Impact of ultra-pulse carbon dioxide laser on the treatment of chronic refractory ulcer with bone exposure.

BACKGROUND: Chronic refractory ulcers with bone exposure present significant challenges in wound management and necessitate effective treatment strategies to facilitate healing and alleviate patient discomfort. This study aimed to investigate the impact of ultra-pulse carbon dioxide laser on treating chronic refractory ulcers with bone exposure. METHODS: This retrospective observational study enrolled patients diagnosed with chronic refractory ulcers with bone exposure admitted to the wound repair clinic of the Affiliated Hospital of Southwest Medical University between July 2018 and July 2019. RESULTS: A total of 64 patients with chronic refractory ulcers and bone exposure were included, of which 32 patients underwent ultra-pulse carbon dioxide laser drilling. Compared with patients who did not receive ultra-pulse carbon dioxide laser treatment, those who experienced the procedure demonstrated significantly higher wound healing rates on the fourth, eighth, 12th, 16th, and 20th days after treatment (all P < .001), lower scores on the visual analog scale for pain after 20 days of debridement (0.24 ± 0.05 vs 0.58 ± 0.12, P < .001), lower granulation color observation scores on the 12th, 16th, and 20th days (all P = .001), as well as reduced treatment costs (8200 ± 1600 yuan vs 15400 ± 3800 yuan, P < .001). CONCLUSION: Ultra-pulse carbon dioxide laser treatment may enhance the growth of granulation tissue, improve wound healing rates, reduce pain, and lower treatment costs for patients with chronic bone exposure wounds compared to those without such treatment.

[Establishment of a prognostic nomogram model for predicting acute renal injury in patients with moderate and severe burns].

OBJECTIVE: To establish a prediction model of acute kidney injury (AKI) in moderate and severe burn patients, so as to provide basic research evidence for early identification of burn-related AKI. METHODS: Patients who were admitted to the department of plastic burn surgery of the Affiliated Hospital of Southwest Medical University from November 2018 to January 2021 were selected, and their clinical characteristics, laboratory examinations and other indicators were recorded. Multivariate Logistic regression analysis was used to screen out the risk factors of AKI related to moderate and severe burns, and R software was used to establish the nomogram of moderate and severe burn patients complicated with AKI. The Bootstrap method model was used for internal verification by repeating sample for 1 000 times. Consistency index and calibration curve were used to evaluate the accuracy of the model, and the receiver operator characteristic curve (ROC curve) and the area under the curve (AUC) were used to evaluate the prediction efficiency, decision curve analysis (DCA) was used to evaluate the clinical utility of the model. RESULTS: A total of 186 patients with moderate and severe burn were included, among which 54 patients suffered from AKI, and the incidence rate was 29.03%. Multivariate Logistic regression analysis showed that the total burn surface area [TBSA; odds ratio (OR) = 1.072, 95% confidence interval (95%CI) was 1.031-1.115, P = 0.001], estimated glomerular filtration rate (eGFR; OR = 0.960, 95%CI was 0.931-0.990, P = 0.010), neutrophil (NEU; OR = 1.190, 95%CI was 1.021-1.386, P = 0.026), neutrophil/lymphocyte ratio (NLR; OR = 0.867, 95%CI was 0.770-0.977, P = 0.019), D-dimer (OR = 4.603, 95%CI was 1.792-11.822, P = 0.002) were the risk factors for patients with moderate and severe burn complicated with AKI. Taking the above indexes as predictive factors, a nomogram prediction model was established, the ROC curve was plotted with AUC of 0.998 (95%CI was 0.988-1.000). Optimum threshold of ROC curve was -0.862, the sensitivity was 98.0% and the specificity was 98.2%, and the consistency index was 0.998 (95%CI was 0.988-1.000). The calibration curve showed that the prognostic nomogram model was accurate, DCA showed that most patients can benefit from this model. CONCLUSIONS: The burned patients with higher TBSA, NEU, NLR, D-dimer and lower eGFR tend to suffer from AKI. The nomogram based on the above five risk factors has high accuracy and clinical value, which can be used as a predictive tool to evaluate the risk of AKI in moderate and severe burn patients.

Exploration and Validation of Potential Biomarkers and Therapeutic Targets in Ferroptosis of Asthma.

Purpose: Asthma is a chronic inflammatory airway disease involving multiple mechanisms, of which ferroptosis is a form of programmed cell death. Recent studies have shown that ferroptosis may play a crucial role in the pathogenesis of asthma, but no specific ferroptosis gene has been found in asthma, and the exact mechanism is still unclear. The present study aimed to screen ferroptosis genes associated with asthma and find therapeutic targets, in order to contribute a new clue for the diagnosis and therapy of asthma. Methods: Ferroptosis-related differentially expressed genes (FR-DEGs) in asthma were selected by the GSE41861, GSE43696 and ferroptosis datasets. Next, the FR-DEGs were subjected by GO and KEGG enrichment, and the mRNA-miRNA network was constructed. Then, GSEA and GSVA enrichment analysis and Immune infiltration analysis were performed, followed by targeted drug prediction. Finally, the expression of FR-DEGs was confirmed using GSE63142 dataset and RT-PCR assay. Results: We found 13 FR-DEGs by the GSE41861, GSE43696 and ferroptosis database. Functional enrichment analysis revealed that the 13 FR-DEGs were enriched in oxidative stress, immune response, ferroptosis, lysosome, necrosis, apoptosis etc. Moreover, our results revealed the mRNA-miRNA network of the FR-DEGs and identified candidate drugs. Also, immune infiltration revealed that ELAVL1, CREB5, CBR1 and NR1D2 are associated with the immune cells and may be potential targets in asthma. Finally, 10 FR-DEGs were validated by the GSE63142 database. It was verified that 7 FR-DEGs were differentially expressed by collecting asthma patients and healthy controls. Conclusion: This study ultimately identified 7 FR-DEGs for the diagnosis and therapy of asthma. These 7 FR-DEGs contribute to oxidative stress and immune responses. This study provides potential therapeutic targets and biomarkers for asthma patients, shedding further light on the pathogenesis of asthma as well as providing new insights into the treatment of asthma.

​Efficacy and safety of pyrotinib in combination with albumin­bound paclitaxel for the treatment of HER2­positive advanced breast cancer: A real­world study.

The present study aimed to determine the efficacy and safety of pyrotinib in combination with albumin-bound paclitaxel in patients with HER2-positive advanced breast cancer (ABC). A total of 48 patients diagnosed with HER2-positive ABC were included in the present study, and these patients were prescribed a combination of pyrotinib and albumin-bound paclitaxel in routine clinical practice. During a 21-day cycle, the standard dosage of pyrotinib was 400 mg single dose/day, which was administered orally, and 130 mg/m2/day albumin-bound paclitaxel on days 1, 8 and 15, which was administered by intravenous drip. The primary efficacy endpoint was progression-free survival (PFS) and the secondary efficacy endpoint was overall response rate (ORR), which was defined as the percentage of patients with complete remission or partial remission. Safety indicators were also observed in the present study. The results of the present study demonstrated that the median PFS (mPFS) was 8.1 months for all patients, ranging from 3.3-10.6 months. Patients receiving pyrotinib as second-line therapy exhibited a longer mPFS of 8.5 months compared with those receiving it as third- or higher-line therapy (mPFS, 5.9 months). In 17 patients with brain metastases, mPFS was 7.3 months, ranging from 4.8-10.1 months. The results of the present study also demonstrated that the ORR for the 48 patients was 33.3%. Notably, diarrhea was the most common grade 3-4 adverse event, occurring in 22.9% of patients, followed by neutropenia (6.3%), leukopenia (4.2%) and anemia (4.2%). Collectively, the results of the present study indicated that pyrotinib-based treatment is effective for patients with HER2+ ABC, including those who have previously been treated with trastuzumab. Thus, the combination of pyrotinib with albumin-bound paclitaxel is recommended due to high levels of efficacy, convenience and tolerability.

Light Alcohol Consumption Promotes Early Neurogenesis Following Ischemic Stroke in Adult C57BL/6J Mice.

Ischemic stroke is one of the leading causes of death and disability worldwide. Neurogenesis plays a crucial role in postischemic functional recovery. Alcohol dose-dependently affects the prognosis of ischemic stroke. We investigated the impact of light alcohol consumption (LAC) on neurogenesis under physiological conditions and following ischemic stroke. C57BL/6J mice (three months old) were fed with 0.7 g/kg/day ethanol (designed as LAC) or volume-matched water (designed as control) daily for eight weeks. To evaluate neurogenesis, the numbers of 5-bromo-2-deoxyuridine (BrdU)+/doublecortin (DCX)+ and BrdU+/NeuN+ neurons were assessed in the subventricular zone (SVZ), dentate gyrus (DG), ischemic cortex, and ischemic striatum. The locomotor activity was determined by the accelerating rotarod and open field tests. LAC significantly increased BrdU+/DCX+ and BrdU+/NeuN+ cells in the SVZ under physiological conditions. Ischemic stroke dramatically increased BrdU+/DCX+ and BrdU+/NeuN+ cells in the DG, SVZ, ischemic cortex, and ischemic striatum. The increase in BrdU+/DCX+ cells was significantly greater in LAC mice compared to the control mice. In addition, LAC significantly increased BrdU+/NeuN+ cells by about three folds in the DG, SVZ, and ischemic cortex. Furthermore, LAC reduced ischemic brain damage and improved locomotor activity. Therefore, LAC may protect the brain against ischemic stroke by promoting neurogenesis.

TRIM16 exerts protective function on myocardial ischemia/reperfusion injury through reducing pyroptosis and inflammation via NLRP3 signaling.

Myocardial infarction is still a leading cause of morbidity and mortality worldwide, but its pathogenesis has not been fully understood. In the study, we attempted to explore the effects of E3 ligase tripartite motif 16 (TRIM16) on myocardial ischemia-reperfusion (MI/R) injury in vivo and in vitro, and the underlying mechanisms. We identified that TRIM16 was indeed a potent regulator during MI/R progression in murine models and surprisingly showed a negative correlation with the concentrations of cardiac pro-inflammatory cytokines. Adenoviral vectors encoding GFP or TRIM16 (Ad-TRIM16) were subjected to mice through direct injection into the left ventricular (LV). We found that Ad-TRIM16 significantly reduced the infarct size, and improved the cardiac function and structure compared with the Ad-GFP mice after MI/R operation. More studies indicated that TRIM16 over-expression strongly meliorated nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and associated inflammatory response in hearts of MI/R-induced mice, which were validated in hypoxia/reoxygenation (H/R)-exposed primary cardiomyocytes in vitro. In particular, MI/R operation led to cardiac pyroptosis by increasing the cleavage of Caspase-1 and Gasdermin D (GSDMD), while being considerably abrogated upon TRIM16 over-expression. Mechanistically, TRIM16 interacted with NLRP3 and promoted the K48-linked polyubiquitination of NLRP3, ultimately promoted its degradation. Together, we identified TRIM16 as a novel E3 ubiquitin ligase for NLRP3, which played an essential role in modulating its expression, and subsequently influenced inflammatory response and pyroptosis in MI/R murine model, confirming that TRIM16 may be a potential therapeutic target for myocardial infarction.

Tracing brain genotoxic stress in Parkinson's disease with a novel single-cell genetic sensor.

To develop an in vivo tool to probe brain genotoxic stress, we designed a viral proxy as a single-cell genetic sensor termed PRISM that harnesses the instability of recombinant adeno-associated virus genome processing and a hypermutable repeat sequence-dependent reporter. PRISM exploits the virus-host interaction to probe persistent neuronal DNA damage and overactive DNA damage response. A Parkinson's disease (PD)-associated environmental toxicant, paraquat (PQ), inflicted neuronal genotoxic stress sensitively detected by PRISM. The most affected cell type in PD, dopaminergic (DA) neurons in substantia nigra, was distinguished by a high level of genotoxic stress following PQ exposure. Human alpha-synuclein proteotoxicity and propagation also triggered genotoxic stress in nigral DA neurons in a transgenic mouse model. Genotoxic stress is a prominent feature in PD patient brains. Our results reveal that PD-associated etiological factors precipitated brain genotoxic stress and detail a useful tool for probing the pathogenic significance in aging and neurodegenerative disorders.

[Application of free anterolateral thigh flap with fascia lata for diabetic foot ulcers with bone exposure].

OBJECTIVE: To investigate the effectiveness of free anterolateral thigh flap (ALTF) with fascia lata in repairing diabetic foot ulcers (DFUs) with bone exposure. METHODS: Between January 2019 and January 2021, 20 patients with DFUs with bone exposure were admitted. There were 17 males and 3 females with a median age of 57.5 years (range, 48-76 years). There were 10 cases of Wagner grade 3 and 10 cases of grade 4. The DFUs formed 1 to 14 months, with a median time of 3 months. The patients underwent CT angiography, which showed extensive atherosclerosis in both lower limbs; 6 of them were severely narrowed or occluded and underwent percutaneous transluminal angioplasty. The size of wound ranged from 7 cm×6 cm to 27 cm×10 cm after applied first-stage debridement combined with vacuum sealing drainage treatment. In the second-stage, free ALTF with fascia lata was used to repair wounds and partial defects of tendons. The size of flap ranged from 8 cm×5 cm to 28 cm×11 cm. The wound of the donor site was sutured directly. The survival of the flap, the healing time of the wound, and the complications were recorded. The laser speckle blood flow imaging system was used to detect the blood perfusion of the flap and the skin around the flap at 2 weeks and 6 months after operation. The foot function was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) score at 6 months after operation. RESULTS: After operation, effusion under the flap happened in 6 cases, which cured after symptomatic treatment. Flaps survived completely in 14 cases. The tissue necrosis at the edges of the flaps occurred in 3 cases and healed after dressing changes. Venous crisis of flaps occurred in 3 cases, of which 1 case was completely necrotic after exploration, and the other 2 cases were partially alive. The wounds of 3 cases were repaired with skin grafts after debridement and dressing. The flap survival rate was 95.0%, and the limb salvage rate was 100%. The wound healing time after flap transplantation was 14-30 days, with an average of 19.1 days. Two patients had recurrence of peripheral skin ulcers of the flaps within 1 month after healing, which healed after conservative dressing changes. Eighteen cases of incisions at donor site healed by first intention, 2 cases had local skin necrosis and healed by debridement and suture. All patients were followed up 6-30 months, with a median time of 11 months. The texture, appearance, and elasticity of the flaps were good. All patients could walk alone without pain. At 6 months after operation, the AOFAS score was 75.9±11.9, which was significantly different from that (44.7±18.4) before operation ( t=-7.025, P=0.000). The blood perfusion value increased from (38.1±7.8) PU at 2 weeks to (42.7±10.3) PU, and the difference was significant ( t=-4.680, P=0.001). CONCLUSION: Free ALTF with fascia lata has a rich blood supply and a high survival rate. It can be used to repair DFUs with bone exposure. After the free skin flap healed, it can promote revascularization of the affected foot, reduce the probability of ulcer recurrence, and avoid amputation.

Targeted inhibition of ß-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-ß1.

BACKGROUND: TGF-ß1 is a key cytokine involved in both airway inflammation and airway remodeling in asthma because of its anti-inflammatory and profibrotic effect. In our previous study, we found that knockdown of cytosolic ß-catenin alleviated the profibrogenic effect of TGF-ß1 without influencing its anti-inflammatory effect. However, the exact role of targeting ß-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting ß-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. METHODS: We integrated experimental asthma model and asthma related cell model to explore the effect of targeting ß-catenin on airway inflammation and remodeling of asthma. RESULTS: Blocking ß-catenin with ICG001, a small molecule inhibitor of ß-catenin/TCF via binding to cAMP-response elementbinding protein, attenuated airway inflammation by increasing levels of anti-inflammation cytokines IL-10, IL-35 and decreasing levels of T helper (Th)2 cells and Th17 cytokine. Suppressing ß-catenin by ICG001 inhibited airway remodeling via reducing the level of TGF-ß1 and the expressions of Snail, MMP-7, MMP-9 and, up-regulating expression of E-cadherin, down-regulating expressions of α-SMA and Fn. Inhibition of ß-catenin with ICG001 suppressed TGF-ß1 induced proliferation and activation of CCC-REPF-1, blocked TGF-ß1 induced epithelial-mesenchymal transition (EMT) of RLE-6TN. CONCLUSION: Blockade of ß-catenin/TCF not only prevents TGF-ß1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing pro-inflammatory and anti-inflammatory cytokine. In conclusion, targeting ß-catenin specifically via inhibition of ß-catenin/TCF might be a new therapeutic strategy for asthma.The reviews of this paper are available via the supplemental material section.

1α, 25-dihydroxyvitamin D3 inhibits transforming growth factor ß1-induced epithelial-mesenchymal transition via ß-catenin pathway.

BACKGROUND: The transforming growth factor ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/ß-catenin pathway plays an important role, notably with regard to TGF-ß1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-ß1-induced EMT, although the underlying mechanism have not yet been fully elucidated. METHODS: Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-ß1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and ß-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/ß-catenin signaling pathway was analyzed using the Top/Fop flash reporters. RESULTS: Both 1α, 25(OH)2D3 and ICG-001 blocked TGF-ß1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3 suppressed the activity of the Wnt/ß-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001. CONCLUSION: 1α, 25(OH)2D3 synergizes with ICG-001 and inhibits TGF-ß1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/ß-catenin signaling pathway.

Incidence and Prognostic Value of Acute Coagulopathy After Extensive Severe Burns.

Acute burn-induced coagulopathy (ABIC) occurs after severe burns. However, the incidence, prognostic value, and clinical significance of ABIC after an extensive severe burn remain inconclusive due to wide variances in burn severity and coagulation profile evaluation timings in previous studies. This retrospective study explored the incidence and clinical and prognostic significance of early phase ABIC in 129 adult patients with extensive burns (>50% total body surface area [TBSA]) admitted to the burn centers of two hospitals within 10 hours postburn injury during 2009-2017. Demographics (age and sex) and clinical data (burn severity, vital signs, prehospital fluid replacement volume, hemodynamic parameters, coagulation profile, blood gas, and blood biochemical indicators) were collected upon admission. The incidence of ABIC in patients with severe burns and its relationship with their survival and clinical significance were analyzed. The average postburn interval was 5.7 ± 2.7 hours, and the incidence of ABIC was 31% (40/129). A logistic regression analysis identified ABIC as an independent predictor of 4-week severe mortality due to severe burn. The incidence of ABIC was significantly associated with the total burn area, lactic acid levels upon admission, and postburn admission interval, but not with the prehospital fluid replacement volume. In conclusion, approximately 30% of patients with severe burns developed ABIC within 10 hours postburn, and this condition strongly predicts 4-week mortality. Although burn severity and tissue ischemia/hypoxia are main risk factors for ABIC, the pathogenesis is not fully understood and should be explored in future studies.

Dataset of soil bacterial compositions and biochemical properties of a Moso bamboo forest under mulching-intensive management.

Bacterial 16S rRNA dataset of Moso bamboo forest was formed by 20 soil samples in four management modes corresponding to the soil properties data of each soil sample such as concentrations of soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), available phosphorus (AP), NH4 +-N, NO3 --N, water-soluble organic carbon (WSOC), Water-soluble organic nitrogen (WSON), microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN), and soil water content (SWC) and pH value. Due to the special climate in the northern edge of subtropical zone and the characteristics of non wood and non grass of bamboo plants, our data set is helpful for the further studies of soil management, microhabitats variations responding to global carbon, nitrogen and phosphorus cycle. The data is related to the research article "Response of bacterial compositions to soil biochemical properties under mulching-intensive management in a Phyllostachys edulis forest" [1].

A new Bi2MoO6 nano-tremella-based electrochemical immunosensor for the sensitive detection of a carcinoembryonic antigen.

By doping molybdenum (Mo) into bismuth oxide (Bi2O3), we synthesized novel Bi2MoO6 nanohybrids with a unique tremella-like crystal structure via a one-pot hydrothermal method. Such a porous tremella structure of Bi2MoO6 possesses a significantly larger surface area than the spherical structure of Bi2O3, which is favorable for the special functionalization and effective immobilization of molecules such as antibodies on the surface of the tremella flaps. As expected, Au nanoparticles grew easily and uniformly outside the surface of the flaps of the as-prepared Bi2MoO6 NTs (Au@Bi2MoO6 NTs), showing preferable conductivity and biocompatibility, and the anti-carcinoembryonic antigen (anti-CEA) was effectively immobilized outside the obtained Au@Bi2MoO6 NTs. Acting as a novel label-free immunosensing platform, the anti-CEA-immobilized Au@Bi2MoO6 NTs were used to fabricate an electrochemical immunosensor for the quantitative detection of CEA. The as-prepared Au@Bi2MoO6-based immunosensor linearly responded to CEA in a wide concentration range from 1 pg mL-1 to 1 µg mL-1 with a detection limit calculated to be 0.3 pg mL-1 (S/N = 3), significantly comparable to numerous existing immunosensors. Moreover, the minimum detection concentration of the designed immunosensor was about ten times smaller than that of many Bi and Mo-based sensors toward CEA detection, and the detection limit was lower, revealing higher sensitivity. The satisfactory selectivity and stability made the immunosensor potentially applicable for CEA detection in real samples.

Dosage sensitivity intolerance of VIPR2 microduplication is disease causative to manifest schizophrenia-like phenotypes in a novel BAC transgenic mouse model.

Recent genome-wide association studies (GWAS) have identified copy number variations (CNVs) at chromosomal locus 7q36.3 that significantly contribute to the risk of schizophrenia, with all of the microduplications occurring within a single gene: vasoactive intestinal peptide receptor 2 (VIPR2). To confirm disease causality and translate such a genetic vulnerability into mechanistic and pathophysiological insights, we have developed a series of conditional VIPR2 bacterial artificial chromosome (BAC) transgenic mouse models of VIPR2 CNV. VIPR2 CNV mouse model recapitulates gene expression and signaling deficits seen in human CNV carriers. VIPR2 microduplication in mice elicits prominent dorsal striatal dopamine dysfunction, cognitive, sensorimotor gating, and social behavioral deficits preceded by an increase of striatal cAMP/PKA signaling and the disrupted early postnatal striatal development. Genetic removal of VIPR2 transgene expression via crossing with Drd1a-Cre BAC transgenic mice rescued the dopamine D2 receptor abnormality and multiple behavioral deficits, implicating a pathogenic role of VIPR2 overexpression in dopaminoceptive neurons. Thus, our results provide further evidence to support the GWAS studies that the dosage sensitivity intolerance of VIPR2 is disease causative to manifest schizophrenia-like dopamine, cognitive, and social behavioral deficits in mice. The conditional BAC transgenesis offers a novel strategy to model CNVs with a gain-of -copies and facilitate the genetic dissection of when/where/how the genetic vulnerabilities affect development, structure, and function of neural circuits. Our findings have important implications for therapeutic development, and the etiology-relevant mouse model provides a useful preclinical platform for drug discovery.

Application of pulse index continuous cardiac output system in elderly patients with acute myocardial infarction complicated by cardiogenic shock: A prospective randomized study.

BACKGROUND: Cardiogenic shock (CS) secondary to acute myocardial infarction (AMI) complicates management of the condition, and often leads to poor prognosis. Prompt and accurate monitoring of cardiovascular and accompanying hemodynamic changes is crucial in achieving adequate management of the condition. Advances in technology has availed procedures such as pulse index continuous cardiac output (PiCCO), which can offer precise monitoring of cardiovascular functions and hemodynamic parameters. In this study, PiCCO is evaluated for its potential utility in improving management and clinical outcomes among elderly patients with AMI complicated by CS. AIM: To assess whether use of the PiCCO system can improve clinical outcomes in elderly patients with AMI complicated by CS. METHODS: Patients from emergency intensive care units (EICU) or coronary care units (CCU) were randomized to receive PiCCO monitoring or not. The APACHE II score, SOFA score, hs-TnI, NT-proBNP, PaO2/FiO2 ratio and lactate levels on day 1, 3 and 7 after treatment were compared. The infusion and urine volume at 0-24 h, 24-48 h and 48-72 h were recorded, as were the cardiac index (CI), extravascular lung water index (EVLWI), intrathoracic blood volume index (ITBVI) and global end diastolic volume index (GEDVI) at similar time intervals. RESULTS: Sixty patients with AMI complicated by CS were included in the study. The PiCCO group had a significantly lower APACHE II score, SOFA score, hs-TnI and NT-proBNP levels on day 1, 3 and 7 after treatment. The infusion and urine volume during 0-24 h in the PiCCO group were significantly greater, and this group also showed significantly higher ADL scores. Furthermore, the PiCCO group spent lesser days on vasoactive agents, mechanical ventilation, and had a reduced length of stay in EICU/CCU. Additionally, the CI was significantly higher at 48 h and 72 h in the PiCCO group compared with that at 24 h, and the EVLWI, ITBVI and GEDVI were significantly decreased at 48 h and 72 h. CONCLUSION: Applying the PiCCO system could improve the clinical outcomes of elderly patients with AMI complicated by CS.

Electrical stimulation facilitates the angiogenesis of human umbilical vein endothelial cells through MAPK/ERK signaling pathway by stimulating FGF2 secretion.

Electrical stimulation (ES) is able to enhance angiogenesis by stimulating fibroblasts. Fibroblast growth factor 2 (FGF2) is an independent angiogenesis inducer. The present study aimed to evaluate the role of ES-induced FGF2 secretion in affecting angiogenesis during wound healing via the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Fibroblasts and human umbilical vein endothelial cells (HUVECs) were exposed to ES, and the HUVECs were cocultured with ES-treated fibroblast culture solution. ES exposure showed no toxic effects on fibroblasts or HUVECs. ES led to enhanced growth of fibroblasts and HUVECs as well as FGF2 secretion, which is induced through the NOS pathway. ES-induced FGF2 secretion was shown to increase vascular endothelial growth factor (VEGF) protein and enhance migration, invasion, and angiogenesis of HUVECs. Also, ES-induced FGF2 secretion activated the MAPK/ERK signaling pathway. However, inhibition of the MAPK/ERK signaling pathway reversed the positive effects of ES-induced FGF2 secretion. In vitro experiments showed positive effects of ES on wound healing. Taken together, the findings suggested that ES promoted FGF2 secretion and then activated the MAPK/ERK signaling pathway by facilitating angiogenesis and promoting wound healing.

Erasure of striatal chondroitin sulfate proteoglycan-associated extracellular matrix rescues aging-dependent decline of motor learning.

Cognitive decline is a feature of aging. Accumulating evidence suggests that the brain extracellular matrix (ECM) is involved in the process of aging-dependent cognitive impairment and neurodegeneration by regulating synaptic neurotransmission and affecting neuroplasticity. Age-related changes in brain structure and cognition are not uniform across the whole brain. Being one of the most vulnerable brain regions to aging-dependent alterations, striatum is integral to several central nervous system functions, such as motor, cognition, and affective control. However, the striatal ECM is largely understudied. We first describe 2 major types of chondroitin sulfate proteoglycan (CSPG)-associated ECM in striatum: perineuronal nets and diffusive ECM. Both types of ECM accumulate in an aging-dependent manner. The accumulation of CSPG-associated ECM correlates with aging-dependent decline in striatum-related cognitive functions, including motor learning and working memory. Enzymatic depletion of CSPG-associated ECM in aged mice via chondroitinase ABC significantly improves motor learning, suggesting that changes in neural ECM CSPGs regulate striatal plasticity. Our study provides a greater understanding of the role of neural ECM underlying striatal plasticity, which is an important precursor to design appropriate therapeutic strategies for normal and pathologic aging.

Kawasaki disease: multiple giant coronary aneurysms intervention and pacemaker implantation due to complete heart block-a case report.

Early intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD) to reduce the incidence of coronary aneurysms. Patients with atypical presentation or who live in a rural area are less likely to receive treatment in the early stage of presentation and are more likely to develop severe complications. There is little consensus on how to treat coronary aneurysms effectively in the acute or subacute stage especially when giant aneurysms develop that compromise cardiac function. This case study is of a 19-month-old girl who initially was not treated as KD and developed multivessel giant coronary artery aneurysms (CAAs) (>8 mm), acute myocardial infarction, and complete heart block despite late intravenous IVIG administration. Multiple attempts of percutaneous coronary intervention (PCI) failed to open the occlusion in the right artery; therefore, bradycardia persisted. The girl received a permanent pace-maker and was doing well at 12-month follow up.

Aberrant frequency of TNFR2+ Treg and related cytokines in patients with CIN and cervical cancer.

Regulatory T (Treg) cells expressing tumor necrosis factor receptor 2 (TNFR2) are highly suppressive and are associated with immune homeostasis in various diseases. However, the role of TNFR2+Treg subset and relevant cytokines in the development of cervical cancer (CC) remained unclear. In this study, 72 patients with CC, 30 patients with cervical intraepithelial neoplasia (CIN) and 30 healthy volunteers were enrolled. The level of circulating TNFR2+Tregs was investigated through flow cytometry. The plasma concentrations of soluble TNFR1 (s-TNFR1) and soluble TNFR2 (s-TNFR2) were determined by enzyme-linked immunosorbent assay. In addition, the mRNA expression levels of TNF-α, TNFR1, TNFR2, and Foxp3 were measured using real-time polymerase chain reaction. Results showed that both peripheral and tumor infiltrating TNFR2+Tregs significantly increased in patients with CIN and CC and levels of circulating s-TNFR1 and s-TNFR2 increased in patients with CC. Moreover, the percentage of peripheral TNFR2+Tregs was inversely correlated with the clinical stages of CC. Furthermore, the mRNA expression levels of TNF-α, TNFR2, and Foxp3 increased in patients with CIN and CC. Overall, these results indicate that TNFR2+Tregs and relevant cytokines contribute to CC development and are promising targets in future immunotherapeutic approaches.

Highly Efficient Glioma Targeting of Tat Peptide-TTA1 Aptamer-Polyephylene Glycol-Modified Gelatin-Siloxane Nanoparticles.

Gliomas are the most common type of intracranial malignant tumor; however, current treatment approaches are often ineffective due to limited penetration of genes or drugs through the blood-brain barrier (BBB). Here we describe the synthesis of gelatin-siloxane nanoparticles (GS NPs) as candidate gene carriers through a two-step sol-gel process. To increase the efficiency of glioma targeting, human immunodeficiency virus-derived Tat, tumor-targeting aptamer (TTA)1, and polyethylene glycol (PEG) were conjugated to the GS NPs to generate Tat-TTA1-PEG-GS NPs. In vivo imaging revealed that these modified NPs not only evaded capture by the reticulo-endothelial system, but were able to cross the BBB to reach gliomas. Our results suggest that Tat-TTA1-PEG-GS NPs are a new type of non-viral vector that can deliver therapeutic DNA or drugs for highly efficient glioma treatment.