bluuebunny/crossref_metadata_2025 huggingface dataset:
Glomerular filtration in the aging population
Authors: Noronha Irene L. , Santa-Catharina Guilherme P. , Andrade Lucia , Coelho Venceslau A. , Jacob-Filho Wilson , Elias Rosilene M.
Published: September 2022

In the last decades, improvements in the average life expectancy in the world population have been associated with a significant increase in the proportion of elderly people, in parallel with a higher prevalence of non-communicable diseases, such as hypertension and diabetes. As the kidney is a common target organ of a variety of diseases, an adequate evaluation of renal function in the approach of this population is of special relevance. It is also known that the kidneys undergo aging-related changes expressed by a decline in the glomerular filtration rate (GFR), reflecting the loss of kidney function, either by a natural senescence process associated with healthy aging or by the length of exposure to diseases with potential kidney damage. Accurate assessment of renal function in the older population is of particular importance to evaluate the degree of kidney function loss, enabling tailored therapeutic interventions. The present review addresses a relevant topic, which is the effects of aging on renal function. In order to do that, we analyze and discuss age-related structural and functional changes. The text also examines the different options for evaluating GFR, from the use of direct methods to the implementation of several estimating equations. Finally, this manuscript supports clinicians in the interpretation of GFR changes associated with age and the management of the older patients with decreased kidney function.
Evaluation of retina and microvascular changes in the patient with Parkinson’s disease: A systematic review and meta-analysis
Authors: Deng Yu , Jie Chuanhong , Wang Jianwei , Liu Ziqiang , Li Yuanyuan , Hou Xiaoyu
Published: September 2022

Background

Parkinson’s disease (PD) is a multifaceted neurodegenerative disease. The optic nerve, as a window into the central nervous system (CNS), is known to be an important part of the CNS and can be detected non-invasively. With the widespread availability of optical coherence tomography (OCT) devices, an increasing number of studies have paid attention to the neuropathological disorders in the retina of PD patients in recent years. However, it is still controversial whether OCT can be used as a complementary tool for PD diagnosis.

Methods

This review is registered with PROSPERO, number CRD42022301258. The Embase, PUBMED, and The Cochrane Library databases were independently retrieved by 2 investigators to identify relevant papers published from 1 January 2017 to 24 January 2022. These studies used OCT or OCTA to evaluate the difference in the retinal nerve fiber layer (RNFL) thickness, ganglion cell layer(GCL) thickness, macula thickness, Cup and disk area superficial retinal capillary plexus (SCP), and deep retinal capillary plexus(DCP). The standard mean difference (SMD) with the 95% confidence interval (CI) was pooled for continuous outcomes.

Results

In total, 26 studies had been enrolled in this meta-analysis with a total number of 2,790 eyes, including 1,343 eyes from the PD group along with 1,447 eyes from the HC group. The results revealed that the RNFL thickness (SMD: −0.53; 95%CI, −0.71∼−0.35; P < 0.00001), GCL thickness (SMD: −0.43; 95%CI, −0.66 to −0.19; P = 0.0003), macula thickness (SMD: −0.22; 95%CI, −0.22 to −0.11; P < 0.0001) were significantly thinner in patients with PD. The SCP (SMD: −0.61; 95%CI, −1.31to −0.10; P = 0.02) was significantly lower in PD patients. The DCP (SMD: −0.48; 95%CI, −1.02 to −0.06; P = 0.08) is lower in PD patients, but the difference was statistically insignificant.

Conclusion

Retinal nerve fiber layer thickness, GCL thickness, macular thickness, and SVD of PD patients are lower than those of healthy control. OCT and OCTA could detect morphological retinal changes in PD and might be objective and reproducible auxiliary tools to assist clinician diagnosis.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022301258].
Potential limitations in systematic review studies assessing the effect of the main intervention for treatment/therapy of COVID-19 patients: An overview
Authors: Mohseni Mahsa , Ameri Hosein , Arab-Zozani Morteza
Published: September 2022

Background

Although several studies have assessed the safety, efficacy, and effectiveness of interventions in treating the COVID-19, many of them have limitations that can have an immense impact on their results. This study aims to assess the potential limitations in systematic reviews (SRs) that evaluate the effect of interventions on the treatment of the COVID-19.

Methods

PubMed, Scopus, and Web of Sciences (WOS) databases were searched from inception to January 1, 2022. All systematic reviews investigated the effectiveness, efficacy, safety, and outcome of the main intervention (Favipiravir, Remdesivir, Hydroxychloroquine, Ivermectin, Lopinavir/Ritonavir, or Tocilizumab) for the treatment of COVID-19 patients and reported the potential limitations of the included studies. We assessed the quality of the included studies using the Quality Assessment Tool (QAT) for review articles. We conducted a content analysis and prepared a narrative summary of the limitations.

Results

Forty-six studies were included in this review. Ninety one percent of the included studies scored as strong quality and the remaining (9%) as moderate quality. Only 29.7% of the included systematic reviews have a registered protocol. 26% of the included studies mentioned a funding statement. The main limitations of the included studies were categorized in 10 domains: sample size, heterogeneity, follow-up, treatment, including studies, design, definitions, synthesis, quality, and search.

Conclusion

Various limitations have been reported in all the included studies. Indeed, the existence of limitations in studies can affect their results, therefore, identifying these limitations can help researchers design better studies. As a result, stronger studies with more reliable results will be reported and disseminated. Further research on COVID-19 SRs is essential to improve research quality and also, efficiency among scientists across the world.
Case report: Total percutaneous post-closure of femoral arterial access sites after veno-arterial extracorporeal membrane oxygenation
Authors: Tian Lun , Zhang Libin , Zhang Naiding , Xu Xin , Xu Yongshan , Liu Zhenjie , Huang Man
Published: September 2022

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) which is a form of circulatory and gas exchange support. Following VA-ECMO, total percutaneous closure of the site of femoral arterial puncture with perclose Proglide (PP) has become widespread, enhancing patient comfort and lessening the incidence of wound infections and lymphatic fistulas in a short closure time. The preclose technique with perclose Proglide provides numerous benefits, however, it prolongs extra time during the VA-ECMO procedure, adds additional post-operative care to workloads, and increases the potential for Proglide stitch infection. The modified technique-percutaneous post-closure, described here by a case of a 65-year-old man with heart attack who underwent VA-ECMO, is a simple, rapidly applied technique to wean VA-ECMO also suitable for emergency cannulation. The patient was administered mechanically ventilated and sedated and the femoral artery access site and evaluated by ultrasound for precise positioning, then the VA-ECMO arterial cannula was withdrawn, and a 0.035-in guidewire was left in the artery. The first set of sutures was deployed after the Proglide device was inserted over the guidewire. The second sutures were then replaced in the same way but at a different angle. After hemostasis was achieved, the guidewire was removed, and additional manual compression was used to control any residual blood seeping. No hematoma, pseudoaneurysm, major bleeding, minor bleeding, acute arterial thrombosis, arteriovenous fistula, groin infection, lymphocele, or arterial dissection and stenosis occurred during the periprocedural period or during the 30-day post-procedural follow-up. In conclusion, the standardized algorithm we established, total percutaneous post-closure of femoral arteriotomies utilizing Perclose ProGlide device is feasible and safe with a low incidence of access site complications.
Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
Authors: Hu Huaiyue , Hu Zhiqiang , Zhang Yingying , Wan Hongping , Yin Zhongqiong , Li Lixia , Liang Xiaoxia , Zhao Xinghong , Yin Lizi , Ye Gang , Zou Yuan-Feng , Tang Huaqiao , Jia Renyong , Chen Yaqin , Zhou Hao , Song Xu
Published: September 2022

Myricetin, a polyhydroxyflavone compound, is one of the main ingredients of various human foods and therefore also known as dietary flavonoids. Due to the continuous emergence of resistant strains of herpesviruses, novel control measures are required. In the present study, myricetin exhibited potent antiviral activity against pseudorabies virus (PRV), a model organism of herpesvirus. The suppression rate could reach up to 96.4% at a concentration of 500 μM in cells, and the 50% inhibitory concentration (IC50) was 42.69 μM. Moreover, the inhibitory activity was not attenuated by the increased amount of infective dose, and a significant reduction of intracellular PRV virions was observed by indirect immunofluorescence. A mode of action study indicated that myricetin could directly inactivate the virus in vitro, leading to inhibition of viral adsorption, penetration and replication in cells. In addition to direct killing effect, myricetin could also activate host antiviral defense through regulation of apoptosis-related gene expressions (Bcl-2, Bcl-xl, Bax), NF-κB and MAPK signaling pathways and cytokine gene expressions (IL-1α, IL-1β, IL-6, c-Jun, STAT1, c-Fos, and c-Myc). In PRV-infected mouse model, myricetin could enhance the survival rate by 40% at 5 days post infection, and viral loads in kidney, liver, lung, spleen, and brain were significantly decreased. The pathological changes caused by PRV infection were improved by myricetin treatment. The gene expressions of inflammatory factors (MCP-1, G-CSF, IL-1α, IL-1β, and IL-6) and apoptotic factors (Bcl-xl, Bcl-2, and Bax) were regulated by myricetin in PRV-infected mice. The present findings suggest that myricetin can effectively inhibit PRV infection and become a candidate for development of new anti-herpesvirus drugs.
Induced pluripotent stem cell-derived brain organoids as potential human model system for chemotherapy induced CNS toxicity
Authors: Scholz Sophie , Lewis Karyn , Saulich Frederik , Endres Matthias , Boehmerle Wolfgang , Huehnchen Petra
Published: September 2022

Neurotoxic phenomena are among the most common side effects of cytotoxic agents. The development of chemotherapy-induced polyneuropathy (CIPN) is a well-recognized adverse reaction in the peripheral nervous system, while changes of cognitive functions (post-chemotherapy cognitive impairment (PCCI)) are more diffuse and have only recently drawn scientific interest. PCCI in patients most often displays as short-term memory loss, reduced multitasking ability or deficits in language. Not least, due to a lack of preclinical human model systems, the underlying molecular mechanisms are poorly understood, and treatments are missing. We thus investigated whether induced pluripotent stem cell (iPSC)-derived brain organoids can serve as a human model system for the study of chemotherapy induced central nervous system toxicity. We robustly generated mature brain organoids from iPSC-derived neuronal precursor cells (NPC), which showed a typical composition with 1) dividing NPCs forming ventricle like structures 2) matured neurons and 3) supporting glial cells closer to the surface. Furthermore, upon stimulation the brain organoids showed functional signaling. When exposed to increasing concentrations of paclitaxel, a frequently used chemotherapy drug, we observed time dependent neurotoxicity with an EC50 of 153 nM, comparable to a published murine model system. Histological analysis after paclitaxel exposure demonstrated dose dependent apoptosis induction and reduced proliferation in the organoids with further Western blot analyses indicating the degradation of neuronal calcium sensor one protein (NCS-1) and activation of Caspase-3. We could also provide evidence that paclitaxel treatment negatively affects the pool of neuronal and astrocyte precursor cells as well as mature neurons. In summary our data suggests that human iPSC derived brain organoids are a promising preclinical model system to investigate molecular mechanisms underlying PCCI and to develop novel prevention and treatment strategies.
Resting-state electroencephalographic correlates of cognitive reserve: Moderating the age-related worsening in cognitive function
Authors: Buján Ana , Sampaio Adriana , Pinal Diego
Published: September 2022

This exploratory study aimed to investigate the resting-state electroencephalographic (rsEEG) correlates of the cognitive reserve from a life span perspective. Current source density (CSD) and lagged-linear connectivity (LLC) measures were assessed to this aim. We firstly explored the relationship between rsEEG measures for the different frequency bands and a socio-behavioral proxy of cognitive reserve, the Cognitive Reserve Index (CRI). Secondly, we applied moderation analyses to assess whether any of the correlated rsEEG measures showed a moderating role in the relationship between age and cognitive function. Moderate negative correlations were found between the CRI and occipital CSD of delta and beta 2. Moreover, inter- and intrahemispheric LLC measures were correlated with the CRI, showing a negative association with delta and positive associations with alpha 1, beta 1, and beta 2. Among those correlated measures, just two rsEEG variables were significant moderators of the relationship between age and cognition: occipital delta CSD and right hemispheric beta 2 LLC between occipital and limbic regions. The effect of age on cognitive performance was stronger for higher values of both measures. Therefore, lower values of occipital delta CSD and lower beta 2 LLC between right occipital and limbic regions might protect or compensate for the effects of age on cognition. Results of this exploratory study might be helpful to allocate more preventive efforts to curb the progression of cognitive decline in adults with less CR, possibly characterized by these rsEEG parameters at a neural level. However, given the exploratory nature of this study, more conclusive work on these rsEEG measures is needed to firmly establish their role in the cognition–age relationship, for example, verifying if these measures moderate the relationship between brain structure and cognition.
Incidence, lethality, and post-stroke functional status in different Brazilian macro-regions: The SAMBA study (analysis of stroke in multiple Brazilian areas)
Authors: Santos Emily dos , Wollmann Giulia M. , Nagel Vivian , Ponte Herminia M. S. , Furtado Luis E. T. A. , Martins-Filho Rui K. V. , Weiss Gustavo , Martins Sheila C. O. , Ferreira Leslie E. , França Paulo H. C. de , Cabral Norberto L.
Published: September 2022

Background

Stroke is the second leading cause of death in Brazil. The social and financial burden of stroke is remarkable; however, the epidemiological profile remains poorly understood.

Objective

The aim of this study was to report the incidence, lethality, and functional status at 30 and 90 days post-stroke in the cities of different Brazilian macro-regions.

Methods

This is an observational, prospective, and population-based study, led in Canoas (South), Joinville (South, reference center), Sertãozinho (Southeast), and Sobral (Northeast) in Brazil. It was developed according to the three-step criteria recommended by the World Health Organization to conduct population-based studies on stroke. Using different sources, all hospitalized and ambulatory patients with stroke were identified and the same criteria were kept in all cities. All first events were included, regardless of sex, age, or type of stroke. Demographic and risk factor data were collected, followed by biochemical, electrocardiographic, and radiological test results. Functional status and lethality were obtained using the mRankin scale through telephonic interview (validated Brazilian version).

Results

In 1 year, 932 stroke cases were registered (784 ischemic stroke, 105 hemorrhagic stroke, and 43 subarachnoid hemorrhage). The incidence rates per 100,000 inhabitants, adjusted for the world population, were 63 in Canoas, 106 in Joinville, 72 in Sertãozinho, and 96 in Sobral. The majority (70.8%) were followed for 90 days. Kaplan–Meier curves showed that 90-day survival was different among cities. Sobral, which has the lowest socioeconomic indexes, revealed the worst results in terms of lethality and functional status.

Conclusion

This study expands the knowledge of stroke epidemiology in Brazil, a middle-income country with enormous socioeconomic and cultural diversity. The discrepancy observed regarding the impact of stroke in patients from Joinville and Sobral highlights the need to improve the strategic allocation of resources to meet the health priorities in each location.
Encephalic Schistosoma japonicum resembles brainstem neoplasm: Case report and literature review
Authors: Wu Kang , Zhao Hong Yu , Shu Kai , Lei Ting , Zeng Liang
Published: September 2022

Encephalic schistosomiasis is a rare and severe parasitic disease which manifests as granuloma formation around ectopic eggs that migrate to the brain. We present a rare case of a pseudotumoral form of Schistosoma japonicum in the brainstem that was initially misidentified as a malignant tumor. The patient presented with intermittent headaches, diplopia, and left limb weakness. Neurological examination revealed hypoesthesia of the left lower limb, limitation of right eye abduction, and decreased muscle strength of the left upper limb. The cerebrospinal fluid tested positive for antibodies against S. japonicum. After standard treatment for schistosomiasis, the patient achieved complete remission. This case highlights that encephalic schistosomiasis can occur in the brainstem and resemble a neoplasm on magnetic resonance imaging. Once diagnosed, however, complete remission is achievable by non-invasive medical treatment.
The human brain in a high altitude natural environment: A review
Authors: Zhang Xinjuan , Zhang Jiaxing
Published: September 2022

With the advancement ofin vivomagnetic resonance imaging (MRI) technique, more detailed information about the human brain at high altitude (HA) has been revealed. The present review aimed to draw a conclusion regarding changes in the human brain in both unacclimatized and acclimatized states in a natural HA environment. Using multiple advanced analysis methods that based on MRI as well as electroencephalography, the modulations of brain gray and white matter morphology and the electrophysiological mechanisms underlying processing of cognitive activity have been explored in certain extent. The visual, motor and insular cortices are brain regions seen to be consistently affected in both HA immigrants and natives. Current findings regarding cortical electrophysiological and blood dynamic signals may be related to cardiovascular and respiratory regulations, and may clarify the mechanisms underlying some behaviors at HA. In general, in the past 10 years, researches on the brain at HA have gone beyond cognitive tests. Due to the sample size is not large enough, the current findings in HA brain are not very reliable, and thus much more researches are needed. Moreover, the histological and genetic bases of brain structures at HA are also needed to be elucidated.
Using substantial reductant concentration with chelation therapy to enhance small aggregate dispersal, iron mobilization, and its clearance in neurodegenerative diseases
Authors: Muhoberac Barry B.
Published: September 2022

Connections between altered iron homeostasis and certain neurodegenerative diseases are highlighted by numerous studies suggesting iron neurotoxicity. Iron causes aggregation in neurodegenerative disease-linked proteins as well as others and additionally facilitates oxidative damage. Iron and oxidative damage can cause cell death including by ferroptosis. As treatment for neurodegeneration, chelation therapy alone is sometimes used with modest, varying efficacy and has not in general proven to reverse or halt the damage long term. Questions often focus on optimal chelator partitioning and fine-tuning binding strength; however iron oxidation state chemistry implies a different approach. More specifically, my perspective is that applying a redox-based component to iron mobilization and handling is crucial because ferrous iron is in general a more soluble, weaker biological binder than ferric. Once cellular iron becomes oxidized to ferric, it binds tenaciously, exchanges ligands more slowly, and enhances protein aggregation, which importantly can be reversed by iron reduction. This situation escalates with age as brain reducing ability decreases, iron concentration increases, autophagic clearance decreases, and cell stress diminishes iron handling capacity. Taken together, treatment employing chelation therapy together with a strong biological reductant may effectively remove inappropriately bound cellular iron or at least inhibit accumulation. This approach would likely require high concentration ascorbate or glutathione by IV along with chelation to enhance iron mobilization and elimination, thus reducing cumulative cellular damage and perhaps restoring partial function. Potential treatment-induced oxidative damage may be attenuated by high reductant concentration, appropriate choice of chelator, and/or treatment sequence. Comprehensive study is urged.
The functional connectivity of the middle frontal cortex predicts ketamine’s outcome in major depressive disorder
Authors: Zhang Fan , Wang Chengyu , Lan Xiaofeng , Li Weicheng , Fu Ling , Ye Yanxiang , Liu Haiyan , Wu Kai , Zhou Yanling , Ning Yuping
Published: September 2022

Background

Ketamine, a robust antidepressant, has promising potential in the treatment of major depressive disorder (MDD). However, it does not work for all MDD patients, and the mechanism underlying its anti-depressive effects is unclear. Researchers have explored the mechanisms of ketamine action in MDD patients through MRI, a technique that measures brain activity intuitively. Notably, many MRI results were inconsistent because they selected different brain regions as seeds, particularly with respect to functional connectivity (FC) analysis. To eliminate the influence of prior seeds as much as possible, we used the significantly different results in degree centrality (DC) analysis as seeds to explore the FC changes in MDD patients to identify an imaging biomarker of ketamine’s effect.

Methods

Forty-four MDD patients and 45 healthy controls (HCs) were included in the study. Patients, aged 18–65, received six intravenous ketamine injections over 12 days. Depressive symptoms were estimated and MRI scans were performed at baseline and the day after the sixth infusion. We estimated FC differences between responders, non-responders and HCs using the region that showed significant differences between responders and non-responders in DC analysis as the seed. The correlation between the MADRS changes and zFC values was performed, and the potential of zFC values to be a neuroimaging biomarker was explored using the receiver operating characteristic curve.

Result

Compared with non-responders, responders had significantly decreased DC values in the right middle frontal gyrus (MFG). In the analysis of FC using the region that showed significant differences in DC as a seed, there was a significant difference in the region of the right supplementary motor area (SMA) among responders, non-responders, and HCs. This region also overlapped with the bilateral median cingulate gyrus. In post hoc analysis, responders had higher FC than non-responders and HCs, and non-responders had lower FC than HCs. Importantly, the FC between the MFG and SMA (overlapping bilateral median cingulate gyrus) was correlated with the improvement of symptoms, which was estimated by the Mongomery-Asberg Depression Scale (MADRS). FC has the potential to be an imaging biomarker that can predict the ketamine effect in MDD patients according to the receiver operating characteristic curve analysis.

Conclusion

Our results revealed that FC between the SMG and SMA and mACC was highly correlated with depressive symptoms and has the potential to be a neuroimaging biomarker to predict the effect of ketamine in MDD.
A stratification system of ferroptosis and iron-metabolism related LncRNAs guides the prediction of the survival of patients with esophageal squamous cell carcinoma
Authors: Niu Ren , Zhao Fangchao , Dong Zefang , Li Zhirong , Li Shujun
Published: September 2022

Ferroptosis and iron-metabolism have been widely reported to play an important role in cancer. Long non-coding RNAs (lncRNAs) are increasingly recognized as the crucial mediators in the regulation of ferroptosis and iron metabolism. A systematic understanding of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in esophageal squamous cell carcinoma (ESCC) is essential for prognosis prediction. Herein, Pearson’s correlation analysis was carried out between ferroptosis and iron-metabolism-related genes (FIRGs) and all lncRNAs to derive the FIRLs. Based on weighted gene co-expression network exploration (WCGNA), least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis, a risk stratification system, including 3 FIRLs (LINC01068, TMEM92-AS1, AC243967.2), was established. According to Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, and univariate and multivariate Cox regression analyses, the risk stratification system had excellent predictive ability and clinical relevance. The validity of the established prognostic signature was further examined in TCGA (training set) and GEO (validation set) cohorts. A nomogram with enhanced precision for forecasting OS was set up on basis of the independent prognostic elements. Functional enrichment analysis revealed that three FIRLs took part in various cellular functions and signaling pathways, and the immune status was varied in the high-risk and low-risk groups. In the end, the oncogenic effects of LINC01068 was explored using in vitro researches. Overall, a risk stratification system of three FIRLs was found to have significant prognostic value for ESCC and may serve as a ferroptosis-associated therapeutic target in the clinic.
Rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways
Authors: Semlali Abdelhabib , Papadakos Sofia , Contant Camille , Zouaoui Ikram , Rouabhia Mahmoud
Published: September 2022

Treatment of oral cancer is based exclusively on surgery combined with or without chemotherapy. However, it has several side effects. Targeting a new, more effective therapy has become an urgent matter. The purpose of this study was to evaluate the anti-tumor activity of rapamycin in oral cancer and its mechanism of action. Human gingival carcinoma cells were stimulated with different concentrations of rapamycin to assess proliferation, colony formation, cell migration, as well as apoptosis, and autophagy. The expression of proteins involved in the cell cycle (cyclin D1, p15, p21, p27) and autophagy, as well as that of oncogenes and tumor suppressor genes, were determined by quantitative PCR. The signaling pathways were evaluated by Western blotting. Our results show that rapamycin has a selective effect at a low dose on cancer cell growth/survival. This was confirmed by low colony formation and the inhibition of cell migration, while increasing cell apoptosis by activating caspase-9 and -3. Rapamycin promoted cell autophagy and increased mitochondrial oxidative stress by being involved in DNA damage in the exposed cells. Finally, rapamycin exhibits potent anti-oral cancer properties through inhibition of several cancer-promoting pathways (MAPK, NF-κB, and Wnt/beta-catenin). These results indicate that rapamycin could be a potential agent for the treatment of oral cancer and for a prevention strategy.
Beta-adrenergic receptor blockade in angiosarcoma: Which beta-blocker to choose?
Authors: Embaby Alaa , van Merendonk Lisanne , Steeghs Neeltje , Beijnen Jos , Huitema Alwin
Published: September 2022

Beta-blockers are currently studied to improve therapeutic options for patients with angiosarcoma. However, most of these patients have no cardiovascular co-morbidity and it is therefore crucial to discuss the most optimal pharmacological properties of beta-blockers for this population. To maximize the possible effectiveness in angiosarcoma, the use of a non-selective beta-blocker is preferred based on in vitro data. To minimize the risk of cardiovascular adverse events a beta-blocker should ideally have intrinsic sympathomimetic activity or vasodilator effects, e.g. labetalol, pindolol or carvedilol. However, except for one case of carvedilol, only efficacy data of propranolol is available. In potential follow-up studies labetalol, pindolol or carvedilol can be considered to reduce the risk of cardiovascular adverse events.
Expression and clinical significance of CD31, CD34, and CD105 in pulmonary ground glass nodules with different vascular manifestations on CT
Authors: Guo Chen-ran , Han Rui , Xue Feng , Xu Lin , Ren Wan-gang , Li Meng , Feng Zhen , Hu Ben-chuang , Peng Zhong-min
Published: September 2022

Blood vessel passage on CT exerts a vital part in early diagnosis as well as treatment of carcinoma of the lungs. Intratumoral microvascular density (iMVD) has gradually become the focus of research on biological behavior, appearance, and evolution of malignant tumors nowadays. The aim of this paper was to verify whether there is a correlation between the iMVD and the vascular morphology of ground glass nodules (GGNs). A total of 109 patients with pulmonary GGN were classified into three groups (I,II, and III) according to the vascular morphology on CT, and their expression of CD31-, CD34-, and CD105-labeled iMVD was detected by the streptoavidin–biotin method, statistically analyzing the iMVD values of each group. The expression of CD31, CD34, and CD105 in different lung tissues was significantly different, with remarkably higher iMVD in lung cancer tissues than in adjacent normal lung tissues. In the imaging sort of types I, II, and III according to the means of vascular passage, the iMVD expression of CD31, CD34, and CD105 was significantly different between groups. These data suggest that the presence and the abnormal morphology of vessels seen within GGNs indicate the occurrence and progression of lung cancer in pathology. It offers a strong theoretical foundation for early diagnosis of carcinoma of the lungs, thus providing a more precise clinical diagnosis and prognosis of early-stage lung cancer.
Clinical implication of minimal residual disease assessment by next-generation sequencing-based immunoglobulin clonality assay in pediatric B-acute lymphoblastic leukemia
Authors: Lee Jae Wook , Kim Yonggoo , Ahn Ari , Lee Jong Mi , Yoo Jae Won , Kim Seongkoo , Cho Bin , Chung Nack-Gyun , Kim Myungshin
Published: September 2022

Measuring minimal residual disease (MRD) during treatment is valuable to identify acute lymphoblastic leukemia (ALL) patients who require intensified treatment to avert relapse. We performed the next-generation sequencing (NGS)-based immunoglobulin gene (Ig) clonality assay and evaluated its clinical implication in pediatric B-ALL patients to assess MRD. Fifty-five patients who were diagnosed and treated with de novo (n = 44) or relapsed/refractory B-ALL (n = 11) were enrolled. MRD assessment was performed using the LymphoTrack® Dx IGH and IGK assay panels. The percentage of the clonal sequences per total read count was calculated as MRD (% of B cells). The data were normalized as the proportion of total nucleated cells (TNC) by LymphoQuant™ Internal control or the B-cell proportion in each sample estimated by flow cytometry or immunohistochemistry. Clonal Ig rearrangement was identified in all patients. The normalized MRD value was significantly lower than the unnormalized MRD value (p < 0.001). When categorizing patients, 27 of 50 patients (54%) achieved normalized MRD <0.01%, while 6 of them did not achieve MRD <0.01% when applying the unnormalized value. The normalized post-induction MRD value of 0.01% proved to be a significant threshold value for both 3-year event-free survival (100% for MRD <0.01% vs. 60.9% ± 10.2% for MRD ≥0.01%, p = 0.007) and 3-year overall survival (100% for MRD <0.01% vs. 78.3% ± 8.6% for MRD ≥0.01%, p = 0.011). However, unnormalized MRD was not a significant factor for outcome in this cohort. Our study demonstrated that MRD assessment by NGS-based Ig clonality assay could be applied in most pediatric B-ALL patients. Normalized post-induction MRD <0.01% was a significant prognostic indicator.
Current understanding on the role of CCT3 in cancer research
Authors: Liu Wenlou , Lu Yu , Yan Xiang , Lu Quansheng , Sun Yujin , Wan Xiao , Li Yizhi , Zhao Jiaqin , Li Yuchen , Jiang Guan
Published: September 2022

Chaperonin containing TCP1 Subunit 3 (CCT3) is an important member of the chaperone protein family, providing a favorable environment for the correct folding of proteins in cell division, proliferation, and apoptosis pathways, which is involved in a variety of biological processes as well as the development and invasion of many malignant tumors. Many malignancies have been extensively examined with CCT3. It is presently used as a possible target for the treatment of many malignancies since it is not only a novel biomarker for the screening and diagnosis of different tumors, but it is also closely associated with tumor progression, prognosis, and survival. Recent studies have shown that the expression of CCT3 is up-regulated in some tumors, such as liver cancer, breast cancer, colon cancer, acute myeloid leukemia, etc. In this paper, we review the role of CCT3 in various tumors.
Application progress of liquid biopsy in gastric cancer
Authors: Ma Xiaoting , Ou Kai , Liu Xiu , Yang Lin
Published: September 2022

Gastric cancer (GC) is one of the most common malignant tumors globally. Guiding the individualized treatment of GC is the focus of research. Obtaining representative biological samples to study the biological characteristics of GC is the focus of diagnosis and treatment of GC. Liquid biopsy technology can use high-throughput sequencing technology to detect biological genetic information in blood. Compared with traditional tissue biopsy, liquid biopsy can determine the dynamic changes of tumor. As a noninvasive auxiliary diagnostic method, liquid biopsy can provide diagnostic and prognostic information concerning the progression of the disease. Liquid biopsy includes circulating tumor cells, circulating tumor DNA, circulating tumor RNA, tumor educated platelets, exosomes, and cytokines. This article describes the classification of liquid biopsy and its application value in the occurrence, development, and therapeutic efficacy of GC.
Radiation therapy for de novo anorectal cancer in patients with a history of prostate radiation therapy
Authors: Hilal Lara , Wu Abraham J. , Reyngold Marsha , Cuaron John J. , Navilio John , Romesser Paul B. , Dreyfuss Alexandra , Yin Sean , Zhang Zhigang , Bai Xing , Berry Sean L. , Zinovoy Melissa , Nusrat Maliha , Pappou Emmanouil , Zelefsky Michael J. , Crane Christopher H. , Hajj Carla
Published: September 2022

Introduction

Radiation therapy (RT) for anorectal cancer after prior prostate cancer RT is usually avoided due to concern for complications. Data on this topic is scarce. Our aim was to evaluate tolerability, toxicity, and clinical outcomes associated with a second course of pelvic radiation in men with de novo anorectal cancers previously treated with RT for prostate cancer.

Materials/methods

We conducted a single-institution retrospective study of men treated with RT for rectal or anal cancer after prior prostate RT. Toxicity data were collected. Treatment plans were extracted to assess doses to organs at risk and target coverage. Cumulative incidence was calculated for local and distant progression. Kaplan-Meier curves were used to estimate overall survival (OS) and progression-free survival (PFS).

Results

We identified 26 patients who received anorectal RT after prostate cancer RT: 17 for rectal cancer and 9 for anal cancer. None had metastatic disease. Prior prostate RT was delivered using low dose rate brachytherapy (LDR), external beam RT (EBRT), or EBRT + LDR. RT for rectal cancer was delivered most commonly using 50.4Gy/28 fractions (fr) or 1.5 Gy twice-daily to 30-45 Gy. The most used RT dose for anal cancer was 50Gy/25 fr. Median interval between prostate and anorectal RT was 12.3 years (range:0.5 - 25.3). 65% and 89% of rectal and anal cancer patients received concurrent chemotherapy, respectively. There were no reported ≥Grade 4 acute toxicities. Two patients developed fistulae; one was urinary-cutaneous after prostate LDR and 45Gy/25fr for rectal cancer, and the other was recto-vesicular after prostate LDR and 50Gy/25fr for anal cancer. In 11 patients with available dosimetry, coverage for anorectal cancers was adequate. With a median follow up of 84.4 months, 5-yr local progression and OS were 30% and 31% for rectal cancer, and 35% and 49% for anal cancer patients, respectively.

Conclusion

RT for anorectal cancer after prior prostate cancer RT is feasible but should be delivered with caution since it poses a risk of fistulae and possibly bleeding, especially in patients treated with prior LDR brachytherapy. Further studies, perhaps using proton therapy and/or rectal hydrogel spacers, are needed to further decrease toxicity and improve outcomes.
Updates in the management of unknown primary of the head and neck
Authors: Kalavacherla Sandhya , Sanghvi Parag , Lin Grace Y. , Guo Theresa
Published: September 2022

Squamous cell carcinoma (SCC) from an unknown primary tumor (SCCUP) accounts for 2.0%–5.0% of all head and neck cancers. SCCUP presents as enlarged cervical lymph nodes without evidence of a primary tumor upon physical examination. Primary site detection is important to target treatment and avoid treatment-related morbidity. In this review, we discuss updates in SCCUP management. Diagnostic workup should focus on localization of the primary tumor in SCCUP. Initial workup centers on neck biopsy to confirm the presence of SCC. Given the increasing incidence of HPV-related SCC in the oropharynx, HPV testing is crucial. An HPV-positive status can localize the tumor to the oropharynx, a common site for occult tumors. Imaging includes neck CT and/or MRI, and PET/CT. After imaging, panendoscopy, palatine tonsillectomy or diagnostic transoral robotic surgery can facilitate high rates of primary tumor localization. Primary tumor localization influences treatments administered. SCCUP has traditionally been treated aggressively with large treatment fields to all potential disease sites, which can induce weight loss and swallowing dysfunction. As a result, primary localization can reduce radiation fields and provide possible de-escalation to primary surgical management. Advances in intensity-modulated radiation therapy and dose management also have the potential to improve functional outcomes in SCCUP patients. Given the improved prognosis associated with HPV-positive SCCs, HPV tumor status may also inform future treatment de-intensification to reduce treatment-related toxicity.
Autonomic nervous system markers of music-elicited analgesia in people with fibromyalgia: A double-blind randomized pilot study
Authors: Lepping Rebecca J. , McMillan Miranda L. , Chadwick Andrea L. , Mansour Zaid M. , Martin Laura E. , Gustafson Kathleen M.
Published: September 2022

Purpose

To investigate the feasibility of using music listening by adults with fibromyalgia (FM) as a potential tool for reducing pain sensitivity.

Patients and methods

We report results from a double-blind two-arm parallel randomized pilot study (NCT04059042) in nine participants with FM. Pain tolerance and threshold were measured objectively using quantitative sensory tests; autonomic nervous system (ANS) reactivity was measured with an electrocardiogram. Participants were randomized to listen to instrumental Western Classical music or a nature sound control to test whether music listening elicits greater analgesic effects over simple auditory distraction. Participants also completed separate control testing with no sound that was counterbalanced between participants.

Results

Participants were randomized 1:1 to music or nature sounds (four Music and five Nature). Although the groups were not different on FM scores, the Music group had marginally worse temporal pain summation (p= 0.06), and the Nature group had higher anxiety scores (p< 0.05). Outcome measures showed a significant difference between groups in the magnitude of change in temporal summation between sessions (p< 0.05), revealing that the Nature group had greater pain reduction during audio compared to silence mode, while the Music group had no difference between the sessions. No significant effects were observed for either mechanical pain tolerance or ANS testing. Within the Music group, there was a trend of vagal response increase from baseline to music listening, but it did not reach statistical significance; this pattern was not observed in the Nature group.

Conclusion

Auditory listening significantly altered pain responses. There may be a greater vagal response to music vs. nature sounds; however, results could be due to group differences in pain and anxiety. This line of study will help in determining whether music could be prophylactic for people with FM when acute pain is expected.
Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments
Authors: Xu Xiaotong , Li Naping , Wu Yongrong , Yan Ke , Mi Yilin , Yi Nanxing , Tan Xuyi , Kuang Gaoyan , Lu Min
Published: September 2022

Background: Knee osteoarthritis (KOA), a chronic degenerative disease, is mainly characterized by destruction of articular cartilage and inflammatory reactions. At present, there is a lack of economical and effective clinical treatment. Zhuifeng Tougu (ZFTG) capsules have been clinically approved for treatment of OA as they relieve joint pain and inflammatory manifestations. However, the mechanism of ZFTG in KOA remains unknown.

Purpose: This study aimed to investigate the effect of ZFTG on the TLR4/MyD88/NF-κB signaling pathway and its therapeutic effect on rabbits with KOA.

Study design:In vivo, we established a rabbit KOA model using the modified Videman method. In vitro, we treated chondrocytes with IL-1β to induce a pro-inflammatory phenotype and then intervened with different concentrations of ZFTG. Levels of IL-1β, IL-6, TNF-α, and IFN-γ were assessed with histological observations and ELISA data. The effect of ZFTG on the viability of chondrocytes was detected using a Cell Counting Kit-8 and flow cytometry. The protein and mRNA expressions of TLR2, TLR4, MyD88, and NF-κB were detected using Western blot and RT-qPCR and immunofluorescence observation of NF-κB p65 protein expression, respectively, to investigate the mechanism of ZFTG in inhibiting inflammatory injury of rabbit articular chondrocytes and alleviating cartilage degeneration.

Results: The TLR4/MyD88/NF-κB signaling pathway in rabbits with KOA was inhibited, and the levels of IL-1β, IL-6, TNF-α, and IFN-γ in blood and cell were significantly downregulated, consistent with histological results. Both the protein and mRNA expressions of TLR2, TLR4, MyD88, NF-κB, and NF-κB p65 proteins in that nucleus decreased in the ZFTG groups. Moreover, ZFTG promotes the survival of chondrocytes and inhibits the apoptosis of inflammatory chondrocytes.

Conclusion: ZFTG alleviates the degeneration of rabbit knee joint cartilage, inhibits the apoptosis of inflammatory chondrocytes, and promotes the survival of chondrocytes. The underlying mechanism may be inhibition of the TLR4/MyD88/NF-kB signaling pathway and secretion of inflammatory factors.
The pharmacokinetic study of tacrolimus and Wuzhi capsule in Chinese liver transplant patients
Authors: Qu Jinlong , Bian Rongrong , Liu Binguo , Chen Jiani , Zhai Jingwen , Teng Fei , Guo Wenyuan , Wei Hua
Published: September 2022

Objectives: Wuzhi Capsule (WZC) is often administrated with tacrolimus in liver transplant patients to reduce the toxicity of tacrolimus and relieve the financial burden of patients. We aimed to investigate the interaction between Wuzhi Capsule (WZC) and tacrolimus in liver transplant patients.

Methods: We applied the LC-MS/MS analytical method previously established to study the pharmacokinetic characteristics of the analytes in 15 liver transplant patients. CYP3A5 genotypes were determined in 15 donors and recipients, and they were categorized into CYP3A5 expressers and non-expressers respectively.

Results: The influences of CYP3A5 in donors and recipients on the pharmacokinetics of tacrolimus with or without WZC were also studied. We found that 1) WZC could influence the metabolism of tacrolimus, which shortened the Tmax of tacrolimus and decreased V/F and CL/F. 2) Moreover, our results showed that, in donors, the CL/F of tacrolimus were significantly lower in CYP3A5 (CYP3A5*1) expressers (decreased from 24.421 to 12.864) and non-expressers (decreased from 23.532 to 11.822) when co-administration with WZC. For recipients, the decreased trend of CL/F of tacrolimus was seen when co-administrated with WZC by 15.376 and 12.243 in CYP3A5 expressers and non-expressers, respectively.

Conclusion: In this study, the pharmacokinetics effects of WZC on tacrolimus were identified. The co-administration of WZC can increase the tacrolimus blood concentration in Chinese liver transplant patients in clinical practice.
mGlu2 mechanism-based interventions to treat alcohol relapse
Authors: Vengeliene Valentina , Spanagel Rainer
Published: September 2022

Recently we identified a deficiency in metabotropic glutamate receptor 2 (mGlu2) function in the corticoaccumbal pathway, as a common pathological mechanism underlying alcohol-seeking and relapse behavior. Based on this mechanism, we hypothesized that mGlu2/3 agonists and mGlu2 positive allosteric modulators (PAMs) may be effective in reducing relapse-like behavior. Two mGlu2/3 agonists, LY379268 and LY354740 (a structural analog of LY379268 six-fold more potent in activating mGlu2 over mGluR3), were tested in a well-established rat model of relapse, the alcohol deprivation effect (ADE) with repeated deprivation phases. Since these agonists do not readily discriminate between contributions of mGlu2 and mGluR3, we also tested LY487379, a highly specific PAM that potentiates the effect of glutamate on the mGlu2 with less specificity on other mGlu receptor subtypes. Both LY379268 and LY354740 significantly and dose-dependently reduced the expression of the ADE. No significant changes in water intake, body weight and locomotor activity were observed. Importantly, repeated administration of mGlu2/3 agonist did not lead to tolerance development. mGlu2 PAM LY487379 treatment significantly reduced expression of the ADE in both male and female rats. Combination treatment of mGlu2/3 agonist and PAM had similar effect on relapse-like drinking to that seen in mGlu2/3 agonist treatment alone. Together with other preclinical data showing that PAMs can reduce alcohol-seeking behavior we conclude that mGlu2 PAMs should be considered for clinical trials in alcohol-dependent patients.