The biodiversity of fungi in taxonomy and the biotopes in which they inhabit leads to the production of a variety of secondary metabolites that display a broad range of bioactivities, from which some very important medicines have been discovered. Even though the fungal secondary metabolites are an important source of drug leads, it has become increasingly difficult to discover new natural product scaffolds due to extensive screening of common soil fungi. Those special types of fungi have been largely neglected, presumably due to the difficulty in collecting and culturing of the organisms. Therefore, fungi of significantly underexplored taxonomic and ecological groups provide limitless metabolic potential for the production of new bioactive natural products, and systematic investigations of these fungal species will definitely play a key role in the discovery of new drug leads and understanding the chemical and biological bases for their living strategies. During the past four years, our research group has mainly focused on special types of fungi as sources of new bioactive metabolites, such as the endophytic fungi and the Cordyceps-colonizing fungi. Some results from this work are summarized herein.

OBJECTIVETo investigate the effect of carbachol(CAR) on oxygen dynamic parameters and hyperlactacidemia during oral fluid resuscitation of burn shock.

METHODSTwelve male Beagle dogs were surgically prepared for cannulation of carotid and jugular vein, and enterostomy, 24 hours later they were subjected to a 50% (total body surface area, TBSA) full-thickness flame injury under a 10-15 minute anesthesia by IV injection of propofol. The dogs were randomized to gastric fluid infusion group (GI group)and gastric fluid infusion plus CAR group (GI + CAR). Either a glucose-electrolyte solution(GES) or GES containing CAR (20 microg/kg) were intragastricly given to animals in GI group or GI+ CAR groups. The delivery rate and volume of GES was in accordance with that of Parkland formula. Mean arterial pressure (MAP), intestinal mucosal blood flow (IMBF) and blood lactic acid were determined, and blood gas analysis evaluated for oxygen delivery (DO2), oxygen consumption (VO2) and oxygen uptake (O2ext) at 0, 2, 4, 8, 24, 48 and 72 hours after injury.

RESULTSThe levels of MAP and IMBF markedly reduced, and LAC obviously increased in both groups after burn. MAP returned to 0 h level at 72 h post burn, while IMBF, and LAC were still higher or lower than 0 h levels. The level of MAP of GI + CAR group was significantly higher than that of GI group at 2 h, and those showed no significant differences between two groups after then. Carbochol administration led to a markedly higher levels of IMBF, and significant lower levels of LAC from 8 h after burn compared with those of GI group (P < 0.05 or P < 0.01). The levels of DO2 VO2 and Oext were reduced markedly after burn in both groups. At 72 h after burn, DOQ returned to 0 h level; while VO2 and Oext though still much lower than 0 h levels. The level of DO2. VO2 and Oext of GI + CAR group were significantly higher than those of GI group from 8 h after burn (P < 0.05 or P < 0.01). Three of six animals died in GI+ CAR group, which was lower than two of six in GI group.

CONCLUSIONThe results indicates that carbachol promotes intragastric fluid resuscitative effect of burn shock by increasing oxygen delivery and decreasing hyperlactacidemia.

Animals ; Burns ; complications ; physiopathology ; therapy ; Carbachol ; pharmacology ; Dogs ; Electrolytes ; administration & dosage ; Fluid Therapy ; methods ; Glucose ; administration & dosage ; Intestinal Absorption ; drug effects ; Male ; Oxygen ; metabolism ; Resuscitation ; methods ; Shock ; etiology ; physiopathology ; therapy

According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was (12.7 ± 1.9) μmol x L(-1) against A-549 cells, similar to cisplatin [IC50 = (8.0 ± 1.5) μmol x L(-1)], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of (9.5 ± 1.8) μmol x L(-1) and (11.5 ± 0.9) μmol x L(-1) respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Drug Design ; Humans ; Organophosphonates ; chemical synthesis ; pharmacology

OBJECTIVETo study the resuscitative effect of hypertonic electrolyte glucose solution (HEGS) in enteral resuscitation of burn shock.

METHODSEighteen Beagle dogs with 35% TBSA full-thickness flame injury were used in this study. They were randomized to a control group (no-fluid resuscitation, N group), a HEGS resuscitation group (H group) or an isotonic electrolyte glucose solution (IEGS) resuscitation group (I group). The solution enterally was given for resuscitation from half an hour after burn. The volumes and rates of fluid infusion in the H group were basically in accordance with 2 ml/(kg x 1%TBSA), those in the I group were basically in accordance with parkland formula [4 ml/(kg x 1%TBSA)]. The haemodynamic parameters, global end-diastolic volume index, plasma volume, osmotic pressure of plasma, intestinal absorptive rates of water and Na(+), and intestine mucosa blood flow were continuously assessed.

RESULTSThe cardiac output index, global end-diastolic volume index, plasma volume and intestine blood mucosa flow reduced markedly after burn in the three groups, and then gradually returned from 2 h after burn in two resuscitation groups, which were higher than that in the N group (P < 0.05). The activities of diamine oxidase in plasma in the two resuscitation groups were higher than that in N group (P < 0.05). The intestinal absorption rates of water and Na(+) reduced markedly after burn in two resuscitation groups with the lowest levels, and then returned from 6 h after burn. The rates of water in H group were lower than that in I group (P < 0.05); the rates of Na(+) in H group were higher than in I group (P < 0.05).

CONCLUSIONThe results indicated that 35%TBSA III degrees burn-injury dogs be resuscitated effectively with 1.8% hypertonic electrolyte-glucose solution by enteral, which 1/2 volume of an isotonic electrolyte glucose solution.

Animals ; Burns ; therapy ; Disease Models, Animal ; Dogs ; Enteral Nutrition ; Fluid Therapy ; methods ; Glucose Solution, Hypertonic ; administration & dosage ; therapeutic use ; Random Allocation ; Resuscitation ; methods ; Saline Solution, Hypertonic ; administration & dosage ; therapeutic use

OBJECTIVETo study the change in intestinal barrier and organ functions of burned dog after enteral administration of hypertonic electrolyte glucose solution (HEGS) in shock stage.

METHODSTwenty-four Beagle dogs inflicted with 35% TBSA full-thickness burn were divided into no-fluid group (NF), intravenous infusion with isotonic electrolyte glucose solution (IEGS) group (II group), enteral infusion with IEGS group (EI), and enteral infusion with HEGS group (EH) according to the random number table, with 6 dogs in each group. Saline, containing 50 g/L glucose, was intravenously or enterally infused into dogs in II group and EI group respectively 0.5 hour post injury (PIH) for resuscitation. Total infusion volume within PIH 24 was 4 mL x kg(-1) x %TBSA(-1) (half of the total volume was infused in the first 8 hours in a constant speed, the other half volume was infused in the rest 16 hours in a constant speed). HEGS, containing 18 g/L NaCl and 50 g/L glucose, was enterally infused into dogs in EH group. Total infusion volume within PIH 24 was 2 mL x kg(-1) x %TBSA(-1), with the same infusion speed as that in II and EI groups. Liver and kidney function indexes [activity of ALT and CK-MB, expression levels of creatinine and blood urea nitrogen (BUN) in serum], activity of diamine oxidase (DAO), and activity of Na(+)-K(+)-ATPase in intestinal mucosa at PIH 24 were determined.

RESULTSALT activity in each group was close to one another. Serum levels of creatinine and BUN in II, EI, and EH groups were significantly lower than those in NF group. CK-MB activity obviously increased at PIH 2 in every group. CK-MB activity in EH group at PIH 2 to 8 was respectively lower than that in NF and II groups. DAO activity in serum in II, EI, and EH groups decreased since PIH 4 or PIH 6, respectively from (3.9 + or - 0.6) U/L to (3.6 + or - 0.5) U/L, (4.8 + or - 0.4) U/L to (2.8 + or - 0.8) U/L, (6.4 + or - 1.8) U/L to (3.5 + or - 0.8) U/L, all were significantly lower than those in NF group [from (12.5 + or - 0.4) U/L to (9.7 + or - 1.1) U/L, comparison between EH group and NF group, t value at PIH 4, 6, 8, 24 was respectively 10.25, 12.44, 17.99, 16.21, P values all below 0.05]. The order of Na(+)-k(+)-ATPase activity in intestinal mucosa at PIH 24 in each group from high to low was II group, EH group, EI group, and NF group (comparison between former 3 groups and NF group, t value was respectively 10.09, 4.96, 8.32, F value was 26.79, P values all below 0.05).

CONCLUSIONSHEGS does not cause significant harm to the barrier function of intestinal mucosa of shock dog after burn. Compared with NF, HEGS can significantly improve functions of heart, liver, and kidney, and it can achieve the same resuscitation effect as enteral or intravenous infusion of IEGS with only half of the solution volume.

Animals ; Burns ; drug therapy ; metabolism ; physiopathology ; Disease Models, Animal ; Dogs ; Fluid Therapy ; Glucose Solution, Hypertonic ; administration & dosage ; therapeutic use ; Heart ; physiopathology ; Intestinal Mucosa ; metabolism ; Intestine, Small ; physiopathology ; Kidney ; physiopathology ; Liver ; physiopathology

OBJECTIVETo investigate the role of tumor necrosis factor (TNF) alpha on the homing efficiency of hematopoietic stem/progenitor cells (HS/PC) into bone marrow and its mechanism.

METHODSCFSE-labeled umbilical cord blood (UCB) CD34+ cells were transplanted into irradiated (control group) or combined with TNF alpha prepared (experimental group) BALB/c recipient mice. The distribution in peripheral blood, liver, lung and homing characteristics in bone marrow and spleen of UCB CD34+ cells, in BALB/c recipient mice were determined 20 hours after xenotransplantation by flow cytometry (FACS) and their homing efficiency was calculated. ELISA was used to measure serum SDF-1 alpha level. CXCR4 expression levels of on UCB CD34+ cells were assessed by FACS pre-/post-manipulation with TNF alpha. SDF-1 alpha expression level in bone marrow and spleen was tested by immunohistochemistry.

RESULTSUCB CD34+ cells mainly home into recipient mice bone marrow and spleen; The homing efficiency in experimental group bone marrow [(0.65 +/- 0.13)%] was significantly higher than that in control ones [(0.30 +/- 0.09)%, P < 0.01], whereas the homing efficiency in experimental group spleen was dramatically lower than that in control ones (P < 0.01); Treatment with TNF alpha did not affect recipient serum SDF-1 alpha level; After 18 hours co-cultured with TNF alpha, the CXCR4e expression level on UCB CD34+ cells was similar to that on fresh ones; TNF alpha treatment induced significantly higher SDF-1 alpha expression on osteoblastic and stromal cells in bone marrow, and reversed spleen SDF-1 alpha gradient that was originally favorable for CD34+ cells homing.

CONCLUSIONTNF alpha enhances the homing efficiency of HS/PC via up-regulating SDF-1 alpha gradient in bone marrow, and might be an useful enhancer for HS/PC homing in clinical practice.

Animals ; Antigens, CD34 ; Bone Marrow ; Cell Movement ; Cell Separation ; Chemokine CXCL12 ; metabolism ; Female ; Fetal Blood ; cytology ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; drug effects ; immunology ; metabolism ; Humans ; Mice ; Mice, Inbred BALB C ; Receptors, CXCR4 ; metabolism ; Transplantation Conditioning ; Transplantation, Heterologous ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo investigate the effect of early oral fluid resuscitation on hemodynamic and tissue perfusion in dogs with severe burn shock.

METHODSEighteen male Beagle dogs with intubation of carotid artery, jugular vein, stomach, jejunum and bladder for 24 h were subjected to a 50%TBSA full-thickness burn, then were equally divided into non fluid resuscitation (NR), oral resuscitation (OR) and intravenous resuscitation(IR) groups, (each n = 6). Dogs in IR and OR groups were given glucose-electrolyte solution (GES) by gastric tube or intravenous infusion according to Parkland formula within 24 h after burn, while those in NR group were not given any treatment. Dogs in each group were given intravenous fluid resuscitation from 24 h after burn. The mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance (SVR), dp/dt max of left ventricular contractility (dp/dt(max)), gastric carbon dioxide pressure (PgCO2), intestinal mucosal blood flow (IMBF), and urinary output were determined before burn (0 h) and 2, 4, 8, 24, 48 and 72 h after burn at no anaesthesia state. Mortality rate of 72 h after burn was also recorded.

RESULTSMAP, CO, dp/dt(max), IMBF greatly decreased, and SVR and PgCO2 obviously increased from 2 h after burn in each group (P < 0.01). The measurements except IMBF of IR group returned to pre-injury levels at 72 h after burn, while CO, SVR, PgCO2 and IMBF of OR group still worse compared with 0 h (P < 0.01). All measurements of NR group kept on worsen, and died with anuria within 24 h after burn. Parameters of hemodynamic and tissue perfusion of OR group were significantly superior to those of NR group, but it inferior to those of IR group. At 72 h after burn, 6 (6/6) survived in IR group, 3 (3/6) in OR group and 0 (0/6) in NR group.

CONCLUSIONSAlthough oral resuscitation with GES is not as efficient as intravenous resuscitation in a 50%TBSA burn injury, it still can promote hemodynamic, improve the tissue perfusion and reduce the mortality comparing to no resuscitation. Oral resuscitation might be an ideal alternative way of intravenous resuscitation, especially in wars or other site of mass casualties.

Animals ; Body Surface Area ; Burns ; Disease Models, Animal ; Dogs ; Fluid Therapy ; Hemodynamics ; drug effects ; Resuscitation

OBJECTIVETo observe the clinical effect of the concentrated suture fixation method on skin transplantation on deep burn wound or wound of cicatricial deformity after burn in the jaw and neck region.

METHODSOne hundred and fourteen patients, hospitalized from April 2002 to December 2011, with deep burn or cicatricial deformity after burn in the jaw and neck region, were divided into packaging group and concentrated suture group according to the random number table. Each group had 57 patients including 48 cases with deep burn and 9 cases with cicatricial deformity. Traditional suture-package fixation method and concentrated suture fixation method were respectively used in packaging group and concentrated suture group to fix the autologous medium split-thickness skin in transplantation on wounds or scars. On post operation day (POD) 14, the skin microcirculatory perfusion flow of skin graft was measured, and the occurrence of ecchymoma, infection, and necrosis of skin in operative region were observed. The elasticity and contracture of grafted skin and scar hyperplasia on wound edge were observed 6 months after operation. Measurement data were processed with u test, while enumeration data with Fisher's exact test or Chi-square test.

RESULTS(1) On POD 14, the skin microcirculatory perfusion flow in concentrated suture group [(2.86 +/- 0.8) V] was significantly higher than that in packaging group [(2.33 +/- 0.15) V, u = 17.776, P < 0.05]. (2) Ecchymoma occurred in 4 patients of packaging group and 3 patients of concentrated suture group, but the difference between two groups was not statistically significant (chi 2 = 0.152, P > 0.05). (3) Infection in operative region was observed in 1 patient of packaging group, while no patient in concentrated suture group showed this symptom. The difference between two groups was not statistically significant (P > 0.05). (4) Grafted skin in 6 patients of packaging group showed foliated necrosis, which was not observed on those of patients in concentrated suture group. The difference between two groups was statistically significant (P < 0.05). (5) Centipede leg-like scar hyperplasia on wound edge occurred in 21 patients in packaging group and 6 patients in concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 10.920, P < 0.05). (6) Poor elasticity of grafted skin was detected in 17 patients of packaging group and 4 patients of concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 9.865, P < 0.05). (7) Obvious contracture of grafted skin was observed in 15 patients of packaging group and 4 patients of concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 11.684, P < 0.05).

CONCLUSIONSConcentrated suture fixation method is suitable for application in transplantation of big sheet skin on wound in the jaw and neck region. It has high survival rate and is convenient for postoperative observation.

Adult ; Burns ; surgery ; Cicatrix ; surgery ; Female ; Humans ; Jaw ; surgery ; Male ; Middle Aged ; Neck ; surgery ; Skin Transplantation ; methods ; Sutures ; Transplantation, Autologous ; Treatment Outcome

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.