bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo detection of severity of optic nerve crush using manganese-enhanced magnetic resonance imaging in rats
Authors: Yun Feng , Lisha Luo , Zhizhong Ma , Xiaodong Sun , Yuntao Hu
Published: January 2024

Background

Traumatic optic neuropathy (TON) is one of the reasons for permanent vision loss. Currently, the clinical practices may not be sufficient for direct assessments and comprehensively determining the location and extent of the patients with optic nerve injury in traumatic optic neuropathy. Magnetic resonance imaging (MRI) provides a non-invasive option. However, rare reports have found whether the differentdegree of injury of the optic nerve can be detected by manganese-enhanced MRI (MEMRI). This study aimed to explore the efficacy of MEMRI in the visual pathway for different severity of opitic nerve injury in rats.

Methods

The different injuries of mild, moderate, and heavy damages were created by modified reverse tweezer and were evaluated by counting retinal ganglion cells (RGCs) and VEP ananlysis. Sprague-Dawley (SD) rats were intravitreally injected with 2 l of 25 mmol/L MnCl2, which has been confirmed as a safe injection concentration. The contrast-to-noise ratio (CNR) of MEMRI for optic nerve enhancement at different injury levels was measured.

Results

The location of the significantly decreased signal point on optic nerve (ON) was corresponding to the location we made. However, similar findings are not obvious, or even have not been observed in 28 days in each group and also in 14 days at F100 group, indicating that MEMRI could be directly intuitive positioned in the early stage on the optic nerve injury.

Conclusions

The possibility of using MEMRI in optic nerve injury in a safe injection concentration of 25 mmol/L is confirmed. Therefore, it is possible to detect the severity of the optic nerve by MEMRI examination.
Theanine improves the function of dendritic cells via the downregulation of cyclooxygenase-2 expression
Authors: Mingsheng Lei , Jianhong Zuo , Min Li , Qihua Gu , Chengping Hu
Published: January 2024

Background

Tumor cells can reduce the number of dendritic cells (DCs) in the tumor environment and cause DC dysfunction through autocrine or paracrine pathways. We sought to measure cyclooxygenase-2 (COX-2) expression in bombesin-inhibited DCs treated with theanine in vitro and to explore the protection and activation effects of theanine on DCs.

Methods

Enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting were used to analyze the effects of theanine on COX-2 expression and interleukin (IL)-12/IL-10 secretion of bombesin-treated DCs.

Results

DCs acquired an impaired phenotype as a result of bombesin treatment. Theanine increased the expression of mature DC surface molecules. The number of cell apoptosis with the treatment of bombesin and theanine significantly decreased, accounting for 15.9%, compared with 26.1% of cell apoptosis with bombesin. COX-2 expression in bombesin-treated DCs was inhibited by theanine in a dose-dependent manner. Theanine promoted DC secretion of IL-12. IL-12 levels reached (137.4±4.9) pg/ml with theanine at 200 μmol/L. However, theanine inhibited the secretion of IL-10 in a dose-dependent manner. IL-10 levels were only (58.4±6.9) pg/ml with theanine at 200 μmol/L.

Conclusion

Theanine inhibits the transcription and translation of COX-2 and regulates the balance of IL-10/IL-12 secretion in bombesin-inhibited DCs, leading to the recovery of a state of activation in DCs.
Measuring health care efficiency with a tripartite configuration under the “National” Health Insurance system
Authors: Kreng Victor B. , Yang Shao-wei , Lin Chien-Hsu
Published: January 2024

Background

The “National” Health Insurance (NHI) in Taiwan, China is a single-payer system that was introduced in 1995 to provide universal health care. It is worth noting that three stakeholders are involved in Taiwan’s NHI, which can be seen as a triangular governance regime between the Bureau of “National” Health Insurance (BNHI), the insured and providers. Accordingly, this study intended to assess the efficiency of various different production processes that occur among these stakeholders in Taiwan’s NHI system.

Methods

A two-stage relational Data Envelopment Analysis (DEA) model is adopted to investigate the sub-process efficiencies of the health care resources held by 23 cities and counties through stages I or II, where the outputs of the first stage serve the inputs of the second. The dataset was collected from the annual reports published by the Department of Health, Taiwan, China.

Results

Under the proposed framework, the efficiency of the whole process can be obtained from the product of productivity and allocative efficiency. Ten DMUs are efficient either in stages I or II, with only two DMUs being efficient with regard to both sub-processes.

Conclusion

The relational DEA model not only demonstrates the physical relationship between the whole process and the sub-process components, but also produces reliable outcomes in efficiency measurement among different stakeholders in Taiwan’s NHI system.
Effectiveness and safety of endoscopic submucosal dissection for intraepithelial neoplasia of the esophagogastric junction
Authors: Jing Wen , Enqiang Linghu , Yunsheng Yang , Qingsen Liu , Jing Yang , Shufang Wang , Xiangdong Wang , Hong Du , Jiangyun Meng , Hongbin Wang , Zhongsheng Lu
Published: January 2024

Background

Endoscopic submucosal dissection of the esophagogastric junction is the most difficult gastric and esophageal dissection procedure. No reports of endoscopic submucosal dissection for Siewert type II carcinoma of the esophagogastric junction have compared the outcomes of endoscopic submucosal dissection for all three Siewert types of adenocarcinoma. This study aimed to evaluate the efficacy and safety of endoscopic submucosal dissection for intraepithelial neoplasia of the esophagogastric junction.

Methods

From October 2008 to June 2013, 73 patients underwent endoscopic submucosal dissection for intraepithelial neoplasia of the esophagogastric junction. The patients were prospectively evaluated regarding the executability of the technique, short-term results of the procedure, en bloc resection rate, curative resection rate, complications and additional treatment after endoscopic submucosal dissection, and follow-up outcomes.

Results

Sixty-eight of the 73 patients (93.2%) underwent en bloc resection; the mean maximum specimen diameter was 33.7 mm. Fifty-seven of 61 patients (93.4%) who underwent curative resection were successfully followed-up for 1.0 to 56.0 months (average, 24.1 months). Local recurrence developed in one patient with high-grade intraepithelial neoplasm. Twelve patients underwent noncurative resection, including lateral resection margin residues in three, vertical resection margin residues in one, signet ring cell carcinoma or undifferentiated adenocarcinoma in four, lymphatic or vessel invasion in one, vertical residual margin residues combined with signet ring cell carcinoma in one, and undifferentiated adenocarcinoma with lymphatic or vessel invasion in two. In the noncurative resection group, one patient was lost to follow-up, seven underwent additional surgery, and the remaining four were periodically followed up; none had local recurrence or distant metastases. The only complication was delayed bleeding in three patients, which was successfully controlled by conservative treatment or endoscopic therapy.

Conclusions

Endoscopic submucosal dissection is safe and effective for intraepithelial neoplasia of the esophagogastric junction. R0 en bloc resection is possible and can avoid the risk of local recurrence.
Effect of human rhinovirus infection in pediatric patients with influenza-like illness on the 2009 pandemic influenza A(H1N1) virus
Authors: Sun Yu , Zhu Ru’nan , Zhao Linqing , Deng Jie , Wang Fang , Ding Yaxin , Yuan Yi , Qu Dong , Qian Yuan
Published: January 2024

Background

Some research groups have hypothesized that human rhinoviruses (HRVs) delayed the circulation of the 2009 pandemic influenza A(H1N1) virus (A(H1N1)pdm09) at the beginning of Autumn 2009 in France. This study aimed to evaluate the relationship between HRV and A(H1N1)pdm09 in pediatric patients with influenza-like illness in Beijing, China.

Methods

A systematic analysis to detect A(H1N1)pdm09 and seasonal influenza A virus (FLU A) was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1, 2009 to February 28, 2010, while a one-step real-time RT-PCR (rRT-PCR) assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.

Results

During the survey period, only one wave of A(H1N1)pdm09 was observed. The percentage of positive cases for A(H1N1)pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010. Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September (2.2%) and October (3.3%), revealing that the peak of HRV infection in 2009 was similar to that of other years. Among the 1 146 specimens examined for HRVs, 21 (1.8%) were HRV-positive, which was significantly lower than that reported previously in Beijing (15.4% to 19.2%) (P <0.01). Overall, 6 samples were positive for both A(H1N1)pdm09 and HRV, which represented a positive relative frequency of 1.60% and 2.08% HRV, considering the A(H1N1)pdm09-positive and -negative specimens, respectively. The odds ratio was 0.87 (95% CI 0.32; 2.44, P=0.80).

Conclusions

HRVs and A (H1N1)pdm09 co-circulated in this Chinese population during September and October 2009, and the HRV epidemic in 2009 did not affect A(H1N1)pdm09 infection rates in Beijing, China as suggested by other studies. However, the presence of A(H1N1)pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.
Lateral migration with telescoping of a trochanteric fixation nail in the treatment of an intertrochanteric hip fracture
Authors: Liu Wanjun , Wang Junqiang , Weaver Michael J. , Vrahas Mark S. , Zhou Dongsheng
Published: January 2024

Background

The trochanteric fixation nail (TFN) can be used to treat stable and unstable fractures of intertrochanteric hip fractures. We study the common lateral migration that occurs with telescoping of intertrochanteric hip fractures treated with TFN and identify the predictors and relationships to clinical outcomes.

Methods

Patient demographic information, fracture type (Arbeitsgemeinschaft für Osteosynthesefragen (AO)/Orthopaedic Trauma Association (OTA) classification), radiographic data, and clinical data were collected. Lateral migration with telescoping was measured. Statistical analyses were performed to determine which variables predicted lateral migration with telescoping. Patient outcome scores were recorded using the Modified Harris Hip Score (MHHS), Hip Outcome Score-Activity of Daily Living (HOS-ADL), and Visual Analog Scale for pain.

Results

Two hundred and twenty-three patients (67 males, 156 females) fitted the radiographic and follow-up (average 24.6 months) criteria. The average age was 77.2 years. The average lateral migration with telescoping was 4.8 mm. Twenty-one patients (9.4%) had excessive lateral migration with telescoping (≥10 mm). The quality of calcar reduction (P=0.01) and unstable fracture patterns (P=0.006) were significant predictive factors of lateral migration with telescoping. The mean outcome scores (MHHS and HOS-ADL) were 80.1 points and 78.7 points, respectively. All subjects had no significant relationship to lateral migration with telescoping (P >0.05). Of all the patients who developed lateral migration with telescoping, only one required removal of the blade for hip pain and all patients went on to uneventful union at an average time of 4.5 months.

Conclusions

Lateral migration with telescoping is a common mechanical complication of intertrochanteric hip fracture treated with the TFN procedure. It was predicted by the quality of calcar reduction and fracture type. However, this did not affect stable fixation and fracture healing, so rarely leads to clinical problems.
Relative frequency and survival of primary cutaneous lymphomas: a retrospective analysis of 98 patients
Authors: Liu Jie , Yu Xin , Liu Yuehua , Jin Hongzhong , Ma Donglai , Qu Tao , Wang Tao , Sun Qiuning
Published: January 2024

Background

The World Health Organization and European Organization for Research and Treatment of Cancer (WHOEORTC) classification in 2005 promoted the comparisons of primary cutaneous lymphoma (PCL) subtypes between different countries. The relative frequency of PCL varied according to geography. The study aimed to analyze the relative frequency and survival of PCLs in China and to compare the data with the published results from other countries.

Methods

We analyzed 98 patients with PCLs over a 6-year period and reclassified them according to the most recent WHO-EORTC classification (2005). Disease-specific survival rate and curves according to specific subtypes such as mycosis fungoides, lymphomatoid papulosis, and primary cutaneous peripheral T-cell lymphoma, unspecified was also calculated.

Results

The relative rate of PCL in China was distinct from those in Western countries. Our study showed a higher frequency of cutaneous T- and NK-cell lymphomas (CTCLs) (94%), and a lower frequency of cutaneous B-cell lymphomas (CBCLs) (6%). The 5-year survival rate of the total PCLs was 82%. There was no significant difference in the 5-year survival rate (P >0.05 by Log-rank test) between CTCL (80%) and CBCL (100%).

Conclusions

The higher percentage of CTCL in China may provide a clue to further study the etiological factors of PCLs. Racial variations in factors such as HLA determinants may play a role in the development of CTCL.
High levels of interleukin-6 and 8-iso-prostaglandin in the exhaled breath condensate and serum of patients with chronic obstructive pulmonary disease related pulmonary hypertension
Authors: He Haiyan , Tao Yijiang , Chen Xiaoxiao , Qiu Haiyan , Zhu Jie , Zhang Jianhui , Ma Hang
Published: January 2024

Background

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD.

Methods

We measured the levels of interleukin-6 (IL-6) and 8-iso-prostaglandin (8-iso-PSG) in exhaled breath condensate (EBC) and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure (PASP) was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg.

Results

Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH ((8.27±2.14) ng/L vs. (4.95±1.19) ng/L, P <0.01). The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group ((72.8±21.6) ng/L vs. (43.58±13.38) ng/L, P <0.01). Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group (EBC: (9.00±2.49) ng/L vs. (5.96±2.31) ng/L, P <0.01 and serum: (41.87±9.75) ng/L vs. (27.79±11.09) ng/L, P <0.01). Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum (r=0.477-0.589, P <0.05).

Conclusion

The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.
Automated brain tumor segmentation in magnetic resonance imaging based on sliding-window technique and symmetry analysis
Authors: Yanyun Lian , Zhijian Song
Published: January 2024

Background

Brain tumor segmentation from magnetic resonance imaging (MRI) is an important step toward surgical planning, treatment planning, monitoring of therapy. However, manual tumor segmentation commonly used in clinic is time-consuming and challenging, and none of the existed automated methods are highly robust, reliable and efficient in clinic application. An accurate and automated tumor segmentation method has been developed for brain tumor segmentation that will provide reproducible and objective results close to manual segmentation results.

Methods

Based on the symmetry of human brain, we employed sliding-window technique and correlation coefficient to locate the tumor position. At first, the image to be segmented was normalized, rotated, denoised, and bisected. Subsequently, through vertical and horizontal sliding-windows technique in turn, that is, two windows in the left and the right part of brain image moving simultaneously pixel by pixel in two parts of brain image, along with calculating of correlation coefficient of two windows, two windows with minimal correlation coefficient were obtained, and the window with bigger average gray value is the location of tumor and the pixel with biggest gray value is the locating point of tumor. At last, the segmentation threshold was decided by the average gray value of the pixels in the square with center at the locating point and 10 pixels of side length, and threshold segmentation and morphological operations were used to acquire the final tumor region.

Results

The method was evaluated on 3D FSPGR brain MR images of 10 patients. As a result, the average ratio of correct location was 93.4% for 575 slices containing tumor, the average Dice similarity coefficient was 0.77 for one scan, and the average time spent on one scan was 40 seconds.

Conclusions

An fully automated, simple and efficient segmentation method for brain tumor is proposed and promising for future clinic use. Correlation coefficient is a new and effective feature for tumor location.
Prenatal diagnosis of Down syndrome using cell-free fetal DNA in amniotic fluid by quantitative fluorescent polymersase chain reaction
Authors: Wu Dan , Chi Hongbin , Shao Minjie , Wu Yao , Jin Hongyan , Wu Baiyan , Qiao Jie
Published: January 2024

Backgroud

Amniotic fluid (AF) supernatant contains cell-free fetal DNA (cffDNA) fragments. This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis, which could be combined with simple quantitative fluorescent polymerase chain reaction (QF-PCR) to provide an ancillary method for the prenatal diagnosis of trisomy 21 syndrome.

Methods

AF supernatant samples were obtained from 27 women carrying euploid fetuses and 28 women carrying aneuploid fetuses with known cytogenetic karyotypes. Peripheral blood samples of the parents were collected at the same time. Short tandem repeat (STR) fragments on chromosome 21 were amplified by QF-PCR. Fetal condition and the parental source of the extra chromosome could be determined by the STR peaks.

Results

The sensitivity of the assay for the aneuploid was 93% (26/28; confidence interval, CI: 77%-98%) and the specificity was 100% (26/26; CI: 88%-100%). The determination rate of the origin of the extra chromosome was 69%. The sensitivity and the specificity of the assay in the euploid were 100% (27/27).

Conclusions

Trisomy 21 can be prenatally diagnosed by the QF-PCR method in AF supernatant. This karyotype analysis method greatly reduces the requirement for the specimen size. It will be a benefit for early amniocentesis and could avoid pregnancy complications. The method may become an ancillary method for prenatal diagnosis of trisomy 21.
Genome-wide association study knowledge-driven pathway analysis of alcohol dependence implicates the calcium signaling pathway
Authors: Li Danni , Li Jinming , Guo Yanfang
Published: January 2024

Background

Alcohol dependence (AD) is a serious and common public health problem. The identification of genes that contribute to the AD variation will improve our understanding of the genetic mechanism underlying this complex disease. Previous genome-wide association studies (GWAS) and candidate gene genetic association studies identified individual genes as candidates for alcohol phenotypes, but efforts to generate an integrated view of accumulative genetic variants and pathways under alcohol drinking are lacking.

Methods

We applied enrichment gene set analysis to existing genetic association results to identify pertinent pathways to AD in this study. A total of 1 438 SNPs (P <1.0×10-3) associated to alcohol drinking related traits have been collected from 31 studies (10 candidate gene association studies, 19 GWAS of SNPs, and 2 GWAS of copy number variants).

Results

Among all of the KEGG pathways, the calcium signaling pathway (hsa04020) showed the most significant enrichment of associations (21 genes) to alcohol consumption phenotypes (P=5.4×10-5). Furthermore, the calcium signaling pathway is the only pathway that turned out to be significant after multiple test adjustments, achieving Bonferroni P value of 0.8×10-3 and FDR value of 0.6×10-2, respectively. Interestingly, the calcium signaling pathway was previously found to be essential to regulate brain function, and genes in this pathway link to a depressive effect of alcohol consumption on the body.

Conclusions

Our findings, together with previous biological evidence, suggest the importance of gene polymorphisms of calcium signaling pathway to AD susceptibility. Still, further investigations are warranted to uncover the role of this pathway in AD and related traits.
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.
Genetic environment of β-lactamase genes of extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates from patients with lower respiratory tract infection in China
Authors: Lin Liu , Xiaorong Wang , Shuchang An , Xiangyan Zhang , Lin Chen , Yuqian Li , Li Xu , Yijie Zhang , Zhancheng Gao
Published: January 2024

Background

Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) is one of the most popular pathogens that cause refractory respiratory tract infection. The genetic environment, including insertion sequences and the types of promoter, plays a key role in exploration of the mechanism of prevalence and dismission of the ESBL-producing K. pneumoniae isolates. The aim of the investigation was to target analysis the genetic environment and promoter sequences of bla
CTX-M, bla
SHV and bla
TEM, the most popular β-lactamase genes harbored by ESBL-producing K. pneumoniae isolates.

Methods

From February 2010 to July 2011, 158 of 416 K. pneumoniae isolates producing ESBL from patients with lower respiratory tract infection were collected from seven tertiary hospitals from Beijing, Anhui, Fujian, Liaoning, Hebei and Inner Mongolia Autonomous Region in China. The genetic environment including promoters of 10 types of bla
CTX-M, 18 types of bla
SHV and 2 types of bla
TEM were analyzed by amplification and direct sequencing with various sets of PCR primers.

Results

ISEcp1 was located upstream of the 5' end of the bla
CTX-M gene in 130 (97.0%) out of 134 K. pneumoniae isolates harboring bla
CTX-M and provided a conserved promoter to bla
CTX-M. A non-coding sequence preceded by kdpC and recF was identified in all of the bla
SHV genes except bla
SHV-12 and bla
SHV-2a. IS26 was also found upstream of 1 bla
CTX-M-15, 10 bla
SHV-1 strains, 4 bla
TEM-1 and all of the bla
SHV-2,
bla
SHV-2a, bla
SHV-5 and bla
SHV-12. Eighty-seven of 91 strains harboring bla
TEM-1 carried a copy of Tn2 and IS26-bla
TEM-1 fragments were also detected in 4 strains. With respect to K. pneumoniae, the genetic environment of bla
CTX-M-38, bla
SHV-142 and bla
TEM-135 were firstly elaborated, and four kinds of novel genetic environment of bla
CTX-M-3, bla
CTX-M-15 and bla
TEM-1 have been detected as well.

Conclusions

Perfective implementation of the genetic environment information of β-lactamase gene needs to be further explored and supplemented. ISEcp1 and IS26 elements are widespread upstream of the bla
CTX-M, bla
SHV and bla
TEM genes and contribute to horizontal transmission and genetic expression.