Preventable readmission to intensive care unit in critically ill cancer patients / 世界急诊医学杂志（英文）

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 critical y il 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.

Assessment of a predictive score for pulmonary complications in cancer patients after esophagectomy / 世界急诊医学杂志（英文）

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 (χ2=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.

Respiratory and Cardiac Characteristics of ICU Patients Aged 90 Years and Older: A Report of 12 Cases / 中国医学科学杂志(英文版)

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.

Prognosis of patients with shock receiving vasopressors / 世界急诊医学杂志（英文）

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% confi dential 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 specifi city 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.

Risk factors and prognosis of critically ill cancer patients with postoperative acute respiratory insuffi ciency / 世界急诊医学杂志（英文）

BACKGROUND: This study aimed to investigate the risk factors and outcome of critically ill cancer patients with postoperative acute respiratory insuffi ciency.METHODS: The data of 190 critically ill cancer patients with postoperative acute respiratory insuffi ciency were retrospectively reviewed. The data of 321 patients with no acute respiratory insuffi ciency as controls were also colected. Clinical variables of the fi rst 24 hours after admission to intensive care unit were colected, 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 insuffi ciency, the patients with acute respiratory insuffi ciency 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 insuffi ciency 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 insuffi ciency. 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.

Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-β-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>In the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-β-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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Two acute kidney injury risk scores for critically ill cancer patients undergoing non-cardiac surgery / 世界急诊医学杂志（英文）

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.

The protective effect of the limb ischemia preconditioning on the hepatic injury related to NO/ET-1 system in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Clinical effect of lower tidal volume combine with lung recruitment maneuver on ARDS for post operative esophageal carcinoma surgery patients / 中华外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Hypoxemia of ARDS following esophageal carcinoma surgery can be improved by lower tidal volume combine with lung recruitment maneuver.</p>

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 / 中国医学科学院学报

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Expression NOS in acute lung injury following limb ischemia/reperfusion and its significance in rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the expression and role of inducible NOS (iNOS) and endothelial NOS (eNOS) in acute lung injury following limb ischemia/reperfusion (4h/4h).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

The protect effect of ischemic preconditioning on the gastric mucosal injury following ischemia/reperfusion of hind limbs of rats / 中国应用生理学杂志

<p><b>AIM</b>To observe the degree of gastric mucosal injury following limb ischemia/reperfusion (LI/R), and to investigate the mechanism of gastric mucosal injury and the protection of ischemic preconditioning (IPC) on gastric mucosal injury.</p><p><b>METHODS</b>The model rats which underwent 4 hours of ischemia and 4 hours of reperfusion of hind limbs were made. Then we respectively observed and determined the histologic lesion score after I/R and IPC + I/R. The gastric barrier mucus in mucus were measured in different groups. The values of MPO, SOD, MDA and XOD in gastric mucosa and the values of MDA, XOD, SOD, LDH in plasma were detected.</p><p><b>RESULTS</b>In the LI/R group, the histologic lesion score increased significantly. The content of gastric barrier mucus in mucus decreased significantly. The value of MPO, MDA, XOD in gastric mucosa and the values of MDA, XOD, LDH in plasma increased remarkably and SOD activity in gastric mucosa and in plasma decreased. However in the IPC group, the histologic lesion score decreased significantly and the content of gastric barrier mucus in mucus increased significantly and the value of MPO MDA XOD LDH in gastric mucosa or in plasma decreased remarkably and the SOD activity increased compared to LI/R group.</p><p><b>CONCLUSION</b>LI/R will lead to the development of stress ulcer, oxygen free radicals play an important role in it. IPC can alleviate the damage of gastric mucosa following ischemia/reperfusion of hind limbs. The decrease of OFR is one of the protection mechanism of IPC.</p>

Melatonin suppressing the proliferation of E2-induced pituitary prolactin-secreting tumor in rat involves the effects of estrogen receptor / 中国应用生理学杂志

<p><b>AIM</b>To investigate effects of melatonin on estrogen receptor at the primary stage of melatonin (MLT) inhibiting the proliferation of 17-beta-estradiol (E2)-induced pituitary prolactin-secreting tumor (prolactinoma) and its mechanisms in the rat.</p><p><b>METHODS</b>MLT inhibiting the proliferation of 17-beta-E2-induced prolactinoma was created by administrating different concentration of melatonin subcutaneously at 18:00 in every group of SD rat in vivo. We also examined the expression of MLT receptor in prolactinoma cells and the effects of MLT on the expression of estrogen receptor (ER) by in situ hybridization and the effects of MLT on the binding of ER to estrogen response element (ERE) by electrophoretic mobility shift assay (EMSA)in primary culture cells iv vitro.</p><p><b>RESULTS</b>The results showed that the weights of prolactinomas in MLT groups, in which 0.25 mg or 0.50 mg/day/rat melatonin was administrated subcutaneously at 18:00, were decreased significantly (P < 0.01 and P < 0.05). The expression of MLT1a and MLT1b were shown in pituitary prolactinoma cells. Compared with the prolactinoma, the expression of ER and the bind of ER to ERE in prolactinoma treated with 0.25 mg/day/rat or 0.50 mg/day/rat MLT was decreased (P < 0.01 and P < 0.01).</p><p><b>CONCLUSION</b>These data indicate that some dosage of MLT inhibit the development of E2-induced prolactinoma in SD rat. One of the mechanisms is involved in suppressing the expression of estrogen receptor and partly inhibiting the bind of ER to ERE.</p>

The effect of NO, ET-1 on brain injury after hind limbs ischemia/reperfusion in rats / 中国应用生理学杂志

<p><b>AIM</b>To study the roles of nitric oxide (NO) and ET-1 in brain injury after hind limbs ischemia/reperfusion in rats and to investigate the effect of NO/ ET-1 balance on brain injury.</p><p><b>METHODS</b>On a model of the hind limbs ischemia/reperfusion (LI/R) of rats, we used L-Arg(L-arginine, L-Arg), one of the substrates in the process of nitric oxide, aminoguanidine (AG) which inhibits nitric oxide synthase(NOS) and ETA receptor antagonist BQ123, to observe the changes of NO, ET-1, MDA, XOD, SOD, LDH in plasma and tNOS, iNOS, cNOS, NO, ET-1, MDA, XOD, MPO, SOD in brain tissue.</p><p><b>RESULTS</b>Compared with the control group, the content of MDA, XOD, LDH in plasma and MDA, XOD, MPO in brain tissue increased. The activity of SOD decreased (P < 0.01). The content of tNOS, iNOS in brain tissue increased, cNOS decreased (P < 0.01). The content of NO, ET-1 in I/R group in plasma and brain tissue increased, the ratio of NO/ET-1 decreased. The brain injury was deteriorated. After using L-Arg and BQ123, the ratio of NO/ET-1 in plasma and brain tissue increased, the brain injury lightened. Whereas after using AG, the ratio of NO/ET-1 decreased, brain injury became more serious.</p><p><b>CONCLUSION</b>The NO/ET-1 ratio decreased after LI/R, brain injury became more serious.</p>

Melatonin inhibits the proliferation of pituitary prolactin-secreting tumor by suppressing the enhancer elements mutation of PRL gene in the rat / 生理学报

In order to investigate the molecular mechanisms of the inhibition of the proliferation of 17-beta-estradiol (E(2))-induced pituitary prolactin-secreting tumor (prolactinoma) by melatonin (MLT) in the rat, we examined the inhibitory effects of MLT on the proliferation of E(2)-induced prolactinoma of the rat and the suppressing effects of MLT on the enhancer elements mutation of PRL gene in vivo and in vitro. The results showed that the weights of prolactinomas in MLT groups, in which 0.25 mg or 0.50 mg per day per rat of MLT was administered subcutaneously at 18:00, were decreased significantly. Out of the dosage of MLT, such as 0.05, 1.00 mg and 2.00 mg per day per rat, the antitumor action of MLT is less or disappointing. Polymerase chain reaction (PCR) and DNA sequencing showed five mutations in the enhancer elements of PRL gene in prolactinoma, such as -1885 point mutation (C --> G), -1857 - -1855 substitution (ACA --> G), -1792 - -1791 insertion G, -1383 - -1382 insertion (GGTGTGTG), -1265 - -1250 deletion (GTGTGTGTGTGTGTGT). Excluding of -1885 point mutation (C --> G), the mutation in the prolactinoma treated with 0.25 mg per day per rat MLT was decreased, such as -1792 - -1791 without insertion of G, -1856 - -1855 deletion AC, -1385 - -1384 deletion TG, -1250 - -1253 deletion GTGT. Firefly luciferase reporter gene systems showed that the luminosity of enhancer elements-luciferase reporter fusion gene in normal pituitary, prolactinoma treated without or with 0.25 mg per day per rat MLT were (13448.17+/-3012.74), (161831.67+/-60996.01), and (10212.17+/-634.71) OD units. Compared with the normal pituitary, the activity of PRL gene enhancer elements in prolactinoma was increased by 11 times (P<0.001). Compared with the prolactinoma, the activity of PRL gene enhancer elements in prolactinoma treated with MLT was decreased by 93.69% (P<0.001). Analysis of the space structure of PRL gene enhancer elements showed that the bending index in prolactinoma was higher than that in prolactinoma treated with MLT, which was higher than that in the normal pituitary. These results demonstrate that one of the important molecular mechanisms of MLT inhibiting the proliferation of prolactinoma is related to the reduction of enhancer elements mutation of PRL gene. These data also suggest that MLT-induced attenuation of enhancer elements mutation of PRL gene is involved in decreasing the bending index and attenuating the higher expression of PRL gene.