bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Blood Pressure Within 6 h After Endovascular Thrombectomy and Functional Outcomes in Ischemic Stroke Patients With Successful Recanalization
Authors: Zhang Xuening , Cui Ting , Zhu Qiange , Wang Changyi , Wang Anmo , Yang Yuan , Li Shucheng , Hu Fayun , Wu Bo
Published: April 2022

Background and Purpose

Blood pressure in the days following endovascular thrombectomy (EVT) can influence functional outcomes of patients who have suffered an acute ischemic stroke, but whether the same is true of blood pressure during the first few hours after EVT is unclear.

Methods

Several blood pressure parameters were retrospectively analyzed in acute ischemic stroke patients who underwent EVT at West China Hospital from March 2016 to December 2019. Baseline blood pressure, speed of blood pressure reduction, postoperative blood pressure, degree of blood pressure reduction, and quality of blood pressure management were evaluated during the first 24 h after EVT. We explored whether these parameters during different time windows correlated significantly with patients' modified Rankin Scale (mRS) score at 90 days.

Results

Analysis of 163 patients showed that poor functional outcome (mRS scores 3–6) correlated significantly with higher postoperative blood pressure and worse blood pressure management during the first 6 h after EVT. Postoperative systolic blood pressure at 37 min after EVT was significantly higher in patients with poor outcome (141 mmHg) than in those with good outcome (mRS scores 0–2; 122 mmHg, p = 0.006), and systolic pressure >136 mmHg at this time point was associated with a significantly higher risk of poor outcome, before and after adjusting for other risk factors (adjusted OR 0.395, 95% CI 0.20–0.79).

Conclusions

Among acute ischemic patients who successfully undergo recanalization, adequate blood pressure management during the first 30–40 min after EVT may be important for ensuring good 90-day functional outcomes.
An Exponential Curve Relationship Between Serum Urate and Migraine: A Cross-Section Study From NHANES
Authors: Hong Peiwei , Liu Yao , Wan Yang , Xiong Hai , Xu Yanming
Published: April 2022

Background

Migraine is a common neurological disease and an important cause of disability worldwide. Serum urate is the end product of purine metabolism in Homo sapiens and other hominoids. Previous studies about the serum urate level in migraine were contradictory. Hence, we present a cross-section study to clarify the association between serum urate and migraine and explore the dose effect of serum urate on migraine.

Materials and Methods

The data for this cross-section study were acquired from the National Health and Nutrition Examination Survey (NHANES). A diagnosis of migraine was made through patient the self-reported and prescription medication. For data analysis, the weighted linear regression model, weighted chi-square test, logistic regression models, smooth curve fittings, and the two-piecewise linear regression model were utilized for data analysis. All data analysis was conducted on Empower software.

Results

Totally, 18,637 participants were enrolled in this study, of which 208 were migraineurs. The rest were set as control. There existed a statistically significant difference in mean age (p = 0.0389), gender (p< 0.0001), race (p< 0.0001), data release cycle (p = 0.048), drug usage, blood albumin (p< 0.0001), blood total protein (p< 0.0001), hemoglobin (p< 0.0001), serum iron (p< 0.0001), and serum urate (p< 0.0001) between the two groups. According to logistic regression models, there existed no consistent linear relationship between serum urate and migraine before (model 1: odd ratio (OR) = 0.83, p = 0.0004) or after adjusting for confounders (model 2: OR = 0.96, p = 0.5198; model 3: OR = 0.84, p = 0.0184). However, smooth curve fittings found an exponential curve relationship between serum urate and migraine. Furthermore, when serum urate was more than 7.8 mg/dl, higher serum urate was correlated with higher migraine occurrence (model 1: OR = 1.54, p = 0.0022; model 2: OR = 1.51, p = 0.0050; model 3: OR = 1.77, p = 0.0348). Besides, 8 out of the 208 migraineurs had a serum urate higher than 7.8 mg/dl.

Conclusions

In conclusion, there existed an exponential curve relationship between serum urate and migraine, with an infliction point of 7.8 mg/dl. When serum urate was more than 7.8 mg/dl, increased serum urate was correlated with higher migraine occurrence.
Neural Phenomenon in Musicality: The Interpretation of Dual-Processing Modes in Melodic Perception
Authors: Gande Nathazsha
Published: April 2022

The confluence of creativity in music performance finds itself in performance practices and cultural motifs, the communication of the human body along with the instrument it interacts with, and individual performers’ perceptual, motor, and cognitive abilities that contribute to varied musical interpretations of the same piece or melodic line. The musical and artistic execution of a player, as well as the product of this phenomena can become determinant causes in a creative mental state. With advances in neurocognitive measures, the state of one’s artistic intuition and execution has been a growing interest in understanding the creative thought process of human behavior, particularly in improvising artists. This article discusses the implementation on the concurrence of spontaneous (Type-1) and controlled (Type-2) processing modes that may be apparent in the perception of non-improvising artists on how melodic lines are perceived in music performance. Elucidating the cortical-subcortical activity in the dual-process model may extend to non-improvising musicians explored in the paradigm of neural correlates. These interactions may open new possibilities for expanding the repertoire of executive functions, creativity, and the coordinated activity of cortical-subcortical regions that regulate the free flow of artistic ideas and expressive spontaneity in future neuromusical research.
Visual Evoked Potentials to Monitor Myelin Cuprizone-Induced Functional Changes
Authors: Marenna Silvia , Huang Su-Chun , Dalla Costa Gloria , d’Isa Raffaele , Castoldi Valerio , Rossi Elena , Comi Giancarlo , Leocani Letizia
Published: April 2022

The visual system is one of the most accessible routes to study the central nervous system under pathological conditions, such as in multiple sclerosis (MS). Non-invasive visual evoked potential (VEP) and optical coherence tomography (OCT) were used to assess visual function and neuroretinal thickness in C57BL/6 taking 0.2% cuprizone for 7 weeks and at 5, 8, 12, and 15 days after returning to a normal diet. VEPs were significantly delayed starting from 4 weeks on cuprizone, with progressive recovery off cuprizone, becoming significant at day 8, complete at day 15. In contrast, OCT and neurofilament staining showed no significant axonal thinning. Optic nerve histology indicated that whilst there was significant myelin loss at 7 weeks on the cuprizone diet compared with healthy mice, at 15 days off cuprizone diet demyelination was significantly less severe. The number of Iba 1+ cells was found increased in cuprizone mice at 7 weeks on and 15 days off cuprizone. The combined use of VEPs and OCT allowed us to characterize non-invasively, in vivo, the functional and structural changes associated with demyelination and remyelination in a preclinical model of MS. This approach contributes to the non-invasive study of possible effective treatments to promote remyelination in demyelinating pathologies.
What Is Adult Hippocampal Neurogenesis Good for?
Authors: Kempermann Gerd
Published: April 2022

Adult hippocampal neurogenesis is a unique and exceptional process in the mammalian brain that in a lifelong and activity-dependent way generates new excitatory principal neurons. A comprehensive view on their function in greater contexts has now emerged, revealing to which extent the hippocampus (and hence brain and mind) depend on these neurons. Due to a postmitotic period of heightened synaptic plasticity they bias incoming excitation to the dentate gyrus to non-overlapping subnetworks, resulting in pattern separation and the avoidance of catastrophic interference. Temporally, this promotes the flexible integration of novel information into familiar contexts and contributes to episodic memory, which in humans would be critical for autobiographic memory. Together these local effects represent a unique strategy to solve the plasticity-stability dilemma that all learning neuronal networks are facing. Neurogenesis-dependent plasticity also improves memory consolidation. This relates to the surprising involvement of adult neurogenesis in forgetting, which is also hypothesized to be critically relevant for negative plasticity, for example in post-traumatic stress disorder. In addition, adult-born neurons also directly mediate stress-resilience and take part in affective behaviors. Finally, the activity- and experience-dependent plasticity that is contributed by adult neurogenesis is associated with an individualization of the hippocampal circuitry. While a solid and largely consensual understanding of how new neurons contribute to hippocampal function has been reached, an overarching unifying theory that embeds neurogenesis-dependent functionality and effects on connectomics is still missing. More sophisticated multi-electrode electrophysiology, advanced ethologically relevant behavioral tests, and next-generation computational modeling will let us take the next steps.
The Prevalence and Risk Factors of Iron Deficiency Anemia Among Pregnant Women in Malaysia: A Systematic Review
Authors: Abd Rahman Raudah , Idris Idayu Badilla , Isa Zaleha Md , Rahman Rahana Abdul , Mahdy Zaleha Abdullah
Published: April 2022

Anemia in pregnancy is defined as a hemoglobin level of <11 g/dl, and is commonly due to iron deficiency. This systematic review was conducted to determine the prevalence and risk factors of anemia and iron deficiency among pregnant women in Malaysia. A systematic literature search was conducted in Google Scholar, PubMed, and Cochrane Library databases. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. Eight studies comprising a total number of 2,638 pregnant women were included in this review. Only two studies focused on iron deficiency, whereas the other six investigated anemia in pregnancy without specifying iron deficiency or any other nutritional cause for the anemia, signifying the lack of published literature on this important public health nutritional issue in Malaysia. The overall prevalence of anemia in pregnancy ranged from 19.3 to 57.4%, while the prevalence of iron deficiency was 31.6 to 34.6%. Factors that were significantly associated with anemia in pregnancy were extremes of reproductive age, late antenatal booking, non-compliance to hematinics, Indian ethnicity, being in the second or third trimester, low maternal educational level, low family income, and unemployment. The prevalence of anemia in pregnancy was found to be higher in rural compared to urban areas. Meanwhile, in terms of iron deficiency anemia, grandmultiparity, late antenatal booking and Indian ethnicity were significant determinants. It is certainly plausible that the anemia in pregnancy reported in these studies is not entirely secondary to iron deficiency and may be attributable to other nutritional deficiencies, emphasizing the importance of researching deeper into this subject. Nevertheless, in the meantime, focusing on iron supplementation in high-risk mothers with emphasis on compliance, seems to be the best option, in view of the high prevalence of iron deficiency found in this review.
The Nutritional Properties, Chemical Compositions, and Functional Characteristics of the Aerial Parts of Adonis coerulea
Authors: Dai Lixia , Li Bing , Yang Xiaorong , Wang Yu , Pan Hu , Zhang Jiyu , Shang Xiaofei
Published: April 2022

The nutrition and active compounds from plants are very important to regulate the immunity of the body by improving the oxidant and inflammatory response. In this article, we aimed to investigate the nutritional profile and the phytochemical compositions of Adonis coerulea; the functional characteristics and its possible mechanism were studied. Results showed that the aerial parts of Adonis coerulea (ACAP) contained the abundant of proteins (16.15%) and the minerals (31.02.09 mg/100 g dried ACAP); promisingly, the content of essential amino acids (8.25%) and fatty acids (13,220.45 mg/100 g) also were obtained to regulate the immunity and prevent some chronic diseases. The methanol extract of ACAP played the anti-inflammatory activity via peroxisome proliferators-activated receptor (PPAR)-γ-mediated nuclear factor kappa B (NF-κB) pathway. Among the 18 identified compounds, linolenic acid from fatty acids and licochalcone A were active compounds by inhibiting nitric oxide (NO) production of RAW264.7 cells induced by lipopolysaccharide (LPS). The alleviation of inflammatory response results in the decrease of oxidative stress; ACAP showed the antioxidant activity by attenuating antioxidant enzymes, improving mitochondrial membrane potential and reactive oxygen species. These results highlight the potential of A. coerulea as a source of active ingredients in pharmaceutical industries.
Effect of High Temperature Stress During the Reproductive Stage on Grain Yield and Nutritional Quality of Lentil (Lens culinaris Medikus)
Authors: Choukri Hasnae , El Haddad Noureddine , Aloui Khawla , Hejjaoui Kamal , El-Baouchi Adil , Smouni Abdelaziz , Thavarajah Dil , Maalouf Fouad , Kumar Shiv
Published: April 2022

High temperature during the reproductive stage limits the growth and development of lentil (Lens culinarisMedikus). The reproductive and seed filling periods are the most sensitive to heat stress, resulting in limited yield and nutritional quality. Climate change causes frequent incidents of heat stress for global food crop production. This study aimed to assess the impact of high temperature during the reproductive stage of lentil on grain yield, nutritional value, and cooking quality. Thirty-six lentil genotypes were evaluated under controlled conditions for their high temperature response. Genotypic variation was significant (p< 0.001) for all the traits under study. High temperature-induced conditions reduced protein, iron (Fe) and zinc (Zn) concentrations in lentils. Under heat stress conditions, mineral concentrations among lentil genotypes varied from 6.0 to 8.8 mg/100 g for Fe and from 4.9 to 6.6 mg/100 g for Zn. Protein ranged from 21.9 to 24.3 g/100 g. Cooking time was significantly reduced due to high temperature treatment; the range was 3–11 min, while under no stress conditions, cooking time variation was from 5 to 14 min. Phytic acid variation was 0.5–1.2 g/100 g under no stress conditions, while under heat stress conditions, phytic acid ranged from 0.4 to 1.4 g/100 g. All genotypes had highly significant bioavailable Fe and moderately bioavailable Zn under no stress conditions. Whereas under heat stress conditions, Fe and Zn bioavailability was reduced due to increased phytic acid levels. Our results will greatly benefit the development of biofortified lentil cultivars for global breeding programs to generate promising genotypes with low phytic acid and phytic acid/micronutrient ratio to combat micronutrient malnutrition.
Preparation of Natural Food-Grade Core-Shell Starch/Zein Microparticles by Antisolvent Exchange and Transglutaminase Crosslinking for Reduced Digestion of Starch
Authors: Wang Chaofan , Qin Kaili , Sun Qingjie , Qiao Xuguang
Published: April 2022

The purpose of this study was to slow down the digestibility of starch granules by encapsulating it in zein shells. Drop of the preformed swollen corn starch (CS) granule suspension into thermal-treated zein ethanolic solution enables antisolvent precipitation of thermal-treated zein on the surface of the preformed swollen CS granules, leading to the formation of core-shell starch/zein microparticles. Confocal laser scanning microscopy images showed that the preformed swollen CS granules were coated by thermal-treated zein shells with a thickness of 0.48–0.95 μm. The volume average particle diameter of core-shell starch/zein microparticles was 14.70 μm and reached 18.59–30.98 μm after crosslinking by transglutaminase. The results of X-ray diffraction and Fourier transform infrared spectroscopy demonstrated that an interaction occurred between the preformed swollen CS granules and the thermal-treated zein. The results for thermodynamic characteristics, pasting properties, and swelling power indicated that the compact network structure of core-shell starch/zein microparticles crosslinked by transglutaminase could improve starch granule thermal stability and resistance to shearing forces. Compared to native CS, the peak gelatinization temperatures of core-shell starch/zein microparticles increased significantly (p < 0.05), with a maximum value of 76.64°C. The breakdown values and the swelling power at 95°C of core-shell starch/zein microparticles significantly (p < 0.05) decreased by 52.83–85.66% and 0.11–0.28%, respectively. The in vitro digestibility test showed that the contents of slowly digestible starch and resistant starch in the core-shell starch/zein microparticles increased to ∼42.66 and ∼34.75%, respectively, compared to those of native CS (9.56 and 2.48%, respectively). Our research supports the application of food-grade core-shell starch/zein microparticles to formulate low-digestibility food products.
The Polymorphism and Expression of EGFL7 and miR-126 Are Associated With NSCLC Susceptibility
Authors: Liu Weipeng , Zhang Yunyun , Huang Fengdan , Ma Qianli , Li Chuanyin , Liu Shuyuan , Liang Yan , Shi Li , Yao Yufeng
Published: April 2022

Previous investigations have reported that microRNA-126 (miR-126) and its host gene, epidermal growth factor-like domain-containing protein 7 (EGFL7) are involved in lung cancer progression, suggesting EGFL7 and miR-126 play a joint role in lung cancer development. In this study, we analyzed the methylation-associated regulation of EGFL7 and miR-126 in non-small cell lung cancer (NSCLC) and further investigated the association between EGFL7/miR-126 polymorphisms and NSCLC susceptibility in the Han Chinese population. Based on our data, relative to those in adjacent normal tissue, both EGFL7 expression and miR-126 expression were decreased significantly in lung cancer tissue (P = 3x10-4 and P < 1x10-4), and the expression of EGFL7 mRNA and miR-126 was significantly correlated in both NSCLC tissue n = 46, r = 0.43, P = 0.003 and adjacent normal tissue n = 46, r = 0.37, P = 0.011. Differential methylation analysis indicated that methylation levels of multiple CG loci in EGFL7 were significantly higher in the lung cancer samples than in the normal samples (P < 0.01). Moreover, EGFL7 mRNA and miR-126 were significantly upregulated after treatment with the DNA demethylating agent 5-aza-2′-deoxycytidine (5-Aza-CdR) in lung cancer cell lines. In addition, the A allele of rs2297538 was significantly associated with a decreased NSCLC risk (OR = 0.68, 95% CI: 0.52~0.88), and the expression of EGFL7 and miR-126 was significantly lower in rs2297538 homozygous G/G tumor tissue than in A/G+A/A tumor tissue (P = 0.01 and P = 0.002). Our findings suggest that the expression of EGFL7 and miR-126 in NSCLC can be concomitantly downregulated through methylation and the EGFL7/miR-126 polymorphism rs2297538 is correlated with NSCLC risk. Together, these results provide new insights into the pathogenesis of NSCLC.
How Immunotherapy Modified the Therapeutic Scenario of Endometrial Cancer: A Systematic Review
Authors: Maiorano Brigida Anna , Maiorano Mauro Francesco Pio , Cormio Gennaro , Maglione Annamaria , Lorusso Domenica , Maiello Evaristo
Published: April 2022

Background

Endometrial cancer (EC) represents the sixth most common female tumor. In the advanced setting, the prognosis is dismal with limited treatment options. Platinum-based chemotherapy represents the actual standard of care in first-line chemotherapy, but no standard second-line chemotherapy is approved, with less than 1/4 of patients responding to second-line chemotherapy. In the last 10 years, immune checkpoint inhibitors (ICIs) have changed the treatment landscape of many solid tumors.

Methods

The review was conducted according to the PRISMA guidelines. We searched EMBASE, MEDLINE, Cochrane Database, and conference abstracts from international societies, up to November 2021. Clinical trials employing ICIs in advanced EC, written in English, were included. Reviews, letters, and commentaries were excluded. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety (number and grade of treatment-related adverse events [TRAEs]) were evaluated.

Results

15 studies, for a total of 1,627 patients, were included: 14 non-randomized phase I/II trials and 1 randomized phase III trial. Anti-PD1 (pembrolizumab, nivolumab, dostarlimab) and anti-PD-L1 agents (avelumab, atezolizumab, durvalumab) were administered as single agents; pembrolizumab and nivolumab were combined with the tyrosine-kinase inhibitors (TKI) lenvatinib and cabozantinib, respectively; and durvalumab was associated with anti-CTLA4 tremelimumab. 4 studies selected only MSI patients. Single agents determined an ORR from 26.7% to 58% among MSI patients, from 3% to 26.7% among MSS patients. DCR ranged from 53.5% to 88.9% in MSI, 31.4% to 35.2% in MSS patients. The combination of TKI and ICIs determined 32% to 63.6% of ORR in all-comers, 32%–36.2% in MSS patients. 54.2% to 76% of patients developed TRAEs. The combination of ICIs and TKI achieved a higher toxicity rate than single agents (≥G3 TRAEs 88.9%).

Conclusion

ICIs represent an effective option for pretreated advanced EC patients with a tolerable profile. Given the encouraging results in MSI patients, every woman diagnosed with EC should be investigated for MS status. In MSS women, the combination of ICIs and TKI is more effective than monotherapy, notwithstanding safety concerns. PD-L1 cannot predict ICI response, whereas other biomarkers such as MSI and tumor mutational burden seem more accurate. Ongoing randomized trials will further clarify the role of these therapeutic options.

Systematic Review Registration

PROSPERO, CRD42021293538.
Radioisotope-Guided Sentinel Lymph Node Biopsy in Penile Cancer: A Long-Term Follow-Up Study
Authors: Nemitz Lena , Vincke Anna , Michalik Bianca , Engels Svenja , Meyer Luca-Marie , Henke Rolf-Peter , Wawroschek Friedhelm , Winter Alexander
Published: April 2022

Lymph node (LN) management is critical for survival in patients with penile cancer. However, radical inguinal lymphadenectomy carries a high risk of postoperative complications such as lymphedema, lymphocele, wound infection, and skin necrosis. The European Association of Urology guidelines therefore recommend invasive LN staging by modified inguinal lymphadenectomy or dynamic sentinel node biopsy (DSNB) in clinically node-negative patients (cN0) with intermediate- and high-risk tumors (≥ T1G2). However, the timing of DSNB (simultaneous vs. subsequent to partial or total penile resection) is controversial and the low incidence of penile cancer means that data on the long-term outcomes of DSNB are limited. The present study aimed to analyze the reliability and morbidity of DSNB in patients with penile cancer during long-term follow-up. This retrospective study included 41 patients (76 groins) who underwent radioisotope-guided DSNB simultaneously or secondarily after penile surgery from June 2004 to November 2018. In total, 193 sentinel LNs (SLNs) and 39 non-SLNs were removed. The median number of dissected LNs was 2.5 (interquartile range 2–4). Histopathological analysis showed that five of the 76 groins (6.6%) contained metastases. None of the non-SLNs were tumor-positive. In accordance with the guidelines, all inguinal regions with positive SLNs underwent secondary radical inguinal lymphadenectomy, which revealed three additional metastases in one groin. Regional LN recurrence was detected in three patients (four groins) during a median follow-up of 70 months, including two patients in whom DSNB had been performed secondarily after repetitive penile tumor resections. DSNB-related complications occurred in 15.8% of groins. Most complications were mild (Clavien–Dindo grade I; 50%) or moderate (II; 25%), and invasive intervention was only required in 3.9% of groins (IIIa: n = 1; IIIb: n = 2). In summary, this study suggests that the current radioisotope-guided DSNB procedure may reduce the complication rate of inguinal lymphadenectomy in patients with cN0 penile cancer. However, DSNB and penile surgery should be performed simultaneously to minimize the false-negative rate. Recent advances, such as new tracers and imaging techniques, may help to reduce the false-negative rate of DSNB further.
Influencing Factors of Total Skin Irradiation With Helical Tomotherapy
Authors: Wang Haiyang , Pi Yifei , Guo Yuexin , Pei Xi , Xu Xie George
Published: April 2022

Purpose

To investigate the influencing factors of total skin irradiation (TSI) with helical tomotherapy for guiding the clinical selection of the suitable parameters and optimizing the plan quality and efficiency.

Materials and Methods

Six patients with mycosis fungoides (MF) who received TSI were retrospectively selected. They were all dressed with 5 mm thick diving suits during the CT scan and treatment as a bolus to increase the superficial dose through buildup. The dose prescription was 24 Gy in 20 fractions and 5 times per week. During the planned pretreatment, Ring0, Ring1, Ring2, Ring3, and Ring4 of 1 cm thick away from the planning target volume (PTV) at the distances of 0, 1, 2, 3, and 4 cm and other normal tissues (NTs) were generated, respectively. The auxiliary structures were completely blocked during planning; while the field widths were 5 and 2.5 cm, the pitches were 0.287 and 0.215, the modulation factors were 4 and 3, and the other parameters remained consistent. Finally, the dose parameters of PTV and auxiliary structures, as well as the beam on time (BOT) and gantry period, were compared and analyzed.

Results

when the auxiliary structures were completely blocked with distance to PTV (dPTV) above 3 cm were used, the mean dose (Dmean), conformity index (CI), and heterogeneity index (HI) of the PTV met the clinical requirements. As the dPTV gradually increased, the BOT decreased while the volume of normal tissue that received excessive radiation increased correspondingly. If the dPTV was less than 3 cm, the clinical requirements were not met. The field widths (FWs), pitches, and modulation factors (MFs) had no effect on PTVmean and the HI. The FW of 2.5 cm was slightly better than 5 cm for the CI. The FW and MF had a significant impact on the BOT, which gradually increased with decreasing FW and increasing MF. Pitch had no effect on the BOT.

Conclusion

During planning with TSI patients, dPTV is the key factor that has a significant influence on the plan quality. We found that the plan with the dPTV above 3 cm can meet clinical objectives. The BOT increases as the dPTV increases. The FWs also have an effect on the CI and BOT. Therefore, it is necessary to comprehensively balance these factors to optimize the quality and efficiency of the plan. We also found that different MFs and pitches have no obvious effect on the results.
The Role and Mechanism of microRNA-1224 in Human Cancer
Authors: Ma Mingwei , Li Jie , Zhang Zimu , Sun Juan , Liu Zhen , Zeng Ziyang , Ouyang Siwen , Kang Weiming
Published: April 2022

microRNAs (miRNAs) are a type of small endogenous non-coding RNAs composed of 20-22 nucleotides, which can regulate the expression of a gene by targeting 3’ untranslated region (3’-UTR) of mRNA. Many studies have reported that miRNAs are involved in the occurrence and progression of human diseases, including malignant tumors. miR-1224 plays significant roles in different tumors, including tumor proliferation, metastasis, invasion, angiogenesis, biological metabolism, and drug resistance. Mostly, it serves as a tumor suppressor. With accumulating proofs of miR-1224, it can act as a potential bio-indicator in the diagnosis and prognosis of patients with cancer. In this article, we review the characteristics and research progress of miR-1224 and emphasize the regulation and function of miR-1224 in different cancer. Furthermore, we conclude the clinical implications of miR-1224. This review may provide new horizons for deeply understanding the role of miR-1224 as biomarkers and therapeutic targets in human cancer.
Chordin-Like 1 Regulates Epithelial-to-Mesenchymal Transition and Metastasis via the MAPK Signaling Pathway in Oral Squamous Cell Carcinoma
Authors: Wu Qiuyu , Zheng Zhichao , Zhang Junwei , Piao Zhengguo , Xin Mengyu , Xiang Xi , Wu Antong , Zhao Tianyu , Huang Songkai , Qiao Yu , Zhou Jiayu , Xu Shaofen , Cheng Haoyu , Wu Lihong , Ouyang Kexiong
Published: April 2022

Background

Accumulating evidence suggests that dysregulation of Chordin-like 1 (CHRDL1) is associated with malignant biological behaviors in multiple cancers. However, the exact function and molecular mechanism of CHRDL1 in oral squamous cell carcinoma (OSCC) remain unclear.

Methods

The expression levels of CHRDL1 in OSCC tissues and CAL27 cells were determined by RT-qPCR. Immunohistochemical staining was applied to detect CHRDL1 protein expression in sample tissues from OSCC patients. Gain of function and knockdown by lentivirus were further used to examine the effects of CHRDL1 on cell proliferation, migration, invasion, and adhesion in OSCC. Tail vein injection of CAL27 cells with dysregulated CHRDL1 expression was further used to examine the effect of CHRDL1 on lung colonization. RNA sequencing was performed to explore the molecular mechanisms of CHRDL1 that underlie the progression of OSCC.

Results

CHRDL1 was significantly downregulated in OSCC tissues and CAL27 cells compared to controls. CHRDL1 knockdown enhanced migration, invasion, adhesion, and EMT, but not proliferation, in CAL27 cells. Overexpression of CHRDL1 had the opposite effects. Moreover, CHRDL1 was proven to inhibit tumor metastasisin vivo. Mechanistically, MAPK signaling pathway components, including ERK1/2, p38, and JNK, were found to regulate the malignant biological behaviors of CAL27 cells.

Conclusions

Our results suggest that CHRDL1 has an inhibitory effect on OSCC metastasisviathe MAPK signaling pathway, which provides a new possible potential therapeutic target against OSCC.
Serglycin Is Involved in TGF-β Induced Epithelial-Mesenchymal Transition and Is Highly Expressed by Immune Cells in Breast Cancer Tissue
Authors: Tellez-Gabriel Marta , Tekpli Xavier , Reine Trine M. , Hegge Beate , Nielsen Stephanie R. , Chen Meng , Moi Line , Normann Lisa Svartdal , Busund Lill-Tove R. , Calin George A. , Mælandsmo Gunhild M. , Perander Maria , Theocharis Achilleas D. , Kolset Svein O. , Knutsen Erik
Published: April 2022

Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT). Functional studies provide evidence that serglycin plays an important role in the regulation of the transition between the epithelial and mesenchymal phenotypes, and it is a significant EMT marker gene. We further find that serglycin is more expressed by breast cancer cell lines with a mesenchymal phenotype as well as the basal-like subtype of breast cancers. By examining immune staining and single cell sequencing data of breast cancer tissue, we show that serglycin is highly expressed by infiltrating immune cells in breast tumor tissue.
Risk Factors for High-Arched Palate and Posterior Crossbite at the Age of 5 in Children Born Very Preterm: EPIPAGE-2 Cohort Study
Authors: Herrera Sandra , Pierrat Véronique , Kaminski Monique , Benhammou Valérie , Marchand-Martin Laetitia , Morgan Andrei S. , Le Norcy Elvire , Ancel Pierre-Yves , Germa Alice
Published: April 2022

Introduction:

Children born very preterm have an immature sucking reflex at birth and are exposed to neonatal care that can impede proper palate growth.

Objectives

We aimed to describe the frequency of high-arched palate and posterior crossbite at the age of 5 in children born very preterm and to identify their respective risk factors.

Methods

Our study was based on the data from EPIPAGE-2, a French national prospective cohort study, and included 2,594 children born between 24- and 31-week gestation. Outcomes were high-arched palate and posterior crossbite. Multivariable models estimated by generalized estimation equations with multiple imputation were used to study the association between the potential risk factors studied and each outcome.

Results

Overall, 8% of children born very preterm had a high-arched palate and 15% posterior crossbite. The odds of high-arched palate were increased for children with low gestational age (24–29 vs. 30–31 weeks of gestation) [adjusted odds ratio (aOR) 1.76, 95% confidence interval (CI) 1.17, 2.66], thumb-sucking habits at the age of 2 (aOR 1.53, 95% CI 1.03, 2.28), and cerebral palsy (aOR 2.18, 95% CI 1.28, 3.69). The odds of posterior crossbite were increased for children with pacifier-sucking habits at the age of 2 (aOR 1.75, 95% CI 1.30, 2.36).

Conclusions

Among very preterm children, low gestational age and cerebral palsy are the specific risk factors for a high-arched palate. High-arched palate and posterior crossbite share non-nutritive sucking habits as a common risk factor. The oro-facial growth of these children should be monitored.
HyProCure for Pediatric Flexible Flatfoot: What Affects the Outcome
Authors: Chen Cheng , Jiang JianTao , Fu ShaoLing , Wang Cheng , Su Yan , Mei GuoHua , Xue JianFeng , Zou Jian , Li XueQian , Shi ZhongMin
Published: April 2022

Background

The high success rate, minimal invasion, and safety of subtalar arthroereisis (SA) have made it a primary mode of surgical management for pediatric flexible flatfoot. The HyProCure procedure is a new surgery for SA, However, very few available studies reported the therapeutic effects of the HyProCure procedure, especially in pediatric flexible flatfoot. The main aim of the present study was to investigate the clinical and radiological outcomes of the HyProCure procedure for pediatric flexible flatfoot and analyze the risk factors for therapeutic outcomes and sinus tarsi pain.

Methods

In this retrospective cohort study, 69 pediatric flexible flatfoot patients (107 feet) who underwent the HyProCure procedure were included between July 2015 and September 2020. All patients underwent the HyProCure procedure with or without gastrocnemius recession. The Maryland foot score (MFS), visual analog scale (VAS), radiographic data, and complications were assessed at a minimum 1-year follow-up and statistically analyzed.

Results

The mean follow-up was 35.9 months (range, 13–73 months). At the last follow-up, VAS (0.64 ± 1.16) was significantly lower than the preoperative VAS (4.06 ± 1.43) (p < 0.001); MFS (90.39 ± 12.10) was significantly higher than the preoperative MFS (71.36 ± 10.25) (p < 0.001). The AP talar-second metatarsal angle (T2MT angle) significantly decreased from 17.0 ± 5.4° preoperatively to 11.4 ± 5.2° at the last follow-up (p < 0.001). The lateral talar-first metatarsal angle (Meary's angle) significantly decreased from 13.8 ± 6.4° preoperatively to 6.3 ± 5.0° at the last follow-up (p < 0.001). The calcaneal declination angle (Pitch angle) significantly increased from 13.5 ± 4.9° preoperatively to 14.8 ± 4.4° at the last follow-up (p < 0.001). Logistic regression analysis indicated that patients with a longer distance from the tail end of the implant exceeding the longitudinal talar bisection line had 275.8% greater odds of MFS < 90. Yet, no risk factors were found in connection with sinus tarsi pain.

Conclusions

The HyProCure procedure for pediatric flexible flatfoot achieved satisfactory curative effects with a low complication rate; implant depth was associated with unsatisfactory postoperative outcome.
Platycodon grandiflorum Triggers Antitumor Immunity by Restricting PD-1 Expression of CD8+ T Cells in Local Tumor Microenvironment
Authors: Yang Ruijie , Pei Tianli , Huang Ruifei , Xiao Yue , Yan Jiangna , Zhu Jinglin , Zheng Chunli , Xiao Wei , Huang Chao
Published: April 2022

In the tumor microenvironment (TME), the activation of programmed death-1 (PD-1)–programmed death ligand-1 (PD-L1) pathway is one of the main signals of immune escape and tumor deterioration. Clinically, the application of monoclonal antibodies slows down the progression of various malignancies and prolongs the survival of patients effectively. However, these treatments result in serious immune-related adverse events (irAEs) owning to systemic immune activation. Therefore, to achieve long-term therapeutic effects and low side effects, it is necessary to find drugs inhibiting the local PD-1/PD-L1 signaling pathway of the TME. Here, we discovered that Platycodon grandiflorum (PG), a medicine and food homology herb, reduced the expression of PD-1 on the surface of CD8+ T cells to exert antitumor effects in non-small cell lung cancer (NSCLC). Firstly, by combining systems pharmacology strategies and clinical data analysis, we found that PG has the potential to immunomodulate T cells and suppress tumors. Secondly, in vivo and in vitro experiments have confirmed the antitumor effect of the combination of Platycodin D and Platycodin D3, which is preferred and representative of the compounds. Mechanistically, PG increased the infiltration and killing activity of CD8+ T cells, which was related to the decrease of PD-1+ CD8+ T cells. Furthermore, we confirmed that PG regulated the expression of PD-1 on the surface of CD8+ T cells via reducing the secretion of VEGF-A regulated by the level of P-STAT3 in tumor cells. Additionally, PG also positively impacted the biological processes downstream of STAT3. Overall, we demonstrated that PG-mediated downregulation of PD-1 on the surface of CD8+ T cells represents a promising strategy to locally enhance T-cell responses and improve antitumor immunity.
Economic Evaluation of Dapagliflozin in the Treatment of Patients With Heart Failure: A Systematic Review
Authors: Wu Meiyu , Qin Shuxia , Wang Liting , Tan Chongqing , Peng Ye , Zeng Xiaohui , Luo Xia , Yi Lidan , Wan Xiaomin
Published: April 2022

Objective:The objective of this study is to systematically review the economic evaluations of dapagliflozin in the treatment of patients with heart failure (HF) and describe their general and methodological features.

Methods:This systematic review followed the PRISMA guidelines. MEDLINE/PubMed, Website Of Science, Embase, The Cochrane Library, ScienceDirect, CNKI, and Wanfang databases were searched to collect relevant studies, and the retrieval time ended on 31 October 2021. Articles on the economic evaluation of dapagliflozin in the treatment of heart failure were included. Secondary studies, incomplete economic indicators, and non-English-language and non-Chinese-language studies were excluded. Standard drug treatment was selected as the comparison. Basic characteristics, methods, and main results were extracted and analyzed systematically.

Result:A total of eight studies were identified, and the overall quality was accepted, which were performed in nine developed countries (Austria, United States, Korea, Japan, Singapore, Spanish, Germany, and United Kingdom) and three developing countries (the Philippines, Thailand, and China). With the exception of the Philippines, the remaining countries considered that dapagliflozin was cost effective. In the analyses of all included studies, the incremental cost-effectiveness ratios were most sensitive to the cost of dapagliflozin, cardiovascular mortality, the duration of dapagliflozin effectiveness, and the probability of HF hospitalization.

Conclusion:Dapagliflozin in the treatment of patients with heart failure with reduced ejection fraction was considered cost effective. Further studies are needed to evaluate the comprehensive value of dapagliflozin on HF.
Rutin Inhibits Cardiac Apoptosis and Prevents Sepsis-Induced Cardiomyopathy
Authors: Meng Xiang-Long , Yu Mu-Ming , Liu Yan-Cun , Gao Yu-Lei , Chen Xin-Sen , Shou Song-Tao , Chai Yan-Fen
Published: April 2022

Rutin is a flavanol-type polyphenol that consists of flavanol quercetin and the disaccharide rutinose, which has been reported to exert various biological effects such as antioxidant and anti-inflammatory activities. It is not clear whether rutin has a protective effect on sepsis-induced cardiomyopathy (SIC). In this study, we used male C57BL/6 mice and cecal ligation and puncture (CLP) surgery to establish the model of SIC. Rutin was precautionarily treated (50, 100, 200 mg/kg per day, 7 days) before CLP. The results showed that rutin pretreatment (100, 200 mg/kg per day, 7 days) reduced the mortality of murine sepsis. We chose the 100 mg/kg dose for further studies. Mice were pretreatment with rutin (100 mg/kg per day, 7 days) before subjected to CLP, and myocardial tissue and blood samples were collected 24 h after CLP. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cTNT decreased, while interleukin-10 (IL-10) increased with rutin pretreatment. The cardiomyocytes apoptosis and mitochondrial dysfunction were also alleviated with rutin pretreatment. In conclusion, this study confirmed the efficacy of rutin-enriched diet in the prophylaxis of cardiac apoptosis and cardiac injury induced by CLP in mouse model. It provides a potential new approach on SIC prophylaxis in sepsis.
Association of Plasma Bilirubin Levels With Peripheral Arterial Disease in Chinese Hypertensive Patients: New Insight on Sex Differences
Authors: Shi Yumeng , Zhou Wei , Cheng Mingshu , Yu Chao , Wang Tao , Zhu Lingjuan , Bao Huihui , Hu Lihua , Li Ping , Cheng Xiaoshu
Published: April 2022

Background and aims: Previous studies have indicated that Plasma total bilirubin (TBiL) might play an essential role in peripheral arterial disease (PAD). However, the effects of different levels of TBiL on PAD development remain uncertain. We aimed to examine the TBiL and the prevalence of PAD among Chinese adults with hypertension, with particular attention paid to sex differences.

Methods: A total of 10,900 hypertensive subjects were included in the current study. The mean age of our study participants was 63.86 ± 9.25 years, and there were 5,129 males and 5,771 females. The outcome was peripheral arterial disease (PAD), defined as present when the ankle-brachial index (ABI) of either side was ≤0.90. The association between TBiL and PAD was examined using multivariate logistic regression analysis and the restricted cubic spline.

Results: Of 10,900 hypertensive participants, 350 (3.21%) had PAD, and the mean plasma total bilirubin was 14.66 (6.86) μmol/L. The mean TBiL was 15.67 μmol/L in men and 13.76 μmol/L in women. The smoothing curve showed that a U-shaped curve association existed between TBiL and the prevalence of PAD in Chinese adults with hypertension. When stratified by sex, TBiL was significantly U-shaped associated with PAD among men but not women. Among males, the inflection point was 11.48 μmol/L; to the left inflection point, the effect size and 95% CI were 0.08, 0.01, 0.66, respectively; to the right inflection point, OR, 5.16; 95% CI,1.64, 16.25.

Conclusions: We found an independent U-shaped association between TBiL and the prevalence of PAD among hypertensive subjects and a differential association between men and women. We further revealed a turning point by threshold effect analysis.
Contribution of Peripheral Chemoreceptors to Exercise Intolerance in Heart Failure
Authors: Kulej-Lyko Katarzyna , Niewinski Piotr , Tubek Stanislaw , Ponikowski Piotr
Published: April 2022

Peripheral chemoreceptors (PChRs), because of their strategic localization at the bifurcation of the common carotid artery and along the aortic arch, play an important protective role against hypoxia. Stimulation of PChRs evokes hyperventilation and hypertension to maintain adequate oxygenation of critical organs. A relationship between increased sensitivity of PChRs (hyperreflexia) and exercise intolerance (ExIn) in patients with heart failure (HF) has been previously reported. Moreover, some studies employing an acute blockade of PChRs (e.g., using oxygen or opioids) demonstrated improvement in exercise capacity, suggesting that hypertonicity is also involved in the development of ExIn in HF. Nonetheless, the precise mechanisms linking dysfunctional PChRs to ExIn remain unclear. From the clinical perspective, there are two main factors limiting exercise capacity in HF patients: subjective perception of dyspnoea and muscle fatigue. Both have many determinants that might be influenced by abnormal signalling from PChRs, including: exertional hyperventilation, oscillatory ventilation, ergoreceptor oversensitivity, and augmented sympathetic tone. The latter results in reduced muscle perfusion and altered muscle structure. In this review, we intend to present the milieu of abnormalities tied to malfunctioning PChRs and discuss their role in the complex relationships leading, ultimately, to ExIn.
Alternative Splicing Regulation of Glycine-Rich Proteins via Target of Rapamycin-Reactive Oxygen Species Pathway in Arabidopsis Seedlings Upon Glucose Stress
Authors: Du Chang , Bai Hai-yan , Chen Jing-jing , Wang Jia-hui , Wang Zhi-feng , Zhang Zhong-hui
Published: April 2022

Glucose can serve as both the source of energy and regulatory signaling molecule in plant. Due to the environmental and metabolic change, sugar levels could affect various developmental processes. High glucose environment is hardly conductive to the plant growth but cause development arrest. Increasing evidence indicate that alternative splicing (AS) plays a pivotal role in sugar signaling. However, the regulatory mechanism upon glucose stress remains unclear. The full-length transcriptomes were obtained from the samples of Arabidopsis seedlings with 3% glucose and mock treatment, using Oxford Nanopore sequencing technologies. Further analysis indicated that many genes involved in photosynthesis were significantly repressed and many genes involved in glycolysis, mitochondrial function, and the response to oxidative stress were activated. In total, 1,220 significantly differential alternative splicing (DAS) events related to 619 genes were identified, among which 75.74% belong to intron retention (IR). Notably, more than 20% of DAS events come from a large set of glycine-rich protein (GRP) family genes, such as GRP7, whose AS types mostly belong to IR. Besides the known productive GRP transcript isoforms, we identified a lot of splicing variants with diverse introns spliced in messenger RNA (mRNA) region coding the glycine-rich (GR) domain. The AS pattern of GRPs changed and particularly, the productive GRPs increased upon glucose stress. These ASs of GRP pre-mRNAs triggered by glucose stress could be abolished by AZD-8055, which is an ATP competitive inhibitor for the target of rapamycin (TOR) kinase but could be mimicked by H2O2. Additionally, AS pattern change of arginine/serine-rich splicing factor 31(RS31) via TOR pathway, which was previously described in response to light and sucrose signaling, was also induced in a similar manner by both glucose stress and reactive oxygen species (ROS). Here we conclude that (i) glucose stress suppresses photosynthesis and activates the glycolysis-mitochondria energy relay and ROS scavenging system; (ii) glucose stress triggers transcriptome-wide AS pattern changes including a large set of splicing factors, such as GRPs and RS31; (iii) high sugars regulate AS pattern change of both GRPs and RS31 via TOR-ROS pathway. The results from this study will deepen our understanding of the AS regulation mechanism in sugar signaling.