The effect of the underlying malignancy on short- and medium-term survival of critically ill patients admitted to the intensive care unit: a retrospective analysis based on propensity score matching.

BACKGROUND: Advances in oncology led to a substantial increase in the number of patients requiring admission to the ICU. It is significant to confirm which cancer critical patients can benefit from the ICU care like noncancer patients. METHODS: An observational retrospective cohort study using intensive care unit (ICU) admissions of Medical Information Mart for Intensive Care III from the Beth Israel Deaconess Medical Center in Boston, MA, USA between 2001 and 2012 was conducted. Propensity score matching was used to reduce the imbalance between two matched cohorts. ICU patients with cancer were compared with those without cancer in terms of patients' characteristics and survival. RESULTS: There were 38,508 adult patients admitted to ICUs during the period. The median age was 65 years (IQR, 52-77) and 8308 (21.6%) had an underlying malignancy diagnosis. The noncancer group had a significant survive advantage at the point of 28-day, 90-day, 365-day and 1095-day after ICU admission compared with cancer group (P < 0.001 for all) after PSM. Subgroup analysis showed that the diagnosis of malignancy didn't decrease 28-day and 90-day survive when patients' age ≥ 65-year, patients in surgical intensive care unit or cardiac surgery recovery unit or traumatic surgical intensive care unit, elective admissions, patients with renal replacement therapy or vasopressor support (P > 0.05 for all). CONCLUSIONS: Malignancy is a common diagnosis among ICU patients. Patients without cancer have a survive advantage compared with patients with cancer in the short- and medium-term. However, in selected groups, cancer critical patients can benefit from the ICU care service like noncancer patients in the short-term.

A randomized controlled trial comparing the efficacy of tigecycline versus meropenem in the treatment of postoperative complicated intra-abdominal infections.

BACKGROUND: The efficacy and safety of tigecycline in the treatment of complicated intra-abdominal infections (cIAIs) is potentially controversial. Here we conducted the non-inferiority study to assess the efficacy and safety of tigecycline versus meropenem in the treatment of postoperative cIAIs. METHODS: Data of abdominal tumor surgery patients with postoperative cIAIs admitted to intensive care unit (ICU) between October 2017 and December 2019 were collected. A prospective, randomized controlled trial was conducted in which 56 eligible patients with cIAIs randomly received intravenous tigecycline or meropenem for 3 to 14 days. Patients and clinicians were not blinded to the group allocation. RESULTS: The total of 56 patients were enrolled, which were divided into 2 groups, one group included 30 patients receiving meropenem and another group included 26 receiving tigecycline therapy. The 2 groups were similar at demographic and baseline clinical characteristics. Microorganisms were isolated from 46 of 56 patients (82.14%), with a total of 107 pathogens were cultured in two groups. The two groups had similar distribution of infecting microorganisms. The primary end point was the clinical response at the end-oftherapy (EOT) visit and upon discharge visit and comprehensive efficacy. The clinical success rates were 83.33%, 76.67% for meropenem versus 76.92%, 88.46% for tigecycline at the EOT visit and upon discharge visit (P>0.05), respectively. Comprehensive efficacy did not significantly differ between two groups either. There were no significant differences in 30-day and 60-day all-cause mortality between two groups (P>0.05). The univariable analysis identified that serum albumin at admission ICU, colorectal cancer on oncology type, postoperative abdominal bleeding were the risk factors for 60-day all-cause mortality. The multivariable analysis showed that postoperative abdominal bleeding were independent predictors of 60-day all-cause mortality. Gastrointestinal disorders and antibacterials-induced Fungal Infection were the most frequently reported adverse events (AEs). The incidence of AEs was similar between meropenem and tigecycline groups (P>0.05). CONCLUSIONS: Taken together, the study demonstrated that tigecycline is as effective and safe as meropenem for postoperative cIAIs in abdominal tumors patients. Tigecycline is non-inferior to meropenem.

Neoadjuvant therapy does not adversely affect the short-term outcome of critically ill cancer patients who underwent surgery.

BACKGROUND: There were conflicting data regarding the effects of neoadjuvant therapy (NT) on the short-term outcomes of critically ill cancer patients. The aim of this study was to investigate whether NT adversely affect the short-term outcomes of critically ill cancer patients who underwent surgery. METHODS: This was a retrospective study which enrolled all critically ill cancer patients who admitted to intensive care unit (ICU) of Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College between September 2017 and September 2018. Patients were divided into two groups: NT group and no NT (nNT) group. The primary outcome was ICU mortality rate. Propensity score analysis and Logistic regression analysis were used to investigate risk factors of ICU death. RESULTS: Hundred and twenty-eight patients received NT and 737 patients did not. The ICU mortality was higher in NT group than that in nNT group (3.9% vs. 1.4%, P=0.041) before propensity score matching analysis. After matching, there were no significant difference in ICU mortality between NT group and nNT group. Univariable logistic analysis demonstrated that a history of coronary heart disease (P=0.008), NT (P=0.041), unplanned admission to ICU (P<0.001), simplified acute physiology score (SAPS) 3 on ICU admission (P<0.001), sequential organ failure assessment (SOFA) on ICU admission (P<0.001), acute kidney injury (P<0.001), and mechanical ventilation (P<0.001) were predictive of ICU death in all 865 patients. Multivariable logistic regression analysis demonstrated that history of coronary heart disease (P=0.010; OR =9.614; 95% CI, 1.731-53.405), SAPS 3 on ICU admission (P=0.026; OR =1.070; 95% CI, 1.008-1.135) and SOFA on ICU admission (P=0.031; OR =1.289; 95% CI, 1.024-1.622) were independent risk factors of ICU death, while NT was not predictive of ICU death (P=0.118). CONCLUSIONS: NT was not a risk factor for ICU death in critically ill cancer patients who underwent surgery.

The 28-day survive for critically ill cancer patients undergoing continuous renal replacement with postoperative acute kidney injure: a retrospective study of 86 cases.

BACKGROUND: Advances in oncology led to a substantial increase in the number of patients requiring admission to the intensive care unit (ICU). It remains controversial to start continuous renal replacement therapy (CRRT) for acute kidney injure (AKI) in critically ill patients with cancer because of the poor outcome and high costs. METHODS: In this retrospective study, we collected data from patients with cancer with postoperative AKI-stage 3 [Kidney Disease: Improving Global Outcomes (KDIGO), 2012] undergoing CRRT in the ICU of Cancer Hospital, Chinese Academy of Medical Sciences from January 2010 to January 2019. Patients were followed up until the time of death or the point of 28-day after ICU admission. Univariate and multivariate analysis was performed to identify risk factors for 28-day survive. RESULTS: Of 8,030 cancer patients after surgical operation admitted by ICU, a total of 86 (1.1%) patients developed postoperative AKI: male/female: 62/24, median age 61 [27-82] years. The number of digestive tract/lung/other types of cancer was 59, 10 and 17, respectively. The median Simplified Acute Physiology Score III (SAPS III) was 65 [49-109] and the median Sequential Organ Failure Assessment (SOFA) score was 6 [1-19]. There were 35 deaths eventually and all the deaths occur within 28 days after ICU admission. Twenty-eight-day survive rate was 57.1%±5.8%. In multivariate cox regression analysis, two risk factors independently affected 28-day survive: SAPS III score ≥65 [hazard ratio (HR): 3.451 (1.272-9.365), P=0.015], the presence of shock at the start of CRRT [HR: 10.262 (2.210-47.660), P=0.003]. The cancer status (P=0.076), cancer types (P>0.05 for both) and neoadjuvant therapy associated with cancer (P=0.949) showed no effects on 28-day survive. CONCLUSIONS: For cancer patients, postoperative AKI-stage 3 is a serious complication with a low 28-day survive rate. Patients with the presence shock at the start of CRRT or SAPS III ≥65 will have a poor 28-day survive. It should be emphasized that the cancer characteristics (status, types or treatment) don't affect 28-day survive.

Preventable readmission to intensive care unit in critically ill cancer patients.

BACKGROUND: Readmission to intensive care unit (ICU) after discharge to ward has been reported to be associated with increased hospital mortality and longer length of stay (LOS). The objective of this study was to investigate whether ICU readmission are preventable in critically ill cancer patients. METHODS: Data of patients who readmitted to intensive care unit (ICU) at National Cancer Center/Cancer Hospital of Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) between January 2013 and November 2016 were retrospectively collected and reviewed. RESULTS: A total of 39 patients were included in the final analysis, and the overall readmission rate between 2013 and 2016 was 1.32% (39/2,961). Of 39 patients, 32 (82.1%) patients were judged as unpreventable and 7 (17.9%) patients were preventable. There were no significant differences in duration of mechanical ventilation, ICU LOS, hospital LOS, ICU mortality and in-hospital mortality between patients who were unpreventable and preventable. For 24 early readmission patients, 7 (29.2%) patients were preventable and 17 (70.8%) patients were unpreventable. Patients who were late readmission were all unpreventable. There was a trend that patients who were preventable had longer 1-year survival compared with patients who were unpreventable (100% vs. 66.8%, log rank=1.668, P=0.196). CONCLUSION: Most readmission patients were unpreventable, and all preventable readmissions occurred in early period after discharge to ward. There were no significant differences in short term outcomes and 1-year survival in critically ill cancer patients whose readmissions were preventable or not.

Respiratory and Cardiac Characteristics of ICU Patients Aged 90 Years and Older: A Report of 12 Cases.

Objective To investigate the respiratory and cardiac characteristics of elderly Intensive Care Unit (ICU) patients.Methods Twelve senior ICU patients aged 90 years and older were enrolled in this study. We retrospectively collected all patients' clinical data through medical record review. The basic demographics, primary cause for admission, the condition of respiratory and circulatory support, as well as prognosis were recorded. Shock patients and pneumonia patients were specifically analyzed in terms of clinical manifestations, laboratory variables, echocardiography, and lung ultrasound Results.Results The mean age of the included patients was 95 years with a male predominance (8 to 4, 66.7%). Regarding the reasons for admission, 6 (50.0%) patients had respiratory failure, 1 (8.3%) patient had shock, while 5 (41.7%) patients had both respiratory failure and shock. Of the 6 patients who suffered from shock, only 1 was diagnosed with distributive shock, 5 with cardiogenic shock. Of the 5 cardiogenic shock patients, 1 was diagnosed with acute coronary syndrome. The rest 4 cardiogenic shock patients were diagnosed with Takotsubo cardiomyopathy. The patient with ST-segment elevation myocardial infarction died within 24 hours. Of the 4 Takotsubo patients, 1 died on day-6 and the other 3 patients were transferred to ward after heart function recovered in 1 to 2 weeks. Of the 10 pneumonia patients, 3 were diagnosed as community acquired pneumonia, and 7 as hospital acquired pneumonia. Only 3 patients were successfully weaned from ventilator. The others required long-term ventilation complicated with heart failure, mostly with diastolic heart failure. Lung ultrasound of 6 patients with diastolic dysfunction showed bilateral B-lines during spontaneous breathing trial.Conclusions Elderly patients in shock tend to develop Takotsubo cardiomyopathy. Diastolic heart dysfunction might be a major contributor to difficult weaning from ventilator in elderly patients. Bedside lung ultrasonography and echocardiography could help decide the actual cause of respiratory failure and shock more accurately and effectively.

The value of esophagectomy surgical apgar score (eSAS) in predicting the risk of major morbidity after open esophagectomy.

BACKGROUND: Recently, surgical apgar score (SAS) has been reported to be strongly associated with major morbidity after major abdominal surgery. The aim of this study was to assess the value of esophagectomy SAS (eSAS) in predicting the risk of major morbidity after open esophagectomy in a high volume cancer center. METHODS: The data of all patients who admitted to intensive care unit (ICU) after open esophagectomy at Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from September 2008 through August 2010 was retrospectively collected and reviewed. Preoperative and perioperative variables were recorded and compared. The eSAS was calculated as the sum of the points of EBL, lowest MAP and lowest HR for each patient. Patients were divided into high-risk (below the cutoff) and low-risk (above the cutoff) eSAS groups according to the cutoff score with optimal accuracy of eSAS for major morbidity. Univariable and multivariable regression analysis were used to define risk factors of the occurrence of major morbidity. RESULTS: Of 189 patients, 110 patients developed major morbidities (58.2%) and 30-day operative mortality was 5.8% (11/189). There were 156 high risk patients (eSAS ≤7) and 33 low risk (eSAS >7) patients. Univariable analysis demonstrated that forced expiratory volume in one second of predicted (FEV1%) ≤78% (44% vs. 61%, P=0.024), McKeown approach (22.7% vs. 7.6%, P=0.011), duration of operation longer than 230 minutes, intraoperative estimated blood loss (347±263 vs. 500±510 mL, P=0.015) and eSAS ≤7 (62.2% vs. 90.0%, P=0.001) were predictive of major morbidity. Multivariable analysis demonstrated that FEV1% ≤78% (OR, 2.493; 95% CI, 1.279-4.858, P=0.007) and eSAS ≤7 (OR, 2.810; 95% CI, 1.105-7.144; P=0.030) were independent predictors of major morbidity after esophagectomy. Compared with patients who had eSAS >7, patients who had eSAS ≤7 had longer hospital length of stay (25.39±14.36 vs. 32.22±22.66 days, P=0.030). However, there were no significant differences in ICU length of stay, duration of mechanical ventilation, ICU death, 30-day death rate and in-hospital death rate between high risk and low risk patients. CONCLUSIONS: The eSAS score is predictive of major morbidity, and lower eSAS is associated with longer hospital length of stay in esophageal cancer patients after open esophagectomy.

Assessment of a predictive score for pulmonary complications in cancer patients after esophagectomy.

BACKGROUND: Esophagectomy is a very important method for the treatment of resectable esophageal cancer, which carries a high rate of morbidity and mortality. This study was undertaken to assess the predictive score proposed by Ferguson et al for pulmonary complications after esophagectomy for patients with cancer. METHODS: The data of patients who admitted to the intensive care unit after transthoracic esophagectomy at Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College between September 2008 and October 2010 were retrospectively reviewed. RESULTS: Two hundred and seventeen patients were analyzed and 129 (59.4%) of them had postoperative pulmonary complications. Risk scores varied from 0 to 12 in all patients. The risk scores of patients with postoperative pulmonary complications were higher than those of patients without postoperative pulmonary complications (7.27±2.50 vs. 6.82±2.67; P=0.203). There was no significant difference in the incidence of postoperative pulmonary complications as well as in the increase of risk scores (χ (2)=5.477, P=0.242). The area under the curve of predictive score was 0.539±0.040 (95%CI 0.461 to 0.618; P=0.324) in predicting the risk of pulmonary complications in patients after esophagectomy. CONCLUSION: In this study, the predictive power of the risk score proposed by Ferguson et al was poor in discriminating whether there were postoperative pulmonary complications after esophagectomy for cancer patients.

Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-ß-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro.

BACKGROUND: Our earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats. Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells. This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma. METHODS: In the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-ß-estradiol (E2)-treated male rats. In the in vitro study, prolactinoma cells mitochondria were harvested. Activities of the four mitochondrial respiratory complexes were assayed using fluorometer. ATP production of prolactinoma cells was estimated using bioluminescent methods. RESULTS: Elevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells. Moreover, in both in vivo and in vitro studies, melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells. CONCLUSIONS: There is a link between mitochondrial function increase and tumorigenesis. Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

Risk factors and prognosis of critically ill cancer patients with postoperative acute respiratory insufficiency.

BACKGROUND: This study aimed to investigate the risk factors and outcome of critically ill cancer patients with postoperative acute respiratory insufficiency. METHODS: The data of 190 critically ill cancer patients with postoperative acute respiratory insufficiency were retrospectively reviewed. The data of 321 patients with no acute respiratory insufficiency as controls were also collected. Clinical variables of the first 24 hours after admission to intensive care unit were collected, including age, sex, comorbid disease, type of surgery, admission type, presence of shock, presence of acute kidney injury, presence of acute lung injury/acute respiratory distress syndrome, acute physiologic and chronic health evaluation (APACHE II) score, sepsis-related organ failure assessment (SOFA), and PaO2/FiO2 ratio. Duration of mechanical ventilation, length of intensive care unit stay, intensive care unit death, length of hospitalization, hospital death and one-year survival were calculated. RESULTS: The incidence of acute respiratory insufficiency was 37.2% (190/321). Multivariate logistic analysis showed a history of chronic obstructive pulmonary diseases (P=0.001), surgery-related infection (P=0.004), hypo-volemic shock (P<0.001), and emergency surgery (P=0.018), were independent risk factors of postoperative acute respiratory insufficiency. Compared with the patients without acute respiratory insufficiency, the patients with acute respiratory insufficiency had a prolonged length of intensive care unit stay (P<0.001), a prolonged length of hospitalization (P=0.006), increased intensive care unit mortality (P=0.001), and hospital mortality (P<0.001). Septic shock was shown to be the only independent prognostic factor of intensive care unit death for the patients with acute respiratory insufficiency (P=0.029, RR: 8.522, 95%CI: 1.243-58.437, B=2.143, SE=0.982, Wald=4.758). Compared with the patients without acute respiratory insufficiency, those with acute respiratory insufficiency had a shortened one-year survival rate (78.7% vs. 97.1%, P<0.001). CONCLUSION: A history of chronic obstructive pulmonary diseases, surgery-related infection, hypovolemic shock and emergency surgery were risk factors of critically ill cancer patients with postoperative acute respiratory insufficiency. Septic shock was the only independent prognostic factor of intensive care unit death in patients with acute respiratory insufficiency. Compared with patients without acute respiratory insufficiency, those with acute respiratory insufficiency had adverse short-term outcome and a decreased one-year survival rate.

Prognosis of patients with shock receiving vasopressors.

BACKGROUND: Consensus guidelines suggested that both dopamine and norepinephrine may be used, but specific doses are not recommended. The aim of this study is to determine the predictive role of vasopressors in patients with shock in intensive care unit. METHODS: One hundred and twenty-two patients, who had received vasopressors for 1 hour or more in intensive care unit (ICU) between October 2008 and October 2011, were included. There were 85 men and 37 women, with a median age of 65 years (55-73 years). Their clinical data were retrospectively collected and analyzed. RESULTS: The median simplified acute physiological score 3 (SAPS 3) was 50 (42-55). Multivariate analysis showed that septic shock (P=0.018, relative risk: 4.094; 95% confidential interval: 1.274-13.156), SAPS 3 score at ICU admission (P=0.028, relative risk: 1.079; 95% confidential interval: 1.008-1.155), and norepinephrine administration (P<0.001, relative risk: 9.353; 95% confidential interval: 2.667-32.807) were independent predictors of ICU death. Receiver operating characteristic curve analysis demonstrated that administration of norepinephrine ≥0.7 µg/kg per minute resulted in a sensitivity of 75.9% and a specificity of 90.3% for the likelihood of ICU death. In patients who received norepinephrine ≥0.7 µg/kg per minute there was more ICU death (71.4% vs. 44.8%) and in-hospital death (76.2% vs. 48.3%) than in those who received norepinephrine <0.7 µg/kg per minute. These patients had also a decreased 510-day survival rate compared with those who received norepinephrine <0.7 µg/kg per minute (19.2% vs. 64.2%). CONCLUSION: Septic shock, SAPS 3 score at ICU admission, and norepinephrine administration were independent predictors of ICU death for patients with shock. Patients who received norepinephrine ≥0.7 µg/kg per minute had an increased ICU mortality, an increased in-hospital mortality, and a decreased 510-day survival rate.

Two acute kidney injury risk scores for critically ill cancer patients undergoing non-cardiac surgery.

BACKGROUND: Several risk scoures have been used in predicting acute kidney injury (AKI) of patients undergoing general or specific operations such as cardiac surgery. This study aimed to evaluate the use of two AKI risk scores in patients who underwent non-cardiac surgery but required intensive care. METHODS: The clinical data of patients who had been admitted to ICU during the first 24 hours of ICU stay between September 2009 and August 2010 at the Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively collected and analyzed. AKI was diagnosed based on the acute kidney injury network (AKIN) criteria. Two AKI risk scores were calculated: Kheterpal and Abelha factors. RESULTS: The incidence of AKI was 10.3%. Patients who developed AKI had a increased ICU mortality of 10.9% vs. 1.0% and an in-hospital mortality of 13.0 vs. 1.5%, compared with those without AKI. There was a significant difference between the classification of Kheterpal's AKI risk scores and the occurrence of AKI (P<0.001). There was no significant difference between the number of Abelha's AKI risk scores and the occurrence of AKI (P=0.499). Receiver operating characteristic curves demonstrated an area under the curve of 0.655±0.043 (P=0.001, 95% confidence interval: 0.571-0.739) for Kheterpal's AKI risk score and 0.507±0.044 (P=0.879, 95% confidence interval: 0.422-0.592) for Abelha's AKI risk score. CONCLUSION: Kheterpal's AKI risk scores are more accurate than Abelha's AKI risk scores in predicting the occurrence of AKI in patients undergoing non-cardiac surgery with moderate predictive capability.

G1 cell cycle arrest signaling in hepatic injury after intraperitoneal sepsis in rats.

OBJECTIVE AND DESIGN: Hepatocytes emerge from a quiescent state into a proliferative state to recover from septic injury. We hypothesize that hepatocyte cell cycle regulation after sepsis potentially contributes to the recovery of liver function. METHODS: An animal model of sepsis was induced by cecal ligation and puncture (CLP) in rats. At serial time points after CLP, hepatocyte expression of p21, P53, cyclin D1, cyclin E, CDK2, CDK4 and PCNA was determined by immunoblot analysis, and the DNA content of isolated hepatocytes was analyzed using flow cytometry. RESULTS: Sepsis-induced liver injury of rats was associated with G1 cell cycle arrest. Recovery of liver function was related to cell cycle progression 48 h after CLP. The upregulation of p53 and p21 correlated with G1 cell arrest 48 h after CLP. The upregulation of cyclin D1/CDK4 and cyclin E/CDK2 also correlated with the G1/S transition 48 h after CLP, resulting in PCNA expression. CONCLUSIONS: The data suggests that G1 cell cycle arrest and p53, p21, CDKs, cyclins and PCNA expression may be involved in the injury/recovery of liver function after intraperitoneal sepsis.

[Clinical effect of lower tidal volume combine with lung recruitment maneuver on ARDS for post operative esophageal carcinoma surgery patients].

OBJECTIVE: To study clinical effectiveness and possible side effects of lower tidal volume combine with lung recruitment on acute respiratory distress syndrome (ARDS) for post operative esophageal carcinoma surgery patients. METHODS: Twenty six hypoxemie post operative esophageal carcinoma surgery patients from Cancer Hospital and Peking Union Medical College Hospital were included from 1st January 2007 to 30th September 2009. There were 20 male and 6 female with an average age of 65.5 years (51 - 76 years). Circulation was stable among them. They could not weaned from mechanical ventilation due to ARDS. Bedside monitoring included noninvasive continuous artery blood pressure (NBP), pulse oximetry saturation (SPO2). Patients were ventilated on volume control mode. Tidal volumes set to 6 ml/kg. Recruitment maneuvers were conducted by stepwise rising of positive end expiratory pressure (PEEP) level. PEEP, fraction of inspired oxygen (FiO2), static compliance of lung (CLS) and arterial blood gas analysis (ABG) before and at 30 min after each of twice applying recruitment maneuvers were measured. RESULTS: Fifty-two recruitments were completed on these 26 cases. PaO2/FiO2 improved significantly in 26 cases. The level of FiO2 were significantly lowered, CLS were increased significantly 30 min after each of twice applying recruitment maneuvers in all 26 cases. No complication was encountered. All patients were discharged successfully. CONCLUSION: Hypoxemia of ARDS following esophageal carcinoma surgery can be improved by lower tidal volume combine with lung recruitment maneuver.

[The protective effect of the limb ischemia preconditioning on the hepatic injury related to NO/ET-1 system in rats].

OBJECTIVE: To study the relationship between the disturbance of nitric oxide/endothelin-I (NO/ET-1) and the hepatic injury following limb ischemia/reperfusion (I/R) in rats as well as the regulation of NO/ET-1 system by limb ischemia preconditioning (IPC). METHODS: Using limb ischemia/reperfusion injury model rats, animals were randomly divided into three groups (n = 6): control group, I/R group and IPC group. The contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the plasma as well as nitric oxide (NO), endothelin-1 (ET-1), nitric oxide/endothelin-1 (NO/ET-1) in the plasma and the liver were measured. The levels of total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS), constitutive nitric oxide synthase (cNOS) in the liver were determined. The expression of iNOS and endothelial NOS (eNOS) were detected by the immunohistochemical method. The morphologic changes stained with hematoxylineosin were observed under microscope. RESULTS: It was found that the levels of NO, ET-1 in the plasma and the liver tissue all increased after reperfusion, while the values of ALT, AST, NO/ET-1 decreased. Liver pathology revealed that after limb I/R there were edema, villous microvascular congestion, infiltration of polymorphonuclear neutrophil (PMN), cell degeneration in part cells of the liver. The hepatic damage was deteriorated. While the expression of iNOS elevated, cNOS (mainly eNOS) reduced and total NOS increased. The protection of the limb IPC attenuated the disturbance of NO/ET-1. CONCLUSION: The hepatic injury following limb I/R is related to the disturbance of NO/ ET-1. The protection of the limb IPC might be conducted by its regulation of NO/ET-1 system. The elevation of endothelial NOS and the reduction of non-endothelial NOS generated the NO in this situation.

Acute renal failure during sepsis: potential role of cell cycle regulation.

OBJECTIVES: This study aimed to evaluate cell cycle regulation in acute kidney injury after intraperitoneal sepsis in rats. METHODS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in rats. At 0, 6, 12, 24, 48, and 72 h after CLP, serum creatinine was evaluated. DNA content of isolated kidney cells was analyzed using flow cytometer. Furthermore, the expression of p21, p53, cyclin D1, cyclin E, CDK2, CDK4 and P-pRb was also measured by western blot. RESULTS: After sepsis-induced by CLP, kidney injury of rat was associated with G1 cell cycle arrest, however, recovery of renal function related to cell cycle progression 48h after CLP. Results also showed that the upregulation of p53 and p21 was correlated with G1 cell arrest in 48h after CLP. Nevertheless, upregulation of cyclin D1/CDK4 and cyclin E/CDK2 induced pRb phosphorylation, which resulted in the G1/S transition 48 h after CLP. CONCLUSION: The data suggest that G1 cell cycle arrest may play a role in the initiation of kidney injury, whereas, through regulating cell cycle, p53, p21, CDKs, cyclins and P-pRb may be involved in the injury or recovery of renal function after intraperitoneal sepsis.

Antiproliferative effects of melatonin on the growth of rat pituitary prolactin-secreting tumor cells in vitro.

Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the growth of pituitary prolactin-secreting tumor cells. Primary cultured prolactinoma cells from E(2)-induced rat pituitary prolactin-secreting tumor were treated with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days. Apoptosis was evaluated using flow cytometry and the TdT-mediated dUTP nick-end labeling (TUNEL) method. In addition, cell viability was analyzed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that incubation of prolactinoma cells with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days inhibited cell growth and increased cell apoptosis. Furthermore, melatonin increased caspase-3 activity, Bax mRNA expression, and cytochrome c protein expression. Conversely, Bcl-2 mRNA expression and mitochondrial membrane potential were inhibited by melatonin treatment. Our results further suggest that melatonin inhibits tumor growth by inducing apoptosis of rat pituitary prolactin-secreting tumor directly via the damage of mitochondria.

Inhibitory effects of melatonin on the growth of pituitary prolactin-secreting tumor in rats.

The in vivo effects of melatonin on proliferation and apoptosis of 17-beta-estradiol (E2)-induced pituitary prolactin-secreting tumor (prolactinoma) were investigated in rats kept in 12 L/12 D (lights on: 06:00-18:00 hr). As melatonin was shown to induce apoptosis of breast and liver tumor cells, we examined whether melatonin would induce apoptosis of rat pituitary prolactinoma cells. 0.125, 0.25, 0.50 or 1.0 mg melatonin/day/rat was administrated subcutaneously at 17:30-18:00 hr. The weight of prolactinomas was measured. Apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method. It was found that treatment with 0.25 and 0.50 mg melatonin for 97 days inhibited prolactinoma cell proliferation and increased prolactinoma cell apoptosis. Furthermore, melatonin induced mRNA expression of Bax and cytochrome c protein expression. Conversely, mRNA expression of Bcl-2, and mitochondrial membrane potential were inhibited by melatonin treatment. These results suggest that melatonin inhibits the proliferation and induces apoptosis of rat pituitary prolactin-secreting tumor via perturbation of mitochondria physiology.

[Analysis of different mutations in regulatory sequence of prolactin gene during the formation of 17 beta-estradiol-induced prolactinoma in eutopic and ectopic pituitary of rats].

OBJECTIVE: To analyze different mutations in regulatory sequence of prolactin (PRL) gene during the formation of 17 beta-estradiol (E2 ) -induced prolactinoma in eutopic and ectopic pituitary of rats. METHODS: Male Sprague-Dawley rats transplanted with an isologaus pituitary under renal capsule were treated with subcutaneous implantation of an empty or E2-laden silastic capsule. Reverse transcription-polymerase chain reaction was employed to evaluate the expression of PRL mRNA in pituitary glands, and DNA sequencing was used to analyze the mutation in regulatory sequence of PRL gene. RESULTS: After treated with E2 for 120 days, both the eutopic and ectopic pituitaries were three times more heavier than those from control group (P < 0. 01) , and the body weight of rats was decreased to 42. 90% of the control group (P < 0 01 ). The PRL mRNA expressions in glands from the eutopic and ectopic pituitaries 120 days after treated with E2 were much more than those in untreated pituitary glands (P <0. 01). DNA sequencing showed seven mutations in the regulatory sequence of PRL gene in the eutopic pituitaries 120 days after treated with E2 , while the mutation in the ectopic pituitaries was decreased. CONCLUSIONS: Prolactinomas can be induced by chronic treatment with E2 in both the eutopic and the ectopic pituitaries transplanted under renal capsule distant from the hypothalamus. Different mechanisms exist in the formation of eutopic and ectopic prolactinomas.

[Expression NOS in acute lung injury following limb ischemia/reperfusion and its significance in rats].

AIM: To investigate the expression and role of inducible NOS (iNOS) and endothelial NOS (eNOS) in acute lung injury following limb ischemia/reperfusion (4h/4h). METHODS: Wistar rats were randomized into four groups: control group, ischemia/reperfusion (I/R) group, L-Arginine (L-Arg) pretreatment group, Aminoguanidine (AG) pretreatment group. The lung tissue of each group was subjected to assay of content of MDA, MPO, W/D and NO2-/NO3-. The expression of iNOS and eNOS was examined with immunohistological staining. The pulmonary morphologic changes were observed under microscope respectively. RESULTS: The acute lung injury existed after limb ischemia/reperfusion. The eNOS downregulation and iNOS upregulation among I/R, L-Arg and AG groups were observed contrasted to the control group. There was no expressional and statistical difference of iNOS between I/R group and L-Arg group. The expression of eNOS was similar between IR and AG but iNOS expression was downregulated in AG. The parameters of MDA, MPO, W/D and NO2-/NO3- in pulmonary tissue were significantly increased in I/R groups compared with those of the control group. The parameters of L-Arg and AG pretreatment groups in comparison with those of the I/R group showed significantly difference. Based on the results of pulmonary pathology, the congestion and infiltration of inflammatory cells existed obviously in IR group. L-Arg played definite role in militating lung injury and AG might make lung injury aggravated. CONCLUSION: The NO definite production from iNOS is possible to play a competitivly protective role in acute lung injury following limb ischemia/reperfusion and antagonist of iNOS may aggravate the lung injury.