bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial Doppler Ultrasonography detection on cerebrovascular flow for evaluating neonatal hypoxic-ischemic encephalopathy modeling
Authors: Liu Jin-Xiang , Fang Chang-Le , Zhang Kun , Ma Rui-Fang , Zhou Hong-Su , Chen Li , Wang Qiu-Lin , Lu Yu-Xuan , Wang Ting-Hua , Xiong Liu-Lin 
Published: May 2023

ObjectiveThis study aimed to investigate the feasibility of Transcranial Doppler Ultrasonography (TCD) in evaluating neonatal hypoxic-ischemic encephalopathy (NHIE) modeling through monitoring the alteration of cerebrovascular flow in neonatal hypoxic-ischemic (HI) rats.MethodsPostnatal 7-day-old Sprague Dawley (SD) rats were divided into the control group, HI group, and hypoxia (H) group. TCD was applied to assess the changes of cerebral blood vessels, cerebrovascular flow velocity, and heart rate (HR) in sagittal and coronal sections at 1, 2, 3, and 7 days after the operation. For accuracy, cerebral infarct of rats was examined by 2,3,5-Triphenyl tetrazolium chloride (TTC) staining and Nissl staining to simultaneously verify the establishment of NHIE modeling.ResultsCoronal and sagittal TCD scans revealed obvious alteration of cerebrovascular flow in main cerebral vessels. Obvious cerebrovascular back-flow was observed in anterior cerebral artery (ACA), basilar artery (BA), middle cerebral artery (MCA) of HI rats, along with accelerated cerebrovascular flows in the left internal carotid artery (ICA-L) and BA, decreased flows in right internal carotid artery (ICA-R) relative to those in the H and control groups. The alterations of cerebral blood flows in neonatal HI rats indicated successful ligation of right common carotid artery. Besides, TTC staining further validated the cerebral infarct was indeed caused due to ligation-induced insufficient blood supply. Damage to nervous tissues was also revealed by Nissl staining.ConclusionCerebral blood flow assessment by TCD in neonatal HI rats contributed to cerebrovascular abnormalities observed in a real-time and non-invasive way. The present study elicits the potentials to utilize TCD as an effective means for monitoring the progression of injury as well as NHIE modeling. The abnormal appearance of cerebral blood flow is also beneficial to the early warning and effective detection in clinical practice.
Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model
Authors: Zheng Guoli , Harms Anna-Kathrin , Tail Mohamed , Zhang Hao , Nimmo Alan , Skutella Thomas , Kiening Karl , Unterberg Andreas , Zweckberger Klaus , Younsi Alexander 
Published: May 2023

ObjectiveDisruption of the blood-spinal cord barrier (BSCB) with subsequent edema formation and further neuroinflammation contributes to aggravation of spinal cord injury (SCI). We aimed to observe the effect of antagonizing the binding of the neuropeptide Substance-P (SP) to its neurokinin-1 (NK1) receptor in a rodent SCI model.MethodsFemale Wistar rats were subjected to a T9 laminectomy with or without (Sham) a T9 clip-contusion/compression SCI, followed by the implantation of an osmotic pump for the continuous, seven-day-long infusion of a NK1 receptor antagonist (NRA) or saline (vehicle) into the intrathecal space. The animals were assessed via MRI, and behavioral tests were performed during the experiment. 7 days after SCI, wet &amp; dry weight and immunohistological analyses were conducted.ResultsSubstance-P inhibition via NRA showed limited effects on reducing edema. However, the invasion of T-lymphocytes and the number of apoptotic cells were significantly reduced with the NRA treatment. Moreover, a trend of reduced fibrinogen leakage, endothelial and microglial activation, CS-GAG deposition, and astrogliosis was found. Nevertheless, only insignificant general locomotion recovery could be observed in the BBB open field score and the Gridwalk test. In contrast, the CatWalk gait analysis showed an early onset of recovery in several parameters.ConclusionIntrathecal administration of NRA might reinforce the integrity of the BSCB in the acute phase after SCI, potentially attenuating aspects of neurogenic inflammation, reducing edema formation, and improving functional recovery.
Vitamin K supplementation and vascular calcification: a systematic review and meta-analysis of randomized controlled trials
Authors: Li Te , Wang Yun , Tu Wei-ping 
Published: May 2023

BackgroundVascular calcification (VC) is a complex process that has been linked to conditions including cardiovascular diseases and chronic kidney disease. There is an ongoing debate about whether vitamin K (VK) can effectively prevent VC. To assess the efficiency and safety of VK supplementation in the therapies of VC, we performed a systematic review and meta-analysis of recent studies.MethodsWe searched major databases, including PubMed, the Cochrane Library, Embase databases, and Web of Science up until August 2022. 14 randomized controlled trials (RCTs) describing the outcomes of treatment for VK supplementation with VC have been included out of 332 studies. The results were reported in the change of coronary artery calcification (CAC) scores, other artery and valve calcification, vascular stiffness, and dephospho-uncarboxylated matrix Gla protein (dp-ucMGP). The reports of severe adverse events were recorded and analyzed.ResultsWe reviewed 14 RCTs, comprising a total of 1,533 patients. Our analysis revealed that VK supplementation has a significant effect on CAC scores, slowing down the progression of CAC [I2 = 34%, MD= −17.37, 95% CI (−34.18, −0.56), p = 0.04]. The study found that VK supplementation had a significant impact on dp-ucMGP levels, as compared to the control group, where those receiving VK supplementation had lower values [I2 = 71%, MD = −243.31, 95% CI (−366.08, −120.53), p = 0.0001]. Additionally, there was no significant difference in the adverse events between the groups [I2 = 31%, RR = 0.92, 95% CI (−0.79,1.07), p = 0.29].ConclusionVK may have therapeutic potential for alleviating VC, especially CAC. However, more rigorously designed RCTs are required to verify the benefits and efficacy of VK therapy in VC.
Minimally invasive Ivor Lewis esophagectomy in the elderly patient: a multicenter retrospective matched-cohort study
Authors: Capovilla Giovanni , Uzun Eren , Scarton Alessia , Moletta Lucia , Hadzijusufovic Edin , Provenzano Luca , Salvador Renato , Pierobon Elisa Sefora , Zanchettin Gianpietro , Tagkalos Evangelos , Berlth Felix , Lang Hauke , Valmasoni Michele , Grimminger Peter P. 
Published: May 2023

IntroductionSeveral studies reported the advantages of minimally invasive esophagectomy over the conventional open approach, particularly in terms of postoperative morbidity and mortality. The literature regarding the elderly population is however scarce and it is still not clear whether elderly patients may benefit from a minimally invasive approach as the general population. We sought to evaluate whether thoracoscopic/ laparoscopic (MIE) or fully robotic (RAMIE) Ivor-Lewis esophagectomy significantly reduces postoperative morbidity in the elderly population.MethodsWe analyzed data of patients who underwent open esophagectomy or MIE/RAMIE at Mainz University Hospital and at Padova University Hospital between 2016 and 2021. Elderly patients were defined as those ≥ 75 years old. Clinical characteristics and the postoperative outcomes were compared between elderly patients who underwent open esophagectomy or MIE/RAMIE. A 1-to-1 matched comparison was also performed. Patients &lt; 75 years old were evaluated as a control group.ResultsAmong elderly patients MIE/RAMIE were associated with a lower overall morbidity (39.7% vs. 62.7%, p=0.005), less pulmonary complications (32.8 vs. 56.9%, p=0.003) and a shorter hospital stay (13 vs. 18 days, p=0.03). Comparable findings were obtained after matching. Similarly, among &lt; 75 years-old patients, a reduced morbidity (31.2% vs. 43.5%, p=0.01) and less pulmonary complications (22% vs. 36%, p=0.001) were detected in the minimally invasive group.DiscussionMinimally invasive esophagectomy improves the postoperative course of elderly patients reducing the overall incidence of postoperative complications, particularly of pulmonary complications.
Metastatic insulinoma: exploration from clinicopathological signatures and genetic characteristics
Authors: Zhang Jingcheng , Jiang Rui , Hong Xiafei , Wu Huanwen , Han Xianlin , Wu Wenming 
Published: May 2023

BackgroundInsulinoma is a rare type of pancreatic neuroendocrine tumor with low incidence and low-malignant features. While very few insulinomas present with malignant behaviours, such as lymph node and liver metastasis, only a few studies have focused on this field owing to the limitation of samples. Existing evidence suggests that metastatic insulinoma largely derive from non-functional pancreatic neuroendocrine tumor. However, we found a portion of metastatic insulinomas may derive from non-metastatic insulinomas and explored their clinicopathological signatures and genetic characteristics.MethodsFour metastatic insulinoma patients with synchronous liver metastasis or lymph node metastasis at the Peking Union Medical College Hospital between October 2016 and December 2018 were enrolled, and whole exon and genome sequencing were performed on fresh frozen tissues and peripheral blood samples. Clinicopathological information and genomic sequencing results were collected and matched to explore the characteristics of the metastatic insulinomas.ResultsThese four metastatic insulinoma patients underwent surgery or interventional therapy, and their blood glucose levels immediately increased and maintained within standard range after treatment. For these four patients, the proinsulin/insulin molar ratio &lt;1 and primary tumors were all present as PDX1+, ARX-, and insulin+, which were similar to non-metastatic insulinomas. However, the liver metastasis showed PDX1+ and ARX+, insulin+. Meanwhile, genomic sequencing data showed no recurrently mutations and typical CNV patterns. However, one patient harboured the YY1 T372R mutation, a recurrently mutated gene in non-metastatic insulinomas.ConclusionsA portion of metastatic insulinomas were largely derived from non-metastatic insulinomas in hormone secretion and ARX/PDX1 expression patterns. Meanwhile, the accumulation of ARX expression may be involved in the progression of metastatic insulinomas.
Combined genetic screening and traditional newborn screening to improve the screening efficiency of congenital hypothyroidism
Authors: Ye Liang , Yin Yifan , Chen Min , Gong Nian , Peng Yong , Liu Hao , Miao Jingkun 
Published: May 2023

BackgroundCongenital hypothyroidism (CH) is an neonatal endocrine disorder. Traditional newborn screening is the mainstream method of CH screening, so as to ensure the early detection and treatment of CH. This method is limited as it has high rates of false positives and negatives. Genetic screening can be used to address the shortcomings of traditional newborn Screening (NBS); however, the comprehensive clinical value of genetic screening is yet to be systematically studied.MethodsA total of 3,158 newborns who accepted the newborn screening and genetic screening were recruited for this study. Biochemical screening and genetic screening were performed at the same time. The level of TSH with the DBS was detected by time-resolved immunofluorescence assay. High-throughput sequencing technology based on targeted gene capture was used for genetic screening. The suspected neonatal was recalled and tested serum TSH, and FT4. Finally, the effectiveness of traditional NBS and combined screening was compared.ResultsIn this study, 16 cases were diagnosed by traditional NBS. 10 cases of DUOX2 mutation were found in newborn CH-related genetic screening, including 5 homozygous and 5 compound heterozygous variations. We found that the c.1588A &gt; T mutations in DUOX2 constituting the predominant site in the present cohort.Compared with NBS and genetic screening, the sensitivity of combined screening increased by 11.1% and 55.6%, respectively. Compared with NBS and genetic screening, the negative predictive value of combined screening increased by 0.1% and 0.4%, respectively.ConclusionsCombined traditional NBS and genetic screening reduces the false negative rate of CH screening and improves the early and accurate identification of neonates with CH. Our research explains the mutation spectrum of CH in this region, and provisionally demonstrates the necessity, feasibility and significance of genetic screening in newborns and provides a solid basis for future clinical developments.
A specific SNP-based multiplex PCR assay for the simultaneous identification of two biological ingredients for the Chinese patent medicine, Danggui Buxue pill
Authors: Liu Yinrong , Yang Yingying , Zhou Zishan , Fan Jia’er , Diao Jianxin , Chao Zhi , Tian Enwei 
Published: May 2023

Background: An increasing number of Chinese patent medicines (CPM) have been widely used in East Asian and North American countries, and the safety and efficacy of CPM have highly attracted public attention. However, it is difficult to supervise the authenticity of multiple biological ingredients within CPM based on microscopic inspection and physical and chemical detection. The raw materials may have similar characteristics of tissue structures and ergastic substances or similar chemical composition and contents when substitutes and/or adulterants are added. DNA molecular markers have been used to distinguish the biological ingredients within CPM based on conventional PCR assay. However, it was proved to be time- and labor-consuming and reagent-wasting, as multiple PCR amplification strategies were required for identifying the complex species composition within CPM. Here, we took the CPM (Danggui Buxue pill) as an example and aimed to establish a specific SNP-based multiplex PCR assay and simultaneously determine the authenticity of the two biological ingredients (Angelicae Sinensis Radix and Astragali Radix) within this CPM.Methods: We, respectively, designed the species-specific primers based on highly variable nrITS for discriminating Angelicae Sinensis Radix and Astragali Radix from their common substitutes and adulterants. The specificity of the primers was checked through conventional PCR assay and multiplex PCR assay. Furthermore, we used a handcrafted Danggui Buxue pill sample (DGBXP) to optimize annealing temperatures for the primers with multiplex PCR, and the sensitivity was also assessed. Finally, fourteen batches of commercial Danggui Buxue pills were used to verify the stability and practicability of the established multiplex PCR assay.Results: Two pairs of highly species-specific primers for amplifying Angelicae Sinensis Radix and Astragali Radix were screened, and our established multiplex PCR assay showed high specificity and sensitivity (lowest detection concentration: 4.0 × 10−3 ng/μL) at an optimal annealing temperature of 65°C. The method could simultaneously identify both biological ingredients within the Danggui Buxue pill.Conclusion: The specific SNP-based multiplex PCR provided a simple, time-, and labor-saving method for the simultaneous identification of the two biological ingredients within Danggui Buxue pills. This study was expected to provide a novel qualitative quality control strategy for CPM.
Efficacy and safety of the herbal formula Naesohwajung-tang for functional dyspepsia: a randomized, double-blind, placebo-controlled, multi-center trial
Authors: Ha Na-Yeon , Ko Seok-Jae , Park Jae-Woo , Kim Jinsung 
Published: May 2023

Background: Current treatment and management options for functional dyspepsia (FD) often fail to alleviate symptoms. Naesohwajung-tang (NHT) is a herbal formula frequently used to treat functional dyspepsia in traditional Korean medicine. However, few animal and case reports on the use of Naesohwajung-tang for functional dyspepsia treatment exist, and the clinical evidence remains deficient.Objectives: This study aimed to evaluate the efficacy of Naesohwajung-tang in patients with functional dyspepsia.Methods: We enrolled 116 patients with functional dyspepsia at two study sites in this 4 weeks, randomized, double-blind, placebo-controlled trial and randomly assigned them to either the Naesohwajung-tang or placebo group. To evaluate the efficacy of Naesohwajung-tang, the primary endpoint was a score on the total dyspepsia symptom (TDS) scale after treatment. The overall treatment effect (OTE), single dyspepsia symptom (SDS) scale, food retention questionnaire (FRQ), Damum questionnaire (DQ), functional dyspepsia-related quality of life (FD-QoL) questionnaire, and gastric myoelectrical activity measured using electrogastrography were evaluated as secondary outcomes. Laboratory tests were performed to confirm the safety of the intervention.Results: The 4 weeks administration of Naesohwajung-tang granules demonstrated a significantly higher reduction in the total dyspepsia symptom (p &lt; 0.05) and a higher degree of improvement in the total dyspepsia symptom (p &lt; 0.01) than the placebo group. Patients who underwent Naesohwajung-tang had a significantly higher overall treatment effect and a greater increase in the degree of improvement in scores such as epigastric burning, postprandial fullness, early satiation, functional dyspepsia-related quality of life, and Damum questionnaire (p &lt; 0.05). Additionally, the Naesohwajung-tang group showed a greater effect in preventing a decrease in the percentage of normal gastric slow waves after meals than the placebo group. As a result of subgroup analyses using the degree of improvement in total dyspepsia symptom, Naesohwajung-tang was found to be more effective than placebo in female, younger patients (&lt;65 years), with a high body-mass index (≥22), overlap type, food retention type, and Dampness and heat in the spleen and stomach systems pattern. There was no significant difference in the incidence of adverse events between the two groups.Conclusion: This is the first randomized clinical trial to verify that Naesohwajung-tang leads on symptom relief in patients with functional dyspepsia.Clinical Trial Registration:https://cris.nih.go.kr/cris/search/detailSearch.do/17613, identifier KCT0003405
Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19
Authors: Lu Jiayue , Cai Hong , Hao Yujun , Lin Zhang , Liu Shang , Zhan Yaping , Ding Li , Huang Meilan , Li Zhenyuan , Xu Lan , Yan Xiujuan , Yang Li , Zhang He , Zhang Wei , Zhao Li , Zhao Junli , Wang Ting , Gu Leyi 
Published: May 2023

Background: Hemodialysis patients have a high risk of severe/critical COVID-19 and related high mortality, but nirmatrelvir/ritonavir is not recommended for hemodialysis patients with COVID-19 infection because of lack of evidence of safety.Objectives: Our study aims to evaluate the minimum plasma concentration (Cmin) of nirmatrelvir and its safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19.Method: This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150 mg or 300 mg once a day (another 75 mg or 150 mg supplied after hemodialysis) and ritonavir 100 mg twice daily for 5 days, respectively. The primary outcome was the safety of nirmatrelvir/ritonavir, including the Cmin of nirmatrelvir and the number of adverse events (AE). The secondary outcome was the time of viral elimination in hemodialysis patients.Results: Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively (p = 0.025). Among them, 2 and 6 participants were identified as drug-related adverse events (p = 0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (p = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (p = 0.001 compared to step 2 and p = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (p = 0.232).Conclusion: In our study, two doses of nirmatrelvir/ritonavir appeared to be excessive for hemodialysis patients. Although all of the patients tolerated 5-day administration, nearly half of the patients experienced drug-related adverse events. In addition, the medication group did not show a significant advantage in the time of viral elimination.
Proarrhythmia associated with antiarrhythmic drugs: a comprehensive disproportionality analysis of the FDA adverse event reporting system
Authors: Wang Feifei , Zhou Bingfeng , Sun Hongwei , Wu Xinan 
Published: May 2023

Objective: This study aimed to identify the different associations between antiarrhythmic drugs (AADs) and arrhythmias, and to determine whether pharmacokinetic drug interactions involving AADs increase the risk of AAD-related arrhythmias compared to using AADs alone.Materials and methods: The disproportionality analysis of AAD-associated cardiac arrhythmias, including AAD monotherapies and concomitant use of pharmacokinetic interacting agents involving AADs, was conducted by using reporting odds ratio (ROR) and information component (IC) as detection of potential safety signals based on FAERS data from January 2016 to June 2022. We compared the clinical features of patients reported with AAD–associated arrhythmias between fatal and non-fatal groups, and further investigated the onset time (TTO) following different AAD regimens.Results: A total of 11754 AAD–associated cardiac arrhythmias reports were identified, which was more likely to occur in the elderly (52.17%). Significant signals were detected between cardiac arrhythmia and all AAD monotherapies, with ROR ranging from 4.86 with mexiletine to 11.07 with flecainide. Regarding four specific arrhythmias in High Level Term (HLT) level, the AAD monotherapies with the highest ROR were flecainide in cardiac conduction disorders (ROR025 = 21.18), propafenone in rate and rhythm disorders (ROR025 = 10.36), dofetilide in supraventricular arrhythmias (ROR025 = 17.61), and ibutilide in ventricular arrhythmias (ROR025 = 4.91). Dofetilide/ibutilide, ibutilide, mexiletine/ibutilide and dronedarone presented no signal in the above four specific arrhythmias respectively. Compared with amiodarone monotherapy, sofosbuvir plus amiodarone detected the most significantly increased ROR in arrhythmias.Conclusion: The investigation showed the spectrum and risk of AAD–associated cardiac arrhythmias varied among different AAD therapies. The early identification and management of AAD-associated arrhythmias are of great importance in clinical practice.