bluuebunny/crossref_metadata_2025 huggingface dataset:
FAM46C as a Potential Marker for Pan-Cancer Prognosis and Predicting Immunotherapeutic Efficacy
Authors: Deng Jiehua , Xiao Wei , Wang Zheng
Published: February 2022

Background:FAM46C is a common mutated gene in tumours. A comprehensive understanding of the relationship between FAM46C expression and pan-cancer can guide clinical prognosis and broaden the immunotherapeutic targets.

Methods: Data from The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases were obtained, and gene expression of different tumour types and stages was analysed. Immunohistochemical analysis was performed to detect differences in the FAM46C protein levels in normal and cancerous tissues. The genetic variation of FAM46C was characterised using cBioPortal. The clinical prognostic value of FAM46C and the impact of FAM46C expression levels on the prognosis of patients with different types of cancer were assessed based on Kaplan–Meier and Cox regression analyses. Gene set enrichment analysis (GSEA) was used to analyse the pathways associated with FAM46C. Correlations between FAM46C expression levels and immune infiltration were assessed using the TIMER2 database and CIBERSORT algorithm, and correlations between FAM46C expression and the ESTIMATE, immune and stromal scores were analysed using the ESTIMATE algorithm. In addition, we also analysed the correlation between FAM46C expression and immune activation, suppression genes and immune chemokines.

Results: The expression level of FAM46C was correlated with the prognosis of most tumours, and low expression levels often suggested a poor prognosis. FAM46C was positively correlated with the abundance of CD4+ T cells, CD8+ T cells and plasma B lymphocytes in the tumour microenvironment. FAM46C exhibited a strong correlation with immunomodulatory pathways, immunomodulatory factors and immune markers. In addition, high FAM46C expression correlated with tumour mutational burden in acute myeloid leukaemia and microsatellite instability in endometrial cancer.

Conclusion: Our study suggests that FAM46C can be a potential prognostic marker for pan-cancer, is closely associated with immune regulation and may be an immune checkpoint to guide future clinical immunotherapy.
A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations
Authors: Chakraborty Chiranjib , Sharma Ashish Ranjan , Bhattacharya Manojit , Lee Sang-Soo
Published: February 2022

The infective SARS-CoV-2 is more prone to immune escape. Presently, the significant variants of SARS-CoV-2 are emerging in due course of time with substantial mutations, having the immune escape property. Simultaneously, the vaccination drive against this virus is in progress worldwide. However, vaccine evasion has been noted by some of the newly emerging variants. Our review provides an overview of the emerging variants’ immune escape and vaccine escape ability. We have illustrated a broad view related to viral evolution, variants, and immune escape ability. Subsequently, different immune escape approaches of SARS-CoV-2 have been discussed. Different innate immune escape strategies adopted by the SARS-CoV-2 has been discussed like, IFN-I production dysregulation, cytokines related immune escape, immune escape associated with dendritic cell function and macrophages, natural killer cells and neutrophils related immune escape, PRRs associated immune evasion, and NLRP3 inflammasome associated immune evasion. Simultaneously we have discussed the significant mutations related to emerging variants and immune escape, such as mutations in the RBD region (N439K, L452R, E484K, N501Y, K444R) and other parts (D614G, P681R) of the S-glycoprotein. Mutations in other locations such as NSP1, NSP3, NSP6, ORF3, and ORF8 have also been discussed. Finally, we have illustrated the emerging variants’ partial vaccine (BioNTech/Pfizer mRNA/Oxford-AstraZeneca/BBIBP-CorV/ZF2001/Moderna mRNA/Johnson & Johnson vaccine) escape ability. This review will help gain in-depth knowledge related to immune escape, antibody escape, and partial vaccine escape ability of the virus and assist in controlling the current pandemic and prepare for the next.
A Novel Combined Use of Dupilumab for Treatment of Aggressive Refractory Pemphigus Vulgaris Complicated With Pulmonary Tuberculosis: A Case Report and the RNA-seq Analysis
Authors: Chen Siji , Zhan Shaowei , Hua Chunting , Tang Yi , Cheng Hao
Published: February 2022

Background

Pemphigus vulgaris (PV) is a kind of IgG-mediated autoimmune blistering disease (AIBD) that is characterized by loss of keratinocyte adhesion in the epithelium of mucous membranes or skin. Recently, pemphigus vulgaris was thought to be associated with classical T helper 2 (TH2)-type cytokines such as interleukin‐4 (IL-4) and interleukin‐17 (IL-17) signaling pathway. A humanized monoclonal IgG4 antibody called dupilumab binds to the alpha subunit of the interleukin‐4 receptor (IL‐4Rα) and inhibits the signaling of IL-4 and interleukin‐13 (IL-13), which has been successfully applied for atopic dermatitis and asthma. Currently, the clinical trial evaluating dupilumab in bullous pemphigoid is ongoing.

Objective

To determine whether dupilumab may be of benefit in the aggressive refractory pemphigus vulgaris.

Methods

We report a 35-year old male with refractory pemphigus vulgaris and pulmonary tuberculosis who received treatment with dupilumab for 10 weeks. The mRNA expression of peripheral blood mononuclear cells (PBMCs) was analyzed by RNA sequencing (RNA-seq) which showed the gene expression changes after treatment.

Results

The skin lesions of the patient improved in response to the combined use of dupilumab, moderate dose of glucocorticosteroids, and intravenous immune globulin (IVIG). Downregulations of inflammatory response-related genes and IL-17 signaling pathway-related genes were observed in PBMCs.

Conclusion

We describe a patient with refractory pemphigus vulgaris and pulmonary tuberculosis who had the disease under control with combined use of dupilumab as an add-on treatment. Dupilumab may provide a beneficial effect in aggressive refractory pemphigus vulgaris.
Clinical and Multi-Mode Imaging Features of Eyes With Peripapillary Hyperreflective Ovoid Mass-Like Structures
Authors: Xie Xiao , Liu Tingting , Wang Wenqi , Tian Ge , Wang Jinyan , Guan Jitian , Chen Meng , Wang Xunchang , Zhou Qingjun
Published: February 2022

Purpose

To observe and analyze the clinical and multi-mode imaging features of eyes with PHOMS, and to introduce two cases of PHOMS which underwent multi-mode imaging.

Methods

Retrospective clinical observational study. A total of 26 patients (37 eyes) with hyperreflective structures surrounded by hyporeflective edges around the optic discs who were examined and diagnosed at Shandong Eye Hospital between January 2019 and June 2021 were included in the study. Among these patients, 12 were male and 14 were female. Fifteen were monocular. The average age was 39 years. All patients underwent the following examinations: Best-corrected visual acuity (BCVA), intraocular pressure examinations, slit-lamp anterior segment examinations, indirect ophthalmoscopy, visual field examinations, fundus color photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA). Some of the patients were examined with fundus fluorescein angiography (FFA). Clinical data and imaging characteristics from the OCT, OCTA, and FFA were analyzed retrospectively.

Results

We found the hyperreflective structures surrounded by hyporeflective edges around the optic discs in 37 eyes. EDI-OCT results revealed hyperreflective structures surrounded by hyporeflective edges around the optic discs in all eyes. Typical hyperreflexia lesions occurred around the optic disc, located subretinally and above Bruch's membrane. OCTA revealed that the highly reflective perioptic material also had vascular structures.

Conclusion

EDI-OCT of PHOMS showed hyperreflective structures surrounded by hyporeflective edges around all of the optic discs. Infra-red photography showed temporal hyperreflexia. These characteristics can be seen in a variety of diseases and may be a relatively common feature revealed by EDI-OCT scanning. These characteristics may also be seen in elderly patients as well as children. PHOMS may be found in optic disc drusen (ODD), tilted disc syndrome (TDS), optic neuritis, ischemic optic neuropathy, and in white dot syndromes. Few patients may be developed into macular neovascularization (MNV). In order to improve the accuracy and robustness of the conclusions and provide better clinical guidance, we need to conduct more comprehensive research in the subsequent clinical work.
Analgesic Efficacy of Spinal Morphine in Comparison With Transversus Abdominis Plane Block for Postoperative Pain Management in Patients Undergoing Cesarean Section Under Spinal Anesthesia: A Randomized Controlled Trial
Authors: Jemal Bedru , Mohammed Fetiha , Tesema Hailemariam Getachew , Ahmed Siraj , Mohammed Ayub , Regasa Teshome , Obsa Mohammed Suleiman
Published: February 2022

Background

Cesarean section (CS) has been one of the most frequently performed major surgical interventions and causes severe postoperative pain. Spinal opioid and abdominal field block have been investigated as effective analgesia for postoperative pain and reduce the need for systemic medications and associated side effects. The aim of the current study is to compare spinal morphine (SM) and bilateral landmark oriented transversus abdominis plane (TAP) block for postoperative pain management.

Method

In this randomized controlled trial, 114 pregnant mothers scheduled for CS under spinal anesthesia were allocated randomly to receive either SM 0.1 mg (group SM; n = 56) or bilateral landmark-oriented TAP block with 20 ml of 0.25% of bupivacaine (group TAP; n = 52). A comparison of numerical variables between study groups was done using unpaired student t-test and Mann–Whitney test for symmetric and asymmetric data, respectively. Time to event variable was analyzed by using Kaplan–Meir's survival function. A p-value of < 0.05 was considered statistically significant.

Result

A total of 114 patients were recruited and randomly assigned and received interventions. Among them, 108 patients completed this study. Time to first analgesic request was significantly shorter in the TAP block compared to SM. Twenty-four-hour median morphine consumption was reduced in the SM group compared to the TAP block (p < 0.001). Median postoperative pain score during movement and rest shows statistically significant differences between groups (p < 0.001).

Conclusion

The addition of preservative-free 100 μg SM provides prolonged postoperative analgesia time, superior postoperative analgesia, and less postoperative opioid consumption compared to the TAP block.
Overcoming Multidrug Resistance in Salmonella spp. Isolates Obtained From the Swine Food Chain by Using Essential Oils: An in vitro Study
Authors: Lauteri Carlotta , Maggio Francesca , Serio Annalisa , Festino Anna Rita , Paparella Antonello , Vergara Alberto
Published: February 2022

Antimicrobial resistance (AMR) is a global concern, and new approaches are needed to circumvent animal and food-borne resistant pathogens. Among the new strategies, the combination of antibiotics with natural compounds such as essential oils (EOs) could be an alternative to challenge bacterial resistance. The present study evaluates the phenotypic and genotypic antibiotic resistance of 36 Salmonella enterica (16 S. Typhimurium, 3 monophasic variant S. Typhimurium, 8 S. Enteritidis, 6 S. Rissen, 1 S. Typhi, and 2 S. Derby) strains, isolated from the swine production chain. The isolates displayed phenotypic resistance to gentamicin, amikacin, tobramycin, and tetracycline, while the resistance genes most commonly detected were parC, catA, nfsB, nfsA, blaTEM, tetA, and tetB. Then 31/36 Salmonella isolates were chosen to evaluate resistance to tetracycline and Thymus vulgaris, Eugenia caryophyllata, and Corydothymus capitatus EOs by determining minimum inhibitory concentrations (MICs). Finally, the synergistic effect between tetracycline and each EOs was evaluated by the checkerboard method, calculating the fractional inhibitory concentration (FIC) index. Among the EOs, C. capitatus displayed the best bioactivity in terms of MICs, with the lowest values (0.31 and 0.625 μl/ml). On the contrary, the strains showed the ability to grow in the presence of the maximum concentration of tetracycline employed (256 μg/ml). While not displaying a real synergism according to the FIC index, the combination of tetracycline compounds and the three EOs resulted in a significant reduction in the MIC values to tetracycline (4 μg/ml), suggesting a restoration of the susceptibility to the antibiotic in Salmonella spp.
Antiretroviral Imprints and Genomic Plasticity of HIV-1 pol in Non-clade B: Implications for Treatment
Authors: Bimela Jude S. , Nanfack Aubin J. , Yang Pengpeng , Dai Shaoxing , Kong Xiang-Peng , Torimiro Judith N. , Duerr Ralf
Published: February 2022

Combinational antiretroviral therapy (cART) is the most effective tool to prevent and control HIV-1 infection without an effective vaccine. However, HIV-1 drug resistance mutations (DRMs) and naturally occurring polymorphisms (NOPs) can abrogate cART efficacy. Here, we aimed to characterize the HIV-1polmutation landscape in Cameroon, where highly diverse HIV clades circulate, and identify novel treatment-associated mutations that can potentially affect cART efficacy. More than 8,000 functional Cameroonian HIV-1polsequences from 1987 to 2020 were studied for DRMs and NOPs. Site-specific amino acid frequencies and quaternary structural features were determined and compared between periods before (≤2003) and after (2004–2020) regional implementation of cART. cART usage in Cameroon induced deep mutation imprints in reverse transcriptase (RT) and to a lower extent in protease (PR) and integrase (IN), according to their relative usage. In the predominant circulating recombinant form (CRF) 02_AG (CRF02_AG), 27 canonical DRMs and 29 NOPs significantly increased or decreased in RT during cART scale-up, whereas in IN, no DRM and only seven NOPs significantly changed. The profound genomic imprints and higher prevalence of DRMs in RT compared to PR and IN mirror the dominant use of reverse transcriptase inhibitors (RTIs) in sub-Saharan Africa and the predominantly integrase strand transfer inhibitor (InSTI)-naïve study population. Our results support the potential of InSTIs for antiretroviral treatment in Cameroon; however, close surveillance of IN mutations will be required to identify emerging resistance patterns, as observed in RT and PR. Population-wide genomic analyses help reveal the presence of selective pressures and viral adaptation processes to guide strategies to bypass resistance and reinstate effective treatment.
The Relationship Between Convergent IGH Signatures and Severity of COVID-19 Patients by Next-Generation Sequencing of B-Cell Repertoire
Authors: Cai Hongliu , Hu Juan , Huang Lingtong , Gao Chunhua , Xu Mi , Gao Yuzhi , Sun Tao , Fang Xueling
Published: February 2022

Object

To reveal convergent IGH signatures and the association with severity of coronavirus disease 2019 (COVID-19) patients.

Method

A total of 25 COVID-19 inpatients were classified into three clinical conditions: mild, severe, and critical. We analyzed convergent IGH signatures by ImmuHub® B-cell receptor (BCR) profiling system.

Results

IGH singleton frequency in patients is significantly lower than that of healthy donors (HDs). The clonality index of IGH in patients is significantly higher than that in HDs. Nevertheless, no significant difference was observed among the three groups. The difference in IGH clonality (top five clones) between post- and pretreatment was significant in the improvement and deterioration groups. Three common public motifs were shared by all COVID-19 patients: ARDYGG, RWYFDY, and YYYYGMDV.

Conclusion

B cells could recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and produce clonal expansion. Patients who had better outcomes after treatment had higher IGH clonality. Three common public motifs—ARDYGG, RWYFDY, and YYYYGMDV—might be used for vaccine development (ChiCTR2000029626).
A Spatiotemporal Brain Network Analysis of Alzheimer’s Disease Based on Persistent Homology
Authors: Xing Jiacheng , Jia Jiaying , Wu Xin , Kuang Liqun
Published: February 2022

Current brain network studies based on persistent homology mainly focus on the spatial evolution over multiple spatial scales, and there is little research on the evolution of a spatiotemporal brain network of Alzheimer’s disease (AD). This paper proposed a persistent homology-based method by combining multiple temporal windows and spatial scales to study the spatiotemporal evolution of brain functional networks. Specifically, a time-sliding window method was performed to establish a spatiotemporal network, and the persistent homology-based features of such a network were obtained. We evaluated our proposed method using the resting-state functional MRI (rs-fMRI) data set from Alzheimer’s Disease Neuroimaging Initiative (ADNI) with 31 patients with AD and 37 normal controls (NCs). In the statistical analysis experiment, most network properties showed a better statistical power in spatiotemporal networks than in spatial networks. Moreover, compared to the standard graph theory properties in spatiotemporal networks, the persistent homology-based features detected more significant differences between the groups. In the clustering experiment, the brain networks on the sliding windows of all subjects were clustered into two highly structured connection states. Compared to the NC group, the AD group showed a longer residence time and a higher window ratio in a weak connection state, which may be because patients with AD have not established a firm connection. In summary, we constructed a spatiotemporal brain network containing more detailed information, and the dynamic spatiotemporal brain network analysis method based on persistent homology provides stronger adaptability and robustness in revealing the abnormalities of the functional organization of patients with AD.
Beta3Gn-T7 Is a Keratan Sulfate β1,3 N-Acetylglucosaminyltransferase in the Adult Brain
Authors: Takeda-Uchimura Yoshiko , Nishitsuji Kazuchika , Ikezaki Midori , Akama Tomoya O. , Ihara Yoshito , Allain Fabrice , Uchimura Kenji
Published: February 2022

Keratan sulfate (KS) glycan is covalently attached to a core protein of proteoglycans. KS is abundant in neuropils and presents densely in close proximity to the perineuronal region of the perineuronal net-positive neurons in the adult brain under physiological conditions. We previously showed that the synthesis of KS positive for the R-10G antibody in the adult brain is mediated by GlcNAc-6-sulfotransferase 3 (GlcNAc6ST3; encoded by Chst5). Deficiency in both GlcNAc6ST3 and GlcNAc6ST1, encoded by Chst2, completely abolished KS. Protein-tyrosine phosphatase receptor type z1 (Ptprz1)/phosphacan was identified as a KS scaffold. KS requires the extension of GlcNAc by β1,3 N-acetylglucosaminyltransferase (Beta3Gn-T). Members of the Beta3Gn-T family involved in the synthesis of adult brain KS have not been identified. In this study, we show by a method of gene targeting that Beta3Gn-T7, encoded by B3gnt7, is a major Beta3Gn-T for the synthesis of KS in neuropils and the perineuronal region in the adult brain. Intriguingly, the B3gnt7 gene is selectively expressed in oligodendrocyte precursor cells (OPCs) and oligodendrocytes similar to that of GlcNAc6ST3. These results indicate that Beta3Gn-T7 in oligodendrocyte lineage cells may play a role in the formation of neuropils and perineuronal nets in the adult brain through the synthesis of R-10G-positive KS-modified proteoglycan.
Changes in Physicochemical Properties, Volatile Profiles, and Antioxidant Activities of Black Apple During High-Temperature Fermentation Processing
Authors: Zhu Zuoyi , Zhang Yu , Wang Wei , Sun Suling , Wang Junhong , Li Xue , Dai Fen , Jiang Yunzhu
Published: February 2022

Black apple is a new elaborated product obtained from whole fresh apple through fermentation at controlled high temperature (60~90°C) and humidity (relative humidity of 50~90%). The appearance, color, texture, and taste of black apple changed dramatically compared with those of fresh apple. In this study, changes in the physicochemical and phytochemical properties, volatile profiles, and antioxidant capacity of apple during the fermentation process were investigated. Results showed that the browning intensity and color difference increased continuously during the whole 65-day fermentation process (p < 0.05). Sugars decreased in the whole fermentation process (p < 0.05), whereas the contents of organic acids increased first and then decreased with prolonged 35 days of fermentation (p < 0.05). Total polyphenol content of black apple showed an increase of 1.5-fold as that of fresh apple, whereas 12 common polyphenolic compounds present in fresh apple decreased dramatically in the whole fermentation process (p < 0.05). The analysis of flavor volatiles showed that high-temperature fermentation decreased the levels of alcohols and esters and resulted in the formation of furanic and pyranic compounds, which are the main products of Maillard reaction (MR). Antioxidant activities of black apple were enhanced compared with those of fresh apple, and results indicated that the enhancement of antioxidant activities was related to the polyphenols and products of MR.
Efficacy and Safety of Systemic Treatments Among Colorectal Cancer Patients: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Hoang Tung , Sohn Dae Kyung , Kim Byung Chang , Cha Yongjun , Kim Jeongseon
Published: February 2022

Background

Systemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This study aimed to provide the complete efficacy and safety profiles and ranking of systemic therapies for the treatment of unresectable advanced or metastatic CRC.

Methods

We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until June 30, 2021, and also the bibliographies of relevant studies. Randomized controlled trials comparing two or more treatments, namely, at least capecitabine, 5-fluorouracil, leucovorin, irinotecan, bevacizumab, cetuximab, oxaliplatin, or panitumumab were investigated. A network meta-analysis using the Bayesian approach was performed to compare the efficacy and safety of treatments. The surface under the cumulative ranking curve (SUCRA) was calculated for the probability of each treatment as the most effective. The overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), adverse events (AEs) grade ≥3, and serious adverse events (SAEs) were evaluated.

Results

One hundred two publications with 36,147 participants were assigned to 39 different treatments. Among 11 treatments with full information on six outcomes, FOLFIRI/FOLFOX/FOLFOXIRI + bevacizumab significantly improved both the ORR and DCR, compared to FOLFIRI. Although FOLFOX and FOLFIRI/FOLFOX + cetuximab significantly prolonged both OS and PFS, treatments were comparable in terms of AEs grade ≥3 and SAEs. The top highest SUCRA values were observed in the FOLFOXIRI + panitumumab group for ORR (96%) and DCR (99%), FOLFIRI + bevacizumab + panitumumab group for OS (62%) and PFS (54%), and FOLFOXIRI + bevacizumab group for AEs grade ≥3 (59%) and SAEs (59%) outcomes.

Conclusions

These findings suggest an available range of systemic treatment therapies with different efficacy and safety profiles with patients. Further investigations of the side effects and mutation status are required to confirm our findings.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42019127772
Case Report: H3K27M-Mutant Glioblastoma Simultaneously Present in the Brain and Long-Segment Spinal Cord Accompanied by Acute Pulmonary Embolism
Authors: Maimaiti Buajieerguli , Mijiti Salamaitiguli , Jiang Ting , Xie Yinyin , Zhao Weixuan , Cheng Yu , Meng Hongmei
Published: February 2022

Background

Glioblastoma multiforme (GBM) is a highly malignant glioma that rarely presents as an infratentorial tumor. Multicentric (MC) gliomas involve lesions widely separated in space or time, and MC gliomas involving supra- and infratentorial brain regions are rare. In most cases, the infratentorial lesion is seen after surgical manipulation or radiation therapy; it is typically located in the cerebellum or the cervical region, manifesting as metastasis originating from the brain. Besides, venous thromboembolism in brain tumors is usually seen after craniotomy.

Case Presentation

We present an uncommon adult case of symptomatic H3K27M-mutant MC glioblastoma simultaneously present in the brain, fourth ventricle, and cervical and lumbar spinal cord regions accompanied by acute pulmonary artery embolism in an adult woman who had not undergone previous therapeutic interventions. We also review the literature on this interesting presentation.

Conclusion

Our report highlights that clinicians should be alert to the potential alarming presentation of GBM. The incidence of spinal metastasis of cerebral GBM is increasing. Patients with a prior diagnosis of GBM with or without any new onset in the spinal cord should undergo an early MRI of the spinal cord to confirm the diagnosis at an early stage. While management of GBM remains controversial, more research is needed to explore molecular features of GBM further and develop novel targeted therapies for these patients.
Current Status and Prospects of Anesthesia and Breast Cancer: Does Anesthetic Technique Affect Recurrence and Survival Rates in Breast Cancer Surgery?
Authors: Kim Ryungsa , Kawai Ami , Wakisaka Megumi , Kin Takanori
Published: February 2022

The relationship between the anesthetic technique and cancer recurrence has not yet been clarified in cancer surgery. Surgical stress and inhalation anesthesia suppress cell-mediated immunity (CMI), whereas intravenous (IV) anesthesia with propofol and regional anesthesia (RA) are known to be protective for CMI. Surgical stress, general anesthesia (GA) with inhalation anesthesia and opioids contribute to perioperative immunosuppression and may increase cancer recurrence and decrease survival. Surgical stress and GA activate the hypothalamic-pituitary-adrenal axis and release neuroendocrine mediators such as cortisol, catecholamines, and prostaglandin E2, which may reduce host defense immunity and promote distant metastasis. On the other hand, IV anesthesia with propofol and RA with paravertebral block or epidural anesthesia can weaken surgical stress and GA-induced immunosuppression and protect the host defense immunity. IV anesthesia with propofol and RA or in combination with GA may reduce cancer recurrence and improve patient survival compared to GA alone. We review the current status of the relationship between anesthesia and breast cancer recurrence using retrospective and prospective studies conducted with animal models and clinical samples, and discuss the future prospects for reducing breast cancer recurrence and improving survival rates in breast cancer surgery.
AFF4 Predicts the Prognosis of Colorectal Cancer Patients and Suppresses Colorectal Cancer Metastasis via Promoting CDH1 Expression
Authors: Fang Yi , Cao Hua , Gong Xiaoyong , Chen Yanqing , Zhuang Yugang , Zhou Shuqin , Chen Yuanzhuo , Jiang Yimei , Ji Xiaopin , Peng Hu , Jing Xiaoqian
Published: February 2022

Introduction

AF4/FMR2 family member 4 (AFF4) is a core component of super elongation complex (SEC) and regulates the transcription elongation of many genes. AFF4 depletion or amplification is associated with multiple cancers, but its role in colorectal cancer (CRC) has not been investigated so far.

Methods

qRT-PCR and Western blot analyzed AFF4 expression in the paired clinical CRC tissues. The patients’ overall survival curve was determined using the Kaplan-Meier plotter. In vitro experiments, such as cell proliferation, migration, and invasion, were used to preliminarily ascertain the role of AFF4 in CRC. A CRC cell liver metastasis animal model was well established. Livers were harvested and examined histologically by a series of indicators, such as tumor nodules, liver weight, ALT/AST activity, and tumor cell identification by hematoxylin-eosin (HE) staining.

Results

We firstly examined the expression of AFF4 in colorectal cancer and normal tissues by collecting paired CRC tissues and adjacent normal tissues, revealing that AFF4 was significantly downregulated in CRC patients and lower expression of AFF4 was correlated with poor prognosis. Next, we observed that presence or absence of AFF4 in CRC cells had no effect on cancer cell proliferation, while AFF4 depletion significantly promoted the migration or invasion of CRC cells in vitro. Furthermore, we confirmed that AFF4 deficiency enhanced the metastatic capacity of CRC cells in vivo. Mechanistically, we found that AFF4 upregulated the transcription of CDH1 gene, which encodes E-cadherin and suppresses the epithelial-mesenchymal transition (EMT). Knockdown of AFF4 interfered with CDH1 transcription, resulting in downregulation of E-cadherin expression and the progression of CRC. Moreover, restored CDH1 expression could rescue the phenotype of CRC cells without AFF4.

Conclusions

Collectively, our data demonstrated that AFF4 served as a significant novel regulator of CRC via CDH1 transcriptional regulation and a potential effective therapy target for patients with CRC.
The COMT Genetic Factor Regulates Chemotherapy-Related Prospective Memory Impairment in Survivors With HER2−/+ Breast Cancer
Authors: Li Wen , Zhang Qianqian , Cai Yinlian , Chen Tingting , Cheng Huaidong
Published: February 2022

Background

Previous findings indicated that polymorphism in gene catechol-O-methyltransferase (COMT) had been linked to chemotherapy-related cognitive impairment (CRCI). Nevertheless, the motivation of COMT polymorphisms in regulating cognitive impairment in breast cancer survivors with disparate status of human epidermal growth factor receptor 2 (HER2) was still vague.

Objective

The current research aimed to evaluate the regulation of the risk by COMT genotype on CRCI in breast cancer survivors with disparate status of HER2.

Methods

Breast cancer survivors (103 with HER2− and 118 with HER2+) underwent neuropsychological tests before and after chemotherapy, containing event- and time-based prospective memory (EBPM and TBPM). Three single-nucleotide polymorphisms (SNPs) were estimated by providing peripheral blood, containing COMT (rs165599, rs737865, and rs4680).

Results

The EBPM and TBPM performances was lower as compared with these before chemotherapy (z = −7.712, z = −2.403, respectively, p < 0.01). Furthermore, the EBPM and TBPM performances of HER2− group survivors were lower than those of HER2+ group survivors after chemotherapy (z = −7.181, p < 0.01; z = −2.205 p < 0.05, respectively). The survivors with COMT (rs165599) A/A genotype carriers had a meaningfully poorer chance of memory descend [dominant model: adjusted, OR = 2.21, CI (95%) = 1.156–4.225, p = 0.016] and showed better on TBPM test, relative to G/G genotype. Patients with the COMT (rs737865) A/G and G/G genotype showed protective function than the patients with the A/A and performed better on MMSE and TBPM tests.

Conclusion

The types of HER2 may be correlated to chemotherapy-related prospective memory impairments in breast cancer survivors. Furthermore, the COMT (rs165599, rs737865) polymorphisms were correlated to the risk of TBPM decline scores and possibly be a potential genetic identifying for increasing risk of CRCI in breast cancer patients with disparate status of HER2.
Baseline Amide Proton Transfer Imaging at 3T Fails to Predict Early Response to Induction Chemotherapy in Nasopharyngeal Carcinoma
Authors: Liu Zhou , Zou Liyan , Yang Qian , Qian Long , Li Tianran , Luo Honghong , Che Canwen , Lei Yuanyuan , Chen Peng , Qiu Chunyan , Liu Xin , Wu Yin , Luo Dehong
Published: February 2022

Background

Early identification of nasopharyngeal carcinoma (NPC) patients with high risk of failure to induction chemotherapy (IC) would facilitate prompt individualized treatment decisions and thus reduce toxicity and improve overall survival rate. This study aims to investigate the value of amide proton transfer (APT) imaging in predicting short-term response of NPC to IC and its potential correlation with well-established prognosis-related clinical characteristics.

Methods and Materials

A total of 80 pathologically confirmed NPC patients receiving pre-treatment APT imaging at 3T were retrospectively enrolled. Using asymmetry analysis, APT maps were calculated with mean (APTmean), 90th percentile (APT90) of APT signals in manually segmented NPC measured. APT values were compared among groups with different histopathological subtypes, clinical stages (namely, T, M, N, and overall stages), EBV-related indices (EBV-DNA), or responses to induction chemotherapy, using Mann–Whitney U test or Kruskal–Wallis H test.

Results

NPC showed significantly higher APTmean than normal nasopharyngeal tissues (1.81 ± 0.62% vs.1.32 ± 0.56%, P <0.001). APT signals showed no significant difference between undifferentiated and differentiated NPC subtypes groups, different EBV-DNA groups, or among T, N, M stages and overall clinical stages of II, III, IVA and IVB (all P >0.05). Similarly, baseline APT-related parameters did not differ significantly among different treatment response groups after IC, no matter if evaluated with RECIST criteria or sum volumetric regression ratio (SVRR) (all P >0.05).

Conclusion

NPC showed significantly stronger APT effect than normal nasopharyngeal tissue, facilitating NPC lesion detection and early identification. However, stationary baseline APT values exhibited no significant correlation with histologic subtypes, clinical stages and EBV-related indices, and showed limited value to predict short-term treatment response to IC.
Chemoresistance Transmission via Exosome-Transferred MMP14 in Pancreatic Cancer
Authors: Li Xinyuan , Li Kai , Li Mengmeng , Lin Xiaoyu , Mei Yu , Huang Xuemei , Yang Huanjie
Published: February 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. Gemcitabine is the most commonly used chemotherapy for the treatment of PDAC, but the development of drug resistance still remains challenging. Recently, exosomes have emerged as important mediators for intercellular communication. Exosomes affect recipient cells’ behavior through the engulfed cargos, however the specific cargos responsible for gemcitabine resistance in PDAC are poorly understood. Here, we reported that exosomes could transfer gemcitabine resistance via a metalloproteinase 14 (MMP14)-dependent mechanism. MMP14 was identified as a major differentially secreted protein from the gemcitabine-resistant PDAC cells by comparative secretome. It was packaged into the exosomes and transmitted from the chemoresistant cells to the sensitive ones. The exosome-transferred MMP14 could enhance drug resistance and promotes the sphere-formation and migration abilities of the recipient sensitive PDAC cells. Mechanically, exosome-transferred MMP14 promotes the stability of CD44, the cancer stem cell marker in the recipient cells. Our results indicate that MMP14 is a key player for exosome-mediated transfer of gemcitabine resistance, thus targeting MMP14 in exosomes may represent a novel strategy to limit gemcitabine resistance in PDAC.
Kawasaki Disease With Combined Cholestatic Hepatitis and Mycoplasma pneumoniae Infection: A Case Report and Literature Review
Authors: Huang Shen-Wen , Lin Sheng-Chieh , Chen Shih-Yen , Hsieh Kai-Sheng
Published: February 2022

Kawasaki disease (KD), also called mucocutaneous lymph node syndrome, is a febrile multisystem vasculitis mainly affecting children younger than 5 years. KD typically manifests as skin lesions and in the lymph nodes and oral and conjunctival mucosa. It may induce coronary artery abnormalities, such as aneurysms, but gastrointestinal and hepatobiliary involvement are not common. We reviewed 32 cases of patients with a diagnosis of KD with hepatobiliary involvement between 2000 and 2021 and present the case of a 4-year-old girl who received a diagnosis of KD with combined cholestatic hepatitis and Mycoplasma pneumoniae infection. In the 33 cases reviewed, in addition to the classical clinical findings of KD, the most common clinical presentations were jaundice and abdominal pain. Moreover, abnormal laboratory results indicating hyperbilirubinemia, cholestasis, and hepatitis, among other conditions, were noted. Abdominal ultrasonography revealed abnormal findings in more than half children with KD with hepatobiliary involvement. Furthermore, cardiac involvement was noted in a high proportion of the patients. In particular, we noted the case of a 4-year-old girl with a rare presentation of 3-day fever combined with abdominal pain and jaundice. Her levels of aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase were 489 (15–50) U/L, 253 (5–45) U/L, 4.3 (<1.5) mg/dl, 2.4 (<0.2) mg/dl, 337 (134–315) U/L, and 145 (5–32) U/L, respectively. These results were indicative of cholestatic hepatitis. Furthermore, her serological test results for mycoplasma infection were positive. KD was diagnosed because the patient had high fever for more than 5 days and presented with lymphadenopathy on the left side of neck, a polymorphic skin rash, redness of oral mucosa with strawberry tongue, and nonpurulent conjunctival congestion. After intravenous immunoglobulin injection (IVIG) and acetylsalicylic acid administration, the fever subsided rapidly and clinical manifestations, such as jaundice and abdominal pain, were mitigated. The laboratory parameters gradually returned to within normal ranges. Echocardiography revealed no aneurysm. In conclusion, KD with cholestatic hepatitis should be considered when pediatric patients present with fever combined with abdominal pain and jaundice. Early treatment with IVIG and aspirin is recommended and can effectively relieve cholestatic hepatitis.
Cognitive and Psychological Outcomes Following Pediatric Cardiac Arrest
Authors: Huebschmann Nathan A. , Cook Nathan E. , Murphy Sarah , Iverson Grant L.
Published: February 2022

Cardiac arrest is a rare event in children and adolescents. Those who survive may experience a range of outcomes, from good functional recovery to severe and permanent disability. Many children experience long-term cognitive impairment, including deficits in attention, language, memory, and executive functioning. Deficits in adaptive behavior, such as motor functioning, communication, and daily living skills, have also been reported. These children have a wide range of neurological outcomes, with some experiencing specific deficits such as aphasia, apraxia, and sensorimotor deficits. Some children may experience emotional and psychological difficulties, although many do not, and more research is needed in this area. The burden of pediatric cardiac arrest on the child's family and caregivers can be substantial. This narrative review summarizes current research regarding the cognitive and psychological outcomes following pediatric cardiac arrest, identifies areas for future research, and discusses the needs of these children for rehabilitation services and academic accommodations.
Severe Retinopathy of Prematurity Associated With Neurodevelopmental Disorder in Children
Authors: Choi Young-Jin , Hong Eun Hee , Shin Yong Un , Bae Gi Hwan , Kim Inah , Cho Heeyoon
Published: February 2022

Objective

This study aimed to investigate whether severe retinopathy of prematurity (ROP) could be an association factor for neurodevelopmental disorders in premature infants without other risk factors—such as congenital anomalies, birth injuries, and neurological diseases—that may cause developmental delay.

Methods

We used health claims data recorded between 2007 and 2018 in the Korean National Health Insurance Service (KNHIS) database. We recruited a total of 18,256 premature infant born between 2007 and 2008 without congenital anomaly or birth injury (with ROP 6,995, without ROP 11,261) and divided them into four groups as follows: Group A, 209 extremely premature infants [gestational age (GA) < 28] with mild ROP; Group B, 75 extremely premature infants (GA < 28) with severe ROP; Group C, 6,510 other premature infants (28 ≤ GA <37)with mild ROP; and Group D, 201 other premature infants (28 ≤ GA < 37) with severe ROP. Using regression analysis, we analyzed whether there was a correlation between ROP prevalence, severity, and developmental delay in premature infants without other risk factors.

Results

The prevalence of developmental delay, according to GA and ROP severity, was higher in patients with severe ROP than in the other patients. The prevalence gradually decreased after birth. Among extremely premature infants with ROP, those with severe ROP had a 3.082-fold higher association with neurodevelopmental complications than those with mild ROP (p < 0.001). Compared with other premature infants with ROP, those with severe ROP had a 3.269-fold higher association with neurodevelopmental complications than those with mild ROP.

Conclusion

The severity of ROP may be associated with neurodevelopmental disorders in premature infants.
Research Progress on the Antiemetic Effect of Traditional Chinese Medicine Against Chemotherapy-Induced Nausea and Vomiting: A Review
Authors: Zhao Yao-Zhong , Dai Yong-Zhao , Nie Ke
Published: February 2022

Chemotherapy-induced nausea and vomiting (CINV), a common side effect in antineoplastic treatment, dramatically decreases the quality of life as well as the compliance of cancer patients. Although numerous antiemetic agents have been used for CINV treatment, its adverse reactions as well as its inadequate control toward delayed emesis still limit its clinical usage. Traditional Chinese medicine (TCM), with more than 3,000 years of practical history in Asia, has been successfully applied to mitigate chemotherapy-induced side effects. Growing attention is drawn to the antiemetic effect of TCM against CINV due to its promising therapeutic property and higher safety recently. In this review, we summarize the classic antiemetic TCM-based treatment and its mechanisms, so as to provide a theoretical basis for further investigations of TCM against CINV in the future.
Impact of Pharmacist-Led Diabetes Self-Care Education on Patients With Type 2 Diabetes in Pakistan: A Randomized Controlled Trial
Authors: Bukhsh Allah , Khan Tahir Mehmood , Phisalprapa Pochamana , Duangjai Acharaporn , Saokaew Surasak , Nawaz Muhammad Sarfraz , Ahmed Hafiz Sajjad , Goh Bey-Hing
Published: February 2022

Introduction: There is a little evidence on efficacy of pharmacy-based interventions on clinical outcomes of type 2 diabetes mellitus (T2DM) patients in Pakistan.

Objective: To appraise the impact of pharmacist-led self-care education on glycemic control, self-care practices and disease knowledge of T2DM patients with poor glycemic control (HbA1c ≥ 7%).

Methods: In this 6-months, randomized controlled trial (RCT), n = 75, T2DM patients seeking care at a diabetes clinic were randomized in to two groups. Intervention group (n = 38) received two face-to-face educational sessions (at enrollment and on week 12), whereas control group (n = 37) received usual care. Outcome measures such as glycemic control, self-care practices and disease knowledge were assessed at the time of enrollment and after 6-months in both groups.

Results: Thirty-three intervention and thirty-three participants from the control group completed the study. Mean glycated hemoglobin (% HbA1c) significantly reduced in the intervention group from 9.00 ± 1.43 to 8.09 ± 1.16 (p < .01). However, no significant change was observed in the control group (9.20 ± 1.24 to 8.93 ± .97; p = .06). Cohen’s d effect size of the intervention on HbA1c was .78. Percentage of participants achieving glycemic control (HbA1c < 7%) were significantly higher (p < .05) in the intervention group as compared to the control group (twenty-four vs. six), after 6 months of the trial. A significant (p < .01) improvement in mean scores for disease knowledge and self-care activities was also observed in the intervention group participants, whereas no significant improvements (p > .05) were observed in the control group.

Conclusion: The study demonstrated an improvement in glycemic control, disease knowledge and self-care activities of T2DM patients who received pharmacist-led educational intervention. The study findings support clinical significance of integrating pharmacy-based interventions in diabetes management.
Effect of Ibandronate Therapy on Serum Chemerin, Vaspin, Omentin-1 and Osteoprotegerin (OPG) in Postmenopausal Osteoporotic Females
Authors: Tariq Saba , Tariq Sundus , Abualhamael Shahad Abduljalil , Shahzad Muhammad
Published: February 2022

Osteoporosis is a condition in which bone mineral density is reduced due to altered bone microstructure, which results in increased skeletal fragility and incidence of various types of fractures. Adipokines such as chemerin, vaspin, omentin-1 and osteoprotegerin are involved in bone remodeling. The current study was designed to determine the changes in circulating chemerin, vaspin, omentin-1, and osteoprotegerin levels after treatment with oral ibandronate 150 mg in postmenopausal osteoporotic females. The present study enrolled 107 postmenopausal osteoporotic females from a tertiary care hospital in Faisalabad, Pakistan, based on stringent inclusion and exclusion criteria. Sixty-six healthy postmenopausal, non-osteoporotic females with no systemic illness were chosen from the general population. The assessment of bone mineral density (BMD) was done using a DEXA scan. Serum levels of chemerin, vaspin, omentin-1 and osteoprotegerin were estimated using commercially available enzyme-linked immunosorbent assay kits. The collected data were analyzed with the Statistical Package for Social Sciences (SPSS) version 24. Following 6 months of ibandronate treatment, there was a significant decrease of 24.24% (p < .033) in serum chemerin levels, as well as a significant increase in serum vaspin levels 343.32% (p < .001) and osteoprotegerin levels 19.57% (p < .001), with no significant change in omentin-1 levels. Thus, an increase in serum chemerin levels and a decrease in serum vaspin and osteoprotegerin levels could be implicated in osteoporosis.