Development of a Decafluorobiphenyl Cyclized Peptide Targeting the NEMO-IKKα/ß Interaction that Enhances Cell Penetration and Attenuates Lipopolysaccharide-Induced Acute Lung Injury.

Aberrant canonical NF-κB signaling has been implicated in diseases, such as autoimmune disorders and cancer. Direct disruption of the interaction of NEMO and IKKα/ß has been developed as a novel way to inhibit the overactivation of NF-κB. Peptides are a potential solution for disrupting protein-protein interactions (PPIs); however, they typically suffer from poor stability in vivo and limited tissue penetration permeability, hampering their widespread use as new chemical biology tools and potential therapeutics. In this work, decafluorobiphenyl-cysteine SNAr chemistry, molecular modeling, and biological validation allowed the development of peptide PPI inhibitors. The resulting cyclic peptide specifically inhibited canonical NF-κB signaling in vitro and in vivo, and presented positive metabolic stability, anti-inflammatory effects, and low cytotoxicity. Importantly, our results also revealed that cyclic peptides had huge potential in acute lung injury (ALI) treatment, and confirmed the role of the decafluorobiphenyl-based cyclization strategy in enhancing the biological activity of peptide NEMO-IKKα/ß inhibitors. Moreover, it provided a promising method for the development of peptide-PPI inhibitors.

Ultra-efficient radio-immunotherapy for reprogramming the hypoxic and immunosuppressive tumor microenvironment with durable innate immune memory.

Radiosensitization efficacy of conventional tumor radiosensitizers has been frequently limited by insufficient competence for tumor microenvironment (TME) regulation and unfavorable cellular uptake at biological barriers. Here, we reported an ultra-efficient radiotherapy (RT) strategy by synthesizing an extracellular vesicles (EVs)-encapsulated hollow MnO2 to load metformin (Met@HMnER). It demonstrated significant RT enhancement by morphological control of catalyst and cellular respiratory depression against conventional solid MnO2. Furthermore, the target-modified EVs clothing retains outstanding metformin loading capacity while endowing enhanced biological barrier penetration. A noticeably durable innate immune activation of NK cells was triggered with this nanoplatform via the cGAS-STING pathway. The enhanced immunocompetence was verified on distal metastasis and in-situ recurrence model in vivo, This work paved a new path for synergistic and robust innate immunity in clinical cancer treatment.

Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury.

Radiation-induced skin injury (RISI) is an important challenge for clinical treatments. The main causes of RISI include hypoxia in the wound microenvironment, reactive oxygen species (ROS) activation, and downregulation of DNA repair proteins. Here, a multiple radioresistance strategy was designed for microRNA therapy and attenuating hypoxia. A novel mesoporous silica (MS) firmly anchored and dispersed cerium (IV) oxide (CeO2) nanoparticles to form MS-CeO2 nanocomposites, which exhibit superior activity in inhibiting radiation-induced ROS and HIF-1α activation and ultimately promote RISI wound healing. The miR129 serum concentrations in patients can promote radioresistance by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, MS-CeO2 nanocomposites with miR129 were conjugated with iRGD-grafted polyoxyethylene glycol (short for nano-miR129), which increased the stability and antibacterial character, efficiently delivered miR129 to wound blood capillaries, and exhibited low toxicity. Notably, nano-miR129 promoted radioresistance and enhanced anti-ROS therapeutic efficacy in a subcutaneous RISI mouse model. Overall, this MS-CeO2 nanozyme and miR129-based multiresistance radiotherapy protection strategy provided a promising therapeutic approach for RISI.

An IFI6-based hydrogel promotes the healing of radiation-induced skin injury through regulation of the HSF1 activity.

Radiation-induced skin injury (RISI) is a common complication of radiotherapy. Interferon-alpha inducible protein 6 (IFI6) significantly reduces the radiation sensitivity of HaCaT cells. Sodium alginate (SA) has substantial moisturizing properties. Graphene oxide (GO) is a suitable substrate with physical antibacterial properties. Therefore, we designed materials to modify IFI6 using the biogule of polydopamine (PDA) connected to GO/SA. The structure, size, morphology, and elemental compositions of IFI6-PDA@GO/SA were analyzed. Cytological studies suggested that IFI6-PDA@GO/SA is non-toxic to HaCaT cells, with antibacterial properties. It promotes migration and vascularization and inhibits apoptosis. These cells express IFI6 after irradiation. The mouse model suggested that IFI6-PDA@GO/SA promotes wound healing and reduces reactive oxygen species expression. IFI6-PDA@GO/SA accelerates RISI healing, possibly by initiating the SSBP1/HSF1 signaling pathway. In addition, IFI6-PDA@GO/SA improves the immune microenvironment. This study constitutes the first use of IFI6 as a RISI wound-healing material.

Bioadhesive injectable hydrogel with phenolic carbon quantum dot supported Pd single atom nanozymes as a localized immunomodulation niche for cancer catalytic immunotherapy.

Immunotherapy is a powerful way to treat cancer, however, systemic treatment-associated adverse effects remain a major concern. In this study, a bioadhesive injectable hydrogel is developed to provide localized immune niches for tumor microenvironment immunomodulation and cancer catalytic immunotherapy. First, a phenolic single atom nanozyme (SAN) was developed by in situ synthesis of Pd single atom on catechol-grafted carbon-quantum-dot (DA-CQD@Pd) templates. Then, the bioadhesive injectable hydrogel consisting of DA-CQD@Pd SAN and immune adjuvant CpGODN was formed through SAN-catalyzed free-radical polymerization. The SAN exhibited peroxidase-like activity to generate ROS and kill tumor cells through catalytic therapy. The hydrogel locally released CpGODN in a sustained manner, which limited the risk of systemic exposure, reducing the impact of CpGODN toxicity, and protecting CpGODN from degradation. The bioadhesive hydrogel immobilized around solid tumor to provide an immune response site after injection. When combined it with the administration of immune checkpoint inhibitor anti-PD-L1, the hydrogel realized localized immunomodulation, maximized therapeutic efficacy and prevents tumor metastasis via a catalytic immunotherapy.

Cisplatin loaded multiwalled carbon nanotubes reverse drug resistance in NSCLC by inhibiting EMT.

BACKGROUND: Lung cancer is one of the important health threats worldwide, of which 5-year survival rate is less than 15%. Non-small-cell lung cancer (NSCLC) accounts for about 80% of all lung cancer with high metastasis and mortality. METHODS: Cisplatin loaded multiwalled carbon nanotubes (Pt-MWNTS) were synthesized and used to evaluate the anticancer effect in our study. The NSCLC cell lines A549 (cisplatin sensitive) and A549/DDP (cisplatin resistant) were used in our in vitro assays. MTT was used to determine Cancer cells viability and invasion were measured by MTT assay and Transwell assay, respectively. Apoptosis and epithelial-mesenchymal transition related marker proteins were measured by western blot. The in vivo anti-cancer effect of Pt-MWNTs were performed in male BALB/c nude mice (4-week old). RESULTS: Pt-MWNTS were synthesized and characterized by X-ray diffraction, Raman, FT-IR spectroscopy and scan electron microscopy. No significant cytotoxicity of MWNTS was detected in both A549/DDP and A549 cell lines. However, Pt-MWNTS showed a stronger inhibition effect on cell growth than free cisplatin, especially on A549/DDP. We found Pt-MWNTS showed higher intracellular accumulation of cisplatin in A549/DDP cells than free cisplatin and resulted in enhanced the percent of apoptotic cells. Western blot showed that application of Pt-MWNTS can significantly upregulate the expression level of Bax, Bim, Bid, Caspase-3 and Caspase-9 while downregulate the expression level of Bcl-2, compared with free cisplatin. Moreover, the expression level of mesenchymal markers like Vimentin and N-cadherin was more efficiently reduced by Pt-MWNTS treatment in A549/DDP cells than free cisplatin. In vivo study in nude mice proved that Pt-MWNTS more effectively inhibited tumorigenesis compared with cisplatin, although both of them had no significant effect on body weight. CONCLUSION: Pt-MWNT reverses the drug resistance in the A549/DDP cell line, underlying its possibility of treating NSCLC with cisplatin resistance.

Effects of IL-1ß and TNF-α on the Expression of P311 in Vascular Endothelial Cells and Wound Healing in Mice.

OBJECTIVE: This study aimed to define the role of interleukine-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the expression of P311 in vascular endothelial cells (VECs) and in wound healing. METHODS: DAPI staining, a CCK-8 assay, cell migration assay, and an angiogenesis assay were used to assess the effects exerted by TNF-α and IL-1ß at various concentrations on morphology, proliferation, migration, and angiogenesis of VECs. Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) models were employed to observe the effects exerted by proteins related to the nuclear factor-kappa B (NF-κB) signaling pathway and P311 mRNA expression. Bioinformatics analysis was performed on the binding sites of P311 and NF-κB. Finally, to investigate the effects of IL-1ß and TNF-α on wound healing and the length of new epithelium in mice, we established a full-thickness wound defect model in mice. Immunohistochemistry was used to measure changes in P311, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), CD31 (platelet endothelial cell adhesion molecule-1, PECAM-1/CD31), as well as other related proteins. RESULTS: When levels of TNF-α and IL-1ß were both 20 ng/ml, their effects on cell proliferation, cytoskeleton protein expression, cell migration, and angiogenesis were the greatest (P < 0.05). IL-1ß and TNF-α at moderate concentrations effectively promoted P311 mRNA and p-NF-κB protein expression (P < 0.05), while p-NF-K b protein expression was decreased (P < 0.05). Luciferase assays showed that P311 expression was also relatively greater when stimulated at moderate concentrations (P < 0.05), while relative expression was significantly lower when the p-NF-K b inhibitor CAPE was added (P < 0.05). On 7-day wound healing rate comparison, the control, IL-1ß, IL-1ßab, TNF-α, and TNF-αab groups were 18, 37, 35, 39, and 36%, respectively, while control group + P311 siRNA was 31% (P < 0.05). New epithelial length, granulation tissue thickness, and number of blood vessels trends were also the same. In the control group, P311 showed lower relative expression levels than the others (P < 0.05). P311 relative expression levels trended as follows: control group > IL-1ßab > IL-1ß > TNF-αab > TNF-α (P < 0.05). CONCLUSION: When IL-1ß and TNF-α concentrations are moderate, they effectively promote the proliferation, expression, migration, and angiogenesis of VECs, possibly by promoting the expression of the NF-K b pathway and thereby promoting the expression of P311. In vitro experiments on mice suggest that P311 effectively promotes wound healing, and its mechanism may be closely related to PCNA, CD31, and VEGF.

Programmed Death Ligand-1 (PD-L1) Regulated by NRF-2/MicroRNA-1 Regulatory Axis Enhances Drug Resistance and Promotes Tumorigenic Properties in Sorafenib-Resistant Hepatoma Cells.

Sorafenib, a multityrosine kinase inhibitor, is a standard treatment for advanced hepatocellular carcinoma (HCC), but the clinical response to sorafenib is seriously limited by drug resistance. Programmed death ligand-1 (PD-L1) is one of the most important inhibitory molecules involved in tumor immune evasion. Recently, it has been reported that PD-L1 could play crucial roles in drug resistance of many kinds of cancers. However, the expression, function, and regulation of PD-L1 in sorafenib-resistant hepatoma cells remain unclear. In this study, we reported that PD-L1 was overexpressed in sorafenib-resistant hepatoma cells, and shRNA-mediated PD-L1 depletion attenuated drug resistance and suppressed the migration, invasion, colony formation, and tumorigenesis in sorafenib-resistant hepatoma cells in vitro and in vivo. Mechanistic investigations indicated that loss of microRNA-1 (miR-1), a tumor-suppressive microRNA, contributed to the PD-L1 upregulation in sorafenib-resistant hepatoma cells, and PD-L1 was a direct regulatory target of miR-1. Further study revealed that an oncogenic transcriptional factor, nuclear factor E2-related factor 2 (NRF-2), was induced in sorafenib-resistant hepatoma cells and inhibited expression of miR-1 in vitro. From molecular mechanism insight back to the functional verification, we eventually demonstrated that miR-1 executed its tumor-suppressive effects on drug resistance and other malignant properties in sorafenib-resistant hepatoma cells partially by PD-L1 inhibition in vitro and in vivo. In conclusion, our data suggested that a NRF-2/miR-1/PD-L1 regulatory axis contributed to the development and maintenance of drug resistance and other tumorigenic properties in sorafenib-resistant hepatoma cells and provided a potential therapeutic target for overcoming sorafenib resistance in HCC.

Short fluorocarbon chains containing hydrophobic nanofibrous membranes with improved hemocompatibility, anticoagulation and anti-fouling performance.

Thromboembolic diseases have become one of the most hazardous and mortal diseases to human life. In this paper, a highly hydrophobic nanofibrous membrane was prepared via electrospinning of PCL-b-PHFBA (polycaprolactone -b- poly (heptafluoro butyl acrylate)) block copolymers. The nanofibrous membranes showed high hydrophobicity with a water contact angle of ˜136° due to their rough nanofibrous surface morphology and contained small portion of short fluorocarbon chain polymer PHFBA. According to the results of whole blood clotting time (CT), prothrombin time (PT), activated partial thromboplastin time (APTT), plasma re-calcification time test (PRT), platelets adhesion and the ultra-low hemolysis rate of 1.13% to red blood cells (RBCs), the membranes exhibited interesting anticoagulant and decreased-platelet adhesion performance. PCL-b-PHFBA nanofibrous membranes showed mild anti-fouling activity, reduced Bovine Serum albumin (BSA) protein absorption and bacterial adhesion compared with PCL nanofibrous membranes. The introduction of PHFBA component did not lead to any obvious cytotoxicity according to the cytocompatibility and cell adhesion study, suggesting that the PCL-b-PHFBA nanofibrous membranes are promising for blood related applications by minimizing the coagulation, hemolysis, BSA protein adsorption, bacterial attachment and platelet adhesion.

Study of the mechanism of environmentally friendly translucent balsa-modified lysozyme dressing for facilitating wound healing.

OBJECTIVE: This study aimed to prepare an eco-friendly dressing using a balsa-derived membrane with lysozymes designed for antibacterial purposes. METHODS: The groups included controls, balsa (group A), translucent balsa (group B), translucent balsa-lysozymes (group C), and translucent balsa-modified lysozymes (group D). Physical and chemical methods were used to characterize the materials, and the function of the materials was evaluated by in vivo and in vitro experiments. RESULTS: Antibacterial activity against Escherichia coli and Staphylococcus aureus was ordered D > C > B ≈ A (P<0.05). Healing rates in the control, A, B, C, and D groups were 30.6%, 48.3%, 56.7%, 70.9%, and 79.2%, respectively at 7 days after injury. The lengths of new epithelia of the wound surface were ordered D > C > B ≈ A > control (P<0.05). Reverse-transcription polymerase chain reaction showed that expression of Wnt3a, ß-catenin, and PCNA mRNA were ordered D > C > B ≈ A > control (P<0.05). The order of expression of PCNA was D > C > B ≈ A > control (P<0.05). There were no differences in GSK3ß expression (P>0.05). The order of expression of axin was D < C < B ≈ A < control (P<0.05). The cell-migration rate at 24 hours was ordered D > C > B ≈ A > control (P<0.05). CONCLUSION: This translucent balsa-modified lysozyme dressing is characterized by strong antibacterial properties, stable and persistent release, no cytotoxicity, and capacity to promote antibacterial ability and epithelial growth, as well as cell proliferation and migration.

Preparation of chitin-amphipathic anion/quaternary ammonium salt ecofriendly dressing and its effect on wound healing in mice.

OBJECTIVE: This study aimed to prepare an eco-friendly dressing using a chitin-derived membrane with amphipathic anion/quaternary ammonium salt designed for antibacterial purposes. METHODS: Four dressings were prepared and group A was chitin, group B was chitin + amphiphilic ion, group C was chitin + quaternary ammonium salt, group D was chitin + amphiphilic ion + quaternary ammonium salt. RESULTS: In the group D material, precipitation of adherent composite ions was observed. The contact angle test showed that the material was hydrophilic. The drug loading rate in groups B, C, and D was 40-50 (ug:mg), the entrapment efficiency was 70%-75% (P>0.05), and the cumulative release percentages were 87.3%, 88.7%, and 90.2% after 72h for group B, C, and D, respectively. The anti-bacterial activity in vitro was in the order D>C>B>A> control (P>0.05). The anti-pollution activity in vitro was in the order D>B>C>A (P<0.05). The cell proliferation inhibition test showed slight proliferation inhibition (P<0.05) only on the seventh day for group D. Seven days after injury, the wound healing rate was in the order D>C> commercial chitin dressing >B>A> control (P<0.05), and the length of the neonatal epithelium also showed the same trend. Additionally, PCNA and CD31 expression indicated that cell proliferation and angiogenesis were enhanced when skin defects were covered with the D group material (P<0.05). CONCLUSION: chitin-amphiphilic ion/quaternary ammonium salt dressing was successfully prepared. The antibacterial and antipollution effects of the prepared material (group D) were both very good, acting to promote wound healing.

Epidemiologic Investigation of Chemical Burns in Southwestern China from 2005 to 2016.

The epidemiological characteristics of chemical burns vary in different regions of the world. This study aims to survey the epidemiology, outcomes, and costs of chemical burns in southwest China, to determine associated risk factors and to obtain data for developing an effective approach to prevent and treat chemical burns. This retrospective study includes 410 cases with chemical burns admitted to the Institute of Burn Research of Southwest Hospital from 2005 to 2016. Data, including demographic, etiology, outcomes, and costs, were collected and analyzed. A total of 410 cases admitted to our burn center were included. The average age of the burn patients was 38.58 ± 14.66 years. The incidence of chemical burns peaked in autumn. The most common etiology were acids. Limbs were the most common burn sites (59.51%). Average total body surface area (TBSA) was 12.37 ± 18.67%. The percentage of patients who underwent procedures and the number of procedures were significantly greater for TBSA and full-thickness burns. The mortality of chemical burns was 1.22%. The median length of stay (LOS) and cost were 21 days and 65,852 CNY, respectively. The major risk factors for cost were the number of procedures, TBSA and full-thickness burns, the major risk factors for LOS were the number of procedures and outcome. Chemical burns mainly occurred in adult males with occupational exposures to chemical agents due to inappropriate operation. Emphasis on safety education for the public and professional pre-employment training for workers should become key preventive targets to reduce the incidence of chemical burns.

Polydimethylsiloxane incorporated with reduced graphene oxide (rGO) sheets for wound dressing application: Preparation and characterization.

Toward fabricating a novel multifunctional wound dressing material, we incorporated a series of contents of reduced graphene oxide (rGO) sheets into polydimethylsiloxane (PDMS) matrix to prepare the rGO-PDMS composite membrane and be used for wound dressing. The pore structure, dispersion of rGO, physical properties, water vapor transmission rate (WVTR), cytotoxicity and antibacterial activity were studied. Finally, the effect of the rGO-PDMS composite membrane on wound healing was investigated on a murine full-thickness skin wound model. The rGO-PDMS composite membrane exhibited bionic performance (ordered pore structure and suitable WVTR), improved mechanical properties, good compatibility and effective antibacterial activity. In vivo experiment indicated that the rGO-PDMS composite membrane could accelerate wound healing via enhancement of the re-epithelialization and granulation tissue formation. These findings suggest that rGO doping PDMS uniquely resulted in a multifunctional material for potential use in wound dressing.

Preparation of a balsa-lysozyme eco-friendly dressing and its effect on wound healing.

This study aims to prepare an eco-friendly dressing using a balsa derived membrane with lysozyme included for anti-bacterial purposes. The balsa-lysozyme was prepared using delignification (control) and dopamine (group A) methods for mussel-inspired adhesion of 5, 10, 15 and 20 mg ml-1 lysozyme (groups B, C, D and E). Fourier infrared spectra and the contact angle test showed that lysozyme adhered to the membrane. With increasing concentration of lysozyme, the drug-loading rate of balsa-lysozyme increased and the encapsulation efficiency decreased (P < 0.05). The cumulative release percentages after 72 h were 80.7%, 90.6%, 91.4%and 92.3% in groups B, C, D and E, respectively. There was a significant in vitro antibacterial effect against both E. coli and S. aureus. The cytotoxicity of the wood dressing was not detected until day 7. On day 7, the healing rates were 30.7%, 38.3%, 50.7%, 61.2%, 61.9% and 62.4% for the control, A, B, C, D and E group (P < 0.05). Similarly, the lengths of the new epithelium were 631.7 µm, 702.5 µm, 759.4 µm, 825.3 µm, 831.7 µm and 836.6 µm for the control group, A, B, C, and D, E respectively (P < 0.05). Furthermore, PCNA and CD31 expression indicated enhanced cell proliferation and angiogenesis in the C, D and E group (P < 0.05).

P311 Deficiency Leads to Attenuated Angiogenesis in Cutaneous Wound Healing.

P311 was identified to markedly promote cutaneous wound healing by our group. Angiogenesis plays a key role in wound healing. In this study, we sought to define the role of P311 in skin wound angiogenesis. It was noted that P311 was expressed in endothelial cells in the dermis of murine and human skin wounds. The expression of P311 was confirmed in cultured murine dermal microvascular endothelial cells (mDMECs). Moreover, it was found that knockout of P311 could attenuate the formation of tubes and motility of mDMECs significantly in vitro. In the subcutaneous Matrigel implant model, the angiogenesis was reduced significantly in P311 knockout mice. In addition, wound healing was delayed in P311 knockout mice compared with that in the wild type. Granulation tissue formation during the defective wound healing showed thinner and blood vessel numbers in wound areas in P311 knockout mice were decreased significantly. A reduction in VEGF and TGFß1 was also found in P311 KO mice wounds, which implied that P311 may modulate the exprssion of VEGF and TGFß1 in wound healing. Together, our findings suggest that P311 plays an important role in angiogenesis in wound healing.

Optimization and integration of nanosilver on polycaprolactone nanofibrous mesh for bacterial inhibition and wound healing in vitro and in vivo.

Bacterial infection is a major hurdle to wound healing, and the overuse of antibiotics have led to global issue, such as emergence of multidrug-resistant bacteria, even "super bacteria". On the contrary, nanosilver (NS) can kill bacteria without causing resistant bacterial strains. In this study, NS was simply generated in situ on the polycaprolactone (PCL) nanofibrous mesh using an environmentally benign and mussel-inspired dopamine (DA). Scanning electron microscopy showed that NS uniformly formed on the nanofibers of PCL mesh. Fourier transform infrared spectroscopy revealed the step-by-step preparation of pristine PCL mesh, including DA coating and NS formation, which were further verified by water contact angle changing from hydrophobic to hydrophilic. To optimize the NS dose, the antibacterial activity of PCL/NS against Staphylococcus aureus, Escherichia coli and Acinetobacter baumannii was detected by bacterial suspension assay, and the cytotoxicity of NS was evaluated using cellular morphology observation and Cell Counting Kit-8 (CCK8) assay. Then, inductively coupled plasma atomic emission spectrometry exhibited that the optimized PCL/NS had a safe and sustained silver release. Moreover, PCL/NS could effectively inhibit bacterial infection in an infectious murine full-thickness skin wound model. As demonstrated by the enhanced level of proliferating cell nuclear antigen (PCNA) in keratinocytes and longer length of neo-formed epidermis, PCL/NS accelerated wound healing by promoting re-epithelialization via enhancing keratinocyte proliferation in infectious wounds.

Epidemiological analysis of 9,596 patients with acute lung injury at Chinese Military Hospitals.

Acute lung injury (ALI) is a common and severe disease that has been associated with significant morbidity and mortality. Understanding the epidemiology of ALI is vital for its prevention and treatment. The present study aimed to analyze the epidemiology of ALI by collecting data from patients that were submitted between 2000 and 2008 into the 'No. 1 Military Medical Project' information system. A total of 9,596 ALI patients were analyzed retrospectively, including 7,284 males (75.91%) and 2,312 females (24.09%). The median age of the patients was 44 years (interquartile range, 31-63 years), and there was a significant difference between the median ages of male and female patients (P<0.01). The number of patients with ALI admitted to the hospitals showed an increasing trend over time. However, there was no significant difference in the annual gender distribution (P>0.05). In addition, ALI was more prevalent in May, July, August, October, November and December, as compared with the other months. ALI occurred at any age, although 40-years-old was the peak age. There was a significant difference in the age group distributions of male and female ALI patients (P<0.01). Among the predisposing conditions, pulmonary contusion represented the highest proportion (45.71%), followed by pneumonia or respiratory tract infection (23.68%) and pulmonary malignant tumor (6.30%). Of the 581 (6.05%) mortalities, pneumonia was the most common cause (37.87%), followed by malignancies (16.87%) and pulmonary embolism (11.02%). However, the highest mortality rate was associated with cardiopulmonary resuscitation (48.28%). In conclusion, the results of the present study suggested that ALI should be increasingly monitored in the future, and predisposing conditions should be regarded as one of the most important features determining the management of ALI.

Establishment and evaluation of an experimental rat model for high-altitude intestinal barrier injury.

In the present study an experimental high-altitude intestinal barrier injury rat model was established by simulating an acute hypoxia environment, to provide an experimental basis to assess the pathogenesis, prevention and treatment of altitude sickness. A total of 70 healthy male Sprague-Dawley rats were divided into two groups: Control group (group C) and a high-altitude hypoxia group (group H). Following 2 days adaptation, the rats in group H were exposed to a simulated 4,000-m, high-altitude hypoxia environment for 3 days to establish the experimental model. To evaluate the model, bacterial translocation, serum lipopolysaccharide level, pathomorphology, ultrastructure and protein expression in rats were assessed. The results indicate that, compared with group C, the rate of bacterial translocation and the apoptotic index of intestinal epithelial cells were significantly higher in group H (P<0.01). Using a light microscope it was determined that the intestinal mucosa was thinner in group H, there were fewer epithelial cells present and the morphology was irregular. Observations with an electron microscope indicated that the intestinal epithelial cells in group H were injured, the spaces among intestinal villi were wider, the tight junctions among cells were open and lanthanum nitrate granules (from the fixing solution) had diffused into the intestinal mesenchyme. The expression of the tight junction protein occludin was also decreased in group H. Therefore, the methods applied in the present study enabled the establishment of a stable, high-altitude intestinal barrier injury model in rats.

Body mass index and risk of non-melanoma skin cancer: cumulative evidence from prospective studies.

Prospective epidemiologic studies that investigated the association between body mass index (BMI) and non-melanoma skin cancer (NMSC) yielded inconsistent findings. A dose-response meta-analysis was conducted to quantitatively summarize the evidence. PubMed and Embase databases were searched for relevant studies. Study-specific relative risk (RR) and 95% confidence interval (CI) for an increase in BMI of 5 kg/m2 was computed with the generalized least squares trend estimation, and these risk estimates were combined with the random-effects model. Nine publications were included in the final analyses, consisting of 18 independent cohorts with 22 risk estimates (971,795 participants and 50,561 NMSC cases). Results of the dose-response analyses showed a nonlinear inverse relationship between BMI and NMSC (RR = 0.88, 95% CI: 0.85-0.91, I2 = 71.2%, P-nonlinearity <0.001), which persisted when limiting to the studies with adjustment for important potential confounders including sun exposure and sensitivity factors. The risk estimates were very similar for squamous cell carcinoma and basal cell carcinoma. Sex appeared a source of heterogeneity (P-difference = 0.06), with a weaker, but still significant inverse association in men than in women. This dose-response meta-analysis suggests a nonlinear inverse association between BMI and NMSC.

Vitamin D receptor Fok I polymorphism is associated with low bone mineral density in postmenopausal women: a meta-analysis focused on populations in Asian countries.

OBJECTIVE: To explore the associations between vitamin D receptor (VDR) gene polymorphisms (including Fok I, Bsm I and Apa I) and bone mineral density (BMD) in postmenopausal Asian women. STUDY DESIGN: Databases of Medline, Embase and Wangfang were retrieved to identify eligible studies, with update to 1st February 2012. Standardized mean difference (SMD) and 95% confidence intervals were calculated by using fixed- or random-effect model. Best genetic comparison model was determined by using the Thakkinstian method. RESULTS: A total of 14 studies with 3243 healthy postmenopausal Asian women were included in this meta-analysis. Overall, pooled analyses indicated that the f allele of VDR Fok I was significantly associated with decreased BMD in the lumbar spine (ff vs. FF: SMD (95% CI): -0.87 (-1.38, -0.35); P=0.001 for lumbar spine; -0.43 (-0.93, 0.06), P=0.086 for femoral neck). In contrast, we did not observe overall associations between VDR Bsm I and Apa I polymorphisms and BMD in either lumbar spine or femoral neck (Bsm I bb vs. BB: SMD (95% CI): 0.61 (-1.30, 2.53), P=0.531 for lumbar spine; Apa I aa vs. AA: SMD (95% CI): 0.66 (-0.16, 1.48), P=0.113 for lumbar spine). When subgroup analyses were conducted according to countries, Indians carrying the VDR Fok I ff genotype were at risk of low BMD at lumbar spine (ff vs. FF: SMD (95% CI): -0.57 (-0.85, -0.29), P<0.001). Sensitivity analyses indicated that no single study had substantial influence on all combined analyses. In addition, no publication bias was identified. CONCLUSIONS: This meta-analysis indicated that VDR Fok I, rather than Bsm I and Apa I polymorphisms, is associated with bone mineral density in postmenopausal Asian women (especially for Indian women), and can probably be used with other genetic markers together to identify individuals at high risk of osteoporosis.