Severe burns trigger the stress response, cause different degrees of damage to the body, and participate in the occurrence and development of immune dysfunction and hypermetabolism after burn. Rational application of analgesic and sedative drugs is the major method of inhibiting the severe burn-induced stress response, which can alleviate the organ damages and reduce the incidence of burn sepsis. Furthermore, integrated approaches including wound management, infection control, nutritional support, and gastrointestinal tract protection, as well as sleep management, etc., collectively contribute to the alleviation of stress response after burn injury. To further improve the success rate of severe burn treatment, it is essential to study the changes of various stresses, endocrine hormones and immune patterns in patients with severe burn, to explore the mechanism and regulation of burn-induced hypermetabolism, and to reach a consensus on sedation and analgesia strategy, the management of stress response and hypermetabolism after severe burns.

Objective:To compare the effects of the modified lytic cocktail and the classic lytic cocktail on organ function of severely scalded rats.Methods:The experimental study method was applied. Twenty-four about 10-week-old male Sprague-Dawley rats were assigned into sham injury group, scald alone group, classic lytic cocktail group, and modified lytic cocktail group according to the random number table, with 6 rats in each group. In scald alone group, classic lytic cocktail group, and modified lytic cocktail group, rats were subjected to a 30% total body surface area (TBSA) full-thickness scald on the back. Rats in sham injury group underwent a simulated injury process to mimic a sham injury. Immediately after injury, rats in classic lytic cocktail group were intraperitoneally injected with a classic lytic cocktail (12 mL/kg) consisting of pethidine, chlorpromazine, and promethazine, supplemented with gavage using normal saline; and rats in modified lytic cocktail group were intraperitoneally injected with a mixed drug (2 mL/kg) consisting of midazolam and fentanyl, supplemented with gavage using cetirizine. Subsequently, rats in four groups were all intraperitoneally injected with lactated Ringer's solution for fluid resuscitation, with a total fluid and administration volume of 2 mL·kg -1·TBSA -1. On the following day, rats in the two lytic cocktail groups were administered medication once again as above. On post injury day (PID) 3, the abdominal aortic blood, liver, small intestine, and lung tissue were collected from rats in each group. The plasma levels of interleukin-1β (IL-1β), IL-10, and IL-6 were measured using an enzyme-linked immunosorbent assay. The plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), LDH isoenzyme 1 (LDH-1), creatine kinase (CK), CK isoenzyme (CK-MB), urea, creatinine, and uric acid were detected using an automated biochemical analyzer. The histological changes of liver, small intestine, and lung tissue were observed after performing hematoxylin and eosin staining. Data were statistically analyzed with one-way analysis of variance and Tukey's test. Results:On PID 3, the plasma level of IL-10 of rats in classic lytic cocktail group was (44±16) pg/mL, which was significantly higher than (20±9) pg/mL in modified lytic cocktail group and (21±6) pg/mL in scald alone group (with P values all <0.05); there was no statistically significant difference in the plasma levels of IL-1β or IL-6 of rats among the four groups ( P>0.05). On PID 3, the plasma levels of ALT and AST of rats in scald alone group were (77±14) and (213±65) U/L, respectively, which were significantly higher than (59±5) and (108±10) U/L in sham injury group ( P<0.05); the plasma levels of ALT and AST in modified lytic cocktail group were (61±3) and (116±11) U/L, respectively, which were significantly lower than (81±13) and (207±54) U/L in classic lytic cocktail group ( P<0.05); the plasma level of AST of rats in modified lytic cocktail group was significantly lower than that in scald alone group ( P<0.05). On PID 3, there was no statistically significant difference in the plasma levels of γ-GT, ALP, LDH, LDH-1, CK, CK-MB, creatinine, or uric acid of rats among the four groups ( P>0.05); although there was a statistically significant overall difference in the plasma level of urea of rats among the four groups ( P<0.05), the comparisons between scald alone group and each of sham injury group, classic lytic cocktail group, and modified lytic cocktail group, and the comparison between classic lytic cocktail group and modified lytic cocktail group showed no statistically significant differences ( P>0.05). On PID 3, compared with those in sham injury group, rats in scald alone group exhibited diffuse microvesicular and vacuolar degeneration of hepatocytes in liver tissue, noticeable loose edema in the villous stroma in small intestine tissue, and significantly widened alveolar septa in large area of lung tissue. Compared with those in scald alone group, rats in the two lytic cocktail groups showed alleviated hepatocellular steatosis and vacuolar degeneration, relieved thickening of alveolar walls and edema in the villous stroma of the intestine. The histopathological manifestations of organs in rats of modified lytic cocktail group were closer to those in sham injury group. Conclusions:The classic lytic cocktail may have a stronger anti-inflammatory effect, while the modified lytic cocktail exhibits better protection of liver function, but both of the two lytic cocktails can alleviate the histopathological injury of the liver, lungs, and small intestine in severely scalded rats. For the liver, lungs, and small intestine, the modified lytic cocktail provides organ protection comparable to that of the classic lytic cocktail.

Objective:To investigate the effects of hypoxia-pretreated rat adipose-derived mesenchymal stem cells (ADSCs) conditioned medium on wound healing of rats with full-thickness defects.Methods:(1) A 6-week-old male Sprague-Dawley rat was sacrificed by cervical dislocation, the bilateral inguinal adipose tissue was collected, the third generation ADSCs were isolated by collagenase digestion method, and the cells morphology was observed. The cells were harvested and divided into adipogenic induction group and osteogenic induction group according to the random number table (the same grouping method below), with 6 wells in each group. The cells in adipogenic induction group were cultured for 14 days to observe adipogenesis, and cells in osteogenic induction group were cultured for 28 days to observe osteogenesis. (2) The third generation ADSCs were collected and divided into normoxic group and hypoxic group. Cells in normoxic group was incubated in normal oxygen incubator with oxygen volume fraction of 21%, and cells in hypoxic group was incubated in low oxygen incubator with oxygen volume fraction of 2% respectively, with 3 samples in each group for each time point. Three samples in normoxic group on 3 h of culture and in hypoxic group on 3, 6, 12, 24, and 48 h of culture were collected for detecting the following indexes. The mRNA expressions of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and peroxisome proliferator-activated receptor γ (PPAR-γ) were detected by real time fluorescent quantitative reverse transcription polymerase chain reaction. The cell culture supernatant in the two groups was collected, centrifuged, and filtered to obtain normoxic conditioned medium (normo-CM ) and hypoxic conditioned medium (hypo-CM). Enzyme linked immunosorbent assay was used to detect content of VEGF, transforming growth factor β (TGF-β), epidermal growth factor (EGF), and insulin-like growth factor (IGF) in conditioned medium. (3) Twenty-seven male Sprague-Dawley rats aged 6-8 weeks were collected and divided into phosphate buffer solution (PBS) group, normo-CM group, and hypo-CM group, with 9 rats in each group. A circular full-thickness skin defect wound with diameter of 1 cm was made on the back of each rat, and the wounds of rats in PBS, normo-CM, and hypo-CM groups were respectively dropped with 50 μL PBS, normo-CM, and hypo-CM. On post injury day (PID) 0, 3, 5, 7, 9, and 11, the gross condition of wound was observed, wound area was measured, and the non-healing rate of wound was calculated. The wound tissue was collected for hematoxylin eosin staining to observe inflammatory reaction of wound on PID 3, 9, and 11 and re-epithelialization of wound on PID 9. Masson staining was used to observe the collagen deposition and analyze collagen volume fraction of wound on PID 11. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, t test, and Bonferroni correction. Results:(1) The isolated cells showed a fusiform, in adherent growth and close arrangement when in low fusion degree. On 14 d of culture, the red lipid droplets stained with oil red O were observed in cells in adipogenic induction group, and on 28 d of culture, the red nodules stained with alizarin red S were observed in cells in osteogenic induction group. The cells were identified as ADSCs. (2) Compared with that in normoxic group, the mRNA expression of HIF-1α was significantly increased at 12 and 24 h of culture ( t=5.43, 5.11, P<0.05), the mRNA expression of VEGF was significantly increased at 6 and 12 h of culture ( t=3.29, 2.33, P<0.05 or P<0.01), the mRNA expression of bFGF was significantly increased at 12 h of culture ( t=12.59, P<0.01) and significantly reduced at 48 h of culture (t=9.34, P<0.01), and the mRNA expression of PPAR-γ was significantly reduced at 3, 12, and 24 h of culture in hypoxic group ( t=5.14, 6.56, 4.97, P<0.05). (3) Compared with that in normoxic group, the VEGF content was significantly increased at 3, 6, 12, 24, and 48 h of culture ( t=5.74, 12.37, 14.80, 15.70, 34.63, P<0.05 or P<0.01), and the IGF content was significantly increased at 6, 12, 24, and 48 h of culture ( t=5.65, 8.06, 20.12, 22.99, P<0.05 or P<0.01), and the content of TGF-β and EGF showed no obvious change at 3, 6, 12, 24, and 48 h of culture in hypoxic group. (4) From PID 0 to 11, the wound of rats in the three groups shrank to varying degrees, with no obvious infection or exudate. On PID 11, the wound area of rats in PBS group was still large, which was larger than that in normo-CM group, and the wound area of rats in hypo-CM group was basically healed. On PID 0, 3, and 5, the non-healing rates of wound of rats in the three groups were similar. On PID 7, the non-healing rates of wound of rats in normo-CM and hypo-CM groups were significantly lower than that in PBS group ( t=10.26, 16.03, P<0.05). On PID 9, the non-healing rate of wound of rats in hypo-CM group was significantly lower than that of PBS group and normo-CM group, respectively ( t=17.25, 6.89, P<0.05 or P<0.01), and the non-healing rate of wound of rats in normo-CM group was significantly lower than that in PBS group ( t=8.81, P<0.05). On PID 11, the non-healing rate of wound of rats in hypo-CM group was (2.4±1.5)%, which was significantly lower than (20.0±5.0)% in PBS group and (7.7±1.7)% in normo-CM group ( t= 30.15, 84.80, P<0.05). (5) On PID 3, the infiltration of inflammatory cells in the wound of rats in hypo-CM group was obviously more than those in the other two groups. On PID 9, the infiltration of inflammatory cells in the wound of rats in hypo-CM and normo-CM groups was obviously less than that in PBS group. On PID 11, the infiltration of inflammatory cells in the wound of rats in hypo-CM group was obviously less than those in PBS and normo-CM groups. On PID 9, the length of " epidermal migration tongue" on the wound of rats in hypo-CM group was longer than those of the other two groups, and the epidermis thickness was close to normal skin. On PID 11, compared with those in PBS and normo-CM groups, a large number of collagen deposits with dense structure, neat arrangement, and higher maturity were seen in the wound of rats in hypo-CM group. The wound collagen volume fraction of rats in PBS group was (22.90±1.25)%, which was significantly lower than (31.96±0.14)% in normo-CM group and (56.10±1.50)% in hypo-CM group ( t=12.48, 29.43, P<0.05), and the wound collagen volume fraction of rats in normo-CM group was significantly lower than that in hypo-CM group ( t=27.73, P<0.05). Conclusions:Hypoxia-pretreated can significantly enhance paracrine effect of rat ADSCs. Hypoxia-pretreated rat ADSC conditioned medium can accelerate the healing of full-thickness skin defect wound in rats by regulating inflammatory cell infiltration, promoting re-epithelialization and collagen deposition in the wound.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.