bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between plasma selenium and risk of ischemic stroke: A community-based, nested, and case-control study
Authors: Wang Zhuo , Hu Shiyu , Song Yun , Liu Lishun , Huang Zhengzheng , Zhou Ziyi , Wei Yaping , Lin Tengfei , Huang Meiqing , Zhang Hao , Guo Huiyuan , Sun Yong , Wang Binyan , Qin Xianhui , Xu Xiping , Chi Feng , Ren Bohua , Ren Lijie
Published: November 2022

Background

The prospective association between plasma Se and stroke risk remains inconclusive. The relationship between Se and ischemic stroke among a low circulating Se status population deserves more attention, especially for Chinese people who were a high-risk group for Se deficiency.

Objective

The relationship between plasma Se concentration and ischemic stroke risk in a large-scale Chinese community-based population and any potential effect modifiers were investigated.

Methods

A nested, case-control study, using data from the “China H-type Hypertension Registry Study” were conducted. A total of 1,904 first ischemic stroke cases and 1,904 controls matched for age, sex, and village were included in this study. The association between plasma Se and first ischemic stroke was evaluated by conditional logistic regression analyses.

Results

The median value of plasma Se was 65.8 μg/L among total participants. Overall, a significant inverse relationship between plasma Se and first ischemic stroke risk was found (per SD increment; adjusted OR: 0.87; 95% CI: 0.80 and 0.95). Accordingly, a significantly lower risk of first ischemic stroke was found in participants in quartile 3 (65.8−<77.8 μg/L) (adjusted OR: 0.78; 95% CI: 0.63 and 0.96) and quartile 4 (≥77.8 μg/L) (adjusted OR: 0.76; 95% CI: 0.59 and 0.96), compared with those in quartile 1 (<56.0 μg/L). Furthermore, a significantly lower ischemic stroke risk was found in those with lower low-density lipoprotein cholesterol (LDL-C) levels (<3.4 vs. ≥3.4 mmol/L; P for interaction = 0.015) or those with lower homocysteine levels (<12.1 (median) vs. ≥12.1 μmol/L; P for interaction = 0.027) at baseline.

Conclusion

Plasma Se was significantly inversely associated with the risk of first ischemic stroke among a large-scale Chinese community-based population (most adults with hypertension and elevated total homocysteine), especially among those with lower LDL-C and lower homocysteine levels.
Advanced glycation end products in diabetic retinopathy and phytochemical therapy
Authors: Kang Qingzheng , Dai Haiyu , Jiang Suwei , Yu Li
Published: November 2022

Advanced glycation end products (AGEs) are generated by the nonenzymatic glycation of proteins or lipids. Diabetic retinopathy (DR) is one common complication in patients with diabetes. The accumulation of AGEs in retinal cells is strongly associated with the development of DR. AGEs can induce the breakdown of redox balance and then cause oxidative stress in retinal cells, exerting cytopathic effects in the progression of DR. The interaction between AGEs and the receptor for AGE (RAGE) is involved in multiple cellular pathological alterations in the retina. This review is to elucidate the pathogenetic roles of AGEs in the progression of DR, including metabolic abnormalities, lipid peroxidation, structural and functional alterations, and neurodegeneration. In addition, disorders associated with AGEs can be used as potential therapeutic targets to explore effective and safe treatments for DR. In this review, we have also introduced antioxidant phytochemicals as potential therapeutic strategies for the treatment of DR.
Vitamin D insufficiency is high in Malaysia: A systematic review and meta-analysis of studies on vitamin D status in Malaysia
Authors: Mohd Saffian Shamin , Jamil Nor Aini , Mohd Tahir Nor Asyikin , Hatah Ernieda
Published: November 2022

Purpose

To estimate the vitamin D status of participants residing in Malaysia.

Methods

PubMed, Scopus, Web of Science, and MyJurnal were searched up to June 2022 without language restrictions. Studies that reported the 25-hydroxyvitamin D [25(OH)D] concentrations and defined their cut-off for deficiency or insufficiency from healthy participants residing in Malaysia were included. The random effects model was used to pool vitamin D status using established cut-offs of <30, <50, and <75 nmol/L according to age group.

Results

From 299 studies screened, 32 studies were included in the meta-analysis. The pooled proportion for <30 nmol/L was 21% (95% CI 9–36, n = 2,438 from 10 studies), while the pooled proportion <50 nmol/L was 64% (95% CI 56–72, n = 13,977 from 30 studies), and <75 nmol/L was 85% (95% CI 61–100, n = 1,376 from five studies). Heterogeneity was high (I2 ranged from 98–99%). Higher proportions of vitamin D insufficiency (defined as <50 nmol/L) were found in participants living in the urban areas (compared to rural areas), in females (compared to males), and in Malays and Malaysian Indians (compared to Malaysian Chinese) ethnicities.

Conclusion

More than half of Malaysians have insufficient vitamin D levels, despite being a country that is close to the equator. We strongly urge prompt public health measures to improve the vitamin D status in Malaysia.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021260259].
Association between maternal sugar-sweetened beverage consumption and the social-emotional development of child before 1 year old: A prospective cohort study
Authors: Gao Rui , Liu Xuemei , Li Xiuxiu , Zhang Yuanxing , Wei Min , Sun Peng , Zhang Jianan , Cai Li
Published: November 2022

Background

Excessive consumption of sugar-sweetened beverages (SSBs) has become an international public health issue. Adverse effects of sugary beverage consumption on both mother and child during pregnancy continue to be found. However, evidence regarding maternal SSB consumption and social-emotional development of children is lacking.

Methods

Based on the Shenzhen Birth Cohort Study (loss rate: 10.97%), we included 985 mother-infant pairs from 2018 to 2022. All mothers had a singleton live birth without hypertension, diabetes, tumor, or serious immune system disease before pregnancy. We used a chart of frequency distribution to show maternal SSB consumption, including non-diet soda, tea drinks (not 100% tea), fruit drinks, Sugar-sweetened coffee, bubble tea, or cocoa drinks, and total SSBs. A multivariate logistic regression model was used to estimate the odds ratios of the potential delay on social-emotional development of each child was monitored at both 6 months and 12 months of age based on maternal SSB consumption.

Results

Among the mothers, 728 (73.91%) drank SSBs <1 time per week, 194 (19.70%) drank SSBs 1–2 times per week, 43 (4.37%) drank SSBs 3–4 times per week, and 20 (2.03%) drank SSBs 5 or more times per week. Children aged 12 months with mothers who drank SSBs five or more times per week during pregnancy had an increased risk of potential delay on social-emotional development compared to those with mothers who drank SSBs less than once per week [odds ratio: 3.08 (1.13–8.39)]. Regarding the specific kinds of SSBs, we found that tea drinks (not 100% tea) were positively associated with potential delay on social-emotional development in children aged 6 months.

Conclusion

Nearly three-quarters of mothers consumed almost no SSBs during pregnancy. High SSB intake during pregnancy was associated with an increased risk of the potential delay on social-emotional development of a child at 6 and 12 months of age.
Oral arsenic trioxide for treating acute promyelocytic leukaemia: Implications for its worldwide epidemiology and beyond
Authors: Kumana Cyrus R. , Kwong Yok-Lam , Gill Harinder
Published: November 2022

This account describes how orally administered Arsenic-trioxide (ATO) therapy influences the epidemiology of acute promyelocytic leukaemia (APL), and how the experience that ensued may expand the indications for oral ATO as a treatment for diseases/disorders other than APL. Over the last two decades, experience with APL patients in Hong Kong treated with an oral regimen comprising ATO, all-trans retinoic acid (ATRA), and ascorbic acid (also known as “AAA”) has confirmed a dramatic improvement in overall survival. Over that period, there has been an estimated 60-fold increase in the prevalence of APL (proportion of surviving APL patients in the population on December 31 including those deemed to be ‘cured’). In contrast to regimens entailing intravenous (IV) ATO, the consequential therapeutic benefits of using oral ATO have been achieved with much less patient inconvenience and quality of life disruption, reduced burdens on health care facilities (hospitalisations and staff involvement), and much enhanced affordability (retail drug & other cost reductions). Numerous experimental and a few clinical studies suggest that ATO may also have a therapeutic role in many other diseases/disorders. Several such diseases (e.g. autoimmune disorders & idiopathic pulmonary fibrosis) are far more prevalent than APL, which means that very large numbers of patients may potentially benefit from ATO treatment, even if its efficacy is limited to selected populations with these diseases. The known safety of oral ATO and its advantages over repeated long-term IV delivery suggests that this route be used in future clinical studies of its possible role in treating such patients. If the clinical utility of oral ATO treatment is validated for patients enduring any such non-APL diseases, very large numbers of patients may stand to benefit.
A cancer-associated fibroblast gene signature predicts prognosis and therapy response in patients with pancreatic cancer
Authors: Zhang Jinbao , Chen Meiling , Fang Chuanfa , Luo Peng
Published: November 2022

Pancreatic cancer is a lethal malignancy with a 5-year survival rate of about 10% in the United States, and it is becoming an increasingly prominent cause of cancer death. Among pancreatic cancer patients, pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of all cases and has a very poor prognosis with an average survival of only 1 year in about 18% of all tumor stages. In the past years, there has been an increasing interest in cancer-associated fibroblasts (CAFs) and their roles in PDAC. Recent data reveals that CAFs in PDAC are heterogeneous and various CAF subtypes have been demonstrated to promote tumor development while others hinder cancer proliferation. Furthermore, CAFs and other stromal populations can be potentially used as novel prognostic markers in cancer. In the present study, in order to evaluate the prognostic value of CAFs in PDAC, CAF infiltration rate was evaluated in 4 PDAC datasets of TCGA, GEO, and ArrayExpress databases and differentially expressed genes (DEGs) between CAF-high and CAF-low patients were identified. Subsequently, a CAF-based gene expression signature was developed and studied for its association with overall survival (OS). Additionally, functional enrichment analysis, somatic alteration analysis, and prognostic risk model construction was conducted on the identified DEGs. Finally, oncoPredict algorithm was implemented to assess drug sensitivity prediction between high- and low-risk cohorts. Our results revealed that CAF risk-high patients have a worse survival rate and increased CAF infiltration is a poor prognostic indicator in pancreatic cancer. Functional enrichment analysis also revealed that “extracellular matrix organization” and “vasculature development” were the top enriched pathways among the identified DEGs. We also developed a panel of 12 genes, which in additional to its prognostic value, could predict higher chemotherapy resistance rate. This CAF-based panel can be potentially utilized alone or in conjunction with other clinical parameters to make early predictions and prognosticate responsiveness to treatment in PDAC patients. Indeed, it is necessary to conduct extensive prospective investigations to confirm the clinical utility of these findings.
Case report: Emergency management of spontaneous rupture of the inflammatory myofibroblastic tumor of the urinary bladder
Authors: Sun Zhenfu , Qi Lei , Guo Zhifan , Yuan Wei , Du Yuancheng , Gao Haitao , Hong Xuekai , Zang Yunjiang
Published: November 2022

Acute abdomen caused by spontaneous rupture of the inflammatory myofibroblastic tumor of the urinary bladder (IMTUB) is a rare clinical emergency of the urinary system.It is difficult to distinguish it from spontaneous rupture of bladder caused by other causes before surgery. An emergency case of spontaneous rupture of IMTUB was reported. A 57-year-old middle-aged woman was admitted to the hospital because of “acute lower abdominal pain for 5 hours”. No history of smoking and gross hematuria. The physical examination revealed visible abdominal tenderness as well as signs of shock. A pelvic CT scan shows a space-occupying lesion above the bladder with massive accumulation of blood. When the nature of the tumor could not be determined, emergency laparotomy and partial cystectomy were performed, and postoperative pathology confirmed cystitis myofibroblastic tumor. No local recurrence or distant metastasis of the tumor was observed during the regular follow-up period of 6 months. IMTUB should focus on prevention and treatment, with a combination of preoperative examination and postoperative pathology, and finally implement highly individualized treatment.
Consolidatory ablative stereotactic body radiation therapy after induction chemotherapy for unresectable pancreatic cancer: A single center experience
Authors: Lee Hye In , Kang Hyun-Cheol , Chie Eui Kyu
Published: November 2022

Background and purpose

Consolidatory radiotherapy in form of stereotactic body radiation therapy (SBRT) with an ablative dose following induction chemotherapy is emerging as a promising treatment scheme for unresectable pancreatic cancer. Outcomes of given treatment at a single center for contiguous patients with unresectable pancreatic cancer were evaluated to build the optimal treatment strategy.

Materials and methods

In this retrospective study, a total of 50 patients with unresectable pancreatic cancer who underwent induction chemotherapy and ablative dose SBRT were included. SBRT dose was 40–50 Gy in five fractions. Two strategies were adopted to adhere to the organs at risk (OAR) dose constraints: simultaneous integrated protection (SIP) technique and magnetic resonance (MR)-guided adaptive technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated from the start date of SBRT.

Results

The median follow-up period for survivors was 21.1 months (range, 6.2–61.0 months). Eleven (22.0%) patients underwent resection after SBRT, which were all R0 resection. In patients with non-metastatic disease, the median OS was 26.5 months (range, 4.1–61.0 months), and the 1- and 3-year LPFS were 90.0% (95% confidence interval [CI], 72.0–96.7%) and 57.4% (95% CI, 31.7–76.4%), respectively. Patients with oligometastatic disease had inferior survival outcomes, but there was no survival difference among responders to induction chemotherapy. In the multivariable analysis, tumor size ≤4 cm, non-metastatic status, and good response to induction chemotherapy were associated with improved LPFS. In dosimetric analysis, GTV Dmin ≥50.5 Gy was the strongest prognosticator against local progression. Grade ≥3 adverse events occurred in two (4.0%) patients with non-adaptive RT, but none in patients with MR-guided adaptive RT.

Conclusion

Ablative dose SBRT following induction chemotherapy is an effective strategy for selected patients with unresectable pancreatic cancer. The SIP technique and MR-guided adaptive RT were attributed to minimizing the risk of adverse events. Further studies are needed to identify the best candidates for consolidatory SBRT in unresectable pancreatic cancer.
Hypofractionated concurrent chemoradiotherapy related lymphopenia and its association with survival in locally advanced non-small cell lung cancer patients
Authors: Liu FangJie , Wu YingJia , Shao JianHui , Qiu Bo , Guo SuPing , Luo QiaoTing , Guo JinYu , Wang DaQuan , Chu Chu , Zhou Rui , Chen NaiBin , Ai XinLei , Liu Hui
Published: November 2022

Background

To evaluate longitudinal changes of concurrent chemoradiotherapy (CCRT) related lymphopenia and its association with survival in locally advanced non-small cell lung cancer (LA-NSCLC) patients.

Methods

Total lymphocyte count (TLC) at baseline, weekly intervals during CCRT and monthly intervals up to 12 months after CCRT were documented. The Common Terminology Criteria for Adverse Events version 5.0 was used to grade the severity of lymphopenia. Cox regression analysis was performed to evaluate the association between overall survival (OS) and CCRT related lymphopenia at different timepoints. Logistic regression model was used to determine the clinical factors associated with TLC level.

Results

381 LA-NSCLC patients treated with definitive CCRT without consolidation therapy (NCT02573506/NCT02577341) between 2011 to 2020 were analyzed. With a median follow-up of 45.8 months, the median OS was 41.0 months for all patients. Univariable analysis demonstrated that the 3 weeks during CCRT Grade (G) 4 lymphopenia (P=0.018), 2 months after CCRT G1-4 lymphopenia (P=0.004), 6 months after CCRT (6m-post-CCRT) G1-4 lymphopenia (P=0.001), and TLC nadir (P=0.020) were significantly associated with poorer OS. Multivariable analysis suggested that 6m-post-CCRT G1-4 lymphopenia (HR 2.614; P=0.041) were one of the independent predictors of OS. Further analysis inferred that radiation dose (OR: 1.328; P=0.005), GTV volume (OR: 1.004; P=0.036), and baseline TLC (OR: 0.288; P=0.001) were associated with 6m-post-CCRT lymphopenia.

Conclusion

The persistent lymphopenia at 6 months after CCRT was an independent prognostic factor of OS in LA-NSCLC patients. Higher radiation dose, larger gross tumor volume and lower baseline TLC were significantly related to 6m-post-CCRT lymphopenia.
“Pain, Stress, and Emotions”: Uncontrolled trial of a single-session, telehealth, emotional awareness and expression therapy class for patients with chronic pain
Authors: Ziadni Maisa S. , Sturgeon John A. , Lumley Mark A.
Published: November 2022

Objectives

Trauma- and emotion-focused chronic pain interventions, particularly Emotional Awareness and Expression Therapy (EAET), show much promise for reducing pain and improving functioning. We developed a novel, single-session, telehealth-delivered EAET class (“Pain, Stress, and Emotions”; PSE) and tested it on adults with chronic pain of mixed etiology.

Methods

After an initial developmental phase, we conducted an uncontrolled trial, providing PSE to 74 individuals with chronic pain (63.5% female; 64.9% White; 60.8% with pain duration >5 years) in four class administrations. Participants completed self-report measures (primary outcomes: pain intensity and pain interference) at baseline and multiple follow-ups to 12 weeks. Linear mixed-models examined changes over time, and effect sizes were calculated on change from baseline to 4-week (primary endpoint) and 12-week follow-ups. The trial was registered with clinicaltrials.gov (NCT05014126)

Results

Participants reported high satisfaction with the PSE class. Pain intensity showed a significant, medium reduction across time (p < .001; d = 0.60 at 4 weeks); one-quarter of participants had clinically meaningful pain reduction (≥30%). Pain interference had a large reduction (p < .001; d = 0.74). There were significant but smaller improvements in most secondary outcomes (ds = 0.15 to 0.55; ps < .01). Effects were generally maintained or increased at 12-week follow-up. Higher education and baseline ambivalence over emotional expression predicted greater pain reductions.

Conclusions

People taking this EAET class had reduced pain severity and interference and improvements in other pain-related outcomes. The single-session, telehealth class holds promise as an easily delivered, efficient, and potentially impactful intervention for some patients with chronic pain, although controlled trials are needed.
Seasonal variation of ambulatory blood pressure in Chinese hypertensive adolescents
Authors: Zhou Yi , Zhao Lin , Meng Xu , Cai Qiu-Jing , Zhao Xiao-Lei , Zhou Xian-Liang , Hu Ai-Hua
Published: November 2022

Background

Blood pressure (BP) exhibits seasonal variation with lower levels at higher temperatures and vice versa. This phenomenon affects both sexes and all age groups. So far, only a few research studies have investigated this condition in adolescents and none of them were based on hypertensive population or ever applied ambulatory blood pressure monitor (ABPM). Therefore, we carried out the first study that used ABPM to record seasonal variation of blood pressure in hypertensive adolescents.

Methods

From March 2018 to February 2019, 649 ABPMs from hypertensive adolescents between 13 and 17 years who were referred to wear an ABPM device in Beijing and Baoding were extracted. Seasonal change in ambulatory BP value, dipping status, and prevalence of different BP phenotypes were analyzed and compared.

Results

Mean age of participants was 14.9 ± 1.5 years and 65.8% of them were boys. Of the participants, 75.3% met the criteria of overweight or obesity. From summer to winter, average 24-hour, day-time, and night-time BP showed significant rise, which was 9.8/2.8, 9.8/3.0, and 10.9/3.4 mmHg, respectively. This seasonal effect on BP was not dependent on the obesity degree. In addition, higher prevalence of nondippers and risers existed in winter while white coat hypertension was more frequent in warmer seasons.

Conclusion

Hypertensive adolescents showed evident seasonal change in their ABPM results, which was featured by elevated BP level and more frequent abnormal dipping patterns in winter. On the contrary, higher prevalence of white coat hypertension was found in warmer seasons. Physicians should take seasonal variation into consideration when managing adolescent hypertension.
Tactile stimulation in very preterm infants and their needs of non-invasive respiratory support
Authors: Kaufmann Maxi , Seipolt Barbara , Rüdiger Mario , Mense Lars
Published: November 2022

Aim

Despite the lack of evidence, current resuscitation guidelines recommend tactile stimulation in apneic infants within the first minutes of life. The aim was to investigate whether timing, duration or intensity of tactile stimulation influences the extent of non-invasive respiratory support in extremely preterm infants during neonatal resuscitation.

Methods

In an observational study, we analyzed 47 video recordings and physiological parameters during postnatal transition in preterm infants below 320/7 weeks of gestational age. Infants were divided into three groups according to the intensity of respiratory support.

Results

All infants were stimulated at least once during neonatal resuscitation regardless of their respiratory support. Only 51% got stimulated within the first minute. Rubbing the feet was the preferred stimulation method and was followed by rubbing or touching the chest. Almost all very preterm infants were exposed to stimulation and manipulation most of the time within their first 15 min of life. Tactile stimulation lasted significantly longer but stimulation at multiple body areas started later in infants receiving prolonged non-invasive respiratory support.

Conclusion

This observational study demonstrated that stimulation of very preterm infants is a commonly used and easy applicable method to stimulate spontaneous breathing during neonatal resuscitation. The concomitant physical stimulation of different body parts and therefore larger surface areas might be beneficial.
Alveolar soft part sarcoma in childhood and adolescence: Report of three cases and review of literature
Authors: Zhang Yudi , Wang Ying , Wang Hao , Wen Chuan , Wu Xiaochuan
Published: November 2022

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma with unique tumor characteristics, which is rare in children. Herein, we present the immunophenotype, treatment, and prognosis of three children with ASPS from The Second Xiangya Hospital of Central South University, and 51 children with ASPS have been reported in the previous literature, along with a focused review of the clinical features, pathological features, differential diagnosis, treatment, and prognosis of ASPS in pediatric patients.
Case report: A novel mutation in TRPS1 identified in a Chinese family with tricho-rhino-phalangeal syndrome I: A therapeutic challenge
Authors: Huang Qi , Jiang Cheng , Sun Jiazhong , Xue Junli , Zhang Victor Wei
Published: November 2022

Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant malformation caused by mutations involving the TRPS1 gene. Patients with TRPS exhibit distinctive craniofacial and skeletal abnormalities. This report presents three intra-familial cases with TRPS1 gene mutations that showed the characteristic features of TRPS. A 13-year-old boy was admitted to Department of Endocrinology for the evaluation of short stature. Physical examination revealed that the boy had thin sparse hair, pear-shaped nose, protruding ears, small jaw and brachydactyly. A survey of his family history indicated that the boy's sister and mother shared the same clinical features. Radiological techniques demonstrated a different degree of skeletal abnormalities in these siblings. Next-generation sequencing and quantitative PCR were performed and showed a novel deletion mutation in exons 3–5 in the three familial cases, confirming the diagnosis of TRPS I. The healthy father did not carry the deletion mutation. Currently, there was no specific therapy for TRPS I; however, genetic consultation may be useful for family planning
Gαs, adenylyl cyclase, and their relationship to the diagnosis and treatment of depression
Authors: Schappi Jeffrey M. , Rasenick Mark M.
Published: November 2022

The relationship between depression, its etiology and therapy, and the cAMP signaling system have been studies for decades. This review will focus on cAMP, G proteins and adenylyl cyclase and depression or antidepressant action. Both human and animal studies are compared and contrasted. It is concluded that there is some synteny in the findings that cAMP signaling is attenuated in depression and that this is reversed by successful antidepressant therapy. The G protein that activates adenylyl cyclase, Gαs, appears to have diminished access to adenylyl cyclase in depression, and this is rectified by successful antidepressant treatment. Unfortunately, attempts to link specific isoforms of adenylyl cyclase to depression or antidepressant action suffer from discontinuity between human and animal studies.
Identification of a novel oxidative stress-related prognostic model in lung adenocarcinoma
Authors: Zhu Yifan , Tang Quanying , Cao Weibo , Zhou Ning , Jin Xin , Song Zuoqing , Zu Lingling , Xu Song
Published: November 2022

Background: Oxidative stress (OxS) participates in a variety of biological processes, and is considered to be related to the occurrence and progression of many tumors; however, the potential diagnostic value of OxS in lung cancer remains unclear.

Methods: The clinicopathological and transcriptome data for lung adenocarcinoma (LUAD) were collected from TCGA and GEO database. LASSO regression was used to construct a prognostic risk model. The prognostic significance of the OxS-related genes was explored using a Kaplan-Meier plotter database. The prediction performance of the risk model was shown in both the TCGA and GSE68465 cohorts. The qRT-PCR was performed to explore the expression of genes. CCK-8, Edu and transwell assays were conducted to analyze the role of CAT on cell proliferation migration and invasion in lung cancer. Immune infiltration was evaluated by CIBERSORT and mutational landscape was displayed in the TCGA database. Moreover, the relationship between risk score with drug sensitivity was investigated by pRRophetic.

Results: We identified a prognosis related risk model based on a four OxS gene signature in LUAD, including CYP2D6, FM O 3, CAT, and GAPDH. The survival analysis and ROC curve indicated good predictive power of the model in both the TCGA and GEO cohorts. LUAD patients in the high-risk group had a shorter OS compared to the low-risk group. QRT-PCR result showed that the expression of four genes was consistent with previous analysis in cell lines. Moreover, overexpression of CAT could decrease the proliferation, invasion and migration of lung cancer cells. The Cox regression analysis showed that the risk score could be used as an independent prognostic factor for OS. LUAD patients in the high-risk score group exhibited a higher tumor mutation burden and risk score were closely related to tumor associated immune cell infiltration, as well as the expression of immune checkpoint molecules. Both the high- and low-risk groups have significant differences in sensitivity to some common chemotherapy drugs, such as Paclitaxel, Docetaxel, and Vinblastine, which may contribute to clinical treatment decisions.

Conclusion: We established a robust OxS-related prognostic model, which may contribute to individualized immunotherapeutic strategies in LUAD.
Deficiency of endothelial FGFR1 alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice
Authors: Long Yanrong , Chen Hongbin , Deng Junchao , Ning Junjie , Yang Pengbo , Qiao Lina , Cao Zhongwei
Published: November 2022

Disrupted neonatal lung angiogenesis and alveologenesis often give rise to bronchopulmonary dysplasia (BPD), the most common chronic lung disease in children. Hyperoxia-induced pulmonary vascular and alveolar damage in premature infants is one of the most common and frequent factors contributing to BPD. The purpose of the present study was to explore the key molecules and the underlying mechanisms in hyperoxia-induced lung injury in neonatal mice and to provide a new strategy for the treatment of BPD. In this work, we reported that hyperoxia decreased the proportion of endothelial cells (ECs) in the lungs of neonatal mice. In hyperoxic lung ECs of neonatal mice, we detected upregulated fibroblast growth factor receptor 1 (FGFR1) expression, accompanied by upregulation of the classic downstream signaling pathway of activated FGFR1, including the ERK/MAPK signaling pathway and PI3K-Akt signaling pathway. Specific deletion of Fgfr1 in the ECs of neonatal mice protected the lungs from hyperoxia-induced lung injury, with improved angiogenesis, alveologenesis and respiratory metrics. Intriguingly, the increased Fgfr1 expression was mainly attributed to aerosol capillary endothelial (aCap) cells rather than general capillary endothelial (gCap) cells. Deletion of endothelial Fgfr1 increased the expression of gCap cell markers but decreased the expression of aCap cell markers. Additionally, inhibition of FGFR1 by an FGFR1 inhibitor improved alveologenesis and respiratory metrics. In summary, this study suggests that in neonatal mice, hyperoxia increases the expression of endothelial FGFR1 in lung ECs and that deficiency of endothelial Fgfr1 can ameliorate hyperoxia-induced BPD. These data suggest that FGFR1 may be a potential therapeutic target for BPD, which will provide a new strategy for the prevention and treatment of BPD.
CP-25 exerts a protective effect against ConA-induced hepatitis via regulating inflammation and immune response
Authors: Li Nan , Wu Jing-Jing , Qi Meng , Wang Zi-Ying , Zhang Sheng-Nan , Li Xiu-Qin , Chen Ting-Ting , Wang Mei-Fang , Zhang Ling-Ling , Wei Wei , Sun Wu-Yi
Published: November 2022

Hepatitis is a complex multifactorial pathological disorder, which can eventually lead to liver failure and even potentially be life threatening. Paeoniflorin-6′-O-benzene sulfonate (CP-25) has proven to have critical anti-inflammatory effects in arthritis. However, the effects of CP-25 in the pathogenesis of hepatitis remains unclear. In this experiment, mice were intragastrically administered with CP-25 (25, 50 and 100 mg/kg), and then ConA (25 mg/kg) was intravenous injected to establish hepatitis model in vivo. CP-25 administration attenuated liver damage and decreased ALT and AST activities in mice with hepatitis. Besides, CP-25 modulated immune responses including down-regulated the proportions of activated CD4+, activated CD8+ T cells, and ratio of Th1/Th2 in ConA-injected mice. Furthermore, ConA-mediated production of reactive oxygen species (ROS), release of inflammatory cytokines including IFN-γ, TNF-α, activation of MAPK pathways and nuclear translocation of nuclear factor-kappaB (NF-κB) were significantly decreased in CP-25 administrated mice. In ConA-stimulated RAW264.7 cells, CP-25 suppressed inflammatory cytokines secretion and reduced ROS level, which were consistent with animal experiments. Otherwise, the data showed that CP-25 restrained phosphorylation of ERK, JNK and p38 MAPK pathways influenced by ROS, accompanied with inhibiting NF-κB nuclear translocation. In conclusion, our findings indicated that CP-25 protected against ConA-induced hepatitis may through modulating immune responses and attenuating ROS-mediated inflammation via the MAPK/NF-κB signaling pathway.
Virtual screening and drug repositioning of FDA-approved drugs from the ZINC database to identify the potential hTERT inhibitors
Authors: Afzaal Hasan , Altaf Reem , Ilyas Umair , Zaman Shaiq Uz , Abbas Hamdani Syed Damin , Khan Saifullah , Zafar Hajra , Babar Mustafeez Mujtaba , Duan Yongtao
Published: November 2022

The length of the telomeres is maintained with the help of the enzyme telomerase constituting of two components, namely, a core reverse transcriptase protein (hTERT) and RNA (hTR). It serves as a significant and universal cancer target. In silico approaches play a crucial role in accelerating drug development processes, especially cancer drug repurposing is an attractive approach. The current study is aimed at the repurposing of FDA-approved drugs for their potential role as hTERT inhibitors. Accordingly, a library of 2,915 sets of FDA-approved drugs was generated from the ZINC database in order to screen for novel hTERT inhibitors; later on, these were subjected to molecular docking analysis. The top two hits, ZINC03784182 and ZINC01530694, were shortlisted for molecular dynamic simulation studies at 100 ns based on their binding scores. The RMSD, RMSF, Rg, SASA, and interaction energies were calculated for a 100-ns simulation period. The hit compounds were also analyzed for antitumor activity, and the results revealed promising cytotoxic activities of these compounds. The study has revealed the potential application of these drugs as antitumor agents that can be useful in treating cancer and can serve as lead compounds for further in vivo, in vitro, and clinical studies.
Low-dose naloxone for prophylaxis of sufentanil-induced choking and postoperative nausea and vomiting
Authors: Qian Yiling , Huang Zhifei , Wang Guilong , Han Jinghong , Zhou Difei , Ding Hailei , Zhang Xin
Published: November 2022

Sufentanil, a potent opioid, serves as the first option for perioperative analgesia owing to its analgesic effect, long duration and stable hemodynamics, whereas its side effects frequently blunt its application. The intravenous (IV) injection of sufentanil during anesthesia induction has high incidence of choking or bucking reaction, which is defined as sufentanil-induced cough (SIC). Moreover, postoperative nausea and vomiting (PONV) is a common and stressful complication, which is also related to the usage of opioid. High incidence of PONV is reported in the patients with SIC. Hence, we sought to determine whether naloxone, an opioid antagonist, at low dose would decrease the incidences of SIC and PONV. 216 female patients undergoing gynecological laparoscopic operation (<2 h) under general anesthesia were recruited in this study, and randomly assigned into two groups: Group N (patients receiving naloxone and Group C (patients receiving vehicle). Sufentanil (0.5 μg/kg within 5 s) was given in anesthesia induction, and low-dose naloxone (1.25 μg/kg) or identical vehicle was initially injected 5 min prior to induction, with the incidence and severity of SIC estimated. Subsequently, naloxone or vehicle was continuously infused at the rate of 0.5 μg/kg/h in the initiation of operation until the end of the operation, and the transverse abdominal fascia block (TAP) was performed for postoperative analgesia. The PONV profiles such as incidence and the severity, grading, and the frequencies of antiemetic usage within 24 h were evaluated, with VAS scores and remedial measures for analgesia during the first 24 h postoperatively were recorded. Our results revealed that one bolus of low-dose naloxone prior to the induction significantly mitigated the incidence of SIC, and intraoperative continuous infusion of low-dose naloxone reduced the incidence and the severity of PONV, so that the postoperative VAS scores and further remedial analgesia were not altered. These results not only provide clinical solutions for prophylaxis of SIC and PONV, but also suggests that opioids may act as a key role in both SIC and PONV, whereas opioid antagonist may hit two tasks with one stone. Moreover, further investigations are required to address the underlying mechanism of SIC and PONV.

Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2200064865].
Buprenorphine exposure levels to optimize treatment outcomes in opioid use disorder
Authors: Laffont Celine M. , Ngaimisi Eliford , Gopalakrishnan Mathangi , Ivaturi Vijay , Young Malcolm , Greenwald Mark K. , Heidbreder Christian
Published: November 2022

The severity of the ongoing opioid crisis, recently exacerbated by the COVID-19 pandemic, emphasizes the importance for individuals suffering from opioid use disorder (OUD) to have access to and receive efficacious, evidence-based treatments. Optimal treatment of OUD should aim at blocking the effects of illicit opioids while controlling opioid craving and withdrawal to facilitate abstinence from opioid use and promote recovery. The present work analyses the relationship between buprenorphine plasma exposure and clinical efficacy in participants with moderate to severe OUD using data from two clinical studies (39 and 504 participants). Leveraging data from placebo-controlled measures assessing opioid blockade, craving, withdrawal and abstinence, we found that buprenorphine plasma concentrations sustained at 2–3 ng/ml (corresponding to ≥70% brain mu-opioid receptor occupancy) optimized treatment outcomes in the majority of participants, while some individuals (e.g., injecting opioid users) needed higher concentrations. Our work also included non-linear mixed effects modeling and survival analysis, which identified a number of demographic, genetic and social factors modulating treatment response and retention. Altogether, these findings provide key information on buprenorphine plasma levels that optimize clinical outcomes and increase the likelihood of individual treatment success. NLM identifiers: NCT02044094, NCT02357901.
Systematic review of efficacy, safety and pharmacokinetics of intravenous and intraventricular vancomycin for central nervous system infections
Authors: Liu Shu-Ping , Xiao Jing , Liu Ya-Li , Wu Yue-E , Qi Hui , Wang Zhuang-Zhuang , Shen A-Dong , Liu Gang , Zhao Wei
Published: November 2022

Objective: The decision of vancomycin dosage for central nervous system (CNS) infections is still a challenge because its bactericidal nature in cerebrospinal fluid (CSF) has not been confirmed by human studies. This study systematically reviewed the literatures on vancomycin in patients with meningitis, ventriculitis, and CNS device-associated infections, to assess efficacy, safety, and pharmacokinetics to better serve as a practical reference.

Methods: Medline, Embase, and Cochrane Library were searched using terms vancomycin, Glycopeptides, meningitis, and central nervous system infections. Data were extracted including characteristics of participants, causative organism(s), administration, dosage, etc., The clinical response, microbiological response, adverse events and pharmacokinetic parameters were analyzed.

Results: Nineteen articles were included. Indications for vancomycin included meningitis, ventriculitis, and intracranial device infections. No serious adverse effects of intravenous (IV) and intraventricular (IVT) vancomycin have been reported. Dosages of IV and IVT vancomycin ranged from 1000–3000 mg/day and 2–20 mg/day. Duration of IV and IVT vancomycin therapy most commonly ranged from 3–27 days and 2–21 days. Therapeutic drug monitoring was conducted in 14 studies. Vancomycin levels in CSF in patients using IV and IVT vancomycin were varied widely from 0.06 to 22.3 mg/L and 2.5–292.9 mg/L. No clear relationships were found between vancomycin CSF levels and efficacy or toxicity.

Conclusion: Using vancomycin to treat CNS infections appears effective and safe based on current evidence. However, the optimal regimens are still unclear. Higher quality clinical trials are required to explore the vancomycin disposition within CNS.
Identification of potential extracellular signal-regulated protein kinase 2 inhibitors based on multiple virtual screening strategies
Authors: Yang Ruoqi , Zhao Guiping , Zhang Lili , Xia Yu , Yu Huijuan , Yan Bin , Cheng Bin
Published: November 2022

The integration of multiple virtual screening strategies facilitates the balance of computational efficiency and prediction accuracy. In this study, we constructed an efficient and reliable “multi-stage virtual screening-in vitro biological validation” system to identify potential inhibitors targeting extracellular signal-regulated protein kinase 2 (ERK2). Firstly, we rapidly obtained 10 candidate ERK2 inhibitors with desirable pharmacokinetic characteristics from thousands of named natural products in ZINC database based on machine learning classification models and ADME/T prediction. The structure-based molecular docking approach was then used to obtain four further hits with lower binding free energy compared to the positive control molecule Magnolipin. Subsequently, the two compounds were purchased for in vitro biological validation considering commercial availability and economic cost, and the results showed that Dodoviscin A exhibited acceptable inhibitory activity on ERK2 (IC50 = 10.79 μm). Finally, the mechanism of action and binding stability of this natural product inhibitor were investigated by binding mode analysis and molecular dynamics simulation.
Combining NSP and NER for public opinion event extraction model
Authors: Zhang Qingchuan , Wei Siwei , Li Zihan , Yan Wenjing
Published: November 2022

Event extraction in the field of public opinion aims to extract important event arguments and their corresponding roles from the moment-to-moment generated opinion reports. Most of the existing research methods divide the task into three subtasks: event trigger extraction, event type detection, and event argument extraction. Despite the remarkable achievements of the event argument extraction paradigm combining part-of-speech (POS) and event trigger features, the performance of POS features in combinatorial event argument extraction tasks is struggling due to its inherent semantic diversity in Chinese. In addition, previous research work ignored the deep semantic interaction between event trigger and text. To address the aforementioned problems, this paper proposes an opinion event extraction model (NN-EE) combining NSP and NER, which alleviates the lack of performance of combinatorial event argument extraction by introducing NER technology. Meanwhile, the event trigger features are incorporated into the NSP mechanism of the pre-trained language model BERT to prompt the model to learn the deep semantic interaction between the event trigger and original text. The results of the self-constructed food opinion report dataset (FD-OR) in this paper show that the NN-EE model achieves optimal performance.
Reconstruction of the interplanetary magnetic field from the magnetosheath data: A steady-state approach
Authors: Toepfer S. , Narita Y. , Schmid D.
Published: November 2022

In the steady-state picture, the magnetic field can be formulated by a curl-free potential field in the magnetosheath region, and the sheath field is uniquely and linearly determined by the upstream field and the transformation matrix which contains the effect of field cancellation making the magnetospheric cavity. The curl-free sheath model can be used to reconstruct the upstream field for a given magnetic field data set in the magnetosheath region. The applicability and the limits are theoretically evaluated such that the reconstruction works reasonably as far as the sheath sampling position is not close to the magnetopause, and that the upstream field can be estimated within an error ranging from 10 to 40 percent, depending on the region of sampling.
Optoelectronic integrated circuits for analog optical computing: Development and challenge
Authors: Dan Yihang , Fan Zeyang , Chen Qi , Lai Yihang , Sun Xiaojuan , Zhang Tian , Xu Kun
Published: November 2022

Over the past 2 decades, researches in artificial neural networks (ANNs) and deep learning have flourished and enabled the applications of artificial intelligence (AI) in image recognition, natural language processing, medical image analysis, molecular and material science, autopilot and so on. As the application scenarios for AI become more complex, massive perceptual data need to be processed in real-time. Thus, the traditional electronic integrated chips for executing the calculation of ANNs and deep learning algorithms are faced with higher requirements for computation speed and energy consumption. However, due to the unsustainability of Moore’s Law and the failure of the Dennard’s scaling rules, the growth of computing power of the traditional electronic integrated chips based on electronic transistors and von Neumann architecture could difficultly match the rapid growth of data volume. Enabled by silicon-based optoelectronics, analog optical computing can support sub-nanosecond delay and ∼fJ energy consumption efficiency, and provide an alternative method to further greatly improve computing resources and to accelerate deep learning tasks. In Chapter 1, the challenges of electronic computing technologies are briefly explained, and potential solutions including analog optical computing are introduced. Then, separated by four photonic platforms, including coherent integration platform, incoherent integration platform, space-propagation optical platform, and optical fiber platform, the recent important research progresses in analog optical computing are outlined in Chapter 2. Then, the nonlinearity and training algorithm for analog optical computing are summarized and discussed in Chapter 3. In Chapter 4, the prospects and challenges of analog optical computing are pointed out.