bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intake of Soy, Soy Isoflavones and Soy Protein and Risk of Cancer Incidence and Mortality
Authors: Fan Yahui , Wang Mingxu , Li Zhaofang , Jiang Hong , Shi Jia , Shi Xin , Liu Sijiao , Zhao Jinping , Kong Liyun , Zhang Wei , Ma Le 
Published: March 2022

Background and AimsAssociations between soy intake and risk of cancer have been evaluated in prospective observational studies with inconsistent results. Whether the potential anticancer effects offered by soy were attributed to soy isoflavones and soy protein still needs to be elucidated. This study aimed to comprehensively quantify the association of soy, soy isoflavones and soy protein intake with risk of cancer incidence and cancer mortality by conducting a meta-analysis of all available studies.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were searched up to 16 September 2021. Prospective cohort studies that examined the effect of soy, soy isoflavones and soy protein on cancer incidence and cancer mortality were identified. Random-effects models were used to pool the multivariable-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs). The potential dose-response relations were explored by using generalized least-squares trend estimation.ResultsEighty one prospective cohort studies were included in the meta-analysis. A higher intake of soy was significantly associated with a 10% reduced risk of cancer incidence (RR, 0.90; 95% CI, 0.83–0.96). Each additional 25 g/d soy intake decreased the risk of cancer incidence by 4%. Intake of soy isoflavones was inversely associated with risk of cancer incidence (RR, 0.94; 95% CI, 0.89–0.99), whereas no significant association was observed for soy protein. The risk of cancer incidence was reduced by 4% with each 10 mg/d increment of soy isoflavones intake. Similar inverse associations were also found for soy in relation to site-specific cancers, particularly lung cancer (RR, 0.67; 95%CI, 0.52–0.86) and prostate cancer (RR, 0.88; 95%CI, 0.78–0.99). However, high intake of soy, soy isoflavones and soy protein were not associated with cancer mortality.ConclusionsHigher intake of soy and soy isoflavones were inversely associated with risk of cancer incidence, which suggested that the beneficial role of soy against cancer might be primarily attributed to soy isoflavones. These findings support recommendations to include soy as part of a healthy dietary pattern for the prevention of cancer.
Tumor Burden Score Stratifies Prognosis of Patients With Intrahepatic Cholangiocarcinoma After Hepatic Resection: A Retrospective, Multi-Institutional Study
Authors: Li Hui , Liu Rongqiang , Qiu Haizhou , Huang Yang , Liu Wenbin , Li Jiaxin , Wu Hong , Wang Genshu , Li Dewei 
Published: March 2022

BackgroundThe prognostic significance of tumor burden score (TBS) on patients who underwent curative-intent resection of intrahepatic cholangiocarcinoma (ICC) has not been evaluated. The present study aimed to investigate the impact of TBS and its synergistic effect with CA19-9 (combination of TBS and CA19-9, CTC grade) on long-term outcomes.MethodsPatients who underwent radical resection of ICC between 2009 and 2017 were retrospectively identified from a multi-center database. The overall survival (OS) and recurrence-free survival (RFS) were examined in relation to TBS, serum preoperative CA19-9, and CTC grade.ResultsA total of 650 patients were included in our study (509 in the derivation cohort and 141 in the validation cohort). Kaplan–Meier curves showed that both TBS and CA19-9 levels were strong predictors of survival outcomes. Patients with elevated TBS grade or elevated CA19-9 were associated with worse OS and RFS (both p &lt; 0.001). As expected, CTC grade also performed well in predicting long-term outcomes. Patients with low TBS/low CA19-9 (CTC grade 1) were associated with the best OS as well as RFS, while high TBS/high CA19-9 (CTC grade 3) correlated to the worst outcomes. In the validation cohort, TBS grade, preoperative CA19-9, and CTC grade also stratified prognosis among patients (p &lt; 0.001 for each).ConclusionsBoth tumor morphology (tumor burden) and tumor-specific biomarker (serum CA19-9) were important when evaluating prognosis of patients with resectable ICC. Serum CA19-9 and TBS showed a synergistic effect on prognostic evaluation. CTC grade was a promising tool in stratifying prognosis of ICC patients after curative resection.
An Innovative Breast-Conserving Oncoplastic Technique for Treating Small to Medium Volume Breasts With a Tumor in the Lower Quadrant: The Folding Flap Technique
Authors: Shi Wenjie , Wang Maoli , Torres-de la Roche Luz Angela , Shi Xuefeng , Gong Zhenyu , Dong Jie , Chen Zihao , Zeng Jiajia , Jiang Yicheng , Chen Zhitong , Wu Kejin , Zhuo Rui , De Wilde Rudy Leon 
Published: March 2022

BackgroundHere, we describe an innovative oncoplastic technique for small to medium volume breasts with a tumor in the lower quadrant and this technique could provide sufficient tissue to avoid visible defects after tumor removal and help reshape the natural shape of the breast.MethodsA detailed procedure for the folding flap technique is described step by step. Then, the results of a retrospective analysis of patients treated using this technique, including complications and disease recurrence rate, between January 2017 and November 2021 are reported. Aesthetic outcomes were evaluated on a 5-point scale proposed by the Paris Breast Center.ResultsA total of 52 patients underwent surgery with the folding flap technique, The average operation time was 98.4 min (range, 75–120 min), and the mean bleeding volume was 56.5 mL (range, 20–100 mL). A margin-positive result was confirmed in 1 patient who underwent re-excision. Short-term postoperative complications were observed in 7 patients, including 4 with fat liquefaction, 2 with seroma, and 1 with skin redness and swelling. No flap necrosis was observed. The median follow-up time was 28.6 months (range, 9–58 months), and 2 patients experienced local recurrence. The mean aesthetic score was 4.7 points, with 36 patients scoring 5 points and 26 patients scoring 4 points, respectively.ConclusionsThe folding flap technique, as an innovative and favorable oncoplastic technique for treating small- to medium-volume breasts with a tumor in the lower quadrant, could retain sufficient tissue to fill the residual cavity after the operation while improving the aesthetic outcome of the breast.
Exploring the Pharmacological Mechanisms of Xihuang Pills Against Prostate Cancer via Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo
Authors: Wu Yongrong , You Xujun , Lin Qunfang , Xiong Wei , Guo Yinmei , Huang Zhen , Dai Xinjun , Chen Zhengjia , Mei Si , Long Yan , Tian Xuefei , Zhou Qing 
Published: March 2022

Background: Drug resistance is the major cause of increasing mortality in prostate cancer (PCa). Therefore, it an urgent to develop more effective therapeutic agents for PCa treatment. Xihuang pills (XHP) have been recorded as the efficient anti-tumor formula in ancient Chinese medical literature, which has been utilized in several types of cancers nowadays. However, the effect protective role of XHP on the PCa and its underlying mechanisms are still unclear.Methods: The active ingredients of XHP were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and BATMAN-TCM. The potential targets of PCa were acquired from the Gene Cards and OMIM databases. R language and Perl language program were utilized to clarify the interaction between the PCa-related targets and the potential targets of XHP. The potential targets of XHP for prostate cancer were gathered from the Gene ontology and KEGG pathway. Furthermore, cell proliferation assays were verified by PC3 and LNCaP cells. The efficacy and potential mechanism tests were confirmed by the PCa PC3 cells and mice subcutaneous transplantation. The effects of PI3K/Akt/mTOR-related proteins on proliferation, apoptosis, and cell cycle of PCa cells were measured by the Cell Counting Kit-8(CCK8), TUNEL assay, real-time quantitative reverse transcription PCR (QRT-PCR), and Western Blotting, respectively.Results: The active components of four traditional Chinese medicines in XHP were searched on the TCMSP and Batman TCM database. The biological active components of XHP were obtained as OB ≥30% and DL ≥0.18. The analysis of gene ontology and KEGG pathway identified the PI3K/Akt/mTOR signaling pathway as the XHP-associated pathway. Collectively, the results of in vitro and in vivo experiments showed that XHP had the effect of inhibiting on the proliferation of PC3 and LNCaP cells. XHP promoted the apoptosis and restrained the cell cycle and invasion of the PC3 cells and subcutaneous transplantation. Meanwhile, the suppression of XHP on the level of expression of PI3K, Akt, and mTOR-pathway-related pathway proteins has been identified in a dose-dependent manner.Conclusion: PI3K/Akt/mTOR pathway-related pathway proteins were confirmed as the potential XHP-associated targets for PCa. XHP can suppress the proliferation of prostate cancer via inhibitions of the PI3K/Akt/mTOR pathway.
Comparative Efficacy of Different Drugs for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Bayesian Network Meta-Analysis
Authors: Fan Zhinan , Shi Hongjin , Zhang Jinsong , Wang Haifeng , Wang Jiansong 
Published: March 2022

Background: Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are common in middle-aged and elderly men. The current drugs for treating this disease include α1-adrenoceptor antagonists (ABs), muscarinic receptor antagonists (MRAs), phosphodiesterase five inhibitors (PDE5-Is), and β3-adrenoceptor agonists (B3As). However, direct comparative studies analyzing different therapies are limited; therefore, we conducted a network meta-analysis (NMA) to evaluate the efficacy of different drug regimens for treating BPH/LUTS.Methods: The PubMed, EMbase, Web of Science, and Cochrane Library databases were searched to collect randomized controlled trials (RCTs) of different drug treatments for BPH/LUTS from January 2000 to April 2021. The NMA was performed using R 4.1 software.Results: Fifty-five RCTs were included among a total of 1639 trials. ① ABs + PDE5-Is, ABs + B3As, ABs + MRAs, ABs, and PDE5-IS were superior to the placebo in improving the total International Prostate Symptom Score (IPSS), IPSS-Voiding, and IPSS-storage. ② For increasing the maximum flow rate (Qmax), ABs + PDE5-Is, ABs + MRAs, and ABs were more effective than the placebo. ③ Regarding reducing post-void residual urine (PVR), none of the six treatment plans had significant effects.Conclusion: Combination therapy showed greater efficacy than monotherapy, and ABs + PDE5-Is was the most successful treatment for improving the overall IPSS score. ABs are a primary therapeutic measure to increase Qmax, and ABs + PDE5-I may be a more suitable choice for enhancing Qmax. The combination of MRA and AB+ MRA may lead to an increase in PVR.Systematic Review Registration: [website], identifier [registration number].
Special Thai Oolong Tea: Chemical Profile and In Vitro Antidiabetic Activities
Authors: Rujanapun Narawadee , Jaidee Wuttichai , Duangyod Thidarat , Phuneerub Pravaree , Paojumroom Napassawan , Maneerat Tharakorn , Pringpuangkeo Chuchawal , Ramli Salfarina , Charoensup Rawiwan 
Published: March 2022

Special Thai oolong tea is oolong tea (Camellia sinensis (L.) Kuntze) steamed with selected Thai botanical drugs. Oolong tea steamed with ginger (Zingiber officinale), lemongrass (Cymbopogon citratus), and celery (Anathallis graveolens L.) is called eternity tea (EN), whereas peaceful rest (PR) tea is made of oolong tea leaves steamed with Indian gooseberry (Phyllanthus emblica), Turkey berry (Solanum torvum), and wild betel leaf bush leaves (Piper sarmentosum). Oolong tea is known for its numerous biological activities including antidiabetic properties. However, the effect of the additional botanical drugs on the biological activities of special oolong teas has not yet been explored. From the results, the PR extract exhibited the best activity in the in vitro assays relevant to antidiabetic properties such as chemical antioxidant, anti-inflammation, anti-adipogenesis, enzyme inhibition, and glucose uptake and consumption. The UHPLC-QTOF-MS/MS profiles of PR and EN extracts indicated chemical profiles different from oolong tea. For instance, gingerdiol and gingerol were detected in EN, whereas piperettine I was detected in PR. Therefore, it was inferred that among the three tea extracts, the additional compounds in PR contributed to good activities compared to oolong and EN. It is also important to highlight that the PR extract inhibited glucose uptake and consumption by adipocytes and skeletal muscles at concentrations of 500 and 100 μg/ml, respectively, as well as metformin activity (p &lt; 0.05). Findings from this study support the antidiabetic potential of PR tea.
Effects of Antihypertensive Drugs on Thyroid Function in Type 2 Diabetes Patients With Euthyroidism
Authors: Yang Lijuan , Sun Xiuqin , Zhao Yi , Tao Hong 
Published: March 2022

Objective: There is little literature about whether antihypertensive drugs would affect thyroid function in patients with euthyroid type 2 diabetes, which was significant in maintaining a proper balance of thyroid function. A retrospective cohort study was conducted to evaluate the influence of antihypertensive drugs on thyroid function in patients with type 2 diabetes with euthyroidism.Design and Methods: The study involved dividing 698 patients with antihypertensive monotherapy into five groups according to the antihypertensive drugs they were treated with. Antihypertensive drugs included in this study were β-blockers, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB). The clinical data and thyroid function level between or within groups were compared. Multiple logistic regression analysis was conducted to evaluate the association of antihypertensive drugs with thyroid function level.Results: Selective β1- adrenergic receptor blockers treatment was related to thyroid-stimulating hormone (TSH), increasing in patients with diabetes and euthyroidism as shown by multiple logistic regression analysis. The association existed after adjustment for confounding factors. No significant influence on thyroid function was found among other antihypertensive drugs.Conclusion: These data show the TSH-lifting effect of selective β1-adrenergic receptor blockers in patients with type 2 diabetes with euthyroidism.
Statin Therapy for Hyperlipidemic Patients With Chronic Kidney Disease and End-Stage Renal Disease: A Retrospective Cohort Study Based on 925,418 Adults in Taiwan
Authors: Sung Fung-Chang , Jong Ying-Chin , Muo Chih-Hsin , Hsu Chih-Cheng , Tsai Wen-Chen , Hsu Yueh-Han 
Published: March 2022

Background: For non-dialysis patients with hyperlipidemia, statins may provide clinical benefits in reducing mortality risk; however, the optimal treatment for dialysis patients with hyperlipidemia remains debatable. We evaluated the mortality risks for hyperlipidemic patients with renal disorders associated with statin therapy (ST), using the insurance claims data of Taiwan.Methods: From hyperlipidemic patients diagnosed in 2000–2011, we identified 555,153 patients receiving statin treatment for at least 90 days continuously and 1,141,901 non-statin users, and then randomly selected, from both groups, the propensity score-matched subcohorts of statin users and nonusers in a 1:1 pair by renal function: 415,453 pairs with normal renal function , 43,632 pairs with chronic kidney disease (CKD), and 3,624 pairs with end-stage renal disease (ESRD). We compared the mortalities, by the end of 2016, from all causes, cancer, heart disease, and septicemia between statin users and non-users and between hydrophilic-statin users and lipophilic-statin users. The Cox method estimated ST users to non-user hazard ratios. The time-dependent model was also conducted as sensitivity analysis.Results: The mean ages were 58.7 ± 10.7, 64.2 ± 10.7, and 62.2 ± 10.8 years in normal renal function, CKD, and ESRD groups, respectively. Compared with non-users, statin users had reduced mortality risks from all causes for 32%–38%, from cancer for 37%–46%, from heart disease for 6%–24%, and from septicemia for 17%–21% in all three renal groups. The hydrophilic statin therapy was superior than the lipophilic statin therapy, particularly for reducing deaths from all-causes and cancer. The results under the time-dependent model were similar.Conclusion: Statin therapy is associated with reduced all-causes and non-cardiovascular mortality in ESRD patients.
The Abcc6a Knockout Zebrafish Model as a Novel Tool for Drug Screening for Pseudoxanthoma Elasticum
Authors: Van Gils M. , Willaert A. , Coucke P. J. , Vanakker O. M. 
Published: March 2022

Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by pathogenic variants in the ABCC6 gene. Though complications of the disease can be treated, PXE itself remains currently intractable. A strategy for rapid and cost-effective discovery of therapeutic drugs would be to perform chemical compound screening using zebrafish, but this approach remains to be validated for PXE. In this paper, we validate a stable CRISPR/Cas9 abcc6a knockout zebrafish model–which has spinal column hypermineralization as its primary phenotypic feature–as a model system for compound screening in ectopic mineralization. We evaluated the anti-mineralization potential of five compounds, which had (anecdotal) positive effects reported in Abcc6 knockout mice and/or PXE patients. Abcc6a knockout zebrafish larvae were treated from 3 to 10 days post-fertilization with vitamin K1, sodium thiosulfate, etidronate, alendronate or magnesium citrate and compared to matching controls. Following alizarin red S staining, alterations in notochord sheath mineralization were semiquantified and found to largely congrue with the originally reported outcomes. Our results demonstrate that the use of this abcc6a knockout zebrafish model is a validated and promising strategy for drug discovery against ectopic mineralization.
Disulfiram Produces Potent Anxiolytic-Like Effects Without Benzodiazepine Anxiolytics-Related Adverse Effects in Mice
Authors: Saitoh Akiyoshi , Nagayama Yoshifumi , Yamada Daisuke , Makino Kosho , Yoshioka Toshinori , Yamanaka Nanami , Nakatani Momoka , Takahashi Yoshino , Yamazaki Mayuna , Shigemoto Chihiro , Ohashi Misaki , Okano Kotaro , Omata Tomoki , Toda Etsuko , Sano Yoshitake , Takahashi Hideyo , Matsushima Kouji , Terashima Yuya 
Published: March 2022

Disulfiram is an FDA approved drug for the treatment of alcoholism. The drug acts by inhibiting aldehyde dehydrogenase, an enzyme essential to alcohol metabolism. However, a recent study has demonstrated that disulfiram also potently inhibits the cytoplasmic protein FROUNT, a common regulator of chemokine receptor CCR2 and CCR5 signaling. Several studies have reported that chemokine receptors are associated with the regulation of emotional behaviors in rodents, such as anxiety. Therefore, this study was performed to clarify the effect of disulfiram on emotional behavior in rodents. The anxiolytic-like effects of disulfiram were investigated using an elevated plus-maze (EPM) test, a typical screening model for anxiolytics. Disulfiram (40 or 80 mg/kg) significantly increased the amount of time spent in the open arms of the maze and the number of open arm entries without affecting the total open arms entries. Similar results were obtained in mice treated with a selective FROUNT inhibitor, disulfiram-41 (10 mg/kg). These disulfiram-associated behavioral changes were similar to those observed following treatment with the benzodiazepine anxiolytic diazepam (1.5 mg/kg). Moreover, disulfiram (40 mg/kg) significantly and completely attenuated increased extracellular glutamate levels in the prelimbic-prefrontal cortex (PL-PFC) during stress exposure on the elevated open-platform. However, no effect in the EPM test was seen following administration of the selective aldehyde dehydrogenase inhibitor cyanamide (40 mg/kg). In contrast to diazepam, disulfiram caused no sedation effects in the open-field, coordination disorder on a rotarod, or amnesia in a Y-maze. This is the first report suggesting that disulfiram produces anxiolytic-like effects in rodents. We found that the presynaptic inhibitory effects on glutaminergic neurons in the PL-PFC may be involved in its underlying mechanism. Disulfiram could therefore be an effective and novel anxiolytic drug that does not produce benzodiazepine-related adverse effects, such as amnesia, coordination disorder, or sedation, as found with diazepam. We propose that the inhibitory activity of disulfiram against FROUNT function provides an effective therapeutic option in anxiety.
A Loading Dose of Dexmedetomidine With Constant Infusion Inhibits Intraoperative Neuromonitoring During Thoracic Spinal Decompression Surgery: A Randomized Prospective Study
Authors: Liu Tun , Qin Yue , Qi Huaguang , Luo Zhenguo , Yan Liang , Yu Pengfei , Dong Buhuai , Zhao Songchuan , Wu Xucai , Chang Zhen , Liu Zhian , Liu Xuemei , Yuan Tao , Li Houkun , Xiao Li , Wang Gang 
Published: March 2022

Background:The effect of a bolus dose of dexmedetomidine on intraoperative neuromonitoring (IONM) parameters during spinal surgeries has been variably reported and remains a debated topic.Methods:A randomized, double-blinded, placebo-controlled study was performed to assess the effect of dexmedetomidine (1 μg/kg in 10 min) followed by a constant infusion rate on IONM during thoracic spinal decompression surgery (TSDS). A total of 165 patients were enrolled and randomized into three groups. One group received propofol- and remifentanil-based total intravenous anesthesia (TIVA) (T group), one group received TIVA combined with dexmedetomidine at a constant infusion rate (0.5 μg kg−1h−1) (D1group), and one group received TIVA combined with dexmedetomidine delivered in a loading dose (1 μg kg−1in 10 min) followed by a constant infusion rate (0.5 μg kg−1h−1) (D2group). The IONM data recorded before test drug administration was defined as the baseline value. We aimed at comparing the parameters of IONM.Results:In the D2group, within-group analysis showed suppressive effects on IONM parameters compared with baseline value after a bolus dose of dexmedetomidine. Furthermore, the D2group also showed inhibitory effects on IONM recordings compared with both the D1group and the T group, including a statistically significant decrease in SSEP amplitude and MEP amplitude, and an increase in SSEP latency. No significance was found in IONM parameters between the T group and the D1group.Conclusion:Dexmedetomidine delivered in a loading dose can significantly inhibit IONM parameters in TSDS. Special attention should be paid to the timing of a bolus dose of dexmedetomidine under IONM. However, dexmedetomidine delivered at a constant speed does not exert inhibitory effects on IONM data.