The causal effects of circulating cytokines on sepsis: a Mendelian randomization study.

Background: In observational studies, sepsis and circulating levels of cytokines have been associated with unclear causality. This study used Mendelian randomization (MR) to identify the causal direction between circulating cytokines and sepsis in a two-sample study. Methods: An MR analysis was performed to estimate the causal effect of 41 cytokines on sepsis risk. The inverse-variance weighted random-effects method, the weighted median-based method, and MR-Egger were used to analyze the data. Heterogeneity and pleiotropy were assessed using MR-Egger regression and Cochran's Q statistic. Results: Genetically predicted beta-nerve growth factor (OR = 1.12, 95% CI [1.037-1.211], P = 0.004) increased the risk of sepsis, while RANTES (OR = 0.92, 95% CI [0.849-0.997], P = 0.041) and fibroblast growth factor (OR = 0.869, 95% CI [0.766-0.986], P = 0.029) reduced the risk of sepsis. These findings were robust in extensive sensitivity analyses. There was no clear association between the other cytokines and sepsis risk. Conclusion: The findings of this study demonstrate that beta-nerve growth factor, RANTES, and fibroblast growth factor contribute to sepsis risk. Investigations into potential mechanisms are warranted.

Synthesis of Fe3O4core/MIL-100(Fe) shell nanocomposites for tumor chemo-ferroptosis combination therapy and MR imaging.

The application of both chemotherapy and ferrotherapy together has shown great potential in increasing the effectiveness of cancer treatment. To achieve such a combination, we herein have synthesized Fe3O4core/MIL-100(Fe) shell nanocomposites (FM) that can be used for tumor chemo-ferroptosis combination therapy. In these nanocomposites, the anticancer drug 10-hydroxycamptothecin (HCPT) and iron ions could be co-delivered into tumors. On one hand, the released HCPT molecules can enter the cell nucleus and bind with DNA, resulting in induction of tumor cell apoptosis. On the other hand, the iron ions could react with H2O2leading to the production of ROS through the Fenton reaction, thereby triggering tumor cell ferroptosis. Consequently, a superior antitumor effect was achieved through the combination of the apoptosis and ferroptosis. Additionally, the Fe3O4core endowed FM with high performance for magnetic resonance imaging, which further provided novel avenues for imaging guidance therapy. Therefore, we anticipate that application of these nanocomposites could have great potential in the field of tumor therapy.

Differences in pulmonary nodular consolidation and pulmonary cavity among drug-sensitive, rifampicin-resistant and multi-drug resistant tuberculosis patients: the Guangzhou computerized tomography study.

Background: Pulmonary nodular consolidation (PN) and pulmonary cavity (PC) may represent the two most promising imaging signs in differentiating multidrug-resistant (MDR)-pulmonary tuberculosis (PTB) from drug-sensitive (DS)-PTB. However, there have been concerns that literature described radiological feature differences between DS-PTB and MDR-PTB were confounded by that MDR-PTB cases tend to have a longer history. This study seeks to further clarify this point. Methods: All cases were from the Guangzhou Chest Hospital, Guangzhou, China. We retrieved data of consecutive new MDR cases [n=46, inclusive of rifampicin-resistant (RR) cases] treated during the period of July 2020 and December 2021, and according to the electronic case archiving system records, the main PTB-related symptoms/signs history was ≤3 months till the first computed tomography (CT) scan in Guangzhou Chest Hospital was taken. To pair the MDR-PTB cases with assumed equal disease history length, we additionally retrieved data of 46 cases of DS-PTB patients. Twenty-two of the DS patients and 30 of the MDR patients were from rural communities. The first CT in Guangzhou Chest Hospital was analysed in this study. When the CT was taken, most cases had anti-TB drug treatment for less than 2 weeks, and none had been treated for more than 3 weeks. Results: Apparent CT signs associated with chronicity were noted in 10 cases in the DS group (10/46) and 9 cases in the MDR group (10/46). Thus, the overall disease history would have been longer than the assumed <3 months. Still, the history length difference between DS patients and MDR patients in the current study might not be substantial. The lung volume involvement was 11.3%±8.3% for DS cases and 8.4%±6.6% for MDR cases (P=0.022). There was no statistical difference between DS cases and MDR cases both in PN prevalence and in PC prevalence. For positive cases, MDR cases had more PN number (mean of positive cases: 2.63 vs. 2.28, P=0.38) and PC number (mean of positive cases: 2.14 vs. 1.38, P=0.001) than DS cases. Receiver operating characteristic curve analysis shows, PN ≥4 and PC ≥3 had a specificity of 86% (sensitivity 25%) and 93% (sensitivity 36%), respectively, in suggesting the patient being a MDR cases. Conclusions: A combination of PN and PC features allows statistical separation of DS and MDR cases.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.

NIR Light-Activated and RGD-Conjugated Ultrasmall Fe/PPy Nanopolymers for Enhanced Tumor Photothermal Ferrotherapy and MR Imaging.

Iron-based nanomaterials have shown great promise for tumor ferrotherapy in recent years. However, nanoparticle-induced ferroptosis has low therapeutic efficacy owing to unsatisfactory Fenton reaction activity in a typical tumor microenvironment. In this study, NIR light-activated Fe/PPy-RGD nanopolymers were developed to combine photothermal therapy and ferrotherapy and achieve enhanced antitumor activity. Importantly, Fe/PPy-RGD exhibited excellent therapeutic performance under NIR light activation both in vitro and in vivo. Under irradiation with NIR light, the heat generated by Fe/PPy-RGD not only induced a therapeutic photothermal effect but also enhanced the release of iron ions and the Fenton reaction by inducing ferroptosis. Additionally, by virtue of RGD conjugation and its ultrasmall size, Fe/PPy-RGD could effectively accumulate at tumor sites in living mice after systemic administration and could be monitored via MR imaging. Hence, this study provides a promising approach for integrating ferrotherapy with photothermal therapy to achieve enhanced tumor treatment.

Effects of external environment on promoter methylation of PIK3R5 and related pathway regulation in steroid-induced femoral head necrosis.

BACKGROUND: Steroid-induced Avascular Necrosis of the Femoral Head (SANFH) is a condition characterized by the necrosis of the femoral head caused by long-term or high-dose hormone usage. Studies have shown that the PI3K/AKT pathway plays a crucial regulatory role in the development of SANFH. The aim of this study is to determine how external environmental factors induce changes in endogenous hormone levels, how these changes lead to steroid-induced femoral head necrosis, and the interrelationship between the changes in PIK3R5 promoter methylation levels and the regulation of the associated signaling pathways. METHODS: Femoral head samples underwent molecular sequencing analysis. Candidate genes were screened by differential gene analysis and functional enrichment analysis.Methylation level of candidate gene PIK3R5 was verified by methylation-specific PCR(MS-PCR). SANFH model was constructed in New Zealand white rabbits, and the model results were verified by magnetic resonance imaging (MRI) and haematoxylin-eosin (HE) staining.The expression of PIK3R5, PI3K and AKT in rabbit models and human specimens was verified by real-time fluorescence quantitative PCR(RT-qPCR) and Western Blot(WB), respectively. RESULTS: Human femoral head sequencing results indicate distinct differences in the methylation level and mRNA expression of PIK3R5 in SANFH. MS-PCR results showed the methylation level of SANFH patients was significantly higher than that of the control group (P < 0.01). The RT-qPCR results showed that PIK3R5 and PI3K expression levels in the SANFH group were lower than those in the control group (P < 0.05), and the WB experiment results were consistent with the RT-qPCR results. The MRI and HE staining results showed that the rabbit model of SANFH was successfully constructed, and the results of RT-qPCR and WB were consistent with the results of human tissues. CONCLUSION: During the occurrence and development of SANFH, PIK3R5 gene regulates the PI3K/AKT pathway through methylation modification, promotes the oxidative stress response of cells, and accelerates the disease process.

Two birds with one stone: Ratiometric sensing platform overcoming cross-interference for multiple-scenario detection and accurate discrimination of tetracycline analogs.

Environmental pollution caused by tetracycline antibiotics (TCs) is a major concern for public health worldwide. Trace detection and reliable discrimination of tetracycline and its analogs are consequently essential to determine the distribution characteristics of various tetracycline family members. Here, a dual-response sensor was constructed by integrating the fluorescence emission of fluorescein isothiocyanate (FITC) doped SiO2 and Eu3+. A portable Lab-on-Paper device is further fabricated through probe immobilization, which allows convenient visual detection of tetracycline using a smartphone. In addition, for the coexistence of multiple tetracycline analogs, dimensionality reduction via principal component analysis is applied to the spectra, realizing accurate differentiation of the four most widely used tetracycline analogs (tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC), and doxycycline (DOX)). The dual-response nanoplatform enabled a wide-gamut color variation crossing from green to red, with limit of detection (LOD) of 2.9 nM and 89.8 nM for spectrometer- and paper-based sensors, respectively. Analytical performance was examined in multiple real samples, including food, environmental, and biological settings, confirming robust environmental adaptability and resistance. Compared to previous TC sensors, this method has several notable improvements, including improved ecological safety, accessibility, reproducibility, practicality, and anti-cross-interference capacity. These results highlight the potential of the proposed "two birds with one stone" strategy, providing an integrated methodology for synchronous quantitative detection and derivative identification toward environmental contaminants.

Polymorphisms and gene expression of Notch4 in pulmonary tuberculosis.

Background: Tuberculosis (TB) is a serious public health problem to human health, but the pathogenesis of TB remains elusive. Methods: To identify novel candidate genes associated with TB susceptibility, we performed a population-based case control study to genotype 41SNPs spanning 21 genes in 435 pulmonary TB patients and 375 health donors from China. Results: We found Notch4 gene rs206018 and rs422951 polymorphisms were associated with susceptibility to pulmonary tuberculosis. The association was validated in another independent cohort including 790 TB patients and 1,190 healthy controls. Moreover, we identified that the rs206018 C allele was associated with higher level of Notch4 in PBMCs from pulmonary TB patients. Furthermore, Notch4 expression increased in TB patients and higher Notch4 expression correlated with the severer pulmonary TB. Finally, we explored the origin and signaling pathways involved in the regulation of Notch4 expression in response to Mycobacterium tuberculosis (Mtb) infection. We determine that Mtb induced Notch4 and its ligand Jagged1expression in macrophages, and Notch4 through TLR2/P38 signaling pathway and Jagged1 through TLR2/ERK signaling pathway. Conclusion: Our work further strengthens that Notch4 underlay an increased risk of TB in humans and is involved in the occurrence and development of TB, which could serve as a novel target for the host-targeted therapy of TB.

Controllable synthesis of variable-sized magnetic nanocrystals self-assembled into porous nanostructures for enhanced cancer chemo-ferroptosis therapy and MR imaging.

Magnetic-based nanomaterials are promising for cancer diagnosis and treatment. Herein, we develop a self-assembled approach for the preparation of a porous magnetic nanosystem, DOX/Mn(0.25)-Fe3O4-III NPs, which can simultaneously achieve chemotherapy, ferroptosis therapy and MRI to improve the therapeutic efficacy. By tuning its porous structures, whole particle sizes and compositions, this nanosystem possesses both a high drug loading capacity and excellent Fenton reaction activity. Owing to the synergetic catalysis effect of iron and manganese ions, the Fenton catalytic activity of Mn(0.25)-Fe3O4-III NPs (K cat = 1.2209 × 10-2 min-1) was six times higher than that of pure porous Fe3O4 NPs (K cat = 1.9476 × 10-3 min-1), making them greatly advantageous in ferroptosis-inducing cancer therapy. Moreover, we found out that these Mn(0.25)-Fe3O4-III NPs show a pH-dependent Fenton reaction activity. At acidic tumorous pH, this nanosystem could catalyze H2O2 to produce the cytotoxic ˙OH to kill cancer cells, while in neutral physiological conditions it decomposed H2O2 into biosafe species (H2O and O2). In vivo studies demonstrated that DOX/Mn(0.25)-Fe3O4-III NPs exhibited a significant synergistic anticancer effect of combining chemotherapy and ferroptosis therapy and effective T2-weighted MRI with minimal side effects. Therefore, this porous magnetic nanoplatform has a great potential for combined diagnosis and therapy in future clinical applications.

Real-Time MRI Monitoring of GelMA-Based Hydrogel-Loaded Kartogenin for In Situ Cartilage Regeneration.

The cartilage has poor ability to mount a sufficient healing response. Herein, kartogenin (KGN), an emerging stable non-protein compound with the ability to recruit bone marrow mesenchyme stem cells (BMSCs) to promote chondrogenic differentiation, was grafted onto dopamine-Fe(III) chelating nanoparticles, followed by involving a gelatin- and dextran-based injectable hydrogel to mimic the extracellular matrix to promote cartilage repair. The in vitro results demonstrated that KGN underwent long-term sustained release behavior and availably promoted the deep migration of BMSC cells in yielding hydrogels. Furthermore, in vivo New Zealand white rabbits' cartilage defect model repairing results showed that cartilage defect obtained significant regeneration post operation in the 12th week, and the defect edge almost disappeared compared to adjacent normal cartilage tissue. Meanwhile, the T2-weighted magnetic resonance imaging (MRI) property resulting from dissociative Fe (III) can significantly monitor the degradation degree of the implanted hydrogels in the defect site. This integrated diagnosis and treatment system gives insight into cartilage regeneration.

One-Pot Synthesis of Ag/Quaternary Ammonium Salt Co-Decorated Mesoporous Silica Nanoparticles for Synergistic Treatment of Cancer and Bacterial Infections.

Developing drug delivery nanosystems with both anticancer and antibacterial effects is of great clinical value. Herein, we report a facile approach to synthesize Ag and quaternary ammonium salt (QAS) co-decorated mesoporous silica nanoparticles (MSNs), namely, Ag/QAS-MSNs, for synergistic treatment of cancer and bacterial infections. In vitro studies demonstrated that Ag/QAS-MSNs not only had a strong antibacterial activity against the bacterial pathogens but also could efficiently induce cancer cell death through an apoptotic pathway. Moreover, in vivo combination therapy with Ag and QAS in Ag/QAS-MSNs was also tested in a nude mouse tumor model, and a significant synergistic anticancer effect, which is superior to that obtained by therapy with Ag-MSNs or QAS-MSNs alone, was achieved. Such excellent anticancer and antibacterial activity of Ag/QAS-MSNs could be attributed to the synergistic effect of Ag ions and QAS. Thus, Ag/QAS-MSNs have a promising future as potent anticancer agents with high antibacterial performance.

Dynamic tracking of p21 mRNA in living cells by sticky-flares for the visual evaluation of the tumor treatment effect.

Monitoring the expression level of the intracellular tumor suppressor gene p21 mRNA is essential to reveal the progress and prognosis of a tumor. Methods widely reported for the detection of p21 mRNA are the real-time polymerase chain reaction and Northern blot. However, these methods only detect mRNA in vitro and cannot realize the in situ monitoring of the p21 mRNA expression level in living cells. Additionally, the sensor for the real-time tracking and monitoring of the p21 mRNA location without the help of a transfection reagent in living cells is still limited. Herein, a novel sticky-flare was constructed for the dynamic monitoring of the temporal and spatial variations of p21 mRNA in living cells. The nanoprobe consists of AuNP, a recognition sequence modified with Cy5, and a thiol-modified DNA sequence. The thiol oligonucleotide strand could act partially complementary to the Cy5-modified oligonucleotide strand to form a double-stranded DNA linked to AuNP, resulting in the fluorescence quenching of Cy5 due to the energy transfer from Cy5 to the gold sphere. In the presence of p21 mRNA, the Cy5-modified recognition nucleic acid specifically bound to p21 mRNA to form a more stable double chain and escaped from the gold sphere, leading to the recovery of red fluorescence. Our method is better than other methods in its ability to quantify the spatial distribution and expression level of p21 mRNA in living cells and discriminate various tumor cell lines with different p21 mRNA expression levels by the naked eye. Particularly, the sticky-flare probe used in this assay could allow the visual evaluation of the tumor treatment effect and the determination of the tumor progression stage by enabling monitoring of the relative expression level of p21 mRNA in tumor cells after cisplatin treatment. The method reported here is accurate, reliable and needs no auxiliary tools (transfection reagent), and thereby provides a promising route for the prognostic evaluation and drug development of cancer treatment in the future.

Analysis of the application of "psycho-cardiology" model in nursing care of acute stroke patients with depression.

OBJECTIVE: To evaluate the effect of "psycho-cardiology" model in nursing care of acute stroke patients with depression. METHODS: Seventy-eight acute stroke patients with depression were selected for this prospective study, and they were divided into two groups according to the random number table method. The control group (n=39) were given usual care, and the study group (n=39) were given nursing intervention of "psycho-cardiology" model in addition to usual care. The changes of mental state (Hamilton Depression Scale, HAMD; Hamilton Anxiety Scale, HAMA), the neurological function (National Institute of Health Stroke scale, NIHSS), and the cognitive function (Mini-Mental State Examination, MMSE), the prognostic indicator (Fugl-Meyer Assessment, FMA; Barthel Index, BI) were compared between the two groups before and after the intervention. The incidence of complications and nursing satisfaction were also compared between the two groups. RESULTS: After nursing, the scores of HAMA and HAMD in the study group were significantly lower than those in the control group (P<0.05). The NIHSS score of the study group was significantly lower than that of the control group (P<0.05). The score of MMSE in the study group was significantly higher than that of the control group (P<0.05). The scores of FMA and BI in the study group were significantly higher than those of the control group (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). The nursing satisfaction of the study group was significantly higher than that of the control group (P<0.05). CONCLUSION: Nursing intervention of "psycho-cardiology" model for acute stroke patients with depression can effectively alleviate the mental stress of patients, improve neurological function and cognitive function, reduce the occurrence of complications, improve prognosis and nursing satisfaction.

Theoretical Study on the Mechanism of the Acylate Reaction of ß-Lactamase.

Using density functional theory and a cluster approach, we study the reaction potential surface and compute Gibbs free energies for the acylate reaction of ß-lactamase with penicillin G, where the solvent effect is important and taken into consideration. Two reaction paths are investigated: one is a multi-step process with a rate-limit energy barrier of 19.1 kcal/mol, which is relatively small, and the reaction can easily occur; the other is a one-step process with a barrier of 45.0 kcal/mol, which is large and thus makes the reaction hard to occur. The reason why the two paths have different barriers is explained.

Identification of MMP1 and MMP2 by RNA-seq analysis in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the most common histologic subtype of laryngeal cancer characterized by a poor prognosis. Determining gene expression changes in LSCC should improve our understanding of putative risk factors and provide potential targets for therapy. OBJECTIVES: To assess differential gene expression between LSCC tissue and paired normal laryngeal tissue, and to provide gene targets for future studies of this type of laryngeal cancer. MATERIALS AND METHODS: Three paired-sample groups (tumor and normal tissue) from patients with laryngeal squamous cell carcinoma were analyzed by RNA sequencing (RNA-seq). RESULTS: The six cDNA libraries generated raw reads ranging from 15,195,586 to 21,443,488 counts. Changes in gene expression levels were determined in 40,205 of these counts, with 18,466 deferentially expressed genes in all three groups. Compared to normal tissue, the expression levels of MMP1 and MMP2 increased significantly in tumor tissue of patients with laryngeal squamous cell carcinoma. CONCLUSIONS: Whole transcriptome sequencing revealed that MMP1 and MMP2 are highly expressed in LSCC. These genes may be useful both as biomarkers for LSCC diagnosis and as targets for therapy, as well as for increasing our understanding of LSCC tumorigenesis.

MRI Enhancement and Tumor Targeted Drug Delivery Using Zn2+-Doped Fe3O4 Core/Mesoporous Silica Shell Nanocomposites.

Developing of multifunctional nanoplateforms for simultaneous accurate cancer detection and target therapy is essential in cancer treatment. Herein, we present a facile synthesis of DOX/MNPs-FA nanocomposites for high-performance MRI and tumor-targeted drug delivery. In such core-shell structured DOX/MNPs-FA nanocomposite, the high magnetism of iron oxide core can be tuned and achieved by controlling the Zn2+ dopant amount, making them suitable as excellent contrasts in T2-weighted MR imaging. The outer porous silica shell with large pores about 5.4 nm in diameter possesses high surface area and pore volume. Anticancer drug (DOX molecules) can be stored in the large pore channels and is triggered to be released under acidic condition (pH 4-6). Importantly, the presence of folic acid on the surface of DOX/MNPs-FA allows the targeted delivery of the DOX to tumor cells, and therefore improves tumor chemotherapy efficiency. Our in vitro studies also demonstrated that DOX/MNPs-FA could be efficiently internalized into HeLa cells via the folate receptor-mediated endocytosis, and generate a greater cytotoxicity toward cancer cells compared to free DOX and DOX/MNPs. Therefore, these DOX/MNPs-FA multifunctional nanocomposites have great potential applications for simultaneous tumor diagnosis and targeted chemotherapy.

Toward an Expert Level of Lung Cancer Detection and Classification Using a Deep Convolutional Neural Network.

BACKGROUND: Computed tomography (CT) is essential for pulmonary nodule detection in diagnosing lung cancer. As deep learning algorithms have recently been regarded as a promising technique in medical fields, we attempt to integrate a well-trained deep learning algorithm to detect and classify pulmonary nodules derived from clinical CT images. MATERIALS AND METHODS: Open-source data sets and multicenter data sets have been used in this study. A three-dimensional convolutional neural network (CNN) was designed to detect pulmonary nodules and classify them into malignant or benign diseases based on pathologically and laboratory proven results. RESULTS: The sensitivity and specificity of this well-trained model were found to be 84.4% (95% confidence interval [CI], 80.5%-88.3%) and 83.0% (95% CI, 79.5%-86.5%), respectively. Subgroup analysis of smaller nodules (<10 mm) have demonstrated remarkable sensitivity and specificity, similar to that of larger nodules (10-30 mm). Additional model validation was implemented by comparing manual assessments done by different ranks of doctors with those performed by three-dimensional CNN. The results show that the performance of the CNN model was superior to manual assessment. CONCLUSION: Under the companion diagnostics, the three-dimensional CNN with a deep learning algorithm may assist radiologists in the future by providing accurate and timely information for diagnosing pulmonary nodules in regular clinical practices. IMPLICATIONS FOR PRACTICE: The three-dimensional convolutional neural network described in this article demonstrated both high sensitivity and high specificity in classifying pulmonary nodules regardless of diameters as well as superiority compared with manual assessment. Although it still warrants further improvement and validation in larger screening cohorts, its clinical application could definitely facilitate and assist doctors in clinical practice.

Effects of altered CXCL12/CXCR4 axis on BMP2/Smad/Runx2/Osterix axis and osteogenic gene expressions during osteogenic differentiation of MSCs.

This study investigated the effects of altered CXCL12/CXCR4 axis on the bone morphogenetic protein 2 (BMP-2)/Smad/runt-related transcription factor 2 (Runx2)/Osterix (Osx) signal axis and osteogenic gene expression during osteogenic differentiation of mesenchymal stem cells (MSCs), to gain understanding of the link between migration and osteogenic differentiation signal axis and MSCs osteogenic differentiation mechanisms. The pHBAd-MCMV- CXCL12-GFP vector (Ad-CXCL12) was constructed and quantitative polymerase chain reaction (qPCR)/western blotting used to determine CXCL12 expression in Ad-CXCL12-transfected MSCs. MSCs were treated with Ad-CXCL12 and AMD3100 (CXCL12 inhibitor) to detect BMP-2/Smad/Runx2/Osterix expression, bone sialoprotein (BSP), osteocalcin (OCN) and osteopontin (OPN) mRNA expression, and alkaline phosphatase (ALP) activity. PCR and sequencing confirmed successful construction of Ad-CXCL12. qPCR and enzyme-linked immunosorbent assay indicated that Ad-CXCL12 transfection promoted CXCL12 expression in MSCs. At 72 hours, Runx2 and Osterix, and Smad1/5/8 mRNA and protein expressions were significantly higher in the Ad-CXCL12 group than in the control group (P < 0.01). At 1 and 2 weeks, ALP activity and BSP mRNA expression were significantly higher in the Ad-CXCL12 group than in the control group (P < 0.01), respectively. No significant difference in OCN and OPN mRNA expression was determined between Ad-CXCL12 and control groups (P > 0.05). At 3 weeks, no significant difference in mineralized nodule staining was observed between groups (P > 0.05). Changes in the CXCL12/CXCR4 migration axis affected the BMP-2/Smad/Runx2/Osterix axis and BSP, OCN and OPN mRNA expression in early-stage, but not mid-/latestage, MSCs osteogenic differentiation, therefore affecting the ability of MSCs to undergo osteogenic differentiation.

Potential mechanisms underlying the Runx2 induced osteogenesis of bone marrow mesenchymal stem cells.

Bone marrow derived mesenchymal stem cells (BM-MSCs) belong a type of pluripotent stem cells and can be induced to differentiate into osteoblasts (OB). Runt-related transcription factor 2 (Runx2) is an osteogenesis specific transcription factor and plays an important role in osteogenesis of BM-MSCs. It can promote the expression of osteogenesis related genes, regulate cell cycle progression, improve bone microenvironment and affect functions of chondrocytes and osteoclasts, which have involvement of a large amount of signal molecules including TGF-ß, BMP, Notch, Wnt, Hedgehog, FGF and microRNA. In this paper, we summarize the mechanisms underlying the Runx2 induced osteogenesis of BM-MSCs.

[The effects of different mechanical ventilation flow model on the peak airway pressure during cardiopulmonary resuscitation].

OBJECTIVE: To observe the method of mechanical ventilation in the chest compressions during cardiopulmonary resuscitation (CPR), and to explore the influence of the flow pattern selection of square-wave and decelerating-wave on airway pressure of patients. METHODS: A prospective self-pairing study was conducted. Forty patients undergoing CPR admitted to Department of Emergency of Lishui City Central Hospital from January 2011 to February 2013 were enrolled. Using Respironics Eisprit ventilator, the working mode and parameters of ventilator were set reasonably according to previous research, while the chest compressions was performed in a stable state by the same doctor,. Each patient received different flow, waves, including square-wave and decelerating-wave, and the highest peak airway pressure was recorded as a pair of data when the time-pressure and time-flow waveform were frozen. Two pairs of data by different doctors were collected in each patient. Eighty pairs of data from 40 patients were collected for statistical analysis by paired t test. RESULTS: The highest peak airway pressure of decelerating-wave was (38.15 ± 5.99) cmH2O (1 cmH2O=0.098 kPa), which was (5.71 ± 1.98) cmH2O lower than that of square wave [(43.86 ± 6.68) cmH2O] with significantly statistical difference (t=22.010, P=0.000). 73.75% patients undergoing square wave with peak airway pressure over 40 cmH2O were found, but only 45.00% patients were found in decelerating-wave. CONCLUSIONS: Because decelerating-wave used in mechanical ventilation during CPR can obviously reduce the peak airway pressure, the occurrence of barotrauma, and the probability of triggering high pressure ventilator alarm, and improve the compliance of ventilator, so decelerating-wave is more reasonable than square-wave.