at moderate doses, and this may be a key mechanism for LMQXM in the treatment of ADHD.
Characterization of tumor microenvironment and programmed death-related genes to identify molecular subtypes and drug resistance in pancreatic cancer
Authors: Yu Liang , He Risheng , Cui Yunfu
Published: March 2023

Background: Immunotherapy has been a key option for the treatment of many types of cancer. A positive response to immunotherapy is heavily dependent on tumor microenvironment (TME) interaction. However, in pancreatic adenocarcinoma (PAAD), the association between TME mode of action and immune cell infiltration and immunotherapy, clinical outcome remained unknown.

Methods: We systematically evaluated 29 TME genes in PAAD signature. Molecular subtypes of distinct TME signatures in PAAD were characterized by consensus clustering. After this, we comprehensively analyzed their clinical features, prognosis, and immunotherapy/chemotherapy response using correlation analysis, Kaplan-Meier curves analysis, ssGSEA analysis. 12 programmed cell death (PCD) patterns were acquired from previous study. Differentially expressed genes (DEGs) were acquired based on differential analysis. Key genes affecting overall survival (OS) of PAAD were screened by COX regression analysis and used to develop a RiskScore evaluation model. Finally, we assessed the value of RiskScore in predicting prognosis and treatment response in PAAD.

Results: We identified 3 patterns of TME-associated molecular subtypes (C1, C2, C3), and observed that clinicopathological characteristics, prognosis, pathway features and immune features, immunotherapy/chemosensitivity of patients were correlated with the TME related subtypes. C1 subtype was more sensitive to the four chemotherapeutic drugs. PCD patterns were more likely to occur at C2 or C3. At the same time, we also detected 6 key genes that could affect the prognosis of PAAD, and 5 genes expressions were closely associated to methylation level. Low-risk patients with high immunocompetence had favorable prognostic results and high immunotherapy benefit. Patients in the high-risk group were more sensitive to chemotherapeutic drugs. RiskScore related to TME was an independent prognostic factor for PAAD.

Conclusion: Collectively, we identified a prognostic signature of TME in PAAD patients, which could help elucidate the specific mechanism of action of TME in tumors and help to explore more effective immunotherapy strategies.