Evolution of the flat band and the role of lattice relaxations in twisted bilayer graphene.

Magic-angle twisted bilayer graphene exhibits correlated phenomena such as superconductivity and Mott insulating states related to the weakly dispersing flat band near the Fermi energy. Such a flat band is expected to be sensitive to both the moiré period and lattice relaxations. Thus, clarifying the evolution of the electronic structure with the twist angle is critical for understanding the physics of magic-angle twisted bilayer graphene. Here we combine nano-spot angle-resolved photoemission spectroscopy and atomic force microscopy to resolve the fine electronic structure of the flat band and remote bands, as well as their evolution with twist angle from 1.07° to 2.60°. Near the magic angle, the dispersion is characterized by a flat band near the Fermi energy with a strongly reduced band width. Moreover, we observe a spectral weight transfer between remote bands at higher binding energy, which allows to extract the modulated interlayer spacing near the magic angle. Our work provides direct spectroscopic information on flat band physics and highlights the important role of lattice relaxations.

[Association Between Dietary Diversity and Caregiver Self-Efficacy for Complementary Feeding Among Infants and Young Children Aged 6-23 Months in Rural Nanchong City,Sichuan Province].

Objective To analyze the current situation of dietary diversity and caregiver self-efficacy for complementary feeding among infants and young children aged 6 to 23 months in rural Nanchong city,Sichuan province,and to explore the relationship between dietary diversity and caregiver self-efficacy. Methods Multi-stage randomized cluster sampling method was used to select infants and young children aged 6 to 23 months and their caregivers in rural areas of Nanchong city,Sichuan province as the subjects.A structured questionnaire was designed to collect the basic information of the subjects,dietary diversity,and caregiver self-efficacy for complementary feeding.Multivariate Logistic regression was adopted to analyze the relationship between the dietary diversity and caregiver self-efficacy for complementary feeding of infants and young children. Results A total of 770 pairs of infants and young children and their caregivers were included.The minimum pass rate of dietary diversity was 61.56%(474/770) for all the infants and young children and 45.00%(108/240),69.16%(287/415),and 68.70%(79/115) for the infants and young children aged 6 to 11,12 to 17,and 18 to 23 months,respectively.The results of regression analysis showed that the caregiver self-efficacy of complementary feeding was a contributing factor for qualified dietary diversity of infants and young children in the case of other confounders being controlled(OR=1.42,95%CI=1.17-1.73,P<0.001). Conclusion The dietary diversity for infants and young children in rural Nanchong city,Sichuan province needs to be improved,and caregivers with higher self-efficacy of complementary feeding are more likely to provide diversified complementary feeding for infants and young children.

[Association between Yingyangbao cognition and feeding behavior of caregivers in rural areas of Sichuan Province:the mediating effect of self-efficacy].

OBJECTIVE: To describe the current situation of Yingyangbao feeding in rural areas of Sichuan, and to explore the mechanism among micronutrient powder cognition, self-efficacy and feeding behavior. METHODS: The multi-stage cluster sampling method was adopted. In October 2019, in 2 Han counties, 2 Tibetan counties, and 2 Yi counties in Sichuan Province, a total of 108 villages in 36 townships in 6 sample counties were included in the cluster. Caregivers of infants and young children aged 6-24 months were selected as the research subjects, and a face-to-face interview survey was conducted using a self-designed structured questionnaire. RESULTS: A total of 765 caregivers of infants and young children aged 6-24 months were included in this study. The effective feeding rate of the Yingyangbao was 54.43%. The average scores of caregivers Yingyangbao cognition, self-efficacy and feeding behavior were 3.80±1.16, 7.96±1.53 and 0.83±0.38, and there was a significant positive correlation between them. Self-efficacy played a partial mediating effect between caregivers' Yingyangbao cognition and feeding behavior, and the mediating effect accounted for 23.37% of the total effect. CONCLUSION: Yingyangbao cognition directly affects feeding behavior and indirectly affects feeding behavior through self-efficacy.

[Factors Associated With Coronary Heart Disease Among Adult Residents in Jinjiang District,Chengdu City].

Objective To analyze the prevalence of coronary heart disease among community residents over 18 years old in Jinjiang district of Chengdu city,Sichuan province,and explore its associated factors,so as to provide a reference for the prevention and control of coronary heart disease in communities.Methods From October 15 to November 10 in 2021,a total of 5220 adult residents from 33 communities in Jinjiang were selected by multi-stage stratified random sampling for face-to-face questionnaire survey,physical examination,and laboratory blood test.Binary Logistic regression was employed to predict the factors associated with coronary heart disease among adult residents in Jinjiang.Results The crude and standard prevalence rates of coronary heart disease among 5220 adult residents were 3.39% and 2.11%,respectively.Logistic regression analysis showed that age (OR=1.068,95%CI=1.051-1.086,P<0.001),depressive symptoms (OR=1.639,95%CI=1.037-2.591,P=0.034),regular exercise (OR=0.584,95%CI=0.378-0.902,P=0.015),elevated blood pressure (OR=3.529,95%CI=2.344-5.312,P<0.001),dyslipidemia (OR=2.152,95%CI=1.291-3.587,P=0.003),and core knowledge score of chronic diseases (OR=1.144,95%CI=1.066-1.228,P<0.001) were associated with coronary heart disease among adult residents in Jinjiang.Conclusions The prevalence of coronary heart disease is high among adult residents in Jinjiang district of Chengdu.The urban residents who are older,have depressive symptoms,lack of exercise,elevated blood pressure,dyslipidemia,and score higher on core knowledge of chronic diseases are prone to coronary heart disease.

NRF2-ARE signaling is responsive to haloacetonitrile-induced oxidative stress in human keratinocytes.

Humans are exposed to disinfection by-products through oral, inhalation, and dermal routes, during bathing and swimming, potentially causing skin lesions, asthma, and bladder cancer. Nuclear factor E2-related factor 2 (NRF2) is a master regulator of the adaptive antioxidant response via the antioxidant reaction elements (ARE) orchestrating the transcription of a large group of antioxidant and detoxification genes. Here we used an immortalized human keratinocyte model HaCaT cells to investigate NRF2-ARE as a responder and protector in the acute cytotoxicity of seven haloacetonitriles (HANs), including chloroacetonitrile (CAN), bromoacetonitrile (BAN), iodoacetonitrile (IAN), bromochloroacetonitrile (BCAN), dichloroacetonitrile (DCAN), dibromoacetonitrile (DBAN), and trichloroacetonitrile (TCAN) found in drinking water and swimming pools. The rank order of cytotoxicity among the HANs tested was IAN ≈ BAN Ëƒ DBAN Ëƒ BCAN ˃ CAN Ëƒ TCAN Ëƒ DCAN based on their LC50. The HANs induced intracellular reactive oxygen species accumulation and activated cellular antioxidant responses in concentration- and time-dependent fashions, showing elevated NRF2 protein levels and ARE activity, induction of antioxidant genes, and increased glutathione levels. Additionally, knockdown of NRF2 by lentiviral shRNAs sensitized the HaCaT cells to HANs-induced cytotoxicity, emphasizing a protective role of NRF2 against the cytotoxicity of HANs. These results indicate that HANs cause oxidative stress and activate NRF2-ARE-mediated antioxidant response, which in turn protects the cells from HANs-induced cytotoxicity, highlighting that NRF2-ARE activity could be a sensitive indicator to identify and characterize the oxidative stress induced by HANs and other environmental pollutants.

The efficacy of myo-inositol supplementation to reduce the incidence of gestational diabetes: a meta-analysis.

INTRODUCTION: Myo-inositol supplementation is used to reduce the incidence of gestational diabetes, but its efficacy is not well established. This meta-analysis aims to explore the influence of myo-inositol supplementation on the prevention of gestational diabetes. METHODS: This meta-analysis has been conducted up to March 2022 to identify randomized clinical trials comparing the efficacy of myo-inositol supplementation to prevent gestational diabetes. Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systemically. RESULTS: We have included eight RCTs in this meta-analysis. Compared with control group in pregnant women, myo-inositol supplementation was found to significantly decrease the incidence of gestational diabetes (OR = 0.40; 95% CI = 0.19 to 0.84; p = .01), 2-h glucose OGTT (SMD = -0.22; 95% CI = -0.41 to -0.02; p = .03), HOMA-IR (SMD = -0.25; 95% CI = -0.42 to -0.08; p = .004) and preterm delivery (OR = 0.41; 95% CI = 0.23 to 0.73; p = .003), but demonstrated no obvious impact on gestational age at birth (SMD = 0.12; 95% CI = -0.05 to 0.29; p = .18) or birth weight (SMD = -0.04; 95% CI = -0.20 to 0.13; p = .68). CONCLUSIONS: Myo-inositol supplementation is effective to reduce the incidence of gestational diabetes, 2-h glucose OGTT, HOMA-IR and preterm delivery, which suggested that myo-inositol supplementation should be recommended to prevent gestational diabetes.

The Three-Dimensional Structure of Porcine Bladder Scaffolds Alters the Biology of Murine Diabetic Wound Healing.

OBJECTIVE: To determine if the various three-dimensional structures of bioscaffolds affect wound healing by investigating the efficacy of different porcine-derived urinary bladder matrix (UBM) structures in treating murine diabetic wound healing. METHODS: The authors studied three different UBM structures: particulate (pUBM), one-layer freeze-dried sheet (fdUBM), and three-layer laminated sheet (lmUBM). Scanning electron microscopy images of the structures were used to calculate a wound-exposed surface-area-to-volume ratio. A 1.0 × 1.0-cm full-thickness dorsal wound was excised on 90 db/db mice. Mice were either untreated (blank, n = 15), treated with one UBM structure (pUBM, n = 15; fdUBM, n = 15; lmUBM, n = 15), or treated with a combination of either the one- or three-layer sheet over the particulate matrix (fdUBM + pUBM, n = 15; lmUBM + pUBM, n = 15). The authors obtained macroscopic images of the wounds and harvested tissues for analyses at multiple time points. RESULTS: The surface area available to interact with the wound was highest in the pUBM group and lowest in the lmUBM group. Greater wound bed thickness was noted in the fdUBM, fdUBM + pUBM, and lmUBM groups compared with the blank group. Cellular proliferation was significantly higher in the fdUBM and fdUBM + pUBM groups than in the blank group. The lmUBM + pUBM group had the highest collagen deposition. The pUBM group induced significantly higher leukocyte infiltration compared with the lmUBM, lmUBM + pUBM, and blank groups. Microvessel density was highest in the fdUBM + pUBM group. Significant differences in the wound closure rate were noted between the blank group and the fdUBM and fdUBM + pUBM groups. CONCLUSIONS: Assessment of the three UBM bioscaffold structures highlighted differences in the wound-exposed surface area. Variations in wound healing effects, including collagen deposition, cellular proliferation, and angiogenesis, were identified, with combinations of the structures displaying synergistic effects. This study serves as a platform for future scaffold design and offers promising evidence of the benefits of combining various structures of scaffolds.

The Rising Interest in Canthoplasty: An Analysis of Online Search Trends.

ABSTRACT: Canthoplasty as a cosmetic procedure appears to be on the rise in the West. Online search query data offers a powerful tool for analyzing population trends, including changes in patient interest in surgical procedures. Cosmetic surgeons can utilize the internet to increase patient education and interest, as well as to provide information and address misinformation. In this study we sought to verify the increase in cosmetic canthoplasty, for the first time, through analysis of Internet search data, and to establish trends in the interest of Internet users for cosmetic canthoplasty. These trends were subsequently compared with trends in literature publication to establish whether there is a correlation between patient and surgeon interest in the procedure.

Alterations of B Cells in Immunosuppressive Phase of Septic Shock Patients.

OBJECTIVES: Septic shock is a subset of sepsis related to acute circulatory failure characterized by severe immunosuppression and high mortality. Current knowledge about B-cell status in the immunosuppressive phase of septic shock is sparse. The aim of this study was to investigate the alterations of B Cells in the immunosuppressive phase of septic shock. DESIGN: Prospective cohort study. SETTING: Adult ICUs at a university hospital. PATIENTS: Adult septic shock patients without any documented immune comorbidity. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The absolute counts of lymphocytes and B cells of 81 patients and 13 healthy controls, and serum immunoglobulin levels of 64 patients and 10 healthy controls were determined by clinical laboratory. The percentages and counts of B-cell subsets of 33 patients and 10 healthy controls and the immunoglobulin M expression on B-cell subsets of 20 patients and five healthy controls were quantified by flow cytometry. Immunoglobulin levels produced by B cells after stimulation in vitro of 20 patients and five healthy controls were tested by enzyme-linked immunosorbent assay. Redistribution and selective depletion of B-cell subsets in septic shock patients were discovered, and a decrease in immunoglobulin M levels was associated with a reduction in resting memory B-cell counts. These alterations were more pronounced in nonsurvivors compared with survivors. Additionally, receiver operating characteristic curve analysis showed that the data of B-cell subsets had the best predictive value for mortality risk. CONCLUSIONS: Severe B-cell abnormalities are present in the immunosuppressive phase of septic shock and are associated with prognosis.

Recent advances in dielectrophoresis-based cell viability assessment.

Dielectrophoresis (DEP) is a non-destructive, accurate, and label-free cell manipulating technique and DEP applications have been found in various fields. Assessment of cell viability is one of the important applications and many investigations have been reported. In this paper, cell polarization and its modeling, some key parameters employed for living/dead cell separation, as well as electrode configurations are reviewed. Focus is given to the latest development of DEP devices employed for the assessment of cell viability. Experimentally determined factors for separating living/dead cells, such as the conductivity of suspending medium and the frequency of applied electric field, are summarized. The future directions and potential challenges in this field are also outlined.

Nanoparticle and microorganism detection with a side-micron-orifice-based resistive pulse sensor.

This paper presents the detection of nanoparticles and microorganisms using a recently developed side-orifice-based resistive pulse sensor (SO-RPS). By decreasing the channel height of the detection section of the SO-RPS, the detection sensitivity was increased and an average signal to noise ratio (S/N) of about 3 was achieved for 100 nm polystyrene particles. It was also found that spherical particles generate symmetrical signals. Algae with irregular shapes generate signals with more complex patterns. A scatter plot of signal magnitude versus signal width was proven to be reliable for differentiating bacteria from the nanoparticles and two types of algae. The side orifice for detecting heterogeneous nanoparticles and microorganisms is advantageous to avoid orifice clogging and the large flow resistance.

Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis.

Sepsis-associated encephalopathy (SAE) manifested clinically in acute and long-term cognitive impairments and associated with increased morbidity and mortality worldwide. The potential pathological changes of SAE are complex and remain to be elucidated. Pyroptosis, a novel programmed cell death, is executed by caspase-1-cleaved GSDMD N-terminal (GSDMD-NT) and we investigated it in peripheral blood immunocytes of septic patients previously. Here, a caspase-1 inhibitor VX765 was treated with CLP-induced septic mice. Novel object recognition test indicated that VX765 treatment reversed cognitive dysfunction in septic mice. Elevated plus maze, tail suspension test and open field test revealed that depressive-like behaviors of septic mice were relieved. Inhibited caspase-1 suppressed the expressions of GSDMD and its cleavage form GSDMD-NT, and reduced pyroptosis in brain at day 1 and day 7 after sepsis. Meantime, inhibited caspase-1 mitigated the expressions of IL-1ß, MCP-1 and TNF-α in serum and brain, diminished microglia activation in septic mice, and reduced sepsis-induced brain-blood barrier disruption and ultrastructure damages in brain as well. Inhibited caspase-1 protected the synapse plasticity and preserved long-term potential, which may be the possible mechanism of cognitive functions protective effects of septic mice. In conclusion, caspase-1 inhibition exerts brain-protective effects against SAE and cognitive impairments in a mouse model of sepsis.

Mixed exposure to haloacetaldehyde disinfection by-products exacerbates lipid aggregation in the liver of mice.

Haloacetaldehyde disinfection by-products (HAL-DBPs) are among the top three unregulated DBPs found in drinking water. The cytotoxicity and genotoxicity of HALs are much higher than that of the regulated trihalomethanes and haloacetic acids. Previous studies have mainly focused on the toxic effects of single HAL, with few examining the toxic effects of mixed exposures to HALs. The study aimed to observe the effects of mixed exposures of 1∼1000X the realistic level of HALs on the hepatotoxicity and lipid metabolism of C57BL/6J mice, based on the component and concentration of HALs detected in the finished water of Shanghai. Exposure to realistic levels of HALs led to a significant increase in phosphorated acetyl CoA carboxylase 1 (p-ACC1) in the hepatic de novo lipogenesis (DNL) pathway. Additionally, exposure to 100X realistic levels of HALs resulted in significant alterations to key enzymes of DNL pathway, including ACC1, fatty acid synthase (FAS), and diacylglycerol acyltransferase 2 (DGAT2), as well as key proteins of lipid disposal such as carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator activated receptor α (PPARα). Exposure to 1000X realistic levels of HALs significantly increased hepatic and serum triglyceride levels, as well as total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase levels, significantly decreased high-density lipoprotein. Meanwhile, histopathological analysis demonstrated that HALs exacerbated tissue vacuolization and inflammatory cell infiltration in mice livers, which showed the typical phenotypes of non-alcoholic fatty liver disease (NAFLD). These results suggested that the HALs mixture is a critical risk factor for NAFLD and is significantly highly toxic to C57BL/6J mice.

Haloacetamides disinfection by-products, a potential risk factor for nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by abnormal lipid deposition, with oxidative stress being a risk factor in its onset and progression. Haloacetamides (HAcAms), as unregulated disinfection by-products in drinking water, may alter the incidence and severity of NAFLD through the production of oxidative stress. We explored whether HAcAms at 1, 10, and 100-fold concentrations in Shanghai drinking water perturbed lipid metabolism in normal human liver LO-2 cells. CRISPR/Cas9 was used to construct a LO-2 line with stable NRF2 knock-down (NRF2-KD) to investigate the mechanism underlying abnormal lipid accumulation and hepatocyte damage caused by mixed exposure to HAcAms. At 100-fold real-world concentration, HAcAms caused lipid deposition and increased triglyceride accumulation in LO-2 cells, consistent with altered de novo lipogenesis. Differences in responses to HAcAms in normal and NRF2-KD LO-2 cells indicated that HAcAms caused hepatocyte lipid deposition and triglyceride accumulation by activation of the NRF2/PPARγ pathway and aggravated liver cell toxicity by inducing ferroptosis. These results indicate that HAcAms are important risk factors for NAFLD. Further observations and verifications of the effect of HAcAms on NAFLD in the population are warranted in the future.

Observation of dichotomic field-tunable electronic structure in twisted monolayer-bilayer graphene.

Twisted bilayer graphene (tBLG) provides a fascinating platform for engineering flat bands and inducing correlated phenomena. By designing the stacking architecture of graphene layers, twisted multilayer graphene can exhibit different symmetries with rich tunability. For example, in twisted monolayer-bilayer graphene (tMBG) which breaks the C2z symmetry, transport measurements reveal an asymmetric phase diagram under an out-of-plane electric field, exhibiting correlated insulating state and ferromagnetic state respectively when reversing the field direction. Revealing how the electronic structure evolves with electric field is critical for providing a better understanding of such asymmetric field-tunable properties. Here we report the experimental observation of field-tunable dichotomic electronic structure of tMBG by nanospot angle-resolved photoemission spectroscopy (NanoARPES) with operando gating. Interestingly, selective enhancement of the relative spectral weight contributions from monolayer and bilayer graphene is observed when switching the polarity of the bias voltage. Combining experimental results with theoretical calculations, the origin of such field-tunable electronic structure, resembling either tBLG or twisted double-bilayer graphene (tDBG), is attributed to the selectively enhanced contribution from different stacking graphene layers with a strong electron-hole asymmetry. Our work provides electronic structure insights for understanding the rich field-tunable physics of tMBG.

Effect of 12-week shen-based qigong exercise on the residual symptoms of schizophrenia: Study protocol for a single-centre randomised controlled trial.

Introduction: Negative symptoms and cognitive impairment are common residual symptoms of schizophrenia that seriously affect the quality of life and social function of patients. The intervention of residual symptoms is an important part of schizophrenia rehabilitation. Traditional Chinese exercise has been applied as a supplementary rehabilitation method for schizophrenia. However, research on its use and pertinence in the rehabilitation of residual symptoms remains lacking. In this study, we will verify the intervention effect of a new method, namely, shen-based qigong exercise, on the residual symptoms of schizophrenia, in the hopes of finding a safe and effective rehabilitation method for the residual symptoms of schizophrenia. Methods: This is a single-centre randomised controlled trial. A total of 60 schizophrenics who meet the criteria will be randomly divided into the control and intervention groups in accordance with the ratio of 1:1. Conventional drug treatment will remain unchanged in both groups. In this case, the control group will be given daily rehabilitation, whereas the intervention group will be given daily rehabilitation and shen-based qigong exercise intervention. The intervention period will be 12 weeks. The primary outcome will be negative symptoms assessed by the Scale for the Assessment of Negative Symptoms. The secondary outcome will be the global cognitive function assessed by the Repeatable Battery for the Assessment of Neuropsychological Status and event-related potential P300. Other outcomes will include specific cognitive domain (i.e. working memory), quality of life and social function. The results will be measured within 1 week before and after the intervention. Discussion: The results of this study will likely help find an economical and convenient rehabilitation method for the residual symptoms of schizophrenia and, at the same time, may promote the popularisation and application of traditional Chinese exercises and traditional Chinese medicine theories in the treatment of mental diseases. Trial registration: ClinicalTrials.gov registry number: NCT05310955.

Inhibition of DDX3X ameliorated CD4+ T cells pyroptosis and improves survival in septic mice.

Over-expression of DDX3X mRNA is associated with T cell loss in septic patients. This study aimed to investigate the molecular mechanism of DDX3X on T cell reduction in sepsis. The sepsis model was established using lipopolysaccharide stimulation in vitro and cecal ligation and puncture (CLP) surgery in vivo. Results showed that the expression of DDX3X was significantly upregulated in CD4+ T cells in sepsis. RK-33, the inhibitor of DDX3X, was found to dramatically increase CD4+ T cell counts and prolong the survival rate of mice with sepsis. The results also showed that the expression of caspase-1/GSDMD in CD4+ T cells was significantly increased in vitro and in vivo, and RK-33 can substantially reduce CD4+ T cell pyroptosis through inhibiting NLRP3/caspase-1/GSDMD. Globally, our results suggest that DDX3X is involved in the loss of CD4+ T cells partly through activating the pyroptotic pathway during sepsis, which may provide potential targets for therapeutic interventions in this highly lethal disease.

Negative-Pressure Wound Therapy Induces Lymphangiogenesis in Murine Diabetic Wound Healing.

BACKGROUND: Decreased lymphangiogenesis contributes to impaired diabetic wound healing. Although negative-pressure wound therapy (NPWT) has been shown to be effective in the treatment of recalcitrant wounds, its impact on lymphangiogenesis remains to be elucidated. In this study, the authors investigate the mechanisms of lymphangiogenesis following NPWT treatment of diabetic murine wound healing. METHODS: Full-thickness dorsal skin wounds (1 × 1 cm 2 ) were excised on 30 db/db mice. The mice were either treated with occlusive covering (control group, n = 15), or received a 7-day treatment of continuous NPWT at -125 mmHg (NPWT group, n = 15). The wounds were photographed on days 0, 7, 10, 14, 21, and 28. Wound tissue was harvested on days 10, 14, 21, and 28 for quantitative analysis. Functional analysis of lymphatic drainage was performed on days 14 and 28 with Evans blue dye tracing. RESULTS: Lymphatic density and diameter, as visualized through podoplanin probing, was significantly higher in the NPWT group compared to the control group ( P < 0.001). NPWT up-regulated the expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) at the protein level ( P = 0.04), and significant differences were noted in lymphatic density as assessed by LYVE-1 staining ( P = 0.001). Leukocyte infiltration was significantly higher in the NPWT group ( P = 0.01). A higher speed of wound closure ( P < 0.0001) and greater wound bed thickness ( P < 0.0001) were noted in the NPWT group compared to the control group. CONCLUSIONS: NPWT increased the lymphatic vessel density and diameter with LYVE-1 up-regulation. NPWT therefore plays a positive role in lymphangiogenesis in diabetic wound healing. CLINICAL RELEVANCE STATEMENT: The authors' study investigates the association of NPWT and lymphatics and underlines the importance of a more in-depth investigation of the role of lymphatic vessels in wound healing.

Inhibition of DDX3X alleviates persistent inflammation, immune suppression and catabolism syndrome in a septic mice model.

OBJECTIVE: DDX3X is involved in various pathological processes such as infection, immunity and cell death. This study aimed to investigate the effect of RK-33, a specific inhibitor of DDX3X, on the progression of sepsis to persistent inflammation, immune suppression and catabolism syndrome(PICS). METHODS: The septic mice model was established using caecal ligation and perforation (CLP). The mice were randomly divided into four groups: sham group, sham + RK-33 group (20 mg/kg, intraperitoneal injection, once a day), CLP group and CLP + RK-33 group (20 mg/kg, intraperitoneal injection, once a day). The number of inflammatory cells in the peripheral blood, spleen and bone marrow was calculated, and inflammatory cytokines were detected using an enzyme-linked immunosorbent assay. The septic mice's body weight and skeletal muscle mass were measured, and skeletal muscle tissues were examined using eosin staining. Western blotting was performed to detect the expression levels of MuRF1, atrogin1 and NLRP3 in the skeletal muscle of septic mice. Additionally, reactive oxidative species, superoxide dismutase and malondialdehyde were measured using commercial kits. RESULTS: RK-33 reduced inflammatory cell counts and cytokine levels in CLP mice, ameliorated the decline in CD4 and CD8 T cells and prevented the loss of body weight and skeletal muscle mass in septic mice. Additionally, RX-33 reduced oxidative stress in the skeletal muscle of septic mice. CONCLUSION: In the established sepsis mouse model, RK-33 alleviated inflammation and oxidative stress, ameliorated CLP-induced immunosuppression and skeletal muscle atrophy and improved survival. These findings suggest that RK-33 could be a novel potential therapeutic agent for preventing the progression of sepsis to PICS.

The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma.

BACKGROUND: The long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC. METHODS: Between June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded. RESULTS: The median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9-32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9-25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed. CONCLUSION: TACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.