bluuebunny/crossref_metadata_2025 huggingface dataset:
A qPCR-Based Method for Quantification of RCA Contaminants in Oncolytic Adenovirus Products
Authors: Gao Menghan , Yngve Erik , Yu Di , Jin Chuan
Published: May 2022

Oncolytic adenovirus is one of the most promising treatments against cancer and is widely evaluated clinically. During high titer production, “Wild-type-” like replication-competent adenovirus (RCA) contaminants can be generated through recombination events due to the DNA sequence similarity between oncolytic virus and host cells. These RCA contaminants raise various safety concerns in clinics. Cell culture-based methods have been developed to detect RCA contaminants in replication-deficient adenovirus vectors. These methods were based on that only RCA contaminants, but not the vectors, are able to grow in and lyse the test cell line. However, these methods are not suitable for distinguishing RCA contaminants from the oncolytic adenovirus products because both can replicate in test cell lines. Herein, we reported a qPCR-based method to quantify RCA contaminants quickly and reliably in E1B-deleted oncolytic adenovirus products. This method is based on specific detection of the E1B gene, which can be acquired during production via recombination events between viral and host cell DNA. The assay is sensitive with the limit of detection at 10 VP of the RCA contaminants and the limit of quantification at 75 VP of the RCA contaminants in each 40 µL qPCR reaction. We have also validated the method on virus batches produced in the non-GMP and GMP conditions. Our results showed that this qPCR-based method was reliable and robust for detecting and quantifying RCA contaminants in oncolytic adenovirus products. The method may also be adapted for other oncolytic adenoviruses products by switching primer sets.
Does Cognitive Training Improve Mobility, Enhance Cognition, and Promote Neural Activation?
Authors: Marusic Uros , Verghese Joe , Mahoney Jeannette R.
Published: May 2022

A close inter-relationship between mobility and cognition is reported in older adults, with improvements in gait performance noticeable after cognitive remediation in frail individuals. The aim of this study was to evaluate the efficacy of computerized cognitive training (CCT) on mobility in healthy, independently living older adults, and to determine whether CCT is associated with changes in neural activation for mobility-related brain processes. Using a randomized single-blind control design, sixty-three non-demented adults age 60 y and older (mean age = 67 y; 76% female, mean Montreal Cognitive Assessment [MoCA] score = 27) were recruited from a local Senior Activity Center. Participants were randomly assigned to either a 2-month CCT program (8 weeks, 3x/week, 40 min/session) or a wait-list control group. Primary outcome was self-selected gait speed during single- and dual-task walking. Secondary outcome was executive function on Trail Making Test (TMT), Part B. Neural activity was assessed via electroencephalography/event-related potentials (EEG/ERPs) targeting lower-limb performance. Results from a linear mixed effect model, adjusted for baseline MoCA score, age, gender, and study completion revealed that compared to controls, CCT improved gait speed during the dual-task (p = 0.008) but not during the single-task walking condition (p = 0.057). CCT also improved executive function (p = 0.024). Further, shorter foot reaction time responses (p = 0.019) were found with enhanced neural activation over sensorimotor areas, with shorter ERP latencies during the P2 component (p = 0.008) and enhanced motor responses (p = 0.009) also evident in the CCT group after the intervention. Overall, the electrophysiological findings suggest possible neural adaptations that could explain improvements in mobility and executive functions associated with CCT in healthy older adults.
Influence of Hyperglycaemia and CRP on the Need for Mechanical Ventilation in Guillain-Barré Syndrome
Authors: Štětkářová Ivana , Ehler Edvard , Židó Michal , Lauer David , Polák Jan , Keller Jiří , Peisker Tomáš
Published: May 2022

Objectives

Elevated blood glucose and CRP (C-reactive protein) are usually related to a worsened clinical outcome in neurological diseases. This association in Guillain-Barré syndrome (GBS) has been studied rarely. We tried to analyse if hyperglycaemia and CRP at admission may influence the outcome of GBS, including mechanically ventilated (MV) patients.

Methods

We retrospectively studied 66 patients (40 males, 19–93 years, average 56 years) without diabetes mellitus and free of corticoid treatment, who fulfilled the clinical criteria for diagnosis of GBS. Hyperglycaemia (the level of fasting plasma glucose, FPG) was defined as blood glucose level >5.59 mmol/L according to our laboratory. CRP >5 mg/L was considered as an abnormally elevated value.

Results

At admission, 32 GBS patients (48%) had hyperglycaemia according to FPG level. A severe form of GBS (>4 according to Hughes GBS scale) was observed in 17 patients (26%); and 8 of them (47%) had hyperglycaemia. Fourteen patients (21%) were MV, and in 10 of them (71%) hyperglycaemia was present. CRP was significantly increased in MV patients. The linear model revealed a significant relationship between CRP and glycemia (p = 0.007) in subjects without MV (p = 0.049). In subjects with MV the relationship was not significant (p = 0.2162, NS).

Conclusion

In the acute phase of GBS at admission, hyperglycaemia and higher CRP occur relatively frequently, and may be a risk factor for the severity of GBS. Stress hyperglycaemia due to impaired glucose homeostasis could be one explanation for this condition.
Weight and Abdominal Pressure-Induced Shunt Trouble in Patients With Shunted Normal Pressure Hydrocephalus: A Comprehensive Study on Pressure Environment of Shunt System
Authors: Kamo Masatsugu , Kajimoto Yoshinaga , Ohmura Tomohisa , Kameda Masahiro , Tucker Adam , Miyake Hiroji , Wanibuchi Masahiko
Published: May 2022

Objectives

We identified a new type of shunt malfunction (SM) in patients with normal pressure hydrocephalus (NPH). It is induced by weight change and can be treated with valve readjustment. There were two types of SM as follows: Underdrainage induced by the weight gain and overdrainage induced by the weight loss. This study aims to elucidate this mechanism by assessing the shunt pressure environment.

Methods

The total pressure environment of the shunt system was prospectively studied in patients with shunted NPH at Osaka Medical College Hospital from 1999 to 2005. We measured the pressure environment during the initial pressure setting of the valve by the intracranial pressure (ICP) guide, after setting the valve, and when SM was suspected. We evaluated ICP, intra-abdominal pressure (IAP), and hydrostatic and perfusion pressures of the shunt system in the sitting and supine positions. The target ICP for valve setting was empirically set at the range from −8 to −13 mm Hg in the sitting position, referring to the external auditory meatus. During the study period, we identified five cases of SM induced by weight change and assessed the changes in the pressure environment across pre-SM, SM, and post-SM.

Results

In four cases of underdrainage, gait disturbance worsened with an average weight gain of 6.8 ± 1.2 kg. With weight gain, IAP and ICP increased by 8.8 ± 1.6 and 4.8 ± 1.0 mm Hg, respectively. Consequently, ICP increased to −6.5 ± 1.9 mm Hg. One overdrainage patient developed an asymptomatic chronic subdural hematoma (CSDH) with a weight loss of 10 kg. With the weight loss, both IAP and ICP decreased by 5 mm Hg, and concomitantly, ICP decreased to −18 mm Hg. In all patients, the valve readjustment restored their ICP to the target pressure. After the valve readjustment, the gait disturbance improved immediately, and the CSDH disappeared after 1 month.

Conclusion

In patients with shunts, the weight change was linked to ICP via IAP. Due to the weight change, the underdrainage occurred when ICP was above the target pressure, and the overdrainage occurred when ICP was below it. We named this SM as the weight and abdominal pressure-induced shunt trouble. The patients with SM along with weight changes should be the first to be tried for the valve readjustment.
Case Report: A Novel CACNA1A Mutation Caused Flunarizine-Responsive Type 2 Episodic Ataxia and Hemiplegic Migraine With Abnormal MRI of Cerebral White Matter
Authors: Yuan Xiaoqiu , Zheng Yiming , Gao Feng , Sun Wei , Wang Zhaoxia , Zhao Guiping
Published: May 2022

Episodic ataxia type 2 (EA2) is one autosomal-dominant neurological disorder characterized by debilitating attacks of ataxia. It is mainly caused by loss-of-function mutations of the CACNA1A gene, which encodes the pore-forming α1A subunit of Cav2.1 (P/Q type voltage-gated calcium channel). Sporadic hemiplegic migraine (SHM) is another rare disease involving CACNA1A variants, which seldom coexists with EA2. Here we report a novel pathogenic mutation in CACNA1A (c.3836dupA, exon 23, p.Y1279X) of a 16-year-old female, who complained about paroxysmal dizziness, headache, and unsteady gait. Her brain MRI revealed a slightly atrophic cerebellum and numerous asymptomatic hyperintense lesions of the cerebral white matter. The diagnosis of EA2 combined with SHM was made. Administration of 5-mg flunarizine once daily at night effectively reduced the attacks and attenuated her symptoms for a month.
Stakeholder Network Analysis for Front-of-Pack Labeling in China
Authors: Yin Xuejun , Ye Lihong , Xin Xin , Xiang Lin , Yu Yue , Yan Ruijie , Wen Kehan , Tian Maoyi , Jones Alexandra , Pettigrew Simone , Zhang Juan
Published: May 2022

Background

Front-of-pack (FoP) labeling on packaged foods is recommended by the World Health Organization (WHO) to reduce diet-related non-communicable diseases, but it has not yet been implemented in China. The introduction of FoP labeling is driven by multiple institutions and stakeholders. This study aimed to identify key institutional actors involved in FoP labeling and describe links between actors to support future FoP labeling policies and programmes in China.

Methods

The Net-Map method was adopted. We conducted Net-map activities with eight participants using face-to-face interviews between November 2020 and May 2021. Participants were asked to identify actors involved in the development and implementation of FoP labeling in China, describe networks among actors according to pre-defined link types (command, dissemination, funding, and technical assistance), and estimate influence of each actor within the FoP labeling landscape. Social network analysis measures of cohesion and centrality were used to describe each network. Gephi software was used for social network analysis and network visualization.

Results

Forty-one unique actors were identified across seven actor categories including government agencies (n = 14), technical support agencies (n = 7), professional associations (n = 10), food industry groups (n = 2), media groups (n = 4), international organizations (n = 3), and a consumer group (n = 1). Weighted influence scores among actors ranged from 0.13 to 3.13. The Department of Food Safety Standards, Risk Surveillance and Assessment of the National Health Commission (DFSSRSA of NHC) was the actor with the highest weighted influence score, followed by the Bureau of Disease Prevention and Control of National Health Commission, Chinese Nutrition Society, and the National Institute for Nutrition and Health of Chinese Center for Disease Control and Prevention. DFSSRSA of NHC played a central role in both command and technical assistance networks. State-owned media had the greatest betweenness and outdegree centrality in the dissemination network. The Chinese Nutrition Society was in the central position and provided funding to diverse actors in the funding network.

Conclusions

A variety of multisectoral actors have an interest in the introduction of FoP labeling policies and programmes. Effectively engaging key actors identified in this study can generate a multisectoral commitment to advance FoP labeling policies and programmes in China.
The Prognostic Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography-Based Analyses of Metabolic Response Rates in Newly Diagnosed Diffuse Large B Cell Lymphoma Patients
Authors: Li Cong , Yu Haifeng , Chen Xi , Han Shuiyun , Peng Shuailing , Lei Tao , Yang Haiyan
Published: May 2022

Background

Roughly one third of diffuse large B cell lymphoma (DLBCL) patients experience relapsed or refractory disease, and their prognosis is unsatisfactory. It is thus important to identify patients who respond poorly to first-line treatment. Some studies have evaluated the prognostic value of interim PET-CT (iPET-CT) or end-of-treatment PET-CT (ePET-CT) in lymphoma patients, but there have been few studies exploring the prognostic value of metabolic response rates in the evaluation of DLBCL patients.

Methods

Consecutive newly diagnosed DLBCL patients were screened from March 2013 to June 2020. Patients received at least four cycles of chemotherapy, and underwent baseline, iPET-CT and ePET-CT scanning. Kaplan-Meier survival curves with log-rank tests were employed to assess survival outcomes including overall survival (OS) and progression-free survival (PFS). Independent predictors of survival were identified through univariable and multivariable Cox regression analyses.

Results

307 patients were evaluated. At the time of iPET-CT scanning, 250, 45, and 12 patients exhibited complete response (CR), partial response (PR), and stable disease (SD)/progressive disease (PD), respectively. The percentage of negative iPET-CT was 81.4% (250/307). Among 295 patients with ePET-CT, 262 (88.8%) achieved negativity and 33 (11.2%) exhibited positivity including 26 PR and 7 PD. The 2-year PFS and 2-year OS for patients with iPET-CT positivity were 50.7% and 76.5%, respectively, and were significantly shorter than those for patients with iPET-CT negativity (2-year PFS 82.7%, p<0.001; 2-year OS 94.2%, p<0.001). Patients with ePET-CT positivity had significant poorer 2-year PFS (48.1%) and 2-year OS (78.5%) compared with those ePET-CT negativity (2-year PFS 83.8%, p<0.001; 2-year OS 94.9%, p<0.001). The positivity rates on iPET-CT and ePET-CT evaluation were significantly higher in patients in the high/high-intermediate risk group compared with patients in the low/low-intermediate group. In a multivariable analysis, high/high-intermediate international prognostic index (IPI) and ePET-CT positivity were independently associated with poor PFS and OS.

Conclusions

Our results suggest that the speed of metabolic response to treatment is of limited prognostic value in newly diagnosed DLBCL patients. Patients exhibiting PR at iPET-CT evaluation should carefully consider whether to change chemotherapy regimen.
Induction Chemotherapy Followed by Chemoradiotherapy With or Without Consolidation Chemotherapy Versus Chemoradiotherapy Followed by Consolidation Chemotherapy for Esophageal Squamous Cell Carcinoma
Authors: Xiang Mingyue , Liu Bo , Zhang Guifang , Gong Heyi , Han Dali , Ma Changsheng
Published: May 2022

Objective

This study aimed to compare the efficacy and safety of induction chemotherapy followed by concurrent chemoradiotherapy (I-CCRT), induction chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy (I-CCRT-C), and concurrent chemoradiotherapy followed by consolidation chemotherapy (CCRT-C) for locally advanced esophageal squamous cell carcinoma (ESSC).

Patients and Methods

Patients with locally advanced ESCC who underwent definitive chemoradiotherapy with cisplatin plus fluorouracil or docetaxel from February 2012 to December 2018 were retrospectively reviewed. Kaplan–Meier curve was used to estimate survival. Efficacy was assessed using RECIST, version 1.0. Prognosis factors were identified with Cox regression analysis.

Results

Patients were treated with CCRT-C (n = 59), I-CCRT (n = 20), and I-CCRT-C (n = 48). The median follow-up duration was 73.9 months for the entire cohort. The ORR of the CCRT-C, I-CCRT, and I-CCRT-C groups was 89.8%, 70.0%, and 77.1%, respectively (p = 0.078). The median PFS in the CCRT-C, I-CCRT, and I-CCRT-C groups was 32.5, 16.1, and 27.1 months, respectively (p = 0.464). The median OS of the CCRT-C, I-CCRT, and I-CCRT-C groups was 45.9, 35.5, and 54.0 months, respectively (p = 0.788). Cox regression analysis indicated that I-CCRT-C and I-CCRT did not significantly prolong PFS and OS compared with CCRT-C (p > 0.05). Neutropenia grade ≥3 in CCRT-C, I-CCRT, and I-CCRT-C groups was 47.5%, 15%, and 33.3% of patients, respectively (p = 0.027).

Conclusions

I-CCRT and I-CCRT-C using cisplatin plus fluorouracil or docetaxel regimen are not superior to CCRT-C in survival but seem to have less severe neutropenia than CCRT-C. Further randomized controlled studies are warranted.
Safety and Feasibility of Microwave Ablation for Hepatocellular Carcinomas in the Elderly: A Systematic Review
Authors: Liang Weiren , Hao Weiyuan , Shao Guoliang , Zheng Jiaping , Zeng Hui , Zhou Danping , Yao Hefeng
Published: May 2022

Background

Microwave ablation (MWA) for hepatocellular carcinomas (HCCs) in the elderly has been the subject of new research in recent years. However, there are currently no strong lines of evidence for the prognosis following MWA treatment for HCC in the elderly. Therefore, we conducted a systematic review to assess the safety and feasibility of MWA for HCC in elderly patients.

Methods

Up until August 15, 2021, a comprehensive literature search was undertaken in PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases for all published articles. Observational studies reporting the safety and feasibility of MWA for HCC in elderly patients were included. The Newcastle–Ottawa Scale (NOS) was used to measure the quality assessment.

Results

Our review, composed of 7 observational studies, including a total of 7,683 HCC patients, looked at the safety and feasibility of MWA for HCC in the elderly. Current lines of evidence on the risks and outcomes of MWA of HCC treatments in elderly patients are discussed.

Conclusions

According to our findings, elderly patients, even those with a high comorbidity index, benefited from MWA of HCC similar to younger patients. More clinical data are needed to determine selection criteria for elderly HCC patients to increase the possibility of receiving MWA as a potential lifesaving option. As such, further studies evaluating the outcomes of MWA for HCC treatment modalities in elderly patients are warranted.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021273091.
Tumor Microbiome in Nasopharyngeal Carcinoma and Its Association With Prognosis
Authors: Zhong Guihua , Wei Wei , Liao Wei , Wang Rong , Peng Yingpeng , Zhou Yuling , Huang Xiaotao , Xian Shiping , Peng Shunli , Zhang Zhaoyuan , Feng Shaoyan , Liu Ye , Hong Haiyu , Xia Yunfei , Yan Yan , Liu Qiaodan , Liu Zhigang
Published: May 2022

Introduction

Previous studies have reported a close relationship between cancer and microbes, particularly gut and tumor microbiota; however, the presence of tumor microbiome in nasopharyngeal carcinoma (NPC) and its role in the prognosis of NPC remain unclear.

Methods

We collected 64 samples including tissues from 50 patients with NPC (NPC group) and 14 patients with chronic nasopharyngitis (control group) receiver operating characteristics and we applied 16S ribosome RNA gene sequencing of all samples to assess microbiome profiles and immunohistochemistry to detect tumor microbiome in NPC.

Results

Patients in the control group harbored higher species diversity than those in the NPC group; however, the beta diversity was more distinct in the NPC group. In total, three genera with statistically significant differences between the two groups were identified. The area under the receiver operating characteristics (ROC) curve (AUC) was calculated using the relative abundance of these three significant genera, and a value of 0.842 was achieved. Furthermore, Turicibacter was confirmed as a potentially independent prognostic factor for NPC patients, and the progression-free survival (PFS) was markedly prolonged in patients with a low relative abundance of Turicibacter compared to patients with a high relative abundance of this genus (cutoff: 0.0046, hazard ratio: 5.10, 95% confidence interval: 2.04–12.77, p = 0.004).

Conclusions

The present study provided strong evidence of a correlation between tumor microbiome and NPC; the tumor microbiome may be considered a biomarker for early NPC diagnosis. Turicibacter potentially served as a independently prognostic indicator for NPC patients.
Galectin Family Members: Emerging Novel Targets for Lymphoma Therapy?
Authors: Shi Yuanwei , Tang Danting , Li Xiaoqi , Xie Xiaoli , Ye Yufu , Wang Lijuan
Published: May 2022

The galectin family of proteins has high affinity with β-galactoside-containing glycans. These proteins participate in cell growth and differentiation, cell adhesion, cell signal transduction, cell apoptosis, and other cellular activities. In recent years, a large number of studies have described the expression and correlation of galectins in different tumors. Each member of the family plays a vital role in tumor growth, progression, angiogenesis, adhesion, and tumor immune escape. Studies on the roles of galectins in lymphoma have mainly involved galectin-1, -3, -7, and -9. The results suggest that galectins may become novel targets for precise tumor treatment. This article reviews current research progress regarding galectins in lymphoma and provides new ideas for exploring them as novel targets for treating lymphoma and other important medical issues.
Ostomy Does Not Lead to Worse Outcomes After Bowel Resection With Ovarian Cancer: A Systematic Review
Authors: He Xinlin , Li Zhengyu
Published: May 2022

Background

Debulking cytoreduction surgery with bowel resection is a common intervention for ovarian cancer. It is controversial whether ostomy causes worse survival outcomes and how clinical physicians should choose which patients to undergo ostomy. During this study, we performed a systematic review to determine whether ostomy leads to worse outcomes after bowel resection compared to anastomosis. We also summarized the possible indications for ostomy.

Methods

We searched PubMed, Embase, and Cochrane for articles containing the phrase “ovarian cancer with bowel resection” that were published between 2016 and 2021. We included studies that compared primary anastomosis with ostomy. We mainly focused on differences in the anastomotic leakage rate, length of hospital stay, overall survival, and other survival outcomes associated with the two procedures.

Results and Conclusion

Of the 763 studies, three were ultimately included in the systematic review (N=1411). We found that ostomy did not contribute to worse survival outcomes, and that the stoma-related complications were acceptable. Indications for ostomy require further study. Bowel resection segment margins and the distance from the anastomosis to the anal verge require consideration.
Discovery of Novel Tetrahydro-β-carboline Containing Aminopeptidase N Inhibitors as Cancer Chemosensitizers
Authors: Xing Xiaoyan , Li Fahui , Hu Yajie , Zhang Lin , Hui Qian , Qin Hongyu , Jiang Qixiao , Jiang Wenyan , Fang Chunyan , Zhang Lei
Published: May 2022

Aminopeptidase N (APN, CD13) is closely associated with the development and progression of cancer. Previous studies suggested APN as a biomarker for cancer stem cells. APN inhibitors have been intensively evaluated as chemosensitizers for cancer treatments. In the present study, tetrahydro-β-carboline scaffold was introduced to the structure of APN inhibitors. The synthesized compounds showed potent enzyme inhibitory activities compared with Bestatin, an approved APN inhibitor, in cell-based enzymatic assay. In combination with chemotherapeutic drugs, representative APN inhibitor molecules D12, D14 and D16 significantly improved the antiproliferative potency of anticancer drugs in the in vitro tests. Further mechanistic studies revealed that the anticancer effects of these drug combinations are correlated with decreased APN expression, increased ROS level, and induction of cell apoptosis. The spheroid-formation assay and colony-formation assay results showed effectiveness of Paclitaxel-APN inhibitor combination against breast cancer stem cell growth. The combined drug treatment led to reduced mRNA expression of OCT-4, SOX-2 and Nanog in the cancer stem cells tested, suggesting the reduced stemness of the cells. In the in vivo study, the selected APN inhibitors, especially D12, exhibited improved anticancer activity in combination with Paclitaxel compared with Bestatin. Collectively, potent APN inhibitors were discovered, which could be used as lead compounds for tumor chemo-sensitization and cancer stem cell-based therapies.
Characterization of 7-Methylguanosine Identified Biochemical Recurrence and Tumor Immune Microenvironment in Prostate Cancer
Authors: Xin Sheng , Deng Yuxuan , Mao Jiaquan , Wang Tao , Liu Jihong , Wang Shaogang , Song Xiaodong , Song Wen , Liu Xiaming
Published: May 2022

Prostate cancer (PCa) has a high incidence rate, mortality rate, and biochemical recurrence (BCR) rate. 7-Methylguanosine (m7G), as one of the RNA modifications, has been considered to be actively involved in cancer-related translation disorders in recent years. Therefore, we first used The Cancer Genome Atlas (TCGA) database to identify prognosis and m7G-related long non-coding RNAs (lncRNAs). Then we randomly divided the samples into the training set and test set and then constructed and verified the m7G lnRNA prognostic model (m7Gscore) by the least absolute shrinkage and selection operator (LASSO) regression analysis. The m7Gscore has been proved to be an independent marker of BCR-free survival in patients with PCa. Furthermore, the m7Gscore was significantly correlated with the tumor immune microenvironment (TIME) and somatic mutation of PCa patients and had the potential to be an indicator for the selection of drug treatment. We also clustered TCGA cohort into three m7G-related patterns (C1, C2, and C3). The Kaplan–Meier survival analysis revealed that C1 had the best BCR-free survival and C3 had the worst. The TIME was also significantly distinct among the three m7G-related patterns. According to the TIME characteristics of the patterns, we defined C1, C2, and C3 as immune-desert phenotype, immune-inflamed phenotype, and immune-excluded phenotype, respectively.
A Multicenter Retrospective Study of Epithelioid Trophoblastic Tumors to Identify the Outcomes, Prognostic Factors, and Therapeutic Strategies
Authors: Liu Wu , Zhou Jianwei , Yang Jie , Huang Xiufeng
Published: May 2022

Background

There is no consensus for the management of epithelioid trophoblastic tumor (ETT) up to date.

Objective

ETT is the rarest form of gestational trophoblastic neplasia (GTN). Our goal was to assess the outcomes and explore the prognostic factors of patients with ETT through this multicenter retrospective analysis and to devise a risk-adapted approach to clinical management.

Methods

A total of 31 patients were validated as ETT pathologically between January 2004 and June 2021 from three tertiary hospitals. We retrospectively analyzed the characteristics, treatments, outcomes, and prognostic factors.

Results

Eight patients experienced a recurrence, and 6 patients died of ETT, resulting in a mortality rate of 19.4%. Five patients with stage I disease had a fertility-preserving treatment. Among them, one patient had a full-term delivery, whereas a 23-year-old patient who declined a hysterectomy died of a recurrent disease. Eight patients of extrauterine ETT with isolated pulmonary lesion were at a young age at diagnosis (median: 30.5 vs. 41, p = 0.003) and had a smaller tumor size (median: 2.4 vs. 4.8 cm, p = 0.003) compared with other patients who had a metastatic disease, and none of them died. The multivariate analyses showed that the number of metastases ≥3 [hazard ratio (HR), 28.16, p = 0.003] was the only significant predictor associated with adverse overall survival, while the number of metastases ≥3 (HR 9.59, p = 0.005) and chemotherapy alone (HR 16.42, p = 0.001) were associated with adverse recurrence-free survival. Patients in stage I or with number of metastases <3 had a favorable prognosis, whereas the prognosis of patients whose number of metastases ≥3 remains poor.

Conclusions

Chemotherapy alone is insufficient for patients with ETT. Surgical procedures are the mainstay of management for ETT patients. Combined surgery and multi-agent chemotherapy are recommended for patients with metastatic disease and localized disease with persistently positive human chorionic gonadotrophin levels after surgery. The number of metastases at ≥3 is the most critical risk factor for ETT.
Positive Youth Development and Internet Use in a Sample of Spanish Adolescents
Authors: Gómez-Baya Diego , Grasmeijer Anna Jean , López-Bermúdez Esther , Gaspar de Matos Margarida , Mendoza Ramón
Published: May 2022

During the COVID-19 pandemic, the use of Internet in the adolescent population has increased. A growing research interest has been developed about the consequences of Internet use for adolescent development. Despite most studies have examined the impact of Internet use on some indicators of psychological maladjustment, few studies have addressed the detrimental impact on the positive indicators of mental health. Positive youth development (PYD) represents a positive view of adolescent transition to adulthood which focuses on building the strengths that make young people more resistant to negative outcomes and more capable to choose a positive life direction. This study aimed to analyze the relationships between different aspects of Internet use and overall PYD in a sample of Spanish adolescents. To reach this aim, a sample of 1,038 adolescents (50.1% boys, M age = 14.19, SD = 1.38), enrolled in 14 high schools in the city of Huelva (Spain), filled in some self-report measures of PYD and Internet use and experience, such as the frequency of Internet use on weekdays or weekends, the different uses of Internet (i.e., social networks, playing online, reading, surfing or looking for information, playing or downloading music, and searching, selling, or buying products), and the subjective experience using the Internet (i.e., acknowledgment of spending too much time playing or in the networks, and being in a bad mood if they do not play or use the networks). Results of a hierarchical regression analysis showed that the more hours using Internet on weekdays, the less PYD. Moreover, the experience of feeling bad when not using the networks and spending too much time with online playing was related to lower PYD. However, the use of Internet for reading or looking for information had a positive association with PYD. These results suggest some implications for practice, such as the need to promote an adaptive Internet use, by providing a safe online context that encourages the acquisition of positive social values and life skills.
Immune Characteristics in Biliary Atresia Based on Immune Genes and Immune Cell Infiltration
Authors: Yang Chenyu , Xing Huiwu , Tan Bingqian , Zhang Mingman
Published: May 2022

Background

Biliary atresia (BA) is a serious biliary disease in infancy. Jaundice is the most visual and prominent symptom, and it mainly involves bile duct cells leading to the loss of intrahepatic and extrahepatic bile ducts. If left untreated, it will eventually progress to liver cirrhosis. The pathogenesis of BA is not clear, and it is now generally accepted that BA is an autoimmune disease. However, few studies have revealed the infiltration of immune cells in the liver of BA from a global perspective. We used liver tissue sequencing data to predict the infiltration and relative content of immune cells in BA.

Methods

The BA datasets GSE46960, GSE15235, and GSE84044, and patient information were downloaded from the Gene Expression Omnibus (GEO) database. After batch normalization, the differentially expressed immune genes (DE-IGs) in BA liver, normal liver, and hepatitis B liver were analyzed with the cut-off value of |log2fold change (log2FC)| >1 and false discovery rate (FDR) <0.05. CIBERSORT software was used to predict the proportions of 22 immune cells in all samples of the datasets.

Results

73 DE-IGs have been screened out between BA and normal tissue; among them, 20 genes were highly expressed and another 53 were expressed at a low level. A total of 30 DE-IGs existed between inflammation and fibrosis livers of BA, and all of them were expressed at low levels in fibrosis livers of BA. In GO term analysis, these DE-IGs were mainly associated with the MHC protein complex, cytokine, chemokine activity, and MHC-II receptor activity. In KEGG pathway analysis, the DE-IGs were mainly enriched in pathways of Th1 and Th2 cell differentiation, Th17 cell differentiation, IL-17 signaling pathway, Toll–like receptor signaling pathway, TNF signaling pathway, and autoimmune diseases. There were significant differences in immune infiltration among different pathological types of BA, and there were also obvious differences in immune infiltration of hepatitis B as a disease control of BA.

Conclusion

Based on immune genes and immune cell infiltration, this study reveals the immune characteristics of BA from a global point of view, which provides a new perspective for understanding the pathogenesis of BA and provides a direction for the diagnosis and treatment of BA.
Role of Pyroptosis in Inflammatory Bowel Disease (IBD): From Gasdermins to DAMPs
Authors: Zhang Shuxia , Liang Yujie , Yao Jun , Li De-feng , Wang Li-sheng
Published: May 2022

Pyroptosis is a pro-inflammatory cell death executed by gasdermin family proteins that involve the formation of pores on cells, recognition of danger signals, and release of pro-inflammatory cytokines IL-1βand IL-18. Pyroptosis modulates mucosal innate immunity and enteropathogenic bacterial infection. Similarly, the gasdermin family has been reported to be involved in the defense of the intestinal epithelium against bacterial infection and in the regulation of intestinal inflammation. Pyroptosis initiates damage signals that activate multiple pathways to cause inflammation, which may be a potential cause of chronic intestinal inflammation. In this review, we discuss the impact of pyroptosis on inflammatory bowel disease (IBD), with a focus on the executive proteins of pyroptosis (GSDMB, GADMD, and GSDME) and IBD-related endogenous damage-associated molecular patterns (DAMPs) produced by pyroptosis.
Qingfei Litan Decoction Against Acute Lung Injury/Acute Respiratory Distress Syndrome: The Potential Roles of Anti-Inflammatory and Anti-Oxidative Effects
Authors: Diao Yirui , Ding Qi , Xu Gonghao , Li Yadong , Li Zhenqiu , Zhu Hanping , Zhu Wenxiang , Wang Peng , Shi Yuanyuan
Published: May 2022

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an acute respiratory failure syndrome characterized by progressive arterial hypoxemia and dyspnea. Qingfei Litan (QFLT) decoction, as a classic prescription for the treatment of acute respiratory infections, is effective for the treatment of ALI/ARDS. In this study, the compounds, hub targets, and major pathways of QFLT in ALI/ARDS treatment were analyzed using Ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) and systemic pharmacology strategies. UHPLC-MS identified 47 main components of QFLT. To explore its anti-inflammatory and anti-oxidative mechanisms, gene ontology (Go) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and network pharmacological analysis were conducted based on the main 47 components. KEGG enrichment analysis showed that TNF signaling pathway and Toll-like receptor signaling pathway may be the key pathways of ALI/ARDS. We explored the anti-inflammatory and anti-oxidative pharmacological effects of QFLT in treatment of ALI/ARDS in vivo and in vitro. QFLT suppressed the levels of proinflammatory cytokines and alleviated oxidative stress in LPS-challenged mice. In vitro, QFLT decreased the levels of TNF-α, IL-6, IL-1β secreted by LPS-activated macrophages, increased GSH level and decreased the LPS-activated reactive oxygen species (ROS) in lung epithelial A549 cells. This study suggested that QFLT may have anti-inflammatory and anti-oxidative effects on ALI/ARDS, combining in vivo and in vitro experiments with systemic pharmacology, providing a potential therapeutic strategy option.
Qingfeiyin Decoction Inhibits H1N1 Virus Infection via Modulation of Gut Microbiota and Inflammatory Pathways in a Murine Model
Authors: Li Xianping , Wang Mingzhe , Liu Chang , Xiao Yuchun , Li Mengde , Ban Chengjun , Huang Yuanming , Cheng Miao , Song Liqiong , Liu Guoxing , Lu Shan , Wang Chengxiang , Ren Zhihong
Published: May 2022

Influenza virus-caused lung infection and its pandemic outbreaks are a persistent public health challenge. The H1N1 subtype is the most common type of influenza infection observed in humans. Maxingshigantang decoction, a classic formula of Chinese herbal medicine, has been used for the prevention and treatment of respiratory infection for many centuries. Qingfeiyin decoction, based on Maxingshigantang, has been used in the clinic for decades. To explore the underlying mechanisms, according to the traditional Chinese medicine theory “the lung and the large intestine are interior–exterior,” which can be translated to the “gut–lung axis” in a contemporary term, the composition of gut microbiota was determined using 16S rRNA and the transcriptome of the colon was determined by RNA sequencing. The results showed that Qingfeiyin decoction decreased the viral load, alleviated the lung injury, increased the survival rate, partly restored the shortening of the colon caused by the H1N1 virus, and downregulated inflammatory pathways including MAPK, TNFα, and JAK-STAT signaling pathways. Qingfeiyin decoction increased the relative abundance of the genera of Coprococcus, Ruminococcus, Lactobacillus, and Prevotella and prevented the H1N1 virus-induced decrease in the abundance of the genera of Escherichia, Parabacteroides, Butyricimonas, and Anacrotruncus. These results will help better understand the mechanisms for Qingfeiyin decoction’s protective effect against influenza virus infection.
Neohesperidin Protects Angiotensin II-Induced Hypertension and Vascular Remodeling
Authors: Zhang Jingsi , Hui Yuanshu , Liu Fengyi , Yang Qian , Lu Yi , Chang Yeting , Liu Qinlong , Ding Yanchun
Published: May 2022

Vascular remodeling due to hypertension is one of the major health challenges facing countries around the world. Neohesperidin, a flavonoid glycoside found in citrus fruits, is an antioxidant. Neohesperidin has been studied for a variety of diseases in addition to hypertension. In this study, angiotensin II was used to induce hypertension in mice (490 ng/kg/min, 14 days). We used H&E, Masson, immunofluorescence, dihydroethidine and qPCR to evaluate the effect of Nehesperidin (50 mg/kg/day, 16 days) on pathological hypertension in mice. Estimating the effect of Nehesperidin on human umbilical vein endothelial cells and vascular smooth muscle cells stimulated by angiotensin II. We found that neohesperidin inhibited angiotensin II-induced hypertension in mice. Neohesperidin reduced angiotensin II-induced vascular hypertrophy, fibrosis, inflammation and oxidative stress in vivo. Neohesperidin inhibited angiotensin II-induced ROS and DNA damage in human umbilical vein endothelial cells. Neohesperidin inhibited angiotensin II-induced migration of vascular smooth muscle cells. The results showed that Nehesperidin acts as an antioxidant and could significantly inhibit angiotensin II induced hypertension and vascular remodeling in vitro and in vivo.
Gut Microbial Dysbiosis and Cognitive Impairment in Bipolar Disorder: Current Evidence
Authors: Dai Wenyu , Liu Jieyu , Qiu Yan , Teng Ziwei , Li Sujuan , Yuan Hui , Huang Jing , Xiang Hui , Tang Hui , Wang Bolun , Chen Jindong , Wu Haishan
Published: May 2022

Recent studies have reported that the gut microbiota influences mood and cognitive function through the gut-brain axis, which is involved in the pathophysiology of neurocognitive and mental disorders, including Parkinson’s disease, Alzheimer’s disease, and schizophrenia. These disorders have similar pathophysiology to that of cognitive dysfunction in bipolar disorder (BD), including neuroinflammation and dysregulation of various neurotransmitters (i.e., serotonin and dopamine). There is also emerging evidence of alterations in the gut microbial composition of patients with BD, suggesting that gut microbial dysbiosis contributes to disease progression and cognitive impairment in BD. Therefore, microbiota-centered treatment might be an effective adjuvant therapy for BD-related cognitive impairment. Given that studies focusing on connections between the gut microbiota and BD-related cognitive impairment are lagging behind those on other neurocognitive disorders, this review sought to explore the potential mechanisms of how gut microbial dysbiosis affects cognitive function in BD and identify potential microbiota-centered treatment.
An Integrated Strategy to Identify and Quantify the Quality Markers of Xinkeshu Tablets Based on Spectrum-Effect Relationship, Network Pharmacology, Plasma Pharmacochemistry, and Pharmacodynamics of Zebrafish
Authors: Wei Yongheng , Nie Lei , Gao Lele , Zhong Liang , Sun Zhongyu , Yang Xiangchun , Yue Jianan , Zeng Yingzi , Li Lian , Sun Jing , Zang Hengchang
Published: May 2022

Xinkeshu tablets (XKST), a traditional Chinese patent medicine (CPM), have served in the clinical treatment of cardiovascular diseases (CVDs) for decades. However, its pharmacodyamic material basis was still unclear, and the holistic quality control has not been well established due to the lack of systematic research on the quality markers. In this experiment, the heart rate recovery rate of a zebrafish larva was used to evaluate the traditional pharmacological effect of XKST i.e., antiarrhythmic effect. The HPLC fingerprints of 16 batches of XKST samples were obtained, and antiarrhythmic components of XKST were identified by establishing the spectrum-effect relationship between HPLC fingerprints and heart rate recovery rate of zebrafish larva with orthogonal signal correction and partial least squares regression (OSC–PLSR) analysis. The anticardiovascular disease components of XKST were identified by mapping the targets related to CVDs in network pharmacology. The compounds of XKST absorbed and exposed in vivo were identified by ultra-high performance liquid chromatography Q-Exactive high-resolution mass spectrometry (UHPLC-Q-Exactive HRMS). Based on the earlier studies, combined with five principles for identifying quality markers and verified by a zebrafish arrhythmia model, danshensu, salvianolic acid A, salvianolic acid B, daidzein, and puerarin were identified as quality markers of XKST. In total, 16 batches of XKST samples were further quantified with the method established in this study. Our study laid the foundation for the quality control of XKST. The integrated strategy used in the study of XKST could be applied for the identification and quantification of quality markers of other CPMs as well.
Exploring the Potential of Eltrombopag: Room for More?
Authors: Tarantini Francesco , Cumbo Cosimo , Anelli Luisa , Zagaria Antonella , Conserva Maria Rosa , Redavid Immacolata , Specchia Giorgina , Musto Pellegrino , Albano Francesco
Published: May 2022

Since its introduction in clinical practice, eltrombopag (ELT) has demonstrated efficacy in heterogeneous clinical contexts, encompassing both benign and malignant diseases, thus leading researchers to make a more in-depth study of its mechanism of action. As a result, a growing body of evidence demonstrates that ELT displays many effects ranging from native thrombopoietin agonism to immunomodulation, anti-inflammatory, and metabolic properties. These features collectively explain ELT effectiveness in a broad spectrum of indications; moreover, they suggest that ELT could be effective in different, challenging clinical scenarios. We reviewed the extended ELT mechanism of action in various diseases, with the aim of further exploring its full potential and hypothesize new, fascinating indications.
A Theoretical Study of Tunable Brillouin Lasers Based on a Diamond Suspended Waveguide
Authors: Wang Wuyue , Yu Yu , Bai Zhenxu , Li Yunfei , Wang Gong , Li Kai , Song Changyu , Wang Zhiyong , Li Sensen , Li Yuhai , Liu Tongyu , Yan Xiusheng , Wang Yulei , Lu Zhiwei
Published: May 2022

In this work we detail the design of a novel, hybrid waveguide structure which enables independent control of phonon modes and optomechanical driving forces, thereby yielding customizable Brillouin coupling over a very broad bandwidth. The Brillouin gain reaches 4400 W−1m−1, with tunable phonon frequencies from 1–95 GHz. This hybrid waveguide relies on tuning of its width and enables photon-phonon conversion based on the Brillouin nonlinear effect, and importantly, it can guide and manipulate the phonons emitted by the Brillouin effect on a chip-level device. There is hence excellent potential for this technique to be applied in microwave sources using the on-chip Brillouin photoacoustic coupling mechanism.
What Did We Learn From Current Progress in Heat Stress Tolerance in Plants? Can Microbes Be a Solution?
Authors: Ahmad Muhammad , Imtiaz Muhammad , Shoib Nawaz Muhammad , Mubeen Fathia , Imran Asma
Published: May 2022

Temperature is a significant parameter in agriculture since it controls seed germination and plant growth. Global warming has resulted in an irregular rise in temperature posing a serious threat to the agricultural production around the world. A slight increase in temperature acts as stress and exert an overall negative impact on different developmental stages including plant phenology, development, cellular activities, gene expression, anatomical features, the functional and structural orientation of leaves, twigs, roots, and shoots. These impacts ultimately decrease the biomass, affect reproductive process, decrease flowering and fruiting and significant yield losses. Plants have inherent mechanisms to cope with different stressors including heat which may vary depending upon the type of plant species, duration and degree of the heat stress. Plants initially adapt avoidance and then tolerance strategies to combat heat stress. The tolerance pathway involves ion transporter, osmoprotectants, antioxidants, heat shock protein which help the plants to survive under heat stress. To develop heat-tolerant plants using above-mentioned strategies requires a lot of time, expertise, and resources. On contrary, plant growth-promoting rhizobacteria (PGPRs) is a cost-effective, time-saving, and user-friendly approach to support and enhance agricultural production under a range of environmental conditions including stresses. PGPR produce and regulate various phytohormones, enzymes, and metabolites that help plant to maintain growth under heat stress. They form biofilm, decrease abscisic acid, stimulate root development, enhance heat shock proteins, deamination of ACC enzyme, and nutrient availability especially nitrogen and phosphorous. Despite extensive work done on plant heat stress tolerance in general, very few comprehensive reviews are available on the subject especially the role of microbes for plant heat tolerance. This article reviews the current studies on the retaliation, adaptation, and tolerance to heat stress at the cellular, organellar, and whole plant levels, explains different approaches, and sheds light on how microbes can help to induce heat stress tolerance in plants.