bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the efficacy and safety of tiotropium bromide (5 μg) inhaled via Respimat in Chinese patients with chronic obstructive pulmonary disease
Authors: Tang Yan , Massey Dan , Zhong Nan-shan 
Published: January 2024

Background
A pharmacokinetic study in an Asian population showed that tiotropium 5 μg via Respimat leads to the same plasma levels compared to 18 μg via HandiHaler. The objective of the trial was to compare the efficacy and safety of long-term treatment (1 year) with tiotropium bromide (5 μg) via Respimat® with placebo in patients with chronic obstructive pulmonary disease (COPD).

Methods
A total of 3991 patients were randomized in this double-blind, placebo controlled, parallel group study, while in China 338 patients (309 males, 29 females) received either tiotropium bromide (n=167) or placebo (n=171). Tiotropium bromide solution or matching placebo was delivered via Respimat® at a dosage of 5 μg (2 × 2.5 μg/puff) once daily for 48 weeks. Co-primary endpoints were trough forced expiratory volume in one second (FEV1) and the time to first exacerbation.

Results
Statistically significant improvements in trough FEV1 and trough forced vital capacity (FVC) in the tiotropium group were achieved at weeks 4, 24, and 48 compared with those in the placebo group. A statistically significant difference (P=0.0027) in favour of tiotropium was also observed for the time to first exacerbation. The total numbers of exacerbations during treatment were 90 and 128 in the tiotropium and placebo groups, respectively, with a rate ratio of 0.69 (P=0.0164). The difference between the treatment groups in the adjusted mean changes from baseline of St. George Respiratory Questionnaire (SGRQ) total score was −3.9 (95% CI: −7.5, −0.2) and was of statistical significance (P=0.0367). The incidences of serious adverse events (SAEs) in the tiotropium and placebo groups were 16.2% and 17.0%, respectively. Seven deaths occurred whilst patients were on treatment, four in the tiotropium group and three in the placebo group, all of which were assessed as non-related study drugs by the investigators.

Conclusions
Tiotropium significantly improved lung function and quality of life, delayed the time to first exacerbation, reduced the number of exacerbations. Overall, tiotropium was well tolerated.
Expression of ectonucleotide pyrophosphatase-1 in end-plate chondrocytes with transforming growth factor beta 1 siRNA interference by cyclic mechanical tension
Authors: XU Hong-guang , LI Zi-rui , WANG Hong , LIU Ping , XIANG Sheng-nan , WANG Chuang-dong , ZHANG Xiao-ling 
Published: January 2024

Background
Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 is a membrane-bound protein that catalyzes the hydrolysis of extracellular nucleoside triphosphates to monophosphate and extracellular inorganic pyrophosphate (ePPi). Mechanical stimulation regulates ENPP-1 expression. This study sought to investigate the changes in ENPP-1 expression after stimulation using cyclic mechanical tension (CMT).

Methods
Rat end-plate chondrocytes were cultured and subjected to CMT (at 3%, 6%, and 9% elongation) for 20, 40, and 60 minutes to observe changes in the expression of ENPP-1. To investigate the pathway, end-plate chondrocytes were exposed to 10 ng/ml of transforming growth factor beta 1 (TGF-β1), TGF-β1 siRNA, or a specific extracellular signal-regulated kinase (ERK)1/2 inhibitor, U0126, in addition to CMT. Changes in ENPP-1 expression were measured by reverse transcription PCR (RT-PCR) and Western blotting.

Results
We observed the largest increase in ENPP-1 expression following 3% elongation CMT stimulation. ENPP-1 expression was also increased when end-plate chondrocytes were exposed to 10 ng/ml of TGF-β1, but decreased after TGF-β1 knockdown with siRNA. ERK1/2 phosphorylation was activated after 3% elongation for 40 minutes, and the stimulatory effect of TGF-β1 on ENPP-1 mRNA and protein expression was inhibited by the suppression of the ERK1/2 pathway using U0126.

Conclusion
CMT increases the expression of ENPP-1 in end-plate chondrocytes in a manner likely dependent on TGF-β1 induction by the ERK1/2 signaling pathway.
Krüppel-like factor 8 is a potential prognostic factor for pancreatic cancer
Authors: Wei Yingxin , Chen Ge , You Lei , Zhao Yupei 
Published: January 2024

Background
Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage. There is a lack of information to predict the prognosis of pancreatic cancer. Krüppel-like factor (KLF) 8 has been found to be deregulated in multiple cancers, and its high expression was correlated with poor prognosis. However, so far, no information was reported about the expression of KLF8 in pancreatic cancer. In the present study, we investigated, possibly for the first time, the expression of KLF8 in pancreatic cancer samples and analyzed its correlation with clinical parameters and overall survival (OS) rate.

Methods
We used immunohistochemical staining to detect KLF8 in 68 samples from patients who underwent surgery and its correlation with the clinicopathological characteristics. We used Kaplan-Meier curve to analyze the relationship between KLF8 expression and the OS time. Univariate analysis was performed in addition to multivariate hazard models with clinicopathological features to assess KLF8 as an independent prognostic factor.

Results
KLF8 was present in the cytoplasm of pancreatic cancer cells and 52.9% of the 68 cases had positive expression. KLF8 expression was not associated with sex, age, tumor location, lymph node stage, and metastasis stage, but was associated with tumor stage (P=0.04). Kaplan-Meier method demonstrated that patients with negative expression of KLF8 had a better prognosis. In univariate and multivariate models, KLF8 was a significant predictor of OS in pancreatic cancer.

Conclusion
Our results revealed that KLF8 may be a potential prognostic factor for pancreatic cancer.
Replication of association study between type 2 diabetes mellitus and IGF2BP2 in Han Chinese population
Authors: ZHANG Si-min , XIAO Jian-zhong , REN Qian , HAN Xue-yao , TANG Yong , YANG Wen-ying , JI Li-nong 
Published: January 2024

Background
The association between IGF2BP2 and type 2 diabetes mellitus (T2DM) has been repeatedly confirmed among different ethnic populations. However, in several genome-wide association studies (GWAS) from the Chinese Han population, the gene IGF2BP2 has not been replicated. The results of relevant studies for the association between IGF2BP2 and T2DM showed controversy in Chinese Han population. It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population.

Methods
Two single-nucleotide polymorphisms (SNPs, rs4402960 and rs1470579) in IGF2BP2 were genotyped in Chinese Han population (3807 controls/4531 T2DM cases) by Illumina GoldenGate Indexing assay. The association between SNPs and T2DM was evaluated by multiple Logistic Regression analysis. A meta-analysis was used to estimate the effects of IGF2BP2 in 20854 Chinese Han individuals.

Results
rs1470579 and rs4402960 were confirmed to have strong association with T2DM in the Chinese Han population (rs1470579 P=1.80×10−7, OR (95% CI)= 1.22 (1.14-1.32), rs4402960 P=7.46×10−9, OR (95% CI)= 1.26 (1.17-1.37), respectively). Moreover, 11 studies for rs4402960 were included in the meta-analysis and 7 studies for rs1470579. The meta-analysis also showed the association between T2DM and IGF2BP2 (rs1470579 OR of 1.15 (95% CI= 1.10-1.19), P <0.0001 under an additive model and rs4402960 OR of 1.14 (95% CI= 1.10-1.18), P<0.0001 under an additive model).

Conclusion

IGF2BP2 was strongly associated with the risk of T2DM in Chinese Han population.
Evaluation of asthma control: a questionnaire-based survey in China
Authors: Su Nan , Lin Jiangtao , Chen Ping , Li Jing , Wu Changgui , Yin Kaisheng , Liu Chuntao , Chen Yiqiang , Zhou Xin , Yuan Yadong , Huang Xingang 
Published: January 2024

Background
Little is known about asthma control and perception of asthma among asthmatic patients in China. This study marked the first survey conducted on a national scale that aimed at obtaining baseline information on asthma control and patients' perception of asthma and providing a point of reference for future studies.

Methods
This face-to-face, questionnaire-based survey was conducted from April 2007 to March 2008 with 3 069 asthmatic patients from the respiratory outpatient clinics of 36 general hospitals located in 10 geographically dispersed cities.

Results
Consistent with the Global Initiative for Asthma (GINA) guidelines, 28.7% and 45.0% of our patients achieved control and partial control, respectively. Of the patients in the study, only 21.8% had used a peak flow meter (PFM), and 6.6% of these patients used it daily. Inhaled corticosteroids (ICS) plus a long-acting β2 agonist (LABA) and ICS were the two most common medication regimens and were used in 45.6% and 30.4% of patients, respectively. Asthma had a significant effect on the patients' life and work. A considerable number of hospitalizations, emergency department visits, and sick days were observed.

Conclusion
Despite improvements in asthma control and ICS and PFM compliance compared with past literature, the current level of asthma control countrywide continues to fall short of the goals set in the GINA.
Combination of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging is an optimal way to evaluate rheumatoid arthritis in rats dynamically
Authors: Zhang Wei-tao , Du Xiang-ke , Huo Tian-long , Wei Zheng-mao , Hao Chuan-xi , An Bei 
Published: January 2024

Background
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder. Many methods have been used to observe the progress of RA. The purpose of this study was to observe the progress of RA in rats with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), magnetic resonance (MR) imaging and arthritis score, and analyze the relationships among different methods in evaluation of RA.

Methods
Sixteen healthy Sprague Dawley (SD) rats about 8-week old were randomly assigned to a RA group and a control group. Bovine type II emulsified incomplete Freud's adjuvant was used to induce arthritis in the RA group. Arthritis score of the rats in two groups were recorded, and 18F-FDG PET/CT, MR imaging were performed both on the corresponding rats every 3 days. All the rats were sacrificed at week 5, and histopathological examination was performed on rat knees stained with haematoxylin and eosin.

Results
The arthritis score and the standard uptake value (SUV) of knee joints in RA rats increased with the progression of arthritis gradually. Both peaks of arthritis score and SUV appeared at 21 days after the first immune injection, then the arthritis score and SUV of knee joints decreased slowly. The arthritis scores of knee joints in RA rats were positively correlated with their SUV changes. The MR images were confirmed by the histopathological studies.

Conclusion
PET/CT can detect the earliest molecular metabolism changes of RA, and MR imaging can follow up the dynamical anatomical changes of RA, all of which indicated that PET/CT and MR imaging may be applied as useful tools to monitor the progress of RA.
Role of Lactobacillus in the prevention of Clostridium difficile -associated diarrhea: a meta-analysis of randomized controlled trials
Authors: WU Zhi-juan , DU Xi , ZHENG Jian 
Published: January 2024

Background

Clostridium difficile-associated diarrhea (CDAD) is a major public health problem because of significant morbidity and mortality, and many clinicians pay attention to Lactobacillus as a potentially effective treatment. The purpose of this meta-analysis was to evaluate the efficacy of Lactobacillus in the prevention of CDAD.

Methods
The databases MEDLINE, the Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, National Institutes of Health, CNKI, VIP, and Wanfang data were searched to locate all reported randomized controlled trials (RCT) from 1990 to December 2012. Only RCT in English and Chinese using Lactobacillus for the prevention of documented CDAD were considered for study inclusion. The data was analyzed by Review Manager and SPSS software.

Results
Seven placebo-controlled RCTs that evaluated the prevention of CDAD, which included 1486 subjects, accorded with inclusion and exclusion criteria. The mean age of the subjects ranged from 4.15 to 64.75 years and the proportion of male subjects ranged from 42.0% to 59.1%. The total daily dose of Lactobacillus ranged from 1.2×109-1.2×1012 colony-forming units (CFU). A low risk of bias was attributed to two studies and four studies evaluated a medium-level risk of bias. The combined risk ratio (RR) of developing CDAD was significantly lower in subjects who received Lactobacillus compared with subjects who received placebo (RR 0.38, 95% confidence interval (CI) 0.22-0.67). A combination regimen of Lactobacillus acidophilus (L. acidophilus) and Lactobacillus casei (L. casei) (RR 0.05, 95% CI 0.01-0.36) showed significant effect sizes for the prevention of CDAD, while single regimens of Lactobacillus plantarum (L. plantarum) and Lactobacillus rhamnosus (L. rhamnosus) did not. Across all trials, positive significant effects of Lactobacillus were observed in the elderly subgroup (RR 0.05, 95% CI 0.01-0.36). Whether the 1×1012-9×1012 CFU/d Lactobacillus could prevent CDAD significantly or not was unclear.

Conclusion
There is a sufficient evidence to recommend Lactobacillus (L. acidophilus and L. casei) as a prevention therapy for CDAD.
Oxaliplatin-based combination chemotherapy is still effective for the treatment of recurrent and platinum-resistant epithelial ovarian cancer: results from a single center
Authors: ZHANG Guo , LI Xiao-ping , LIU Bing-jie , WANG Jian-liu , WANG Shi-jun , CUI Heng , WEI Li-hui 
Published: January 2024

Background
Combination paclitaxel and carboplatin is currently a first-line regimen for ovarian cancer. However, many patients develop tumor recurrence or drug resistance to this regimen. The study aims to investigate the effectiveness and safety of an oxaliplatin + epirubicin + ifosfamide regimen for the treatment of recurrent and drug-resistant epithelial ovarian cancer.

Methods
A retrospective analysis of 73 patients with recurrent and drug-resistant ovarian cancer was performed; 38 cases of them received oxaliplatin + epirubicin + ifosfamide regimens (IAP group), 35 patients received non-oxaliplatinbased chemotherapy regimens (control group). The therapeutic effects and side effects of the oxaliplatin + epirubicin + ifosfamide regimen were analyzed and summarized. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare progression-free and overall survival between the two groups.

Results
Of the 38 patients in the IAP group, 14 patients (36.84%) achieved complete remission, 12 (31.58%) achieved partial remission, 2 (5.26%) achieved stable disease and 10 (26.32%) developed progressive disease. The overall effective rate (complete or partial remission) of the IAP regime was 68.42%. While, of the 35 patients in the control group, 12 patients (34.29%) achieved complete remission, 3 (8.57%) achieved partial remission, 5 (14.29%) achieved stable disease and 15 (42.86%) developed progressive disease. The overall effective rate was 42.86%, which was lower than that in the IAP group (P=0.035, χ2=4.836). Progression-free survival was 9.5 months (0–64 months) in the IAP group vs. 3 months (0–74 months) in the non-oxaliplatin group (P=0.014 by Kaplan-Meier survival curves; HR=2.260; 95%CI 1.117–4.573; P=0.023 by Cox proportional hazards regression). Median overall survival was 46 months (9–124 months) in the IAP group vs. 35 months (9–108 months) in non-oxaliplatin group (P=0.018 by Kaplan-Meier survival curves; HR=2.272; 95% CI 1.123–4.598; P=0.022 by Cox proportional hazards regression). In IAP group, 15.79% (6/38) of the patients suffered grade III-IV bone marrow arrest. The main non-hematological side effects of the IAP regimen included nausea and vomiting (21.05%, 8/38), peripheral neurotoxicity (15.79%, 6/38) and hepatic or renal lesions (2.63%, 1/38). The main side effects of the two chemotherapy regimens showed no statistical difference.

Conclusion
The oxaliplatin-based IAP regimen is potentially effective for salvage chemotherapy in patients with recurrent and drug-resistant ovarian cancer, with a better therapeutic effect and tolerable side effects.
Analysis of transforming growth factor β signaling in chronic rhinosinusitis
Authors: LI Yun-chuan , AN Yun-song , WANG Tong , ZANG Hong-rui 
Published: January 2024

Background
It has been reported that there is a significant difference in the local tissue concentration of transforming growth factor (TGF)-β1 between chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis without nasal polyps (CRSwNP) patients. TGF-β has been reported to play an important role in regulating epithelial cell repair in lower airway remodeling and may be a critical factor involved in the remodeling process of chronic rhinosinusitis (CRS).

Methods
Ethmoidal mucosal samples collected from CRS and healthy control patients were analyzed for TGF-β1, TGF-β receptor I, TGF-β receptor II, Smad3, phospho-Smad3, Smad7, and Smad anchor for receptor activation by Western blotting analysis. The proliferation of sinonasal epithelial cells at baseline and after TGF-β1 and/or EGF stimulation was evaluated by the MTT assay.

Results
In CRSsNP, TGF-β1, TGF-β receptor I, TGF-β receptor II, and Smad3 protein levels were significantly higher than controls. In CRSwNP, TGF-β1, Smad3, and pSmad3 protein levels were significantly lower than controls. Smad7 protein was significantly higher in CRS than controls. In vitro experiments demonstrated that the baseline proliferation levels of sinonasal epithelial cells were lower in CRS than controls.

Conclusions
CRSwNP is characterized by a lower level of TGF-signaling compared with the control. In CRSsNP, although the upstream signaling of TGF-β was enhanced, the high Smad7 protein expression may restrain the downstream signaling components (e.g., pSmad3) and the TGF-β antiproliferative effect on sinonasal epithelium. The difference in the local tissue concentration of TGF-β1 between CRSsNP and CRSwNP patients did not result in significant differences in epithelial proliferation.
Stenting of iliac vein obstruction following catheter-directed thrombolysis in lower extremity deep vein thrombosis
Authors: MENG Qing-you , LI Xiao-qiang , JIANG Kun , QIAN Ai-min , SANG Hong-fei , RONG Jian-jie , DUAN Peng-fei , ZHU Li-wei 
Published: January 2024

Background
Catheter-directed thrombolysis (CDT) for deep venous thrombosis (DVT) of the lower extremity has good effect, but whether iliac vein stent placement after thrombolytic therapy is still controversial. The goal of this study was to evaluate the efficacy of stent placement in the iliac vein following CDT in lower extremity DVT.

Methods
This was a single-center, prospective, randomized controlled clinical trial. After receiving CDT, the major branch of the distal iliac vein was completely patent in 155 patients with lower extremity DVT, and 74 of these patients with iliac vein residual stenosis of >50% were randomly divided into a control group (n=29) and a test group (n=45). In the test group, stents were implanted in the iliac vein, whereas no stents were implanted in the control group. We evaluated the clinical indicators, including patency of the deep vein, C in CEAP classification, Venous Clinical Severity Score (VCSS), and Chronic Venous Insufficiency Questionnaire (CIVIQ) Score.

Results
All patients had postoperative follow-up visits for a period of 6–24 months. Venography or color ultrasound was conducted in subjects. There was a significant difference between the patency rate at the last follow-up visit (87.5% vs. 29.6%) and the 1-year patency rate (86.0% vs. 54.8%) between the test and control groups. The change in the C in CEAP classification pre- and post-procedure was significantly different between the test and control groups (1.61±0.21 vs. 0.69±0.23). In addition, at the last follow-up visit, VCSS and CIVIQ Score were both significantly different between the test and control groups (7.57±0.27 vs. 0.69±0.23; 22.67±3.01 vs. 39.34±6.66, respectively).

Conclusion
The stenting of iliac vein obstruction following CDT in lower extremity DVT may increase the patency of the deep vein, and thus provides better efficacy and quality of life.
Association between C-reactive protein gene +1059 G/C polymorphism and the risk of coronary heart disease: a meta-analysis
Authors: LI Cong-sheng , GUO Bi-rong , GUO Zeng , YANG Jing , ZHENG Hou-feng , WANG Ai-ling 
Published: January 2024

Background
C-reactive protein (CRP) gene +1059 G/C polymorphism has been reported to be associated with coronary heart disease (CHD) risk, but the results remain inconclusive. This meta-analysis was therefore conducted to clarify these controversies.

Methods
A comprehensive search was conducted to identify all case control studies on the association between CRP gene +1059 G/C polymorphism and CHD risk. All the related studies were further strictly selected according to the inclusion criteria. Meta-analysis was performed with STATA 10.1 (StataCorp, USA). The association was assessed by odds ratio (OR) and 95% confidence interval (CI); both Begg's funnel plot and Egger's regression test were used to assess the publication bias.

Results
This meta-analysis on a total of 13 studies comprising 6316 CHD cases and 4467 controls showed no significant association between CRP gene +1059 G/C polymorphism and CHD risk in the overall study (for C/C+C/G vs. G/G: OR=1.01, 95% CI=0.81-1.25, P=0.96; for C/C vs. C/G+G/G: OR=1.17, 95% CI=0.77-1.77, P=0.47; for C/C vs. G/G: OR=1.17, 95% CI=0.77-1.77, P=0.47; for C allele vs. G allele: OR=1.01, 95% CI=0.81-1.24, P=0.96). However, in the subgroup analysis by ethnicity, the results showed significant association between CRP gene +1059 G/C polymorphism and CHD risk among Caucasians (for C/C vs. G/G: OR=2.54, 95% CI=1.13-5.72, P=0.02; C/C vs. C/G+G/G: OR=2.45, 95% CI=1.09-5.51, P=0.03), but not among Asians and Africans (P >0.05).

Conclusion
CRP gene +1059 G/C polymorphism may be associated with increased CHD risk among Caucasians and more evidences need to validate the conclusion.