bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular mechanism of oroxyli semen against triple-negative breast cancer verified by bioinformatics and in vitro experiments
Authors: Chen Lulu , Yang Aishen , Li Yangan , Liu Xin , Jiang Wei , Hu Kehui
Published: September 2023

Objective:

This study aimed to use network pharmacology to predict the therapeutic mechanism of oroxyli semen (OS) on triple-negative breast cancer (TNBC) and validate it through in vitro experiments.

Methods:

The active ingredients and target proteins of OS were retrieved from the Traditional Chinese Medicine Systems Pharmacology database, and the TNBC-related target genes were obtained from the GeneCards database. The overlapping genes were used to construct a protein–protein interaction (PPI) network via the String database. Furthermore, we employed an online bioinformatics analysis platform (https://www.bioinformatics.com.cn/) to perform gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to evaluate biological processes, molecular functions, and cellular components and generate simulated signal pathways. Additionally, molecular docking was used to evaluate the binding ability of small molecule drugs and signaling pathway targets. CCK8 assay was conducted to detect the effect of small molecule drugs on TNBC cell viability, and Western Blot was utilized to verify the expression of AKT, VEGF, and hypoxia-inducible factor 1-alpha (HIF-1α) proteins.

Results:

Fifteen active ingredients and 166 therapeutic targets of OS were obtained from the Traditional Chinese Medicine Systems Pharmacology database. The Venn diagram revealed that 163 targets were related to TNBC. The protein–protein interaction network analysis identified AKT1, IL-6, JUN, vascular endothelial growth factor A (VEGFA), CASP3, and HIF-1α as potential core targets through which OS may treat TNBC. Furthermore, the molecular docking results indicated that the active ingredient chryseriol in OS had good binding ability with VEGFA, and HIF-1α. CCK8 assay results indicated that chryseriol inhibited the viability of MDA-MB-231 and BT-20 cells. Western Blot demonstrated that chryseriol intervention led to a decrease in VEGFA, and HIF-1α protein expression compared with the control group (P < .05), increased the cleaved PARP.

Conclusion:

OS may exert its therapeutic effects on TNBC through multiple cellular signaling pathways. Chryseriol, the active component of OS, can enhance the apoptosis of TNBC cells by targeting VEGFA/HIF-1α pathway. This study provided new insights into the potential therapeutic mechanism of OS for TNBC and may aid in the development of novel therapeutic approaches for TNBC.
Bulk RNA-seq and scRNA-seq reveal SLC7A11, a key regulatory molecule of ferroptosis, is a prognostic-related biomarker and highly related to the immune system in lung adenocarcinoma
Authors: Wu Xiaoyu , Wang Sheng , Chen Kaifang
Published: September 2023

Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer. Ferroptosis is an iron-dependent, non-apoptotic cell death mode, highly correlated with the tumorigenesis and progression of multiple cancers. Solute carrier family 7 member 11 (SLC7A11) maintains the anti-porter activity of cysteine and glutamate to regulate ferroptosis. We collected bulk RNA-seq and scRNA-seq from The Cancer Genome Altas and Gene Expression Omnibus databases. Then, we extracted the expression level of SLC7A11 to perform the differential expression analysis between normal tissues and LUAD tissues. Then, we applied survival, univariate, and multivariate Cox regression analyses to investigate the predictive value of SLC7A11 in LUAD. Gene set enrichment analysis was used to explore the underlying molecular mechanisms of SLC7A11 in LUAD. Finally, we analyzed the relationship of SLC7A11 to the immune status and the curative effect of immunotherapy. The expression level of SLC7A11 in LUAD tissues was markedly increased. The survival analysis, univariate and multivariate Cox regression analysis showed that SLC7A11 was a negative factor for the prognosis of LUAD patients. Gene set enrichment analysis revealed that several immune-related pathways were enriched in the low-level group. The lower SLC7A11 level has a better therapeutic effect of immunotherapy and less probability of immune escape and dysfunction. SLC7A11 was a prognostic-related biomarker and closely correlated with the immune status and therapeutic effect of immunotherapy in LUAD, which could be an effective biomarker for evaluating the prognosis and the therapeutic efficacy of immunotherapy.
Heart failure and diabetes: Understanding the bidirectional relationship
Authors: Elendu Chukwuka , Amaechi Dependable C. , Elendu Tochi C. , Ashna Manizha , Ross-Comptis Jennifer , Ansong Sandra O. , Egbunu Emmanuel O. , Okafor Geraldine C. , Jingwa Klein A. , Akintunde Akinbayo A. , Ogah Chidinma M. , Edeko Melissa O. , Ibitoye Ayodeji V. , Ogunseye Mojetoluwa O. , Alakwe-Ojimba Chisom E. , Omeludike Eunice K. , Oguine Chibuike A. , Afuh Rechner N. , Olawuni Clinton A. , Ekwem Onyekachukwu R. , Oyedele Boluwatife A. , Pius Erica I. , Asekhauno Mercy O. , Ladele John A. , Okoro Chinonso B. , Monika Pouekoua Brandon C. , Adenikinju Joseph S. , Agu-ben Chigozirim M. , Aborisade Ooreofe
Published: September 2023

Heart failure and diabetes mellitus are 2 common and closely intertwined chronic conditions that often coexist in individuals. The relationship between heart failure and diabetes is bidirectional, meaning that each condition can influence the development and progression of the other. Understanding this complex interplay is crucial for optimizing the management and outcomes of patients with these comorbidities. This review comprehensively analyzed the literature to examine the bidirectional relationship between heart failure and diabetes. We searched various electronic databases and included studies that explored the pathophysiological mechanisms, epidemiology, clinical implications, and therapeutic considerations associated with this relationship. The bidirectional relationship between heart failure and diabetes is multifactorial and involves several interconnected mechanisms. Diabetes is a recognized risk factor for heart failure, increasing the risk of its development and accelerating its progression. On the other hand, heart failure can contribute to the development of insulin resistance and worsen glycemic control in patients with diabetes. Shared risk factors, such as obesity, hypertension, and dyslipidemia, contribute to development of both conditions. Additionally, hyperglycemia, insulin resistance, chronic inflammation, oxidative stress, and mitochondrial dysfunction play significant roles in the pathogenesis of heart failure in individuals with diabetes. The bidirectional relationship between heart failure and diabetes has important clinical implications. Patients with heart failure and diabetes have worse outcomes, including higher hospitalization rates, morbidity, and mortality, than those without diabetes. Optimal management strategies should target both conditions simultaneously, focusing on lifestyle modifications, pharmacotherapy, glycemic control, and cardiovascular risk reduction.
Correlation of serum HMGB1 and HMGB2 levels with clinical symptoms in allergic rhinitis children
Authors: Xing Xinxin , Wang Hai
Published: September 2023

This research aimed to explore the serum high-mobility group box 1 (HMGB1) and high-mobility group box 2 (HMGB2) levels in allergic rhinitis (AR) children and its correlation with clinical results. This present prospective observational study enrolled 179 AR children and 100 healthy children who came to our hospital during October 2020 to August 2022. The serum HMGB1, HMGB2, interleukin (IL)-6, IL-1β, interferon-γ, and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay. Demographic and clinical statistics including age, body mass index (BMI), sex, diastolic blood pressure, SBP, family history of allergy, Visual Analogue Score (VAS) and Rhinoconjunctivitis Quality of Life Questionnaire were collected. All data used SPSS 18.0 to statistical analyses. The proportion of family history of allergy was obviously higher in the AR group than that in the healthy group. The serum levels of HMGB1, HMGB2 and cytokines were remarkably enhanced in the AR patients. Spearman analysis supported that positive correlation existed among the HMGB1, HMGB2, CRP, IL-6 and IL-1β levels. Serum IL-6, CRP, HMGB2, IL-1β, VAS score and Rhinoconjunctivitis Quality of Life Questionnaire score levels were significantly higher and serum interferon-γ levels were significantly lower in the HMGB1 high expression group. Similar results were found in in the HMGB2 high group compared to the HMGB2 low group. In addition, HMGB1 and HMGB2 could be potential diagnostic biomarkers of AR patients. Finally, we found that HMGB1, HMGB2, IL-6, IL-1β, and family history of allergy were the risk factors for AR. This study showed that the serum HMGB1 and HMGB2 levels was remarkably enhanced in AR patients and closely associated with cytokines. This study may provide new targets and a comprehensive approach for the treatment of AR patients.
Efficacy of acupotomy combined with sodium hyaluronate versus sodium hyaluronate alone in the treatment of knee osteoarthritis: A meta-analysis
Authors: Wu Qinglin , Wu Zuqing , Lu Zhifu
Published: September 2023

Background:

The efficacy of acupotomy combined with hyaluronic sodium acid in the treatment of knee osteoarthritis (KOA) is unclear. Therefore, this meta-analysis aims to evaluate the efficacy of acupotomy combined with hyaluronic sodium acid compared with hyaluronic sodium acid alone in the treatment of KOA.

Methods:

Studies from 8 Online databases were searched on KOA treatment using acupotomy combined with sodium hyaluronate until May 2022. The primary outcome indicator was clinical effectiveness, and the secondary outcome indicators included the visual analogue scale scores and Lysholm scores. We calculated the weighted mean difference (WMD) or relative risk for all relevant outcomes.

Results:

Nine studies were identified, involving 644 cases. The results showed that acupotomy combined with intra-articular sodium hyaluronate injection for KOA was superior to sodium hyaluronate injection alone in terms of clinical effectiveness (relative risk = 1.17, 95% confidence interval [CI]: 1.09–1.25, P < .001) and visual analogue scale (WMD = −2.1, 95% CI: −2.25 to 1.95, P < .001), Lysholm score (WMD = 13.83, 95% CI: 3.47–24.19, P = .009).

Conclusion:

Acupotomy combined with intra-articular sodium hyaluronate injection for KOA is superior to sodium hyaluronate injection alone. Limited by the number and quality of included studies, this conclusion still needs to be verified by more high-quality Research.

INPLASY registration number:

INPLASY202350029.
Combining ADC values in DWI with rCBF values in arterial spin labeling (ASL) for the diagnosis of mild cognitive impairment (MCI)
Authors: Sui Haijing , Yang Juan , Xiang Honggang , Yan Chenggong
Published: September 2023

We aimed to investigate the role of combined apparent diffusion coefficient (ADC) values and relative cerebral blood flow (rCBF) values in the diagnosis of mild cognitive impairment (MCI) patients. The present prospective research enrolled 156 MCI patients and 58 healthy elderly people who came to our hospital from January 2021 to February 2023. T1W, T2W, diffusion-weighted imaging, and arterial spin labeling sequences were performed on all subjects, and ADC values and rCBF values were measured at the workstation. Clinical and demographic data of all patients were collected while mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores were used to assess patients’ cognitive abilities. The MCI group had significantly lower rCBF values in the left frontal lobe, left occipital lobe, right frontal lobe, and right occipital lobe than the HC group. The ADC values in the left frontal lobe as well as the right frontal lobe were remarkably elevated in the MCI group than in the HC group. MoCA and MMSE scores were positively correlated with rCBF values in the left frontal, right frontal, left occipital, and right occipital lobes and negatively correlated with ADC values in the left and right frontal lobes. Combined ADC values and rCBF values from the left frontal lobe for the diagnosis of MCI had a higher sensitivity and specificity with the AUC was 0.877, sensitivity 81.0%, specificity 82.7%. Additionally, pressure fasting plasma glucose, ADC of the left frontal lobe, right frontal lobe, rCBF of left frontal lobe and rCBF of left frontal lobe were the risk factors of patients with MCI. In summary, our results indicated that the ADC values and rCBF values were changed in MCI group compared to HC group and correlated with MMSE and MoCA scores.
Network pharmacology and molecular docking to explore the mechanism of Sheng Xue Bao mixture against iron deficiency anemia
Authors: Wang Yun , Qinqin Huang , Wang Haixia , Zhang Hongxu , Zhang Xinhua , Liu Weiguo , Xiang Zhenhua , Gu Yuming
Published: September 2023

Based on network pharmacology and molecular docking, we investigated the mechanism of action of Sheng Xue Bao mixture (SXBM) in treating iron deficiency anemia (IDA). We screened the HERB and traditional Chinese medicine systems pharmacology database and analysis platform databases to identify the active ingredients and targets of SXBM. The targets associated with “iron deficiency anemia” were collected from GeneCards, TTD, and OMIM databases. A component-target interaction network was constructed using Cytoscape 3.8.2. The protein-protein interaction network of candidate targets was generated using the STRING database and visualized with Cytoscape 3.8.2 software. Core modules obtained from clustering analysis were subjected to Gene Ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Finally, molecular docking validation of key targets and active components was performed using Autodock Vina software. A total of 174 active components and 111 genes were identified as potential active components and targets for IDA treatment, including quercetin, kaempferol, luteolin, beta-sitosterol, and other flavonoids as main active components. Gene Ontology enrichment analysis show that interleaved genes are enriched in 2328 biological processes, 71 cellular component expression processes, and 157 molecular function processes. Kyoto encyclopedia of genes and genomes analysis mainly envolved Prostate cancer, Hepatitis B, Kaposi sarcoma-associated herpesvirus infection, Endocrine resistance, Lipid and atherosclerosis, Central carbon metabolism in cancer, Human cytomegalovirus infection and HIF-1 signaling pathway. STAT3, SRC, PIK3R1, and GRB2 were selected as core targets. The molecular docking results demonstrated strong interactions between key components and their respective target proteins. Network pharmacological analysis suggested that SXBM could treat IDA by regulating various biological processes and related signaling pathways. It laid the foundation for further elucidating the molecular mechanism of SXBM treatment of IDA.
Pathological mechanism and targeted drugs of ulcerative colitis: A review
Authors: Guo Meitong , Wang Xiaoyan
Published: September 2023

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with abdominal pain, diarrhea, and mucopurulent stools as the main symptoms. Its incidence is increasing worldwide, and traditional treatments have problems such as immunosuppression and metabolic disorders. In this article, the etiology and pathogenesis of ulcerative colitis are reviewed to clarify the targeted drugs of UC in the latest research. Our aim is to provide more ideas for the clinical treatment and new drug development of UC, mainly by analyzing and sorting out the relevant literature on PubMed, summarizing and finding that it is related to the main genetic, environmental, immune and other factors, and explaining its pathogenesis from the NF-κB pathway, PI3K/Akt signaling pathway, and JAK/STAT signaling pathway, and obtaining anti-TNF-α monoclonal antibodies, integrin antagonists, IL-12/IL-23 antagonists, novel UC-targeted drugs such as JAK inhibitors and SIP receptor agonists. We believe that rational selection of targeted drugs and formulation of the best dosing strategy under the comprehensive consideration of clinical evaluation is the best way to treat UC.
A rare complication of people with inflammatory bowel disease after ileostomy: A case report
Authors: Jiang Hong , He Shengduo , Wang Huahong
Published: September 2023

Rationale:

Venous thromboembolism is one of the common complications of inflammatory bowel disease (IBD), which is a significant health problem worldwide. Factors such as inflammation, medications, and abdominal surgery, contribute to the increased risk of venous thromboembolism in patients with IBD. Cavernous transformation of the portal vein (CTPV) is a relatively rare complications of IBD. Subsequent portal hypertension could be fatal and the clinical treatment is difficult. Thus, early prevention is very crucial.

Patient concerns:

A 55-year-old man presented to our department with asthenia, hematemesis, and diarrhea. He was diagnosed with Crohn disease for 9 years. Two years ago, He suffered intestinal perforation and received enterectomy and ileostomy. And, anticoagulants were not given during perioperative period and after surgery because of the history of gastrointestinal bleeding.

Diagnoses:

The patient was given endoscopy inspection showing the varices of esophagus and gastric fundus near cardia. Contrast enhancement CT scan showed portal hypertension, CTPV, gastroesophageal varices, and splenomegaly. Then percutaneous transhepatic portography was performed to make a clear diagnosis.

Interventions:

Concerned about the risk of surgery, he refused surgical shunting. Conservative treatment was recommended due to technical difficulties instead of interventional therapy.

Outcomes:

And after a period of fasting, blood transfusion, and parenteral nutrition treatment, the patient did not experience any further vomiting or hematemesis.

Lessons:

Early identification and treatment of CTPV is difficult. Prevention such as early application of anticoagulant is necessary for patients with IBD undergoing surgery, particularly with simultaneous stoma formation. For IBD patients who are not suitable for anticoagulant therapy, postoperative follow-up monitoring should be more frequent and monitoring time should be extended.
A cross-sectional study from Qatar on the effect of influenza vaccination on the severity of COVID-19
Authors: Thomas Merlin , Ismail Shanima , Hameed Mansoor , Kazi Sabeeha Sayed Tarique , Chandra Prem , Raza Tasleem , Paul Theresa , Sattar Hisham Abdul , Suliman Aasir M. , Mohamed Sara Saeed Ibrahim , Ibrahim Ezzedin A. Salam , Subahi Eihab Abd Alla Abd Elrahim
Published: September 2023

To assess and compare the severity of corona virus disease 2019 (COVID-19) infection in patients with and without a history of influenza vaccination. In this cross-sectional study descriptive statistics were used to analyze COVID-19-related parameters, including demographics, comorbidities, and severity. Normally distributed data with mean, standard deviation, and 95% confidence interval (CI) were reported, while non-normally distributed data was presented with median and inter-quartile range. Categorical data was summarized using frequencies and percentages. Associations were assessed using Pearson Chi-square, Fisher Exact, t test, or Mann–Whitney U test. Univariate and multivariate logistic regression methods were used to evaluate the relationship between disease severity, clinical outcomes, influenza vaccination status, and other predictors. Significance was considered for p values < 0.05. Statistical analyses were done using SPSS V.27.0 (IBM Corp) and Epi Info (CDC) software. Between March 2020 and December 2020 before the availability of COVID-19 vaccination, 148,215 severe acute respiratory syndrome corona virus 2 positive patients were studied, with 3519 vaccinated against influenza, and 144,696 unvaccinated. After random sampling at 1:2 ratio, the final analysis included 3234 vaccinated and 5640 unvaccinated patients. The majority (95.4%) had mild or asymptomatic COVID-19, while 4.6% had severe or critical cases as defined by World Health Organization severity grading. Multivariate logistic regression analysis revealed that the vaccinated group had significantly less severe (adjusted odds ratio [OR] 0.683; 95% CI 0.513–0.911, P = .009) and critical (adjusted OR 0.345; 95% CI 0.145–0.822, P = .016) COVID-19 and were less likely to require oxygen therapy (adjusted OR 0.696; 95% CI 0.531–0.912, P = .009) after adjusting for confounders like age, gender and comorbidities. No significant differences in Intensive care unit admissions (adjusted OR 0.686; 95% CI 0.425–1.11, P = .122), mechanical ventilation (adjusted OR 0.631; 95% CI 0.308–1.295, P = .209) and mortality (adjusted OR 1.105; 95% CI 0.348–3.503, P = .866) were noted between the 2 groups. Influenza vaccination may significantly reduce the severity of COVID-19 but has no significant effect on intensive care unit admissions, mechanical ventilation and all- cause mortality.
Screening potential treatments for mpox from Traditional Chinese Medicine by using a data-driven approach
Authors: Li Linyang , Xu Chengchen , Guo Yinling , Wang Haozhong
Published: September 2023

Mpox (MPX) has escalated into a public health emergency of international concern, necessitating urgent prophylactic and therapeutic measures. The primary goal of this investigation was to systematically extract Wan Quan’s expertise in treating smallpox, as documented in Exclusive Methods for Treating Pox (Dou Zhen Xin Fa in Chinese), with the aim of identifying potential prescriptions, herbs, and components for alternative MPX therapies or drugs. This research utilized data mining to identify high-frequency Chinese Medicines (CMs), high-frequency CM-pairs, and CM compatibility rules. Network pharmacology, molecular docking, and molecular dynamic simulation were employed to reveal the potential molecular mechanisms of the core CM-pair. 119 prescriptions were extracted from Exclusive Methods for Treating Pox. We identified 25 high-frequency CMs and 23 high-frequency CM pairs among these prescriptions. Combined association rule mining analysis, Gancao (Glycyrrhiza uralensis Fisch.), Renshen (Panax ginseng C. A. Mey.), Danggui (Angelica sinensis (Oliv.) Diels), Shengma (Cimicifuga foetida L.), and Zicao (Lithospermum erythrorhizon Siebold & Zucc.) were selected as the core CM-pair for further investigation. Network pharmacology analysis yielded 131 active components and 348 candidate targets for the core CM-pair. Quercetin and celabenzine were chosen as ligands for molecular docking. GO and KEGG enrichment analyses revealed that the core CM-pair could interact with targets involved in immune, inflammatory, and infectious diseases. Moreover, key mpox virus targets, F8-A22-E4 DNA polymerase holoenzyme and profilin-like protein A42R, were docked well with the selected core components. And molecular dynamic simulation indicated that the component (quercetin) could stably bind to the target (profilin-like protein A42R). Our findings identified potential prescriptions, herbs, and components that can offer potential therapies or drugs for addressing the MPX epidemic.
Mitochondrial metabolism-related signature depicts immunophenotype and predicts therapeutic response in testicular germ cell tumors
Authors: Qiu Dandan , Gao Lingling , Zhang Shuo , Lin Gang , Yu Xingwei
Published: September 2023

In recent years, there has been growing evidence linking mitochondrial dysfunction to the development and progression of cancer. However, the role of mitochondrial metabolism-related genes (MMRGs) in testicular germ cell tumor (TGCT) remains unclear. We downloaded clinical pathology, transcriptome, and somatic mutation data for TGCT from public databases and conducted univariate Cox regression analysis to investigate prognostic correlations. We also used consensus clustering to identify molecular subtypes, comparing differential expression genes, biological processes, Kyoto Encyclopedia of Genes and Genomes pathways, mutations, prognosis, immune infiltration, drug sensitivity, and immune therapeutic response between these subtypes. We constructed multi-gene risk features and nomograms for TGCT prognosis. Fifteen MMRGs were significantly correlated with progression-free survival in TGCT patients. Based on these genes, we identified 2 molecular subtypes which showed significant differences in somatic mutations, prognosis, and immune cell infiltration. These subtypes could also indicate drug sensitivity and immune therapeutic response; the subtype with poor prognosis showed a higher potential benefit from some drugs and immunotherapy. Abnormalities in immune-related biological processes and extracellular matrix as well as Kyoto Encyclopedia of Genes and Genomes pathways such as PI3K-AKT signaling pathway, pat5hways in cancer, primary immunodeficiency, and neutrophil extracellular trap formation were associated with significant differences in phenotypes among subtypes. Finally, we constructed an 8-gene TGCT risk feature based on differential expression genes between subtypes which performed well in TGCT patient prognostic evaluation. Our study elucidated the prognostic correlation between MMRGs and TGCT and established MMRG-derived molecular subtypes and risk features for personalized treatment of TGCT which have potential clinical application value.
lncRNA HOTAIR promotes ROS generation and NLRP3 inflammasome activation by inhibiting Nrf2 in diabetic retinopathy
Authors: You Hui , Li Hongyu , Gou Wenjun
Published: September 2023

Background:

Diabetic retinopathy (DR) is a microvascular complication associated with damage to the retina due to inflammation induced by high glucose. Activation of the NLRP3 inflammasome plays a critical role in DR and its prevention is beneficial to patients. However, the regulation of long non-coding RNA (lncRNA) in NLRP3 inflammasome activation of DR is incompletely understood. So, this study aimed to uncover the functional and regulatory mechanism of the lncRNA HOTAIR in NLRP3 inflammasome activation in Dr

Methods:

The vitreous humor was collected from the patients and detected the inflammatory and oxidative stress makers. Human retinal endothelial cells (HRECs) were cultured and stimulated in low D-glucose (5 mmol/L) or high D-glucose (20 mmol/L). Additionally, HRECs were knocked down HOTAIR with a si-RNA. Then, the NLRP3 inflammasome activation was analyzed by western blotting and pyroptosis cell imaging. The ROS was measured by specific probe. The activation of Nrf2 measured by Immunofluorescent staining. The interaction between HOTAIR and Nrf2 was evaluated by co-immunoprecipitation and RNA immunoprecipitation.

Results:

The expression of HOTAIR was significantly increased in the vitreous of patients with DR and in HRECs stimulated with high glucose. Furthermore, HOTAIR knockdown relieved NLRP3 inflammasome activation. More specifically, HOTAIR knockdown suppressed the expression of NLRP3, pro-caspase-1, and pro-IL-1β, as well as IL-1β maturation and pyroptosis. HOTAIR knockdown also interfered with the ROS generation induced by high glucose. Moreover, HOTAIR promoted the interaction between Nrf2 and Keap1 by binding and inactivating Nrf2.

Conclusion:

The lncRNA HOTAIR promotes NLRP3 inflammasome activation and ROS generation by inhibiting Nrf2 in Dr
The relationship between learning burnout, professional commitment, and psychological capital in undergraduate clinical medical students
Authors: Yu Shaojie , Li Wei , Yu Huizu , Ju Xuehong , Ling Chunguang
Published: September 2023

This study examines the current status of and relationship between learning burnout, professional commitment, and psychological capital in undergraduate clinical medical students. A total of 249 undergraduate students were randomly selected from a 5-year clinical medical program at a medical university in Shandong, China. The study employed the Learning Burnout Scale, Professional Commitment Scale, Psychological Capital Scale to survey the sample, and performed structural equation modeling and multiple regression to test the proposed research model using SPSS 19.0. Significant differences in learning burnout were found among students in terms of their gender, years in the medical program, and student leadership (t = 1.811, F = 22.091, t = −2.295; P < .01). There were also significant differences in their professional commitment according to their gender, years in the program, and student leadership (t = −2.711, F = 4.275, t = 3.389; P < .01). Psychological capital differed significantly based on gender, years in the program, and student leadership (t = 8.709, F = 6.182, P < .01, t = 2.086, P < .05). Learning burnout showed significant negative correlations with professional commitment and psychological capital (r = −0.311, r = −0.291; P < .01). The psychological capital and professional commitment of undergraduate students of clinical medicine serve as predictors of learning burnout. Psychological capital partially mediates the relationship between professional commitment and learning burnout.
Network pharmacology and molecular docking predictions of the active compounds and mechanism of action of Huangkui capsule for the treatment of idiopathic membranous nephropathy
Authors: Cai Meng , Xiang Yongjing , Li Zhengsheng , Xie Juan , Wen Fulong
Published: September 2023

Background:

Huangkui Capsule is a single herbal concoction prepared from the flower of Abelmoschus manihot, which is used to treat idiopathic membranous nephropathy (IMN), a frequent pathologically damaging kidney condition. It has been widely utilized to treat a variety of renal disorders, including IMN, in clinical practice. However, the active compounds and mechanism of action underlying the anti-IMN effects of Huangkui Capsule remain unclear. In this study, we aimed to predict the potential active compounds and molecular targets of Huangkui Capsule for the treatment of IMN.

Methods:

The possible active components of Huangkui were located using the SymMap v2 database. The targets of these drugs were predicted using Swiss Target Prediction, while IMN-related genes with association scores under 5 were gathered from the GeneCards and DisGeNET databases. The common targets of the disease and the components were determined using VENNY 2.1. Using Cytoscape 3.8.0, a drug-disease network diagram was created. Molecular docking was carried out with Pymol, AutoDock Tools, and AutoDock Vina.

Results:

With 1260 IMN-related illness genes gathered from GeneCards and DisGeNET databases, we were able to identify 5 potentially active chemicals and their 169 target proteins in Huangkui. Based on degree value, the top 6 targets for Huangkui treatment of IMN were chosen, including AKT, MAPK3, PPARG, MMP9, ESR1, and KDR.

Conclusion:

This work theoretically explains the mechanism of action of Huangkui Capsule in treating IMN and offers a foundation for using Huangkui Capsule in treating IMN in clinical settings. The findings require additional experimental validation.
Clinical and radiological features of a case of primary encephalitis induced by SARS-CoV-2 omicron variant infection: A case report
Authors: Zhang Xiong , Hu Ruiting , Zhao Fanyu
Published: September 2023

Rationale:

In 2022, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron spread widely around the world. In the context of most literature reporting weakened virulence of the virus, immunocompromised patients who have not been vaccinated should be vigilant for the development of encephalitis following SARS-CoV-2 infection.

Patient concerns:

A 58-year-old male patient with immunodeficiency presented with respiratory and psychiatric symptoms after contracting SARS-CoV-2 Omicron variant.

Diagnoses:

The patient was diagnosed with coronavirus disease 2019 infection and associated acute primary encephalitis.

Interventions:

The patient was received comprehensive treatment including Azvudine antiviral therapy, immunoglobulin infusion, and methylprednisolone anti-inflammatory therapy.

Outcomes:

The patient’s condition improved and he was discharged smoothly. One month after discharge, the patient returned for follow-up, and the occipital lobe still had a few slow waves on electroencephalogram, but the patient reported no seizure events since discharge.

Lessons:

During the prevalence of the SARS-CoV-2 Omicron variant, we believe that it is still necessary to be vigilant about immunocompromised patients developing encephalitis. Early use of cranial magnetic resonance imaging as a diagnostic assistance is conducive to early diagnosis and treatment of patients.
The efficacy of the leg swing and quadriceps strengthening exercises versus platelet-rich plasma and hyaluronic acid combination therapy for knee osteoarthritis: A retrospective comparative study
Authors: Ma Cong , Li Xuejing , Pan Ying , Tian Hua , Wang Zhongzheng , Zhang Xiaoyang , Zheng Xiaozuo , Liu Guoqiang , Duan Kunfeng , Qie Suhui
Published: September 2023

The aim of this was to investigate the efficacy of physical exercise (leg swing and quadriceps strengthening exercises) versus platelet-rich plasma (PRP) and hyaluronic acid (HA) combination therapy. From January 2020 to August 2021, 106 patients with Kellgren–Lawrence Grade I–III knee osteoarthritis were divided into leg swing and quadriceps strengthening exercises (Group A) and intra-articular combination injections of PRP and HA (Group B) according to the treatment strategies. Patients in Group A received regular leg swing and quadriceps strengthening exercises for 3 months. Patients in Group B received 2 intra-articular combination injections of PRP (2 mL) and HA (2 mL) every 2 weeks. The primary outcome measures were the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities (WOMAC) score. Secondary outcomes included single leg stance test and functional activity by 2-minute walk test and time up and go test. All outcomes were evaluated at baseline and again 1, 3, 6, and 12 months. The VAS and WOMAC scores were similar in both groups at 1 and 3 months after treatment (P > .05); however, Group A patients had significantly superior VAS and WOMAC scores than Group B patients at 6 and 12 months after treatment. For the single leg stance test, 2-minute walk test, and time up and go test, Group A patients were significantly superior to Group B throughout follow-up (P < .001). The leg swing and quadriceps strengthening exercises resulted in a significantly better clinical outcomes than the combined PRP and HA therapy, with a sustained lower pain score and improved quality of life, balance ability, and functional activity within 12 months.
Prognostic significance of MALAT1 in clear cell renal cell carcinoma based on TCGA and GEO
Authors: Liu Kai , Gao Yingxue , Zhang Quanwu
Published: September 2023

Long noncoding RNAs metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) can regulate tumorigenesis and progression of various cancers. However, there is little known about the tumor biology and regulatory mechanism of MALAT1 in clear cell renal cell carcinoma (ccRCC). The objective of this study was to evaluate the prognostic value and potential functions of MALAT1 in ccRCC based on the cancer genome atlas. Through bioinformatics research, we analyzed the expression of MALAT1 in ccRCC, and the relationship with clinicopathological features, overall survival and infiltration of immune cells, and established the prognostic models. The results showed that MALAT1 was highly expressed in ccRCC tissues and predicted poor ccRCC patient outcome. The expression level of MALAT1 was significantly correlated with histologic grade, pathologic grade, T stage, M stage. ROC curve showed that MALAT1 had a good diagnostic accuracy, area under the curve of 0.752. The univariate and multivariate cox regression analysis showed that high MALAT1 expression was an independent prognostic factor for overall survival in the cancer genome atlas (hazard ratio = 2.271, 95% confidence interval: 1.435–3.593, P < .001). Gene set enrichment analysis revealed that MALAT1 expression was associated with the DNA methylation, epigenetic regulation of gene expression signaling pathway. In addition, the prognostic models were established to predict 1-, 3- and 5-year survival. This study showed that high expression of MALAT1 might be a potential diagnostic and prognostic biomarker.
Pancreatic Acinar Cystic Transformation
Authors: Aguilera Munoz Lina , Boros Carina , Bonvalet Fanny , Ronot Maxime , Rebours Vinciane
Published: September 2023

Pancreatic acinar cystic transformation (ACT) is a recently described entity of the pancreatic cysts' spectrum. It is a nonneoplastic pancreatic lesion, mostly asymptomatic, and is considered a rare disease, with less than 100 reported cases. Its benign nature and the absence of reported cases of malignant transformation or invasive lesions were a plea for a conservative approach. As a consequence, little is known about the pathogenesis of this lesion. No familial history of ACT has been previously described. Here, we report a familial case of 2 siblings with typical ACT imaging lesions giving evidence for familial aggregation. No obvious environmental exposure was identified as a potential risk factor for ACT development. No physiological data exist to suggest a congenital nature of these lesions, but for the first patient, the calcifications seem to have appeared with time. Further research, with high throughput sequencing technologies, may elucidate genetic polymorphisms explaining potential ACT familial phenotype. In practice, careful family history collection must be performed to identify a possible familial form of ACT when this diagnosis is proposed.
Lactated Ringer's or Normal Saline for Initial Resuscitation in Patients Hospitalized With Acute Pancreatitis
Authors: Antoniak Derrick , Twohig Patrick , Olson Kristin , Samson Kaeli , Mitchell Christine , Eichele Derrick
Published: September 2023

Objectives

Fluid resuscitation is required in acute pancreatitis (AP) to prevent hypovolemia and organ hypoperfusion. Lactated Ringer's (LR) is a buffered crystalloid with possible advantages in AP versus normal saline (NS). We aim to assess outcomes in patients hospitalized with AP based on fluid used for resuscitation.

Methods

In this retrospective analysis, we identified hospital admissions to Veterans Affairs facilities for AP from 2011 to 2017 and grouped by initial resuscitation fluid: LR versus NS. Outcomes included major complications and mortality at 30 and 365 days. Multivariable models were used to adjust for confounding variables.

Results

A total of 20,049 admissions were included in the study, of which 10% received LR as initial fluid. After adjustment for all available confounders, resuscitation with LR was associated with lower 1-year mortality compared with NS (adjusted odds ratio, 0.61 [95% confidence interval, 0.50–0.76]). Major complication and early mortality were similar between groups.

Conclusions

In this study, we demonstrate an association between use of LR as initial resuscitation fluid and reduced 1-year mortality in a large retrospective sample of veterans hospitalized with AP. These results support the use of LR for resuscitation for most patients hospitalized with AP.
Successful Development of a Natural Language Processing Algorithm for Pancreatic Neoplasms and Associated Histologic Features
Authors: Harrison Jon Michael , Yala Adam , Mikhael Peter , Roldan Jorge , Ciprani Debora , Michelakos Theodoros , Bolm Louisa , Qadan Motaz , Ferrone Cristina , Fernandez-del Castillo Carlos , Lillemoe Keith Douglas , Santus Enrico , Hughes Kevin
Published: September 2023

Objectives

Natural language processing (NLP) algorithms can interpret unstructured text for commonly used terms and phrases. Pancreatic pathologies are diverse and include benign and malignant entities with associated histologic features. Creating a pancreas NLP algorithm can aid in electronic health record coding as well as large database creation and curation.

Methods

Text-based pancreatic anatomic and cytopathologic reports for pancreatic cancer, pancreatic ductal adenocarcinoma, neuroendocrine tumor, intraductal papillary neoplasm, tumor dysplasia, and suspicious findings were collected. This dataset was split 80/20 for model training and development. A separate set was held out for testing purposes. We trained using convolutional neural network to predict each heading.

Results

Over 14,000 reports were obtained from the Mass General Brigham Healthcare System electronic record. Of these, 1252 reports were used for algorithm development. Final accuracy and F1 scores relative to the test set ranged from 95% and 98% for each queried pathology. To understand the dependence of our results to training set size, we also generated learning curves. Scoring metrics improved as more reports were submitted for training; however, some queries had high index performance.

Conclusions

Natural language processing algorithms can be used for pancreatic pathologies. Increased training volume, nonoverlapping terminology, and conserved text structure improve NLP algorithm performance.
Stem nodulation: diversity and occurrence inAeschynomeneandSesbanialegumes from wetlands of Madagascar
Authors: Manantsoa Faustin F. , Rakotoarisoa Marrino F. , Chaintreuil Clémence , Razakatiana Adamson T.E. , Gressent Frédéric , Pervent Marjorie , Bourge Mickaël , Andrianandrasana Martial D. , Nouwen Nico , Randriambanona Herizo , Ramanankierana Heriniaina , Arrighi Jean-François
Published: September 2023

As an adaptation to flooding, few legume species have the original ability to develop nitrogen-fixing nodules on the stem. By surveying wetlands of Madagascar, we found a large occurrence and diversity of stem nodulation in Aeschynomene and Sesbania legumes. They represent opportunities to investigate different modalities of the nitrogen-fixing symbiosis in legumes.
Leveraging Machine Learning to Uncover the Hidden Links between Trusting Behavior and Biological Markers
Authors: Cao Zimu , Setoyama Daiki , Monica-Natsumi Daudelin , Matsushima Toshio , Yada Yuichiro , Watabe Motoki , Hikida Takatoshi , Kato Takahiro A , Naoki Honda
Published: September 2023

Understanding the decision-making mechanisms underlying trust is essential, particularly for patients with mental disorders who experience difficulties in developing trust. We aimed to explore biomarkers associated with trust-based decision-making by quantitative analysis. However, quantification of decision-making properties is difficult because it cannot be directly observed. Here, we developed a machine learning method based on Bayesian hierarchical model to quantitatively decode the decision-making properties from behavioral data of a trust game. By applying the method to data of patients with MDD and healthy controls, we estimated model parameters regulating trusting decision-making. The estimated model was able to predict behaviors of each participant. Although there is no difference of the estimated parameters between MDD and healthy controls, several biomarkers were associated with the decision-making properties in trusting behavior. Our findings provide valuable insights into the trusting decision-making, offering a basis for developing targeted interventions to improve their social functioning and overall well-being.
Developmental priming of cancer susceptibility
Authors: Panzeri Ilaria , Fagnocchi Luca , Apostle Stefanos , Tompkins Megan , Wolfrum Emily , Madaj Zachary , Hostetter Galen , Liu Yanqing , Schaefer Kristen , Chih-Hsiang Yang , Bergsma Alexis , Drougard Anne , Dror Erez ,   PERMUTE, Chandler Darrell , Schramek Daniel , Triche Timothy J. , Pospisilik J. Andrew
Published: September 2023

DNA mutations are necessary drivers of cancer, yet only a small subset of mutated cells go on to cause the disease. To date, the mechanisms that determine which rare subset of cells transform and initiate tumorigenesis remain unclear. Here, we take advantage of a unique model of intrinsic developmental heterogeneity (Trim28+/D9) and demonstrate that stochastic early life epigenetic variation can trigger distinct cancer-susceptibility ‘states’ in adulthood. We show that these developmentally primed states are characterized by differential methylation patterns at typically silenced heterochromatin, and that these epigenetic signatures are detectable as early as 10 days of age. The differentially methylated loci are enriched for genes with known oncogenic potential. These same genes are frequently mutated in human cancers, and their dysregulation correlates with poor prognosis. These results provide proof-of-concept that intrinsic developmental heterogeneity can prime individual, life-long cancer risk.
Valency of Ligand-Receptor Binding from Pair Potentials
Authors: Morton William , Vácha Robert , Angioletti-Uberti Stefano
Published: September 2023

Molecular dynamics simulations have been crucial for investigating the dynamics of nanoparticle uptake by cell membranes via ligand-receptor interactions. Use of coarsegrained models has enabled evaluation of the effects of nanoparticle size, shape, ligand distribution on nanoparticles surface, or used thoroughly in the past decade, where a percentage of lipid heads, receptors, are attracted to sites on the nanoparticle surface, ligands. However, when pair-potentials are used to represent ligand-receptor interactions, the number of receptors interacting with one ligand, valency, may vary. We demonstrate that the curvature of a nanoparticle, strength of ligand-receptor interactions, and ligand or receptor concentration change the valency - ranging from 3.4 to 5.1 in this study. Such change in valency can create inaccurate comparisons between nanoparticles, or even result in the uptake of smaller nanoparticles than would be expected. To rectify this inconsistency we propose the adoption of a model based on bond-formation and use it to determine the extent to which previous studies may have been effected. This work recommends avoiding pair-potentials for modeling ligandreceptor interactions to ensure methodological consistency in nanoparticle studies.

TOC Graphic

A rendering of a ligand coated nanoparticle coming into contact with a lipid bilayer membrane. The receptor in the membrane is highlighted for clarity.
Intracellular K+limits T cell exhaustion and preserves antitumor function
Authors: Collier Camille , Wucherer Kelly , McWhorter Matthew , Jenkins Chelsea , Bartlett Alexandra , Roychoudhuri Rahul , Eil Robert
Published: September 2023

The cancer-killing activity of T cells is often compromised within tumors, allowing disease progression. We previously found that intratumoral elevations in extracellular K+related to ongoing cell death constrained CD8+T cell Akt-mTOR signaling and effector function (1,2). To alleviate K+mediated T cell suppression, we pursued genetic means to lower intracellular K+.

Transcriptomic analysis of CD8+T cells demonstrated the Na+/K+ATPase to be robustly and dynamically expressed. CRISPR-Cas9 mediated deletion of the catalytic alpha subunit of the Na+/K+ATPase lowered intracellular K+but produced tonic hyperactivity in multiple signal transduction cascades along with the acquisition of co-inhibitory receptors and terminal differentiation in mouse and human CD8+T cells. Mechanistically, Na+/K+ATPase disruption led to ROS accumulation due to depletion of intracellular K+in T cells. Antioxidant treatment or high K+media preventedAtp1a1deficient T cells from exhausted T (TEx) cell formation. Consistent with transcriptional and proteomic data suggesting a TExcell phenotype, T cells lackingAtp1a1had compromised persistence and antitumor activity in a syngeneic model of orthotopic murine melanoma. Translational application of these findings will include efforts to lower intracellular K+while limiting ROS accumulation within tumor specific T cells.

Synopsis

High extracellular K+(↑[K+]e) is found within tumors and suppresses T cell effector function. Collier et al. find that deletion of the Na+/K+ATPase in T cells lowers intracellular K+and promotes ROS accumulation, tonic signal transduction and T cell exhaustion owing to ROS accumulation. Engineering T cell ion transport is an important consideration for cancer immunotherapy.