bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential biomarkers predicting risk of pulmonary hypertension in congenital heart disease: the role of homocysteine and hydrogen sulfide
Authors: Sun Ling , Sun Shuo , Li Yufen , Pan Wei , Xie Yumei , Wang Shushui , Zhang Zhiwei 
Published: January 2024

Background
Pulmonary hypertension (PH) is a common complication of congenital heart disease (CHD). Although risk stratification is vital for prognosis and therapeutic guidance, the need for understanding the role of novel biomarkers cannot be overlooked. The aim of the present study was to investigate the changes of homocysteine and hydrogen sulfide levels and find potential biomarkers for early detection and treatment.

Methods
Between September 2012 and April 2013, we prospectively collected data on 158 pediatric patients with left to right shunt CHD at our institution. Standard right heart catheterizations were performed in all cases. Seventy-seven cases were associated with PH. The levels of homocysteine and hydrogen sulfide were detected with fluorescence polarization immunoassay and a sensitive silver-sulphur electrode, respectively. Enzyme-linked immunosorbent assay was used to determine the expression of methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS), and cystathionine gamma-lyase (CSE). Radioimmunoassays were used to obtain folic acid and vitamin B12 levels.

Results
The difference in the levels of homocysteine, folic acid, vitamin B12, hydrogen sulfide, as well as the MTHFR and CSE expression between patients with PH and without PH were statistically significant (all P <0.05). Homocysteine had the best sensitivity and specificity to predict PH (P <0.001). Subgroup analysis showed that the levels of homocysteine and hydrogen sulfide, and the expression of CSE and MTHFR between patients with dynamic and obstructive PH were significantly different (all P <0.05). Based on the ROC curve, homocysteine had the best sensitivity and specificity to predict obstructive PH (P=0.032), while CSE had the most significant sensitivity and specificity to predict the dynamic PH (P=0.008).

Conclusions
Increased levels of homocysteine and decreased levels of hydrogen sulfide were significantly negatively correlated in PH associated with CHD. The underlying mechanism involved the decreased expression of MTHFR and CSE along with vitamin B12 deficiency. Homocysteine and hydrogen sulfide are potential biomarkers to predict PH.
Helicobacter pylori infection: an overview in 2013, focus on therapy
Authors: Rongli Cui , Liya Zhou 
Published: January 2024

Objective
This article aimed to review the incidence of Helicobacter pylori (H. pylori) infection and its therapy.

Data sources
Relevant articles published in English were identified by searching in PubMed from 2000 to 2013, with keywords “H. pylori”. Important references from selected articles were also retrieved from Elsevier, Wiley, EBSCO, and SPRINGER. The Chinese articles published were searched from China National Knowledge Infrastructure (CNKI).

Study selection
Articles about “prevalence”, “gastric carcinoma”, “peptic ulcer”, “gastroesophageal reflux disease”, “functional dyspepsia”, “pathogenic mechanism”, “therapy”, “eradication rate”, “antibiotic resistance”, and “gene polymorphisms” were selected.

Results
The decreased infection rates of H. pylori could also be linked to the changed disease spectrum, such as the decreased morbidity and recurrence rate of H. pylori-related peptic ulcer, and the increased morbidity of gastroesophageal reflux. Although different treatment regimens have been used for H. pylori infection, the H. pylori eradication rate declined gradually. Due to primary resistance to antibiotics, the gene polymorphism of host and infected strain, and the therapy regimes, H. pylori eradication became even more difficult.

Conclusions
The prevalence of H. pylori infection had been decreasing, but the rate of eradication failure has dramatically risen in many countries due to resistance to antibiotic. H. pylori therapy in clinical practice is becoming progressively more difficult.
Rapamycin attenuates bleomycin-induced pulmonary fibrosis in rats and the expression of metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in lung tissue
Authors: Jin Xiaoguang , Dai Huaping , Ding Ke , Xu Xuefeng , Pang Baosen , Wang Chen 
Published: January 2024

Background
Idiopathic pulmonary fibrosis (IPF) is the most common and devastating form of interstitial lung disease (ILD) in the clinic. There is no effective therapy except for lung transplantation. Rapamycin is an immunosuppressive drug with potent antifibrotic activity. The purpose of this study was to examine the effects of rapamycin on bleomycin-induced pulmonary fibrosis in rats and the relation to the expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).

Methods
Sprague-Dawley rats were treated with intratracheal injection of 0.3 ml of bleomycin (5 mg/kg) in sterile 0.9% saline to make the pulmonary fibrosis model. Rapamycin was given at a dose of 0.5 mg/kg per gavage, beginning one day before bleomycin instillation and once daily until animal sacrifice. Ten rats in each group were sacrificed at 3, 7, 14, 28 and 56 days after bleomycin administration. Alveolitis and pulmonary fibrosis were semi-quantitatively assessed after HE staining and Masson staining under an Olympus BX40 microscope with an IDA-2000 Image Analysis System. Type I and III collagen fibers were identified by Picro-sirius-polarization. Hydroxyproline content in lung tissue was quantified by a colorimetric-based spectrophotometric assay, MMP-9 and TIMP-1 were detected by immunohistochemistry and by realtime quantitative reverse transcriptase polymerase chain reaction (RT-PCR).

Results
Bleomycin induced alveolitis and pulmonary fibrosis of rats was inhibited by rapamycin. Significant inhibition of alveolitis and hydroxyproline product were demonstrated when daily administration of rapamycin lasted for at least 14 days. The inhibitory efficacy on pulmonary fibrosis was unremarkable until rapamycin treatment lasted for at least 28 days (P <0.05). It was also demonstrated that rapamycin treatment reduced the expression of MMP-9 and TIMP-1 in lung tissue that was increased by bleomycin.

Conclusion
These results highlight the significance of rapamycin in alleviating alveolitis and pulmonary fibrosis, which is associated with decreased expression of MMP-9 and TIMP-1.
Urotensin II promotes monocyte chemoattractant protein-1 expression in aortic adventitial fibroblasts of rat
Authors: Zhang Yonggang , Bao Shilin , Kuang Zejian , Ma Yanjun , Hu Yanchao , Mao Yanyan 
Published: January 2024

Background
Urotensin II (UII), a potent vasoconstrictive peptide, is able to stimulate phenotypic differentiation of adventitial fibroblasts. This study aimed to determine the effect of UII on monocyte chemoattractant protein-1 (MCP-1) expression in rat aortic adventitial fibroblasts, so as to explore possible mechanisms in the development of vascular inflammation.

Methods
Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII (10-10-10-7 mol/L) and inhibitors of signal transduction pathways for 1 to 24 hours. MCP-1 mRNA and protein expression and secretion were determined by RT-PCR, Western blotting analysis and enzyme-linked immunosorbent assay (ELISA), respectively.

Results
UII dose- and time-dependently promoted MCP-1 mRNA and protein expression and secretion in cells, with maximal effect at 10-8 mol/L at 3 hours for mRNA expression, 24 hours for protein expression in the cells, and 12 hours for protein secretion from the cells. Furthermore, the UII effects were significantly inhibited by treatment with its receptor antagonist SB710411, Rho kinase inhibitor Y27632, protein kinase C (PKC) inhibitor H7, mitogen-activated protein kinase inhibitor PD98059, calcineurin inhibitor cyclosporine A, and the Ca2+channel blocker nicardipine.

Conclusion
UII may stimulate MCP-1 expression in rat aortic adventitial fibroblasts through its receptor and Rho kinase, PKC, mitogen-activated protein kinase, calcineurin and Ca2+ channel signal transduction, thus contributing to adventitial inflammation.
Lycopene can reduce prostate-specific antigen velocity in a phase II clinical study in Chinese population
Authors: Zhang Xin , Yang Yong , Wang Qi 
Published: January 2024

Background
Epidemiological studies have shown that lycopene has anti-prostate cancer effect. In vitro tests also confirmed that it can promote apoptosis of prostate cancer cells. We investigated the effect of whole-tomato supplement lycopene on the prostate-specific antigen velocity in selected prostate cancer patients.

Methods
Twenty selected prostate cancer patients were given whole-tomato supplement lycopene 10 mg per day for about 6 months. Blood samples of patients were collected weekly to measure serum prostate-specific antigen (PSA) values. PSA velocity slope, which reflects the change of PSA, and the degree of change were also calculated. By comparing the values of average PSA velocity slope (rise or fall of PSA) before and after the administration of lycopene, the effect of lycopene can be evaluated. Blood chemistry analysis was regular followed as safety control.

Results
Three patients in the research group withdrew within 3 weeks because of inability to conform. The rest 17 patients continued for an average period of 6 months. Two patients withdrew because of cancer progression (PSA rise) who later received active treatment. The average fall in PSA was equivalent to 2.56% over (i.e. an average slope/d of -0.000 28) the first 3 months. In the last 3 months, average fall in PSA was equivalent to 31.58% (i.e. an average slope/d of -0.003 51). The Wilcoxon rank-sum test showed a statistically significant decrease of PSA velocity slope overall (P=0.000 9). Analysis of the PSA doubling time (pre- vs. post-treatment) showed a median increase over 3 months but this was not statistically significant (P=0.21). No toxic side effect was observed during the whole process. The results indicate that the average PSA change is “decline” in patients, and the degree of the decline is accelerated.

Conclusion
Administration of lycopene was able to reduce PSA velocity in this study group.
Intravitreal ranibizumab for the treatment of pathological myopia associated with choroidal neovascularization in Chinese patients
Authors: Xu Yang , Hong Dai 
Published: January 2024

Background
Pathological myopia (PM) is the leading cause for choroidal neovascularization (CNV) in people below 50 years of age, the anti-vascular endothlial growth factor (VEGF) medicine is now available to treat CNV secondary to PM. This study aimed to observe the efficacy of intravitreal ranibizumab for PM associated with subfoveal or juxtafoveal CNV in Chinese patients.

Methods
Fifty-four eyes of 52 consecutive patients were included, they treated with intravitreal ranibizumab 0.5 mg for PM associated with CNV. The best corrected visual acuity (BCVA) of Snellen chart, letters of ETDRS chart, retinal thickness, leakage of CNV lesion, and complications with surgery were analyzed pre- and post-treatment. Eligibility criteria included diopter ≥-8.0 D or eye axis ≥28 mm with fundus changes of PM (lacquer crack, optic disc atrophy, chorioretinal atrophy, posterior scleral staphyloma); CNV secondary to PM; subfoveal or juxtafoveal CNV.

Results
For 54 affected eyes of 52 consecutive patients, the average BCVA of Snellen chart and letters of ETDRS chart were 0.29 and 30.4, respectively; fundus fluorescein angiography (FFA)/indocyanine green angiography (ICGA) showed CNV leakage, and average retinal thickness on optical coherence tomography (OCT) was 267.2 μm before treatment. Injections of ranibizumab ranged from 1 to 4 (mean 2.2). Follow-up time varied from 12 to 36 months (mean 31.9 months). At the last visit, the BCVA of Snellen chart was increased by three lines (mean 0.65) (P <0.01); the letters of ETDRS chart were increased to 17.0 letters (mean 47.4, P <0.01); the visual acuity increased more than 15 letters in 30 eyes (55.5%), decreased in 1 eye (1.9%); the retinal thickness on OCT images was decreased by 17.0 μm (mean 250.2 μm) (P=0.082); no active leakage from the CNV lesion occurred in 18 eyes (33.3%), reduced leakage in 30 eyes (55.6%), and no change in 6 eyes (11.1%) as shown by FFA/ICGA. Increased retinoschisis was observed in one eye after the second injection.

Conclusions
Intravitreal ranibizumab for neovascular PM was well tolerated in Chinese patients, with functional and anatomic improvements in a short-term study, while a long-term study is still needed.
Short-term intensive atorvastatin therapy improves endothelial function partly via attenuating perivascular adipose tissue inflammation through 5-lipoxygenase pathway in hyperlipidemic rabbits
Authors: Xiaoqiao Wang , Yongqin Lin , Niansang Luo , Zhongqing Chen , Miaoning Gu , Jingfeng Wang , Yangxin Chen 
Published: January 2024

Background
Atherosclerosis is a kind of disease with multiple risk factors, of which hyperlipidemia is a major classical risk factor resulting in its pathogenesis and development. The aim of this study was to determine the effects of short-term intensive atorvastatin (IA) therapy on vascular endothelial function and explore the possible mechanisms that may help to explain the clinical benefits from short-term intensive statin therapy.

Methods
After exposure to high-fat diet (HFD) for 8 weeks, the animals were, respectively, treated with IA or low-dose atorvastatin (LA) for 5 days. Blood lipids, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), endothelin-1 (ET-1), and endothelium-dependent vasorelaxation function were, respectively, measured. mRNA and protein expression of CRP, TNF-α, IL-6, macrophage chemoattractant protein-1 (MCP-1), and 5-lipoxygenase (5-LO) were also evaluated in pericarotid adipose tissue (PCAT) and cultured adipocytes.

Results
HFD increased serum inflammatory factor levels; induced significant hyperlipidemia and endothelial dysfunction, including imbalance between NO and ET-1; enhanced inflammatory factors and 5-LO expression; and promoted macrophage infiltration into adipose tissue. Five-day IA therapy could significantly decrease serum inflammatory factor levels and their expression in PCAT; restore the balance between NO and ET-1; and improve endothelial function and macrophage infiltration without significant changes in blood lipids. However, all of the above were not observed in LA therapy. In vitro experiment found that lipopolysaccharide (LPS) enhanced the expression of inflammatory factors and 5-LO in cultured adipocytes, which could be attenuated by short-time (6 hours) treatment of high-dose (5 μmol/L) but not low-dose (0.5 μmol/L) atorvastatin. In addition, inhibiting 5-LO by Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC, a potent and direct 5-LO inhibitor) could significantly downregulate the above-mentioned gene expression in LPS-treated adipocytes.

Conclusion
Short-term IA therapy could significantly ameliorate endothelial dysfunction induced by HFD, which may be partly due to attenuating inflammation of PCAT through inhibiting 5-LO pathway.
Epigenetic regulation of putative tumor suppressor TGFBI in human leukemias
Authors: Fang Hongbo , Liu Jing , Guo Dan , Liu Peixiang , Zhao Yongliang 
Published: January 2024

Background
Both in vitro and in vivo data have demonstrated the TGFBI gene functions as a putative tumor suppressor and is frequently downregulated in human tumors of different histological types. The hypermethylation of the TGFBI promoter, as one of the main regulatory mechanisms, is associated with TGFBI silencing. In this study, we used a methylation-specific PCR (MSP) method to evaluate the methylation status of the TGFBI promoter in human leukemias.

Methods
Real-time RT-PCR and methylation-specific PCR approaches were performed to define the TGFBI expression and promoter methylation in human leukemia cell lines and clinical samples. Genomic DNA was isolated from peripheral blood mononuclear cells from leukemia patients, bisulfite-converted, and analyzed by the MSP method.

Results
Hypermethylation of the TGFBI promoter occurred in leukemia cell lines and demethylation treatment re-expressed TGFBI at a substantially increased level in most of leukemia cell lines tested. Furthermore, a much higher level of CpG island methylation and a significantly lower TGFBI expression were also identified in clinical leukemia samples.

Conclusion
The results suggest an important role of promoter methylation in regulating TGFBI expression in leukemia, which provides a useful diagnostic marker for clinical management of human leukemias.
Fibroblasts weaken the anti-tumor effect of gefitinib on co-cultured non-small cell lung cancer cells
Authors: Yong Xiao , Wang Peiqin , Jiang Tao , Yu Wenchen , Shang Yan , Han Yiping , Zhang Pingping , Li Qiang 
Published: January 2024

Background
Non-small cell lung cancer (NSCLC) is the most common lung malignancy worldwide. The metastatic potential of NSCLC cells has been shown to be associated with the tumor microenvironment, which consists of tumor cells, stroma, blood vessels, immune infiltrates and the extracellular matrix. Fibroblasts can produce numerous extracellular matrix molecules and growth factors. Gefitinib has been evaluated as a first-line treatment in selected patients, and it has shown favorable efficacy especially in NSCLC, but it is not effective for everyone.

Methods
In this study, we examined the antitumor activity of gefitinib on lung fibroblasts co-cultured of lung cancer cells. A series of co-culture experiments that employed cell counting kit-8 (CCK8), transwells, real-time polymerase chain reaction (RT-PCR) and Western blotting with HFL-1 fibroblasts and A549 human lung carcinoma cells were performed to learn more about tumor cell proliferation, migration and invasion; and to determine any change of epithelial mesenchymal transition (EMT)-associated tumor markers vimentin, matrix metallopro-teinase 2 (MMP2) and chemotaxis cytokines receptor 4 (CXCR4) mRNA levels.

Results
A549 cell proliferation in the presence of HFL-1 cells was not significantly increased compared with A549 cells alone, but A549 cell spheroid body formation was increased after co-culture, and treatment with gefitinib increased further. Our study also revealed that fibroblasts attenuated the lung cancer cell inhibition ratio of migration and invasion after gefitinib treatment in vitro. To further study this mechanism, RT-PCR analysis showed that vimentin, MMP2 and CXCR4 mRNA levels were more highly expressed in the lung cancer cells after co-culture, but did not obviously decrease compared with the control cells following gefitinib treatment. This suggests the mechanism by which fibroblasts attenuate gefitinib-induced expression of EMT-associated tumor markers. Finally, our results demonstrated that co-culture with A549 lung cancer cells does not alter the cell cycle distribution of HFL-1 fibroblasts. Furthermore, HFL-1 fibroblasts had no effect on the cell cycle distribution of HFL-1 cells treated with gefitinib.

Conclusion
Gefitinib has lower anti-tumor activity on A549 lung cancer cells when co-cultured with HFL-1 fibroblasts.
Preparation and characterization of paclitaxel-loaded poly lactic acid-co-glycolic acid coating tracheal stent
Authors: Kong Yingying , Zhang Jie , Wang Ting , Qiu Xiaojian , Wang Yuling 
Published: January 2024

Background
In-stent restenosis caused by airway granulation poses a challenge due to the high incidence of recurrence after treatment. Weekly applications of anti-proliferative drugs have potential value in delaying the recurrence of airway obstruction. However, it is not practical to subject patients to repeated bronchoscopy and topical drug applications. We fabricated novel pacilitaxel-eluting tracheal stents with sustained and slow pacilitaxel release, which could inhibit the formation of granulation tissue. And we assessed the quality and drug release behaviors of drug-eluting stents (DESs) in vitro.

Methods
Stents were dipped vertically into a coating solution prepared by dissolving 0.5 g (2% w/v) of poly lactic acid-co-glycolic acid (PLGA) and 0.025 g (0.1% w/v) of pacilitaxel in 25 ml of dichloromethane. DES morphology was examined by scanning electron microscopy (SEM). Pacilitaxel release kinetics from these DESs was investigated in vitro by shaking in PBS buffer followed by high performance liquid chromatography (HPLC).

Results
Using an orthogonal experimental design, we fabricated numerous pacilitaxel/PLGA eluting tracheal stents to assess optimum coating proportions. The optimum coating proportion was 0.1% (w/v) pacilitaxel and 2% (w/v) PLGA, which resulted in total pacilitaxel loading of (16.380 6±0.002 1) mg/stent. By SEM the coating was very smooth and uniform. Pacilitaxel released from DES was at (0.376 3±0.003 8) mg/d, which is a therapeutic level. There was a prolonged, sustained release of pacilitaxel of >40 days.

Conclusions
Paclitaxel-loaded PLGA coating tracheal stents were successfully developed and evaluated. Quality assessments demonstrated favorable surface morphology as well as sustained and effective drug release behavior, which provides an experimental reference for clinical practitioners.
Fundus autofluorescence characteristics in patients with diabetic macular edema
Authors: Yinchen Shen , Xun Xu , Kun Liu 
Published: January 2024

Background
Diabetic macular edema (DME) is one of the major causes of visual impairment in patients with diabetes mellitus. DME shows a variety of clinical characteristics with unpredictable results to treatment. The purpose of this study was to investigate the characteristics of fundus autofluorescence (FAF) in DME, which is a rapid, noninvasive technique for fundus diseases.

Methods
A total of 18 patients (30 eyes) with clinically significant macular edema (CSME) were enrolled. FAF imaging was performed with a confocal scanning laser ophthalmoscope. Other ophthalmic examinations included best corrected visual acuity (BCVA), MP-1 microperimetry, and spectral-domain optical coherence tomography (SD-OCT). Main outcome measurements included BCVA, macular sensitivity (MS), central retinal thickness (CRT), central retinal volume (CRV), the integrity of the inner segment-outer segment junction (IS/OS), and the integrity of the external limiting membrane (ELM).

Results
Among the 30 eyes, four eyes (13.3%) had normal foveal FAF and 26 eyes (86.7%) had abnormal FAF. Abnormal FAF was mainly divided into three types: cystoid increased FAF (iFAF) 16 eyes (53.3%), spot iFAF six eyes (20%), irregular decreased FAF (dFAF) four eyes (13.3%). According to the FAF morphology, patients were categorized into four groups: normal, cystoid iFAF, spot iFAF, and irregular dFAF. There was a significant difference in BCVA (P <0.001) and MS (P <0.05) among the four groups. The visual function of patients with spot iFAF and irregular dFAF was relatively poor. However, there was no difference in CRT (P=0.186) and CRV (P=0.191) among the four groups. In the normal FAF group, the photoreceptor layers were mostly intact. Regarding the cystoid iFAF group, the photoreceptor layers were relatively intact, while in the other two groups, IS/OS and ELM were disrupted in most patients. No one had intact IS/OS or ELM layer.

Conclusions
FAF might reflect the damage of the retina and had a relationship with visual function as well as photoreceptor integrity, which gives new insight into the evaluation of DME. Dynamic FAF monitoring helps to better evaluate the disease progression of DME as well as visual function.