Publications by authors named "Hao Yu"

1,680 Publications

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Lesional Intractable Epileptic Spasms in Children: Electroclinical Localization and Postoperative Outcomes.

Front Neurol 2022 22;13:922778. Epub 2022 Jul 22.

Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.

To analyze the influence of seizure semiology, electroencephalography (EEG) features and magnetic resonance imaging (MRI) change on epileptogenic zone localization and surgical prognosis in children with epileptic spasm (ES) were assessed. Data from 127 patients with medically intractable epilepsy with ES who underwent surgical treatment were retrospectively analyzed. ES semiology was classified as non-lateralized, bilateral asymmetric, and focal. Interictal epileptiform discharges were divided into diffusive or multifocal, unilateral, and focal. MRI results showed visible local lesions for all patients, while the anatomo-electrical-clinical value of localization of the epileptogenic zone was dependent on the surgical outcome. During preoperative video EEG monitoring, among all 127 cases, 53 cases (41.7%) had ES only, 46 (36.2%) had ES and focal seizures, 17 (13.4%) had ES and generalized seizures, and 11 (8.7%) had ES with focal and generalized seizures. Notably, 35 (27.6%) and 92 cases (72.4%) showed simple and complex ES, respectively. Interictal EEG showed that 22 cases (17.3%) had bilateral multifocal discharges or hypsarrhythmia, 25 (19.7%) had unilateral dominant discharges, and 80 (63.0%) had definite focal or regional discharges. Ictal discharges were generalized/bilateral in 71 cases (55.9%) and definite/lateralized in 56 cases (44.1%). Surgically resected lesions were in the hemisphere (28.3%), frontal lobe (24.4%), temporal lobe (16.5%), temporo-parieto-occipital region (14.2%), and posterior cortex region (8.7%). Seizure-free rates at 1 and 4 years postoperatively were 81.8 and 72.7%, respectively. There was no significant difference between electroclinical characteristics of ES and seizure-free rate. Surgical treatment showed good outcomes in most patients in this cohort. Semiology and ictal EEG change of ES had no effect on localization, while focal or lateralized epileptiform discharges of interictal EEG may affect lateralization and localization. Complete resection of epileptogenic lesions identified MRI was the only factor associated with a positive surgical outcome.
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http://dx.doi.org/10.3389/fneur.2022.922778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353030PMC
July 2022

Amide Proton Transfer Weighted MR Imaging for Predicting Meningioma Stiffness: A Feasibility Study.

J Magn Reson Imaging 2022 Aug 5. Epub 2022 Aug 5.

Department of Radiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Background: Stiffness of meningioma is an important factor affecting the surgical resection and the prognosis of patients.

Purpose: To examine the feasibility of APTw-magnetic resonance imaging (MRI) in evaluating meningioma stiffness.

Study Type: Retrospective.

Population: Seventy-one patient with meningiomas, 39 were male and 32 were female; the mean age was 51 ± 10 years.

Field Strength/sequence: 3.0T; Turbo-spin-echo T -weighted and Gd-T -weighted sequence; Turbo-spin-echo T -weighted sequence; 2D fat-suppressed, turbo-spin-echo APTw pulse sequence.

Assessment: The T WI signal intensity score, T WI signal intensity score, APTw , APTw , and APTw values were compared between soft, medium stiff and stiff meningiomas or non-stiff meningiomas and stiff meningiomas group.

Statistical Tests: Chi-square test, one-way ANOVA analysis, independent-samples t-test, intra-class correlation coefficient, rank-sum test, receiver operating characteristic curve analysis. P < 0.05 was considered statistically significant in all tests.

Results: APTw and APTw in the stiff group were significantly lower than that in the non-stiff group (2.79% ± 0.42% vs. 1.90% ± 0.60% and 3.20% ± 0.31% vs. 2.55% ± 0.61%). APTw and APTw in the stiff group were significantly lower than that in the medium stiff and soft groups (1.90% ± 0.60% vs. 2.69% ± 0.40% and 3.12% ± 0.32%, 2.55% ± 0.61% vs. 3.17% ± 0.33% and 3.39% ± 0.18%), APTw in the medium stiff group was significantly lower than in the soft group, there was no significant difference in APTw between the medium stiff and soft groups (P = 0.190). APTw showed the best diagnostic performance for evaluating meningioma stiffness with an area under the curve of 0.913, when the APTw was lower than 2.4%, the meningioma was defined as a stiff tumor, the sensitivity, specificity, and accuracy were 87.1%, 87.5%, and 85.9%, respectively.

Data Conclusion: APTw-MRI could be used to evaluate meningioma stiffness, with APTw having the best evaluative efficiency.

Level Of Evidence: 3 TECHNICAL EFFICACY: Stage 1.
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http://dx.doi.org/10.1002/jmri.28379DOI Listing
August 2022

Unusual Appearance of Nasal Collagenous Fibroma (Desmoplastic Fibroblastoma) on Imaging.

J Coll Physicians Surg Pak 2022 Aug;32(8):1064-1066

Department of Radiology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Collagenous fibroma (CF) is a benign soft tissue tumour with good prognosis. Preoperative imaging diagnosis is essential to avoid unnecessarily extended resection, which may result in irreversible functional damage. However, few studies published to date have reported on the imaging features, associated with this condition. We, therefore, present a patient with histologically proven CF on the dorsum of nose, associated with an unusual appearance on magnetic resonance imaging. Low signal intensity on T2-weighted images and rim enhancement on gadolinium-DTPA (Gd-DTPA) enhanced images are reported in some previously reported cases. However, the unique point about this case is the markedly enhanced nodule revealed in the middle part of the lesion five hours after the administration of contrast media. To our knowledge, this is the first description of late gadolinium enhancement features associated with the condition. Key words: Benign, Soft tissue, Collagenous fibroma, Magnetic resonance imaging.
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http://dx.doi.org/10.29271/jcpsp.2022.08.1064DOI Listing
August 2022

ELF4 is critical to zygotic gene activation and epigenetic reprogramming during early embryonic development in pigs.

Front Vet Sci 2022 19;9:954601. Epub 2022 Jul 19.

Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun, China.

Zygotic gene activation (ZGA) and epigenetic reprogramming are critical in early embryonic development in mammals, and transcription factors are involved in regulating these events. However, the effects of ELF4 on porcine embryonic development remain unclear. In this study, the expression of ELF4 was detected in early porcine embryos and different tissues. By knocking down ELF4, the changes of H3K9me3 modification, DNA methylation and ZGA-related genes were analyzed. Our results showed that was expressed at all stages of early porcine embryos fertilized (IVF), with the highest expression level at the 8-cell stage. The embryonic developmental competency and blastocyst quality decreased after ELF4 knockdown (20.70% control vs. 17.49% si-scramble vs. 2.40% si-; < 0.001). Knockdown of ELF4 induced DNA damage at the 4-cell stage. Interfering with ELF4 resulted in abnormal increases in H3K9me3 and DNA methylation levels at the 4-cell stage and inhibited the expression of genes related to ZGA. These results suggest that ELF4 affects ZGA and embryonic development competency in porcine embryos by maintaining genome integrity and regulating dynamic changes of H3K9me3 and DNA methylation, and correctly activating ZGA-related genes to promote epigenetic reprogramming. These results provide a theoretical basis for further studies on the regulatory mechanisms of ELF4 in porcine embryos.
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http://dx.doi.org/10.3389/fvets.2022.954601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343831PMC
July 2022

Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure.

J Am Coll Cardiol 2022 Aug;80(6):584-594

Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Background: Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily.

Objectives: This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF.

Methods: Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32.

Results: We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm.

Conclusions: The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).
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http://dx.doi.org/10.1016/j.jacc.2022.05.027DOI Listing
August 2022

Effects of protease inhibitors on dentin erosion: an in situ study.

Clin Oral Investig 2022 Aug 4. Epub 2022 Aug 4.

Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.

Objective: This in situ study aimed to evaluate the effects of the inhibitors of matrix metalloproteinases (MMPs) and cysteine cathepsins on dentin erosion.

Materials And Methods: Ten volunteers participated in this study. Each volunteer wore an intraoral appliance containing 4 dentin specimens subjected to different treatments: deionized water as a control, 1 mM 1,10-phenanthroline (an MMP inhibitor), 50 µM E-64 (a cysteine cathepsin inhibitor), and 1 mM 1,10-phenanthroline + 50 µM E-64. The specimens were dipped in 5 ml of the respective solutions for 30 min at room temperature and then exposed to in vivo erosive challenges by rinsing with 150 ml of a cola drink (4 × 5 min/day) for 7 days. The substance loss of the specimens was measured by profilometry. The transverse sections of the specimens were examined using scanning electron microscopy. Thereafter, the demineralized organic matrix (DOM) of the specimens was removed using type I collagen enzyme and assessed by performing profilometry. The differences in substance loss and DOM thickness among the groups were analyzed by one-way repeated-measures analysis of variance (ANOVA) and Bonferroni's test at a level of P < 0.05.

Results: Protease inhibitors significantly reduced substance loss in comparison to that of the control group (all P < 0.05). A significantly thicker DOM was observed for the specimens treated with protease inhibitors than for the control specimens (all P < 0.05). No significant differences in substance loss or DOM thickness were found among the MMP inhibitor, cysteine cathepsin inhibitor, and MMP + cysteine cathepsin inhibitor groups.

Conclusions: The use of MMP and cysteine cathepsin inhibitors was shown to increase the acid resistance of human dentin, which may be due to the preservation of the DOM.

Clinical Relevance: The application of protease inhibitors could be considered an appropriate preventive strategy for dentin erosion.
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http://dx.doi.org/10.1007/s00784-022-04657-wDOI Listing
August 2022

Chromium oxide modified mesoporous zirconium dioxide: Efficient heterogeneous catalysts for the synthesis of 5-hydroxymethylfurfural.

Chem Asian J 2022 Aug 4. Epub 2022 Aug 4.

Shandong University of Science and Technology, College of Energy Storage Technology, CHINA.

Achieving the highly efficient carbohydrates conversion to 5-hydroxymethylfurfural (5-HMF) is a promising method to achieve green and sustainable development. However, most currently reported strategies are energy consuming and the 5-HMF yield is relatively lower in the aqueous phase. Herein, a facile method was reported to obtain the effective Cr/ZrO2 catalysts with high acidity and their catalytic performances were investigated for catalyzing fructose to 5-HMF at different temperatures and times. With the catalysis of 15% Cr/ZrO2 catalyst, the highest fructose conversion of 98%, 5-HMF yield of 48.8%, and 5-HMF selectivity of 49.8% are achieved in green solvent with good recyclability. The possible reaction process of the improved catalysis performance is attributed to the highly crystalline and strong acidity of the Cr/ZrO2 catalyst. The Lewis acid sites could increase the overall rate of fructose conversion by promoting side reactions and might suppressing fructose to glucose isomerization. In addition, Cr leakage during the reaction might act as the Bronsted acids to catalyze the fructose dehydration to 5-HMF. The reported method of introducing chromium oxides into ZrO2 catalyst will open a new avenue to promote the practical application of biomass and sustainable development in the future.
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http://dx.doi.org/10.1002/asia.202200653DOI Listing
August 2022

Metallo-alginate hydrogel can potentiate microwave tumor ablation for synergistic cancer treatment.

Sci Adv 2022 08 3;8(31):eabo5285. Epub 2022 Aug 3.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123 Jiangsu, PR China.

Microwave ablation (MWA) as a local tumor ablation strategy suffers from posttreatment tumor recurrence. Development of adjuvant biomaterials to potentiate MWA is therefore of practical significance. Here, the high concentration of Ca fixed by alginate as Ca-surplus alginate hydrogel shows enhanced heating efficiency and restricted heating zone under microwave exposure. The high concentration of extracellular Ca synergizes with mild hyperthermia to induce immunogenic cell death by disrupting intracellular Ca homeostasis. Resultantly, Ca-surplus alginate hydrogel plus MWA can ablate different tumors on both mice and rabbits at reduced operation powers. This treatment can also elicit antitumor immunity, especially if synergized with Mn, an activator of the stimulation of interferon genes pathway, to suppress the growth of both untreated distant tumors and rechallenged tumors. This work highlights that in situ-formed metallo-alginate hydrogel could act as microwave-susceptible and immunostimulatory biomaterial to reinforce the MWA therapy, promising for clinical translation.
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http://dx.doi.org/10.1126/sciadv.abo5285DOI Listing
August 2022

LINC00665 knockdown confers sensitivity in irradiated non-small cell lung cancer cells through the miR-582-5p/UCHL3/AhR axis.

J Transl Med 2022 08 2;20(1):350. Epub 2022 Aug 2.

Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, West Huanhu Road, Tiyuanbei, Hexi District, Tianjin, 300060, People's Republic of China.

Background: The resistance to radiotherapy remains a major obstacle that limits the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). This study aims to illustrate the molecular mechanism underlying the role of LINC00665 in the radiosensitivity of NSCLC, which involves ubiquitin C-terminal hydrolase L3 (UCHL3).

Methods And Results: The expression of UCHL3 was determined in clinical tissue samples collected from NSCLC patients and NSCLC cell lines. We found that UCHL3 overexpression occurred in both NSCLC tissues and cells, associated with poor prognosis in NSCLC patients. Mechanistically, UCHL3 stabilized aryl hydrocarbon receptor (AhR) protein through deubiquitination, thereby promoting PD-L1 expression. UCHL3 reduced the radiosensitivity of NSCLC cells by stabilizing AhR protein. Upstream microRNAs (miRNAs) and lncRNAs of UCHL3 were predicted by microarray profiling and validated by functional experiments. LINC00665 functioned as a sponge of miR-582-5p and thus up-regulated the expression of the miR-582-5p target UCHL3. Gain- and loss- of function assays were performed to assess the effects of LINC00665, UCHL3 and miR-582-5p on the in vitro cell malignant behaviors and immune escape as well as on the in vivo tumor growth. Silencing LINC00665 or overexpressing miR-582-5p enhanced the sensitivity of NSCLC cells to radiotherapy. LINC00665 augmented the immune escape of NSCLC cells in vitro and in vivo through stabilizing AhR protein via the miR-582-5p/UCHL3 axis.

Conclusions: Overall, LINC00665 reduced the radiosensitivity of NSCLC cells via stabilization of AhR through the miR-582-5p/UCHL3 axis.
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http://dx.doi.org/10.1186/s12967-022-03516-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344728PMC
August 2022

State Mandatory Paid Sick Leave Associated With A Decline In Emergency Department Use In The US, 2011-19.

Health Aff (Millwood) 2022 Aug;41(8):1169-1175

Hefei Wen Harvard University and Harvard Pilgrim Health Care Institute.

Paid sick leave provides workers with job-protected paid time off to address short-term illnesses or seek preventive care for themselves and their family members. We studied the impact of mandatory paid sick leave at the state level on emergency department (ED) visit rates, using all-payer, longitudinal ED data from the Healthcare Cost and Utilization Project for the period 2011-19. We found that state implementation of paid sick leave mandates was associated with a 5.6 percent reduction in the total ED visit rate relative to the baseline, equivalent to 23 fewer visits per 1,000 population per year. The reduction was concentrated in Medicaid patients. Some of the largest reductions were ED visits related to adult dental conditions, adult mental health or substance use disorders, and pediatric asthma. Mandatory paid sick leave may be an effective policy lever to reduce excess ED use and costs.
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http://dx.doi.org/10.1377/hlthaff.2022.00098DOI Listing
August 2022

Platelet Count/Spleen Thickness Ratio and the Risk of Variceal Bleeding in Cirrhosis With Esophagogastric Varices.

Front Med (Lausanne) 2022 14;9:870351. Epub 2022 Jul 14.

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Introduction: The platelet count/spleen thickness ratio (PC/ST ratio) is associated with the grade of esophagogastric varices (EGV) in cirrhotic patients, but little is known about its relationship with esophagogastric variceal bleeding (EGVB). The aim of this study was to investigate the association between the PC/ST ratio and the risk of EGVB within 1 year in cirrhotic patients.

Methods: A total of 1,354 patients with cirrhosis who had EGV were enrolled in this cohort study. A logistic regression model was used to determine the association between the PC/ST ratio and the risk of EGVB within 1 year in patients with cirrhosis by adjusting the PC/ST ratio with all the important clinical variables and confounders.

Results: The quartile values of the PC/ST ratio were 1.01, 1.36, and 1.98, respectively. The PC/ST ratio was an independent risk factor for variceal bleeding in cirrhotic patients with moderate or severe EGV. After adjusting for multiple variables, the relationship was still unchanged. The odds ratios of the first EGVB in these patients were 5.07-fold at non-adjustment and 3.28-fold after multivariate adjustment. The odds ratios of rebleeding in these patients from the lowest to the highest quartile were 2.34-fold at non-adjustment and 2.01-fold after multivariable adjustment. The PC/ST ratio ≤ 1.36 elevated the 1-year risk of first-time variceal bleeding or rebleeding in cirrhotic patients with moderate or severe EGV (All < 0.05).

Conclusion: The PC/ST ratio ≤ 1.36 is an independent risk factor for the onset of first bleeding or rebleeding in cirrhotic patients with moderate or severe EGV.
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http://dx.doi.org/10.3389/fmed.2022.870351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329511PMC
July 2022

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study.

Lancet Reg Health West Pac 2022 Sep 26;26:100520. Epub 2022 Jul 26.

Shanghai Municipal Center for Disease Control and Prevention, No. 1380 Zhongshan West Street, Changning District, Shanghai City 200051, China.

Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China.

Methods: In 2020-2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death).

Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions.

Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms.

Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436].
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http://dx.doi.org/10.1016/j.lanwpc.2022.100520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335373PMC
September 2022

Does Splinting the Direct Copings Increase the Impression Accuracy of Two-Unit Nonparallel Implant Restorations? A Systematic Review and Meta-analysis.

Int J Oral Maxillofac Implants 2022 Jul-Aug;37(4):653-659

Purpose: The purpose of this systematic review and meta-analysis was to evaluate the effects of splinting impression copings on the accuracy of conventional impressions for two-unit nonparallel implant restorations.

Materials And Methods: MEDLINE via PubMed, Embase, and Web of Science databases were searched with no publication year or language limits, and studies comparing the accuracy of conventional impressions for two-unit nonparallel implant restorations made using splinted impression copings and nonsplinted impression copings were identified. A meta-analysis was performed using Review Manager software. The mean difference (MD) with 95% confidence interval (95% CI) for the framework strain and marginal gap of the implant-framework connection between impressions using splinted and nonsplinted copings were statistically analyzed (α = .05).

Results: Initially, 142 articles were identified after the removal of duplicates. Five in vitro studies were included in the systematic review, and four in vitro studies were included in the meta-analysis. All the included studies were focused on internal-connection implants and implant-level impressions. The implant angulation in the included studies ranged from 8 to 30 degrees. Impressions using splinted impression copings exhibited significantly smaller marginal gaps than those using nonsplinted impression copings (P = .02; mean difference [MD] = -13.34; 95% CI = -24.31 to -2.36). Moreover, with respect to the framework strain, no significant differences were found between impressions using splinted impression copings and nonsplinted impression copings (P = .47; MD = -12.64; 95% CI = -47.32 to 22.03).

Conclusions: Significantly larger marginal gaps were found in the impressions using splinted impression copings, but the clinical significance was low. Based on the limited number of studies included, splinting copings is unnecessary when making conventional impressions for two-unit nonparallel implant restorations.
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http://dx.doi.org/10.11607/jomi.9577DOI Listing
August 2022

Anger, Fear, and Sadness: Relations to Socioeconomic Status and the Amygdala.

J Cogn Neurosci 2022 Jul 22:1-11. Epub 2022 Jul 22.

University of Pennsylvania.

Here, we test three often proposed hypotheses about socioeconomic status (SES), affect, and the brain, for which evidence is mixed or lacking. The first hypothesis, that negative affect is more common at lower levels of SES, has ample evidence from studies of psychiatric symptoms but is tested for the first time here across multiple measures of negative emotions in healthy young adults. The second hypothesis is actually a set of hypotheses, that SES is associated with three structural and functional properties of the amygdala. Third, and most important for the affective neuroscience of SES, is the hypothesis that SES differences in the amygdala are responsible for the affective differences. Despite the intuitive appeal of this hypothesis, it has rarely been tested and has never been confirmed. Here, we review the literature for evidence on each of these hypotheses and find in a number of cases that the evidence is weak or nonexistant. We then subject each hypothesis to a new empirical test with a large sample of healthy young adults. We confirm that negative affect is more common at lower levels of SES and we find a positive relation between SES and amygdala volume. However, evidence is weak on the relation of SES to functional properties of amygdala. Finally, the tendency toward negative affect in lower SES individuals cannot be accounted for by the structural or functional characteristics of the amygdala measured here.
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http://dx.doi.org/10.1162/jocn_a_01892DOI Listing
July 2022

Insight into the Catalytic Role of Defect-Enriched Vanadium Sulfide for Regulating the Adsorption-Catalytic Conversion Behavior of Polysulfides in Li-S Batteries.

ACS Appl Mater Interfaces 2022 Aug 28;14(31):35833-35843. Epub 2022 Jul 28.

National Base for International Science and Technology Cooperation, National Local Joint Engineering Laboratory for Key Materials of New Energy Storage Battery, Hunan Province Key Laboratory of Electrochemical Energy Storage and Conversion, School of Chemistry, Xiangtan University, Xiangtan 411105, China.

The performance promotion of Li-S batteries relies primarily on inhibition of the shuttle effect and improvement of the catalytic-conversion reaction kinetics of polysulfides. Herein, we prepare defect-enriched VS nanosheets (VS) as catalysts for Li-S batteries and further study the catalytic mechanism of VS via ex situ X-ray diffraction and in situ UV-vis spectroscopy. A multifunctional S cathode was also obtained by assembling VS on a C cloth to achieve high S loading for Li-S batteries. It was found that VS catalysts undergo a lithiation process in the work voltage of Li-S batteries, and the triggered LiVS intermediates reciprocate VS with a high catalytic activity so as to enhance the performance of Li-S batteries by promoting the dissociation process of S to S. Consequently, Li-S batteries with a C/VS/S cathode deliver a high reversible capacity (1471 mAh g at 0.1 C) and good cycling performance (low fading rate of 0.064% per cycle after 400 cycles). Meanwhile, the [email protected]/S cathode with a high S areal loading of 5.6 mg cm can render a satisfactory areal capacity of 4.22 mAh cm at 0.2 C and a cycle stability of over 100 cycles. Therefore, the study on the catalysis of LiVS intermediates provides a scientific view for revealing the catalysis mechanism of a sulfide-based electrocatalyst and boosting the development of an electrocatalyst for Li-S batteries.
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http://dx.doi.org/10.1021/acsami.2c09791DOI Listing
August 2022

Radioimmunotherapy-induced intratumoral changes in cervical squamous cell carcinoma at single-cell resolution.

Cancer Commun (Lond) 2022 Jul 27. Epub 2022 Jul 27.

Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, P. R. China.

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http://dx.doi.org/10.1002/cac2.12342DOI Listing
July 2022

CB2 Agonist GW842166x Protected against 6-OHDA-Induced Anxiogenic- and Depressive-Related Behaviors in Mice.

Biomedicines 2022 Jul 22;10(8). Epub 2022 Jul 22.

Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.

In addition to motor dysfunction, patients with Parkinson's disease (PD) are often affected by neuropsychiatric disorders, such as anxiety and depression. In animal models, activation of the endocannabinoid (eCB) system produces anxiolytic and antidepressant-like behavioral effects. CB2 agonists have demonstrated neuroprotective effects against neurotoxin-induced dopamine neuron loss and deficits in motor function. However, it remains unknown whether CB2 agonism ameliorates anxiogenic- and depressive-like behaviors in PD models. Here, we report that the selective CB2 agonist GW842166x exerted neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic terminals and dopamine release in the striatum, which were blocked by the CB2 antagonist AM630. We found that 6-OHDA-treated mice exhibited anxiogenic- and depressive-like behaviors in the open-field, sucrose preference, novelty-suppressed feeding, marble burying, and forced swim tests but did not show significant changes in the elevated plus-maze and light-dark box test. GW842166x treatments ameliorated 6-OHDA-induced anxiogenic- and depressive-like behaviors, but the effects were blocked by CB2 antagonism, suggesting a CB2-dependent mechanism. These results suggest that the CB2 agonist GW842166x not only reduces 6-OHDA-induced motor function deficits but also anxiogenic- and depressive-like behaviors in 6-OHDA mouse models of PD.
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http://dx.doi.org/10.3390/biomedicines10081776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329798PMC
July 2022

Responses of the Mushroom under Different CO Concentration by Comparative Proteomic Analyses.

J Fungi (Basel) 2022 Jun 21;8(7). Epub 2022 Jun 21.

National Engineering Research Center of Edible Fungi, Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China.

Background: is a popular edible mushroom in East Asian markets. Research on the responses of under different carbon dioxide concentrations is limited.

Methods: Label-free LC-MS/MS quantitative proteomics analysis technique was adopted to obtain the protein expression profiles of fruiting body pileus collected under different carbon dioxide concentrations. The Pearson correlation coefficient analysis and principal component analysis were performed to reveal the correlation among samples. The differentially expressed proteins (DEPs) were organized. Gene ontology analysis was performed to divide the DEPs into different metabolic processes and pathways.

Results: The expansion of stipes was inhibited in the high CO group compared with that in the low CO group. There were 415 DEPs (131 up- and 284 down-regulated) in PH11 treated with 1% CO concentration compared with under atmospheric conditions. Proteins related to hydrolase activity, including several amidohydrolases and cell wall synthesis proteins, were highly expressed under high CO concentration. Most of the kinases and elongation factors were significantly down-regulated under high CO concentration. The results suggest that the metabolic regulation and development processes were inhibited under high CO concentrations. In addition, the sexual differentiation process protein Isp4 was inhibited under high CO concentrations, indicating that the sexual reproductive process was also inhibited under high CO concentrations, which is inconsistent with the small fruiting body pileus under high CO concentrations.

Conclusions: This research reports the proteome analysis of commercially relevant edible fungi under different carbon dioxide concentrations. This study deepens our understanding of the mechanism for CO-induced morphological change in the fruiting body, which will facilitate the artificial cultivation of edible mushrooms.
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http://dx.doi.org/10.3390/jof8070652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321156PMC
June 2022

Crosstalk of Redox-Related Subtypes, Establishment of a Prognostic Model and Immune Responses in Endometrial Carcinoma.

Cancers (Basel) 2022 Jul 12;14(14). Epub 2022 Jul 12.

Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Redox plays a central part in the pathogeneses and development of tumors. We comprehensively determined the expression patterns of redox-related genes (RRGs) in endometrial carcinoma (EC) cohorts from public databases and identified four different RRG-related clusters. The prognosis and the characteristics of TME cell infiltration of RRGcluster C patients were worse than those of other RRG clusters. When it comes to the gene cluster, there were great differences in clinicopathology traits and immunocyte infiltration. The RRG score was calculated by Cox analyses, and an RRG-based signature was developed. The risk score performed well in the EC cohort. Samples were separated into two risk subgroups with the standard of the value of the median risk score. Low-risk patients had a better prognosis and higher immunogenicity. In addition, RRG score was closely associated with immunophenoscore, microsatellite instability, tumor mutation burden, tumor stem cell index, copy number variation and chemotherapy sensitivity. The nomogram accurately predicted the prognosis of patients, and our model showed better performance than other published models. In conclusion, we built a prognostic model of RRGs which can help to evaluate clinical outcomes and guide more effective treatment.
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http://dx.doi.org/10.3390/cancers14143383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319597PMC
July 2022

A review of the zoledronic acid combined with percutaneous vertebroplasty in the osteoporotic vertebral compression fracture.

Asian J Surg 2022 Jul 22. Epub 2022 Jul 22.

The Department of Joint and Hand Orthopedics, The First People's Hospital of Huaihua, Hunan, Huaihua, 418000, China; Department of Sport & Rehabilitation Medicine, Institution of Orthopedics, Medical School of Jishou, University, Jishou, Hunan, 416000, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.07.020DOI Listing
July 2022

Low abundance of mitophagy markers is associated with reactive oxygen species overproduction in cows with fatty liver and causes reactive oxygen species overproduction and lipid accumulation in calf hepatocytes.

J Dairy Sci 2022 Jul 18. Epub 2022 Jul 18.

State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin Province, 130062, China. Electronic address:

Mitochondria are the main site of fatty acid oxidation and reactive oxygen species (ROS) formation. Damaged or dysfunctional mitochondria induce oxidative stress and increase the risk of lipid accumulation. During the process of mitophagy, PTEN induced kinase 1 (PINK1) accumulates on damaged mitochondria and recruits cytoplasmic Parkin to mitochondria. As an autophagy receptor protein, sequestosome-1 (p62) binds Parkin-ubiquitinated outer mitochondrial membrane proteins and microtubule-associated protein 1 light chain 3 (LC3) to facilitate degradation of damaged mitochondria. In nonruminants, clearance of dysfunctional mitochondria through the PINK1/Parkin-mediated mitophagy pathway contributes to reducing ROS production and maintaining metabolic homeostasis. Whether PINK1/Parkin-mediated mitophagy plays a similar role in dairy cow liver is not well known. Thus, the objective of this study was to investigate mitophagy status in dairy cows with fatty liver and its role in free fatty acid (FFA)-induced oxidative stress and lipid accumulation. Liver and blood samples were collected from healthy dairy cows (n = 10) and cows with fatty liver (n = 10) that had a similar number of lactations (median = 3, range = 2 to 4) and days in milk (median = 6 d, range = 3 to 9 d). Calf hepatocytes were isolated from 5 healthy newborn female Holstein calves (1 d of age, 30-40 kg). Hepatocytes were transfected with small interfering RNA targeted against PRKN for 48 h or transfected with PRKN overexpression plasmid for 36 h, followed by treatment with FFA (0.3 or 1.2 mM) for 12 h. Mitochondria were isolated from fresh liver tissue or calf hepatocytes. Serum concentrations of β-hydroxybutyrate were higher in dairy cows with fatty liver. Hepatic malondialdehyde (MDA) and hydrogen peroxide (HO) were greater in cows with fatty liver. The lower protein abundance of PINK1, Parkin, p62, and LC3-II in hepatic mitochondrial fraction of dairy cows with fatty liver indicated the mitophagy was impaired. In hepatocytes, knockdown of PRKN decreased protein abundance of p62 and LC3-II in the mitochondrial fraction, and increased contents of triacylglycerol (TG), MDA, and HO. In addition, protein abundances of PINK1, Parkin, p62, and LC3-II were lower in the mitochondrial fraction from hepatocytes treated with 1.2 mM FFA than the hepatocytes treated with 0.3 mM FFA, whereas the content of TG, MDA, and HO increased. In 1.2 mM FFA-treated hepatocytes, PRKN overexpression increased protein abundance of p62 and LC3-II in the mitochondrial fraction and decreased contents of TG, MDA, and HO. Together, our data demonstrate that low abundance of mitophagy markers is associated with ROS overproduction in dairy cows with fatty liver and impaired mitophagy induced by a high concentration of FFA promotes ROS production and lipid accumulation in female calf hepatocytes.
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http://dx.doi.org/10.3168/jds.2021-21774DOI Listing
July 2022

Reassessing the causal role of obesity in breast cancer susceptibility: a comprehensive multivariable Mendelian randomization investigating the distribution and timing of exposure.

Int J Epidemiol 2022 Jul 15. Epub 2022 Jul 15.

Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Previous Mendelian randomization (MR) studies on obesity and risk of breast cancer adopted a small number of instrumental variables and focused mainly on the crude total effect. We aim to investigate the independent causal effect of obesity on breast cancer susceptibility, considering the distribution of fat, covering both early and late life.

Methods: Using an enlarged set of female-specific genetic variants associated with adult general [body mass index (BMI)] and abdominal obesity [waist-to-hip ratio (WHR) with and without adjustment for BMI, WHR and WHRadjBMI] as well as using sex-combined genetic variants of childhood obesity (childhood BMI), we performed a two-sample univariable MR to re-evaluate the total effect of each obesity-related exposure on overall breast cancer (Ncase = 133 384, Ncontrol = 113 789). We further looked into its oestrogen receptor (ER)-defined subtypes (NER+ = 69 501, NER- = 21 468, Ncontrol = 105 974). Multivariable MR was applied to estimate the independent causal effect of each obesity-related exposure on breast cancer taking into account confounders as well as to investigate the independent effect of adult and childhood obesity considering their inter-correlation.

Results: In univariable MR, the protective effects of both adult BMI [odds ratio (OR) = 0.89, 95% CI = 0.83-0.96, P = 2.06 × 10-3] and childhood BMI (OR = 0.78, 95% CI = 0.70-0.87, P = 4.58 × 10-6) were observed for breast cancer overall. Comparable effects were found in ER+ and ER- subtypes. Similarly, genetically predicted adult WHR was also associated with a decreased risk of breast cancer overall (OR = 0.87, 95% CI = 0.80-0.96, P = 3.77 × 10-3), restricting to ER+ subtype (OR = 0.88, 95% CI = 0.80-0.98, P = 1.84 × 10-2). Conditional on childhood BMI, the effect of adult general obesity on breast cancer overall attenuated to null (BMI: OR = 1.00, 95% CI = 0.90-1.10, P = 0.96), whereas the effect of adult abdominal obesity attenuated to some extent (WHR: OR = 0.90, 95% CI = 0.82-0.98, P = 1.49 × 10-2; WHRadjBMI: OR = 0.92, 95% CI = 0.86-0.99, P = 1.98 × 10-2). On the contrary, an independent protective effect of childhood BMI was observed in breast cancer overall, irrespective of adult measures (adjusted for adult BMI: OR = 0.84, 95% CI = 0.77-0.93, P = 3.93 × 10-4; adjusted for adult WHR: OR = 0.84, 95% CI = 0.76-0.91, P = 6.57 × 10-5; adjusted for adult WHRadjBMI: OR = 0.80, 95% CI = 0.74-0.87, P = 1.24 × 10-7).

Conclusion: Although successfully replicating the inverse causal relationship between adult obesity-related exposures and risk of breast cancer, our study demonstrated such effects to be largely (adult BMI) or partly (adult WHR or WHRadjBMI) attributed to childhood obesity. Our findings highlighted an independent role of childhood obesity in affecting the risk of breast cancer as well as the importance of taking into account the complex interplay underlying correlated exposures.
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http://dx.doi.org/10.1093/ije/dyac143DOI Listing
July 2022

Pyrolysis Characteristics of Indonesian Oil Sand in a Fixed Bed.

ACS Omega 2022 Jul 27;7(27):23315-23321. Epub 2022 Jun 27.

Engineering Research Centre of Oil Shale Comprehensive Utilization, Ministry of Education, School of Energy and Power Engineering, Northeast Electric Power University, Jilin 132012, China.

In this research, pyrolysis experiment of Indonesian oil sand was performed in a fixed bed. Results show that the temperature and heating rate had significant effects on the pyrolysis products. Data studied include yields of products and the gaseous product composition of carbon monoxide, hydrogen, methane, and other hydrocarbons. Four functional group bands (aromatic hydrocarbon, oxygen, aliphatic, and hydroxyl functional groups) are observed from Fourier transform infrared spectroscopy of oil sand. The influence of pyrolysis temperature on the total pore volume and the Brunauer-Emmett-Teller (BET) specific surface area of char was also studied. With increasing temperature, the BET specific surface area showed an increasing trend in the overall temperature range. The specific surface area and the total pore volume showed similar trends except the tiny difference of 5 °C/min from 200 to 300 °C. The heating rate did not influence the development of the pore structure obviously. Mainly, three different reaction regions were observed during pyrolysis of oil sand. This study provides a theoretical foundation for further effective exploitation and economical application of oil sand.
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http://dx.doi.org/10.1021/acsomega.2c01479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280764PMC
July 2022

A comprehensive prognostic and immune analysis of enhancer RNA identifies IGFBP7-AS1 as a novel prognostic biomarker in Uterine Corpus Endometrial Carcinoma.

Biol Proced Online 2022 Jul 15;24(1). Epub 2022 Jul 15.

Department of Biostatistics, School of Public Heath, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, P.R. China.

Background: Long non-coding RNAs (lncRNA) have been implicated in a hand of studies that supported an involvement and co-operation in Uterine Corpus Endometrial Carcinoma (UCEC). Enhancer RNAs (eRNA), a functional subtype of lncRNA, have a key role throughout the genome to guide protein production, thus potentially associated with diseases.

Methods: In this study, we mainly applied the Cancer Genome Atlas (TCGA) dataset to systematically discover crucial eRNAs involving UCEC. For the key eRNAs in UCEC, we employed RT-qPCR to compare eRNA expression levels in tumor tissues and paired normal adjacent tissues from UCEC patients for validation. Furthermore, the relationships between the key eRNAs and immune activities were measured from several aspects, including the analysis for tumor microenvironment, immune infiltration cells, immune check point genes, tumor mutation burden, and microsatellite instability, as well as m6A related genes. Finally, the key eRNAs were verified by a comprehensive pan-cancer analysis.

Results: IGFBP7 Antisense RNA 1 (IGFBP7-AS1) was identified as the key eRNA for its expression patterns of low levels in tumor tissues and favorable prognostic value in UCEC correlated with its target gene IGFBP7. In RT-qPCR analysis, IGFBP7-AS1 and IGFBP7 had down-regulated expression in tumor tissues, which was consistent with previous analysis. Moreover, IGFBP7-AS1 was found closely related with immune response in relevant immune analyses. Besides, IGFBP7-AS1 and its target gene IGFBP7 correlated with a multi-omics pan-cancer analysis.

Conclusions: Finally, we suggested that IGFBP7-AS1 played a key role in impacting on clinical outcomes of UCEC patients for its possible influence on immune activity.
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http://dx.doi.org/10.1186/s12575-022-00172-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284715PMC
July 2022

Subtotal hemispherotomy for intractable lesional hemispheric epilepsy without hemiparesis in children.

Epilepsy Res 2022 Jun 30;185:106973. Epub 2022 Jun 30.

Pediatric Epilepsy Center, Peking University First Hospital, No. 1 Xi'an Men Street, Xicheng District, Beijing 100034, China. Electronic address:

Purpose: We analyzed the surgical indications, outcomes, and prognostic factors of subtotal hemispherotomy for intractable lesional hemispheric epilepsy in children with almost normal motor function and summarized its surgical strategies.

Methods: We retrospectively analyzed 20 children who underwent subtotal hemispherotomy (hemispheric disconnection sparing sensorimotor cortex) between March 2015 and May 2021. The children were divided into seizure-free group and residual seizures group according to their surgical outcomes. The surgical outcome was based on International League Against Epilepsy (ILAE) classification (class 1-6). All presurgical evaluation data were collected and analyzed.

Results: Among the 20 children, the mean age at the time of seizure onset, mean age at the time of surgery, and mean follow-up time was 3.2 ± 2.8, 7.5 ± 4.4, and 3.5 ± 2.1 years, respectively. All children had hemispheric lesion on MRI. At the last follow-up evaluation, 75% (15/20) of children remained seizure-free. Univariate analyses revealed that the electrocorticogram finding of epileptiform discharges in the central cortex after disconnection were poor prognostic factors for seizure outcomes (P < 0.05). Disconnection of the central operculum and insula was a poor prognostic factor for motor function after surgery (P < 0.05).

Conclusions: For intractable lesional hemispheric epilepsy with no hemiparesis, subtotal hemispherotomy can be performed with favorable seizure outcome. Disconnection of the central operculum and insula may increase the possibility of motor function injury.
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http://dx.doi.org/10.1016/j.eplepsyres.2022.106973DOI Listing
June 2022

A Simple Structure-Switch Aptasensor Using Label-Free Aptamer for Fluorescence Detection of Aflatoxin B1.

Molecules 2022 Jul 1;27(13). Epub 2022 Jul 1.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Aflatoxin B1 (AFB1) is one of the mycotoxins produced by and , and it causes contamination in foods and great risk to human health. Simple sensitive detection of AFB1 is important and demanded for food safety and quality control. Aptamers can specifically bind to targets with high affinity, showing advantages in affinity assays and biosensors. We reported an aptamer structure-switch for fluorescent detection of aflatoxin B1 (AFB1), using a label-free aptamer, a fluorescein (FAM)-labeled complementary strand (FDNA), and a quencher (BHQ1)-labeled complementary strand (QDNA). When AFB1 is absent, these three strands assemble into a duplex DNA structure through DNA hybridization, making FAM close to BHQ1, and fluorescence quenching occurs. In the presence of AFB1, the aptamer binds with AFB1, instead of hybridizing with QDNA. Thus, FAM is apart from BHQ1, and fluorescence increases with the addition of AFB1. This assay allowed detection of AFB1 with a detection limit of 61 pM AFB1 and a dynamic concentration range of 61 pM to 4 μM. This aptamer-based method enabled detection of AFB1 in complex sample matrix (e.g., beer and corn flour samples).
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http://dx.doi.org/10.3390/molecules27134257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268478PMC
July 2022

Investigating the shared genetic architecture of uterine leiomyoma and breast cancer: A genome-wide cross-trait analysis.

Am J Hum Genet 2022 07;109(7):1272-1285

Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Solna, Stockholm, Sweden; Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Electronic address:

Little is known regarding the shared genetic architecture or causality underlying the phenotypic association observed for uterine leiomyoma (UL) and breast cancer (BC). Leveraging summary statistics from the hitherto largest genome-wide association study (GWAS) conducted in each trait, we investigated the genetic overlap and causal associations of UL with BC overall, as well as with its subtypes defined by the status of estrogen receptor (ER). We observed a positive genetic correlation between UL and BC overall (r = 0.09, p = 6.00 × 10), which was consistent in ER+ subtype (r = 0.06, p = 0.01) but not in ER- subtype (r = 0.06, p = 0.08). Partitioning the whole genome into 1,703 independent regions, local genetic correlation was identified at 22q13.1 for UL with BC overall and with ER+ subtype. Significant genetic correlation was further discovered in 9 out of 14 functional categories, with the highest estimates observed in coding, H3K9ac, and repressed regions. Cross-trait meta-analysis identified 9 novel loci shared between UL and BC. Mendelian randomization demonstrated a significantly increased risk of BC overall (OR = 1.09, 95% CI = 1.01-1.18) and ER+ subtype (OR = 1.09, 95% CI = 1.01-1.17) for genetic liability to UL. No reverse causality was found. Our comprehensive genome-wide cross-trait analysis demonstrates a shared genetic basis, pleiotropic loci, as well as a putative causal relationship between UL and BC, highlighting an intrinsic link underlying these two complex female diseases.
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http://dx.doi.org/10.1016/j.ajhg.2022.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300879PMC
July 2022

Potential Determinants for Radiation-Induced Lymphopenia in Patients With Breast Cancer Using Interpretable Machine Learning Approach.

Front Immunol 2022 21;13:768811. Epub 2022 Jun 21.

Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Radiation-induced lymphopenia is known for its survival significance in patients with breast cancer treated with radiation therapy. This study aimed to evaluate the impact of radiotherapy on lymphocytes by applying machine learning strategies. We used Extreme Gradient Boosting (XGboost) to predict the event of lymphopenia (grade≥1) and conduced an independent validation. Then, we induced feature attribution analysis (Shapley additive explanation, SHAP) in explaining the XGboost models to explore the directional contribution of each feature to lymphopenia. Finally, we implemented the proof-of-concept clinical validation. The results showed that the XGboost models had rigorous generalization performances (accuracies 0.764 and ROC-AUC 0.841, respectively) in the independent cohort. The baseline lymphocyte counts are the most protective feature (SHAP = 5.226, direction of SHAP = -0.964). Baseline platelets and monocytes also played important protective roles. The usage of taxane only chemotherapy was less risk on lymphopenia than the combination of anthracycline and taxane. By the contribution analysis of dose, we identified that firstly lymphocytes were sensitive to a radiation dose less than 4Gy; secondly the irradiation volume was more important in promoting lymphopenia than the irradiation dose; thirdly the irradiation dose promoted the event of lymphopenia when the irradiation volume was fixed. Overall, our findings paved the way to clarifying the radiation dose volume effect. To avoid radiation-induced lymphopenia, irradiation volume should be kept to a minimum during the planning process, as long as the target coverage is not compromised.
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http://dx.doi.org/10.3389/fimmu.2022.768811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253393PMC
June 2022

Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors.

J Hematol Oncol 2022 07 7;15(1):87. Epub 2022 Jul 7.

Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, 518053, China.

The development of combination immunotherapy based on the mediation of regulatory mechanisms of the tumor immune microenvironment (TIME) is promising. However, a deep understanding of tumor immunology must involve the systemic tumor immune environment (STIE) which was merely illustrated previously. Here, we aim to review recent advances in single-cell transcriptomics and spatial transcriptomics for the studies of STIE, TIME, and their interactions, which may reveal heterogeneity in immunotherapy responses as well as the dynamic changes essential for the treatment effect. We review the evidence from preclinical and clinical studies related to TIME, STIE, and their significance on overall survival, through different immunomodulatory pathways, such as metabolic and neuro-immunological pathways. We also evaluate the significance of the STIE, TIME, and their interactions as well as changes after local radiotherapy and systemic immunotherapy or combined immunotherapy. We focus our review on the evidence of lung cancer, hepatocellular carcinoma, and nasopharyngeal carcinoma, aiming to reshape STIE and TIME to enhance immunotherapy efficacy.
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http://dx.doi.org/10.1186/s13045-022-01307-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264569PMC
July 2022

Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment.

J Transl Med 2022 07 6;20(1):308. Epub 2022 Jul 6.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China.

Background: Tumour-derived exosomes have recently been shown to participate in the formation and progression of different cancer processes, including tumour microenvironment remodelling, angiogenesis, invasion, metastasis, and drug resistance. However, the function and mechanism of exosome-encapsulated nucleic acids and proteins in bladder cancer remain unclear. This study aimed to investigate the effects of tumour-derived exosomes on the tumorigenesis and development of bladder cancer.

Methods: In this study, gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database and two independent Gene Expression Omnibus (GEO) datasets. The nucleic acids and proteins encapsulated in bladder cancer-derived exosomes were obtained from the ExoCarta database. Based on these databases, the expression patterns of exosomal mRNAs and proteins and the matched clinicopathological characteristics were analysed. Furthermore, we carried out a series of experiments to verify the relevant findings.

Results: A total of 7280 differentially expressed mRNAs were found in TCGA data, of which 52 mRNAs were shown to be encapsulated in bladder cancer-derived exosomes. Survival analysis based on the UALCAN database showed that among the top 10 upregulated and the top 10 downregulated exosomal genes, only the expression of KRT6B had a statistically significant effect on the survival of bladder cancer patients. Additionally, clinical correlation analysis showed that the elevated level of KRT6B was highly associated with bladder cancer stage, grade, and metastasis status. GSEA revealed that KRT6B was involved not only in epithelial-mesenchymal transition-related pathways but also in the immune response in bladder cancer. Ultimately, our experimental results were also consistent with the bioinformatic analysis.

Conclusion: KRT6B, which can be detected in bladder cancer-derived exosomes, plays an important role in the epithelial-mesenchymal transition and immune responses in bladder cancer. Further research will enable its potentially prognostic marker and therapeutic target for bladder cancer.
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http://dx.doi.org/10.1186/s12967-022-03508-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258227PMC
July 2022
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