bluuebunny/crossref_metadata_2025 huggingface dataset:
A web-based dynamic nomogram for rupture risk of posterior communicating artery aneurysms utilizing clinical, morphological, and hemodynamic characteristics
Authors: Wei Heng , Han Wenrui , Tian Qi , Yao Kun , He Peibang , Wang Jianfeng , Guo Yujia , Chen Qianxue , Li Mingchang
Published: September 2022

Background

Predicting rupture risk is important for aneurysm management. This research aimed to develop and validate a nomogram model to forecast the rupture risk of posterior communicating artery (PcomA) aneurysms.

Methods

Clinical, morphological, and hemodynamic parameters of 107 unruptured PcomA aneurysms and 225 ruptured PcomA aneurysms were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) analysis was applied to identify the optimal rupture risk factors, and a web-based dynamic nomogram was developed accordingly. The nomogram model was internally validated and externally validated independently. The receiver operating characteristic (ROC) curve was used to assess the discrimination of nomogram, and simultaneously the Hosmer–Lemeshow test and calibration plots were used to assess the calibration. Decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical utility of nomogram additionally.

Results

Four optimal rupture predictors of PcomA aneurysms were selected by LASSO and identified by multivariate logistic analysis, including hypertension, aspect ratio (AR), oscillatory shear index (OSI), and wall shear stress (WSS). A web-based dynamic nomogram was then developed. The area under the curve (AUC) in the training and external validation cohorts was 0.872 and 0.867, respectively. The Hosmer–Lemeshow p > 0.05 and calibration curves showed an appropriate fit. The results of DCA and CIC indicated that the net benefit rate of the nomogram model is higher than other models.

Conclusion

Hypertension, high AR, high OSI, and low WSS were the most relevant risk factors for rupture of PcomA aneurysms. A web-based dynamic nomogram thus established demonstrated adequate discrimination and calibration after internal and external validation. We hope that this tool will provide guidance for the management of PcomA aneurysms.
Effect of vertebrobasilar dolichoectasia on endovascular therapy in acute posterior circulation infarction
Authors: Zhou Jing , Peng Daizhou , Sun Dong , Dai Weipeng , Long Ceng , Meng Renliang , Wang Jing , Yan Zhizhong , Wang Tao , Wang Li , Yue Chengsong , Li Linyu , Zi Wenjie , Wang Lingling , Wang Xiaoming , Wu Youlin , Jiang Guohui
Published: September 2022

Background and purpose

This study aimed to analyze the feasibility and safety of endovascular therapy (EVT) in patients with acute posterior circulation stroke and vertebrobasilar dolichoectasia (VBD).

Materials and methods

BASILAR was a national prospective registry of consecutive patients with symptomatic and imaging-confirmed acute stroke in the posterior circulation within 24 h of symptom onset. We evaluated EVT feasibility and safety in patients with VBD. Primary outcomes included improvement in modified Rankin Scale scores (mRS) at 90 days and mortality within 90 days. The secondary outcome was the rate of favorable functional outcome, defined as mRS ≤ 3 (indicating independent ambulation) at 90 days. Safety outcomes included surgery-related complications and other serious adverse events.

Results

A total of 534 cases were included: 159 with VBD and 375 controls. No significant difference in mRS at 90 days was found between groups, but patients with VBD had a higher baseline National Institutes of Health Stroke Scale (NIHSS) score [30 (19–33) vs. 25 (15–32)] and were older [65 (59–74) vs. 63 (55–72) year]. After propensity score matching, there were no significant differences in baseline NIHSS score between the two groups, and the efficacy and safety of EVT were similar between patients with or without VBD. Furthermore, the prognostic effect of puncture-to-recanalization time on the probability of mortality within 90 days in EVT-treated patients with VBD was significant {adjusted odds ratio, 1.008 [95% confidence interval (1.001–1.015)]}.

Conclusion

Endovascular therapy is safe and feasible in patients with acute posterior circulation stroke and VBD. The puncture-to-recanalization time is important for predicting the prognosis of EVT-treated patients with VBD.
Behavioral features and disorganization of oscillatory activity in C57BL/6J mice after acute low dose MK-801 administration
Authors: Cui Keke , Yu Zhipeng , Xu Le , Jiang Wangcong , Wang Luwan , Wang Xiangqun , Zou Dandan , Gu Jiajie , Gao Feng , Zhang Xiaoqing , Wang Zhengchun
Published: September 2022

Low dose acute administration of N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 is widely used to model cognition impairments associated with schizophrenia (CIAS) in rodents. However, due to no unified standards for animal strain, dose, route of drug delivery, and the duration of administration, how different doses of MK-801 influence behavior and fundamental frequency bands of the local field potential (LFP) in cortical and subcortical brain regions without consistent conclusions. The optimal dose of MK-801 as a valid cognition impairers to model CIAS in C57BL/6J mice remains unclear. The current study characterizes the behavior and neural oscillation alterations induced by different low doses of MK-801 in medial prefrontal cortex (mPFC) and hippocampus CA1 of C57BL/6J mice. The results reveal that mice treated with 0.1 and 0.3 mg/kg MK-801 demonstrate increased locomotion and diminished prepulse inhibition (PPI), while not when treated with 0.05 mg/kg MK-801. We also find that MK-801 dose as low as 0.05 mg/kg can significantly diminishes spontaneous alteration during the Y-maze test. Additionally, the oscillation power in delta, theta, alpha, gamma and HFO bands of the LFP in mPFC and CA1 was potentiated by different dose levels of MK-801 administration. The current findings revealed that the observed sensitivity against spontaneous alteration impairment and neural oscillation at 0.05 mg/kg MK-801 suggest that 0.05 mg/kg will produce changes in CIAS-relevant behavior without overt changes in locomotion and sensorimotor processing in C57BL/6J mice.
The role of hypothalamic endoplasmic reticulum stress in schizophrenia and antipsychotic-induced weight gain: A narrative review
Authors: Zhou Ruqin , He Meng , Fan Jun , Li Ruoxi , Zuo Yufeng , Li Benben , Gao Guanbin , Sun Taolei
Published: September 2022

Schizophrenia (SCZ) is a serious mental illness that affects 1% of people worldwide. SCZ is associated with a higher risk of developing metabolic disorders such as obesity. Antipsychotics are the main treatment for SCZ, but their side effects include significant weight gain/obesity. Despite extensive research, the underlying mechanisms by which SCZ and antipsychotic treatment induce weight gain/obesity remain unclear. Hypothalamic endoplasmic reticulum (ER) stress is one of the most important pathways that modulates inflammation, neuronal function, and energy balance. This review aimed to investigate the role of hypothalamic ER stress in SCZ and antipsychotic-induced weight gain/obesity. Preliminary evidence indicates that SCZ is associated with reduced dopamine D2 receptor (DRD2) signaling, which significantly regulates the ER stress pathway, suggesting the importance of ER stress in SCZ and its related metabolic disorders. Antipsychotics such as olanzapine activate ER stress in hypothalamic neurons. These effects may induce decreased proopiomelanocortin (POMC) processing, increased neuropeptide Y (NPY) and agouti-related protein (AgRP) expression, autophagy, and leptin and insulin resistance, resulting in hyperphagia, decreased energy expenditure, and central inflammation, thereby causing weight gain. By activating ER stress, antipsychotics such as olanzapine activate hypothalamic astrocytes and Toll-like receptor 4 signaling, thereby causing inflammation and weight gain/obesity. Moreover, evidence suggests that antipsychotic-induced ER stress may be related to their antagonistic effects on neurotransmitter receptors such as DRD2 and the histamine H1 receptor. Taken together, ER stress inhibitors could be a potential effective intervention against SCZ and antipsychotic-induced weight gain and inflammation.
The prevalence and associated clinical correlates of hyperuricemia in patients with bipolar disorder
Authors: Li Shuyun , Lu Xiaobing , Chen Xiaodong , Huang Zebin , Zhou Hui , Li Zezhi , Ning Yuping
Published: September 2022

Objective

The prevalence and clinically associated factors of hyperuricemia (HUA) have been widely studied in the general population but rarely in patients with bipolar disorder (BPD) co-morbid with HUA. This study attempted to investigate the prevalence of HUA in BPD patients and analyze the associated correlates of HUA.

Materials and methods

In this study, 182 outpatients with BPD and 182 healthy controls participated. The demographic and clinical information were collected. The body weight, height, waist circumference (WC), hip circumference (HC), and blood pressure (BP) were measured. The levels of serum uric acid (UA), triglyceride (TG), high-density lipoprotein (HDL-C), and fasting blood glucose (FBG) were also determined.

Results

BPD patients had a significantly higher prevalence of HUA (40.7%) compared to healthy controls (30.2%) (χ2 = 4.335, P = 0.037). The systolic blood pressure (SBP), pulse pressure (PP), FBG, UA, and body mass index (BMI) were higher in the BPD group compared with those in the control group, while the diastolic blood pressure (DBP) and HDL-C level were lower (P < 0.05) in BPD patients. The prevalence of HUA was higher in BPD patients who used antipsychotics combined with mood stabilizers than that in BPD subjects receiving the mood stabilizers alone (P < 0.001). The prevalence of HUA and increased serum UA levels were higher in the manic group (62.1%) than in the depressive (34.3%) or euthymia group (17.0%) (P < 0.001). Additionally, the severity of mania was positively correlated with the UA level (r = 0.410, P < 0.001). There were significant differences in terms of MetS (29.7% vs. 14.8%), BMI, HC, WC, TG, and HDL-C between the HUA and the non-HUA groups (P < 0.05). The unconditional logistic regression analysis revealed that high BMI (OR = 1.210; 95%CI: 1.100–1.331) and high TG level (OR = 1.652; 95%CI: 1.058–2.580) were the major risk factorids for HUA in BPD patients.

Conclusion

Our study suggests that patients with BPD are prone to metabolic diseases such as HUA. Higher serum levels of TG and high BMI could be associated with HUA development. Clinicians need to regularly monitor and evaluate BPD patients for their serum UA levels, especially for BPD patients with manic/hypomanic episodes and/or under the treatment of antipsychotics combined with mood stabilizers.
Does high-definition transcranial direct current stimulation change brain electrical activity in professional female basketball players during free-throw shooting?
Authors: Moscaleski Luciane Aparecida , Fonseca André , Brito Rodrigo , Morya Edgard , Morgans Ryland , Moreira Alexandre , Okano Alexandre Hideki
Published: September 2022

Differentiated brain activation in high-performance athletes supports neuronal mechanisms relevant to sports performance. Preparation for the motor action involves cortical and sub-cortical regions that can be non-invasively modulated by electrical current stimulation. This study aimed to investigate the effect of high-definition transcranial direct current stimulation (HD-tDCS) on electrical brain activity in professional female basketball players during free-throw shooting. Successful free-throw shooting (n = 2,361) from seven professional female basketball players was analyzed during two experimental conditions (HD-tDCS cathodic and sham) separated by 72 h. Three spectral bio-markers, Power Ratio Index (PRI), Delta Alpha Ratio (DAR), and Theta Beta Ratio (TBR) were measured (electroencephalography [EEG] Brain Products). Multi-channel HD-tDCS was applied for 20 min, considering current location and intensity for cathodic stimulation: FCC1h, AFF5h, AFF1h (−0.5 mA each), and FCC5h (ground). The within EEG analyses (pre and post HD-tDCS) of frontal channels (Fp1, Fp2, F3, F4, FC1, FC3) for 1 second epoch pre-shooting, showed increases in PRI (p < 0.001) and DAR (p < 0.001) for HD-tDCS cathodic condition, and in TBR for both conditions (cathodic, p = 0.01; sham, p = 0.002). Sub-group analysis divided the sample into less (n = 3; LSG) and more (n = 4; MSG) stable free-throw-shooting performers and revealed that increases in pre to post HD-tDCS in PRI only occurred for the LSG. These results suggest that the effect of HD-tDCS may induce changes in slow frontal frequency brain activities and that this alteration seems to be greater for players demonstrating a less stable free-throw shooting performance.
Effects of different proteins and maltodextrin combinations as wall material on the characteristics of Cornus officinalis flavonoids microcapsules
Authors: Zhao Mengyue , Cao Weiwei , Li Linlin , Ren Aiqing , Ang Yuan , Chen Junliang , Bhandari Bhesh , Wang Zhe , Ren Xing , Ren Guangyue , Duan Xu
Published: September 2022

The flavonoids in Cornus officinalis (CO) have various pharmacological activities, however, the flavonoid instability limits its application in food and pharmaceutical industries. In this study, Cornus officinalis flavonoid (COF) microcapsules were prepared by using a combination of whey isolate protein (WPI), soy isolate protein (SPI), gelatin (GE), and maltodextrin (MD) as wall materials, respectively. Meanwhile, the encapsulation efficiency, solubility, color, particle size, thermal stability and microstructure as well as the antioxidant capacity of microcapsules were assessed. When the protein/MD ratio was 3:7, three kinds of combined wall materials realized high encapsulation efficiency (96.32–98.24%) and water solubility index (89.20–90.10%). Compared with other wall material combinations, the microcapsules with WPI-MD wall ratio at 3:7 had lower particle size (7.17 μm), lower moisture content (6.13%), higher encapsulation efficiency (98.24%), better water solubility index (90.1%), higher thermal stability (86.00°C), brightness L* (67.84) and higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging capacity (6.98 mgVc/g), and better flowability. Results suggested that WPI and MD could be better wall materials applied in encapsulating COF.
Clinical review of alkalization therapy in cancer treatment
Authors: Hamaguchi Reo , Isowa Masahide , Narui Ryoko , Morikawa Hiromasa , Wada Hiromi
Published: September 2022

One of the most unique characteristics of cancer metabolism is activated aerobic glycolysis, which is called the “Warburg effect”, and is a hallmark of cancer. An acidic tumor microenvironment (TME) resulting from activated anaerobic glycolysis is associated with cancer progression, multi-drug resistance, and immune escape. Several in vitro and in vivo studies reported that neutralization of the acidic TME by alkalizing agents, such as bicarbonate, resulted in the suppression of cancer progression and a potential benefit for anti-cancer drug responses. In clinical settings, alkalizing effects were achieved not only by alkalizing agents, but also by a following a particular diet. An epidemiological study demonstrated that more fruits and vegetables and less meat and dairy products are associated with an increase in urine pH, which may reflect the alkalizing effect on the body. However, it remains unclear whether alkaline dietary intervention improves the effects of cancer treatment. Moreover, there are few clinical reports to date regarding cancer treatments being performed on patients together with alkalization therapy. In this review, we investigated whether alkalization therapy, which includes an alkaline diet and/or alkalizing agents, improves cancer treatment.
No survival benefit could be obtained from adjuvant radiotherapy in esophageal cancer treated with neoadjuvant chemotherapy followed by surgery: A SEER-based analysis
Authors: Zheng Si-Yue , Qi Wei-Xiang , Zhao Sheng-Guang , Chen Jia-Yi
Published: September 2022

Background

The aim of this study is to assess the clinical benefit of postoperative radiotherapy (PORT) in patients with esophageal cancer (EC) who treated with neoadjuvant chemotherapy (NAC) and surgery via a national population-based database.

Methods

Patients diagnosed with EC between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival analysis was used to compare the overall survival (OS) and cause-specific survival (CSS) difference between PORT vs. no-radiotherapy (RT) groups before and after propensity score matching (PSM). After PSM for baseline characteristics, Cox proportional hazard regression was performed to investigate the factors associated with OS.

Results

A total of 321 patients were included in the analysis. Of them, 91 patients (28%) received PORT. In the unmatched population, the no-RT group had improved OS compared with PORT (44 vs. 25 months, p = 0.002), and CSS was similar in patients undergoing NAC with or without PORT (42 vs. 71 months, p = 0.17). After PSM for baseline characteristics, the OS benefit of the no-RT group over the PORT group remained significant with a median OS of 46 vs. 27 months (p = 0.02), and CSS remained comparable between groups (83 vs. 81 months, p = 0.49). In subgroup analyses, PORT did not improve the OS among patients with adenocarcinoma in the subgroups of cN0, cN1, and cN2–3 (all p > 0.05). In Cox regression, aged ≥71 years old, cT3–4, cN2–3, and receiving PORT were independent predictors of worse OS, whereas cT4 and cN2–3 were independent predictors of worse CSS (all p < 0.05).

Conclusions

The present study demonstrated that no survival benefit could be obtained from the additional use of PORT after NAC and surgery in patients with EC. Well-designed prospective trials are needed to confirm our findings.
DLC1 inhibits colon adenocarcinoma cell migration by promoting secretion of the neurotrophic factor MANF
Authors: Chu Yi-Min , Xu Ying , Zou Xiu-Qun , Zhou Feng-Li , Deng Yu-Liang , Han Yu-Tong , Li Ji , Yang Da-Ming , Peng Hai-Xia
Published: September 2022

DLC1 (deleted in liver cancer-1) is downregulated or deleted in colorectal cancer (CRC) tissues and functions as a potent tumor suppressor, but the underlying molecular mechanism remains elusive. We found that the conditioned medium (CM) collected from DLC1-overexpressed SW1116 cells inhibited the migration of colon adenocarcinoma cells HCT116 and SW1116, but had no effect on proliferation, which suggested DLC1-mediated secretory components containing a specific inhibitor for colon adenocarcinoma cell migration. Analysis by mass spectrometry identified mesencephalic astrocyte-derived neurotrophic factor (MANF) as a candidate. More importantly, exogenous MANF significantly inhibited the migration of colon adenocarcinoma cells HCT116 and SW1116, but did not affect proliferation. Mechanistically, DLC1 reduced the retention of MANF in ER by competing the interaction between MANF and GRP78. Taken together, these data provided new insights into the suppressive effects of DLC1 on CRC, and revealed the potential of MANF in the treatment of CRC.
Integrated TCR repertoire analysis and single-cell transcriptomic profiling of tumor-infiltrating T cells in renal cell carcinoma identifies shared and tumor-restricted expanded clones with unique phenotypes
Authors: Xu Yuexin , Morales Alicia J. , Towlerton Andrea M. H. , Akilesh Shreeram , Miller Chris P. , Tykodi Scott S. , Warren Edus H.
Published: September 2022

Objective responses of metastatic renal cell carcinoma (RCC) associated with systemic immunotherapies suggest the potential for T-cell-mediated tumor clearance. Recent analyses associate clonally expanded T cells present in the tumor at diagnosis with responses to immune checkpoint inhibitors (ICIs). To identify and further characterize tumor-associated, clonally expanded T cells, we characterized the density, spatial distribution, T-cell receptor (TCR) repertoire, and transcriptome of tumor-infiltrating T cells from 14 renal tumors at the time of resection and compared them with T cells in peripheral blood and normal adjacent kidney. Multiplex immunohistochemistry revealed that T-cell density was higher in clear cell RCC (ccRCC) than in other renal tumor histologies with spatially nonuniform T-cell hotspots and exclusion zones. TCR repertoire analysis also revealed increased clonal expansion in ccRCC tumors compared with non-clear cell histologies or normal tissues. Expanded T-cell clones were most frequently CD8+ with some detectable in peripheral blood or normal kidney and others found exclusively within the tumor. Divergent expression profiles for chemokine receptors and ligands and the Ki67 proliferation marker distinguished tumor-restricted T-cell clones from those also present in blood suggesting a distinct phenotype for subsets of clonally expanded T cells that also differed for upregulated markers of T-cell activation and exhaustion. Thus, our single-cell level stratification of clonally expanded tumor infiltrating T-cell subpopulations provides a framework for further analysis. Future studies will address the spatial orientation of these clonal subsets within tumors and their association with treatment outcomes for ICIs or other therapeutic modalities.
Establishment of lactate-metabolism-related signature to predict prognosis and immunotherapy response in patients with colon adenocarcinoma
Authors: Zou Zhengrong , Chai Yongjie , Li Qi , Lin Xuan , He Qingfang , Xiong Qiusheng
Published: September 2022

The outcome of colon adenocarcinoma (COAD) patients remains dismal, and lactate metabolism has been characterized to promote tumor development and immune evasion. Based on the above background, it is worthwhile to explore novel prognostic and therapeutic biomarkers for COAD patients from the aspect of lactate metabolism. Above all, 228 available lactate-metabolism-related genes (LMRGs) were acquired, and the landscape of copy number variation and the expression difference of mRNA levels between colon normal and tumor samples were investigated among these LMRGs. Importantly, eight overall survival (OS)-involved LMRGs were then distinguished by means of univariate Cox regression analysis in both GSE40967 and TCGA-COAD data sets. Subsequently, prognostic risk scores were established, integrating seven OS-related LMRGs by LASSO Cox regression analysis in the GSE40967 set, and then verified in the TCGA-COAD cohort. From the comprehensive analyses, COAD patients with high risk had comparatively more inferior survival probability in all populations of the study, and they tended to have more severe clinicopathological features with the risk score increasing. Moreover, by integrating age, AJCC T and pathological stage, and risk score, we constructed a prognostic nomogram that demonstrated great prediction effectiveness for OS of COAD patients. Furthermore, the potential effect of various risk score on tumor immune was assessed from enrichment of immune-related pathways, tumor-infiltrating immune cells, and expression levels of immune checkpoints separately. We could draw a conclusion that COAD patients with higher lactate-metabolism-related risk scores may acquire an immunosuppressive tumor microenvironment, which subsequently led to immune escapes and poor prognoses. Conclusively, all findings in the present study illustrate a great prognostic value of the lactate-metabolism-related risk signature, providing more in-depth insights into the indispensable function of lactate metabolism in prognosis and tumor immunity of COAD.
Multifunctionality of Calebin A in inflammation, chronic diseases and cancer
Authors: Brockmueller Aranka , Mueller Anna-Lena , Kunnumakkara Ajaikumar B. , Aggarwal Bharat B. , Shakibaei Mehdi
Published: September 2022

Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge worldwide, because of their complexity and many inflammatory pathways such as JNK, p38/MAPK, MEK/ERK, JAK/STAT3, PI3K and NF-κB among others being implicated in their pathogenesis. Together with the versatility of chronic disease classical mono-target therapies are often insufficient. Therefore, the anti-inflammatory as well as anti-cancer capacities of polyphenols are currently investigated to complement and improve the effect of classical anti-inflammatory drugs, chemotherapeutic agents or to overcome drug resistance of cancer cells. Currently, research on Calebin A, a polyphenolic component of turmeric (Curcuma longa), is becoming of growing interest with regard to novel treatment strategies and has already been shown health-promoting as well as anti-tumor properties, including anti-oxidative and anti-inflammatory effects, in diverse cancer cells. Within this review, we describe already known anti-inflammatory activities of Calebin Aviamodulation of NF-κB and its associated signaling pathways, linked with TNF-α, TNF-β and COX-2 and further summarize Calebin A’s tumor-inhibiting properties that are known up to date such as reduction of cancer cell viability, proliferation as well as metastasis. We also shed light on possible future prospects of Calebin A as an anti-cancer agent.
Primary squamous cell carcinoma of the ovary. Review of the literature
Authors: Luo Yan , Bian Ce
Published: September 2022

Pure primary ovarian squamous cell carcinoma (oSCC) is very rare, with about 42 cases have been reported in the literature. Lacking effective treatment guidelines, the prognosis of oSCC is extremely poor. Here, we report a 52-year-old postmenopausal woman diagnosed with pure primary oSCC in our center. The patient received debulking surgery followed by chemotherapy with carboplatin, paclitaxel, and bevacizumab. The patient survived 11 months after surgery and died of tumor progression and multiple organ failure. We also present a review of the literature.
The role transition of radiotherapy for the treatment of liver cancer in the COVID-19 era
Authors: Li Zheng , Hu Yue , Zeng Ming , Hu Qinyong , Ye Fei , Liu Ruifeng , Cai Hongyi , Li Qiang , Wang Xiaohu
Published: September 2022

The uncontrollable COVID-19 crises in the SARS-CoV-2 high-prevalence areas have greatly disrupted the routine treatment of liver cancer and triggered a role transformation of radiotherapy for liver cancer. The weight of radiotherapy in the treatment algorithm for liver cancer has been enlarged by the COVID-19 pandemic, which is helpful for the optimal risk-benefit profile.
Drug-induced liver injury associated with dacomitinib: A case report
Authors: Wang Xuanxuan , Huang Anqi , Lu Yun , Gao Suyu , Hu Wen , Cheng Hong
Published: September 2022

Dacomitinib, the second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been used as a first-line treatment in non-small cell lung cancer (NSCLC) patients harboring EGFR mutation. In this case, we report a patient with drug-induced liver injury (DILI) associated with the use of dacomitinib. A 59-year-old man with stage IV NSCLC was prescribed with dacomitinib; 37 days after dacomitinib administration, he was admitted to our hospital because of jaundice. Laboratory examinations revealed elevated serum levels of liver enzymes and bilirubin. Following the immediate discontinuation of dacomitinib, liver enzymes decreased but bilirubin continued to rise. Total bilirubin reached the peak (18-fold) on day 26 after dacomitinib termination and normalized on day 146 after dacomitinib discontinuation. A “probable” cause of DILI by dacomitinib was determined based on the Roussel Uclaf Causality Assessment Method. The severity of DILI was assessed as acute liver failure. To our knowledge, this is the first case of DILI caused by dacomitinib monotherapy in a real-world setting. Clinicians should pay particular attention to the possibility of DILI during dacomitinib treatment.
The role and application of small extracellular vesicles in breast cancer
Authors: Yi Xiaomei , Huang Defa , Li Zhengzhe , Wang Xiaoxing , Yang Tong , Zhao Minghong , Wu Jiyang , Zhong Tianyu
Published: September 2022

Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related deaths in women worldwide. Currently, patients’ survival remains a challenge in BC due to the lack of effective targeted therapies and the difficult condition of patients with higher aggressiveness, metastasis and drug resistance. Small extracellular vesicles (sEVs), which are nanoscale vesicles with lipid bilayer envelopes released by various cell types in physiological and pathological conditions, play an important role in biological information transfer between cells. There is growing evidence that BC cell-derived sEVs may contribute to the establishment of a favorable microenvironment that supports cancer cells proliferation, invasion and metastasis. Moreover, sEVs provide a versatile platform not only for the diagnosis but also as a delivery vehicle for drugs. This review provides an overview of current new developments regarding the involvement of sEVs in BC pathogenesis, including tumor proliferation, invasion, metastasis, immune evasion, and drug resistance. In addition, sEVs act as messenger carriers carrying a variety of biomolecules such as proteins, nucleic acids, lipids and metabolites, making them as potential liquid biopsy biomarkers for BC diagnosis and prognosis. We also described the clinical applications of BC derived sEVs associated MiRs in the diagnosis and treatment of BC along with ongoing clinical trials which will assist future scientific endeavors in a more organized direction.
Absence of high-grade cervical intraepithelial neoplasia in conization specimens from patients with colposcopic biopsy-confirmed high-grade cervical intraepithelial neoplasia: Retrospective study of 1695 cases
Authors: Guo Yulin , Wang Ying , Peng Qiuzi , Li Lu , Zou Miao , Wang Chaonan , Wu Xufeng , Ma Quanfu
Published: September 2022

Few studies have investigated the absence of high-grade cervical intraepithelial neoplasia (CIN) in excised specimens, and sample sizes of these studies were limited. This study retrospectively analyzed clinical characteristics of 1695 patients with CIN 2/3 to determine the incidence rate and relative factors of CIN 1 or less in conization specimens from patients with colposcopic biopsy-confirmed CIN 2/3. The study group comprised 430 cases of CIN 1 or less in conization specimens, and the control group comprised 1142 cases with high-grade CIN lesions in conization specimens. Univariate and multivariate logistic regression models were established to evaluate relative factors. The 1–9 years follow-up data were analyzed to determine the persistence/recurrence rate. Multivariate logistic regression showed that patients aged 18–24 years (OR (95% CI) = 2.224 (1.014, 4.877)); with a negative hrHPV test result (OR (95% CI) = 3.210 (1.627, 6.331)); a cytology test result of normal (OR (95% CI) = 5.184 (3.138, 8.563)), ASC-US (OR (95% CI) = 3.420 (2.102, 5.564)), LSIL (OR (95% CI) = 2.588 (1.475, 4.541)), or ASC-H (OR (95% CI) = 2.434 (1.306, 4.539)); an indication of CIN 2 on biopsy (OR (95% CI) = 2.290 (1.694, 3.096)), and no glandular involvement (OR (95% CI) = 1.616 (1.205, 2.169)) were more likely to have an absence of high-grade dysplasia in conization specimens. There was no difference in the persistence/recurrence rate between the two groups (x2 = 1.55, P = 0.46). An age of 18–24 years, a negative hrHPV test result, a non-HSIL cytology test result, an indication of CIN 2 on biopsy, and no glandular involvement were relative factors for an absence of high-grade dysplasia in conization specimens. For patients with relative factors, especially young women, informed follow-up should be considered.
Monte Carlo simulation of physical dose enhancement in core-shell magnetic gold nanoparticles with TOPAS
Authors: Xu Xiaohan , Wu Jianan , Dai Zhitao , Hu Rui , Xie Yaoqin , Wang Luhua
Published: September 2022

The application of metal nanoparticles (MNPs) as sensitization materials is a common strategy that is used to study dose enhancement in radiotherapy. Recent in vitro tests have revealed that magnetic gold nanoparticles (NPs) can be used in cancer therapy under a magnetic field to enhance the synergistic efficiency in radiotherapy and photothermal therapy. However, magnetic gold NPs have rarely been studied as sensitization materials. In this study, we obtained further results of the sensitization properties of the magnetic gold NPs (Fe3O4@AuNPs) with or without magnetic field using the TOPAS-nBio Monte Carlo (MC) toolkit. We analyzed the properties of Fe3O4@AuNP in a single NP model and in a cell model under monoenergetic photons and brachytherapy, and we investigated whether the magnetic field contributes to the physical sensitization process. Our results revealed that the dose enhancement factor (DEF) of Fe3O4@AuNPs was lower than that of gold nanoparticles (AuNPs) in a single NP and in a cell irradiated by monoenergetic photons. But it’s worth mentioning that under a magnetic field, the DEF of targeted Fe3O4@AuNPs in a cell model with a clinical brachytherapy source was 22.17% (cytoplasm) and 6.89% (nucleus) higher than those of AuNPs (50 mg/mL). The Fe3O4@AuNPs were proved as an effective sensitization materials when combined with the magnetic field in MC simulation for the first time, which contributes to the research on in vitro tests on radiosensitization as well as clinical research in future.
The efficacy and safety of 125I brachytherapy combined with pre-operative transarterial chemoembolization in patients with locally advanced head and neck cancer
Authors: Zhang Menglong , Zhang Jian , Hu Bijuan , Huang Liyin , Song Shanjun , Zhu Haitao , Chen Chao , Chu Cunkun
Published: September 2022

Objective

To evaluate the safety and effectiveness of Iodine-125 (125I) brachytherapy combined with pre-operative transarterial chemoembolization in patients with locally advanced head and neck cancer.

Methods

In this study, a total of thirty-seven individuals suffering from locally advanced head and neck cancer were involved. The patients were subjected to transarterial chemoembolization as well as implantation of 125I seeds under the guidance of CT and ultrasonography. Follow-up was conducted for 36 months to study the following parameters: the local control rate, survival rate, and clinical complications.

Results

In total, thirty-six patients at the end of three months showed an objective response rate of 69.8% and disease control rate of 93.0%, respectively. The 1, 2, and 3-year cumulative overall survival rate was 89.2%, 73.0%, and 45.9%, respectively. The adverse events of the treatment included infection (n=1, Grade III), radiation brachial plexus injury (n=1, Grade III), leukopenia (n=1, Grade III), cerebrovascular embolism (n=1, Grade IV).

Conclusion

The combination of 125I brachytherapy and pre-operative transarterial chemoembolization was safe and effective in patients with locally advanced head and neck cancer.
Multiple rectal neuroendocrine tumors: An analysis of 15 cases and literature review
Authors: Pang Shu , Zong Ye , Zhang Kun , Zhao Haiying , Wang Yongjun , Wang Junxiong , Liu Chuntao , Wu Yongdong , Li Peng
Published: September 2022

Multiple neuroendocrine tumors (M-NETs) are rare in the rectum and there is no consensus on their characteristics and treatments. Here, we report 15 cases of rectal M-NETs and review the previous literature. We discuss the clinical characteristics, endoscopic features and pathological features of rectal M-NETs, aiming to analyze the treatments and follow-up strategies in combination with these characteristics. We retrospectively reviewed and analyzed the data of 15 patients with rectal M-NETs who were diagnosed and treated at Beijing Friendship Hospital, Capital Medical University. Their clinical data, endoscopic findings, pathological features and treatments were analyzed. Follow-up evaluations and literature review were performed. In all, 14 male (93.3%) and 1 female (6.7%) were recruited. The average age at diagnosis was 55.7 years. The clinical manifestations include asymptomatic in 9 patients (60.0%), defecation habits changes in 2 patients (13.3%), anal distension in 2 patients (13.3%), and abdominal distension in 2 patient (13.3%). The largest tumor diameter ≤10mm was found in 13 patients (86.7%) and >10mm in 2 patients (13.3%). All of the lesions originated from the mucous or submucosa layer. WHO grades were all NET G1. The number of tumors diagnosed by pathology in 13 patients was consistent with that observed by endoscopy, while more lesions were observed by pathology than endoscopy in two patients. Lymph node metastasis occurred in 1 patient (6.7%), and vascular or lymphatic invasion occurred in 9 patients (60.0%). Among the 13 patients with the largest tumor diameter being ≤10mm, lymphovascular invasion occurred in 8 patients (61.5%). And among the 2 patients with the largest tumor diameter of >10mm, lymphovascular invasion occurred in 1 patient (50.0%). 14 patients underwent endoscopic resection and 1 underwent surgical excision. Postoperative follow-up was achieved in 13 patients and no recurrence or metastasis was found. The true number of rectal M-NETs may be more than seen under endoscopy. Rectal M-NETs is associated with a high risk of metastasis; therefore, treatment and surveillance strategies should be more radical than single lesion.
FAIM2 is a potential pan-cancer biomarker for prognosis and immune infiltration
Authors: Cai Jiayang , Ye Zhang , Hu Yuanyuan , Wang Yixuan , Ye Liguo , Gao Lun , sun Qian , Tong Shiao , Sun Zhiqiang , Yang Ji'an , Chen Qianxue
Published: September 2022

Fas apoptosis inhibitory molecule 2 (FAIM2) is an important member of the transmembrane BAX inhibitor motif containing (TMBIM) family. However, the role of FAIM2 in tumor prognosis and immune infiltration has rarely been studied. Here, we conducted a pan-cancer analysis to explore the role of FAIM2 in various tumors and further verified the results in glioma through molecular biology experiment. FAIM2 expression and clinical stages in tumor samples and para-cancerous samples were analyzed by TIMER2 database, GEPIA database, and the TISIDB database. The role of FAIM2 on prognosis was analyzed via GEPIA2. We utilized the ESTIMATE algorithm to evaluate the ImmuneScore and StromalScore of various tumors. In addition, we explored the correlation between FAIM2 expression and tumor immune cell infiltration by the TIMER2 database. The immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methylation related to FAIM2 were analyzed based on the TCGA database. The correlation between FAIM2 expression with Copy number variations (CNV) and methylation is explored by GSCA database. Protein-Protein Interaction (PPI) analysis was obtained from the STRING database and the CellMiner database was used to explore the association between FAIM2 expression and drug response. FAIM2 co-expression genes were studied by the LinkedOmics database. Immunohistochemistry, Western Blotting Analysis, Cell Viability Assay, Colony Formation Assay, and Edu staining assay were used in the molecular biology experiments section. The FAIM2 expression was down-regulated in most tumors and highly expressed FAIM2 was associated with a better prognosis in several cancers. FAIM2 plays an essential role in the tumor microenvironment and is closely associated with immune Infiltration in various tumors. The expression of FAIM2 was closely correlated to TMB, MSI, MMR, CNV, and DNA methylation. Furthermore, FAIM2 related genes in the PPI network and its co-expression genes in glioma are involved in a large number of immune-related pathways. Molecular biology experiments verified a cancer suppressor role for FAIM2 in glioma. FAIM2 may serve as a potential pan-cancer biomarker for prognosis and immune infiltration, especially in glioma. Moreover, this study might provide a potential target for tumor immunotherapy.
Prediction for late-onset sepsis in preterm infants based on data from East China
Authors: Shuai Xianghua , Li Xiaoxia , Wu Yiling
Published: September 2022

Aim

To construct a prediction model based on the data of premature infants and to apply the data in our study as external validation to the prediction model proposed by Yuejun Huang et al. to evaluate the predictive ability of both models.

Methods

In total, 397 premature infants were randomly divided into the training set (n = 278) and the testing set (n = 119). Univariate and multivariate logistic analyses were applied to identify potential predictors, and the prediction model was constructed based on the predictors. The area under the curve (AUC) value, the receiver operator characteristic (ROC) curves, and the calibration curves were used to evaluate the predictive performances of prediction models. The data in our study were used in the prediction model proposed by Yuejun Huang et al. as external validation.

Results

In the current study, endotracheal intubation [odds ratio (OR) = 10.553, 95% confidence interval (CI): 4.959–22.458], mechanical ventilation (OR = 10.243, 95% CI: 4.811–21.806), asphyxia (OR = 2.614, 95% CI: 1.536–4.447), and antibiotics use (OR = 3.362, 95% CI: 1.454–7.775) were risk factors for late-onset sepsis in preterm infants. The higher birth weight of infants (OR = 0.312, 95% CI: 0.165–0.588) and gestational age were protective factors for late-onset sepsis in preterm infants. The training set was applied for the construction of the models, and the testing set was used to test the diagnostic efficiency of the model. The AUC values of the prediction model were 0.760 in the training set and 0.796 in the testing set.

Conclusion

The prediction model showed a good predictive ability for late-onset sepsis in preterm infants.
Case report: Clinical manifestations and genotype analysis of a child with PTPN11 and SEC24D mutations
Authors: Miao Yuqi , Chen Jiahui , Guo Xiaoya , Wei Yu , Wu Xiaozhi , Sang Yanmei , Wu Di
Published: September 2022

Background

The PTPN11 gene, located at 12q24. 13, encodes protein tyrosine phosphatase 2C. Mutations in the PTPN11 gene can lead to various phenotypes, including Noonan syndrome and LEOPARD syndrome. The SEC24D gene is located at 4q26 and encodes a component of the COPII complex, and is closely related to endoplasmic reticulum protein transport. Mutations in SEC24D can lead to Cole-Carpenter syndrome-2. To date, dual mutations in these two genes have not been reported in the literature.

Methods

We report a patient with short stature and osteogenesis imperfecta as the primary clinical manifestation. Other clinical features were peculiar facial features, deafness, and a history of recurrent fractures. Whole exome sequencing was performed on this patient.

Results

After whole-exome sequencing, three mutations in two genes were identified that induced protein alterations associated with the patient's phenotype. One was a de novo variant c.1403C>T (p.Thr468Met) on exon 12 of the PTPN11 gene, and the other was a compound heterozygous mutation in the SEC24D gene, a novel variant c.2609_2610delGA (p.Arg870Thrfs*10) on exon 20 and a reported variant c.938G>A (p.Arg313His) on exon 8.

Conclusions

Concurrent mutations in PTPN11 and SEC24D induced a phenotype that was significantly different from individual mutations in either PTPN11 or SEC24D gene. Personalized genetic analysis and interpretation could help us understand the patient's etiology and hence develop treatments and improve the prognosis of these patients.
Tetracycline-grafted mPEG-PLGA micelles for bone-targeting and osteoporotic improvement
Authors: Que Yunduan , Yang Yuhang , Zafar Hajra , Wang Dongming
Published: September 2022

Aim: We aimed to create a nano drug delivery system with tetracycline (TC)-grafted methoxy poly-(ethylene-glycol)‒poly-(D, L-lactic-co-glycolic acid) (mPEG‒PLGA) micelles (TC‒mPEG‒PLGA) with TC and mPEG‒PLGA for potential bone targeting. Prospectively, TC‒mPEG‒PLGA aims to deliver bioactive compounds, such as astragaloside IV (AS), for osteoporotic therapy.

Methods: Preparation and evaluation of TC‒mPEG‒PLGA were accomplished via nano-properties, cytotoxicity, uptake by MC3T3-E1 cells, ability of hydroxyapatite targeting and potential bone targeting in vivo, as well as pharmacodynamics in a rat model.

Results: The measured particle size of AS-loaded TC‒mPEG‒PLGA micelles was an average of 52.16 ± 2.44 nm, which exhibited a sustained release effect compared to that by free AS. The TC‒mPEG‒PLGA demonstrated low cytotoxicity and was easily taken by MC3T3-E1 cells. Through assaying of bone targeting in vitro and in vivo, we observed that TC‒mPEG‒PLGA could effectively increase AS accumulation in bone. A pharmacodynamics study in mice suggested potentially increased bone mineral density by AS-loaded TC‒mPEG‒PLGA in ovariectomized rats compared to that by free AS.

Conclusion: The nano drug delivery system (TC‒mPEG‒PLGA) could target bone in vitro and in vivo, wherein it may be used as a novel delivery method for the enhancement of therapeutic effects of drugs with osteoporotic activity.
Metformin modulates the gut microbiome in broiler breeder hens
Authors: Van Syoc Emily , Weaver Evelyn , Rogers Connie J. , Silverman Justin D. , Ramachandran Ramesh , Ganda Erika
Published: September 2022

Broiler breeder hens, the parent stock of commercial broiler chickens, are genetically selected for rapid growth. Due to a longer production period and the focus of genetic selection on superior carcass traits in their progeny, these hens have the propensity to gain excess adipose tissue and exhibit severe ovarian dysfunction, a phenotype that is similar to human polycystic ovary syndrome (PCOS). Metformin is an antihyperglycemic drug approved for type 2 diabetes that is prescribed off-label for PCOS with benefits on metabolic and reproductive health. An additional effect of metformin treatments in humans is modulation of gut microbiome composition, hypothesized to benefit glucose sensitivity and systemic inflammation. The effects of dietary metformin supplementation in broiler breeder hens have not been investigated, thus we hypothesized that dietary metformin supplementation would alter the gut microbiome of broiler breeder hens. Broiler breeder hens were supplemented with metformin at four different levels (0, 25, 50, and 75 mg/kg body weight) from 25 to 65 weeks of age, and a subset of hens (n = 8–10 per treatment group) was randomly selected to undergo longitudinal microbiome profiling with 16S rRNA sequencing. Metformin impacted the microbial community composition in 75 mg/kg metformin compared to controls (adjusted PERMANOVA p = 0.0006) and an additional dose-dependent difference was observed between 25 mg/kg and 75 mg/kg (adjusted PERMANOVA p = 0.001) and between 50 mg/kg and 75 mg/kg (adjusted PERMANOVA p = 0.001) but not between 25 mg/kg and 50 mg/kg (adjusted PERMANOVA p = 0.863). There were few differences in the microbiome attributed to hen age, and metformin supplementation did not alter alpha diversity. Bacteria that were identified as differentially relatively abundant between 75 mg/kg metformin treatment and the control, and between metformin doses, included Ruminococcus and members of the Clostridia family that have been previously identified in human trials of PCOS. These results demonstrate that metformin impacts the microbiome of broiler breeder hens in a dose-dependent manner and several findings were consistent with PCOS in humans and with metformin treatment in type 2 diabetes. Metformin supplementation is a potentially promising option to improve gut health and reproductive efficiency in broiler breeder hens.