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Nai-Li Wei,1,2,* Zi-Fang Quan,3,4,* Tong Zhao,1,* Xu-Dong Yu,4 Qiang Xie,1 Jun Zeng,1 Fu-Kai Ma,1 Fan Wang,1 Qi-Sheng Tang,1 Heng Wu,3 Jian-Hong Zhu11Fudan University Huashan Hospital, Department of Neurosurgery, State Key Laboratory for Medical neurobiology, Institutes of Brain Science, Shanghai Medical College-Fudan University, Shanghai, 20040, People’s Republic of China; 2Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou Gansu China, 730030, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 4Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, 421001, People’s Republic of China *These authors contributed equally to this workBackground: Stress-related obesity might be related to the suppression of the hypothalamic-pituitary- adrenocortical axis and dysregulation of the metabolic system. Chronic stress also induces the dysregulation of the reward system and increases the risk of food addiction, according to recent clinical findings. However, few studies have tested the effect of chronic stress on food addiction in animal models.Purpose: The objective of this study was to identify whether chronic stress promotes food addiction or not and explore the possible mechanisms.Method: We applied adaily 2 hrsflashing LED irradiation stress to mice fed chow or palatable food to mimic the effect of chronic stress on feeding. After 1 month of chronic stress exposure, we tested their binge eating behaviors, cravings for palatable food, responses for palatable food, and compulsive eating behaviors to evaluate the effect of chronic stress on food addiction-like behaviors. We detected changes in the levels of various genes and proteins in the nucleus accumbens (NAc), ventral tegmental area (VTA) and lateral hypothalamus using qPCR and immunofluorescence staining, respectively.Results: Behaviors results indicated chronic stress obviously increased food addiction score (FAS) in the palatable food feeding mice. Moreover, the FAS had astrong relationship with the extent of the increase in body weight. Chronic stress increased the expression of corticotropin-releasing factor receptor 1(CRFR1) was increased in the NAc shell and core but decreased in the VTA of the mice fed with palatable food. Chronic stress also increased expression of both dopamine receptor 2 (DR2) and mu-opioid receptor (MOR) in the NAc.Conclusion: Chronic stress aggravates the FAS and contributed to the development of stress-related obesity. Chronic stress drives the dysregulation of the CRF signaling pathway in the reward system and increases the expression of DR2 and MOR in the nucleus accumbens.Keywords: chronic stress, obesity, food addiction, dopamine receptor 2, mu-opioid receptor, nucleus accumbens

What Is Already Known and Objective: Sedation is routinely provided for patients undergoing gastrointestinal endoscopy. Remimazolam tosilate is a novel and short-acting sedative agent that has been used for sedation during endoscopic procedures. The optimal dose of remimazolam in gastrointestinal endoscopy for patients with liver cirrhosis has not been elucidated., Background: To determine the effective dose of remimazolam tosilate with adjuvant sufentanil for sedation in patients with liver cirrhosis undergoing oesophagogastric varices screening endoscopy., Material and Methods: Patients aged 18-65 years with liver cirrhosis undergoing screening endoscopy for oesophagogastric varices were recruited. Sufentanil 0.15 μg/kg was given intravenously at 2 min before administration of remimazolam tosilate. The initial dose of remimazolam was 0.1 mg/kg and adjusted by 0.025 mg/kg as a step size, based on the Dixon and Massay up-and-down sequential method. Inclusion of patients was stopped after eight crossovers and the calculated median effective dose (ED 50 ) of remimazolam for successful endoscopy was obtained by calculating the mean of midpoint of all crossovers. Furthermore, a probit regression was applied to establish the dose-response curve of remimazolam and further assess the 95% effective dose (ED 95 ) of remimazolam., Results: The calculated ED 50 of remimazolam for successful endoscopy using the mean of midpoint of all crossovers was 0.097 mg/kg (95% CI, 0.004-0.099 mg/kg). Using the probit regression analysis, the ED 50 and ED 95 of remimazolam for successful endoscopy was 0.097 mg/kg (95% CI, 0.004-0.099 mg/kg) and 0.107 mg/kg (95% CI, 0.103-0.336 mg/kg), respectively. No adverse events were observed throughout the study period., Conclusions: This pilot study suggests that the ED 50 and ED 95 of remimazolam tosilate with adjuvant sufentanil for sedation in liver cirrhosis patients undergoing oesophagogastric varices screening endoscopy was 0.097 and 0.107 mg/kg, respectively., (© 2022 John Wiley & Sons Ltd.)

In China, it is a routine procedure to inject 250 μg of hemabate (sterile solution, an oxytocic, contains the tromethamine salt of the (I5S)-15 methyl analogue of naturally occurring prostaglandin F2α in a solution suitable for intramuscular injection) into the myometrium of patients experiencing uterine inertia after delivery, with an additional dose given in the event that the efficacy is not obvious. Although hemabate is prohibited from being used in patients with active liver disease, there are no restrictions regarding the application of hemabate in positive hepatitis B surface antigen (HbsAg)-positive subjects with normal liver function. Here we report adverse effects of hemabate in 1 HbsAg-positive subject with normal liver function. This subject experienced increased blood pressure, chest tightness, and type II second degree sinoatrial block 25 minutes after an additional injection of hemabate. Thus, special attention should be paid when applying hemabate in HbsAgpositive subjects with normal liver function.

Purpose: Positioning of the patient during and after surgery can have significant implications on recovery. Therefore, the purpose of the present study was to determine the influence of placing patients in a lateral decubitus position for 15 min after combined use of hyperbaric and hypobaric ropivacaine and assess hemodynamic characteristics during spinal anesthesia for caesarean section., Methods: One hundred-forty patients undergoing elective cesarean delivery with combined use of hyperbaric and hypobaric ropivacaine were included in the present study. Patients meeting inclusion criteria (134) were randomly allocated into Group A: immediately turned to the supine position after induction of spinal anesthesia (n = 67) or Group B: maintained in a lateral decubitus position for 15 min before being turned to the supine position (n = 67). Primary endpoints of the study were to compare hemodynamic characteristics and sensory blockade levels in the two groups, while a secondary endpoint was to observe the incidence of complications., Results: Both groups showed similar effects of the combined anesthetic treatment. Incidence of hypotension (43% vs 18%, P = 0.001), systolic AP < 90 mmHg (36% vs. 16%, P = 0.011), usage of ephedrine (43% vs. 18%, P = 0.001) and the total dose of ephedrine [0 (0-24) vs 0 (0-18), P = 0.001] were significantly higher in Group A compared to Group B. Group A had a higher incidence of nausea compared to Group B (25% vs 7%, P = 0.005)., Conclusions: Combined use of hyperbaric and hypobaric ropivacaine had satisfactory anesthetic effects and a more stable hemodynamic characteristic than either drug used alone. Maintaining the patient in a lateral decubitus position for 15 min can significantly decrease the incidence of hypotension.

Background and Purpose: Dexamethasone is known to produce analgesic effects, but the optimal analgesic dosage of dexamethasone remains unclear, especially in patients without postoperative use of other analgesics. The purpose of this study was to explore the effective analgesic dose of dexamethasone in day surgery patients undergoing painless abortion., Methods: 287 patients undergoing painless abortion were randomly assigned to one of four groups: control group receiving saline and dexamethasone groups receiving 0.1, 0.15, or 0.2 mg/kg dexamethasone. Drugs were intravenously injected 30 min before induction of anesthesia. All patients underwent the same anesthesia procedure using propofol and remifentan. The visual analogue scale (VAS) scores and occurrence of nausea, vomiting and drug-induced side effects were recorded at 1, 2 and 24 h after operation., Results: There were no significant differences in patient's clinical characteristics, surgical features and frequency of occurrence of nausea and vomiting among the four groups (P > 0.05). The VAS scores at rest and during coughing at 2 h after operation (time of discharge from the hospital) were significantly lower in patients receiving 0.2 mg/kg dexamethasone compared with control patients (P < 0.05)., Conclusion: Intravenous injection of 0.2 mg/kg dexamethasone before induction of anesthesia can significantly reduce the VAS scores at 2 h after painless abortion.

MicroRNA expression is a research focus in studies of tumors. This article concentrates attention on potential links between tumors caused by mouse mammary tumor virus (MMTV) and human breast cancer, in order to provide theoretical basis for using mouse model to search for miRNA effects mediated by Wnt/beta-catenin signaling in human breast cancer. By analyzing interactions between miRNAs and the Wnt/beta-catenin signaling pathway in breast cancer, we hope to casts light on more biological functions of miRNAs in the process of tumor formation and growth and to explore their potential value in cancer diagnosis, prognosis and treatment. Our endeavor aimed at providing theoretical basis for finding safer, more effective methods for treatment of human breast cancer at the miRNA molecular level.

The discovery of long noncoding RNA (LncRNA) changes our view of transcriptional and posttranscriptional regulation of gene expression. With application of new research techniques such as high-throughput sequencing, the biological functions of LncRNAs are gradually becoming to be understood. Multiple studies have shown that LncRNAs serve as carcinogenic factors or tumor suppressors in breast cancer with abnormal expression, prompts the question of whether they have potential value in predicting the stages and survival rate of breast cancer patients, and also as therapeutic targets. Focusing on the latest research data, this review mainly summarizes the tumorigenic mechanisms of certain LncRNAs in breast cancer, in order to provide a theoretical basis for finding safer, more effective treatment of breast cancer at the LncRNA molecular level.

Objective: To summary the treatment experience of severe acute pancreatitis (SAP)., Methods: From January 1997 to March 2009, a total of 1033 patients suffered SAP were admitted with a mean APACHE II score 12.0 +/- 4.3. There were 622 males and 411 females, aged from 13 to 98 years old. All patients were cared by the multidisciplinary team with intensivist, endoscopists, gastroenterologists, radiologist, nephrologist and surgeons.Patients treated in SICU in the early phase of the disease. In these 1033 patients, 365 cases received mechanical ventilation, 218 with tracheotomy, 159 cases received high-volume continuous venovenous hemofiltration (CVVH), 179 received nasobiliary drainage, 513 were treated with early enteral nutrition. CT-guided percutaneous catheter drainge for peripancreatic fluid collection was pefromed for 477 times and 438 patients received surgical debridement for infected pancreatic necrosis., Results: In all these 1033 cases, 975 patients (94.4%) survived, and 38 patients died (3.7%). The mortality of patients who received surgical debridement for infected pancreatic necrosis was 7.1% (31/438)., Conclusion: The muti-discipline management of severe acute pancreatitis can remarkably improve the prognosis of patients.

Objective: To compare the CT enhancement degree in pancreatic carcinoma (PC) and inflammatory pancreatic mass (IPM), and to study the diagnostic value of CT to these two diseases., Methods: Eighty-five patients with PC or IPM, 47 males and 38 females, aged 62 (37-79), underwent plain CT scanning and enhanced CT scanning in pancreatic phase and delay phase. The CT values of the pancreatic mass and relative normal pancreatic tissue were measured. The diagnosis of PC and IPM was verified by operation, biopsy, etc. Sixty persons without pancreatic diseases were used as controls., Results: Among the 85 patients, 66 were proved to be with PC, and 19 patients were proved to be with IPM. In plain CT scanning, pancreatic-phase CT enhancement, and delay-phase CT enhancement, the CT values of PC were (34+/-7) HU, (54+/-10) HU, and (61+/-14) HU respectively; and the CT values of the relatively normal pancreatic tissue were (42+/-6) HU, (105+/-12) HU, and (77+/-10) HU respectively. In plain CT scanning, pancreatic-phase CT enhancement, and delay-phase CT enhancement, the CT values of IPM were (37+/-6) HU, (58+/-17) HU, and (64+/-10) HU respectively; and the CT values of the relatively normal pancreatic tissue were (40+/-8) HU, (85+/-10) HU, and (72+/-9) HU respectively. The pancreatic-phase enhanced CT values of the mass in the PC group and the IPM group showed no remarkable differences (P>0.05). The pancreatic-phase enhancement intensity of the relatively normal pancreatic tissue is greater in PC than in IPM (P<0.01)., Conclusion: There is a certain limit for CT enhancement in differentiating between PC and IPM. Comprehensive analysis is necessary in diagnosis of PC and IPM.

Objective: To evaluate the effect of glutamine granules on immunofunction in severe burns and trauma patients., Methods: One hundred and twenty patients with severe burns, multiple trauma and post operation who met the requirements of the protocol joined this double-blind randomized controlled, multi-center clinical trail. Patients were randomly divided into two groups: placebo control group (P group, 60 patients) and glutamine granules treatment group (GLN group, 60 patients). There was isonitrogenous and isocaloric intake in both groups. GLN and P group patients had been given glutamine granules or placebo (glycine) at 0.5 g.kg(-1).d(-1) for 7 days, respectively. The level of plasma glutamine and some index of immunofunction were determined, and the complication and side effect were also observed., Results: After 7 days of taking glutamine granules orally, plasma GLN concentration was significantly higher than that in P group [(593 +/- 185) micromol/L vs (407 +/- 190) micromol/L)] (P < 0.01). IL-2 level, CD(4)/CD(8) ratio, PMN swallow ratio in GLN group were significantly higher than those in P group (P < 0.05-0.01), but the concentration of IgG, IgM, C(3)/C(4) were not significantly different when compared with P group (P > 0.05). In addition, the occurrence of side effect in both groups was seldom., Conclusion: Taking glutamine granules could increase plasma GLN concentration, enhance body immunofunction, and using glutamine granules is safe.

Aim: To evaluate the characters, risks and benefits of laparoscopic cholecystectomy (LC) in cirrhotic portal hypertension (CPH) patients., Methods: Altogether 80 patients with symptomatic gallbladder disease and CPH, including 41 Child class A, 32 Child class B and 7 Child class C, were randomly divided into open cholecystectomy (OC) group (38 patients) and LC group (42 patients). The cohorts were well-matched for number, age, sex, Child classification and types of disease. Data of the two groups were collected and analyzed., Results: In LC group, LC was successfully performed in 36 cases, and 2 patients were converted to OC for difficulty in managing bleeding under laparoscope and dense adhesion of Calot's triangle. The rate of conversion was 5.3%. The surgical duration was 62.6+/-15.2 min. The operative blood loss was 75.5+/-15.5 mL. The time to resume diet was 18.3+/-6.5 h. Seven postoperative complications occurred in five patients (13.2%). All patients were dismissed after an average of 4.6+/-2.4 d. In OC group, the operation time was 60.5+/-17.5 min. The operative blood loss was 112.5+/-23.5 mL. The time to resume diet was 44.2+/-10.5 h. Fifteen postoperative complications occurred in 12 patients (30.0%). All patients were dismissed after an average of 7.5+/-3.5 d. There was no significant difference in operation time between OC and LC group. But LC offered several advantages over OC, including fewer blood loss and lower postoperative complication rate, shorter time to resume diet and shorter length of hospitalization in patients with CPH., Conclusion: Though LC for patients with CPH is difficult, it is feasible, relatively safe, and superior to OC. It is important to know the technical characters of the operation, and pay more attention to the meticulous perioperative managements.

Aim: To investigate the potential role of continuous venovenous hemofiltration (CVVH) in hemodynamics and oxygen metabolism in pigs with severe acute pancreatitis (SAP)., Methods: SAP model was produced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight (BW)) and trypsin (2 U/kg BW). Animals were allocated either to untreated controls as group 1 or to one of two treatment groups as group 2 receiving a low-volume CVVH (20 mL/(kg.h)), and group 3 receiving a high-volume CVVH (100 (mL/kg.h)). Swan-Ganz catheter was inserted during the operation. Heart rate, arterial blood pressure, cardiac output, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, central venous pressure, systemic vascular resistance, oxygen delivery, oxygen consumption, oxygen extraction ratio, as well as survival of pigs were evaluated in the study., Results: Survival time was significantly prolonged by low-volume and high-volume CVVHs, which was more pronounced in the latter. High-volume CVVH was significantly superior compared with less intensive treatment modalities (low-volume CVVH) in systemic inflammatory reaction protection. The major hemodynamic finding was that pancreatitis-induced hypotension was significantly attenuated by intensive CVVH (87.4+/-12.5 kPa vs 116.3+/-7.8 kPa, P<0.01). The development of hyperdynamic circulatory failure was simultaneously attenuated, as reflected by a limited increase in cardiac output, an attenuated decrease in systemic vascular resistance and an elevation in oxygen extraction ratio., Conclusion: CVVH blunts the pancreatitis-induced cardiovascular response and increases tissue oxygen extraction. The high-volume CVVH is distinctly superior in preventing sepsis-related hemodynamic impairment.

Objective: To observe the therapeutic effect and possible side effects of glutamine granules per os in patients with trauma, burns and major operations., Methods: Patients inflicted with severe burns, trauma and major operations were enrolled in the study. One hundred and twenty patients were randomly divided into two groups, 60 in control group (C) and 60 in glutamine group (Gln). Randomized double blind and placebo control methods were employed in the study. All the patients in both groups were given diet with equal calories and equal nitrogen content. The patients in Gln group received glutamine granules in dose of 0.5 g.kg(-1).d(-1) orally or by gavage, while those in C group received same dose of placebo (glycine) for 7 days. The changes in the intestinal mucosal barrier function, the protein metabolism, the immune function, hepatic and renal functions, and the incidence of side effects of the medication in both groups of patients were observed and compared before and after the supplementation of glutamine or glycine., Results: The plasma contents of glutamine, proteins and interleukin 2 in both groups were all lower than normal values. But the plasma diamine oxidase (DAO) activity, endotoxin content, intestinal mucosal permeability (urine lactose/mannitol, L/M) and urine excretion of nitrogen increased obviously in both groups. The plasma glutamine concentration in Gln group increased by 38.04% after the administration of Gln for 7 days (P < 0.01). The plasma contents of pro-albumin, transferrin, and IL-2 were obviously higher than those in the C group (the increase rates were 21.19%, 51.11%, 57.54%, respectively, P < 0.01). The plasma DAO activity, L/M ratio, endotoxin content and urine nitrogen excretion in Gln group were evidently lower than those in C group (the decrease rates were 47.26%, 52.18, 22.22% and 27.78%, respectively, P < 0.05 or 0.01). There was no obvious difference in the plasma levels of total protein and albumin, the indices in blood and urine test, or the hepatic and renal functions between the two groups before and after the amino acid supplementation. Mild side effects such as nausea, diarrhea, constipation occurred in both groups, but all of them disappeared spontaneously afterwards (P > 0.05)., Conclusion: Oral administration of glutamine could be helpful to increase plasma concentration of glutamine and to ameliorate obviously the intestinal mucosal injury, to promote systemic protein synthesis and to inhibit protein catabolism and to upgrade systemic immune function with little side effect in patients with severe injury.

Aim: To study the effects of glutamine (Gln) on the change of intestinal permeability and its relationship to systemic inflammatory response in early abdominal postoperative patients., Methods: A prospective, randomized, double-blind and controlled trial was taken. Twenty patients undergoing abdominal surgery were randomized into Gln group (oral administration of glutamine, 30 g/d, for 7 d, n=10) and placebo group (oral administration of placebo, 30 g/d, for 7 d, n=10). Temperatures and heart rates of all patients were daily recorded. White blood cell counts(WBC) and biochemical variables were measured before operation and 4 and 7 d after drug administration. Serum concentrations of glutamine, endotoxin, diamine oxidase and malondialdehyde and urine lactulose/mannito (L/M) ratio were measured before and 7 d after drug administration., Results: The patients in the 2 groups were comparable prior to drug administration. Serum Gln concentration was significantly decreased in the placebo group and increased in the Gln group 7 d after drug administration. Urine L/M ratio was significantly increased in the placebo group and decreased in the Gln group. The serum concentration of endotoxin, diamine oxidase and malondialdehyde was significantly decreased in the Gln group compared with those in the placebo group. Temperatures, heart rates and WBC counts were significantly lower in the Gln group than those in the placebo group., Conclusion: Gut is one of the sources of systemic inflammatory response in abdominal postoperative patients and glutamine can decrease intestinal permeability, maintain intestinal barrier and attenuate systemic inflammatory response in early postoperative patients.

Objective: To evaluate the effect of glutamine granules on protein metabolism in severe burns and trauma patients., Methods: 120 patients with severe burns, multiple trauma and post operation who met the requirements of the protocol joined this double-blind randomized controlled, multi-center clinical trail. Patients were randomly divided into two groups: placebo control group (P group, 60 patients) and glutamine granules treatment group (GLN group, 60 patients). There was isonitrogenous and isocaloric intake in both groups, GLN and P group patents had been given glutamine granules or placebo (glycine) at 0.5 g.kg(-1).d(-1) for 7 days, respectively. The level of plasma glutamine, protein and urine nitrogen exclude were determined, wound healing rate of burn area and hospital stay were recorded, and then observed the complication and side effect., Results: After 7 days of taking glutamine granules orally, plasma GLN concentration was significant higher than that in P group (592.50 +/- 185.23 micro mol/L vs. 407.41 +/- 190.22 micro mol/L) (P < 0.01). Plasma prealbumin and transferrin in GLN group were significant higher than those in P group (P < 0.01), but the concentration of total protein and albumin were no marked changes compare with P group (P > 0.05). The capacity of urine nitrogen exclude in GLN group were significant lower than that in P group. Additional, the wound healing rate was faster and hospital stay days was shorter than P group (P < 0.05), and the occurrence of glutamine granules side effect was seldom., Conclusion: Taking glutamine could promote protein synthesis, abate protein decompose, ameliorate wound healing rate and reduce hospital stay obviously.

Objective: To explore the mechanism of hypoalbuminemia in patients with severe sepsis., Methods: I(125)-labeled albumin was administered intravenously to 10 health volunteers and 10 patients with severe sepsis. Blood samples were taken at 0, 1, 2, 4, 8, 12, 24 hours and 2, 3, 4, 5, 6, 7, 9, 11, 13, 15, 18, 22, 25 days for the measurement of the dose of gamma-radiation and the curve of concentration and time. Then the half-life time (t(1/2)), apparent volume of distribution (V(d)) and transportation rate (K(12)) from center compartment to side compartment of albumin were calculated., Results: The half-life time in septic group was obviously shorter than that in control group (8.2 +/- 1.4 vs. 12.5 +/- 1.7, P < 0.01). The transportation rate in the septic group was higher than that in the control group [(4.4 +/- 1.9) x 10(-2)/h vs. (2.4 +/- 0.6) x 10(-2)/h, P < 0.05]. There was no significant difference in apparent volume of distribution between the two groups., Conclusions: In patients with severe sepsis, the distribution rate of albumin from vessel to tissue was obviously increased and the decomposition rate of albumin was markedly improved.

Aim: To review the experience on the use of endoscopic nasopancreatic drainage (ENPD) in the treatment of severe acute pancreatitis (SAP)., Methods: Since March 1998, under the regular management of SAP with non-operative method, ENPD has been randomly used in 14 patients. The average age of the patients was 41.3+/-15.9 (years), with 8 males and 6 females. The time from onset to admission was 32.9+/-22.8 (hours). 8 cases were found to have gallbladder stone. The daily output of pancreatic fluid was measured. The body temperature, heart rate, WBC count, blood glucose, blood calcium, PaO(2), blood and urine levels of amylase were detected on the fifth day and compared with their respective data on the first day. Therapeutic results and hospitalization times were recorded., Results: The time of drainage was 7.3+/-4.0 days. The daily drainage outputs of the first five days were 236.4+/-176.6, 287.1+/-164.7, 284.6+/-216.4, 435.0+/-357.8 and 377.8+/-223.8 ml, respectively. The decreases in body temperature, heart rate, WBC counts, blood and urine levels of amylase and the increase in PaO(2) were significant on the fifth day when compared with those on the first day. Infection of pancreatic necrosis was found in one patient and controlled by anti-infectives. 6 out of 8 patients with gallbladder stone were operated during hospital stay. All patients were cured and discharged and the average hospital stay was 28.1+/-11.6 days., Conclusion: ENPD is an effective method for the drainage of pancreatic fluid and might have an important role in the treatment of SAP. Further observation, comparison and summary by this method are worthy to be considered.

Rabbits with MOF induced by intraabdominal sepsis were used to observe the effect of TPN with different amount of amino acid nitrogen on organ function, nitrogen balance and urine 3-MH excretion. The results showed that TPN support could improve the impaired organ function and reverse negative nitrogen balance. Low nitrogen burden was helpful to the lung, while high nitrogen appeared to be beneficial to the liver. Low nitrogen was more effective in increasing nitrogen balance and decreasing the urine 3-MH excretion. We conclude that excessive nitrogen burden results in significant thermic effect and an elevation of stress level, just as excessive glucose does.