Successful Treatment of Refractory Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome with Baricitinib, a Janus Kinase Inhibitor.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a rare immune-mediated inflammatory disease, poses diagnostic and therapeutic challenges owing to its multi-system involvement, high heterogeneity, and lack of specific laboratory tests. Additionally, lacking evidence-based treatment recommendations, with the primary approach focusing on symptomatic relief. Herein, we report the case of a 32-year-old Chinese woman who presented with recurrent, generalized multiple osteoarticular pain lasting over one year and skin erythema pustulosis for 11 months. Traditional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and other traditional approaches, yielded no significant effects. Despite the prior use of adalimumab and acitretin capsules, the treatment remained unsatisfying, especially regarding the skin lesions. Considering the complex pathogenesis of SAPHO syndrome, the patient was orally administered baricitinib (2 mg), a Janus kinase (JAK) inhibitor, twice daily. A notable improvement in both skin lesions and osteoarticular pain was observed within two weeks of treatment initiation. Subsequently, the dosage of baricitinib was halved and continued for an additional three months, during which regular follow-ups revealed neither disease recurrence nor adverse effects. Collectively, the successful treatment of refractory SAPHO syndrome with baricitinib presents a promising implication for addressing the therapeutic challenges of this rare autoimmune condition, offering a potential breakthrough in managing its complex manifestations.

Defect and Donor Manipulated Highly Efficient Electron-Hole Separation in a 3D Nanoporous Schottky Heterojunction.

Given the rapid recombination of photogenerated charge carriers and photocorrosion, transition metal sulfide photocatalysts usually suffer from modest photocatalytic performance. Herein, S-vacancy-rich ZnIn2S4 (VS-ZIS) nanosheets are integrated on 3D bicontinuous nitrogen-doped nanoporous graphene (N-npG), forming 3D heterostructures with well-fitted geometric configuration (VS-ZIS/N-npG) for highly efficient photocatalytic hydrogen production. The VS-ZIS/N-npG presents ultrafast interfacial photogenerated electrons captured by the S vacancies in VS-ZIS and holes neutralization behaviors by the extra free electrons in N-npG during photocatalysis, which are demonstrated by in situ XPS, femtosecond transient absorption (fs-TA) spectroscopy, and transient-state surface photovoltage (TS-SPV) spectra. The simulated interfacial charge rearrangement behaviors from DFT calculations also verify the separation tendency of photogenerated charge carriers. Thus, the optimized VS-ZIS/N-npG 3D hierarchical heterojunction with 1.0 wt % N-npG exhibits a comparably high hydrogen generation rate of 4222.4 µmol g-1 h-1, which is 5.6-fold higher than the bare VS-ZIS and 12.7-fold higher than the ZIS without S vacancies. This work sheds light on the rational design of photogenerated carrier transfer paths to facilitate charge separation and provides further hints for the design of hierarchical heterostructure photocatalysts.

Visible-light-driven AgI/Bi4O5I2 S-scheme heterojunction for efficient tetracycline hydrochloride removal: Mechanism and degradation pathway.

The existence of excessive tetracycline hydrochloride (TCH) in the ecological environment has seriously threatened human health, so there is an urgent need to develop a high-performance photocatalyst that can efficiently and greenly remove TCH. Currently, most photocatalysts have the problems of fast recombination of photogenerated charge carriers and low degradation efficiency. Herein, S-scheme AgI/Bi4O5I2 (AB) heterojunctions was constructed for TCH removal. Compared with the single component, the apparent kinetic constant of the 0.7AB is 5.6 and 10.2 time as high as the AgI and Bi4O5I2, and the photocatalytic activity only decreases by 3.0% after four recycle runs. In addition, to verify the potential practical application of the fabricated AgI/Bi4O5I2 nanocomposite, the photocatalytic degradation of TCH was performed under different conditions by regulating the dosage of photocatalyst, the TCH concentration, pH, and the existence of various anions. Systematical characterizations are conducted to investigate the intrinsic physical and chemical properties of the constructed AgI/Bi4O5I2 composites. Based on the synergetic characterizations by in situ X-ray photoelectron spectroscopy, band edge measurements, as well as reactive oxygen species (ROS) detections, the S-scheme photocatalytic mechanism is proved. This work provides a valuable reference for developing efficient and stable S-scheme AgI/Bi4O5I2 photocatalyst for TCH removal.

[Research progress of hypertonic saline in early resuscitation of acute pancreatitis].

Local inflammatory reaction and microcirculation disturbance are the early manifestations of acute pancreatitis (AP). Studies have shown that early and reasonable fluid resuscitation of patients with AP can reduce related complications and prevent the deterioration to severe acute pancreatitis (SAP). Traditional isotonic crystalloid (such as Ringer solution) is considered to be a safe and reliable resuscitation solution, but too much and too fast infusion in the early stage of shock will increase the risk of complications such as tissue edema and abdominal compartment syndrome (ACS). Many scholars have found that hypertonic saline resuscitation solution has the advantages of reducing tissue and organ edema, rapidly restoring hemodynamics, inhibiting oxidative stress and inflammatory signal transduction, thereby improving the prognosis of AP patients and reducing the incidence of SAP and mortality. This article summarizes the mechanisms of hypertonic saline in the resuscitation treatment of AP patients in recent years, in order to provide reference for the clinical application and research of AP patients.

Facile Synthesis of P-Doped ZnIn2S4 with Enhanced Visible-Light-Driven Photocatalytic Hydrogen Production.

ZnIn2S4 (ZIS) is widely used in the field of photocatalytic hydrogen production due to its unique photoelectric properties. Nonetheless, the photocatalytic performance of ZIS usually faces problems of poor conductivity and rapid recombination of charge carriers. Heteroatom doping is often regarded as one of the effective strategies for improving the catalytic activity of photocatalysts. Herein, phosphorus (P)-doped ZIS was prepared by hydrothermal method, whose photocatalytic hydrogen production performance and energy band structure were fully studied. The band gap of P-doped ZIS is about 2.51 eV, which is slightly smaller than that of pure ZIS. Moreover, due to the upward shift of its energy band, the reduction ability of P-doped ZIS is enhanced, and P-doped ZIS also exhibits stronger catalytic activity than pure ZIS. The optimized P-doped ZIS exhibits a hydrogen production rate of 1566.6 µmol g-1 h-1, which is 3.8 times that of the pristine ZIS (411.1 µmol g-1 h-1). This work provides a broad platform for the design and synthesis of phosphorus-doped sulfide-based photocatalysts for hydrogen evolution.

Biallelic mutations in LSS in autosomal-recessive mutilating palmoplantar keratoderma.

Mutilating palmoplantar keratoderma (PPK) is a heterogeneous genetic disease that poses enormous challenges to clinical diagnosis and genetic counselling. Lanosterol synthase (LSS) gene encodes LSS involved in the biosynthesis pathway of cholesterol. Biallelic mutations in LSS were found to be related to diseases such as cataracts, hypotrichosis and palmoplantar keratoderma-congenital alopecia syndrome. The aim of this study was to investigate the contribution of the LSS mutation to mutilating PPK in a Chinese patient. The clinical and molecular characteristics of the patient were evaluated. A 38-year-old male patient with mutilating PPK was recruited in this study. We identified biallelic variants in the LSS gene (c.683C > T, p.Thr228Ile and c.779G > A, p.Arg260His). Immunoblotting revealed that the Arg260His mutant showed a significantly reduced expression level while Thr228Ile showed an expression level similar to that of the wild type. Thin layer chromatography revealed that mutant Thr228Ile retained partial enzymatic activity and mutant Arg260His did not show any catalytic activity. Our findings show the correlation between LSS mutations and mutilating PPK.

Highly efficient and recyclable Z-scheme heterojunction of Ag3PO4/g-C3N4 floating foam for photocatalytic inactivation of harmful algae under visible light.

Harmful algal blooms (HABs) have frequently occurred worldwide, causing marine ecosystems and human health risks. As an advanced and green oxidation technology, photocatalysis has potential to remove red tide algae using solar energy. Herein, in this work, Z-scheme photocatalysts of Ag3PO4/g-C3N4 (APCN) floating foam with different mass ratios were fabricated for the algae inactivation. Under visible light irradiation, the 0.10APCN (0.10 mM AgNO3) composite photocatalyst could cause 91.8% of the loss in Karenia mikimotoi (K. mikimotoi) cell viability following 24 h and the removal rate of algae could reach to 86% after five successive cycles. The underlying mechanism of photocatalytic inactivation of harmful algae is proposed in this system. The photosynthetic efficiency of harmful algae is inhibited with the decrease of photosynthetic pigments, which are inactivated by the high levels of reactive oxygen species (ROS) (superoxide radical •O2- and hydroxyl radical •OH) produced in Z-scheme photocatalytic system of the Ag3PO4/g-C3N4 heterojunction under visible light. Meanwhile, the activities of antioxidant enzymes (i.e. POD, APX and SOD) are up-regulating with the overproduction of ROS going into the algae, causing the cytotoxicity and apoptosis of algae. This work not only reveals the mechanisms of photocatalytic inactivation of harmful algae, but also guides the design the construction of high active composite photocatalysts, and thus provides theoretical and practical significance for highly efficient and recyclable prospect of controlling of harmful algae.

Efficient Charge Transfer and Effective Active Sites in Lead-Free Halide Double Perovskite S-Scheme Heterojunctions for Photocatalytic H2 Evolution.

The practical application of lead-free double perovskite Cs2 AgBiBr6 in photocatalytic H2 evolution is still restricted due to the low activity and poor stability. The rational design of lead-free halide double perovskites heterojunctions with efficient charge transfer and effective active sites is a potential route to achieve the ideal prospect. Herein, in this work an S-scheme heterojunction of Cs2 AgBiBr6 with enriched Br-vacancies and WO3 nanorods (VBr -Cs2 AgBiBr6 /WO3 ) obtaining excellent visible-light responsive photocatalytic H2 evolution performance and durable stability is reported. The S-scheme heterojunction driven by the unaligned Fermi levels of these two semiconductors ensures the efficient charge transfer at the interface, and density functional theory calculations reveal the enriched Br vacancies on Cs2 AgBiBr6 (022) surfaces introduced by atom thermal vibration provide effective active sites for hydrogen evolution. The optimized VBr -Cs2 AgBiBr6 /WO3 S-scheme photocatalyst exhibits the photocatalytic hydrogen evolution rate of 364.89 µmol g-1 h-1 which is 4.9-fold of bare VBr -Cs2 AgBiBr6 (74.44 µmol g-1 h-1 ) and presents long-term stability of 12 h continuous photocatalytic reaction. This work provides deep insights into the photocatalytic mechanism of VBr -Cs2 AgBiBr6 /WO3 S-scheme heterojunctions, which emerges a new strategy in the applications of perovskite-based photocatalysts.

Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model.

Zinc is a fundamental trace element essential for numerous biological processes, and zinc homeostasis is regulated by the Zrt-/Irt-like protein (ZIP) and zinc transporter (ZnT) families. ZnT7 is mainly localized in the Golgi apparatus and endoplasmic reticulum (ER) and transports zinc into these organelles. Although previous studies have reported the role of zinc in animal physiology, little is known about the importance of zinc in the Golgi apparatus and ER in animal development and neurodegenerative diseases. In this study, we demonstrated that ZnT86D, a Drosophila ortholog of ZnT7, plays a pivotal role in the neurodevelopment and pathogenesis of Alzheimer disease (AD). When ZnT86D was silenced in neurons, the embryo-to-adult survival rate, locomotor activity, and lifespan were dramatically reduced. The toxic phenotypes were accompanied by abnormal neurogenesis and neuronal cell death. Furthermore, knockdown of ZnT86D in the neurons of a Drosophila AD model increased apoptosis and exacerbated neurodegeneration without significant changes in the deposition of amyloid beta plaques and susceptibility to oxidative stress. Taken together, our results suggest that an appropriate distribution of zinc in the Golgi apparatus and ER is important for neuronal development and neuroprotection and that ZnT7 is a potential protective factor against AD.

A Novel Variant and a Missense Variant Identified in the DKC1 Gene in Three Chinese Familieswith Dyskeratosis Congenita.

Purpose: Dyskeratosis congenita (DC) is an inherited telomere biology disorder characterized clinically by mucocutaneous triad of reticulate hyperpigmentation, nail changes and oral leukoplakia. Bone marrow failure, pulmonary fibrosis and malignancies are the mainly life-threatening causes. There are X-linked recessive, autosomal dominant and autosomal recessive patterns of DC. DKC1 is the most common pathogenic mutation gene responsible for X-linked DC, and it encodes a protein, dyskerin, which is a component of telomerase holoenzyme complex essential for telomere maintenance. Patients with DC have very short telomeres, but the precise pathogenic mechanism remains unclear. This study aimed to identify the causative mutations in the DKC1 gene in three Chinese families with the X-linked form of DC. Patients and Methods: Three Chinese families with DC were included in this study. Whole exome sequencing and Sanger sequencing were performed to clarify the mutation of DKC1 gene. Measurement of relative telomere length through qPCR. Predictions of protein structure and function were performed using bioinformatics tools, including I-TASSER, Polyphen-2 and SIFT. Results: There were four males with DC and a female carrier in three Chinese pedigrees. The novel mutation c.92A>C (p. Q31P) and the missense mutation c.1058C>T (p. A353V) in DKC1 were identified. Both mutations locally changed the structure of dyskerin. Variant Q31P and A353V were predicted to have "deleterious" and "natural" effects on the function of dyskerin, respectively. Conclusion: The novel variant and missense variant detected in the DKC1 gene improve our understanding of DC and broaden the mutation spectrum of the DKC1 gene.

Propranolol Suppresses Proliferation and Migration of HUVECs through Regulation of the miR-206/VEGFA Axis.

Propranolol has been used in the first-line therapy of infantile hemangioma (IH) for a number of years; however, the mechanisms through which propranolol regulates IH are not yet fully understood. In the present study, microRNA (miRNA/miR) sequencing analysis was performed to identify differentially expressed miRNAs in human umbilical vascular endothelial cells (HUVECs) treated with propranolol. Cell viability and apoptosis were detected using CCK-8 assay and flow cytometry, respectively. Cell migration was assessed using wound healing, Transwell, and tube formation assays. Methylation-specific PCR was then used to investigate the promoter methylation status. The levels of oxidative stress indicators, including superoxide dismutase, glutathione, and malondialdehyde were also detected. Finally, cell cycle analysis was performed using flow cytometry and western blotting. It was observed that propranolol induced the upregulation of miR-206 in HUVECs, which was caused by demethylation of the miR-206 promoter. Moreover, propranolol significantly inhibited the proliferation of HUVECs by inducing apoptosis, while these phenomena were reversed by miR-206 antagomir. VEGFA was found to be a target gene of miR-206. In addition, propranolol notably inhibited the migration and induced G1 arrest of the HUVECs, whereas these results were eliminated by miR-206 antagomir. Collectively, the findings of the present study demonstrated that propranolol may inhibit the proliferation and migration in HUVECs via modulating the miR-206/VEGFA axis. These findings suggest a novel mechanism through which propranolol suppresses the progression of IH.

Construction of Electrostatic Self-Assembled 2D/2D CdIn2S4/g-C3N4 Heterojunctions for Efficient Visible-Light-Responsive Molecular Oxygen Activation.

Molecular oxygen activated by visible light to generate radicals with high oxidation ability exhibits great potential in environmental remediation The efficacy of molecular oxygen activation mainly depends on the separation and migration efficiency of the photoinduced charge carriers. In this work, 2D/2D CdIn2S4/g-C3N4 heterojunctions with different weight ratios were successfully fabricated by a simple electrostatic self-assembled route. The optimized sample with a weight ratio of 5:2 between CdIn2S4 and g-C3N4 showed the highest photocatalytic activity for tetracycline hydrochloride (TCH) degradation, which also displayed good photostability. The enhancement of the photocatalytic performance could be ascribed to the 2D/2D heterostructure; this unique 2D/2D structure could promote the separation and migration of the photoinduced charge carriers, which was beneficial for molecular oxygen activation, leading to an enhancement in photocatalytic activity. This work may possibly provide a scalable way for molecular oxygen activation in photocatalysis.

Linalool Alleviates Aß42-Induced Neurodegeneration via Suppressing ROS Production and Inflammation in Fly and Rat Models of Alzheimer's Disease.

Terpenes are vital metabolites found in various plants and animals and known to be beneficial in the treatment of various diseases. Previously, our group identified terpenes that increased the survival of Alzheimer's disease (AD) model flies expressing human amyloid ß (Aß) and identified linalool as a neuroprotective terpene against Aß toxicity. Linalool is a monoterpene that is commonly present as a constituent in essential oils from aromatic plants and is known to have anti-inflammatory, anticancer, antihyperlipidemia, antibacterial, and neuroprotective properties. Although several studies have shown the beneficial effect of linalool in AD animal models, the mechanisms underlying the beneficial effect of linalool on AD are yet to be elucidated. In the present study, we showed that linalool intake increased the survival of the AD model flies during development in a dose-dependent manner, while the survival of wild-type flies was not affected even at high linalool concentrations. Linalool also decreases Aß-induced apoptosis in eye discs as well as the larval brain. Moreover, linalool intake was found to reduce neurodegeneration in the brain of adult AD model flies. However, linalool did not affect the total amount of Aß42 protein or Aß42 aggregation. Rather, linalool decreased Aß-induced ROS levels, oxidative stress, and inflammatory response in the brains of AD model flies. Furthermore, linalool attenuated the induction of oxidative stress and gliosis by Aß 1-42 treatment in the rat hippocampus. Taken together, our data suggest that linalool exerts its beneficial effects on AD by reducing Aß42-induced oxidative stress and inflammatory reactions.

The linear ubiquitin E3 ligase-Relish pathway is involved in the regulation of proteostasis in Drosophila muscle during aging.

Linear ubiquitination is an atypic ubiquitination process that directly connects the N- and C-termini of ubiquitin and is catalyzed by HOIL-1-interacting protein (HOIP). It is involved in the immune response or apoptosis by activating the nuclear factor-κB pathway and is associated with polyglucosan body myopathy 1, an autosomal recessive disorder with progressive muscle weakness and cardiomyopathy. However, little is currently known regarding the function of linear ubiquitination in muscles. Here, we investigated the role of linear ubiquitin E3 ligase (LUBEL), a DrosophilaHOIP ortholog, in the development and aging of muscles. The muscles of the flies with down-regulation of LUBEL or its downstream factors, kenny and Relish, developed normally, and there were no obvious abnormalities in function in young flies. However, the locomotor activity of the LUBEL RNAi flies was reduced compared to age-matched control, while LUBEL RNAi did not affect the increased mitochondrial fusion or myofiber disorganization during aging. Interestingly, the accumulation of polyubiquitinated protein aggregation during aging decreased in muscles by silencing LUBEL, kenny, or Relish. Meanwhile, the levels of autophagy and global translation, which are implicated in the maintenance of proteostasis, did not change due to LUBEL down-regulation. In conclusion, we propose a new role of linear ubiquitination in proteostasis in the muscle aging.

Effect of miR-184 on Proliferation and Apoptosis of Pancreatic Ductal Adenocarcinoma and Its Mechanism.

OBJECTIVE: Previous studies have shown that abnormal expression of microRNA-184 leads to a variety of cancers, including pancreatic ductal adenocarcinoma, suggesting microRNA-184 as a new treatment target for pancreatic ductal adenocarcinoma. However, the molecular mechanism of microRNA-184 in pancreatic ductal adenocarcinoma remains unclear. It is important to investigate the effect and role of microRNA-184 in pancreatic ductal adenocarcinoma. METHODS: The clinical and laboratory inspection data of 120 patients with pancreatic cancer admitted to the First Affiliated Hospital of Anhui Medical University were compared. MicroRNA-184 expression in tumor tissues and cells was evaluated using reverse transcription polymerase chain reaction. Flow cytometry and Annexin V/propidium iodide staining were performed to examine cell cycle and apoptosis. Western blotting analysis was conducted to measure the protein expression of p-PI3K, p-AKT, JNK1, C-Myc, C-Jun, caspase-9, and caspase-3. RESULTS: MicroRNA-184 expression was low in patients with pancreatic ductal adenocarcinoma. Survival curve showed that patients with lower expression of microRNA-184 in tumor tissues had a worse prognosis and shorter survival time (P < .05), and the multivariate analysis identified that microRNA-184 was an independent prognostic indicator (P < .05). In vitro studies showed that microRNA-184 overexpression induced apoptosis and suppressed cell cycle transition from G1 to S and G2 phases in pancreatic ductal adenocarcinoma cells. Furthermore, molecular studies revealed that inhibition of microRNA-184 promoted the gene expression of p-PI3K, p-AKT, JNK1, C-Myc, and C-Jun compared with the control group. Overexpression of microRNA-184 led to significantly increased expression of caspase-9 and caspase-3 and significantly decreased expression of Bcl-2. CONCLUSION: This study suggests that microRNA-184 inhibits the proliferation and promotes the apoptosis of pancreatic ductal adenocarcinoma cells by downregulating the expression of C-Myc, C-Jun, and Bcl-2. Our verification of the role of microRNA-184 may provide a novel biomarker for the diagnosis, therapy, and prognosis of pancreatic ductal adenocarcinoma.

Neuroprotective Effects of Limonene (+) against Aß42-Induced Neurotoxicity in a Drosophila Model of Alzheimer's Disease.

Forest bathing is suggested to have beneficial effects on various aspects of human health. Terpenes, isoprene based-phytochemicals emitted from trees, are largely responsible for these beneficial effects of forest bathing. Although the therapeutic effects of terpenes on various diseases have been revealed, their effects on neuronal health have not yet been studied in detail. Here, we screened 16 terpenes that are the main components of Korean forests using Drosophila Alzheimer's disease (AD) models to identify which terpenes have neuroprotective effects. Six out of the 16 terpenes, ρ-cymene, limonene (+), limonene (-), linalool, α-pinene (+), and ß-pinene (-), partially suppressed the beta amyloid 42 (Aß42)-induced rough eye phenotype when fed to Aß42-expressing flies. Among them, limonene (+) restored the decreased survival of flies expressing Aß42 in neurons during development. Limonene (+) treatment did not affect Aß42 accumulation and aggregation, but did cause to decrease cell death, reactive oxygen species levels, extracellular signal-regulated kinase phosphorylation, and inflammation in the brains or the eye imaginal discs of Aß42-expressing flies. This neuroprotective effect of limonene (+) was not associated with autophagic activity. Our results suggest that limonene (+) has a neuroprotective function against the neurotoxicity of Aß42 and, thus, is a possible therapeutic reagent for AD.

Hypertonic saline resuscitation protects against kidney injury induced by severe burns in rats.

BACKGROUND: Proper fluid resuscitation can relieve visceral damage and improve survival in severely burned patients. This study compared the effectiveness of resuscitation with 400mEq/L hypertonic saline (HS) and sodium lactate Ringer's solution (LR) in rats with kidney injury caused by burn trauma. METHODS: Rats (Sprague-Dawley) underwent burn injury and were randomized into sham, LR, and HS groups. Samples from the kidney were assayed for water content ratio, histopathology, and oxidative stress (superoxide dismutase (SOD) and malondialdehyde (MDA)). Serum sodium, renal function (creatinine and cystatin (Cys)-C), and inflammatory response (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and high mobility group protein box (HMGB)-1) were also examined as serum markers. RESULTS: Hypertonic saline resuscitation reduced the renal water content ratio and improved renal histopathology caused by severe burns. This effect was accompanied by reductions in serum creatinine and Cys-C as well as TNF-α, IL-1ß, and HMGB1. Serum sodium concentration and SOD activity were increased, whereas MDA content was decreased in the kidney tissue of the HS group. CONCLUSIONS: The data indicate that 400mEq/L HS solution reduces hyponatremia and renal edema, inhibits the release of inflammatory mediators, and alleviates oxidative stress injury, thus protecting against kidney injury induced by severe burns.

[Study on the mechanism of hypertonic salt solution alleviates lung injury of rats at the early stage of severe scald].

OBJECTIVE: To explore the mechanism of hypertonic salt solution (HS) alleviates lung injury of rats at the early stage of severe scald. METHODS: Thirty-two female Sprague-Dawley (SD) rats were randomly assigned to sham group, lactated Ringer solution (LR) group, HS200 group (200 mmol/L HS group, 1 L 200 mmol/L HS contained 955 mL LR and 45 mL 10% NaCl) and HS400 group (400 mmol/L HS group, 1 L 400 mmol/L HS contained 846 mL LR and 154 mL 10% NaCl), with 8 rats in each group. A 30% total body surface area (TBSA) III degree scalded model was reproduced by scalded on the back with 98 centigrade boiling water for 12 seconds, whereas those in the sham group were exposed to 37 centigrade water without liquid resuscitation. Rats in the three drug intervention groups were resuscitated with LR, 200 mmol/L HS and 400 mmol/L HS by caudal vein according to the Parkland formula, respectively. All rats were sacrificed at 8 hours after scald injury to harvest abdominal aorta blood and lung tissues. Interleukins (IL-6, IL-10 and IL-17) in serum were determined by enzyme-linked immunosorbent assay (ELISA). Samples from the lung tissue were used to measure malondialdehyde (MDA) and superoxide dismutase (SOD) levels by ultraviolet spectrophotometer. Expressions of p38 mitogen-activated protein kinase (p38MAPK) and extracellular regulated protein kinase 1/2 (ERK1/2) in the lung were determined by Western Blot. The lung tissue was stained with hematoxylin and eosin (HE), and the pathological changes were observed with a light microscope. RESULTS: Compared with the sham group, the lung tissues in the LR group were damage obviously, which accompanied with more inflammatory cell infiltration, cell edema and pulmonary septum thickening, and the levels of IL-6, IL-10, IL-17 in serum and MDA content, the phosphorylation of p38MAPK and ERK1/2 in lung tissues were increased whereas the activity of SOD was decreased. Compared with the LR group, the lung injury was significantly alleviated, the levels of IL-6, IL-17 in serum and MDA content and the phosphorylation of p38MAPK and ERK1/2 were decreased, and the levels of IL-10 and SOD were increased in both HS groups with a dose-dependent manner. There were significant difference in above parameters between HS400 group and LR group [serum IL-6 (ng/L): 3.76±0.12 vs. 6.72±0.90, serum IL-10 (ng/L): 33.76±3.71 vs. 16.77±3.19, serum IL-17 (ng/L): 103.52±2.78 vs. 124.96±4.96, lung MDA (nmol/mg): 5.59±0.24 vs. 7.09±0.39, lung SOD (U/mg): 226.7±3.9 vs. 172.7±3.4, lung phosphorylation of p38MAPK (p-p38MAPK)/p38MAPK: 0.15±0.09 vs. 0.35±0.19, lung phosphorylation of ERK1/2 (p-ERK1/2)/ERK1/2: 0.27±0.01 vs. 0.70±0.01, all P < 0.01]. CONCLUSIONS: HS protected against lung injury induced by severe burns in rats with a dose-dependent manner, and it was better than LR, and its possible mechanism was related with reducing the expression of p38MAPK and ERK1/2 pathway in lung tissue, increasing the level of anti-inflammatory cytokines and decreasing the release of pro-inflammatory cytokines, thus inhibiting excessive inflammation and oxidative stress injury in lung.

[Effect of different concentrations of hypertonic sodium fluid resuscitation on intestine injury in rats at the early stage of severe burn].

OBJECTIVE: To investigate the effect of different concentrations of hypertonic saline solution (HS) on intestine injury in rats at the early stage of severe burn. METHODS: 104 adult healthy female Sprague-Dawley (SD) rats were randomly divided into five groups: sham group (n = 8), lactated Ringer solution (LR) group (n = 24) and 200, 300, 400 mmol/L HS group (HS200 group, HS300 group, HS400 group, all n = 24). All the rats in LR group and different concentrations of HS groups were scalded for 30% total body surface area (TBSA) with III degree, after immediately, the rats were given burn resuscitation therapy by LR or corresponding concentrations of HS through the tail vein. Eight rats were sacrificed on the 2nd, 8th and 24th post-injury hour (PIH), respectively, to collect abdominal aorta blood and intestinal tissues. The rats in sham group were given simulation of burns without resuscitation, which were immediately sacrificed and the specimens were harvested. The serum Na+ concentration was determined by automatic biochemical analyzer. Tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) contents in serum were determined by enzyme-linked immunosorbent assay (ELISA). The moisture content of intestine reflected by intestine wet/dry weight (W/D) ratio was determined. The content of malondialdehyde (MDA) and the activity of diamine oxidase (DAO) in intestinal tissue were determined by ultraviolet spectrophotometer. The activation of von Willebrand factor (vWF) was assessed by using immunohistochemistry. RESULTS: Compared with sham group, and the contents of TNF-α and IL-1ß in blood and W/D ratio and MDA contents in intestine at each time point after injury in LR group and three HS groups were significantly increased, and the activity of intestinal DAO was significantly decreased. The serum Na+ concentration was significantly reduced in the LR group as compared with that in the sham group, which was significantly higher in the three HS groups than that in the sham group, with the most obvious change on the 8th PIH. Compared with LR group, the serum Na+ concentration and the activity of intestine DAO at each time point after injury in different concentrations of HS groups were significantly increased, and the serum contents of TNF-α, IL-1ß and the W/D ratio, MDA contents in intestine were significantly lowered showing a dose dependent. The changes of HS400 group was the most significantly, and the difference on the 8th PIH was statistically significant as compared with LR group [blood Na+ (mmol/L): 145.51±0.72 vs. 131.52±0.85, intestinal DAO (U/g): 4.85±0.30 vs. 3.50±0.45, blood TNF-α (ng/L): 88.47±4.91 vs. 153.21±13.45, blood IL-1ß (ng/L): 85.77±3.42 vs. 140.57±10.46, intestinal W/D ratio: 3.32±0.05 vs. 3.73±0.09, intestinal MDA (nmol/mg): 0.58±0.01 vs. 0.82±0.04, all P < 0.05]. The immunohistochemical results showed that the vWF activity in the LR group and different concentrations of HS groups was significantly reduced as compared with that of the sham group. Compared with LR group, the activity of intestinal vWF at each time point in different concentration of HS groups was increased to some extent with a dose dependent. The positive staining in HS400 group was the deepest, which showed that the activity of intestinal vWF was the strongest after treated by 400 mmol/L HS. CONCLUSIONS: Compared with LR, HS can attenuate intestinal tissue injury of rats at the early stage of severely burned, and of all, the curative effect of 400 mmol/L HS is the best.