bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of Paeoniae Radix Alba in the Treatment of Non-alcoholic Fatty Liver Disease Based on Sequential Metabolites Identification Approach, Network Pharmacology, and Binding Affinity Measurement
Authors: Luo Zhiqiang , Liu Yang , Han Xing , Yang Wenning , Wang Guopeng , Wang Jing , Jiang Xiaoquan , Sen Muli , Li Xueyan , Yu Guohua , Shi Yuanyuan
Published: September 2021

Screening functional food ingredients (FFI) from medicinal and edible plants (MEP) has still remained a great challenge due to the complexity of MEP and its obscure function mechanisms. Herein, an integrated strategy based on sequential metabolites identification approach, network pharmacology, molecular docking, and surface plasmon resonance (SPR) analysis was proposed for quickly identifying the active constituents in MEP. First, the sequential biotransformation process of MEP, including intestinal absorption and metabolism, and hepatic metabolism, was investigated by oral gavage, and intestinal perfusion with venous sampling method. Then the blood samples were analyzed by UPLC-Q Exactive Orbitrap HRMS. Second, the network pharmacology approach was used to explore the potential targets and possible mechanisms of the in vivo metabolites of MEP. Third, molecular docking and SPR approaches were used to verify the specific interactions between protein targets and representative ingredients. The proposed integrated strategy was successfully used to explore the heptoprotective components and the underlying molecular mechanism of Paeoniae Radix Alba (PRA). A total of 44 compounds were identified in blood samples, including 17 porotypes and 27 metabolites. The associated metabolic pathways were oxidation, methylation, sulfation, and glucuronidation. After further screening, 31 bioactive candidates and 377 related targets were obtained. In addition, the bioactive components contained in PRA may have therapeutic potentials for non-alcoholic fatty liver disease (NAFLD). The above results demonstrated the proposed strategy may provide a feasible tool for screening FFI and elaborating the complex function mechanisms of MEP.
Anti-diabetic Potential of a Stigmasterol From the Seaweed Gelidium spinosum and Its Application in the Formulation of Nanoemulsion Conjugate for the Development of Functional Biscuits
Authors: Poulose Navya , Sajayan Arya , Ravindran Amrudha , Chandran Ambili , Priyadharshini G. Balasubramanian , Selvin Joseph , Kiran G. Seghal
Published: September 2021

The seaweed Gelidium spinosum was selected for the extraction of phytosterol by the Soxhlet method. The extracted phytosterol was chemically characterized as stigmasterol using Fourier-transform infrared spectrometry and gas chromatography–mass spectrometry analysis. The antioxidant and α-amylase inhibitory activity of stigmasterol has been confirmed by in vitro assays. The in vivo studies demonstrated an anti-diabetic effect in streptozotocin (STZ)—induced hyperglycemic rats. Biochemical analysis showed administration of stigmasterol reduced the blood sugar, urea, and creatinine level. The stigmasterol was then nano-emulsified and incorporated into dough for biscuit formulation. The stigmasterol incorporated biscuit showed higher proximate values, low moisture content, lighter color and the textural property revealed lower hardness. Sensorial results showed acceptability when compared to the control. This study demonstrated the stigmasterol reduced hyperglycemic effects and therefore could be used as a supplement in diets for diabetic patients.
Comparative Quality Evaluation of Physicochemical, Technological, and Protein Profiling of Wheat, Rye, and Barley Cereals
Authors: Rani Monika , Singh Gagandeep , Siddiqi Raashid Ahmad , Gill Balmeet Singh , Sogi Dalbir Singh , Bhat Mohd Akbar
Published: September 2021

Agronomically important cereal crops wheat, barley, and rye of the Triticeace tribe under the genus Triticum were studied with special focus on their physical, proximal, and technological characteristics which are linked to their end product utilization. The physiochemical parameters showed variability among the three cereal grains. Lactic acid-solvent retention capacity (SRC) was found to be higher in wheat (95.86–111.92%) as compared to rye (53.78–67.97%) and barley (50.24–67.12%) cultivars, indicating higher gluten strength. Sucrose-SRC and sodium carbonate-SRC were higher in rye as compared to wheat and barley flours. The essential amino acid proportion in barley and rye cultivars was higher as compared to wheat cultivars. Barley and rye flours exhibited higher biological value (BV) owing to their higher lysine content. SDS-PAGE of wheat cultivars showed a high degree of polymorphism in the low molecular range of 27.03–45.24 kDa as compared to barley and rye cultivars. High molecular weight (HMW) proteins varied from 68.38 to 119.66 kDa (4–5 subunits) in wheat, 82.33 to 117.78 kDa (4 subunits) in rye, and 73.08 to 108.57 kDa (2–4 subunits) in barley. The comparative evaluation of barley and rye with wheat cultivars would help in the development of healthy food products.
Quantitative Multiparametric MRI as an Imaging Biomarker for the Prediction of Breast Cancer Receptor Status and Molecular Subtypes
Authors: Yang Zhiqi , Chen Xiaofeng , Zhang Tianhui , Cheng Fengyan , Liao Yuting , Chen Xiangguan , Dai Zhuozhi , Fan Weixiong
Published: September 2021

Objectives

To assess breast cancer receptor status and molecular subtypes by using the CAIPIRINHA-Dixon-TWIST-VIBE and readout-segmented echo-planar diffusion weighted imaging techniques.

Methods

A total of 165 breast cancer patients were retrospectively recruited. Patient age, estrogen receptor, progesterone receptor, human epidermal growth factorreceptor-2 (HER-2) status, and the Ki-67 proliferation index were collected for analysis. Quantitative parameters (Ktrans, Ve, Kep), semiquantitative parameters (W-in, W-out, TTP), and apparent diffusion coefficient (ADC) values were compared in relation to breast cancer receptor status and molecular subtypes. Statistical analysis were performed to compare the parameters in the receptor status and molecular subtype groups.Multivariate analysis was performed to explore confounder-adjusted associations, and receiver operating characteristic curve analysis was used to assess the classification performance and calculate thresholds.

Results

Younger age (<49.5 years, odds ratio (OR) =0.95, P=0.004), lower Kep (<0.704,OR=0.14, P=0.044),and higher TTP (>0.629 min, OR=24.65, P=0.011) were independently associated with progesterone receptor positivity. A higher TTP (>0.585 min, OR=28.19, P=0.01) was independently associated with estrogen receptor positivity. Higher Kep (>0.892, OR=11.6, P=0.047), lower TTP (<0.582 min, OR<0.001, P=0.004), and lower ADC (<0.719 ×10-3 mm2/s, OR<0.001, P=0.048) had stronger independent associations with triple-negative breast cancer (TNBC) compared to luminal A, and those parameters could differentiate TNBC from luminal A with the highest AUC of 0.811.

Conclusions

Kep and TTP were independently associated with hormone receptor status. In addition, the Kep, TTP, and ADC values had stronger independent associations with TNBC than with luminal A and could be used as imaging biomarkers for differentiate TNBC from Luminal A.
The Evolving Role of Radiotherapy for Pediatric Cancers With Advancements in Molecular Tumor Characterization and Targeted Therapies
Authors: Shen Colette J. , Terezakis Stephanie A.
Published: September 2021

Ongoing rapid advances in molecular diagnostics, precision imaging, and development of targeted therapies have resulted in a constantly evolving landscape for treatment of pediatric cancers. Radiotherapy remains a critical element of the therapeutic toolbox, and its role in the era of precision medicine continues to adapt and undergo re-evaluation. Here, we review emerging strategies for combining radiotherapy with novel targeted systemic therapies (for example, for pediatric gliomas or soft tissue sarcomas), modifying use or intensity of radiotherapy when appropriateviamolecular diagnostics that allow better characterization and individualization of each patient’s treatments (for example, de-intensification of radiotherapy in WNT subgroup medulloblastoma), as well as exploring more effective targeted systemic therapies that may allow omission or delay of radiotherapy. Many of these strategies are still under investigation but highlight the importance of continued pre-clinical and clinical studies evaluating the role of radiotherapy in this era of precision oncology.
The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer
Authors: Wu Zi-Xin , Wang Fei , Li Liang , Yao Yuan , Long Jie , Luo Qing-Qing , Zhao Zhi-Bin , Li Wang-Lin , Cao Jie , Lian Zhe-Xiong
Published: September 2021

Objective

The mesentery is a potential site of residual tumor in patients with colorectal cancer (CRC). However, the mesenteric immune microenvironment remains unclear. In this study, we investigated the immune landscape of the mesentery, particularly the role of lymphocytes and its association with the clinicopathological characteristics of CRC.

Methods

Flow cytometry was used to detect lymphocytes in the paired mesenteric tissue specimens adjacent to the colorectal tumors and normal mesenteric tissue specimens 10 cm away from the colorectal tumor edge and preoperative peripheral blood samples obtained from patients with CRC who underwent surgery. T-distributed stochastic neighbor embedding was utilized to analyze multiparameter flow cytometry data. Multiplex immunohistochemistry was performed to evaluate T cells subsets in the paired mesentery adjacent to the colorectal tumors and normal mesentery. The Fisher’s exact test and non-parametric Wilcoxon’s matched-pairs tests were used for statistical analysis. The non-parametric Mann-Whitney U test was used to determine associations between percentage data and clinical parameters of patients with CRC.

Results

We found that immune cells in the normal mesentery were mainly of lymphoid lineage. Compared with peripheral blood, the normal mesentery showed decreased NK cells and the CD4/CD8 ratio and increased CD3+ CD56+, memory CD4+ T, memory CD8+ T, CD4+ tissue-resident memory T (TRM), and CD8+ TRM cells. Compared with the normal mesentery, the mesentery adjacent to the colorectal tumor showed increased B and regulatory T cells and decreased NK, CD3+ CD56+, CD4+ TRM, and CD8+ TRM cells. Moreover, memory CD8+ T cells and plasmablasts are negatively correlated with the depth of invasion of CRC. Increased memory CD4+ T cells are associated with distant metastasis of CRC and high preoperative serum carcinoembryonic antigen levels.

Conclusion

The mesentery shows a specific immune microenvironment, which differs from that observed in peripheral blood. CRC can alter the mesenteric immune response to promote tumor progression.
Detection of Incidental Esophageal Cancers on Chest CT by Deep Learning
Authors: Sui He , Ma Ruhang , Liu Lin , Gao Yaozong , Zhang Wenhai , Mo Zhanhao
Published: September 2021

Objective

To develop a deep learning-based model using esophageal thickness to detect esophageal cancer from unenhanced chest CT images.

Methods

We retrospectively identified 141 patients with esophageal cancer and 273 patients negative for esophageal cancer (at the time of imaging) for model training. Unenhanced chest CT images were collected and used to build a convolutional neural network (CNN) model for diagnosing esophageal cancer. The CNN is a VB-Net segmentation network that segments the esophagus and automatically quantifies the thickness of the esophageal wall and detect positions of esophageal lesions. To validate this model, 52 false negatives and 48 normal cases were collected further as the second dataset. The average performance of three radiologists and that of the same radiologists aided by the model were compared.

Results

The sensitivity and specificity of the esophageal cancer detection model were 88.8% and 90.9%, respectively, for the validation dataset set. Of the 52 missed esophageal cancer cases and the 48 normal cases, the sensitivity, specificity, and accuracy of the deep learning esophageal cancer detection model were 69%, 61%, and 65%, respectively. The independent results of the radiologists had a sensitivity of 25%, 31%, and 27%; specificity of 78%, 75%, and 75%; and accuracy of 53%, 54%, and 53%. With the aid of the model, the results of the radiologists were improved to a sensitivity of 77%, 81%, and 75%; specificity of 75%, 74%, and 74%; and accuracy of 76%, 77%, and 75%, respectively.

Conclusions

Deep learning-based model can effectively detect esophageal cancer in unenhanced chest CT scans to improve the incidental detection of esophageal cancer.
Emerging Evidence of the Gut Microbiome in Chemotherapy: A Clinical Review
Authors: Oh Byeongsang , Boyle Frances , Pavlakis Nick , Clarke Stephen , Guminski Alex , Eade Thomas , Lamoury Gillian , Carroll Susan , Morgia Marita , Kneebone Andrew , Hruby George , Stevens Mark , Liu Wen , Corless Brian , Molloy Mark , Libermann Towia , Rosenthal David , Back Michael
Published: September 2021

Increasing evidence suggests that the gut microbiome is associated with both cancer chemotherapy (CTX) outcomes and adverse events (AEs). This review examines the relationship between the gut microbiome and CTX as well as the impact of CTX on the gut microbiome. A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for “cancer” and “chemotherapy” and “microbiome/microbiota”. The relevant literature was selected for use in this article. Seventeen studies were selected on participants with colorectal cancer (CRC; n=5), Acute Myeloid Leukemia (AML; n=3), Non-Hodgkin’s lymphoma (n=2), breast cancer (BCa; n=1), lung cancer (n=1), ovarian cancer (n=1), liver cancer (n=1), and various other types of cancers (n=3). Seven studies assessed the relationship between the gut microbiome and CTX with faecal samples collected prior to (n=3) and following CTX (n=4) showing that the gut microbiome is associated with both CTX efficacy and toxicity. Ten other prospective studies assessed the impact of CTX during treatment and found that CTX modulates the gut microbiome of people with cancer and that dysbiosis induced by the CTX is related to AEs. CTX adversely impacts the gut microbiome, inducing dysbiosis and is associated with CTX outcomes and AEs. Current evidence provides insights into the gut microbiome for clinicians, cancer survivors and the general public. More research is required to better understand and modify the impact of CTX on the gut microbiome.
Comparison of Perioperative Outcomes of Robotic-Assisted vs Laparoscopic Adrenalectomy for Pheochromocytoma: A Meta-Analysis
Authors: Xia Zhongyou , Li Jinze , Peng Lei , Yang Xiaoying , Xu Yulai , Li Xianhui , Li Yunxiang , Zhang Zongping , Wu Ji
Published: September 2021

Objective

To compare the efficacy and safety of robotic-assisted adrenalectomy (RA) and standard laparoscopic adrenalectomy (LA) for pheochromocytoma (PHEO).

Methods

We systematically searched the Cochrane Library, PubMed, Embase, and Science databases for studies published through January 2021. Controlled trials on RA and LA for PHEOs were included. The meta-analysis was conducted with the Review Manager 5.4 software.

Results

Four studies with 386 patients were included in the analysis. There were no significant differences in OT (WMD: 0.16; 95% CI: -28.50 to 28.82; I2 = 89%; P = 0.99), transfusion rate (OR: 0.70; 95% CI: 0.07 to 7.07; I2 = 64%; P = 0.77), conversion rate (OR: 0.44; 95% CI: 0.07 to 2.88; I2 = 0%; P = 0.39), complication rate (OR: 1.06; 95% CI: 0.62 to 1.82; I2 = 0%; P = 0.84) among patients undergoing RA and LA. However, compared with patients who underwent LA, patients who underwent RA had a shorter LOS (OR: -0.50; 95% CI: -0.55 to 0.45; I2 = 31%; P<0.01), less EBL (WMD: -0.85; 95% CI: -13.56 to -2.54; I2 = 44%; P<0.01), and fewer IHD (OR: 0.34; 95% CI: 0.17 to 0.70; I2 = 0%; P<0.01).

Conclusion

The RA for pheochromocytoma achieve better outcomes over LA in terms of safety and efficacy.
Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer
Authors: Zheng Hong , Shu Tong , Zhu Shan , Zhang Chao , Gao Min , Zhang Nan , Wang Hongguo , Yuan Jie , Tai Zaixian , Xia Xuefeng , Yi Yuting , Li Jin , Guan Yanfang , Xiang Yang , Gao Yunong
Published: September 2021

Platinum-based chemotherapy is still the standard of care after cytoreductive surgery in the first-line treatment for epithelial ovarian cancer. This study aims to integrate novel biomarkers for predicting platinum sensitivity in EOC after initial cytoreductive surgery precisely. To this end, 60 patients were recruited from September 2014 to October 2019. Based on the duration of progress-free survival, 44 and 16 patients were assigned to platinum-sensitive and platinum-resistant group, respectively. Next generation sequencing was performed to dissect the genomic features of ovarian tumors obtained from surgery. Multiple genomic variations were compared between two groups, including single-nucleotide variant, single base or indel signature, loss of heterozygosity (LOH), whole-genome duplication (WGD), and others. The results demonstrated that patients with characteristics including positive SBS10a signature (p < 0.05), or FAM175A LOH (p < 0.01), or negative WGD (p < 0.01) were significantly enriched in platinum-sensitive group. Consistently, patients with positive SBS10a signature (15.8 vs. 10.1 months, p < 0.05), or FAM175A LOH (16.5 vs. 9.2 months, p < 0.05), or negative WGD (16.5 vs. 9.1 months, p < 0.05) have significantly longer PFS than those without these genetic features. By integrating these three biomarkers, a lasso regression model was employed to train and test for all patients, with the AUC value 0.864 in platinum sensitivity prediction. Notably, 388 ovarian cancer patients from TCGA dataset were leveraged as independent validation cohort with AUC value 0.808, suggesting the favorable performance and reliability of this model.
Safety and Efficacy of Anti-CD19-Chimeric Antigen Receptor T Cell Combined With Programmed Cell Death 1 Inhibitor Therapy in a Patient With Refractory Post-Transplant Lymphoproliferative Disease: Case Report and Literature Review
Authors: Feng Gang , Li Qing , Zhu Haibo , Jiang Yanyu , Yuan Jijun , Fu Yingxin , Deng Qi
Published: September 2021

Post-transplant lymphoproliferative disease (PTLD) often exhibits poor prognosis and high mortality, and there are no uniform guidelines for the treatment of this disease. Anti-CD19 chimeric antigen receptor (CAR) T cells show significant efficacy in treatment of relapse/refractory diffuse large B-cell lymphoma (DLBCL). Treatment using anti-CD19-CAR T-cell therapy in PTLD has been limited by immunosuppressants and has not been widely employed. In this study, a refractory post kidney transplant DLBCL patient with a high tumor burden was enrolled in a clinical trial of anti-CD19-CAR T-cell therapy. The tacrolimus dose was not decreased during combination chemotherapy, as the creatinine level of the patient increased. To improve the function of autologous T cells, combination therapy with anti-CD19-CAR T cells and programmed cell death 1 (PD-1) inhibitors was selected. After treatment with the combination therapy, the patient was diagnosed with grade 1 cytokine release syndrome and grade 3 immune effector cell-associated neurotoxicity syndrome. The amplification peak of anti-CD19-CAR T cells reached 9.01% on day 7. With PD-1 inhibitor maintenance therapy, his disease was maintained in partial remission for 18 weeks. However, his tumor suddenly increased in size, and he discontinued the treatment, including radiation therapy. The anti-CD19-CAR T cell and PD-1 inhibitors have a combined effect on PTLD, and this combination therapy needs to be further explored.
Ex Vivo Drug Screening Informed Targeted Therapy for Metastatic Parotid Squamous Cell Carcinoma
Authors: Nykänen Noora , Mäkelä Rami , Arjonen Antti , Härmä Ville , Lewandowski Laura , Snowden Eileen , Blaesius Rainer , Jantunen Ismo , Kuopio Teijo , Kononen Juha , Rantala Juha K.
Published: September 2021

The purpose of ex vivo drug screening in the context of precision oncology is to serve as a functional diagnostic method for therapy efficacy modeling directly on patient-derived tumor cells. Here, we report a case study using integrated multiomics ex vivo drug screening approach to assess therapy efficacy in a rare metastatic squamous cell carcinoma of the parotid gland. Tumor cells isolated from lymph node metastasis and distal subcutaneous metastasis were used for imaging-based single-cell resolution drug screening and reverse-phase protein array-based drug screening assays to inform the treatment strategy after standard therapeutic options had been exhausted. The drug targets discovered on the basis of the ex vivo measured drug efficacy were validated with histopathology, genomic profiling, and in vitro cell biology methods, and targeted treatments with durable clinical responses were achieved. These results demonstrate the use of serial ex vivo drug screening to inform adjuvant therapy options prior to and during treatment and highlight HER2 as a potential therapy target also in metastatic squamous cell carcinoma of the salivary glands.
The Learning Curve of Computer-Assisted Free Flap Jaw Reconstruction Surgery Using 3D-Printed Patient-Specific Plates: A Cumulative Sum Analysis
Authors: Zhu Wang-yong , Choi Wing Shan , Wong May Chun Mei , Pu Jingya Jane , Yang Wei-fa , Su Yu-xiong
Published: September 2021

Background

Computer-assisted jaw reconstruction (CAJR) has benefits in reducing operation time and improving reconstruction accuracy, compared to conventional freehand jaw reconstruction. However, no information is available regarding learning curves in CAJR with the use of 3D-printed patient-specific surgical plates (PSSP). The purpose of this study was to assess surgical outcomes and learning curve for the first 58 consecutive CAJR using 3D-printed PSSP performed by a single surgical team in a single institution.

Methods

In a prospective study, consecutive patients who underwent free flap CAJR using 3D-printed PSSP were included. The determination of proficiency, based on the cumulative sum of surgical success (no major adjustment of 3D-printed PSSP, flap survival) passing the acceptable boundary line of cumulative sum analysis, was the primary outcome. To find out any potential factors influencing the learning curve, baseline characteristics of patients were compared before and after proficiency achievement. Secondary outcomes included inflexion points of the total operation time, blood loss, length of hospital stay, and bone graft deviation, measured by the cumulative sum analysis.

Results

From December 2016 to November 2020, 58 consecutive cases underwent surgery performed by a single surgical team. The overall surgical success rate was 94.8% (55/58). A three-stage learning curve of primary outcome was observed. The proficiency was achieved after 23 cases. The proportions of advanced tumor staging and concomitant surgery after obtaining proficiency were significantly higher than those before achieving proficiency (p = 0.046 and p < 0.001, respectively). Mean values of operation time, intraoperative blood loss, length of hospital stay, and bone graft deviation were 532.5 ± 119.2 min, 1,006.8 ± 547.2 ml, 16.1 ± 6.3 days, and 0.9 ± 1.2 mm, respectively. Two trends of learning curve were observed in the CUSUM analyses of total operation time, length of hospital stay, and bone graft deviation, in which the first and second inflexion points occurred between 8 and 17 cases and between 43 and 46 cases, respectively.

Conclusion

Our results revealed a three-stage learning curve of CAJR with the use of PSSP, including initial learning, plateau, and overlearning. Based on CUSUM analysis, the surgical proficiency was achieved after 23 cases, and total operation time, length of hospital stay, and bone graft deviation stabilized after 8–17 cases.
Genomic Instability-Related LncRNA Signature Predicts the Prognosis and Highlights LINC01614 Is a Tumor Microenvironment-Related Oncogenic lncRNA of Papillary Thyroid Carcinoma
Authors: Dong Xubin , Jin Cong , Chen Danxiang , Chen Yizuo , Ye Zhi-qiang , Zhang Xiaohua , Huang Xiaoli , Zhang Wei , Gu Dian-na
Published: September 2021

Background

Genomic instability (GI) is among the top ten characteristics of malignancy. Long non-coding RNAs (lncRNAs) are promising cancer biomarkers that are reportedly involved in GI. So far, the clinical value of GI-related lncRNAs (GIlncs) in papillary thyroid cancer (PTC) has not been clarified.

Methods

Integrative analysis of lncRNA expression and somatic mutation profiles was performed to identify GIlncs. Analysis of differentially expressed lncRNAs in the group with high- and low- cumulative number of somatic mutations revealed significant GIlncs in PTC. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify hub-GIlncs.

Results

A computational model based on four lncRNAs (FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1) was identified as a quantitative index using an in-silicon discovery cohort. GILS score was significantly associated with poor prognosis, as validated in the TCGA dataset and further tested in our local RNA-Seq cohort. Moreover, a combination of clinical characteristics and the composite GILS-clinical prognostic nomogram demonstrates satisfactory discrimination and calibration. Furthermore, the GILS score and FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1 were also associated with driver mutations and multiple clinical-pathological variables, respectively. Moreover, RNA-Seq confirmed the expression patterns of FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1 in PTC and normal thyroid tissues. Biological experiments demonstrated that downregulated or overexpressed LINC01614 affect PTC cell proliferation, migration, and invasion in vitro. Activation of the stromal and immune cell infiltration was also observed in the high LINC01614 group in the PTC microenvironment.

Conclusion

In summary, we identified a signature for clinical outcome prediction in PTC comprising four lncRNAs associated with GI. A better understanding of the GI providing an alternative evaluation of the progression risk of PTC. Our study also demonstrated LINC01614 as a novel oncogenic lncRNA and verified its phenotype in PTC.
Early Plasma Osmolality Levels and Clinical Outcomes in Children Admitted to the Pediatric Intensive Care Unit: A Single-Center Cohort Study
Authors: Wang Huabin , He Zhongyuan , Li Jiahong , Lin Chao , Li Huan , Jin Ping , Chen Chun
Published: September 2021

Objective: Identifying high-risk children with a poor prognosis in pediatric intensive care units (PICUs) is critical. The aim of this study was to assess the predictive value of early plasma osmolality levels in determining the clinical outcomes of children in PICUs.

Methods: We retrospectively assessed critically ill children in a pediatric intensive care database. The locally weighted-regression scatter-plot smoothing (LOWESS) method was used to explore the approximate relationship between plasma osmolality and in-hospital mortality. Linear spline functions and stepwise expansion models were applied in conjunction with a multivariate logistic regression to further analyze this relationship. A subgroup analysis by age and complications was performed.

Results: In total, 5,620 pediatric patients were included in this study. An approximately “U”-shaped relationship between plasma osmolality and mortality was detected using LOWESS. In the logistic regression model using a linear spline function, plasma osmolality ≥ 290 mmol/L was significantly associated with in-hospital mortality [odds ratio (OR) 1.020, 95% confidence interval (CI) 1.010–1.031], while plasma osmolality <290 mmol/L was not significantly associated with in-hospital mortality (OR 0.990, 95% CI 0.966–1.014). In the logistic regression model with plasma osmolality as a tri-categorical variable, only high osmolality was significantly associated with in-hospital mortality (OR 1.90, 95% CI 1.38–2.64), whereas low osmolality was not associated with in-hospital mortality (OR 1.28, 95% CI 0.84–1.94). The interactions between plasma osmolality and age or complications were not significant.

Conclusion: High osmolality, rather than low osmolality, can predict a poor prognosis in children in PICUs.
Mitragynine (Kratom)-Induced Cognitive Impairments in Mice Resemble Δ9-THC and Morphine Effects: Reversal by Cannabinoid CB1 Receptor Antagonism
Authors: Iman Ismail Nurul , Ahmad Nur Aimi Zawami , Mohd Yusof Nurul Aiman , Talib Ummi Nasrah , Norazit Anwar , Kumar Jaya , Mehat Muhammad Zulfadli , Hassan Zurina , Müller Christian P. , Muzaimi Mustapha
Published: September 2021

Kratom is a widely abused plant-based drug preparation with a global interest in recent years, well beyond its native grounds in Southeast Asia. Mitragynine, its major psychoactive constituent is known to exhibit opioid-like behavioral effects with resultant neuroplasticity in the brain reward system. Its chronic administration is associated with cognitive impairments in animal studies. However, the underlying molecular mechanism for such a deficit remains elusive. In this study, the involvement of cannabinoid type-1 (CB1) receptors in cognitive deficits after chronic mitragynine exposures was investigated for 28 days (with incremental dose sensitization from 1 to 25 mg/kg) in adult male Swiss albino mice using the IntelliCage®system. Chronic high-dose mitragynine exposure (5–25 mg/kg, intraperitoneal [i.p.]), but not low-dose exposure (1–4 mg/kg, i.p.), induced hyperlocomotion, potentiated the preference for sucrose reward, increased resistance to punishment, and impaired place learning and its reversal. Comparable deficits were also observed after chronic treatments with Δ-9-tetrahydrocannabinol (THC, 2 mg/kg, i.p.) or morphine (5 mg/kg, subcutaneous). Mitragynine-, morphine-, and THC-induced learning and memory deficits were reversed by co-treatment with the CB1receptor antagonist, NIDA-41020 (10 mg/kg, i.p.). A significant upregulation of CB1receptor expression was found in the hippocampal CA1 region and ventral tegmental area after chronic high-dose mitragynine and morphine, whereas a downregulation was observed after chronic THC. In conclusion, the present study suggests a plausible role of the CB1receptor in mediating the dose-dependent cognitive deficits after chronic high-dose mitragynine exposure. This also highlights the potential of CB1receptor antagonism in ameliorating the cognitive deficits associated with long-term kratom/mitragynine consumption in humans.
Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism
Authors: Bai Yu , Mo Ke , Wang Guirong , Chen Wanling , Zhang Wei , Guo Yibo , Sun Zhirong
Published: September 2021

As a severe metabolic disease, type 2 diabetes mellitus (T2DM) has become a serious threat to human health in recent years. Gastrodin, as a primary chemical constituent in Gastrodia elata Blume, has antidiabetic effects. However, the possible mechanisms are unclear. The aim of the present study was to investigate the effects and possible mechanisms of gastrodin on the treatment of T2DM. In vivo, after treatment with gastrodin for 6 weeks, fasting blood glucose levels, blood lipid metabolism, and insulin sensitivity index values were remarkably reduced compared with those of the diabetic control group. The values of aspartate aminotransferase and alanine aminotransferase also showed that gastrodin alleviates liver toxicity caused by diabetes. Moreover, gastrodin relieved pathological damage to the pancreas in T2DM rats. In vitro, gastrodin alleviated insulin resistance by increasing glucose consumption, glucose uptake, and glycogen content in dexamethasone-induced HepG2 cells. The Western blotting results showed that gastrodin upregulated the expression of insulin receptors and ubiquitin-specific protease 4 (USP4) and increased the phosphorylation of GATA binding protein 1 (GATA1) and protein kinase B (AKT) in vivo and in vitro. Furthermore, gastrodin decreased the ubiquitin level of the insulin receptor via UPS4 and increased the binding of GATA1 to the USP4 promoter. Additionally, administration of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway inhibitors MK-2206 and LY294002 abolished the beneficial effects of gastrodin. Our results indicate that gastrodin promotes the phosphorylation of GATA1 via the PI3K/AKT pathway, enhances the transcriptional activity of GATA1, and then increases the expression level of USP4, thereby reducing the ubiquitination and degradation of insulin receptors and ultimately improving insulin resistance. Our study provides scientific evidence for the beneficial actions and underlying mechanism of gastrodin in the treatment of T2DM.
Notoginsenoside R1 Reverses Abnormal Autophagy in Hippocampal Neurons of Mice With Sleep Deprivation Through Melatonin Receptor 1A
Authors: Cao Yin , Li Qinglin , Zhou An , Ke Zunji , Chen Shengqi , Li Mingrui , Gong Zipeng , Wang Zhengtao , Wu Xiaojun
Published: September 2021

Sleep deprivation (SD) may cause serious neural injury in the central nervous system, leading to impairment of learning and memory. Melatonin receptor 1A (MTNR1A) plays an important role in the sleep regulation upon activation by melatonin. The present study aimed to investigate if notoginsenoside R1 (NGR1), an active compound isolated from Panax notoginseng, could alleviate neural injury, thus improve impaired learning and memory of SD mice, as well as to explore its underlying action mechanism through modulating MTNR1A. Our results showed that NGR1 administration improved the impaired learning and memory of SD mice. NGR1 prevented the morphological damage and the accumulation of autophagosomes in the hippocampus of SD mice. At the molecular level, NGR1 reversed the expressions of proteins involved in autophagy and apoptosis, such as beclin-1, LC3B, p62, Bcl-2, Bax, and cleaved-caspase 3. Furthermore, the effect of NGR1 was found to be closely related with the MTNR1A-mediated PI3K/Akt/mTOR signaling pathway. On HT-22 cells induced by autophagy inducer rapamycin, NGR1 markedly attenuated excessive autophagy and apoptosis, and the alleviative effect was abolished by the MTNR1A inhibitor. Taken together, NGR1 was shown to alleviate the impaired learning and memory of SD mice, and its function might be exerted through reduction of excessive autophagy and apoptosis of hippocampal neurons by regulating the MTNR1A-mediated PI3K/Akt/mTOR signaling pathway.
Plasma Lysophosphatidylcholine and Lysophosphatidylethanolamine Levels Were Associated With the Therapeutic Response to Olanzapine in Female Antipsychotics-naïve First-episode Patients With Schizophrenia
Authors: Liu Jiahong , Xiu Meihong , Liu Haixia , Wang Jun , Li Xirong
Published: September 2021

Background: Accumulating studies have shown that the pathophysiology of schizophrenia may be associated with aberrant lysophospolipid metabolism in the early stage of brain development. Recent evidence demonstrates that antipsychotic medication can regulate the phospholipase activity. However, it remains unclear whether lysophospolipid is associated with the therapeutic response to antipsychotic medication in schizophrenia. This study aimed to investigate the influence of olanzapine monotherapy on lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) and the association between symptom improvement and changes of LPC and LPE levels during treatment in antipsychotic-naïve first-episode (ANFE) patients.

Materials and Methods: The psychotic symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). 25 ANFE patients were treated with olanzapine for 1 mo. The levels of LPC and LPE were determined and psychotic symptoms were assessed at baseline and at 1-mo follow-up.

Results: Relative to baseline, the psychotic symptoms were significantly reduced after olanzapine treatment, except for negative symptoms. Moreover, the levels of most LPC and LPE increased after treatment. Interestingly, increased LPC(18:3) and LPC(20:2) levels were positively associated with the reduction rates of PANSS positive subscore. In addition, baseline levels of LPE(20:5), LPE(18:3) and LPE(22:5) were predictors for the reduction of positive symptoms.

Conclusion: Our study reveals that the levels of lysophospolipid are associated with the improvement of positive symptoms, indicating that LPC may be a potential therapeutic target for olanzapine in schizophrenia. Moreover, baseline LPE levels were predictive biomarkers for the therapeutic response to olanzapine in the early stage of treatment in ANFE patients.
Neuropsychological Functioning in Users of Serotonergic Psychedelics – A Systematic Review and Meta-Analysis
Authors: Basedow Lukas A. , Riemer Thomas G. , Reiche Simon , Kreutz Reinhold , Majić Tomislav
Published: September 2021

Background: Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT2a receptors. Besides the ability of these substances to facilitate profoundly altered states of consciousness, persisting psychological effects have been reported after single administrations, which outlast the acute psychedelic effects. In this review and meta-analysis, we investigated if repeated SP use associates with a characteristic neuropsychological profile indicating persisting effects on neuropsychological function.

Methods: We conducted a systematic review of studies investigating the neuropsychological performance in SP users, searching studies in Medline, Web of Science, embase, ClinicalTrials.gov, and EudraCT. Studies were included if they reported at least one neuropsychological measurement in users of SPs. Studies comparing SP users and non-users that reported mean scores and standard deviations were included in an exploratory meta-analysis.

Results: 13 studies (N = 539) published between 1969 and 2020 were included in this systematic review. Overall, we found that only three SPs were specifically investigated: ayahuasca (6 studies, n = 343), LSD (5 studies, n = 135), and peyote (1 study, n = 61). However, heterogeneity of the methodological quality was high across studies, with matching problems representing the most important limitation. Across all SPs, no uniform pattern of neuropsychological impairment was identified. Rather, the individual SPs seemed to be associated with distinct neuropsychological profiles. For instance, one study (n = 42) found LSD users to perform worse in trials A and B of the Trail-Making task, whereas meta-analytic assessment (5 studies, n = 352) of eleven individual neuropsychological measures indicated a better performance of ayahuasca users in the Stroop incongruent task (p = 0.03) and no differences in the others (all p > 0.05).

Conclusion: The majority of the included studies were not completely successful in controlling for confounders such as differences in non-psychedelic substance use between SP-users and non-users. Our analysis suggests that LSD, ayahuasca and peyote may have different neuropsychological consequences associated with their use. While LSD users showed reduced executive functioning and peyote users showed no differences across domains, there is some evidence that ayahuasca use is associated with increased executive functioning.
Anlotinib Inhibits PFKFB3-Driven Glycolysis in Myofibroblasts to Reverse Pulmonary Fibrosis
Authors: Chen Weimou , Zhang Jinming , Zhong Wenshan , Liu Yuanyuan , Lu Ye , Zeng Zhaojin , Huang Haohua , Wan Xuan , Meng Xiaojing , Zou Fei , Cai Shaoxi , Dong Hangming
Published: September 2021

Idiopathic pulmonary fibrosis (IPF) is a fatal disease in which the normal alveolar network is gradually replaced by fibrotic scars. Current evidence suggests that metabolic alterations correlate with myofibroblast activation in IPF. Anlotinib has been proposed to have antifibrotic effects, but the efficacy and mechanisms of anlotinib against lung fibrosis have not been systematically evaluated. The antifibrotic effects of anlotinib were evaluated in bleomycin-induced mouse models and transforming growth factor-beta 1 (TGF-β1)-stimulated lung fibroblasts. We measured lactate levels, 2-NBDG glucose uptake and the extracellular acidification rate (ECAR) to assess glycolysis in fibroblasts. RNA-protein coimmunoprecipitation (RIP) and polysome analyses were performed to investigate novel mechanisms of glycolytic reprogramming in pulmonary fibrosis. We found that anlotinib diminished myofibroblast activation and inhibited the augmentation of glycolysis. Moreover, we show that PCBP3 posttranscriptionally increases PFKFB3 expression by promoting its translation during myofibroblast activation, thus promoting glycolysis in myofibroblasts. Regarding mechanism, anlotinib exerts potent antifibrotic effects by downregulating PCBP3, reducing PFKFB3 translation and inhibiting glycolysis in myofibroblasts. Furthermore, we observed that anlotinib had preventative and therapeutic antifibrotic effects on bleomycin-induced pulmonary fibrosis. Therefore, we identify PCBP3 as a protein involved in the regulation of glycolysis reprogramming and lung fibrogenesis and propose it as a therapeutic target for pulmonary fibrosis. Our data suggest that anlotinib has antifibrotic effects on the lungs, and we provide a novel mechanism for this effect. Anlotinib may constitute a novel and potent candidate for the treatment of pulmonary fibrosis.
Update on Novel Non-Operative Treatment for Osteoarthritis: Current Status and Future Trends
Authors: Chen Tao , Weng Weidong , Liu Yang , Aspera-Werz Romina H. , Nüssler Andreas K , Xu Jianzhong
Published: September 2021

Osteoarthritis (OA) is a leading cause of pain and disability which results in a reduced quality of life. Due to the avascular nature of cartilage, damaged cartilage has a finite capacity for healing or regeneration. To date, conservative management, including physical measures and pharmacological therapy are still the principal choices offered for OA patients. Joint arthroplasties or total replacement surgeries are served as the ultimate therapeutic option to rehabilitate the joint function of patients who withstand severe OA. However, these approaches are mainly to relieve the symptoms of OA, instead of decelerating or reversing the progress of cartilage damage. Disease-modifying osteoarthritis drugs (DMOADs) aiming to modify key structures within the OA joints are in development. Tissue engineering is a promising strategy for repairing cartilage, in which cells, genes, and biomaterials are encompassed. Here, we review the current status of preclinical investigations and clinical translations of tissue engineering in the non-operative treatment of OA. Furthermore, this review provides our perspective on the challenges and future directions of tissue engineering in cartilage regeneration.
Non-Diffracting Light Wave: Fundamentals and Biomedical Applications
Authors: Ren Yu-Xuan , He Hongsen , Tang Huajun , Wong Kenneth K. Y.
Published: September 2021

The light propagation in the medium normally experiences diffraction, dispersion, and scattering. Studying the light propagation is a century-old problem as the photons may attenuate and wander. We start from the fundamental concepts of the non-diffracting beams, and examples of the non-diffracting beams include but are not limited to the Bessel beam, Airy beam, and Mathieu beam. Then, we discuss the biomedical applications of the non-diffracting beams, focusing on linear and nonlinear imaging, e.g., light-sheet fluorescence microscopy and two-photon fluorescence microscopy. The non-diffracting photons may provide scattering resilient imaging and fast speed in the volumetric two-photon fluorescence microscopy. The non-diffracting Bessel beam and the Airy beam have been successfully used in volumetric imaging applications with faster speed since a single 2D scan provides information in the whole volume that adopted 3D scan in traditional scanning microscopy. This is a significant advancement in imaging applications with sparse sample structures, especially in neuron imaging. Moreover, the fine axial resolution is enabled by the self-accelerating Airy beams combined with deep learning algorithms. These additional features to the existing microscopy directly realize a great advantage over the field, especially for recording the ultrafast neuronal activities, including the calcium voltage signal recording. Nonetheless, with the illumination of dual Bessel beams at non-identical orders, the transverse resolution can also be improved by the concept of image subtraction, which would provide clearer images in neuronal imaging.
Visible to Mid-infrared Waveband Photodetector Based on Insulator Capped Asymmetry Black Phosphorous
Authors: Han Qi , Jiang Yadong , Han Jiayue , Dong Xiang , Gou Jun
Published: September 2021

Processing layer-dependent direct band gap and good absorption coefficient especially in the mid-infrared band, black phosphorous is believed to make a contribution superior to that of graphene in broadband photodetectors. The narrow band gap of 0.3 eV for bulk black phosphorous helps to absorb infrared radiation while a relatively large dark current under zero gate voltage is inevitable. Few layer black phosphorous sheets with asymmetrical thickness sealed in an insulator for protection is designed and explored for photosensitive mechanism in this work. Saturable absorption dominates the light harvesting process in visible light detection and thus limits maximum photocurrent to 3.3 and 1.4 μA for 520 and 650 nm lasers with a dark current of 0.7 μA. While in near-infrared wavelength, a responsivity of 0.12 A/W is inducted for 808 nm free of adsorption saturation even if the incident power is increased to 200 mW/cm2. Discrimination for the origin of the photo-response in short wavelength is conducted and the abnormal negative and nearly constant photocurrent in mid-infrared, irrelevant to inhomogeneous thickness, reveals the photothermal effect in a black phosphorous sheet. This work unravels various photoelectric features in black phosphorous and paves the way to designing more outstanding broadband photodetectors based on black phosphorous.
Young Swimmers' Anthropometrics, Biomechanics, Energetics, and Efficiency as Underlying Performance Factors: A Systematic Narrative Review
Authors: Morais Jorge E. , Barbosa Tiago M. , Forte Pedro , Silva António J. , Marinho Daniel A.
Published: September 2021

Introduction: In youth swimming, researchers are interested in understanding how anthropometry and parameters related to swimming technique (biomechanics, energetics, and efficiency) influence the performance. However, there is not any review in the literature that consolidates the body of knowledge of this topic. The objective of this study was to review systematically the current body of work on the influence of determinant factors related to swimming technique (biomechanics, energetics, and efficiency) and anthropometry in the young performance of swimmers.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify relevant studies.

Results: After screening, 240 studies were analyzed and 59 related to swimming performance, and its determinant factors were retained for synthesis. Studies revealed a high-quality index by PEDro scale (mean score was 7.17 ± 1.40). Twenty-five studies were longitudinal designs and the remaining 34 cross-sectional designs. Most of the studies (N = 39, 66.1%) reported concurrently two or more determinant factors (anthropometrics, biomechanics, energetics, and efficiency).

Conclusion: Youth swimming research relies on a multifactorial assessment. From the synthesis, it is possible to conclude that the performance of young swimmers is characterized by a multifactorial, holistic, and dynamic phenomenon. Better performance has always been related to better swimming technique and higher anthropometrics. This suggests that both anthropometrics (i.e., nature) and training (i.e., nurture) play key roles in the swimming performance of young swimmers.