On December 20, 2018, a 40-year-old male patient with extremely severe flame burn was admitted to Guangzhou First People's Hospital. A variety of difficult illnesses occurred simultaneously (refractory hyperglycemia, refractory hypernatremia, and progressive wound deepening) and successively (repeatedly postoperative hypotension, nervous system diseases, and secondary diabetes insipidus). The patient underwent treatments such as anti-shock, reducing blood sugar and blood sodium, scab removing, and gradual skin grafting after admission. Although the hyperglycemia and hypernatremia were basically corrected and the wounds were basically repaired, the patient ultimately died of nervous system diseases and secondary diabetes insipidus 5 months later. Although the cause of the above illnesses can not be fully determined, the targeted treatments to improve clinical symptoms, maintain stable internal environment and physiological function, and accelerate the process of wound repair conducted by the team may provide some experience for the treatment of such severe patients.

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, tFNAs have been widely applied in the biomedical field as three-dimensional DNA nanomaterials. Surprisingly, tFNAs exhibit positive effects on cellular biological behaviors and tissue regeneration, which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity, tFNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic tFNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic tFNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone, cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.
Nucleic Acids/chemistry* ; Regenerative Medicine ; Consensus ; Reproducibility of Results ; DNA/chemistry*

Background Coal workers' pneumoconiosis (CWP) is a serious occupational disease. Whether ferroptosis, a form of necrotic regulated cell death, is involved in coal dust induced mouse models of CWP needs further survey. Objective This experiment is designed to elucidate the role of ferroptosis in the formation of CWP induced by coal dust in mice. Methods C57BL/6J mice were randomly assigned to a saline group or a CWP group, with eight mice in each group. The mice were treated with 0.1 mL normal saline or 0.1 mL coal dust suspensions (50g·L^-1) via intra-tracheal instillation. HE staining and Masson staining were used to show lung injury and lung fibrosis. Iron concentration in mouse lung tissues was measured using iron assay kit. Lipid peroxidation was estimated in lung tissues by malondialdehyde (MDA) concentration and immunofluorescence intensity, and the ratio of glutathione (GSH) to L-glutathione oxidized (GSSG). Western blotting and real-time fluorescence-based quantitative PCR were used to test protein and mRNA expression levels of glutathione peroxidase 4 (GPX₄) and ferritin in mice. Results Coal dust injured pulmonary structure, thickened alveolar wall, and caused collagen deposition and infiltration of inflammatory cells in the CWP group. The iron concentration in the CWP group [(10.75 ± 5.42) mg·L⁻¹] was higher than that in the saline group [(1.14 ± 0.37) mg·L⁻¹] (P < 0.01). The MDA concentration in the CWP group [(37.32 ± 12.18) μmol·L⁻¹] was higher than that in the saline group [(18.70 ± 8.22) μmol·L⁻¹] (P <0.01). The immunofluorescence intensity of MDA in the CWP group was stronger than that in the saline group. The GSH/GSSG ratio decreased in CWP treated mice (1.50 ± 1.70) compared with the normal saline treated ones (4.95 ± 2.86) (P < 0.01). Compared with the saline group (38.84 ± 15.61 for GPX₄, 225.90 ± 54.34 for ferritin), the relative expression levels of GPX₄ and ferritin mRNA in the CWP group were downregulated (14.29 ± 7.21 for GPX₄, 106.70 ± 36.70 for ferritin) (P < 0.01). Compared with the saline group (1.47 ± 0.54 for GPX₄, 1.73 ± 0.34 for ferritin), the relative expression levels of GPX₄ and ferritin protein in the CWP group were also downregulated (0.92 ± 0.22 for GPX₄, 0.97 ± 0.09 for ferritin) (P < 0.05). Conclusion Ferroptosis may be involved in the formation of coal workers' pneumoconiosis induced by coal dust in mice.

Objective To observe the incidence of critical illness-related corticosteroid insufficiency (CIRCI) after severe traumatic brain injury (sTBI) and investigate the relationship between CIRCI and prognosis.Methods This prospective cohort study enrolled 89 sTBI patients (68 males and 21 females;at age range of 15-80 years) hospitalized within 24 hours after sTBI from June 2014 to December 2015.The Glasgow coma scale (GCS) was ≤8 points.The causes of injury included extensive contusion of brain (44 cases),subdural hematoma (21 cases),epidural hematoma (11 cases),primary brain stem injury (8 cases) and diffuse axonal injury (5 cases).Adrenocorticotropic hormone (ACTH) stimulation tests were done within 36 hours after sTBI to identify CIRCI patients.The patients were divided into CIRCI group (50 cases) and non-CIRCI group (39 cases).Moreover,the patients were categorized into survival group (62 cases) and death group (27 cases) based on survival status.The GCS score,mechanical ventilation time,cerebral hernia,survival time and mortality within 28 days were observed in two groups.Results The incidence of CIRCI in sTBI patients was as high as 56％ (50/89).Compared with the non-CIRCI group,the CIRCI group had lower GCS [(5.3 ± 1.7) points vs.(6.1 ± 1.4) points,P ＜ 0.05],and sTBI patients with CIRCI were mechanically ventilated for a longer period of time [(9.9 ± 2.8) days vs.(7.5 ± 1.6) days,P ＜ 0.05].In comparison with non-CIRCI patients,the incidence of brain herniation in sTBI patients with CIRCI was higher (58％ vs.21％,P ＜0.01).The total fatality rate within 28 days was 30％ (27/89).The survival time of CIRCI group was significantly shorter than that of non-CIRCI group (P ＜ 0.05).The fatality rate in the CIRCI group was significantly higher than that of the non-CIRCI group [40％ (20/50) vs.18％ (7/39),P ＜0.05].The incidence of CIRCI in death group was significantly higher than that of the survival group [74％ (20/27) vs.48％ (30/62),P ＜ 0.05].Conclusions The incidence of CIRCI in STBI patients is high.The sTBI patients with CIRCI has significantly higher incidence of brain hernia,longer mechanical ventilation time,higher 28-day mortality and shorter survival time compared with non-CIRCI patients.

In the middle of the 20th century, the United States first proposed the medical humanities theory to campus and offered a variety of medical humanities curriculum, hoping that medical students would have a better understanding of diseases, pain, show themselves more compassion, and foster their communication skills. In recent years, the medical humanities education played a positive role in developing and improving medical students’ comprehensive ability as well as their diagnosis and treatment technology. Currently, American pays more attention to establish a unified and objective standard to evaluate the effect of medical humanities curriculum. Meanwhile, many experts give some suggestions to the medical humanities education.

Objective To study the relationship between homocysteine (Hcy)and carotid atherosclerosis in patients with cer-ebral infarction.Methods During January and November 2013,281 patients with cerebral infarction from Affiliated Hospital of Yan’an University were provided the blood samples as cerebral infarction group,140 healthy volunteers served as control group.Serum Hcy was detected by enzymatic cycle assay.According to the results of carotid artery ultrasonography,cerebral infarction group was divided into five groups:artery normal group,intimal thickening group,soft plaque group,mixed plaque group and hard plaque group.The statistically significance was analyzed by SPSS 19.0.Results The serum Hcy level of cer-ebral infarction group was 19.78 ± 5.21 μmol/L,significantly higher than the control group 10.24 ± 3.33 μmol/L (P <0.001).The serum Hcy levels of control group,artery normal group,intimal thickening group,soft plaque group,mixed plaque group and hard plaque group were 10.24±3.33,15.20±2.99,17.03±1.85,25.44±4.24,19.65±4.74 and 18.31 ±3.67 μmol/L respectively.The differences between groups were statistically significant in addition to intimal thickening group and hard plaque group (P =1.106).The positive rates were 16.4%,53.7%,87.1%,95.7%,83.1% and 77.3% re-spectively,the groups which in cerebral infarction group compared with control group,the differences were statistically sig-nificant (P <0.001).Conclusion Hcy played an important role in the occurrence and development of cerebral infarction. Lower serum Hcy concentration,may be an effective way to prevent carotid atherosclerosis and cerebral infarction.

OBJECTIVETo observe the effect of the decomposition products of necrotic tissues from wounds on the serum levels of inflammation factors in comparison with endotoxin.

METHODSThirty adult New Zealand rabbits were randomly divided into 3 groups and received injections of saline, necrotic tissue homogenate or endotoxin. From each rabbit, blood samples (2 ml) were collected from the central artery of the ears at 0, 2, 6, 12, 24, 30, 36, 48, and 60 h after the injection for measurement of serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and IL-6.

RESULTSThe serum level of TNF-α, IL-1 and IL-6 in the rabbits increased 2-4 h after injection of the necrotic tissue homogenate and reached the peak level at 12 h, followed by a gradual reduction since 36 h. No obvious changes in the levels of the inflammatory factors were found in saline group (P<0.01). Compared with endotoxin, necrotic tissue homogenate resulted in an early increment (2-4 h vs 5-6 h) and significantly higher peak levels (at 30 h) of the inflammation factors (P<0.05). Curve fitting showed a distinct difference between necrotic tissue homogenate and endotoxin in their effect on the inflammatory factors.

CONCLUSIONThe necrotic tissue decomposition products contain toxic substances that possess a different toxicity profile from endotoxin, and their toxicity can be even stronger.

Animals ; Endotoxins ; adverse effects ; Inflammation ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Necrosis ; Rabbits ; Tumor Necrosis Factor-alpha ; blood ; Wounds and Injuries ; blood ; pathology

ObjectiveTo evaluate the effect of xuebijing injection on inflammatory response and cellular immune function in patients with severe sepsis.MethodsSixty-two patients with severe sepsis from September 2008 to August 2009 were divided into treatment group(30 patients) and control group (32patients) by random digits table.All the patients received sepsis-bundle therapy and patients in treatment group added xuebijing injection therapy with 100 ml,twice a day,for 7 days.The levels of serum tumor necrosis factor-alpha(TNF-α ),interleukin(IL)-6,IL-10 and C-reactive protein (CRP),peripheral blood T lymphocyte CD4+、CD8+ 、CD4+/CD8+,the expression of human leucocyte antigen (HLA)-DR on CD14+peripheral blood mononuclear cell (PBMC) were detected before and aftertreatment.ResultsThere was no significant difference in the levels of serum TNF-o,IL-6,IL-10,CRP,peripheral blood Tlymphocyte CD4+、CD8+、CD4+/CD8+ and the expression of HLA-DR on CD14+ PBMC before treatment between two groups(P ＞ 0.05).After treatment,compared with those in control group,the levels of serum TNF- α,IL-6,IL-10 and CRP in treatment group were significantly decreased [ ( 64.4 ± 13.5) ng/L vs.(96.1 ± 22.1 ) ng/L,( 153.8 ± 23.8 ) ng/L vs.(180.1 ± 21.7) ng/L,(73.8 ± 13.8) ng/L vs.(101.1 ± 11.7) ng/L,(53.7 ± 18.8) mg/L vs.(91.3 ± 32.8)mg/L,P ＜0.05],while peripheral blood T lymphocyte CD4+/CD8+ and the expression of HLA-DR on CD14+PBMC were significantly increased [ 0.311 ± 0.021 vs.0.424 ± 0.035,0.201 ± 0.017 vs.0.238 ± 0.038,1.78 ±0.21 vs.1.56 ±0.18,(38.4 ± 11.5)％ vs.(18.1 ± 12.1)％,P＜0.05].ConclusionXuebijing injection can reduce the inflammatory response and ameliorate immune disorder in patients with severe sepsis.

Objective To study the clinical significance of the injury and functional change of hypothalamic-pituitary-adrenal (HPA) axis after acute severe traumatic brain injury (TBI) in the rats.Methods A total of 60 adult healthy male Spraque-Dawley rats were randomly (random number) divided into 3 groups (n =20 in each group):sham operation group,model group and treatment group.The TBI models of rats were established by Feeney' s method.A low dose of dexamethasone (0.6 mg/kg) was injected into the abdominal cavity 20 minutes,24 hours and 48 hours after injury in treatment group,while rats of sham operation group and model group received equal volume of normal saline instead.All the rats were injected 1 μg adrenocorticotropic hormone (ACTH) into the abdominal cavity.The related parameters were detected at four time points,3 hours,12 hours,24 hours and 72 hours after cerebral contusion.The plasma corticosterone (CORT) and ACTH levels were measured by chemiluminescence.The hypothalamic,pituitary and adrenal of the rats were taken out for observing interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression detecting by immunohistochemical techniques at 72nd hour after TBI.One-way ANOVA and SNK-q test were used to analyze the results with SPSS 17.0 software package.Results The levels of ACTH and CORT on 3rd hour of model group raised remarkably compared with that of sham operation group,then they reduced gradually.The levels of CORT were lower than that of sham operation group at every time points after ACTH stimulation test (P ＜0.05 or P ＜0.01).The levels of CORT at all time points of treatment group were changed remarkably compared with that of model group.However,the ACTH levels of treatment group on 24 h increased slightly than that of model group.And the tendency of them was similar to model group (P ＜ 0.05 or P ＜ 0.01).The number of the hypothalamus and pituitary cells which express IL-6 and TNF-α in model group was more significantly increased when compared with that in sham operation group (P ＜ 0.01),while the number of this kind of cell in treatment group was significantly decreased than that in model group (P ＜ 0.01).The number of the adrenal cortex cells which express IL-6 in treatment group was more significantly decreased when compared with that in model group (P＜ 0.01),while the number of this kind of cell in model group was significantly increased than that in sham operation group (P ＜ 0.01).However,there was no significant difference of the TNF-α between all the groups (P ＞ 0.05).Conclusions Functional change of adrenal occurs early in the severe acute traumatic brain injury rats,and the response of adrenal to ACTH decreased as time goes by.Low-dose,short-course dexamethasone can delay the pathological changes,reduce the inflammatory response of HPA axis and increase the sensitivity of adrenal response to ACTH.

Objective To study the protective effect of removing inflammatory cytokines by hemoperfusion (HP)on acute kidney injury (AKI) in patients with sepsis. Method A total of 40 patients with sepsis and AKI were randomly divided into two croups: HP treatment group (n = 22) and control group (n = 18). Hemoperfusion carried out in patients of Hp group with HA330 filter once a day for 3 days and the procedure of each hemoperfusion was completed in 2 hours. The patients of control group were treated with routine treatment. Further, the hemodynamics, plasma IL-6, IL-10, C-reactive protein (CRP), serum creatinine (Scr), blood BUN and urine NAG, γ-GTP,α1-MG of patients in both groups were detected before treatment and 3 d,7 d and 14 days after treatment. Results Compared to control group, the levels of plasma interleukins-6, IL-10 and C-reactive protein were significantly lower (P ＜ 0.05), along with increase in urine output, lower levels of blood BUN and Scr, reduction in urine NAG,γ-GT and α1-MG (P ＜ 0.05). In addition, the patients at Ⅰ or Ⅱ stage of AKI treated with hemoperfusion had significantly lower level of Scr in 14 days and lower mortality in intensive care unit in comparison with control group (P ＜ 0.05). Conclusions Hemoperfusion employed in the earlier stage of AKI with the HA type filter may have protective effect on acute kidney injury by the removal of inflammatory cytokines in the setting of sepsis.