Serum metabolomic profiling of patients with liver cirrhosis at different stages.

An accurate and non-invasive diagnosis of the clinical stage is critical for effectively managing liver cirrhosis. This study aimed to identify serum metabolite biomarkers and clinical features that may reliably predict high-risk cirrhosis. This cross-sectional study recruited 94 cirrhotic patients (70 for identification cohort, 24 for validation cohort) from Minhang Hospital Affiliated with Fudan University between 2018 and 2021, who were analyzed by targeted quantitative metabolomics technique. Baseline clinical characteristics were collected, and different stage cirrhosis classification was performed according to the presence or absence of decompensated events. Potential metabolite biomarkers were screened, and a model for predicting the decompensation stage was created. Finally, the incidence of decompensated outcomes was analyzed. A total of 560 metabolites were detected in the identification cohort. Indole-3-propionic acid (IPA) was the most significantly decreased metabolic biomarker in the decompensated group (P<0.01, |log2FC| >2), having the strongest correlation with hyaluronic acid (r=-0.50, P<0.01). It also performed well for differentiating decompensated cirrhosis with an area under the curve (AUC) of 0.79(0.75 at internal validation). Another diagnostic model consisting of indole-3-propionic acid, hemoglobin, and albumin showed better predictive performance with an AUC of 0.97 (0.91 at internal validation). Also, 31 (44.29%) patients developed decompensated events at a median follow-up of 22.76±15.24 months. The cumulative incidence of decompensated events based on IPA subgroups (IPA <39.67ng/ml and ≥39.67ng/ml) showed a significant difference (P<0.01). "Indole-3-propionic acid" and a diagnostic model of hemoglobin and albumin can non-invasively identify cirrhotic populations at risk for decompensation, aiding in future management of liver cirrhosis.

Feasibility study of Syngo iFlow in predicting hemodynamic improvement post-endovascular procedure in peripheral artery disease.

OBJECTIVE: This study endeavors to examine the feasibility of predicting the clinical outcomes of patients suffering from peripheral artery disease (PAD) who undergo endovascular intervention, by employing the Syngo iFlow technology. METHODS: Retrospectively enrolling 76 patients from December 2021 to May 2023, yielding a total of 77 affected limbs, this study employs clinical outcomes (improvement or otherwise) as the gold standard. Two physicians conducted visual assessments on both DSA and iFlow images to gauge patient improvement and assessed inter-observer consistency for each image modality. The Time to Peak (TTP) of regions of interest (ROI) at the femoral head, knee joint, and ankle joint was measured. Differences in pre- and post-procedure TTP were juxtaposed, and statistically significant parameter cutoff values were identified via ROC analysis. Employing these cutoffs for TTP classification, multivariate logistic regression and the C-statistic were utilized to assess the predictive value of distinct parameters for clinical success. RESULTS: Endovascular procedure exhibited technical and clinical success rates of 82.58 and 75.32%, respectively. Diagnostic performance of iFlow image visual assessment surpassed that of DSA images. Inter-observer agreement for iFlow and DSA image evaluations was equivalent (κ = 0.48 vs 0.50). Post-classification using cutoff values, multivariate logistic regression demonstrated the statistical significance of ankle joint TTP in post-procedure iFlow images of the endovascular procedure for clinical success evaluation (OR 7.21; 95% CI 1.68, 35.21; P = 0.010), with a C-statistic of 0.612. CONCLUSION: Syngo iFlow color-encoded imagery holds practical value in assessing the technical success of post-endovascular procedures, offering comprehensive lower limb arterial perfusion visualization. Its quantifiable parameters exhibit promising potential for prognosticating clinical success.

Diagnostic Potential of microRNA-122 for Stage Classification in Patients with HBV-Related Cirrhosis.

Objective: Previous studies have suggested that microRNA-122 has a relatively high diagnostic value for chronic viral hepatitis detection. In this study, we evaluated the diagnostic value of serum microRNA-122 in different stages of HBV-related cirrhosis，and serum microRNA-122 may serve as a potential biomarker for staging HBV related cirrhosis patients.. Methods: A total of 80 patients with HBV-related cirrhosis were included. Patients were characterized according to Child-Pugh score, laboratory parameters, and complications, and divided into compensated cirrhosis group and decompensated cirrhosis group. Wherein, the compensatory group for liver cirrhosis includes 21 patients, the compensatory group has 59 patients. Blood was collected from all patients, and RT-qPCR analyzed the expression levels of microRNA-122. Results: Serum microRNA-122 was decreased, while Child-Pugh score, Meld score, Prothrombin time, total bilirubin, and Direct bilirubin were higher in a decompensated group compared to the compensated group (all P < .05). For further stage classification, the mean serum microRNA-122 level was higher in stage 1 (11.3±5.1, compensated cirrhosis) compared to stage 2~5 (8.5±4.2, 4.9±1.0, 4.7±1.6, 3.5±1.1, decompensated cirrhosis, all P < .05). The expression of serum microRNA-122 independent of Child-Pugh score and complications, including ascites, varices, HCC (P > .05).However it was affected by Meld score and Prothrombin time (P < .05). Moreover, ROC analysis indicated microRNA-122 could differentiate compensated HBV-related cirrhosis (0.97 of AUC, P < .01). Furthermore, it could differentiate patients in stage 1 (compensated cirrhosis without esophageal varices) from HBV-related cirrhosis (0.91 of AUC, P < .01), with a sensitivity of 77.8% and satisfactory specificity of 88.7%. The significance of the relationship between the decrease in serum microRNA-122 levels and the stage of liver cirrhosis will be beneficial. Conclusion: Our results strongly support the diagnostic value of serum microRNA-122 as a potential biomarker of stage classification in patients with HBV-related cirrhosis, which could facilitate risk stratification and careful management. Provide new biomarkers for the diagnosis of patients with hepatitis B cirrhosis.

Prevalence and clonal diversity of carbapenem-resistant Klebsiella pneumoniae causing neonatal infections: A systematic review of 128 articles across 30 countries.

BACKGROUND: Klebsiella pneumoniae is the most common pathogen causing neonatal infections, leading to high mortality worldwide. Along with increasing antimicrobial use in neonates, carbapenem-resistant K. pneumoniae (CRKP) has emerged as a severe challenge for infection control and treatment. However, no comprehensive systematic review is available to describe the global epidemiology of neonatal CRKP infections. We therefore performed a systematic review of available data worldwide and combined a genome-based analysis to address the prevalence, clonal diversity, and carbapenem resistance genes of CRKP causing neonatal infections. METHODS AND FINDINGS: We performed a systematic review of studies reporting population-based neonatal infections caused by CRKP in combination with a genome-based analysis of all publicly available CRKP genomes with neonatal origins. We searched multiple databases (PubMed, Web of Science, Embase, Ovid MEDLINE, Cochrane, bioRxiv, and medRxiv) to identify studies that have reported data of neonatal CRKP infections up to June 30, 2022. We included studies addressing the prevalence of CRKP infections and colonization in neonates but excluded studies lacking the numbers of neonates, the geographical location, or independent data on Klebsiella or CRKP isolates. We used narrative synthesis for pooling data with JMP statistical software. We identified 8,558 articles and excluding those that did not meet inclusion criteria. We included 128 studies, none of which were preprints, comprising 127,583 neonates in 30 countries including 21 low- and middle-income countries (LMICs) for analysis. We found that bloodstream infection is the most common infection type in reported data. We estimated that the pooled global prevalence of CRKP infections in hospitalized neonates was 0.3% (95% confidence interval [CI], 0.2% to 0.3%). Based on 21 studies reporting patient outcomes, we found that the pooled mortality of neonatal CRKP infections was 22.9% (95% CI, 13.0% to 32.9%). A total of 535 neonatal CRKP genomes were identified from GenBank including Sequence Read Archive, of which 204 were not linked to any publications. We incorporated the 204 genomes with a literature review for understanding the species distribution, clonal diversity, and carbapenemase types. We identified 146 sequence types (STs) for neonatal CRKP strains and found that ST17, ST11, and ST15 were the 3 most common lineages. In particular, ST17 CRKP has been seen in neonates in 8 countries across 4 continents. The vast majority (75.3%) of the 1,592 neonatal CRKP strains available for analyzing carbapenemase have genes encoding metallo-ß-lactamases and NDM (New Delhi metallo-ß-lactamase) appeared to be the most common carbapenemase (64.3%). The main limitation of this study is the absence or scarcity of data from North America, South America, and Oceania. CONCLUSIONS: CRKP contributes to a considerable number of neonatal infections and leads to significant neonatal mortality. Neonatal CRKP strains are highly diverse, while ST17 is globally prevalent and merits early detection for treatment and prevention. The dominance of blaNDM carbapenemase genes imposes challenges on therapeutic options in neonates and supports the continued inhibitor-related drug discovery.

Targeting Diverse Wounds and Scars: Recent Innovative Bio-design of Microneedle Patch for Comprehensive Management.

Wounds and the subsequent formation of scars constitute a unified and complex phased process. Effective treatment is crucial; however, the diverse therapeutic approaches for different wounds and scars, as well as varying treatment needs at different stages, present significant challenges in selecting appropriate interventions. Microneedle patch (MNP), as a novel minimally invasive transdermal drug delivery system, has the potential for integrated and programmed treatment of various diseases and has shown promising applications in different types of wounds and scars. In this comprehensive review, the latest applications and biotechnological innovations of MNPs in these fields are thoroughly explored, summarizing their powerful abilities to accelerate healing, inhibit scar formation, and manage related symptoms. Moreover, potential applications in various scenarios are discussed. Additionally, the side effects, manufacturing processes, and material selection to explore the clinical translational potential are investigated. This groundwork can provide a theoretical basis and serve as a catalyst for future innovations in the pursuit of favorable therapeutic options for skin tissue regeneration.

The importance of temperature monitoring in predicting wound healing.

CONCLUSION: Upon wound formation, the wound temperature rises in the first 3-4 days until reaching its peak. It then falls at about one week after wound formation. In the second week after wound formation, the wound temperature decreases steadily to the baseline indicating a good wound condition and progression towards healing. While a continuous high temperature is often a sign of excessive inflammation or infection, which indicates urgent need of intervention and treatment.

Spatiotemporal variations in evapotranspiration and its influencing factors in the semiarid Hailar river basin, Northern China.

Evapotranspiration (ET) is a critical variable in the world's water cycle, and plays a significant role in estimating the impact of environmental change on the regional hydrothermal cycle. Moreover, as an essential of eco-hydrological processes, changes in ET may exceptionally impact the local climate and provide indicative information on the eco-system's functioning. The Hailar River Basin (HRB), located in northern China, is one of the most sensitive areas to climate warming. Under the influence of climate change in recent years, the vegetation dynamics of the basin have been significant and have had profound effects on the regional water cycle conditions and hydrological processes. The HRB is located in a semiarid region and ET is the main mode of water consumption. The ET response to climate change and vegetation dynamics is the focus of research on ecohydrological processes in this basin. In this study, a distributed hydrological model, the BTOPMC model, is used to evaluate the actual ET in the HRB from 1981 to 2020, based on in situ meteorological data as well as LAI data obtained by satellite remote sensing. The seasonal, interannual and spatial dynamics of ET were characterized. The contribution of meteorological factors to ET was calculated by sensitivity analysis and multiple linear regression analysis, and the predominant elements influencing the difference in ET in the HRB were also discussed. The results show that: (1) estimated ET values can clarify over 85% of the seasonal variation in the observed values (R2= 0.79, P < 0.001; R2= 0.84, P < 0.001), which demonstrates that the model has a high precision. (2) Over the past 40 years, the annual ET has shown a clear increasing trend and a large spatial heterogeneity in its spatial distribution, which is consistent with the trend of vegetation. It mainly shows that the eastern forest area is larger than the central forest-grass transition area and the western meadow steppe area. (3) Sensitivity and influential factor contribution analyses show that the main factor driving interannual variability in ET is climate warming, followed by precipitation. At the same time, vegetation dynamics also play a crucial role in ET, especially in areas with different vegetation types and high coverage, while climatic factors also have a strong influence on ET indirectly through vegetation. Due to its special geographic location, the HRB is more sensitive to global climate change and is a typical ecologically fragile area. Therefore, this study has important scientific value and social significance for maintaining ecological security and the sustainable use of water resources.

Root-zone soil moisture estimation based on remote sensing data and deep learning.

Soil moisture in the root zone is the most important factor in eco-hydrological processes. Even though soil moisture can be obtained by remote sensing, limited to the top few centimeters (<5 cm). Researchers have attempted to estimate root-zone soil moisture using multiple regression, data assimilation, and data-driven methods. However, correlations between root-zone soil moisture and its related variables, including surface soil moisture, always appear nonlinear, which is difficult to extract and express using typical statistical methods. The artificial intelligence (AI) method, which is advantageous for nonlinear relationship analysis and extraction is applied for root-zone soil moisture estimation, but by only considering its separate temporal or spatial correlations. The convolutional long short-term memory (ConvLSTM) model, known to capture spatiotemporal patterns of large-scale sequential datasets with the advantage of dealing with spatiotemporal sequence-forecasting problem, was used in this study to estimate root-zone soil moisture based on remote sensing-based variables. Owing to limitation of regional soil moisture observation data, the physical model Hydrus-1D was used to generate large and spatiotemporal vertical soil moisture dataset for the ConvLSTM model training and verification. Then, normalized difference vegetation index (NDVI) etc. remote sensing-based factors were selected as predictive variables. Results of the ConvLSTM model showed that the fitting coefficients (R2) of the root-zone soil moisture estimation significantly increased compared to those achieved by Global Land Data Assimilation System products, especially for deep layers. For example, R2 increased from 0.02 to 0.60 at depth of 40 cm. This study suggests that a combination of the physical model and AI is a flexible tool capable of predicting spatiotemporally continuous root-zone soil moisture with good accuracy on a large scale.

Vegetation patterns governing the competitive relationship between runoff and evapotranspiration using a novel water balance model at a semi-arid watershed.

Vegetation patterns play an important role in precipitation partitioning into hydrological components, especially evapotranspiration and runoff. However, few studies focus on their competitive relationship and the influence of the vegetation on them. In this study, a vegetation threshold was postulated to prevent further decrease of runoff by determining a new hydrological component continuing evapotranspiration (partitioned from total and initial evapotranspiration) through a novel model coupled with the Budyko model (dimensional form) and two-stage partitioning model (nondimensional form) in the semi-arid watershed. The results showed significant correlations between model parameters ε (underlying surface index), λ (ratio of initial evapotranspiration) and vegetation coverage (M) (R2 = 0.95 and 0.97, p < 0.01) b Based on the modified Budyko model and λ. The nondimensional model showed high-precise estimations of KH (Horton index Fraction), KB (Baseflow Fraction), KV (evapotranspiration Fraction), KR (runoff Fraction), and KC (continuing evapotranspiration Fraction) (R2 > 0.98, p < 0.01) as a function of a new aridity index φ. KH, KB, KV, KR, showed symmetrical patterns correlated with φ both at between-subwatershed and between-year scale based on the dimensional model and λ. However, KC showed asymmetrical different correlation with M3 and φ (KC/M3 ∼ φ: in between-subwatershed: R2 = 0.92, p < 0.01; and between-year scale: R2 = 0.74, p < 0.01). Based on the solution of continuing evapotranspiration, the vegetation threshold has been solved with M = 0.73 (+0.09/-0.02) to prevent further decreasing runoff. The framework presented can be applied in other semi-arid watersheds worldwide to better protect the sustainability of the hydro-ecosystems.

Contribution of nonpoint source pollution from baseflow of a typical agriculture-intensive basin in northern China.

Baseflow is an essential component of total surface runoff that is widely considered one of the most influential factors regarding water quality via nonpoint source (NPS) pollution. Previously, many researchers and policy makers have directed their efforts toward surface runoff pollution, largely ignoring nutrient delivery via baseflow. Taking a typical agriculture-intensive basin of northern China as an example, this study explored the spatiotemporal characteristics of baseflow and pollution load in relation to NPS pollution. Baseflow was quantified using digital filtering techniques, and the results together with observed pollution data were used to validate a physically based hydrological model, i.e., the Soil and Water Assessment Tool. Then, the spatial and temporal distribution characteristics of NPS and baseflow pollution were investigated using the modeling results. Results indicated that baseflow contribution to total runoff accounted for more than 70% during the studied years (2016-2018), and 84.15% of the basin area showed non-point source pollution dominated by baseflow pollution; both baseflow and its pollution load were greater in the nonflood seasons (spring, autumn, and winter) than in the flood season (summer); the spatial distribution of baseflow total nitrogen and total phosphorus pollution intensity showed higher values in the east and lower values in the west; the scaling effects of baseflow and its pollution load was found with increasing basin area. The results of our study highlighted the necessity for management of pollution load via baseflow in the river basin and provided reference information for improvement of NPS pollution management in other similar basins.

A novel ecohydrological model by capturing variations in climate change and vegetation coverage in a semi-arid region of China.

Variations in vegetation are influenced by regional climate regimes and, in turn, control the water balance behavior in water-limited regions. Owing to its role in ecohydrological processes, vegetation is an essential link in modeling the relationships among climate conditions, vegetation patterns, and dynamic water balance behavior. However, previous ecohydrological models have been empirical and complex, without physically significant parameters. Here, we propose a novel ecohydrological model (a Budyko model-coupled vegetation model) that combines the impacts of climate change and vegetation variations, featuring simple and deterministic parameters. In addition to accounting for the fundamental water balance model and its factors, mean precipitation, potential evapotranspiration, runoff, and variations in water storage (δS), the model showed better performance when incorporating δS (RMSE = 2.72 mm yr-1) and its parameter ε -, which is mechanically and quantitively subject to the vegetation coverage (R2 = 0.95, p < 0.01). This was estimated as a function of vegetation potential canopy conductance, mean rainstorm depth, mean time between storms, and potential rate of evapotranspiration in a semi-arid watershed with impulsive precipitation in China (R2 = 0.80, p < 0.01). The model also found that vegetation growth was mainly controlled by soil water content and decoupled the impact of the total amount of precipitation on vegetation in the northeastern area of the watershed. Hence, our method presents a new tool for building an ecohydrological model that includes deterministic parameters of mechanical significance.

Refined tumescent liposuction-curettage with pruning in small incisions for treatment of axillary bromhidrosis.

Axillary bromhidrosis is a widespread social problem in our society. Various modalities have been developed for the destruction or removal of the apocrine sweat glands to eliminate underarm odor. However, conventional surgical treatments often result in a high complication rate and frequent recurrence. In this study, we aimed to evaluate the effect of refined tumescent liposuction-curettage with pruning in small incisions as treatment for axillary bromhidrosis. Between July 2013 and April 2019, 110 patients (75 women and 35 men) with axillary bromhidrosis underwent refined tumescent liposuction-curettage with pruning. The results of eliminating underarm odor were evaluated by both the patients and doctors and rated as very satisfied (excellent), satisfied (good), slightly satisfied (fair), and not satisfied (poor). Postoperative complications, such as dehiscence, infection, wound contracture, cyst, subcutaneous hydrops, hematoma, or seroma, were also evaluated. Preoperative and postoperative histological examinations of axillary tissues were performed in two patients. In the subjective evaluation of 110 patients, 33 (30.0%) were very satisfied with the results, 70 (63.6%) were satisfied, and seven (6.4%) were slightly satisfied. The objective evaluation showed that 43 (39.1%) patients graded the results as excellent, whereas others graded the results as good. No serious complications occurred, except three patients with slight local subcutaneous hydrops and hematoma. Histologic examinations showed that the apocrine glands were significantly decreased or destroyed after the surgery. Refined tumescent liposuction-curettage with pruning in small incisions is an effective method for the treatment of axillary bromhidrosis.

The efficacy of fractional CO2 laser in acne scar treatment: A meta-analysis.

Fractional CO2 laser is a good option for treating acne scars. However, the clinical efficacy of this treatment modality requires further evidence. To perform a meta-analysis to assess clinical improvements in acne scars with fractional CO2 laser and non-CO2 laser therapies. Databases (PubMed, Embase, Cochrane Library) were searched using the search strategy to identify eligible studies. All statistical analyses were performed using the Review Manager 5.0, and a meta-analysis was conducted to assess the effects of fractional CO2 laser used as a treatment for acne scars. Eight studies were included for further analysis. There was no significant difference between fractional CO2 laser and non-CO2 laser therapies in terms of clinical improvement, observer assessment (P = .19), patient assessment (P = .91), and incidence of post-inflammatory hyperpigmentation (P = .69). The subgroup analyses showed that the duration of follow-up had little effect on the evaluation of treatment effect. The efficacy of fractional CO2 laser therapy in acne scars appeared to be equal to that of non-CO2 laser therapies. More well designed randomized controlled trials and more credible and standard evaluation criteria are needed, and the efficiency of combination therapy requires further analysis.

Chitosan-calcium alginate dressing promotes wound healing: A preliminary study.

Dressings are necessary during the process of wound healing. Since the early 1980s, several types of wound dressings have been produced, but they cannot always take into account some effects include antibacterial effect, wound healing promotion, and other properties. In this study, we would like to develop an effective dressing with the above properties, especially accelerating wound healing effect. A chitosan-calcium alginate dressing (CCAD) was developed by coating mixture of chitosan with high-low molecular weight on calcium alginate dressing (CAD). We investigated the structural characteristics of CCAD with Fourier-transform infrared spectroscopy (FTIR) and electron microscopy. The cytotoxicity and antibacterial property were evaluated in vitro using CCK-8 and inhibition zone method. Moisture retention was tested on the skin of Sprague-Dawley (SD) rats, and wound healing studies were performed on a full-thickness skin wound model in SD rats. CCAD showed good moisturizing and antibacterial properties with no cytotoxicity. CCAD could inhibit inflammation by decreasing IL-6, and it could also promote angiogenesis by increasing VEGF, resulting in better wound healing than CAD. CCAD is a better choice in wound care due to its antibacterial property, biocompatibility, moisture retention, healing promotion, and non-cytotoxicity characteristics.

CO2 Laser Punch-Assisted Minimally Invasive Surgery for Sebaceous Cysts.

BACKGROUND AND OBJECTIVES: Traditional surgical excision for a sebaceous cyst can completely eradicate the cyst, but the surgical processes are relatively complicated and may cause obvious scarring. Some patients are reluctant to choose this method because of the inconvenient procedures and the risk of conspicuous scarring, especially in esthetically important areas. We present a simple treatment method to prevent formation of a conspicuous scar. STUDY DESIGN/MATERIALS AND METHODS: First, the cyst wall was pre-separated from the surrounding tissues by injecting a large volume of anesthetic around the cyst. Then, the cyst contents were removed through a small hole created by using a CO2 laser on the skin surface, which adhered closely to the cyst. Finally, the cyst wall was removed using a hemostat that clamps it at the base. Between August 2017 and July 2019, 32 patients with 33 sebaceous cysts (12 infected and 21 uninfected) were treated by this method to remove the cyst contents and cyst wall. Mean operative time, complications, and patient satisfaction were evaluated. RESULTS: All patients were satisfied with the good esthetic outcome and the simplicity of the surgical procedure. Only two of the 33 cysts (6.0%) recurred 2 and 3 months postoperatively, including 0 of 21 uninfected cysts (0.0%) and 2 of 12 infected cysts (16.7%). No complications were found during the follow-up period. The mean operation time was 13 ± 2.1 minutes. CONCLUSIONS: CO2 laser punch-assisted surgery was associated with minimal scarring and high patient satisfaction. With acceptable recurrence rates, it is a convenient, effective and minimally-invasive treatment option for sebaceous cysts. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Pulsed electromagnetic fields promote bone formation by activating the sAC-cAMP-PKA-CREB signaling pathway.

The application of pulsed electromagnetic fields (PEMFs) in the prevention and treatment of osteoporosis has long been an area of interest. However, the clinical application of PEMFs remains limited because of the poor understanding of the PEMF action mechanism. Here, we report that PEMFs promote bone formation by activating soluble adenylyl cyclase (sAC), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) signaling pathways. First, it was found that 50 Hz 0.6 millitesla (mT) PEMFs promoted osteogenic differentiation of rat calvarial osteoblasts (ROBs), and that PEMFs activated cAMP-PKA-CREB signaling by increasing intracellular cAMP levels, facilitating phosphorylation of PKA and CREB, and inducing nuclear translocation of phosphorylated (p)-CREB. Blocking the signaling by adenylate cyclase (AC) and PKA inhibitors both abolished the osteogenic effect of PEMFs. Second, expression of sAC isoform was found to be increased significantly by PEMF treatment. Blocking sAC using sAC-specific inhibitor KH7 dramatically inhibited the osteogenic differentiation of ROBs. Finally, the peak bone mass of growing rats was significantly increased after 2 months of PEMF treatment with 90 min/day. The serum cAMP content, p-PKA, and p-CREB as well as the sAC protein expression levels were all increased significantly in femurs of treated rats. The current study indicated that PEMFs promote bone formation in vitro and in vivo by activating sAC-cAMP-PKA-CREB signaling pathway of osteoblasts directly or indirectly.

The source of ACE during scar formation is from both bone marrow and skin tissue.

Angiotensin-converting enzyme (ACE) has been found in the pathogenesis of various fibrosis diseases, and ACE inhibitor (ACEI) may affect wound healing and cutaneous fibrosis. However, there is no scientific evidence as to where the ACE is produced during scar formation. Whether it is from the cutaneous tissue or the bone marrow, or both remains unknown. In this study, we investigated the source of ACE using bone marrow transplantation in genetically modified mice, analyzed the inflammatory milieu and some growth factors in the middle of the wound healing period (4 d after the wound was induced). After having deleted the ACE from bone marrow or skin tissue, the wound/scar width in the low-ACE groups were narrower than those in wild-type (WT) controls. Loosely arranged collagen deposition and reduced vessel density were also detected in ACE-deficient mice. Lower ACE levels during scar formation were also accompanied by lower levels of TGF-ß1. In the middle of the wound healing period, ACE levels affected the inflammatory cells significantly. In the mice with a deficiency in ACE, the expression of TGF-ß1 and TNF-α decreased, but not that of IL-4. Our findings indicate that both bone marrow and skin tissue release ACE during scar formation. Deleting either of them can affect the inflammatory cells and growth factors and reduce the expression of TGF-ß1, resulting in a decreased level of scarring.-Fang, Q.-Q., Wang, X.-F., Zhao, W.-Y., Chen, C.-Y., Zhang, M.-X., Shi, B.-H., Zhang, L.-Y., Tan, W.-Q. The source of ACE during scar formation is from both bone marrow and skin tissue.

Nosocomial bloodstream infection and the emerging carbapenem-resistant pathogen Ralstonia insidiosa.

BACKGROUND: Ralstonia picketti, Ralstonia mannitolilytica, and Ralstonia insidiosa have recently been regarded as emerging pathogens of infectious diseases, in particular as the pathogens responsible for nosocomial infection in immunocompromised patients. R. insidiosa differs from R. picketti and R. mannitolilytica, and its related infections are rarely reported. METHODS: Clinical data from two nosocomial bloodstream infection cases were extracted and analyzed. The causable isolates were identified by the VITEK 2 Compact system, matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and molecular identification methods using PCR with universal and species-specific primers. Antimicrobial susceptibility testing was performed using the broth microdilution method. Both of the isolates were subjected to whole genome sequencing using a HiSeq X10 Sequencer. Antimicrobial resistance genes, virulence factors, and plasmid replicons were identified from assembled genomes. A real-time RT-PCR experiment and a cloning experiment were conducted to explore the related class D ß-lactamase-encoding genes. RESULTS: Both patients recovered under therapy with antibiotics. Isolates were initially misidentified as R. mannitolilytica by the VITEK 2 Compact system rather than R. insidiosa, as identified by both MALDI-TOF MS and 16S rRNA gene sequencing. Both isolates were resistant to aminoglycosides, ß-lactams, and polymyxin B. One isolate harboring blaOXA-570 was resistant to carbapenems. The whole genome sequencing data confirmed species identification based on average nucleotide identity (ANI) and revealed two variants of class D ß-lactamase-encoding gene blaOXA (blaOXA-573 and blaOXA-574). The real-time RT-PCR experiment showed no difference in gene expression between blaOXA-570 and blaOXA-573 in our strains. The cloning experiment showed that variant OXA-573 had no carbapenem hydrolase activity. CONCLUSIONS: We described two cases of nosocomial bloodstream infection caused by R. insidiosa strains. MALDI-TOF MS was cost-effective for rapid species identification. Clinicians should be aware that R. insidiosa can be resistant to commonly used antibiotics, even carbapenems.

Computed Tomography-Assisted Auricular Cartilage Graft for Depression of the Alar Base in Secondary Unilateral Cleft Lip Repair: A Preliminary Report.

OBJECTIVES: To evaluate the feasibility, effectiveness, and safety of computed tomography-assisted auricular cartilage grafting for treating alar base depression secondary to unilateral cleft lip. DESIGN AND SETTING: For patients with obvious depression of the alar base, the difference in heights of the alar base and the piriform margin between the cleft side and the noncleft side were measured with computed tomography. If both were >3.0 mm, the cartilage was harvested postauricularly and subdivided into 2 to 4 pieces. A multiple layer graft was inserted under the depressed alar base. The procedure was performed from 2006 to 2013, and the follow-up period was 3 to 15 months. PARTICIPANTS: Chinese patients with alar base depression secondary to unilateral cleft lip were selected. INTERVENTION: Suture and cartilage graft techniques. MAIN OUTCOMES MEASURES: Differences in bilateral alar base heights and piriform apertures. RESULTS: There was no wound dehiscence, exposure of bone, or donor site morbidity. The difference in heights in the bilateral alar bases and piriform apertures decreased. There were no obvious scars in any of the cases. CONCLUSIONS: This technique has several advantages including ease of operation, minimal trauma, satisfactory outcomes, and useful references for operation provided by computed tomography. It is a superior alternative for reconstruction of secondary alar depression.

[Trends of Antimicrobial Susceptibility of Clostridium difficileIsolates in West China Hospital of Sichuan University from 2015 to 2017].

OBJECTIVE: To summarize the drug sensitivity and its trends of Clostridium difficile diarrhea pathogenic strains in a large tertiary hospital, so as to provide basic reference data for the treatment and control of Clostridium difficile infection. METHODS: There were 73 toxigenic isolates collected from fecal sample of diarrheal patients in West China Hospital of Sichuan University during two periods. One was from August to December in 2015 (44 strains) , and another was from July 2016 to July 2017 (29 strains) . Enhanced nosocomial infection control measures were implemented during the second sample collection period. The toxin gene was amplified by PCR and sequenced for identification. Minimum inhibitory concentration (MIC) of metronidazole, vancomycin, clindamycin, moxifloxacin, rifaximin, fidaxomicin and linezolid were determined using agar double dilution method. We analyzed the drug resistance characteristics of Clostridium difficile and compared the changes of antimicrobial resistance before and after the enhanced control measures implementation. RESULTS: All 73 strains tested were sensitive to metronidazole and vancomycin. Resistance rate to clindamycin, moxifloxacin, tetracycline and rifaximin were 79.5%, 26.0%, 27.4%, and 9.5%, respectively. Fidaxomicin and nitazoxanide were highly susceptible in vitro against these strains with MIC ranges<0.008-0.5 mg/L ( P<0.05). Resistance to clindamycin and moxifloxacin were significantly decreased after enhanced control measures implementation (resistance rates were 99.5% vs. 44.8%, 36.4% vs. 10.3%, P<0.05). Additionally, isolate with decreased susceptibility to tinezolid as MIC 16 mg/L was found. CONCLUSION: Clostridium difficileis highly resistant to clindamycin and quinolones. Since strains remain highly sensitive to metronidazole and vancomycin in our hospital, empirical application is reasonable without routine antimicrobial susceptibility testing.