Deficiency of Trex1 leads to spontaneous development of type 1 diabetes.

BACKGROUND: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. METHODS: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-ß were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. RESULTS: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1-/- rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-ß, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic ß cells. CONCLUSIONS: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

Management of burns of over 80% of total body surface area: a comparative study.

The aim of this retrospective, comparative study was to analyse the management of extensive burns so as to decrease morbidity and mortality. Over 1987-1996, 24 people with burns >80% of total body surface area and >50% full-thickness burn were admitted to the burn unit of Anhui Medical University Hospital (group A); 30 similar admissions over 1997-2006 formed group B. No significant difference was found in age, male:female ratio, % total body surface or full-thickness burn area between the two groups. Severe shock developed in 19/24 cases in group A and 23/30 cases in group B, following inadequate fluid resuscitation, although group B received a higher mean resuscitation fluid volume during the first 24h after burn. Early excision and grafting was performed for 8/24 people in group A and 23/30 in group B. Inhalation injury was seen in 18/24 cases in group A and 28/30 cases in group B. Prophylactic tracheotomy was undergone by 8/24 casualties in group A and 22/30 in group B. Mortality in group A was significantly higher than in group B (95.8% vs. 63.3%, p<0.05) and survival was longer in group B. These results showed that refinements in burn shock resuscitation, and advances in early wound excision, skin grafting and respiratory management were associated with decreased morbidity and mortality after severe burn.

Electrical burns in Chinese fishermen using graphite rods under high-voltage cables.

The 42 patients admitted to our Burn Center from January 1, 1994 to December 31, 2005, with electrical and fire burn injuries caused by electricity-conducting graphite-carbon fishing rods touching overhead high voltage electrical lines were epidemiologically studied retrospectively. All patients were men, with a mean age of 40.33 years. The majority of patients (59.5%) were burned with less than 10%, mostly deep burns. The hand was the predominant electricity "entry" point and foot was the most frequent "exit" point. Admissions increased from 5 in 6 years, 1994 to 2000, to 15 in 3 years, 2000 through 2002, to 22 cases in 3 years, 2003 through 2005. Spring and fall, and months May and October were times of highest incidence. The treatment was complex, difficult, long, and costly. Thirty-eight patients (90.4%) required operations, including early excision and graft (34 patients), and amputation (14 patients). Two patients had an inhalation injury that necessitated a tracheostomy and four victims had additional skin and soft-tissue injury. Thirty-two patients had a record of unconsciousness immediately after the electrical injury and atrial premature beats were a frequently found arrhythmia. A significant (P <.01) increase in serum creatine kinase MB fraction was found in 11 patients. The mean time in hospital of the survivors was 28.97 days. Acute renal failure was the commonest complication and one patient died of sepsis with giving a mortality rate of 2.4%. Caution and preventive measures are warranted while fishing near electrical wires, and improvements in electrical burn treatment are needed.