Effect of quality nursing care on wound pain and anxiety in burn patients: A meta-analysis.

To systematically evaluate the effects of quality nursing care on wound pain and anxiety in burn patients. Computerised searches of PubMed, Google Scholar, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure databases randomised controlled trials (RCTs) on the application of quality nursing care to burn patients were carried out from database inception to October 2023. Literature was screened and evaluated by two researchers based on inclusion and exclusion criteria, and data were extracted from the final included literature. Stata 17.0 software was employed for data analysis. Overall, 15 RCTs and 1115 burn patients were included, including 563 and 552 in the quality care and routine care groups. It was found that, compared with routine care, burn patients who implemented quality care had significantly less wound pain (SMD: -1.79, 95% CI: -2.22 to -1.36, p < 0.001), anxiety (SMD: -2.71. 95% CI: -3.49 to -1.92, p < 0.001) and depression (SMD: -1.74, 95% CI: -2.35 to -1.14, p < 0.001) levels were significantly reduced post-trauma.

Clinical epidemiology and a novel predicting nomogram of central line associated bloodstream infection in burn patients.

Burn patients are at high risk of central line-associated bloodstream infection (CLABSI). However, the diagnosis of such infections is complex, resource-intensive, and often delayed. This study aimed to investigate the epidemiology of CLABSI and develop a prediction model for the infection in burn patients. The study analysed the infection profiles, clinical epidemiology, and central venous catheter (CVC) management of patients in a large burn centre in China from January 2018 to December 2021. In total, 222 burn patients with a cumulative 630 CVCs and 5,431 line-days were included. The CLABSI rate was 23.02 CVCs per 1000 line-days. The three most common bacterial species were Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa; 76.09% of isolates were multidrug resistant. Compared with a non-CLABSI cohort, CLABSI patients were significantly older, with more severe burns, more CVC insertion times, and longer total line-days, as well as higher mortality. Regression analysis found longer line-days, more catheterisation times, and higher burn wounds index to be independent risk factors for CLABSI. A novel nomogram based on three risk factors was constructed with an area under the receiver operating characteristic curve (AUROC) value of 0.84 (95% CI: 0.782-0.898) with a mean absolute error of calibration curve of 0.023. The nomogram showed excellent predictive ability and clinical applicability, and provided a simple, practical, and quantitative strategy to predict CLABSI in burn patients.

First trimester serum PAPP-A is associated with placenta accreta: a retrospective study.

PURPOSE: Our objective of this study was to investigate whether first trimester serum pregnancy-associated plasma protein-A (PAPP-A) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies by a retrospective cohort analysis. METHODS: A total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of BMI and age matched, healthy pregnant controls. PAPP-A multiples of the median (MoM) were acquired from laboratory data files in 1 January 2017-30 September 2019. The probable maternal serum biochemical predictor of placenta accreta was analyzed by using multiple logistic regression analysis. RESULTS: PAPP-A MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.009 < 0.05, p < 0.001). Serum PAPP-A was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, age, smoking, and previous cesarean section history (OR: 3.51; 95% CI: 1.77-6.94; p = 0.0003 < 0.05). In addition, smoking (OR: 9.17; 95% CI: 1.69-49.62; p = 0.010 < 0.05) and previous cesarean section history (OR: 2.75; 95% CI: 1.23-6.17; p = 0.014 < 0.05) were also significantly associated with placenta accreta. CONCLUSION: Increased first trimester serum PAPP-A was significantly positively associated with placenta accreta, suggesting that the potential role of PAPP-A in identifying pregnancies at high risk for placenta accreta. Smoking and previous cesarean section history may be the risk factors for accreta in placenta previa patients.

Clinical profile, management and risk factors for seizure-related burn injuries among patients with epilepsy in southwest China.

Objective: The epidemiological information associated with seizure-related burn injuries is lacking in China. Therefore, this study aims to analyze the clinical profile, management, outcome, and risk factors of burns that are directly caused by seizures among epileptic patients, and identify the epidemiological characteristics to develop effective preventive strategies. Methods: This study was conducted between January 2002 and December 2022 in a large Chinese burn center. Data including clinical profile, wound treatment, and outcome were analyzed. A multiple linear regression was used to screen the risk factors for the length of hospital stay (LOS), and a multiple logistic regression was used to screen the contributory factors for the amputation. Results: A total of 184 burn patients (55.98 % females) were enrolled, with a 0.78 % incidence rate during the study period. The mean age of the patients was 36.16 years (SD: 17.93). Patients aged 20-29 were the most affected age groups (23.37 %). Most burns were caused by flame, accounting for 60.33 % (111/184) of all cases. In total, 76.09 % of the 184 patients underwent at least one operation, and 35 patients (19.02 %) still required amputation during the study period. Burn sites (hands) had the greatest impact on amputation (OR = 3.799), followed by flame burns (OR = 3.723). The mean LOS/TBSA was 6.90 ± 8.53 d, and a larger TBSA, full-thickness burns, and a higher number of operations were identified as the risk factors for a longer LOS. There was one death among the 184 patients, with a mortality rate of 0.54 %. Conclusion: This study demonstrates that burn injuries are extremely harmful to individuals with epilepsy in China because they are at high risk of amputation and disability. Effective healthcare education and preventive programs that focus on lifestyle modifications and seizure control should be implemented to reduce the burn incidence in these populations.

Multidisciplinary treatment for acute massive upper gastrointestinal bleeding secondary to post-burn stress in a paediatric patient: a case report.

BACKGROUND: Severe burns can readily induce gastric and duodenal mucosal erosions and superficial ulcers. In severe cases, haemorrhage or perforation of peptic ulcers might occur, threatening the lives of patients. At present, gastrointestinal haemorrhage after burns is treated mainly with drugs and gastrointestinal endoscopy. However, multidisciplinary treatment of gastroscopy combined with vascular embolization is rare. CASE: A boy aged 3 years and 4 months was admitted to the hospital, scalded by boiling water on multiple parts of the body. On the 8th day after the injury, the patient continuously produced a large amount of tarry black stool, and the faecal occult blood test was positive. Haemostatic drug treatment was ineffective, and severe shock and disseminated intravascular coagulation (DIC) occurred. Under the guidance of a multidisciplinary team (MDT), a gastroscopy examination was performed and showed bleeding from a duodenal bulb ulcer. Due to a small intestinal lumen and thin intestinal wall, bleeding could not be controlled by gastroscopy. However, the bleeding point was clarified by gastroscopy and then gastroduodenal artery embolization was performed efficiently. No active gastrointestinal bleeding was observed after the surgery. The patient was followed for 6 months after discharge, and no gastrointestinal haemorrhage recurred. CONCLUSIONS: This is a rare case of acute massive upper gastrointestinal bleeding secondary to post-burn stress in paediatric patients. For paediatric patients who cannot be treated by endoscopy, transcatheter embolization may be safer and more effective for achieving haemostasis. Through the collaboration of the MDT, gastroscopy combined with interventional embolization was performed, which successfully stopped the massive bleeding and saved the child`s life, making it worthy of clinical reference.

Anomalous spin current anisotropy in a noncollinear antiferromagnet.

Cubic materials host high crystal symmetry and hence are not expected to support anisotropy in transport phenomena. In contrast to this common expectation, here we report an anomalous anisotropy of spin current can emerge in the (001) film of Mn3Pt, a noncollinear antiferromagnetic spin source with face-centered cubic structure. Such spin current anisotropy originates from the intertwined time reversal-odd ([Formula: see text]-odd) and time reversal-even ([Formula: see text]-even) spin Hall effects. Based on symmetry analyses and experimental characterizations of the current-induced spin torques in Mn3Pt-based heterostructures, we find that the spin current generated by Mn3Pt (001) exhibits exotic dependences on the current direction for all the spin components, deviating from that in conventional cubic systems. We also demonstrate that such an anisotropic spin current can be used to realize low-power spintronic applications such as the efficient field-free switching of the perpendicular magnetizations.

The Prognostic Value of N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) in Major Burn Patients With Sepsis.

The aim is to examine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with major burns and sepsis. We collected the data of major burn patients who were admitted to our department. We compared the age, sex, burn area, burn depth, length of hospitalization, and mortality rate between the sepsis group and non-sepsis group and compared NT-proBNP, procalcitonin (PCT), platelet count, Sequential Organ Failure Assessment (SOFA) score, and quick SOFA (qSOFA) score between the survivors and nonsurvivors in the sepsis group. Receiver operating characteristic (ROC) curves were used in sepsis patients to evaluate the prognostic value of NT-proBNP, PCT, SOFA score, qSOFA score, etc. Kaplan-Meier survival curves were used to compare the 90-day survival curves of patients. Logistic regression analysis was used to analyze the risk factors that affect the prognosis of sepsis patients. There were 90 major burn patients with sepsis and 114 major burn patients without sepsis. The mortality rate for the major burn sepsis group was significantly higher than that for the non-sepsis group. The NT-proBNP level in sepsis patients in the nonsurvivor group was 2900 pg/ml, which was significantly higher than that in patients in the survivor group. Survival analysis showed that the mean survival time for the NT-proBNP >2000 pg/ml group was 15.08 days. Multivariate regression analysis indicated that NT-proBNP was an independent risk factor for mortality in burn patients with sepsis. NT-proBNP can be used as a prognostic marker in patients with major burns and sepsis.

IL-1ß/NF-κB signaling inhibits IGF-1 production via let-7f-5p in dendritic epidermal T cells.

Dendritic epidermal T cells (DETCs) are the main source of insulin-like growth factor-1 (IGF-1) in epidermal tissue, which promote re-epithelialization and wound healing. In refractory wounds, IL-1ß has been shown to activate NF-κB and suppress IGF-1 expression in DETCs. Nevertheless, the underlying mechanisms remain unclear. In this study, chromatin immunoprecipitation analysis revealed that IL-1ß did not inhibit NF-κB binding to IGF-1 promoter, indicating that IL-1ß/NF-κB may suppress IGF-1 expression by alternative mechanisms. MiRNAs negatively regulate gene expression predominantly by base pairing to the 3' untranslation region (UTR) of target mRNAs. Let-7f-5p, miR-1a-3p, and miR-98-5p have been identified as IGF-1-specific miRNAs that can bind directly to the 3'UTR of IGF-1 mRNA and dysregulate IGF-1 mRNA and protein levels. In IL-1ß-treated epidermis around wounds or DETCs in vitro, NF-κB promoted the expression of let-7f-5p, and IGF-1 expression was impeded via NF-κB/let-7f-5p pathway. As pre-let-7f-5p, let-7f-1 is located in the 3'UTR of LOC118568094, and let-7f-2 is located in the intron of HUWE1. We discovered that NF-κB p65 bound to the promoters of LOC118568094 and HUWE1 to accelerate let-7f-5p expression, but NF-κB p65 did not affect the methylation levels of LOC118568094 and HUWE1 CpG islands. Injections of Let-7f-5p antagomir into IL-1ß-treated and ischemic wound margins restored IGF-1 secretion in DETCs and promoted wound healing. In conclusion, we demonstrated that NF-κB signaling pathway activated by IL-1ß could increase let-7f-5p expression to inhibit IGF-1 production in DETCs and delay wound healing. And let-7f-5p antagomir utilized in wound margin could effectively promote refractory wound healing.

Vγ4 T cell-derived IL-17A is essential for amplification of inflammatory cascades in ischemic brain tissue after stroke.

BACKGROUND: Through amplifying inflammatory cascades, IL-17A produced by γδ T cells potently attracts neutrophils to the site of injury for exacerbating ischemic tissue damage. Our goal was to identify the precise role of γδ T cell subsets in ischemic brain tissue damage of stroke. METHODS: In a model of experimental stroke, we analyzed the functions of Vγ1 and Vγ4 T cells on γδ T cell-mediated ischemic brain tissue damage of stroke. RESULTS: We identified that, in stroke, Vγ4 T cells are essential for γδ T cell-mediated ischemic brain tissue damage through providing an early source of IL-17A. Both CCL20 and IL-1ß/IL-23 are deeply involved in Vγ4 T cell-mediated amplification of inflammatory responses: CCL20 might promote Vγ4 T cells recruit to infract hemisphere, and IL-1ß/IL-23 powerfully enhance IL-17A production mediated by the infiltrating Vγ4 T cells. Moreover, Vγ4 T cell-derived IL-17A enhances both CCL20 and IL-1ß, and conversely, CCL20 and IL-1ß further enhance both recruitment and IL-17A production of IL-17A-positive cells, in a classic positive feedback loop. CONCLUSION: Our data suggest that in the setting of ischemic stroke, Vγ4 T cell-derived IL-17A, CCL20 and IL-1ß/IL-23 in infract hemisphere coordinately to amplify inflammatory cascades and exacerbate ischemic tissue damage.

Epidemiology and Outcome Analysis of Burns During Explosion Accident at a Major Center in Southwestern China From 2002 to 2016.

Explosions always lead to serious public health, social, and economic problems. We investigated the epidemiology, outcomes, and costs of burn patients caused by explosion accident in Southwest China to explore more effective prevention and treatment strategies. This retrospective study included 497 inpatients with burns during explosion accident admitted to the Institute of Burn Research of Army Medical University from 2002 to 2016. A total of 497 cases (77.78% males) were found, accounting for 2.37% of the total burn patients. The average age was 34.38 ± 15.02 years. The most common etiology was gas explosions (51.51%). Most of the cases were caused by work-related activities. The average TBSA was 31.30 ± 28.32%. The median length of stay (LOS) was 31 days. The LOS was correlated with TBSA, full-thickness burns, older age, number of operations and outcome. The major factors determining the cost were larger TBSA, full-thickness burns, and higher cure rate. The mortality was 6.44%. Larger TBSA and older age were the most important risk factors for the mortality. This study suggested that special attention should be paid to prevent burns during explosion accident in adult males with occupational exposure. In the future, more effective and practical strategies for preventing and treating burns during explosion accident based on related risk factors should be implemented.

First trimester serum PIGF is associated with placenta accreta.

OBJECTIVES: In this retrospective study, we investigated whether first trimester serum placental growth factor (PIGF) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies. METHODS: In 1 January 2017-30 September 2019, a total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of age and BMI-matched, healthy pregnant controls. PIGF multiples of the median (MoM) were acquired from laboratory data files. The predictor of placenta accreta was analyzed by using multiple logistic regression analysis. RESULTS: PIGF MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.0098 < 0.01, p = 0.0002 < 0.01). Serum PIGF was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, and age (OR: 4.83; 95% CI: 1.91-12.24；p = 0.0009 < 0.01). In addition, previous cesarean section history (OR: 2.75; 95% CI: 1.23-6.17; p = 0.014 < 0.05) and smoking (OR: 9.17; 95% CI: 1.69-49.62; p = 0.010 < 0.05) were also significantly associated with placenta accreta. CONCLUSION: Increased first trimester serum PIGF was significantly positively associated with placenta accreta, suggesting that the potential role of PIGF in identifying pregnancies at high risk for placenta accreta. Previous cesarean section history and smoking may be the risk factors for accreta in placenta previa patients.

Epidemiological and clinical characteristics of burns in the older person: a seven-year retrospective analysis of 693 cases at a burn center in south-west China.

BACKGROUND: Burns are one of the major traumas that may affect older individuals. The purpose of this study was to investigate the epidemiological and clinical characteristics of geriatric burns at a major center in south-west China. METHODS: This retrospective study was conducted at the Institute of Burn Research, Southwest Hospital of Army Medical University between 2010 and 2016, and the data collected from medical records included admission date, age, gender, premorbid disease, burn etiology, injured anatomical location, burn area and depth, inhalation injury, number of surgeries, length of stay (LOS), clinical outcome, and medical cost. RESULTS: Of the 693 older burn patients included, 60.75% were male and 56.85% were aged 60-69 years. Burns peaked in December-March and June. Flame was the most common cause of burns, making up 51.95% of all cases, and also dominated in the burn patients aged 60-69 years. Limbs were the most common anatomical sites of burns (69.41%), and the median total body surface area (TBSA) was 5% (interquartile range [IQR]: 2%-15%). The percentage of the patients who underwent surgeries and number of surgeries significantly increased in the cases of contact burns, younger age and full-thickness burns. Six deaths resulted in a mortality of 0.9%. The median LOS was 16 days (IQR: 8-29 days), and the main risk factors were more surgeries, better outcomes, and full-thickness burns. The median cost was 20,228 CNY (IQR: 10,457- 46,581.5 CNY), and major risk factors included longer LOS, larger TBSA, and more surgeries. Furthermore, compared to the earlier data from our center, the proportion of older adults among all burns (7.50% vs. 4.15%), proportion of flame burns (51.95% vs. 33.90%), and mean age (69.05 years vs. 65.10 years) were significantly higher, while the proportion of premorbidities (16.9% vs. 83.9%), mortality (0.9% vs. 7.5%) and median TBSA (5% vs. 21%) were significantly lower. CONCLUSIONS: This study suggested that closer attention should be paid to prevent burn injuries in older people aged 60-69 years, especially males, regarding incidents in the summer and winter, and flame burns. Moreover, tailored intervention strategies based on related risk factors should be under special consideration.

Proinflammatory cytokines increase hepatocellular carcinoma cells thermotolerance: evidence of how local inflammation may negatively impact radiofrequency ablation local control rates.

BACKGROUND: Hepatocellular carcinomas (HCC) associated with inflammation that undergo radiofrequency ablation (RFA) appear to have poorer local control rates. Little is known of how mediators of inflammation influence HCC cellular thermotolerance, which in part is mediated by heat shock protein 70 (HSP70). This study determines how inflammatory mediators affect cellular thermotolerance and provides insight into how associated inflammation may impact HCC RFA local control rates. METHODS: HepG2 cell lines were cultured in control medium (CM) or CM containing conditioned medium of endotoxin-activated macrophage (CMM). Serial dilutions of CMM established microenvironments approximating low, medium, and high CMM. All groups underwent a heat shock challenge (HSC) at 45 degrees C for 10 min. Western blot, Northern blot, densitometric analysis, along with thymidine and clonogenic assays determined how inflammation influenced multiple biological endpoints. RESULTS: Cells cultured in low CMM expressed significantly more HSP70 RNA and protein compared with control cells after HSC. The cells also had a higher proliferative and survival rate after HSC compared with control cells. Medium CMM cultured cells had no significant difference in HSP70 RNA and protein production or proliferation and survival rates after HSC, compared with CM cultured cells. AT high CMM, the inhibitory effects of inflammatory mediators prevailed and all of the measured endpoints were significantly less compared with CM cultured cells. CONCLUSIONS: This study demonstrates that inflammation can alter the responsiveness of HCC cells to a HSC in a dose-dependent manner. This study supports the clinical observation that HCC associated with chronic inflammation have worse RFA local control rates.

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.

Vγ4 T Cells Inhibit the Pro-healing Functions of Dendritic Epidermal T Cells to Delay Skin Wound Closure Through IL-17A.

Dendritic epidermal T cells (DETCs) and dermal Vγ4 T cells engage in wound re-epithelialization and skin inflammation. However, it remains unknown whether a functional link between Vγ4 T cell pro-inflammation and DETC pro-healing exists to affect the outcome of skin wound closure. Here, we revealed that Vγ4 T cell-derived IL-17A inhibited IGF-1 production by DETCs to delay skin wound healing. Epidermal IL-1ß and IL-23 were required for Vγ4 T cells to suppress IGF-1 production by DETCs after skin injury. Moreover, we clarified that IL-1ß rather than IL-23 played a more important role in inhibiting IGF-1 production by DETCs in an NF-κB-dependent manner. Together, these findings suggested a mechanistic link between Vγ4 T cell-derived IL-17A, epidermal IL-1ß/IL-23, DETC-derived IGF-1, and wound-healing responses in the skin.

IL-15 Enhances Activation and IGF-1 Production of Dendritic Epidermal T Cells to Promote Wound Healing in Diabetic Mice.

Altered homeostasis and dysfunction of dendritic epidermal T cells (DETCs) contribute to abnormal diabetic wound healing. IL-15 plays important roles in survival and activation of T lymphocytes. Recently, reduction of epidermal IL-15 has been reported as an important mechanism for abnormal DETC homeostasis in streptozotocin -induced diabetic animals. However, the role of IL-15 in impaired diabetic wound healing remains unknown. Here, we found that, through rescuing the insufficient activation of DETCs, IL-15 increased IGF-1 production by DETCs and thereby promoted diabetic skin wound repair. Regulation of IGF-1 in DETCs by IL-15 was partly dependent on the mTOR pathway. In addition, expression of IL-15 and IGF-1 were positively correlated in wounded epidermis. Together, our data indicated that IL-15 enhanced IGF-1 production by DETCs to promoting diabetic wound repair, suggesting IL-15 as a potential therapeutic agent for managing diabetic wound healing.

A Parallel Nonrigid Registration Algorithm Based on B-Spline for Medical Images.

The nonrigid registration algorithm based on B-spline Free-Form Deformation (FFD) plays a key role and is widely applied in medical image processing due to the good flexibility and robustness. However, it requires a tremendous amount of computing time to obtain more accurate registration results especially for a large amount of medical image data. To address the issue, a parallel nonrigid registration algorithm based on B-spline is proposed in this paper. First, the Logarithm Squared Difference (LSD) is considered as the similarity metric in the B-spline registration algorithm to improve registration precision. After that, we create a parallel computing strategy and lookup tables (LUTs) to reduce the complexity of the B-spline registration algorithm. As a result, the computing time of three time-consuming steps including B-splines interpolation, LSD computation, and the analytic gradient computation of LSD, is efficiently reduced, for the B-spline registration algorithm employs the Nonlinear Conjugate Gradient (NCG) optimization method. Experimental results of registration quality and execution efficiency on the large amount of medical images show that our algorithm achieves a better registration accuracy in terms of the differences between the best deformation fields and ground truth and a speedup of 17 times over the single-threaded CPU implementation due to the powerful parallel computing ability of Graphics Processing Unit (GPU).

Knockdown of WAVE1 enhances apoptosis of leukemia cells by downregulating autophagy.

Chemoresistance of leukemia constitutes a great challenge for successful treatment of leukemia. Autophagy has recently attracted increasing attention for its role in conferring resistance to various conventional anti-neoplastic regiments. In the present study, the authors showed that WAVE1, a member of WASP family verprolin-homologous proteins, is a critical regulator of chemoresistance during autophagy. It is positively correlated with clinical status in pediatric acute myeloblastic leukemia (AML) and leukemia cell lines. The knockdown of WAVE1 expression decreased autophagy was accompanied by an upregulation of autophagic marker microtubule-associated protein light chain 3 (LC3)-Ⅱ, a degradation of SQSTM1/sequestosome 1 (p62) and the formation of autophagosomes. Moreover, a suppression of WAVE1 expression increased the sensitivity of leukemia cells to chemotherapy and apoptosis, and depletion of WAVE1 expression promoted the translocation of Bcl-2 from mitochondria into the cytoplasm. In addition, a knockdown of PI3K-Ⅲ expression significantly inhibited WAVE1-mediated autophagy. Furthermore, suppression of WAVE1 expression blocked the interactions between Beclin1 and PI3K-Ⅲ and the disassociation of Beclin1-Bcl-2 during enhanced autophagy. The above results suggested that WAVE1 is a critical pro-autophagic protein capable of enhancing cell survival and regulating chemoresistance in leukemia cells potentially through the Beclin1/Bcl-2 and Beclin1/PI3K-Ⅲ complex-dependent pathways.

Pharmacokinetics of engineered human monomeric and dimeric CH2 domains.

Therapeutic monoclonal antibodies have several advantages over small molecule drugs and small proteins and peptides, including a long serum half-life. The long serum half-life of IgG is due, in part, to its molecular weight (150kDa) and its ability to bind FcRn. Both the CH2 and CH3 domains of Fc are involved in FcRn binding. Antibody fragments and antibody-like scaffolds have improved penetration into tissues due to their small size, yet suffer from a short serum half-life of less than one hour. The human CH2 domain (CH2D) of IgG1 retains a portion of the FcRn binding site, is amenable to modification for target binding, and may represent the smallest antibody-like scaffold retaining a relatively long serum half-life. Here we describe the generation of a dimeric CH2D (dCH2D) and determination of its pharmacokinetics (PK), as well as the PK of wild-type monomeric CH2D (mCH2D) and a short stabilized CH2D variant (ssCH2D) in normal B6 mice, human FcRn transgenic mice and cynomolgus macaques. The elimination half-life of dCH2D was 9.9, 10.4 and 11.2 hours, and that of ssCH2D was 13.1, 9.9 and 11.4 hours, in B6 mice, hFcRn mice and cynomolgus macaques, respectively. These half-lives were slightly longer than that of mCH2D (6.9 and 8.8 hours) in B6 and hFcRn mice, respectively. These data demonstrate that engineered CH2D-based variants have relatively long serum half-lives, making them a unique scaffold suitable for development of targeted therapeutics.