bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of nuclear factor-κB activity enhanced chemosensitivity to cisplatin in human lung adeno-carcinoma A549 cells under chemical hypoxia conditions
Authors: LI Fang , HUANG Li , SU Xiao-li , GU Qi-hua , HU Cheng-ping
Published: January 2024

Background

Tumor hypoxia, one of the features of solid tumors, is associated with chemo-resistance. Recently, nuclear factor-κB (NF-κB) was found to be activated during hypoxia. However, the impact of NF-κB activation on chemo-resistance during hypoxia remains unknown.

Methods

Human lung adenocarcinoma A549 cells were transfected with NF-κB p65siRNA and treated with cobalt chloride (CoCl2) to mimic hypoxia in the presence or absence of cisplatin. NF-κB expression was measured by Western blotting, immune-fluorescence and real-time PCR. Hypoxia-inducible factor-1α (HIF-1α) and Bcl-2 expression were determined by Western blotting. Cell apoptosis and survival with half-maximum inhibitory concentration (IC50) of cisplatin were determined by Annexin V-FITC/PI and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), respectively.

Results

Exposure of A549 cells to CoCl2 increased nuclear HIF-1α protein expression, and enhanced NF-κB p65 protein nuclear accumulation (the mark of NF-κB activation) in a time and dose dependant manner. CoCl2 did not promote apoptosis in A549 cells; on the contrary, it reduced cisplatin-induced apoptosis and increased the IC50 of cisplatin. However, when we inhibited CoCl2-induced activation of NF-κB through NF-κB p65siRNA, cisplatin-induced apoptosis was increased and IC50 of cisplatin was reduced to levels similar to those in control cells. Meanwhile, CoCl2-induced Bcl-2 over-expression was down-regulated in the presence of cisplatin when NF-κB activity was inhibited.

Conclusion

Up-regulating Bcl-2 might be involved in NF-κB activation induced resistance to cisplatin in A549 cells under CoCl2-induced chemical hypoxia.
Impact of the origin of sinus node artery on recurrence after pulmonary vein isolation in patients with paroxysmal atrial fibrillation
Authors: ZHANG Zhi-jun , CHEN Ke , TANG Ri-bo , SANG Cai-hua , LOPES LAO Edmundo Patricio , YAN Qian , HE Xiao-nan , DU Xin , LONG De-yong , YU Rong-hui , DONG Jian-zeng , MA Chang-sheng
Published: January 2024

Background

Major atrial coronary arteries, including the sinus node artery (SNA), were commonly found in the areas involved in atrial fibrillation (AF) ablation and could cause difficulties in achieving linear block at the left atrial (LA) roof. The SNA is a major atrial coronary artery of the atrial coronary circulation. This study aimed to determine impact of the origin of SNA on recurrence of AF after pulmonary vein isolation (PVI) in patients with paroxysmal AF.

Methods

Seventy-eight patients underwent coronary angiography for suspected coronary heart disease, followed by catheter ablation for paroxysmal AF. According to the origin of SNA from angiographic findings, they were divided into right SNA group (SNA originating from the right coronary artery) and left SNA group (SNA originating from the left circumflex artery). Guided by an electroanatomic mapping system, circumferential pulmonary vein ablation (CPVA) was performed in both groups and PVI was the procedural endpoint. All patients were followed up at 1, 3, 6, 9 and 12 months post-ablation. Recurrence was defined as any episode of atrial tachyarrhythmias (ATAs), including AF, atrial flutter or atrial tachycardia, that lasted longer than 30 seconds after a blanking period of 3 months.

Results

The SNA originated from the right coronary artery in 34 patients (43.6%) and the left circumflex artery in 44 patients (56.4%). Freedom from AF and antiarrhythmic drugs (AADs) at 1 year was 67.9 % (53/78) for all patients. After 1 year follow-up, 79.4% (27/34) in right SNA group and 59.1% (26/44) in left SNA group (P=0.042) were in sinus rhythm. On multivariate analysis, left atrium size (HR=1.451, 95%CI: 1.240-1.697, P <0.001) and a left SNA (HR=6.22, 95%CI: 2.01-19.25, P=0.002) were the independent predictors of AF recurrence.

Conclusions

The left SNA is more frequent in the patients with paroxysmal AF. After one year follow-up, the presence of a left SNA was identified as an independent predictor of AF recurrence after CPVA in paroxysmal AF.
Pattern of instent neointimal formation compared to native atherosclerosis in the coronary bifurcation lesions: volumetric intravascular ultrasound analysis
Authors: XU Jian-qiang , Song Young Bin , Hahn Joo-Yong , Choi Seung-Hyuk , Choi Jin-Ho , LU Cheng-zhi , Lee Sang Hoon , Hong Kyung Pyo , Park Jeung Euy , Gwon Hyeon-Cheol
Published: January 2024

Background

No clinical study has systematically analyzed and compared circumferential neointimal and plaque distribution of stent neointimal proliferation and in native atherosclerotic plaques. This study aimed to investigate and compare the pattern of instent neointimal formation and native atherosclerosis in the coronary bifurcation lesions by volumetric analysis using systematic intravascular ultrasound (IVUS).

Methods

We examined bifurcation lesions in native coronary artery (plaque group, n=102) and stented bifurcations at 9-month follow-up (neointima group, n=51) using volumetric IVUS analysis of both the main vessel (MV) and side branch (SB). Three 5-mm segments were analyzed; the proximal MV (MVp), distal MV (MVd) and SB ostium (SBo). For each segment, volumetric analysis was performed in each of four quadrants (divided according to the branch takeoff and the geometric center of the lumen); carinal, epicardial, abcarinal, and myocardial. The eccentricity index was defined as the ratio of the abcarinal plaque (or neointimal) volume to the carinal plaque (or neointimal) volume.

Results

The plaque distribution differed significantly between the four quadrants, with the largest in the abcarinal quadrant, followed by the myocardial, epicardial, and carinal quadrants. The distribution of neointima was similar in the MV, but the four quadrants in the SB did not differ significantly. The eccentricity indices of both the MVd (P <0.001) and SBo (P=0.001) were significantly higher for the plaque group than the neointima group.

Conclusions

The distribution of neointimal proliferation seems to have a similar pattern to that of atherosclerotic plaque in native coronary arteries, particularly in the main vessel, but the trend is less prominent.
Can “Hybrid stent implantation” improve long-term safety without adversely affecting efficacy when treating multilesion coronary artery disease in the drug-eluting stent era?
Authors: ZHANG Dong , XU Bo , DOU Ke-fei , YANG Yue-jin , CHEN Ji-lin , QIAO Shu-bin , WANG Yang , LI Jian-jun , QIN Xue-wen , YAO Min , LIU Hai-bo , WU Yong-jian , CHEN Jue , YUAN Jin-qing , YOU Shi-jie , LI Wei , GAO Run-lin
Published: January 2024

Background

Though drug-eluting stent (DES) almost solved a problem of restenosis, safety issues related to stent thrombosis are still the major concern of DES. We hypothesized that hybrid stent implantation may decrease the use of DES, probably improving the long-term safety but not affecting efficacy adversely when treating multilesion coronary artery disease in the DES era.

Methods

From April 2004 to October 2006, 848 patients with multilesion disease underwent hybrid stent implantation. During the same period 5647 patients with multilesion coronary heart disease were treated by exclusive DES implantation in Fu Wai Hospital. According to propensity score matching, we chose 823 pairs of patients with multileison coronary artery disease for inclusion into our study. We obtained the 24-month clinical outcome including death, myocardial infarction (MI), thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE, the composite of death, MI, and TVR). We used Cox's proportional-hazard models to assess relative risks of all the outcome measures after propensity match.

Results

At 24 months, patients in the hybrid stent implantation group showed a significantly higher risk of TLR (8.39% vs. 3.28%, HR 2.38, 95% CI: 1.50-3.70), TVR (11.07% vs. 6.32%, HR 1.61, 95% CI: 1.15-2.27) and MACE (13.75% vs. 8.75%, HR 1.37, 95% CI: 1.02-1.85). No significant difference was apparent in terms of mortality (1.22% vs. 1.70%, HR 0.55, 95% CI: 0.24-1.25), MI (1.95% vs. 2.31%, HR 0.73, 95% CI: 0.37-1.42), or thrombosis (definite+probable) (0.73% vs. 1.58%, HR 0.40, 95% CI: 0.15-1.05).

Conclusions

In patients with multilesion coronary artery disease, the exclusive DES implantation was associated with significantly lower risks of TLR, TVR and MACE, and the hybrid stent implantation did not result in any significant improvements regarding safety issues. Prospective studies are needed to confirm our results.
Molecular mechanism of indirubin-3′-monoxime and Matrine in the reversal of paclitaxel resistance in NCI-H520/TAX25 cell line
Authors: LUO Su-xia , DENG Wen-ying , WANG Xin-feng , Hui-fang LÜ , HAN Li-li , CHEN Bei-bei , CHEN Xiao-bing , LI Ning
Published: January 2024

Background

Multidrug resistance (MDR) is a main reason for paclitaxel (TAX) treatment failure. Indirubin-3′-monoxime (IRO) and Matrine are traditional Chinese medicines, which may reverse the resistance of tumor cells to some chemotherapy drugs, but the relationship between paclitaxel resistance and Matrine is still unclear. The aim of this study was to explore the potential molecular mechanism of IRO and Matrine in reversal of TAX resistance.

Methods

In this study, MTT assay was used to measure the non-cytotoxic dosage of IRO and Matrine on NCI-H520/TAX25 cells and determine the reversal extent of TAX resistance under non-toxic doses. In addition, RT-PCR and Western blotting were used to evaluate the mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 cells using semi-quantitative methods.

Results

There was no obvious inhibition on sensitive cell strains and drug-resistant strains, when the final concentration was at lest 4 μmol/L for IRO and 100 μmol/L for Matrine. So 4 μmol/L of IRO and 100 μmol/L of Matrine were considered as the reversal dosage. When 4 μmol/L of IRO or 100 μmol/L of Matrine were used together with TAX, the sensitivity to TAX increased evidently in NCI-H520/TAX2 cells; the reversal rate of IRO and Matrine was about 1.92 (43.56/22.6 nmol/L) and 1.74 (43.56/25.0 nmol/L), respectively. The mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 decreased significantly (P <0.05) after addition of IRO or Matrine in TAX treatment, compared to that of TAX treatment alone.

Conclusion

The decrease in both mRNA expression and protein level of survivin, Oct-4, and Sox-2 might be the molecular mechanism, by which IRO and Matrine mediate the reversal of TAX resistance.
Elective single blastocyst transfer is more suitable for normal responders than for high responders
Authors: WU Ke-liang , ZHAO Hai-bin , LIU Hui , ZHONG Wan-xia , YU Guan-ling , CHEN Zi-jiang
Published: January 2024

Background

Embryo quality and receptivity of the endometrium are two factors that determine the results of in vitro fertilization/intra-cytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). There is no consensus of the optimal transfer strategy for normal responders or high responders. The current study aimed to find the optimal transfer strategy for different subgroups of patients.

Methods

From April 2010 to December 2010, patients who meet the following criteria were included in this study; primary infertility, female age <35 years, FSH level on female cycle day 2-3 ≤12 mIU/ml, at least six good quality embryos available on day three.The clinical outcomes using different transfer strategies between normal responders and high responders were reviewed and compared.

Results

For the normal responders, the clinical pregnancy rate of day three double-embryo transfer (DET) was comparable to that of day five elective single blastocyst transfer (eSBT), 64.04% vs. 60.33% (P>0.05). For the high responders, the clinical pregnancy rate of day five eSBT was significantly lower than that of day three DET, 43.35% vs. 57.21% (P<0.05). For the high responders, the rates of clinical pregnancy and implantation in frozen-thawed embryo transfer (FET) cycles were notably higher than in eSBT cycles (64.56% vs. 43.35% and 62.11% vs. 43.35% respectively) (P<0.05).

Conclusions

For normal responders, eSBT might be an applicable strategy to reduce multiple pregnancy rates while maintaining acceptable overall pregnancy rates. And in order to reduce multiple pregnancies and increase the chance of pregnancy of high responders, FET may be a preferable strategy.
Change of CMTM7 expression, a potential tumor suppressor, is associated with poor clinical outcome in human non-small cell lung cancer
Authors: LIU Qiang , SU Yu , JIANG Guan-chao , ZHOU Zu-li , LIU Bao-cai , BU Liang , YANG Fan , QIAO Fang , WANG Jun
Published: January 2024

Background

CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) located at 3p22.3, is a frequent deletion site and a tumor suppressor gene (TSG) locus in many cancer, which suggests CMTM7 may be a potential TSG. The aim of this study was to investigate the correlations of CMTM7 expression and survival rate in patients with non-small-cell lung cancer (NSCLC).

Methods

Surgical specimens of 180 cases with pathologically confirmed NSCLC were grouped into 18 tissue microarray slides. CMTM7 expression in these specimens were detected by immunohistochemistry staining and representative cases were confirmed by Western blotting. Univariate and multivariate analyses were performed to identify the association of CMTM7 expression with pathological features and survival of patients with NSCLC.

Results

A total of 78.9% of the 180 patients had variations of CMTM7 protein expression, either up-regulated or down-regulated. Univariate analysis showed that the patients' survival rate after surgery was highly correlated with CMTM7 expression (P=0.0091). In addition, prognostic factors were examined by multivariate Cox regression analysis, and results suggested that CMTM7 expression was a unique prognostic factor in NSCLC survival.

Conclusions

The CMTM7 expression may be related to survival of patients with NSCLC and a unique prognostic factor. CMTM7 may play an important role in NSCLC development.
A single-site retrospective study of pediatric arterial ischemic stroke etiology, clinical presentation, and radiologic features
Authors: SUN Dan , WU Xiao-man , WANG Zeng-wu , JIN Run-ming , LIU Zhi-sheng , LIU Fan , HUANG Sui , WANG Hai-qin , HU Jia-sheng
Published: January 2024

Background

Stroke occurs upon obstruction of cerebral blood circulation and is clinically characterized by sudden onset symptoms. Advanced age is the main risk factor of stroke, but cases of pediatric stroke have been rarely reported. This study aimed to determine the etiology, clinical presentation, and radiologic features of neurological deficit for pediatric arterial ischemic stroke (PAIS).

Methods

The medical records of 42 PAIS patients (age range: 9 months to 13 years) treated at Wuhan Children's Hospital between July 2007 and January 2011 were retrospectively reviewed. Infarction location was first determined by craniocerebral computed tomography and magnetic resonance (MR) imaging. The stenotic or occluded main cerebral arteries and/or branches were determined by MR angiography and digital subtraction angiography.

Results

The majority of the 42 PAIS cases (66.7%, n=28) were ≤3 years old (vs. >3 years old: 33.3%, n=14; P<0.05), but the male: female ratio was similar in both groups (P>0.05). The most frequently reported signs and symptoms for both age groups were limited physical activity followed by convulsions and delirium, but convulsions were more prevalent in children ≤3 years-old. Children>3 years-old mainly experienced the limited physical activity symptoms, including hemiparalysis, aphasia, and ataxia. For all 42 cases, the most frequent etiologies were infections (38.1%, n=16), iron deficiency anemia (16.7%, n=7), and moyamoya syndrome (11.9%, n=5). The predominant infarcts among all cases were middle cerebral artery (63.6%, n=21) and basal ganglia (64.3%, n=27).

Conclusions

PAIS occurs more frequently in younger children and this group most frequently presents with convulsion as the initial symptom. The overall etiologies of PAIS may be different from those of adult stroke and the involved regions may be distinguishing features of PAIS or its different forms, but more research is required.
Reversible changes in aqueous outflow facility, hydrodynamics, and morphology following acute intraocular pressure variation in bovine eyes
Authors: ZHU Jing-ying , YE Wen , WANG Ti , GONG Hai-yan
Published: January 2024

Background

Elevated intraocular pressure (IOP) is primarily due to increased aqueous outflow resistance, but how aqueous outflow resistance is generated and regulated are still not fully understood. The aim of this study is to determine whether changes in outflow facility, outflow pattern, and morphology following acute IOP elevation were reversible when the IOP was returned to a normal level in bovine eyes using a two-color tracer technique to label outflow patterns within the same eye.

Methods

Twelve fresh enucleated bovine eyes were perfused with Dulbecco's phosphate buffer saline (PBS) containing 5.5 mmol/L glucose (DBG) at 30 mmHg first to establish the baseline outflow facility followed by a fixed volume of red fluorescent microspheres (0.5 μm, 0.002% v/v). After the red tracer being replaced with DBG in the anterior chamber, perfusion was continued at 7 mmHg with the same volume of green tracer, followed by a fixative. In two control groups, the eyes were constantly perfused at either 30 mmHg (n=6) or 7 mmHg (n=6) using the same methods. The outflow facility (C, μl·min·-1mmHg-1), was continuously recorded. Confocal images were taken along the inner wall (IW) of the aqueous plexus (AP) in frontal sections. The percent of the effective filtration length (PEFL, PEFL=IW length exhibiting tracer labeling/total length of IW) was measured. Sections with AP were processed and examined by light microscopy. The total length of IW and the length exhibiting separation (SL) in the juxtacanalicular connective tissue (JCT) were measured. A minimum of eight collector channel (CC) ostia per eye were analyzed for herniations.

Results

In the experimental (30-7 mmHg) group, the outflow facility was significantly higher at 7 mmHg ((4.81±1.33) μl·min·-1mmHg-1) than that at 30 mmHg ((0.99±0.15) μl·min·-1mmHg-1, P=0.002), corresponding to a significant increase in the PEFL (P=0.0003). The percent of CC ostia exhibiting herniations in the experimental group ((67.40±8.90) μl·min·-1mmHg-1) decreased significantly compared to that in the control at 30 mmHg ((94.44±3.33) μl·min·-1mmHg-1, P=0.03), but higher than that in the control at 7 mmHg ((29.43±4.60) μl·min·-1mmHg-1, P=0.01). Washout-associated separation between the IW and JCT was found by light microscopy and percent separation length (PSL, PSL=SL/total length of IW) was decreased in the control at 30 mmHg compared to that in the experimental group and control at 7 mmHg.

Conclusions

The pressure-induced morphological and hydrodynamic changes were reversible. Changes (collapse of AP, separation between the JCT and IW, and herniation into CC ostia) influence the effective filtration area that regulates outflow facility.
Improved outcomes from transradial over transfemoral access in primary percutaneous coronary intervention for patients with acute ST-segment elevation myocardial infarction and upstream use of tirofiban
Authors: Zhang Qi , Qiu Jian-ping , Zhang Rui-yan , Hu Jian , Yang Zhen-kun , Ding Feng-hua , Du Run , Zhu Tian-qi , Zhang Jian-sheng , Shen Wei-feng
Published: January 2024

Background Transradial access has been increasingly used during primary percutaneous coronary intervention (PCI) for patients with acute ST-segment elevation myocardial infarction (STEMI) in last decade. Clinical benefits of upstream use of tirfiban therapy in STEMI patients treated by primary PCI have been reported. We investigated the merits of transradial vs. transfemoral access in primary PCI for STEMI patients with upstream use of tirofiban.

Methods Patients with STEMI treated with tirofiban between December 2006 and October 2012 then by primary PCI were compared between transradial (n=298) and transfemoral (n=314) access. Baseline demographics, angiographic and PCI features and primary endpoint of major adverse cardiac events (MACE) at 30-day clinical follow-up were recorded.

Results Baseline and procedural characteristics were comparable between the two groups, apart from more patients in transradial group had hypertension and were treated by thrombus aspiration during primary PCI. Significantly fewer MACE occurred in the transradial group (5.4%) compared with the transfemoral group (9.9%) at 30-day clinical follow-up. Major bleeding events at 30-day clinical follow-up were 0 in transradial group and in 2.9% of transfemoral group. Multivariate analysis confirmed transradial approach as an independent negative predictor of 30-day MACE (HR 0.68; 95% CI 0.35-0.91; P=0.03).

Conclusions Using transradial approach in primary PCI for acute STEMI infarction patients treated with tirofiban was clearly beneficial in reducing bleeding complications and improving 30-day clinical outcomes.
Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor-induced interleukin-6 expression via human antigen R
Authors: XU Jin , SU Xin , SHI Jia-Xin , SUN He , WU Ting , SHI Yi
Published: January 2024

Background

Human antigen R (HuR) is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) and HuR participate in the tumor necrosis factor (TNF)-induced expression of interleukin-6 (IL-6).

Methods

Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNA-mediated knockdown of MK2 or HuR. Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points. The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D. Finally, after knockdown of MK2, the cytoplasmic expression of HuR protein was analyzed using Western blotting.

Results

MK2 or HuR knockdown decreased both the mRNA and protein expression of IL-6 in TNF-stimulated cells. In MK2 knockdown cells, the half-life of IL-6 mRNA was reduced to 36 minutes, compared with 67 minutes in the control group. In HuR knockdown cells, the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes. Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm.

Conclusions

MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR.
Role of mitochondrial damage during cardiac apoptosis in septic rats
Authors: Li Li , Hu Bang-chuan , Chen Chang-qin , Gong Shi-jin , Yu Yi-hua , Dai Hai-wen , Yan Jing
Published: January 2024

Background

Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats.

Methods

Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity.

Results

Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge.

Conclusions

Septic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.
Propofol may protect PC12 cells from β-amyloid25-35 induced apoptosis through the GSK-3β signaling pathway
Authors: Zhang Rui , Xu Jie , Liu Yan-yong , Zuo Ping-ping , Yang Nan , Ji Chao , Wang Yun , Wang Hui , Wu An-shi , Yue Yun
Published: January 2024

Background

There are two major pathological hallmarks of Alzheimer's disease. One is the progressive accumulation of beta-amyloid (Aβ) in the form of senile plaques; the other is hyperphosphorylated tau, causing neuronal apoptosis. Some inhalation anesthetics, such as isoflurane and desflurane, have been suggested to induce Aβ accumulation and cause AD-like neuropathogenesis. Whether intravenous anesthetics have similar effects is still unclear. We therefore set out to determine the relationship between propofol and AD-like pathogenesis.

Methods

PC12 cells were cultured in serum-free medium for 12 hours prior to drug treatment. Various concentrations from 5 μmol/L to 80 μmol/L of aggregated Aβ25-35 were added to determine a proper concentration for further study. After exposure to 10 μmol/L Aβ25-35 alone or with 20 μmol/L propofol for 6 hours, PC12 cell viability was determined by MTT assay. Western blotting and immunocytochemical staining were performed to observe the protein expression of the Bcl-2 family, tau phosphorylation at different sites, and tau protein kinases and phosphatases.

Results

Aβ25-35 induced a decrease in PC12 cell viability in a dose-dependent manner. Exposure to 10 μmol/L Aβ25-35 for 6 hours resulted in the mild cell survival, accompanied by a decline in Bcl-2, and an increase in phosphorylation of GSK-3β and tau at different sites. Compared with the Aβ25-35 group, cells treated with propofol alone showed no significant difference, while cells co-incubated with propofol and Aβ25-35 showed a significantly higher survival rate (P <0.01 or P <0.05). Tau phosphorylation at Ser396, Ser404 and Thr231 and the level of GSK-3β in PC12 cells increased after exposure to 10 μmol/L Aβ25-35. Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation.

Conclusions

These data indicate that propofol may protect PC12 cells from Aβ25-35-induced apoptosis and tau hyperphosphorylation through the GSK-3β pathway, therefore it may be a safer anesthesia for AD and elderly patients.
Serum sclerostin levels associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis
Authors: XU Xiao-juan , SHEN Lin , YANG Yan-ping , LU Fu-rong , ZHU Rui , SHUAI Bo , LI Cheng-gang , WU Man-xiang
Published: January 2024

Background

Sclerostin, expressed exclusively by osteocytes, is a negative regulator of bone formation. To gain insights into the action of sclerostin in postmenopausal osteoporosis, we evaluated serum sclerostin levels in postmenopausal women and investigated its possible associations with bone turnover markers in patients with postmenopausal osteoporosis.

Methods

We detected serum sclerostin, and measured lumbar spine bone mineral density in 650 Chinese postmenopausal women. We also assessed serum levels of β-isomerized C-terminal crosslinking of type I collagen, intact N-terminal propeptide of type I collagen, N-mid fragment of osteocalcin, 25-hydroxyvitamin D, and estradiol.

Results

Serum sclerostin levels were lower in postmenopausal osteoporotic women compared with non-osteoporotic postmenopausal women ((38.79±7.43) vs. (52.86±6.69) pmol/L, P <0.001). Serum sclerostin was positively correlated with lumbar spine bone mineral density (r=0.391, P <0.001) and weakly negatively correlated with β-isomerized C-terminal crosslinking of type I collagen, intact N-terminal propeptide of type I collagen, N-mid fragment of osteocalcin (r= −0.225, P <0.001; r= −0.091, P=0.046; r= −0.108, P=0.018; respectively) in postmenopausal osteoporosis. There was no significant association of serum sclerostin with age, body mass index, 25-hydroxyvitamin D, and estradiol (r= −0.004, P=0.926; r=0.067, P=0.143; r=0.063, P=0.165; r= −0.045, P=0.324; respectively).

Conclusion

Sclerostin may be involved in the pathogenesis of postmenopausal osteoporosis and may play a role in bone turnover.
Impact of imipenem treatment on colonic mycobiota in rats with double-hit sepsis
Authors: Guan Jun , Liu Shao-ze , Lin Zhao-fen , Li Wen-fang , Liu Xue-feng , Chen De-chang
Published: January 2024

Background

Broad-spectrum antibiotic administration promotes intestinal colonization of exogenous fungal pathogens in healthy animals and has been recognized as one of the risk factors of invasive fungal infection in clinical settings. It is unclear whether broad-spectrum antibiotic treatment would change the intestinal mycobiota without exogenous fungal challenge in the context of sepsis.

Methods

We established a rat model of double-hit sepsis using burn injury and endotoxin challenge. Rats with burn injury or double-hit sepsis received imipenem treatment for 3 days or 9 days, and their colon contents were sampled for selective fungal culture and isolation counts.

Results

Imipenem treatment promoted the overgrowth of the commensal fungus Geotrichum capitatum in rats with burn injury. Imipenem treatment also promoted colon colonization by exogenous fungi in rats with burn injury and double-hit sepsis, including Trichosporon cutaneum, Candida albicans, Candida krusei, and Candida glabrata. A longer duration of imipenem treatment had a stronger impact on colon colonization by exogenous fungi.

Conclusion

Imipenem treatment facilitates the overgrowth of commensal fungi and colonization by exogenous, potentially pathogenic fungi in the colons of rats with burn injury or double-hit sepsis.
Human decorin regulates proliferation and migration of human lung cancer A549 cells
Authors: LIANG Shuo , XU Jin-fu , CAO Wei-jun , LI Hui-ping , HU Cheng-ping
Published: January 2024

Background

Decorin is a small leucine-rich proteoglycan and it plays an important role in regulation of cell growth and migration in various tumor cell lines. Decorin was found down-regulated in non-small cell lung cancer tissue and may be involved in regulation of lung cancer development.

Methods

In this study, lentivirus-mediated RNA interference and over expression were employed to change the expression levels of decorin in lung cancer A549 cells. We tested the cell cycle of A549 cells and the expression of transforming growth factor (TGF)-β1, cyclin D1, epidermal growth factor receptor (EGFR), P53, and P21.

Results

We found that up-regulation of decorin could inhibit proliferation, block cell cycle at G1 and decrease invasive activity of A549 cells. Moreover, we also show that up-regulation of decorin induced significant decreases of TGF-β1, cyclin D1 expression, phosphorylation of EGFR, and increases of P53 and P21 expression. Opposite results were observed in A549 cells with down-regulation of decorin.

Conclusion

Our results suggest that decorin is a key regulator involved in proliferation and migration of A549 cells.
In vitro cartilage production using an extracellular matrix-derived scaffold and bone marrow-derived mesenchymal stem cells
Authors: ZHAO Yan-hong , YANG Qiang , XIA Qun , PENG Jiang , LU Shi-bi , GUO Quan-yi , MA Xin-long , XU Bao-shan , HU Yong-cheng , ZHAO Bin , ZHANG Li , WANG Ai-yuan , XU Weng-jing , MIAO Jun , LIU Yue
Published: January 2024

Background

Cartilage repair is a challenging research area because of the limited healing capacity of adult articular cartilage. We had previously developed a natural, human cartilage extracellular matrix (ECM)-derived scaffold for in vivo cartilage tissue engineering in nude mice. However, before these scaffolds can be used in clinical applications in vivo, the in vitro effects should be further explored.

Methods

We produced cartilage in vitro using a natural cartilage ECM-derived scaffold. The scaffolds were fabricated by combining a decellularization procedure with a freeze-drying technique and were characterized by scanning electron microscopy (SEM), micro-computed tomography (micro-CT), histological staining, cytotoxicity assay, biochemical and biomechanical analysis. After being chondrogenically induced, the induction results of BMSCs were analyzed by histology and Immunohisto-chemistry. The attachment and viability assessment of the cells on scaffolds were analyzed using SEM and LIVE/DEAD staining. Cell-scaffold constructs cultured in vitro for 1 week and 3 weeks were analyzed using histological and immunohistochemical methods.

Results

SEM and micro-CT revealed a 3-D interconnected porous structure. The majority of the cartilage ECM was found in the scaffold following the removal of cellular debris, and stained positive for safranin O and collagen II. Viability staining indicated no cytotoxic effects of the scaffold. Biochemical analysis showed that collagen content was (708.2±44.7) μg/mg, with GAG (254.7±25.9) μg/mg. Mechanical testing showed the compression moduli (E) were (1.226±0.288) and (0.052±0.007) MPa in dry and wet conditions, respectively. Isolated canine bone marrow-derived stem cells (BMSCs) were induced down a chondrogenic pathway, labeled with PKH26, and seeded onto the scaffold. Immunofluorescent staining of the cell-scaffold constructs indicated that chondrocyte-like cells were derived from seeded BMSCs and excreted ECM. The cell-scaffold constructs contained pink, smooth and translucent cartilage-like tissue after 3 weeks of culture. We observed evenly distributed cartilage ECM proteoglycans and collagen type II around seeded BMSCs on the surface and inside the pores throughout the scaffold.

Conclusion

This study suggests that a cartilage ECM scaffold holds much promise for in vitro cartilage tissue engineering.
Is prophylactic somatostatin effective to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis or hyperamylasemia? A randomized, placebo-controlled pilot trial
Authors: WANG Zi-kai , YANG Yun-sheng , CAI Feng-chun , WANG Yong-hua , SHI Xiao-lin , DING Chen , LI Wen
Published: January 2024

Background

Effects of prophylactic somatostatin on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and hyperamylasemia remain inconclusive. This study aimed to examine whether high-dose, long-term continuous infusion of somatostatin can reduce the incidence of PEP and post-ERCP hyperamylasemia.

Methods

This was a randomized, placebo-controlled pilot trial. One hundred and twenty-four patients scheduled for ERCP from December 2008 to May 2010 randomly received one of the following three interventions: pre-ERCP somatostatin (0.5 mg/h for 24 hours, starting 1 hour prior to ERCP; n=36), post-ERCP somatostatin (0.5 mg/h for 24 hours, starting 1 hour after ERCP; n=47), or placebo (saline for 24 hours, starting 1 hour prior to ERCP; n=41). Serum amylase and lipase concentrations were measured 1 to 3 hours prior to ERCP and 6, 24, and 48 hours after ERCP.

Results

The three groups did not differ in age, gender, medical history, or ERCP procedure (catheterization using contrast or guidewire, pancreatic duct visualization, procedure time, or procedure type). The rate of PEP was 13.7% (17/124) in the overall study sample and 16.7% (6/36), 10.6% (5/47), and 14.6% (6/41) in the pre-ERCP somatostatin, post-ERCP somatostatin, and placebo groups, respectively (P=0.715). The rate of post-ERCP hyperamylasemia was 19.4% (7/36), 21.3% (10/47), and 46.3% (19/41) in the pre-ERCP somatostatin, post-ERCP somatostatin, and placebo groups, respectively (P=0.011).

Conclusions

High-dose, long-term continuous infusion (0.5 mg/h for 24 hours) of somatostatin, performed as either a pre- or post-ERCP, can reduce the incidence of hyperamylasemia, but not PEP.
Device related complications of the Coflex interspinous process implant for the lumbar spine
Authors: ZANG Lei , DU Peng , HAI Yong , SU Qing-jun , LU Shi-bao , LIU Tie
Published: January 2024

Background

Coflex, a type of interspinous process implant, can provide intervertebral dynamic stability for surgical segments and effectively relieve lumbocrural pain. However, few studies have described therapeutic strategies and the avoidance of Coflex implant complications.

Methods

Coflex implant complications in this study included intraoperative or postoperative spinous process fracture, aggravated postoperative lumbocrural pain, dislodgment and malposition. The complications were analyzed, and therapeutic strategies were applied according to the specific complication. The Visual Analogue Scale and Oswestry Disability Index scores were evaluated by using the paired-samples test from SPSS 12.0.

Results

Conservative treatment was provided to seven patients who experienced aggravated lumbocrural pain even though their devices remained in the correct position, and pedicle screw treatment was used as an alternative in four cases. The Visual Analogue Scale and Oswestry Disability Index scores showed evident improvement in these patients. The Visual Analogue Scale and Oswestry Disability Index scores of two patients who underwent revision were also improved.

Conclusions

Coflex implants should be avoided in patients with osteoporosis, a narrow interspinous space and intervertebral coronal spondylolysis, or sagittal instability. Furthermore the device choice, depth of implantation, and clamping intensity should be appropriate. Conservative treatment can be provided to patients with symptoms if the device remains in the correct position; however, revisions and salvages should be undertaken with internal fixation of pedicle screws for patients with device malposition, intraoperative implantation failure, or device intolerance.
Triple antithrombotic therapy versus double antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients requiring chronic oral anticoagulation: a meta-analysis
Authors: Jayswal Saheb K , DENG Bing-qing , HU Qing-song , XIE Shuang-lun , GENG Deng-feng , NIE Ru-qiong
Published: January 2024

Background

Whether an addition of OAC to double antiplatelet therapy for patients with an indication of chronic oral anticoagulation undergoing PCI-S may improve clinical outcomes is still debated. This meta-analysis aimed to update and re-compare the benefits and risks of triple antithrombotic therapy (TT) with double anti-platelet therapy (DAPT) after in patients who requiring oral anticoagulation after percutaneous coronary interventions with stenting (PCI-s).

Methods

Ten reports of observational retrospective or prospective studies were retrieved, including a total of 6296 patients, follow-up period ranging from 1 year to 2 years.

Results

Baseline characteristics were similar in both groups. The main finding of this study is the overall incidence of major adverse cardiovascular events (MACE), myocardial infarction (MI) and stent thrombosis was comparable between two groups. Patients with TT was associated with significant reduction in ischemic stroke (OR: 0.27; 95% CI: 0.13-0.57; P=0.0006) as compared to DAPT. We reaffirmed triple therapy significantly increased the risk of major bleeding (OR: 1.47; 95% CI: 1.22-1.78; P <0.0001) and minor bleeding (OR: 1.55; 95% CI: 1.07-2.24; P=0.02).

Conclusions

Triple therapy is more efficacious in reducing the occurrence of ischemic stroke in PCI-s patients with an indication of chronic oral anticoagulation (OAC), compared with DAPT. However, it significantly increased major and minor risk of bleeding. It is imperative that further prospective randomized controlled trials are required to define the best therapeutic strategy for patients with an indication of chronic OAC undergoing PCI-s.
Gender disparity in early death after ST-elevation myocardial infarction
Authors: ZHANG Bo , ZHANG Wei , HUANG Rong-chong , ZHANG Yan , LIU Jun , ZHENG Zheng-guo , JIANG Da-ming , SUN Yu-jiao , REN Li-na , ZHOU Xu-chen , QI Guo-xian
Published: January 2024

Background

Females with acute myocardial infarction (AMI) have a higher risk of adverse outcomes because of receiving less evidence-based medical care. Our aim was to investigate the gender disparity in early death after ST-elevation myocardial infarction (STEMI) in the current era.

Methods

A total of 1429 consecutive patients with STEMI in the Liaoning district were analyzed. We compared hospital care and cardiac event data by sex for in-patients with acute STEMI within 24 hours of symptom onset.

Results

In the emergency reperfusion group (n=754), in-hospital mortality occurred in 4.2% of the males and 11.2% of the females (P=0.001). In the non-emergency reperfusion group (n=675), in-hospital mortality occurred in 13.0% of the males and 22.9% of the females (P=0.001). Multivariate Logistic regression analysis revealed female sex as an independent risk factor of death for STEMI patients during hospitalization (OR=1.691, P=0.007). After controlling for patients who died within 24 hr after admission, female sex was no longer an independent risk factor (OR=1.409, P=0.259).

Conclusion

Female sex was an independent risk factor for in-hospital mortality of STEMI patients, which is explained by an excess of very early deaths.
Biocompatibility, biodegradation, and neovascularization of human single-unit platelet-rich fibrin glue: an in vivo analysis
Authors: Xiuwen Wu , Jianan Ren , Genhong Yao , Bo Zhou , Gefei Wang , Guosheng Gu , Jianfeng Luan , Jieshou Li
Published: January 2024

Background

The clinical applications of fibrin glue span over several surgical modalities. The aim of this study was to evaluate the biocompatibility and biodegradation of different formulations of platelet-rich fibrin glue in vivo and examine its effects on the neovascularization of wound sites.

Methods

Human-derived single-unit fibrin glue was prepared. Incisions were made on the backs of rats, and these were coated with homemade glues containing different concentrations of aminomethylbenzoic acid (Groups A-F) or commercial adhesives (Group G). A sham control group was included (Group H). The wounds were examined by histological analysis and immunohistochemistry at several time points.

Results

Successful wound closure was achieved in all groups by day 12. Acute inflammation occurred during the first six days, but gradually disappeared. The longest sealant duration was achieved using the lowest concentration of anti-fibrinolytic agent in a 1:10 volume ratio with cryoprecipitate. Expression levels of the platelet endothelial cell adhesion molecule-1 were significantly higher in Groups A and C compared to the control groups (Groups G and H) on day 3 (P <0.05).

Conclusions

Single-unit platelet-rich fibrin glue has excellent biocompatibility and is associated with the upregulation of neovascularization. The addition of aminomethylbenzoic acid could prevent the degradation of fibrin glue.
Establishment of a novel method for primary culture of normal human cervical keratinocytes
Authors: LIU Yu-zhen , LÜ Xiu-ping , PAN Zi-xuan , ZHANG Wei , CHEN Zhao-ri , WANG Hui , LIU Hua , ZHANG You-zhong
Published: January 2024

Background

Cervical keratinocytes are recovered at a low numbers and frequently associated with contaminating human fibroblasts which rapidly overgrow the epithelial cells in culture with medium supplemented with 10% fetal bovine serum (FBS). However, it is difficult to initiate keratinocyte cultures with serum-free keratinocyte growth medium alone because cell attachment can be poor. Therefore, the culture of these cells is extremely difficult. In this study, we described a modified culture medium and coated culture plastics for growing normal human cervical epithelial cells in vitro.

Methods

Normal cervical epithelial tissue pieces were obtained and digested with type I collagenase to dissociate the cells and a single cell suspension produced. The cells were cultured on plastic tissue culture substrate alone or substrate coated with collagen type I from rat tail, with modified keratinocyte serum-free medium (K-SFM) supplemented with 5% FBS. After attachment, the medium were replaced with K-SFM without FBS. The expression of basal keratins of the ectocervical epithelium, K5, K14 and K19 were assayed by immunofluorescence with monoclonal antibodies to identify the cell purity.

Results

Our results indicate that cells attached to the culture plastic more quickly in K-SFM supplemented with 5% FBS than in K-SFM alone, as well as to tissue culture plastic coated with collagen type I than plastic alone. The modified medium composed of K-SFM and 5% FBS combined with a specific tissue culture plastic coated with collagen type I from rat tail was the best method for culture of normal cervical epithelial cells. K5, K14 and K19 were assayed and keratinocyte purity was nearly 100%.

Conclusion

A novel, simple and effective method can be used to rapidly obtain highly purified keratinocytes from normal human cervical epithelium.
Left atrial minimum volume by real-time three-dimensional echocardiography as an indicator of diastolic dysfunction
Authors: LIN Qiong-Wen , WANG Wu-Gang , WU Wei-Chun , WANG Hao
Published: January 2024

Background

Left atrial (LA) maximum volume is becoming a prognostic biomarker for left ventricular (LV) diastolic dysfunction. However, we assessed LV diastolic function by measuring LA phasic volumes using real-time three-dimensional echocardiography (RT3DE) in patients with stable coronary artery disease (CAD).

Methods

Sixty-five stable CAD patients with normal LV ejection fraction (LVEF) were divided into three groups according to degree of coronary stenosis: control (n=15) with <50% stenosis as control group, mildS (n=25) with mild stenosis (50%-70%) and severeS (n=25) with >70% stenosis. LA phasic volumes and function were evaluated and compared using RT3DE and two dimensional echocardiography (2DE). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were examined. The correlations of RT3DE-derived parameters with other conventional indices were analyzed.

Results

Significant correlations between RT3DE and 2DE for LA volume measurements were: control, r=0.93; mildS, r=0.94; severeS, r=0.90 (all P <0.05). Patients with severe coronary stenosis presented higher NT-proBNP level, indices of LA minimum volume and volume before atrial contraction, but lower LA total emptying fraction (LAEF) and LAEFpassive. Significant correlations of RT3DE derived LA volume indices with E/E' (r=0.695) and NF-proBNP (r=0.630) level were found.

Conclusions

RT3DE derived, LA indices correlate well with NT-proBNP level and may be superior to 2DE measurements for the evaluation of LV diastolic dysfunction. Enlargement of LA minimum volume in stable CAD patients without systolic dysfunction appears earlier and may be better correlated with LV diastolic function than that of LA maximum volume.