bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Knowledge in Genetics, Molecular Diagnostic Tools, and Treatments for Mantle Cell Lymphomas
Authors: Sethi Shenon , Epstein-Peterson Zachary , Kumar Anita , Ho Caleb
Published: November 2021

Mantle Cell lymphoma (MCL) is a mature B-cell lymphoma with a well-known hallmark genetic alteration in most cases, t (11,14)(q13q32)/CCND1-IGH. However, our understanding of the genetic and epigenetic alterations in MCL has evolved over the years, and it is now known that translocations involving CCND2, or cryptic insertion of enhancer elements of IGK or IGL gene, can also lead to MCL. On a molecular level, MCL can be broadly classified into two subtypes, conventional MCL (cMCL) and non-nodal MCL (nnMCL), each with different postulated tumor cell origin, clinical presentation and behavior, mutational pattern as well as genomic complexity. This article reviews both the common and rare alterations in MCL on a gene mutational, chromosomal arm, and epigenetic level, in the context of their contribution to the lymphomagenesis and disease evolution in MCL. This article also summarizes the important prognostic factors, molecular diagnostic tools, and treatment options based on the most recent MCL literature.
Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
Authors: Cheng Yi , Wang Guiying , Zhao Lianmei , Dai Suli , Han Jing , Hu Xuhua , Zhou Chaoxi , Wang Feifei , Ma Hongqing , Li Baokun , Meng Zesong
Published: November 2021

Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the effect of PPM on CRC cells. CRC cells were treated with PPM and cell viability was evaluated by CCK-8 assay. Flow cytometry and TUNEL staining were performed to assess cell cycle and apoptosis. Quantitative proteomics has been used to check the proteins differentially expressed by using tandem mass tag (TMT) labeling and liquid chromatography–tandem mass spectrometry. Bioinformatic analysis was undertaken to identify the biological processes that these differentially expressed proteins are involved in. Gene expression was analyzed by western blotting. The effect of PPM in vivo was primarily checked in a subcutaneous xenograft mouse model of CRC, and the gene expression of tumor was checked by histochemistry staining. PPM could inhibit the proliferation of CRC cells in a dose-dependent manner, induce cell apoptosis and promote G0/G1 cell cycle arrest. A total of 539 proteins were identified differentially expressed following PPM treatment, where among those there were 286 genes upregulated and 293 downregulated. PPM treatment caused a pro-apoptosis gene expression profile both in vivo and in vitro, and impaired PI3K/AKT signaling pathway might be involved. In addition, PPM treatment caused less detrimental effects on blood cell, hepatic and renal function in mice, and the anti-cancer effect was found exaggerated by PPM+5-FU combination treatment. PPM may perform anti-CRC effects by promoting cell apoptosis and this might be achieved by targeting PI3K/AKT pathway. PPM might be a safe and promising anti-cancer drug that needs to be further studied.
Impact of Pathology Review in Adverse Histological Characteristics and pT Stages of Upper Tract Urothelial Cancer in a Multicenter Study
Authors: Chang Chia-Hui , Wu Wen-Jeng , Lee Hsiang-Ying , Lin Chih-Hung , Yue Chung-Tai , Jiang Yuan-Hong , Lee Yu-Khun , Huang Kuan Hsun , Tsai Yao Chou
Published: November 2021

Purpose

Pathology reviews for upper urinary tract cancer (UTUC) remained scarce in the literature. Here, we reported the interobserver variation among the review and local pathologies of featured histologic characteristics for UTUC.

Methods

Patients who underwent definitive surgical treatments for UTUC were retrospectively reviewed for eligibility of pathology review. In the Taiwan UTUC Collaboration cohort, 212 cases were reviewed, of which 154 cases were eligible for pathology review. Agreement between original pathology and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic impact was analyzed by the Cox regression model with the estimation of hazard ratios (HR) and 95% confidence intervals.

Results

There were 80 women and 74 men enrolled in this study, and the median age at treatment was 71.7 years. The agreement is moderate agreement for surgical margin status (87.7%; κ = 0.61), tumor grade (82.5%; κ = 0.43), tumor invasiveness (76.6%; κ = 0.45), lymphovascular invasion (70.8%; κ = 0.42) and T stage (67.5%; κ = 0.52). The interobserver agreements for perineural invasion and variant histology identification were slight. Kaplan–Meier analysis for disease-free survival revealed comparable results in local and review pathology for localized (Tis, Ta, T1–2) or advanced T stage (T3–4).

Conclusions

Pathology review of UTUC had minimal impact on clinical practice based on current available disease treatment guidelines. However, significant interobserver variations were observed in featured adverse histopathological characters.
Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?
Authors: Hu Li-Feng , Lan Huan-Rong , Huang Dong , Li Xue-Min , Jin Ke-Tao
Published: November 2021

Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.
Impact of Perioperative Absolute Neutrophil Count on Central Line-Associated Bloodstream Infection in Children With Acute Lymphoblastic and Myeloid Leukemia
Authors: Martynov Illya , Schoenberger Joachim
Published: November 2021

Background

There is lack of evidence concerning safety of placement of tunneled central venous catheters (TCVCs) in neutropenic children with acute leukemias. Here, we evaluate the impact of absolute neutrophil count (ANC) at the time of TCVC placement on development of central line-associated bloodstream infections (CLABSI) in children with lymphoblastic (ALL) or myeloid leukemia (AML).

Materials and Methods

A retrospective observational study of children undergoing TCVC placement at a tertiary referral hospital between January 2000 and December 2019 was performed. Traditional and competing-risks regression models were used to estimate the effect of perioperative ANC on development of CLABSI.

Results

A total of 350 children (median age 6.4 [IQR: 3.1–10.9] years) underwent 498 consecutive TCVC implantations in neutropenic (n = 172, 34.5%) and non-neutropenic conditions (n = 326, 65.5%). The median length of observation per TCVC was 217.1 (IQR: 116.1–260.5) days with a total of 99,681 catheter days (CD). There were no differences in early (within first 30 days after TCVC placement) and overall CLABSI rates between neutropenic and non-neutropenic patients (HR 1.250, p = 0.502; HR 1.633, p = 0.143). We identified female sex (HR 2.640, p = 0.006) and the use of TCVC for treatment of relapsed leukemia (HR 4.347, p < 0.0001) as risk factors for early CLABSI and the use of double-lumen catheters (HR 2.607, p = 0.003) and use of TCVCs during leukemia relapse (HR 2.004, p = 0.005) for overall study period.

Conclusion

The placement of TCVC in children with neutropenia undergoing anticancer therapy for acute leukemia is safe and not associated with an elevated rate of CLABSI.
Microenvironmental Factors Modulating Tumor Lipid Metabolism: Paving the Way to Better Antitumoral Therapy
Authors: Cai Limeng , Ying Minfeng , Wu Hao
Published: November 2021

Metabolic reprogramming is one of the emerging hallmarks of cancer and is driven by both the oncogenic mutations and challenging microenvironment. To satisfy the demands of energy and biomass for rapid proliferation, the metabolism of various nutrients in tumor cells undergoes important changes, among which the aberrant lipid metabolism has gained increasing attention in facilitating tumor development and metastasis in the past few years. Obstacles emerged in the aspect of application of targeting lipid metabolism for tumor therapy, due to lacking of comprehensive understanding on its regulating mechanism. Tumor cells closely interact with stromal niche, which highly contributes to metabolic rewiring of critical nutrients in cancer cells. This fact makes the impact of microenvironment on tumor lipid metabolism a topic of renewed interest. Abundant evidence has shown that many factors existing in the tumor microenvironment can rewire multiple signaling pathways and proteins involved in lipid metabolic pathways of cancer cells. Hence in this review, we summarized the recent progress on the understanding of microenvironmental factors regulating tumor lipid metabolism, and discuss the potential of modulating lipid metabolism as an anticancer approach.
Functional Peptides Encoded by Long Non-Coding RNAs in Gastrointestinal Cancer
Authors: Chen Yao , Long Weili , Yang Liqiong , Zhao Yueshui , Wu Xu , Li Mingxing , Du Fukuan , Chen Yu , Yang Zhihui , Wen Qinglian , Yi Tao , Xiao Zhangang , Shen Jing
Published: November 2021

Gastrointestinal cancer is by far the most common malignancy and the most common cause of cancer-related deaths worldwide. Recent studies have shown that long non-coding RNAs (lncRNAs) play an important role in the epigenetic regulation of cancer cells and regulate tumor progression by affecting chromatin modifications, gene transcription, translation, and sponge to miRNAs. In particular, lncRNA has recently been found to possess open reading frame (ORF), which can encode functional small peptides or proteins. These peptides interact with its targets to regulate transcription or the signal axis, thus promoting or inhibiting the occurrence and development of tumors. In this review, we summarize the involvement of lncRNAs and the function of lncRNAs encoded small peptides in gastrointestinal cancer.
Combination of Endoscopic Resection and Radiofrequency Ablation for the Treatment of Esophageal Squamous Cell Neoplasia With Multiple Lugol-Voiding Lesions
Authors: Chen Zhihao , Dou Lizhou , Liu Yong , Zhang Yueming , He Shun , Xue Liyan , Wang Guiqi
Published: November 2021

Background

Local recurrence of esophageal squamous cell neoplasia (ESCN) and metachronous ESCN was associated with severe background esophageal multiple Lugol-voiding lesions (LVLs) even though the primary early ESCNs were treated with endoscopic resection (ER). The aim of this study is to explore the feasibility and effectiveness of combination treatments of ER and radiofrequency ablation (RFA) in patients with early ESCNs with synchronous multiple LVLs.

Methods

A total of 329 patients with early ESCNs and synchronous multiple LVLs received ER combined with RFA from September 2010 to September 2020. Clinical and pathological features and treatment outcomes were retrospectively reviewed using medical records. Factors associated with background esophageal multiple LVLs before combined treatment were analyzed.

Results

The proportion of complete response (CR) was 96.7% after primary RFA, while 90.3% patients achieved CR for the last endoscopic examinations regardless if inside or outside the treatment area (TA). Degeneration of background esophageal multiple LVLs occurred in 70.2% of patients. The grade of background esophageal multiple LVLs before combined treatment was closely related to gender, smoking, and drinking. The incidence of metachronous ESCNs outside the TA of ER and local recurrence in the TA of ER was 3.9% and 1.2%, respectively.

Conclusions

Prophylactic RFA treatment of multiple LVLs together with ER treatment of the primary ESCNs may be effective in reducing the incidence of metachronous ESCNs and local recurrence through improving the background esophageal mucosa.
Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis
Authors: Polesel Jerry , Menegaldo Anna , Tirelli Giancarlo , Giacomarra Vittorio , Guerrieri Roberto , Baboci Lorena , Casarotto Mariateresa , Lupato Valentina , Fanetti Giuseppe , Boscolo-Rizzo Paolo , Fratta Elisabetta
Published: November 2021

Background

At present, the prognostic significance of programmed cell death receptor ligand 1 (PD-L1) expression in oropharyngeal squamous cell carcinoma (OPSCC) patients is still controversial. In this study, we aim to synthesize relevant studies that have assessed the prognostic value of PD-L1 in patients with primary OPSCC treated according to the current standard-of-care.

Methods

A systematic search of Medline/PubMed, Cochrane, Embase, Web of Science, and Scopus was conducted to define the prognostic role of PD-L1 expression in OPSCC. All studies published before July 31, 2021 were screened. Summary hazard ratios (sHR) with 95% confidence intervals (CIs) were calculated using a random-effects model.

Results

A total of 1522 OPSCC patients from 12 studies were included. PD-L1 expression in OPSCC tumor cells (TCs) was significantly associated with longer overall survival (sHR=0.63, 95% CI 0.50-0.79), and progression-free survival (sHR=0.62, 95% CI 0.49-0.79). A benefit in survival was also observed in PD-L1-positive OPSCC patients who underwent surgery (sHR=0.34, 95% CI 0.18-0.65). Finally, although PD-L1-positive expression was related to better outcomes both in HPV-negative and HPV-positive OPSCC, the difference reached the statistical significance only in the HPV-positive subgroup (sHR=0.37, 95% CI 0.19-0.73). No heterogeneity emerged between studies for all considered outcomes, with I2 ranging from 0% for progression-free survival to 11% for overall survival.

Conclusions

PD-L1 expression on TCs associated with improved survival in OPSCC. In particular, HPV-positive OPSCC most benefited from PD-L1 expression when compared to the PD-L1 negative counterpart. Thus, PD-L1 might represent a useful biomarker to stratify prognosis in OPSCC in addition to HPV status.
Multimodal Deep Learning for Prognosis Prediction in Renal Cancer
Authors: Schulz Stefan , Woerl Ann-Christin , Jungmann Florian , Glasner Christina , Stenzel Philipp , Strobl Stephanie , Fernandez Aurélie , Wagner Daniel-Christoph , Haferkamp Axel , Mildenberger Peter , Roth Wilfried , Foersch Sebastian
Published: November 2021

Background

Clear-cell renal cell carcinoma (ccRCC) is common and associated with substantial mortality. TNM stage and histopathological grading have been the sole determinants of a patient’s prognosis for decades and there are few prognostic biomarkers used in clinical routine. Management of ccRCC involves multiple disciplines such as urology, radiology, oncology, and pathology and each of these specialties generates highly complex medical data. Here, artificial intelligence (AI) could prove extremely powerful to extract meaningful information to benefit patients.

Objective

In the study, we developed and evaluated a multimodal deep learning model (MMDLM) for prognosis prediction in ccRCC.

Design, Setting, and Participants

Two mixed cohorts of non-metastatic and metastatic ccRCC patients were used: (1) The Cancer Genome Atlas cohort including 230 patients and (2) the Mainz cohort including 18 patients with ccRCC. For each of these patients, we trained the MMDLM on multiscale histopathological images, CT/MRI scans, and genomic data from whole exome sequencing.

Outcome Measurements and Statistical Analysis

Outcome measurements included Harrell’s concordance index (C-index) and also various performance parameters for predicting the 5-year survival status (5YSS). Different visualization techniques were used to make our model more transparent.

Results

The MMDLM showed great performance in predicting the prognosis of ccRCC patients with a mean C-index of 0.7791 and a mean accuracy of 83.43%. Training on a combination of data from different sources yielded significantly better results compared to when only one source was used. Furthermore, the MMDLM’s prediction was an independent prognostic factor outperforming other clinical parameters.

Interpretation

Multimodal deep learning can contribute to prognosis prediction in ccRCC and potentially help to improve the clinical management of this disease.

Patient Summary

An AI-based computer program can analyze various medical data (microscopic images, CT/MRI scans, and genomic data) simultaneously and thereby predict the survival time of patients with renal cancer.
Increased Risk for Cerebral Hypoxia During Immediate Neonatal Transition After Birth in Term Neonates Delivered by Caesarean Section With Prenatal Tobacco Exposure
Authors: Wolfsberger Christina Helene , Bruckner Marlies , Schwaberger Bernhard , Mileder Lukas Peter , Pritisanac Ena , Hoeller Nina , Avian Alexander , Urlesberger Berndt , Pichler Gerhard
Published: November 2021

Introduction: Maternal tobacco smoking during pregnancy is a global health problem leading to an increased risk for fetal and neonatal morbidities. So far, there are no data of the potential impact of maternal smoking during pregnancy on the most vulnerable period after birth – the immediate postnatal transition. The aim of the present study was therefore, to compare cerebral oxygenation during immediate postnatal transition in term neonates with and without prenatal tobacco exposure.

Methods: Included in this post-hoc analysis were healthy term neonates, with measurements of cerebral oxygenation (INVOS 5100C) during the first 15 min after birth, and for whom information on maternal smoking behavior during pregnancy was available. Neonates with prenatal tobacco exposure (smoking group) were matched 1:1 according to gestational age (±1 week), birth weight (±100 grams) and hematocrit (±5 %) to neonates without (non-smoking group). Cerebral regional tissue oxygen saturation (crSO2), cerebral fractional tissue oxygen extraction (cFTOE), arterial oxygen saturation (SpO2) and heart rate (HR) within the first 15 min after birth were compared between the two groups.

Results: Twelve neonates in the smoking group with a median (IQR) gestational age of 39.1 (38.8–39.3) weeks and a birth weight of 3,155 (2,970–3,472) grams were compared to 12 neonates in the non-smoking group with 39.1 (38.7–39.2) weeks and 3,134 (2,963–3,465) grams. In the smoking group, crSO2 was significantly lower and cFTOE significantly higher until min 5 after birth. HR was significantly higher in the smoking group in min 3 after birth. Beyond this period, there were no significant differences between the two groups.

Conclusion: Cerebral oxygenation within the first 5 min after birth was compromised in neonates with prenatal tobacco exposure. This observation suggests a higher risk for cerebral hypoxia immediately after birth due to fetal tobacco exposure.
ATLAS2030 Pediatric Gait Exoskeleton: Changes on Range of Motion, Strength and Spasticity in Children With Cerebral Palsy. A Case Series Study
Authors: Delgado Elena , Cumplido Carlos , Ramos Jaime , Garcés Elena , Puyuelo Gonzalo , Plaza Alberto , Hernández Mar , Gutiérrez Alba , Taverner Thomas , Destarac Marie André , Martínez Mercedes , García Elena
Published: November 2021

Background: Cerebral Palsy (CP), the most common motor disability in childhood, affects individual's motor skills, movement and posture. This results in limited activity and a low social participation. The ATLAS2030 exoskeleton is a pediatric device that enables gait rehabilitation for children with neurological or neuromuscular pathologies with gait pathology.

Purpose: To study changes in relation to range of motion (ROM), strength and spasticity in children with CP after using the ATLAS2030 gait exoskeleton.

Methods and Participants: Three children (mean age 8.0 ± 2.0), two girls and one boy, two of them with GMFCS IV and one with GMFCS III, received robot-assisted gait training (RAGT) with ATLAS2030 for one month.

Results: The average time of exoskeleton use was 54.7 ± 10.4 min in all sessions, and all participants were able to perform all exercises. The strength of all muscle groups was increased after the 10 sessions for the participants assessed and the limited ROM in the sagittal plane (hip and knee extension and ankle dorsiflexion) decreased after the use of the exoskeleton compared to the initial state. Spasticity was reduced at the end of the sessions after the use of the exoskeleton compared to their initial state.

Conclusion: The ROM, spasticity and strength were improved after RAGT with ATLAS2030 exoskeleton in these children with CP. However, further studies with larger samples should be carried out to confirm our findings.
The Prevalence of Insufficient Sleep and Bedtime Delay Among Kindergarten Children Aged 3 to 6 Years in a Rural Area of Shanghai: A Cross-Sectional Study
Authors: Chen Xi , Qiang Yan , Liu Xia , Yang Qing , Zhu Qingqing , Li Bin , Wang Ruiping
Published: November 2021

Introduction: Sleep deprivation in children is a global public health problem that affects the physical and mental development of children. Bedtime delay induced by longer screen time and heavy study load is a common cause of sleep deprivation in children. However, the prevalence of insufficient sleep and bedtime delay and related influencing factors among kindergarten children is limited in Shanghai, China.

Methods: In 2018, we selected 8,586 children aged 3 to 6 years and their parents in Songjiang District, Shanghai. Data was collected among parents by face-to-face questionnaire interview with signed informed consent. We defined insufficient sleep as those who slept for < 10 h in children aged 3–5 years or 9 h in children aged 6 years within 24 h, and we define bedtime delay as children with bedtime after 21:00. SAS 9.1.3 software was used to calculate the prevalence of bedtime delay and insufficient sleep, and logistic regression was used to explore potential influencing factors.

Results: The prevalence of insufficient sleep and bedtime delay among children aged 3 to 6 years was 11.67 and 56.85%, respectively. The prevalence of insufficient sleep among boys was slightly higher than among girls [odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.04–1.35]. With the increase of the age of children, the prevalence of insufficient sleep increased gradually (P < 0.05). The prevalence of insufficient sleep was higher among the only child in the family (OR = 1.18, 95% CI: 1.02–1.36) and those with longer hours of TV watching (OR = 109, 95% CI: 1.02–1.16). Meanwhile, the prevalence of bedtime delay was also higher among the only child in the family (OR = 1.17, 95% CI: 1.06–1.79), among those with parents accompanying for sleep (OR = 1.21, 95% CI: 1.10-1.34), and those with longer TV watching time (OR = 1.13, 95% CI: 1.07–1.18).

Conclusions: Insufficient sleep and bedtime delay were prevalent in Chinese children aged 3 to 6 years, especially in boys and older children. TV watching as well as parents accompanying for sleep were associated with insufficient sleep and bedtime delay. We recommend that parents should limit the screen time of children, advocate earlier bedtime and later morning wake-up among children, as well as make their children sleep in separate beds or rooms in younger age.
Preschool Exposure to Online Games and Internet Gaming Disorder in Adolescents: A Cohort Study
Authors: Jeong Hyunsuk , Yim Hyeon Woo , Lee Seung-Yup , Lee Hae Kook , Potenza Marc N. , Shin Yunmi
Published: November 2021

Objectives: Although considerable evidence has already been collected on the effects of early initiation of drug/alcohol consumption on addictive behaviors in adolescents, little is known about the impact of early exposure to online games during preschool ages on the risk of internet gaming disorder (IGD). We evaluated the effects of exposure to online games before entering elementary school on IGD occurrence during the secondary school years using a community-based longitudinal study.

Methods: Data from 1,760 adolescents (seventh grade), who were recruited from the iCURE study and followed for 2 years, were analyzed. A high risk of IGD (HRIGD) was assessed by the Internet Game Use Elicited Symptom Screen, a self-reported questionnaire based on the fifth version of DSM-5 IGD criteria. Early exposure to online gaming was defined as when adolescents played online games during their preschool years. A multivariate generalized-estimating-equation model was applied to examine the independent risk factor of the occurrence of HRIGD during the 2-year follow-up period.

Results: As compared with the later-exposure group, those with early exposure to online games showed an ~1.7-fold greater incidence of HRIGD over the 2-year follow-ups after adjusting for potential confounders including baseline IGD scores (adjusted relative risk:1.69; 95%confidence interval:1.08–2.66). Pre-specified sensitivity analyses showed that the results were robust.

Conclusion: Exposure to online gaming during the preschool years increases the likelihood of occurrence of HRIGD in adolescence. Restricting exposure to online games during the preschool years should be examined as a way to reduce the risk of IGD in adolescents.

Clinical Trial Registration:www.clinicaltrials.gov, identifier: NCT02415322.
Uniportal Thoracoscopic Debridement for Children With Refractory Pleural Empyema: Case Series of 21 Patients
Authors: Huang Jin-Xi , Chen Qiang , Hong Song-Ming , Hong Jun-Jie , Cao Hua
Published: November 2021

Purpose: The effectiveness of video-assisted thoracic surgery (VATS), even uniportal VATS (U-VATS), in the treatment of pleural empyema has recently been demonstrated. However, few works have evaluated its safety and feasibility for children. We review our experience with U-VATS in the treatment of pleural empyema for children under 11 years old.

Methods: From January 2019 to December 2020, we consecutively enrolled 21 children with stage II and stage III pleural empyema in our institution. A 1.0 cm utility port was created in the 5th intercostal space at the anterior axillary line. A rigid 30°5 mm optic thoracoscope was used for vision, and two or three instruments were used through the port. Surgery was based on three therapeutic columns: removal of pleural fluid, debridement, and decortication. A chest tube was inserted through the same skin incision. Perioperative data and outcomes were summarized.

Results: The procedures were successful, and satisfactory debridement of the pleural cavity was achieved in all cases. The mean age was 4.1 years (range: 6 months to 11 years old). The mean operating time was 65.7 ± 23.2 min. No intraoperative conversion or major complications were identified among the patients. The mean hospital stay was 5.0 ± 0.6 days. At a follow-up of more than 4 months after operating, all patients had recovered well without recurrence.

Conclusion: According to our experience, U-VATS debridement is feasible for the surgical management of stage II and III empyema in the pediatric population. Indeed, U-VATS permits easier performance and complete debridement and decortication, with a very low risk for conversion.
Transmitted Drug Resistance in Antiretroviral Therapy-Naive Persons With Acute/Early/Primary HIV Infection: A Systematic Review and Meta-Analysis
Authors: Guo Chunxiang , Wu Yaxin , Zhang Yang , Liu Xinchao , Li Aixin , Gao Meixia , Zhang Tong , Wu Hao , Chen Guanzhi , Huang Xiaojie
Published: November 2021

Background: The widespread use of antiretroviral therapy (ART) has raised concerns about the emergence of HIV transmitted drug resistance (TDR). Acute HIV infection (AHI) was the most appropriate time to detect the spread of TDR. In this meta-analysis, our purpose was to evaluate the level of TDR in ART-naive patients with primary HIV infection (PHI)/AHI/early HIV infection (EHI) and to describe the critical drug-resistant mutations.

Methods: We systematically searched the literature between January 1, 2008, and April 30, 2021, in PubMed, Web of Science, Embase, and the Cochrane Library. To evaluate the overall prevalence of TDR, we extracted raw data and analyzed prevalence estimates using Stata SE.

Results: The data of this meta-analysis come from 12 observational studies, covering 3,558 ART-naive individuals with PHI, AHI, or EHI. The overall prevalence of HIV-TDR is 9.3% (95% CI: 6.8%–11.8%, I2 = 81.1%, in 11 studies). The prevalence of resistance by drug class is the highest for the nonnucleoside reverse transcriptase inhibitors (NNRTIs) at 5.7% (95% CI: 2.9%–8.5%, I2 = 96.6%, in 11 studies), followed by nucleoside reverse transcriptase inhibitors (NRTIs) at 3.4% (95% CI: 1.8%–5.0%, I2 = 86.3%, in 10 studies) and protease inhibitors (PIs) at 3.3% (95% CI: 2.7%–3.9%, I2 = 15.6%, in 10 studies). The prevalence of TDR to integrase inhibitors (INIs) is 0.3% (95% CI: 0.1%–0.7%, I2 = 95.9%, in three studies), which is the lowest among all antiretroviral drugs.

Conclusion: The overall prevalence of TDR is at a moderate level among AHI patients who have never received ART. This emphasizes the importance of baseline drug resistance testing for public health surveillance and guiding the choice of ART. In addition, the prevalence of TDR to NNRTIs is the highest, while the TDR to INIs is the lowest. This may guide the selection of clinical antiretroviral drugs.
Switching Between LC-ESI-MS/MS and EMIT Methods for Routine TDM of Valproic Acid in Pediatric Patients With Epilepsy: What Clinicians and Researchers Need to Know
Authors: Xia Ying , Long Jia-Yi , Shen Meng-Yuan , Dong Na , Guo Hong-Li , Hu Ya-Hui , Lu Xiao-Peng , Ding Xuan-Sheng , Chen Feng , Qiu Jin-Chun
Published: November 2021

Background: Valproic acid (VPA) is a widely used antiseizure medication and its dosing needs to be tailored individually through therapeutic drug monitoring (TDM) to avoid or prevent toxicity. Currently, immune-enzymatic assays such as Enzyme Multiplied Immunoassay Technique (EMIT), and Liquid Chromatography (LC)-based techniques, particularly coupled to Electrospray Ionization Tandem Mass Spectrometry (LC–ESI-MS/MS), resulting a potential lack of concordance between laboratories.

Methods: In this study, plasma VPA concentrations were determined for 711 pediatric patients with epilepsy by a routine EMIT assay and by a validated in-house LC-ESI-MS/MS method on the same group of samples, aimed to address the aforementioned concern. Consistency between two assays was evaluated using linear regression and Bland-Altman analysis.

Results: The calibration curve was linear in the range of 5.00–300 μg/ml for LC-ESI-MS/MS method and 1.00–150 μg/ml for EMIT assay, respectively. The two methods were proven to be accurate with quality control samples. As a result, a significant correlation between two methods was obtained with a regression equation described as [EMIT]=1.214×[LC−ESI−MS/MS]+3.054 (r2 = 0.9281). Bland-Altman plot showed a mean bias of 14.5 μg/ml (95% confidence interval (CI) (−0.2, 29.2) and a mean increase of 27.8% (95% CI (3.3, 52.4) measured by EMIT assay more than that measured by LC-ESI-MS/MS method.

Conclusion: In conclusion, two methods were closely correlated, but EMIT assay overestimate VPA levels in human plasma compared with LC-ESI-MS/MS method. Due to the observed significant discordance between the tested methods, switching from immunoassays to LC-based techniques for TDM of VPA deserves close attention and therapeutic range of 35.0–75.0 μg/ml may be feasible. However, further studies are needed to evaluate the eligibility of this alternative range in the clinical practice. Clinicians should be informed when switching the VPA quantitation methods during the clinical practice.
Hepatotoxicity Comparison of Crude and Licorice-Processed Euodiae Fructus in Rats With Stomach Excess-Cold Syndrome
Authors: Zhang Min , Gao Meng , Wu Shanshan , Zhou Lifen , Cao Lan , Qiao Rifa , Zhong Minyong , Yang Lin , Yuan Jinbin
Published: November 2021

In recent years, drug-induced liver injury (DILI) has become an important issue of public health. Euodiae Fructus (EF) is a commonly used herb with mild toxicity in clinic, and large doses of EF can cause significant liver damage. Licorice processing might reduce the hepatotoxicity of CEF (crude EF), but up to now, studies on the hepatotoxicity of EF have been hardly reported, let alone its material basis and mechanism of detoxification by licorice processing. This work firstly established a stomach excess-cold syndrome animal model induced by intragastric administration of cold Zhimu (Anemarrhena asphodeloides Bge). Secondly, multiple approaches and indexes were used to evaluate the hepatotoxicity of the drugs in the rats including general behavior, biochemical analysis, protein expressions, and histopathological examination. Thirdly, the hepatotoxicity of three doses of three CEF and LPEF (licorice-processed EF) extracts was systematically investigated, and the hepatotoxicity differences were analyzed and compared comprehensively among the three extracts, three doses, and CEF and LPEF. Finally, the connotation of detoxification of EF by licorice processing was preliminarily discussed according to the changes in toxic components after processing, toxicological characteristics, and TCM (traditional Chinese medicine) theory. All extracts of EF were found to have dose-dependent hepatotoxicity, and the toxicity was in the descending order of water extract, ethanol extract, and volatile oil. The hepatotoxic mechanism of EF may be related to peroxidation damage, inflammatory factor, and mitochondrial injury. The CEF hepatotoxicity can be significantly reduced by licorice processing. EF should be safe for short-term use at pharmacopeial dose under the guidance of the TCM theory. The detoxification mechanism is probably related to the reduction of toxic components and antagonistic action of licorice.
The Microbiota in Systemic Lupus Erythematosus: An Update on the Potential Function of Probiotics
Authors: Guo Xirui , Yang Xuerong , Li Qi , Shen Xiaoyan , Zhong Huiyun , Yang Yong
Published: November 2021

Systemic lupus erythematosus (SLE) is a kind of chronic diffuse connective tissue illness characterized by multisystem and multiorgan involvement, repeated recurrence and remission, and the presence of a large pool of autoantibodies in the body. Although the exact cause of SLE is not thoroughly revealed, accumulating evidence has manifested that intake of probiotics alters the composition of the gut microbiome, regulating the immunomodulatory and inflammatory response, which may be linked to the disease pathogenesis. Particularly, documented experiments demonstrated that SLE patients have remarkable changes in gut microbiota compared to healthy controls, indicating that the alteration of microbiota may be implicated in different phases of SLE. In this review, the alteration of microbiota in the development of SLE is summarized, and the mechanism of intestinal microbiota on the progression of immune and inflammatory responses in SLE is also discussed. Due to limited reports on the effects of probiotics supplementation in SLE patients, we emphasize advancements made in the last few years on the function and mechanisms of probiotics in the development of SLE animal models. Besides, we follow through literature to survey whether probiotics supplements can be an adjuvant therapy for comprehensive treatment of SLE. Research has indicated that intake of probiotics alters the composition of the gut microbiome, contributing to prevent the progression of SLE. Adjustment of the gut microbiome through probiotics supplementation seems to alleviate SLE symptoms and their cardiovascular and renal complications in animal models, marking this treatment as a potentially novel approach.
Period 2 Regulates CYP2B10 Expression and Activity in Mouse Liver
Authors: Chen MengLin , Chen Min , Lu Danyi , Wang Yi , Zhang Li , Wang Zhigang , Wu Baojian
Published: November 2021

CYP2B10 is responsible for metabolism and detoxification of many clinical drugs. Here, we aimed to investigate a potential role of Period 2 (PER2) in regulating expression of hepatic CYP2B10. Regulatory effects of PER2 on hepatic expression of CYP2B10 and other enzymes were determined using Per2-deficient mice with exons 4-6 deleted (named Per2Del4-6 mice). In vitro and in vivo metabolic activities of CYP2B10 were probed using cyclophosphamide (CPA) as a specific substrate. Regulatory mechanism was investigated using luciferase reporter assays. Genotyping and Western blotting demonstrated loss of wild-type Per2 transcript and markedly reduced PER2 protein in Per2Del4-6 mice. Hepatic expression of a plenty of drug-metabolizing genes (including Cyp2a4/2a5, Cyp2b10, Ugt1a1, Ugt1a9, Ugt2b36, Sult1a1 and Sult1e1) were altered (and majority were down-regulated) in Per2Del4-6 mice. Of note, Cyp2b10, Ugt1a9 and Sult1a1 were three genes considerably affected with reduced expression. Decreased expression of CYP2B10 was translated to reduced metabolism and altered pharmacokinetics of CPA as well as attenuated CPA hepatotoxicity in Per2Del4-6 mice. Positive regulation of CYP2B10 by PER2 was further confirmed in both Hepa-1c1c7 and AML-12 cells. Based on luciferase reporter assays, it was shown that PER2 regulated Cyp2b10 transcription in a REV-ERBα-dependent manner. REV-ERBα was negatively regulated by PER2 (increased REV-ERBα expression in Per2Del4-6 mice) and itself was also a repressor of CYP2B10. In conclusion, PER2 positively regulates CYP2B10 expression and activity in mouse liver through inhibiting its repressor REV-ERBα.
The Therapeutic Effect of Huo Xue Tong Luo Capsules in Association Research Circulation Osseous (ARCO) Stage II Osteonecrosis of the Femoral Head: A Clinical Study With an Average Follow-up Period of 7.95 Years
Authors: He Xiao-Ming , He Min-Cong , Yang Peng , Zhang Qing-Wen , Chen Zhen-Qiu , He Wei , Wei Qiu-Shi
Published: November 2021

Background: Huo Xue Tong Luo (HXTL) capsules are an oral preparation that could relieve pain and ameliorate osteonecrosis in patients with asymptomatic osteonecrosis of femoral head (ONFH). We wanted to verify whether it could be a treatment option for ARCO stage II ONFH.

Methods: A total of 44 patients (66 hips) with ARCO stage II ONFH were recruited from June 1996 to October 2013 (clinical trial registry number: ChiCTR-RPC-15006,290). HXTL capsules were given under a specific protocol, and the endpoint was set as femoral head collapse. The clinical indicators [including visual analog scale (VAS) and Harris Hip Score (HHS)] and radiological indicators [including Tonnis classification, ARCO stage, Japanese Investigation Committee (JIC) classification, lateral preserved angle (LPA), anterior preserved angle (APA), and combined preserved angle (CPA)] before and after treatment were compared. Kaplan–Meier survival analysis and Cox regression analysis were used to identify the risk factors associated with femoral head collapse.

Result: Twenty-six males and 18 females with an average age of 38.3 ± 2.8 were followed for an average of 7.95 years. Forty-six of the 66 (69.7%) hips had no progression in pain or collapse, and patients exhibited a higher HHS (p < 0.05) after therapy. Twenty of the 66 (30.3%) hips progressed in Tonnis classification and ARCO stage, but only one of the 66 (1.5%) hips required total hip arthroplasty (THA). The Kaplan–Meier survivorship curve suggested that the survival rates were 96.97% at 5 years, 69.15% at 10 years, and 40.33% at 15 years. Patients with type A necrotic lesions on anteroposterior (AP) and frog-leg lateral (FLL) radiographs revealed 100% survival rates. Multivariate Cox regression analysis revealed that patients with an LPA ≤ 60.9 exhibited a 3.87 times higher risk of collapse of the femoral head [95% confidence interval (CI), 1.241–5.673] than did those patients with an LPA>60.9.

Conclusion: HXTL capsules could be a treatment option for ARCO stage II ONFH, resulting in improved hip function and delayed progression to femoral head collapse, especially when the anterior and lateral portions of the femoral head were not affected. However, an LPA of less than 60.9° may be a risk factor for collapse of the femoral head.

Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=10829, identifier ChiCTR-OPC-15007030
The Roles and Mechanisms of lncRNAs in Liver Fibrosis
Authors: Wang Zhifa , Yang Xiaoke , Gui Siyu , Yang Fan , Cao Zhuo , Cheng Rong , Xia Xiaowei , Li Chuanying
Published: November 2021

Long non-coding RNAs (lncRNAs) can potentially regulate all aspects of cellular activity including differentiation and development, metabolism, proliferation, apoptosis, and activation, and benefited from advances in transcriptomic and genomic research techniques and database management technologies, its functions and mechanisms in physiological and pathological states have been widely reported. Liver fibrosis is typically characterized by a reversible wound healing response, often accompanied by an excessive accumulation of extracellular matrix. In recent years, a range of lncRNAs have been investigated and found to be involved in several cellular-level regulatory processes as competing endogenous RNAs (ceRNAs) that play an important role in the development of liver fibrosis. A variety of lncRNAs have also been shown to contribute to the altered cell cycle, proliferation profile associated with the accelerated development of liver fibrosis. This review aims to discuss the functions and mechanisms of lncRNAs in the development and regression of liver fibrosis, to explore the major lncRNAs involved in the signaling pathways regulating liver fibrosis, to elucidate the mechanisms mediated by lncRNA dysregulation and to provide new diagnostic and therapeutic strategies for liver fibrosis.
The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation
Authors: Lv Jinpeng , Yang Ying , Jia Bingyi , Li Siqi , Zhang Ximei , Gao Rongyin
Published: November 2021

The therapeutic use of curcumin and chemically modified curcumin (CMC) for suppressing melanogenesis and tyrosinase activity have been recognized. J147 is a modified version of curcumin with superior bioavailability and stability. However, there is no report about the effects of J147 on pigmentation in vitro and in vivo. In our studies, we investigated the hypopigmentary effects of J147 treatment on melanocytes and explored the underlying mechanism. The present studies suggested that J147 suppressed both basal and α-MSH-induced melanogenesis, as well as decreased melanocyte dendricity extension and melanosome transport. J147 played these roles mainly by activating the extracellular signal-regulated protein kinase (ERK) pathway. Once activated, it resulted in MITF degradation and further down-regulated the expression of tyrosinase, TRP-1, TRP-2, Myosin Va, Rab27a and Cdc42, ultimately inhibited melanin synthesis and melanosome transport. Furthermore, the hypopigmentary effects of J147 were demonstrated in vivo in a zebrafish model and UVB-induced hyperpigmentation model in brown guinea pigs. Our findings also suggested that J147 exhibited no cytotoxicity in vitro and in vivo. Taken together, these data confirmed that J147 may prove quite useful as a safer natural skin-whitening agent.
Mechanism and Therapeutic Opportunities of Histone Modifications in Chronic Liver Disease
Authors: Cai Qiuyu , Gan Can , Tang Chengwei , Wu Hao , Gao Jinhang
Published: November 2021

Chronic liver disease (CLD) represents a global health problem, accounting for the heavy burden of disability and increased health care utilization. Epigenome alterations play an important role in the occurrence and progression of CLD. Histone modifications, which include acetylation, methylation, and phosphorylation, represent an essential part of epigenetic modifications that affect the transcriptional activity of genes. Different from genetic mutations, histone modifications are plastic and reversible. They can be modulated pharmacologically without changing the DNA sequence. Thus, there might be chances to establish interventional solutions by targeting histone modifications to reverse CLD. Here we summarized the roles of histone modifications in the context of alcoholic liver disease (ALD), metabolic associated fatty liver disease (MAFLD), viral hepatitis, autoimmune liver disease, drug-induced liver injury (DILI), and liver fibrosis or cirrhosis. The potential targets of histone modifications for translation into therapeutics were also investigated. In prospect, high efficacy and low toxicity drugs that are selectively targeting histone modifications are required to completely reverse CLD and prevent the development of liver cirrhosis and malignancy.
60-GHz Half-Mode Substrate-Integrated Waveguide Bandpass Filter in 0.15-μm GaAs Technology
Authors: Liu Xu-Juan , Wu Wen , Xu Kai-Da , Guo Ying-Jiang , Chen Qiang
Published: November 2021

A compact 60-GHz on-chip bandpass filter (BPF) is presented using gallium arsenide (GaAs) technology. The miniaturization is achieved by the half-mode substrate-integrated waveguide (HMSIW) structure. Finally, a prototype of the BPF is fabricated and tested to validate the proposed idea, whose simulated and measured results are in good agreement. The measurements show that it has a center frequency at 58.6 GHz with a bandwidth of 17.9%, and the minimum insertion loss within the passband is 1.2 dB. The chip, excluding the feedings, is only about 0.38λg × 0.58λg, where λg is the guided wavelength at the center frequency.
Antihypertensive Treatment and Central Arterial Hemodynamics: A Meta-Analysis of Randomized Controlled Trials
Authors: Cheng Yi-Bang , Xia Jia-Hui , Li Yan , Wang Ji-Guang
Published: November 2021

Background: Antihypertensive treatment may have different effects on central arterial hemodynamics. The extent of the difference in effects between various antihypertensive drugs remains undefined.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials that explored the effects of antihypertensive agents on both central and peripheral systolic blood pressure (SBP) and pulse pressure (PP) or central augmentation index, with a special focus on the comparison between newer [renin-angiotensin-aldosterone system (RAS) inhibitors and calcium-channel blockers (CCBs)] and older antihypertensive agents (diuretics and β- and α-blockers).

Results: In total, 20 studies (n = 2,498) were included. Compared with diuretics (10 studies), β-blockers (16 studies), or an α-blocker (1 study), RAS inhibitors (21 studies), and CCBs (6 studies) more efficaciously (P < 0.001) reduced both central and peripheral SBP by a weighted mean difference of −5.63 (−6.50 to −4.76 mmHg) and −1.97 mmHg (−2.99 to −0.95 mmHg), respectively. Compared with older agents, the newer agents also more efficaciously (P < 0.001) reduced central PP (−3.27 mmHg; −4.95 to −1.59 mmHg), augmentation index (−6.11%; −7.94 to −4.29) and augmentation (−3.35 mmHg; −5.28 to –1.42 mmHg) but not peripheral PP (p ≥ 0.09). Accordingly, the newer agents reduced central-to-peripheral PP amplification significantly less than the older agents (0.11 mmHg; 0.05 to 0.17 mmHg; P < 0.001).

Conclusion: Newer agents, such as RAS inhibitors and CCBs, were significantly more efficacious than older agents in their effects on central hemodynamics.