Dynamic changes of locus coeruleus damage in Parkinson's disease-like mice induced by paraquat / 中华劳动卫生职业病杂志

Objective: To observe the dynamic changes of brainstem locus coeruleus (LC) damage in Parkinson' s disease (PD) -like mice by paraquat (PQ) . Methods: In October 2019, 36 male C57BL/6 mice were randomly divided into the exposure group and the control group, with 18 mice in each group. The mice in the exposure group were given intraperitoneal injection of 15 mg/kg PQ, and the mice in the control group were given intraperitoneal injection of 0.9% saline, twice a week for 8 weeks. Neurobehavioral changes (pole climbing test, swimming test, open field test, tail hanging test, high plus maze test and water maze test) were observed at 4 weeks, 6 weeks and 8 weeks, respectively, and the changes of motor ability, emotion and cognitive function were evaluated. The brain tissue of mice were taken and stained with Hematoxylin-Eosin (HE) to observe the pathological changes of LC. Nissl staining was used to detect the changes of neuronal Nissl bodies in LC. Immunohistochemistry (IHC) staining was used to detect the expression of neuron nuclear antigen (NeuN) , dopamine (DA) neurons and norepinephrine (NE) neuron markers tyrosine hydroxylase (TH) , α-synuclein (α-syn) in substantia nigra (SN) and LC. The expression levels of NeuN, TH and α-syn in the midbrain and brainstem were detected by Western blotting. TUNEL staining was used to detect neuronal apoptosis in LC. Results: Compared with the 4th week of PQ exposure group, the time of pole climbing and swimming immobility were gradually increased, the ratio of open arm residence time of high plus maze test and the number of times of the platform and the residence time of platform quadrant in water maze test were gradually decreased (P<0.05) in the exposure group with the progress of exposure time. The results of HE and Nissl staining showed that the neurons in LC gradually arranged loosely, the nucleus were deeply stained, the cytoplasm was pyknosis, and the number of Nissl bodies gradually decreased (P<0.05) in the exposure group with the progress of exposure time. IHC results showed that the number of NeuN and TH positive cells in SN and LC of mice were gradually decreased, and the positive expression of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. Western blotting results showed that the expression levels of NeuN and TH in the midbrain and brainstem were gradually decreased, and the expression level of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. TUNEL staining showed that the apoptosis rates of neurons in LC were gradually increased (P<0.05) in the exposure group with the progress of exposure time. Conclusion: PQ induces progressive damage in the LC area of PD-like mice, which may be caused by the abnormal accumulation of pathological α-syn in the LC area.

Preliminary study on time-dependent changes of intestinal tract and brain-gut axis in mice model of Parkinson's disease induced by paraquat / 中华劳动卫生职业病杂志

Objective: To observe the intestinal time-dependent changes in Parkinson's disease (PD) mouse model constructed by intraperitoneal injection of paraquat (PQ) and to establish the brain-gut axis connection initially. Methods: In October 2019, 48 mice were randomly divided into treated group and control groups: treated 4-week (P-4) group, treated 6-week (P-6) group, treated 8-week (P-8) group, control 4-week (C-4) group, control 6-week (C-6) group, and control 8-week (C-8) group. The treated group was injected with 15 mg/kg PQ solution and the control group was injected with 0.9% saline (0.2 ml/20 g) by intraperitoneal injection twice a week. After the initial state (0 weeks) and the treatment at the end of 4, 6 and 8 weeks, the mood changes and motor functions of mice were assessed by neurobehavioral tests (open field test, pole climbing test, tail suspension test and elevated plus maze test) . And the number of fecal pellets for 1 h and water content were calculated to assess the functional status of the gastrointestinal tract. Western blotting experiments were performed to detect the expression levels of α-synuclein (α-syn) and tyrosine hydroxylase (TH) in the nigrostriatal region of the mouse brain, the tight junction markers zonula occludens-1 (ZO-1) and Occludin, the inflammatory markers of integrin αM subunit (CD11b) , inducible nitric oxide synthase (iNOS) , high mobility group box 1 (HMGB1) , interleukin-1β (IL-1β) , and the neuronal markers βⅢ-tubulin and α-syn protein in the colon.Immunohistochemical staining was performed to detect the expression levels of colonic tight junction proteins ZO-1 and Occludin. Immunofluorescence staining was performed to detect the expression levels of TH in the substantia nigra region of the midbrain, and the co-localization of colonic intestine neuronal marker (βⅢ-tubulin) and Ser129 α-syn in the colonic. Results: Compared with the initial state (0 weeks) and C-8 group, mice in the P-8 group had significantly higher pole climbing test scores and resting time, and significantly lower total active distance, mean active speed, percentage of open arm entry and 1 h fecal instances (P<0.05) . After poisoning, the 1 h fecal water content of model mice first increased and then decreased, the P-4 and P-6 groups were significantly higher than the simultaneous point control group, and the P-8 groups were significantly lower than the initial state (P<0.05) . Compared with control, P-4 and P-6 groups, the expression levels of ZO-1 and Occludin in the P-8 group were significantly decreased (P<0.05) . Compared with control group, the expression levels of CD11b and IL-1β in the P-4 group were significantly increased (P<0.05) . Compared with control and P-4 group, the expression levels of CD11b, iNOS, HMGB1 and IL-1β in the P-6 and P-8 groups were significantly increased (P<0.05) . Compared with the control and P-4 groups, the expression levels of βⅢ-tubulin in the colon of mice in the P-8 group were significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased (P<0.05) . The expression level of Ser129 α-syn in the colon of model mice was negatively correlated with the expression level of βⅢ-tubulin (r(s)=-0.9149, 95%CI: -0.9771--0.7085, P<0.001) . Ser129 α-syn and βⅢ-tubulin co-localization in the colonic intermuscular plexus region increased gradually with the time of exposure. Compared with the control, P-4 and P-6 groups, the expression level of TH in the nigrostriatal region of the brain was significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased in the P-8 group (P<0.05) . Correlation analysis showed that the relative expression level of Ser129 α-syn in the nigrostriatal region of the brain was negatively correlated with the expression level of TH in the model mice (r(s)=-0.9716, 95% CI: -0.9925--0.8953, P<0.001) . Conclusion: The PD mouse model is successfully established by PQ, and the intestinal function of the model mice is reduced in a time-dependent manner. And on this basis, it is preliminary determined that the abnormal aggregation of α-syn may be an important substance connecting the brain-gut axis.

Characteristics of abdominal hemorrhage in patients with severe acute pancreatitis and its influence on outcomes / 中华危重病急救医学

Objective:To explore the risk factors of abdominal hemorrhage (AH) in patients with severe acute pancreatitis (SAP) and its impact on outcome.Methods:The clinical data of 231 SAP patients admitted to Diagnosis and Treatment Center for SAP of Guizhou Province from January 1, 2015 to December 31, 2019 were retrospectively analyzed. These patients were divided into AH group and non-AH group. The general information, etiology, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, organ failure, complications, interventions, bleeding time, bleeding site and outcome were compared between the two groups. Binary multivariate Logistic regression analysis was used to explore the risk factors of AH in SAP patients and whether the time and location of AH were risk factors affecting the outcome.Results:A total of 231 patients were enrolled in the analysis, including 198 patients without AH and 33 with AH (14.3%). There was no significant difference in gender, age or etiology between the two groups. The scores of APACHE Ⅱ and SOFA in AH group were significantly higher than those in non-AH group [APACHE Ⅱ score: 18 (12, 24) vs. 13 (9, 19), SOFA score: 9 (5, 15) vs. 5 (4, 11), both P < 0.01]. The incidences of acute kidney injury (AKI), gastrointestinal dysfunction, coagulation disorders, necrotic infection, pseudocyst and gastrointestinal fistula in AH group were significantly higher than those in non-AH group (66.7% vs. 47.0%, 36.4% vs. 7.1%, 18.2% vs. 6.6%, 66.7% vs. 9.1%, 66.7% vs. 34.3%, 9.1% vs. 1.5%, all P < 0.05). The proportions of requiring mechanical ventilation (MV) and surgical intervention in AH group were significantly higher than those in non-AH group (69.7% vs. 43.4, 48.5% vs. 14.6%, both P < 0.01). The length of intensive care unit (ICU) stay and hospital stay in AH group were significantly longer than those in non-AH group [length of ICU stay (days): 13 (8, 19) vs. 7 (3, 16), length of hospital stay: 24 (13, 40) vs. 17 (12, 24), both P < 0.01], and the hospital mortality was significantly higher (60.6% vs. 9.6%, P < 0.01). Multivariate Logistic regression analysis showed that APACHE Ⅱ score [odds ratio ( OR) = 1.157, 95% confidence interval (95% CI) was 1.030-1.299, P = 0.014], infectious necrosis ( OR = 12.211, 95% CI was 4.063-36.697, P < 0.01), pseudocyst ( OR = 3.568, 95% CI was 1.238-10.283, P = 0.019) and requiring MV ( OR = 0.089, 95% CI was 1.354-6.625, P = 0.007) were the risk factors of AH in SAP patients. In 33 AH patients, there was no significant difference in hospital mortality between early hemorrhage (occurred within 2 weeks of onset) and late hemorrhage (occurred 2 weeks after onset) groups [66.7% (8/12) vs. 57.1% (12/21), P > 0.05]. All 4 patients in the unspecified bleeding site group died during hospitalization; half or more patients died in the pseudocyst/abscess bleeding (14 cases), mesenteric/intestinal bleeding (13 cases) and gastric variceal bleeding (2 cases) groups (7 cases, 8 cases and 1 case respectively), and there were significant differences among the groups ( P < 0.05). Multivariate Logistic regression analysis showed that neither bleeding time ( OR = 0.989, 95% CI was 0.951-1.028, P = 0.574) nor bleeding site ( OR = 2.009, 95% CI was 0.822-4.907, P = 0.126) was the risk factor of death in patients with SAP combined with AH. Conclusions:Both early and late bleeding significantly increased the length of hospital stay and mortality of SAP patients. APACHE Ⅱ score, infectious necrosis and pseudocyst were the risk factors of AH in SAP patients. Neither bleeding time nor bleeding site was the risk factors of death in patients with SAP combined with AH. However, it still needed to be confirmed by a large sample clinical study.

Clinical characteristics and treatment of patients with refractory spasm tetanus / 中华急诊医学杂志

Objective:To investigate the clinical characteristics and treatment of patients with refractory spasm tetanus.Methods:Tetanus patients admitted to the Affiliated Hospital of Zunyi Medical University from January 2011 to April 2021 were collected and divided into the refractory spasm group and general group according to whether they were refractory spasm. The general demographic characteristics, clinical characteristics, treatment and prognosis of the two groups were compared. The treatment and risk predictors of patients with refractory spasm tetanus were explored.Results:Among the 59 tetanus patients, 35 patients (59.32%) were in the refractory spasm group and 24 patients (40.68%) were in the general group. There were no significant differences in sex, age, latency and trauma site between the two groups ( P>0.05). All patients with refractory spasmodic tetanus were treated with mechanical ventilation, the length of hospital stay was significantly prolonged, and the rate of pulmonary infection was significantly increased ( P<0.05). The incidence of multiple sites muscular rigidity (spasm/limb stiffness, neck stiffness, and angular pedicle tension) in patients with refractory spasmodic on the first day of admission was higher than that in the general group ( P<0.05). The patients' initial symptoms (within 24 h after admission) were muscle spasm/limb stiffness + neck stiffness + angular pedicle inversion, which had the highest specificity for predicting the occurrence of refractory spasm. The proportion of Ablett grade Ⅳ in patients with refractory spasm was higher than that in the general group, and the difference was statistically significant ( P<0.05). The 48.75% patients with refractory spasm tetanus were treated with more than 3 sedatives combined with muscle relaxants, and the duration of sedative use was significantly prolonged ( P<0.05). Conclusions:The mechanical ventilation time and hospitalization time in tetanus patients with refractory spasm are significantly prolonged, and the incidence of pulmonary infection is significantly increased, which requires the combined application of a large number of sedative and muscle relaxants for a long time, and the incidence of refractory spasm is higher in patients with multi-site muscular rigidity at the early stage of the disease.

Superior effects of thoracic epidural block for analgesia in patients with severe acute pancreatitis / 中华麻醉学杂志

Objective:To evaluate the superior effect of thoracic epidural block (TEB) used for analgesia in patients with severe acute pancreatitis (SAP).Methods:Fifty patients of both sexes, aged 18-64 yr, with SAP, with Japanese severity score (JSS) ≥3, onset time of SAP≤12 h, were divided into conventional analgesia group (group C) and TEB group.Sufentanil was intravenously infused for analgesia in group C. TEB was performed for analgesia in group TEB.In group C, sufentanil was intravenously infused at a rate of 0.2-0.3 μg·kg -1·h -1 after admission to hospital.In group TEB, an epidural catheter was placed at T 9, 10 interspace, and 0.66% lidocaine mixed with 0.33% ropivacaine was epidurally infused at a rate of 3-5 ml/h for 120 h after admission to hospital.Visual analog scale (VAS) score and intra-abdominal pressure (IAP) were recorded at 1, 24, 48, 72 and 120 h of analgesia.HR, respiratory rate (RR), oxygenation index, computed tomography severity index (CTSI), JSS and Ranson scores were recorded at 24, 72 and 120 h of analgesia, and the de-criticalization within 72 h following analgesia was evaluated. Results:Compared with group C, VAS score and IAP were significantly deceased at each time point ( P<0.05), the rate of de-criticalization (60%/90%) was increased ( P<0.05), and Ranson score, CTSI score and JSS score were decreased at 120 h of analgesia in group TEB ( P<0.05). Conclusion:TEB can not only produce good analgesic effect, but also improve the development of the disease, which has superior effect compared with routine analgesia when used for the treatment of SAP.

Research progress of mitochondrial unfolded protein response in myocardial ischemia/reperfusion injury / 中华危重病急救医学

Mitochondrial unfolded protein response (UPR mt) is a protein-toxic stress response, which regulates the communication from mitochondria to the nucleus. It is activated when a large number of unfolded or misfolded proteins accumulate in the mitochondria. The activation of UPR mt increases the expression of a series of chaperones and proteases, and maintains the homeostasis and function of mitochondrial proteins. Mitochondria play an important role in maintaining cardiomyocyte homeostasis. The damage of myocardial mitochondria leads to the metabolic disorder of cells suffering from ischemia/reperfusion injury. It is the key mechanism of myocardial cell death. This article mainly reviews the regulatory pathway of UPR mt and the research progress of UPR mt in myocardial ischemia/reperfusion injury (MIRI), in order to provide new ideas for the treatment of MIRI.

Electronic cigarette use among adolescents in Ningxia Hui Autonomous Region / 预防医学

Objective@#To investigate the status of electronic cigarette use among adolescents in Ningxia Hui Autonomous Region, and to provide evidence for tobacco control in adolescents. @*Methods@# Based on the 2019 National Youth Tobacco Epidemic Monitoring Program, multistage proportional sampling method was used to select middle school students from Ningxia Hui Autonomous Region. A questionnaire revised by Chinese CDC was used to collect the general information, the cognition and use of electronic cigarettes, and the access to advertising of electronic cigarettes and related products.@*Results@#Totally 9 019 questionnaires were distributed, 8 401 valid ones were recovered, and the response rate was 93.2%. The rates of electronic cigarette use and attempt among students were 4.3% and 13.4%. The rates of electronic cigarette use and attempt in male students were 7.7% and 22.9%, which were higher than that in female students (0.8% and 3.8%, P<0.05) . The rates of electronic cigarette use and attempt varied in different schools ( P<0.05 ), which were higher in vocational high school students ( 11.5% and 26.8% ). Among 246 students who used electronic cigarettes, 30.1% did not thought electronic cigarettes contained nicotine, while 60.2% did not know whether electronic cigarettes contain nicotine. In the past 30 days, 27.0% of the students had seen the advertisements of electronic cigarettes and related products, mainly through TV, store, supermarket, convenience store, grocery store, electronic cigarette experience store or retail store.@*Conclusions@#The rates of electronic cigarette use and attempt among adolescents in Ningxia Hui Autonomous Region are 4.3% and 13.4%. Boys and vocational high school students have higher rates. Students generally know electronic cigarette and have more access to it.

Myocardial Substrate Metabolic Remodeling in Heart Failure / 中国实验方剂学杂志

Myocardial substrate metabolism is severely impaired after heart failure, and the selection and utilization of substrates, such as glucose and fatty acids, are remodeled, resulting in insufficient myocardial productivity, cardiac dysfunction and progressive left ventricular remodeling. It is believed traditionally that the heart changes from fatty acid metabolism to glucose metabolism during heart failure, which however is contradictory with some findings in recent years. No consistent conclusion can be drawn from studies on the changes of myocardial energy substrate metabolism and its regulatory mechanism after heart failure. Metabolic treatment for heart failure has developed slowly. Therefore, it is necessary to explore the reasons for heterogeneity of these conclusions for defining the metabolic patterns of heart failure substrates and developing metabolically targeted drugs. This review summarizes the metabolic patterns and regulatory mechanisms of normal myocardium under physiological conditions, focuses on the elaboration and comparison of myocardial substrates metabolic abnormalities in heart failure induced by ischemic heart disease, pressure load, volume load and dilated cardiomyopathy in such aspects as etiology, severity, duration of heart failure, species studied, animal models and metabolic detection methods, and makes a preliminary analysis on the consistency and differences of relevant conclusions in various studies, and discusses the future trend of metabolic treatment, with the aim to summarize the rules and molecular mechanism of glucose metabolism and fatty acid metabolism after heart failure and provide clues for the research of metabolic targeted therapy.

Effects of uncoupling protein 2 overexpression on myocardial mitochondrial dynamics in sepsis rats / 中华危重病急救医学

Objective@#To investigate the effects of uncoupling protein 2 (UCP2) overexpression on mitochondrial dynamics (mitochondrial division and fusion) of sepsis myocardial injury in rats.@*Methods@#Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group (Sham group) using normal saline instead of transfection and simulating cecal ligation and perforation (CLP); CLP group using normal saline instead of transfection, performing CLP to induce sepsis; adeno-associated virus (AAV) group using CLP after myocardial transfection with empty virus; UCP2 overexpression group (UCP2 group) CLP was performed 3 weeks after AAV-UCP2 (1×1015 vg/L, a total of 60 μL) myocardial transfection. The rats in each group were examined by echocardiography at 24 hours after the CLP, and then the rats were sacrificed immediately to harvest myocardial tissue. Myocardial ultrastructural changes were observed under the electron microscope, the expression of regulatory proteins related to myocardial mitochondrial dynamics [optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1) and fission 1 (Fis1)] were detected by Western Blot, and the level of mitochondrial adenosine triphosphate (ATP) production was detected by chemiluminescence.@*Results@#①The echocardiographic results showed that there was no significant difference in left ventricular mass (LVM) and stroke volume (SV). Compared with Sham group, left ventricular diastolic anterior wall thickness (LVAWd), left ventricular systolic anterior wall thickness (LVAWs), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular systolic posterior wall thickness (LVPWs), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (LVFS) were significantly increased in CLP group and AAV group, while left ventricular systolic diameter (LVEDs), left ventricular diastolic diameter (LVEDd), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were significantly decreased. Compared with CLP group and AAV group, LVAWs, LVEF, LVFS were significantly decreased in UCP2 group, and LVEDs, LVEDV and LVESV were significantly increased [LVAWs (mm): 3.82±0.42 vs. 4.34±0.30, 4.44±0.12; LVEF: 0.921±0.038 vs. 0.979±0.019, 0.991±0.010; LVFS: (65.33±6.56)% vs. (80.11±8.23)%, (85.31±6.11)%; LVEDs (mm): 1.81±0.36 vs. 0.89±0.54, 0.60±0.17; LVEDV (μL): 137.09±50.05 vs. 89.72±53.04, 85.42±40.99; LVESV (μL): 10.48±4.59 vs. 2.48±3.52, 2.58±2.50, all P < 0.05]. ② Electron microscope showed that the structure of myocardial fibers in the Sham group was clear and aligned with complete intervertebral disc and mitochondrial structure, no damage to mitochondrial membranes, and tight arrangement of cristae. In CLP group and AAV group, muscle fiber breakage, sarcoplasmic reticulum expansion, severe mitochondrial swelling and even cristage structure disorder were observed. In the UCP2 group, only myocardial fiber edema was observed, and the muscle fiber structure was more complete than that of Sham group and AAV group. The mitochondria were slightly swollen and the cristae were intact.③ Western Blot showed that there was no significant difference in the expression of Opa1 and Fis1 in the four groups. The expression of Drp1 in CLP group and AAV group were significantly higher than that in Sham group. The expression of Drp1 in UCP2 group was significantly lower than that in CLP group and AAV group (Drp1/β-actin: 1.01±0.03 vs. 1.39±0.03, 1.49±0.03, both P < 0.05).④ The results of immunofluorescence showed that the ATP content of CLP group and AAV group were significantly lower than that of Sham group; the ATP content of UCP2 group was significantly higher than that of CLP group and AAV group (μmol/L: 1.99±0.15 vs. 1.10±0.17, 1.13±0.19, both P < 0.05).@*Conclusion@#UCP2 overexpression can significantly improve the systemic systolic function of myocardium in sepsis rats, protect myocardial mitochondrial ultrastructure, inhibit mitochondrial division, and improve mitochondrial ATP synthesis.

Effects of uncoupling protein 2 overexpression on myocardial mitochondrial dynamics in sepsis rats / 中华危重病急救医学

Objective To investigate the effects of uncoupling protein 2 (UCP2) overexpression on mitochondrial dynamics (mitochondrial division and fusion) of sepsis myocardial injury in rats. Methods Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group (Sham group) using normal saline instead of transfection and simulating cecal ligation and perforation (CLP); CLP group using normal saline instead of transfection, performing CLP to induce sepsis; adeno-associated virus (AAV) group using CLP after myocardial transfection with empty virus; UCP2 overexpression group (UCP2 group) CLP was performed 3 weeks after AAV-UCP2 (1×1015 vg/L, a total of 60 μL) myocardial transfection. The rats in each group were examined by echocardiography at 24 hours after the CLP, and then the rats were sacrificed immediately to harvest myocardial tissue. Myocardial ultrastructural changes were observed under the electron microscope, the expression of regulatory proteins related to myocardial mitochondrial dynamics [optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1) and fission 1 (Fis1)] were detected by Western Blot, and the level of mitochondrial adenosine triphosphate (ATP) production was detected by chemiluminescence. Results ①The echocardiographic results showed that there was no significant difference in left ventricular mass (LVM) and stroke volume (SV). Compared with Sham group, left ventricular diastolic anterior wall thickness (LVAWd), left ventricular systolic anterior wall thickness (LVAWs), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular systolic posterior wall thickness (LVPWs), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (LVFS) were significantly increased in CLP group and AAV group, while left ventricular systolic diameter (LVEDs), left ventricular diastolic diameter (LVEDd), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were significantly decreased. Compared with CLP group and AAV group, LVAWs, LVEF, LVFS were significantly decreased in UCP2 group, and LVEDs, LVEDV and LVESV were significantly increased [LVAWs (mm): 3.82±0.42 vs. 4.34±0.30, 4.44±0.12;LVEF: 0.921±0.038 vs. 0.979±0.019, 0.991±0.010; LVFS: (65.33±6.56)% vs. (80.11±8.23)%, (85.31±6.11)%;LVEDs (mm): 1.81±0.36 vs. 0.89±0.54, 0.60±0.17; LVEDV (μL): 137.09±50.05 vs. 89.72±53.04, 85.42±40.99;LVESV (μL): 10.48±4.59 vs. 2.48±3.52, 2.58±2.50, all P < 0.05]. ② Electron microscope showed that the structure of myocardial fibers in the Sham group was clear and aligned with complete intervertebral disc and mitochondrial structure, no damage to mitochondrial membranes, and tight arrangement of cristae. In CLP group and AAV group, muscle fiber breakage, sarcoplasmic reticulum expansion, severe mitochondrial swelling and even cristage structure disorder were observed. In the UCP2 group, only myocardial fiber edema was observed, and the muscle fiber structure was more complete than that of Sham group and AAV group. The mitochondria were slightly swollen and the cristae were intact.③ Western Blot showed that there was no significant difference in the expression of Opa1 and Fis1 in the four groups. The expression of Drp1 in CLP group and AAV group were significantly higher than that in Sham group. The expression of Drp1 in UCP2 group was significantly lower than that in CLP group and AAV group (Drp1/β-actin:1.01±0.03 vs. 1.39±0.03, 1.49±0.03, both P < 0.05).④ The results of immunofluorescence showed that the ATP content of CLP group and AAV group were significantly lower than that of Sham group; the ATP content of UCP2 group was significantly higher than that of CLP group and AAV group (μmol/L: 1.99±0.15 vs. 1.10±0.17, 1.13±0.19, both P < 0.05). Conclusion UCP2 overexpression can significantly improve the systemic systolic function of myocardium in sepsis rats, protect myocardial mitochondrial ultrastructure, inhibit mitochondrial division, and improve mitochondrial ATP synthesis.

Effects of uncoupling protein 2 overexpression on myocardial mitochondrial dynamics in sepsis rats / 中华危重病急救医学

Objective To investigate the effects of uncoupling protein 2 (UCP2) overexpression on mitochondrial dynamics (mitochondrial division and fusion) of sepsis myocardial injury in rats. Methods Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group (Sham group) using normal saline instead of transfection and simulating cecal ligation and perforation (CLP); CLP group using normal saline instead of transfection, performing CLP to induce sepsis; adeno-associated virus (AAV) group using CLP after myocardial transfection with empty virus; UCP2 overexpression group (UCP2 group) CLP was performed 3 weeks after AAV-UCP2 (1×1015 vg/L, a total of 60 μL) myocardial transfection. The rats in each group were examined by echocardiography at 24 hours after the CLP, and then the rats were sacrificed immediately to harvest myocardial tissue. Myocardial ultrastructural changes were observed under the electron microscope, the expression of regulatory proteins related to myocardial mitochondrial dynamics [optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1) and fission 1 (Fis1)] were detected by Western Blot, and the level of mitochondrial adenosine triphosphate (ATP) production was detected by chemiluminescence. Results ①The echocardiographic results showed that there was no significant difference in left ventricular mass (LVM) and stroke volume (SV). Compared with Sham group, left ventricular diastolic anterior wall thickness (LVAWd), left ventricular systolic anterior wall thickness (LVAWs), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular systolic posterior wall thickness (LVPWs), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (LVFS) were significantly increased in CLP group and AAV group, while left ventricular systolic diameter (LVEDs), left ventricular diastolic diameter (LVEDd), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were significantly decreased. Compared with CLP group and AAV group, LVAWs, LVEF, LVFS were significantly decreased in UCP2 group, and LVEDs, LVEDV and LVESV were significantly increased [LVAWs (mm): 3.82±0.42 vs. 4.34±0.30, 4.44±0.12;LVEF: 0.921±0.038 vs. 0.979±0.019, 0.991±0.010; LVFS: (65.33±6.56)% vs. (80.11±8.23)%, (85.31±6.11)%;LVEDs (mm): 1.81±0.36 vs. 0.89±0.54, 0.60±0.17; LVEDV (μL): 137.09±50.05 vs. 89.72±53.04, 85.42±40.99;LVESV (μL): 10.48±4.59 vs. 2.48±3.52, 2.58±2.50, all P < 0.05]. ② Electron microscope showed that the structure of myocardial fibers in the Sham group was clear and aligned with complete intervertebral disc and mitochondrial structure, no damage to mitochondrial membranes, and tight arrangement of cristae. In CLP group and AAV group, muscle fiber breakage, sarcoplasmic reticulum expansion, severe mitochondrial swelling and even cristage structure disorder were observed. In the UCP2 group, only myocardial fiber edema was observed, and the muscle fiber structure was more complete than that of Sham group and AAV group. The mitochondria were slightly swollen and the cristae were intact.③ Western Blot showed that there was no significant difference in the expression of Opa1 and Fis1 in the four groups. The expression of Drp1 in CLP group and AAV group were significantly higher than that in Sham group. The expression of Drp1 in UCP2 group was significantly lower than that in CLP group and AAV group (Drp1/β-actin:1.01±0.03 vs. 1.39±0.03, 1.49±0.03, both P < 0.05).④ The results of immunofluorescence showed that the ATP content of CLP group and AAV group were significantly lower than that of Sham group; the ATP content of UCP2 group was significantly higher than that of CLP group and AAV group (μmol/L: 1.99±0.15 vs. 1.10±0.17, 1.13±0.19, both P < 0.05). Conclusion UCP2 overexpression can significantly improve the systemic systolic function of myocardium in sepsis rats, protect myocardial mitochondrial ultrastructure, inhibit mitochondrial division, and improve mitochondrial ATP synthesis.

Alpha-adrenergic receptors in PVT neurons promote recovery from propofol anesthesia / 医学研究生学报

Objective The locus coeruleus noradrenergic system regulates the recovery process of general anesthesia, but its mechanism remains unclear. The locus coeruleus has a large amount of projection to the paraventricular nucleus of the thalamus (PVT). This study was to investigate the effect of the α-noradrenergic receptor in PVT neurons in propofol anesthesia. Methods The immunofluorescence technique was used for comparison of the c-fos expression in the PVT neurons collected from male SD rats under propofol anesthesia (the PA group, n = 4) or no anesthesia (the non-PA group, n = 4) and observation of the activity of PVT neurons. PVT microinjection models were established in 40 rats and randomized into four groups of equal number: noradrenaline, phentolamine, propranolol, and isotonic saline. Under propofol anesthesia, the animals received microinjection of noradrenaline, phentolamine, propranolol, and isotonic saline at 1 μL into the PVT, respectively, and were observed for the time of recovery of righting reflex (RORR) and the δ (1-4 Hz), θ (4-8 Hz), α (8-12 Hz), β (12-25 Hz) and γ waves (25-60 Hz) on EEG before and after microinjection. Results The expression of c-fos was significantly reduced in the PA group compared with that in the non-PA control. The Ca2+ signals in the PVT were significantly increased during the propofol induction of the loss of righting reflex (LORR), but decreased in the early stage of and during propofol anesthesia (P < 0.05), and remarkably increased at the emergence of and during RORR (P < 0.05). In comparison with the isotonic saline control, the noradrenaline group showed markedly shortened time of RORR (837.8 s vs 647.7 s, P < 0.05), reduced rate of δ waves (P < 0.05) and elevated rate of β waves (P < 0.05), while the phentolamine group exhibited prolonged time of RORR (837.8 s vs 1045.1 s, P < 0.05) and increased rate of δ waves after microinjection (P < 0.05). Conclusion The α-noradrenergic receptors in PVT neurons play a critical role in promoting recovery from propofol anesthesia.

Huotan Jiedu Tongluo decoction alleviates early atherosclerosis of rabbits by inhibiting eNOS uncoupling pathway / 中国中药杂志

The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.

Efficacy of different doses of levothyroxinein treatment of subclinical hypothyroidism in elderly patients and the effect on blood lipid level / 药物评价研究

Objective To investigate the clinical effect of different doses of levothyroxine in treatment of subclinical hypothyroidism and its effect on blood lipid level.Methods 98 cases of subclinical hypothyroidism elderly patients accepted in our hospital from March 2013 to May 2016 were divided into group A and B with 49 patients in each.The two groups were treated with different doses of levothyroxine treatment for 6 months.Then the clinical efficacy,thyroid function,blood lipid levels and adverse reactions of two groups were compared.Results The cure rate and total effective rate of group A were 59.18％ and 87.76％ respectively.The cure rate and total effective rate of group B were 61.22％ and 91.84％ respectively.There was no significant differencebetween two groups.After treatment,thethyroid function and blood lipid levels of two groups were better than before treatment.After 4 weeks of treatment,the thyroid function and blood lipid level in group B were better than those in group A (P ＜0.05).There was no significant difference in thyroid function and blood lipid between the two groups after 12 weeks of treatment.The incidence of total adverse reactions in group A was 4.08％,which was significantly lower than that in group B (16.33％),the difference was statistically significant (P ＜ 0.05).Conclusion Different doses of levothyroxine in the treatment ofsubclinical hypothyroidism were similar,and the thyroid function and blood lipids levels were improved after treatment,but the adverse reaction rate of low dose group was less.

Efficacy of different doses of levothyroxinein treatment of subclinical hypothyroidism in elderly patients and the effect on blood lipid level / 药物评价研究

Objective To investigate the clinical effect of different doses of levothyroxine in treatment of subclinical hypothyroidism and its effect on blood lipid level.Methods 98 cases of subclinical hypothyroidism elderly patients accepted in our hospital from March 2013 to May 2016 were divided into group A and B with 49 patients in each.The two groups were treated with different doses of levothyroxine treatment for 6 months.Then the clinical efficacy,thyroid function,blood lipid levels and adverse reactions of two groups were compared.Results The cure rate and total effective rate of group A were 59.18％ and 87.76％ respectively.The cure rate and total effective rate of group B were 61.22％ and 91.84％ respectively.There was no significant differencebetween two groups.After treatment,thethyroid function and blood lipid levels of two groups were better than before treatment.After 4 weeks of treatment,the thyroid function and blood lipid level in group B were better than those in group A (P ＜0.05).There was no significant difference in thyroid function and blood lipid between the two groups after 12 weeks of treatment.The incidence of total adverse reactions in group A was 4.08％,which was significantly lower than that in group B (16.33％),the difference was statistically significant (P ＜ 0.05).Conclusion Different doses of levothyroxine in the treatment ofsubclinical hypothyroidism were similar,and the thyroid function and blood lipids levels were improved after treatment,but the adverse reaction rate of low dose group was less.

Comparison of the safety of docetaxel combined with carboplatin regimen and epirubicin combined with cyclophosphamide sequential docetaxel regimen in phase Ⅲ clinical study of negative breast cancer / 中国生化药物杂志

Objective To compare the clinical efficacy and safety of docetaxel combined with carboplatin (TP) and epirubicin combined with cyclophosphamide sequential docetaxel (EC-T) adjuvant in the treatment of three negative breast cancer in phase III . Methods 62 cases of three negative breast cancer patients in phase III from May 2012 to October 2016 were selected and randomly divided into the control group and the experimental group, with 31 patients in each group. The control group was treated with epirubicin combined with cyclophosphamide and sequential docetaxel, and the experimental group was treated with docetaxel and carboplatin. The clinical indicators were compared and analyzed. Results There was no significant difference in the recent remission rate (77.42%) between the experimental group and the control group (74.19%). Two groups of patients with adverse reactions were restored within one month. There were 10 cases of WBC decrease in the experimental group, with the incidence rate of 32.25%. There were 18 cases of WBC decrease in the control group, the incidence rate was 58.06%, the difference was statistically significant (P<0.05). Conclusion Docetaxel combined with carboplatin and epirubicin adjuvant combined with cyclophosphamide than star sequential docetaxel in the treatment of three patients with negative breast cancer stage III were tolerated, TP occurred leukopenia and alopecia with low probability.

The epidemiologic characteristics and effects of complications on outcome of patients with severe acute pancreatitis in intensive care unit in north area of Guizhou province / 中国中西医结合急救杂志

Objective To investigate the epidemiologic characteristics of patients with severe acute pancreatitis (SAP) and the effects of its complications on prognoses in past 7 years in the north area of Guizhou province. Methods Data of 209 patients with SAP admitted to the Department of Critical Care Medicine of Affiliated Hospital of Zunyi Medical College from January 2009 to January2016 were retrospectively analyzed, and they were divided into a survival group (178 cases) and a death group (31 cases) according to the prognosis. The gender, age, diagnosis (primary and recurrent), the length of stay in hospital, the levels of creatinine and total bilirubin (TBil), the time of blood purification, hematocrit (HCT) level on the first day after admission, pathogenesis, complications [infection, pseudocyst, intra-peritoneal hemorrhage, acute renal failure (ARF), acute respiratory distress syndrome (ARDS), abdominal compartment syndrome (ACS), pancreatic encephalopathy, multiple organ dysfunction syndrome (MODS)], sequential organ failure (SOFA) score (maximum SOFA score during hospital stay), application of hormones, surgical interference, etc. related factors were compared, the SAP epidemiological characteristics, factors affecting prognosis and the effect of complications on prognosis in intensive care unit (ICU) were analyzed in the two groups.Results Of the 209 patients 98 cases were diagnosed biliary pancreatitis accounting for the majority (46.9%), hyperlipidemic pancreatitis 76 cases (36.3%), alcoholic pancreatitis 6 cases (2.8%) and idiopathic pancreatitis29 cases (13.9%). The age (years: 47.1±13.5 vs. 53.2±12.0), creatinine (μmol/L: 109.4±100.3 vs. 335.7±222.4), the ration of intra-peritoneal hemorrhage [4.5% (8) vs. 38.7% (12)], ARF [1.1% (2) vs. 54.8% (17)], ACS [1.1% (2) vs. 9.7% (3)], MODS [18.5% (33) vs. 74.2% (23)] and SOFA score (3.3±2.4 vs. 10.5±5.4), percentage of patients using hormones [5.6% (10) vs. 29.0% (9)] were significantly lowered (allP 0.05). Logistic regression analysis showed that creatinine > 300μmol/L [odds ratio (OR) was 2.651, 95% confidence interval (95%CI) was 1.459-3.935,P = 0.017], intra-peritoneal hemorrhage (OR was 5.231, 95%CI was 3.517-7.159,P = 0.000), ARF (OR was 3.731, 95%CI was 2.641-4.857,P = 0.000), ACS (OR was 2.517, 95%CI was 1.003-3.098,P = 0.000), use of hormone (OR was 1.012, 95%CI was 0.825-2.051,P = 0.000) and SOFA score (OR was 3.179, 95%CI was 2.630-6.021 andP = 0.000), MODS (OR was 4.716, 95%CI was 2.086-7.902 andP = 0.031) were the risk factors having critical effects on the prognosis of thedisease, The higher the creatinine level, the worse the prognosis. The mortality of ARF was very high reaching 89.5%; the mortalities of patients with complications as intra-peritoneal haemorrhage, ACS, MODS, pancreatic encephalopathy, AKI, infection, pancreatic pseudocyst and ARDS were as follows: 60.0%, 60.0%, 41.1%, 33.3%, 32.1%, 23.1%, 17.7%, 13.1% respectively.Conclusion Biliary disease andhyperlipidemia are the major causes of SAP in north area of Guizhou province, creatinine > 300μmol/L, intra-peritoneal hemorrhage, ARF, ACS, SOFA score, use of hormones are the independent risk factors leading to poor outcome in patients with SAP and the use of hormones cannot ameliorate the disease situation.

Comparison of the safety of docetaxel combined with carboplatin regimen and epirubicin combined with cyclophosphamide sequential docetaxel regimen in phase Ⅲ clinical study of negative breast cancer / 中国生化药物杂志

Objective To compare the clinical efficacy and safety of docetaxel combined with carboplatin (TP) and epirubicin combined with cyclophosphamide sequential docetaxel (EC-T) adjuvant in the treatment of three negative breast cancer in phase III . Methods 62 cases of three negative breast cancer patients in phase III from May 2012 to October 2016 were selected and randomly divided into the control group and the experimental group, with 31 patients in each group. The control group was treated with epirubicin combined with cyclophosphamide and sequential docetaxel, and the experimental group was treated with docetaxel and carboplatin. The clinical indicators were compared and analyzed. Results There was no significant difference in the recent remission rate (77.42%) between the experimental group and the control group (74.19%). Two groups of patients with adverse reactions were restored within one month. There were 10 cases of WBC decrease in the experimental group, with the incidence rate of 32.25%. There were 18 cases of WBC decrease in the control group, the incidence rate was 58.06%, the difference was statistically significant (P<0.05). Conclusion Docetaxel combined with carboplatin and epirubicin adjuvant combined with cyclophosphamide than star sequential docetaxel in the treatment of three patients with negative breast cancer stage III were tolerated, TP occurred leukopenia and alopecia with low probability.

Influence of pulmonary function after combined thoracoscopic and laparoscopic esophagectomy for the treatment of esophageal carcinoma / 中华外科杂志

<p><b>OBJECTIVES</b>To investigate the influence of combined thoracoscopic and laparoscopic esophagectomy for early postoperative pulmonary function, and to study the relative factors for postoperative pulmonary complications.</p><p><b>METHODS</b>From September 2009 to December 2010, 61 patients with esophageal cancer had undergone esophagectomy surgery, of which 32 patients had undergone combined thoracoscopic and laparoscopic esophagectomy (CTLE group), and 29 patients had undergone open three-field esophagectomy (open group). Pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)) were measured on the 1(th) preoperative day, 5(th) and 10(th) postoperative day, and arterial blood gas analyses were performed during the same period. Meanwhile, pain scores and other potentially relevant factors were recorded as well.</p><p><b>RESULTS</b>Preoperative pulmonary function and arterial blood gas analysis, including FEV(1)%, FVC%, PaO2 in two groups had no significant difference (t = -1.608 to 0.709, P = 0.113 to 0.481). On the 10(th) postoperative day, FEV(1)%, FVC%, PaO2, and SaO2 of two groups were significantly different (FEV(1)%: 77% ± 17% vs. 53% ± 13%, t = 6.241, P = 0.000; FVC%: 78% ± 13% vs. 57% ± 16%, t = 5.549, P = 0.000; PaO2: (87 ± 9) mmHg vs. (79 ± 14) mmHg, t = 2.477, P = 0.017; SaO2: 96% ± 3% vs. 94% ± 2%, t = 2.313, P = 0.024; 1 mmHg = 0.133 kPa). Pain score of CTLE group was lower than open group, and the scores of two groups had significant difference before the 5(th) day after surgery (t = -4.398 to -1.815, P = 0.000 to 0.049). Postoperative pulmonary complications of CTLE group was lower than open group (6/32 vs. 12/29, χ(2) = 3.745, P = 0.049).</p><p><b>CONCLUSIONS</b>Combined thoracoscopic and laparoscopic esophagectomy has advantages on early postoperative pulmonary function. It can relatively reduce the incidence of pulmonary complications after surgery.</p>

Neoadjuvant chemoradiotherapy followed by combined thoracoscopic and laparoscopic esophagectomy in the treatment of locally advanced esophageal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and efficacy of neoadjuvant chemoradiotherapy followed by combined thoracoscopic and laparoscopic esophagectomy (CTLE) in the treatment of advanced esophageal carcinoma.</p><p><b>METHODS</b>From June 2011 to February 2012, 11 patients with locally advanced esophageal carcinoma underwent neoadjuvant chemoradiotherapy followed by CTLE (clinical stage IIB-IIIA). NP (vinorelbine pin and cisplatin) or TP (program paclitaxel-pin and cisplatin) were applied as preoperative chemotherapy. During the same period, conventional fractionated radiotherapy was used with the radiation dose of 40 Gy/20 F. At four to six weeks after CRT, 11 patients received three-incision CTLE.</p><p><b>RESULTS</b>During chemoradiation, 9 patients developed bone marrow suppression. The interval between completion of chemoradiation and surgery was (49.6±15.4) d. Intraoperative findings revealed local fibrosis in one patient (75 days after chemoradiation) while operative difficulty was not increased in the remaining 10 patients. Compared to 15 patients who received surgery alone, operative time was shorter [(242.3±27.0) min vs.(280.5±27.2) min, P=0.002] and intraoperative blood loss was less [(168.2±95.6) ml vs. (244.5±84.8) ml, P=0.042], the number of removal lymph nodes was similar [(19.5±5.8) vs. (20.5±7.1), P=0.683], postoperative hospital stay was prolonged [(18.9±10.3) d vs. (12.5±4.6) d, P=0.020]. The postoperative complication rate was 36.4% including cervical anastomotic leak with pulmonary infection (n=1), cervical anastomotic fistula and hoarseness (n=1), pulmonary infection with pleural effusion (n=2). Follow up ranged from 1 to 9 months, and no recurrence was found.</p><p><b>CONCLUSION</b>The neoadjuvant chemoradiotherapy followed by combined thoracoscopic and laparoscopic esophagectomy in the treatment of locally advanced esophageal carcinoma is safe, feasible, and the short-term outcomes are favorable.</p>