A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Clinical effect of application of PDCA on reducing the incidence of healthcare-associated infection in department of neurosurgery / 中国感染控制杂志

Objective To study the effect of application of plan-do-check-act (PDCA) on reducing the incidence of healthcare-associated infection(HAI) in department of neurosurgery.Methods Quality control circle activity group was established,programme of activities was formulated,four stages and ten steps of PDCA were adopted,incidences of H AI in department of neurosurgery before (September-November 2015) and after (May-July 2016) the implementation of PDCA were observed,causes were analyzed based on implementation of hand hygiene,aseptic technique manipulation,and environmental sanitation,countermeasures were found out,and continuous quality improvement was performed for 6 months.Results Comparison between before and after implementation of PDCA was conducted,incidence of HAI in department of nerosurgery decreased from 10.9％ to 5.8％,difference was significant(P＜0.05),control rate was 100％,incidence of HAI dropped by 46.8％;hand hygiene implementation rate increased from 27.2％ to 76.9％,aseptic technique implementation rate increased from 76.0％ to 96.9％,environmental sanitation increased from 51.0 ％ to 90.0 ％,differences before and after implementation were all statistically significant(all P＜0.001).Conclusion Quality control circle activities implemented jointly by multiple departments can reduce the incidence of HAI in department of neurosurgery,rules can be observed,measures can be further improved,it is worthy of clinical application.

The dose verification of external electrically-driven multi-leaf collimator in the treatment plan of IMRT / 中国医学装备

Objective:To verify the dose of static and dynamic intensity modulated radiotherapy (IMRT) through 2-dimension ionization chamber matrix after external electrically-driven multi-leaf collimator (MLC) was installed in KB1800 medical linear accelerator. Methods: 40 patients who need receive IMRT were divided into static IMRT group (20cases) and dynamic IMRT group (20cases) as the random number table. The ionization chamber was applied to implement scale dose, and solid water and 2-D ionization chamber matrix was applied to verify dose. Besides, the feasibility of static and dynamic IMRT were compared and researched.Results: The verification results of plane dosage of static IMRT plan and dynamic IMRT plan showed that the passing rates both of them were above 90.0%, and the verification of intensity modulated dosimetry of medical electric linear accelerator KB1800 with external electric MLC was consistent with standard.Conclusion:After the external electrically-driven MLC is installed on the accelerator, the dosage of IMRT can achieve the verification standard, and it can be applied to clinical treatment and can satisfy the requirement of clinical radiotherapy.

The dose verification of external electrically-driven multi-leaf collimator in the treatment plan of IMRT / 中国医学装备

Objective:To verify the dose of static and dynamic intensity modulated radiotherapy (IMRT) through 2-dimension ionization chamber matrix after external electrically-driven multi-leaf collimator (MLC) was installed in KB1800 medical linear accelerator. Methods: 40 patients who need receive IMRT were divided into static IMRT group (20cases) and dynamic IMRT group (20cases) as the random number table. The ionization chamber was applied to implement scale dose, and solid water and 2-D ionization chamber matrix was applied to verify dose. Besides, the feasibility of static and dynamic IMRT were compared and researched.Results: The verification results of plane dosage of static IMRT plan and dynamic IMRT plan showed that the passing rates both of them were above 90.0%, and the verification of intensity modulated dosimetry of medical electric linear accelerator KB1800 with external electric MLC was consistent with standard.Conclusion:After the external electrically-driven MLC is installed on the accelerator, the dosage of IMRT can achieve the verification standard, and it can be applied to clinical treatment and can satisfy the requirement of clinical radiotherapy.

Allergens-induced sensitization alters airway epithelial adhesion molecules expression in mice / 生理学报

To explore the relationship between the epithelial adhesion molecules and immune responses of airway epithelium, we observed the expression of integrin β4 and intercellular adhesion molecule-1 (ICAM-1) in the mice airway epithelium after sensitization with allergens. BALB/c mice were sensitized with intraperitoneal injection of ovalbumin (OVA) or house dust mite (HDM) and then developed airway hyper-responsiveness as determined by barometric whole-body plethysmography. Both OVA and HDM sensitization led to increases of the number of peripheral leukocytes as well as inflammatory cells infiltration in lungs. OVA sensitized mice showed more severe inflammatory cells infiltration than HDM sensitized mice. Immunohistochemistry analysis of mice lung tissues revealed that sensitization with both allergens also led to a decrease of integrin β4 expression and an increase of ICAM-1 expression in airway epithelia. OVA sensitized mice showed a more significant increase of ICAM-1 expression compared with HDM sensitized mice. siRNA mediated silencing of integrin β4 gene in 16HBE cells resulted in an up-regulation of ICAM-1 expression. Our results indicate a possible role of airway epithelial adhesion molecules in allergen-induced airway immune responses.

Hyperbaric Oxygen and Ginkgo Biloba Extract Ameliorate Cognitive and Memory Impairment via Nuclear Factor Kappa-B Pathway in Rat Model of Alzheimer's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperbaric oxygen (HBO) and Ginkgo biloba extract (e.g., EGB 761) were shown to ameliorate cognitive and memory impairment in Alzheimer's disease (AD). However, the exact mechanism remains elusive. The aim of the present study was to investigate the possible mechanisms of HBO and EGB 761 via the function of nuclear factor kappa-B (NF-κB) pathway.</p><p><b>METHODS</b>AD rats were induced by injecting β-amyloid 25-35 into the hippocampus. All animals were divided into six groups: Normal, sham, AD model, HBO (2 atmosphere absolute; 60 min/d), EGB 761 (20 mg·kg-1·d-1 ), and HBO/EGB 761 groups. Morris water maze tests were used to assess cognitive, and memory capacities of rats; TdT-mediated dUTP Nick-End Labeling staining and Western blotting were used to analyze apoptosis and NF-κB pathway-related proteins in hippocampus tissues.</p><p><b>RESULTS</b>Morris water maze tests revealed that EGB 761 and HBO significantly improved the cognitive and memory ability of AD rats. In addition, the protective effect of combinational therapy (HBO/EGB 761) was superior to either HBO or EGB 761 alone. In line, reduced apoptosis with NF-κB pathway activation was observed in hippocampus neurons treated by HBO and EGB 761.</p><p><b>CONCLUSIONS</b>Our results suggested that HBO and EGB 761 improve cognitive and memory capacity in a rat model of AD. The protective effects are associated with the reduced apoptosis with NF-κB pathway activation in hippocampus neurons.</p>

Preparation and quality assessment of high-purity ginseng total saponins by ion exchange resin combined with macroporous adsorption resin separation / 中国天然药物

AIM@#To prepare high-purity ginseng total saponins from a water decoction of Chinese ginseng root.@*METHOD@#Total saponins were efficiently purified by dynamic anion-cation exchange following the removal of hydrophilic impurities by macroporous resin D101. For quality control, ultrahigh-performance liquid chromatography with a charged aerosol detector (CAD) was applied to quantify marker components. The total saponin content was estimated by a colorimetric method using a vanillin-vitriol system and CAD response.@*RESULTS@#D201, which consisted of a cross-linked polystyrene matrix and -N(+)(CH3)3 functional groups, was the best of the four anion exchange resins tested. However, no significant difference in cation exchange ability was observed between D001 (strong acid) and D113 (weak acid), although they have different functional groups and matrices. After purification in combination with D101, D201, and D113, the estimated contents of total saponins were 107% and 90% according to the colorimetric method and CAD response, respectively. The total amount of representative ginsenosides Re, Rd, Rg1, and compound K was approximately 22% based on ultrahigh-performance liquid chromatography-CAD quantitative analysis.@*CONCLUSION@#These findings suggest that an ion exchange resin, combined with macroporous adsorption resin separation, is a promising and feasible purification procedure for neutral natural polar components.

Fundamental aspects of solid dispersion technology for poorly soluble drugs

The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Since a solid dispersion is basically a drug-polymer two-component system, the drug-polymer interaction is the determining factor in its design and performance. In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.

Determination of total ginsenosides in ginseng extracts using charged aerosol detection with post-column compensation of the gradient / 中国天然药物

AIM@#Variation in structure-related components in plant products prompted the trend to establish methods, using multiple or total analog analysis, for their effective quality control. However, the general use of routine quality control is restricted by the limited availability of reference substances. Using an easily available single marker as a reference standard to determine multiple or total analogs should be a practical option.@*METHOD@#In this study, the Ultra-HPLC method was used for the baseline separation of the main components in ginseng extracts. Using a plant chemical component database, ginsenosides in ginseng extracts were identified by Ultra-HPLC-MS analysis. The charged aerosol detection (CAD) system with post-column compensation of the gradient generates a similar response for identical amounts of different analytes, and thus, the content of each ginsenoside in ginseng extracts was determined by comparing the analyte peak area with the reference standard (determination of total analogs by single marker, DTSM). The total ginsenoside content was determined by the summation of reference standard and other ginsenoside components.@*RESULTS@#The results showed that DTSM approaches were available for the determination of total ginsenosides in a high purity ginseng extract because of the removal of impurities. In contrast, DTSM approaches might be suitable for determination of multiple ginsenosides without interference from impurities in the crude ginseng extract.@*CONCLUSION@#Future practical studies similar to the present study should be conducted to verify that DTSM approaches based on CAD with post-column inverse gradient for uniform response are ideal for the quality control of plant products.

Effects of feixin decoction on the contents of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in the rat model of hypoxic pulmonary hypertension / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of Feixin Decoction (FXD) on the hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in the rat model of hypoxic pulmonary hypertension (HPH), and to study its mechanisms for treating HPH.</p><p><b>METHODS</b>Forty healthy male SD rats were randomly divided into four groups, i. e., the normal control group, the HPH model group, the FXD group, and the Nifedipine group, 10 rats in each group. The HPH rat model was prepared using normal pressure intermittent hypoxia method. Except the normal control group, rats in the rest groups were fed in a self-made hypoxic plexiglass cabin, with the poor oxygen condition for 8 h daily for 14 successive days. Then the distilled water (at 30 mL/kg) was given by gastrogavage to rats in the normal control group and the HPH model group. FXD (at 28 g/kg) and Nifedipine (at 20 mg/kg) were given by gastrogavage to rats in the FXD group and the Nifedipine group respectively, once daily, for 14 successive days. Besides, hypoxia was continued for 14 days while medicating. The mean pulmonary artery pressure (mPAP) was detected on the second day after the last medication. The morphology of the pulmonary arteriole was detected. The ratio of pulmonary artery wall area and tube area (WA%) was determined. The protein and mRNA expressions of HIF-1alpha and VEGF were detected using immunohistochemistry and in situ hybridization technique.</p><p><b>RESULTS</b>Compared with the normal control group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly increased in the model group (P < 0.01, P < 0.05). Compared with the HPH model group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha and VEGF significantly decreased in the FXD group (P < 0.01, P < 0.05).</p><p><b>CONCLUSIONS</b>FXD down-regulated the expression of VEGF through decreasing the expression of HIF-1alpha. One of its mechanisms for treating HPH might be partially due to reversing the remodeling of pulmonary vascular smooth muscle.</p>

The expression and possible role of SENP1 in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the dynamic expression and role of SENP1 (SUMO-specific proteases-1) in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension (HPH).</p><p><b>METHODS</b>Forty adult male Wistar rats were randomly divided into 5 groups (n = 8), and exposed to normoxia (Control group) or exposed to hypoxia for 3, 7, 14 or 21 d, respectively. The HPH models were established by normobaric intermittent hypoxia. Mean pulmonary arterial pressure (mPAP), right ventricle hypertrophy index (RVHI), and vessel morphometry were measured. Reverse transcriptase-polymerase chain reaction(RT-PCR) and in situ hybridization were used to determine the mRNA expression of SENP1. Immunohistochemistry and Western blot were used to determine the protein expression of SENP1.</p><p><b>RESULTS</b>The hypoxic rats developed pulmonary vascular remodeling in pulmonary arterioles after 7 d of hypoxia exposure. Pulmonary vascular remodeling in pulmonary arterioles significantly increased after 14 d of hypoxia. The level of mPAP in hypoxic rats increased significantly after 7 d of hypoxia, reached its peak after 14 d of hypoxic exposure. RVHI was markedly increased after 14 d of hypoxia. In situ hybridization and immunohistochemical analysis showed that SENP1 mRNA and protein were positively stained in control. SENP1 mRNA expression had little changes after exposure to hypoxia compared with the control, however, SENP1 protein expression was declined gradually after 7 d of hypoxia. The results of RT-PCR and Western blot showed that the same dynamic expression of SENP1 mRNA and protein in lung tissues of rats. Linear correlation analysis showed that SENP1 protein were negatively correlated with mPAP, pulmonary vascular remodeling index and RVHI.</p><p><b>CONCLUSION</b>Under chronic hypoxia, SENP1 protein can be degradated. The dynamic expression of SENP1 protein may play a role in implicating in the development of HPH.</p>

The effect of transcription factor KLF2 in expression of gamma-GCS depend on regulation by Nrf2 in lung of rats with chronic obstructive pulmonary disease / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the expression of lung Krüppel-like transcription factor (KLF2/LKLF) in lung tissues of rats with chronic obstructive pulmonary disease (COPD) and the relationship between KLF2 and NF-E2-related factor 2 (Nrf2), and make further explore the effects of KLF2 on the expression of gamma-glutamylcysteine synthetase (gamma-GCS).</p><p><b>METHODS</b>Twenty-two male SD rats were randomly divided into a COPD group (n = 10) and a normal control group (n = 11). The rat model of COPD established by cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS), and lung tissues were obtained. The expressions of KLF2, Nrf2, gamma-GCS mRNA and protein in lung tissues were measured by immunohistochemistry (IHC), Western blot, in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR). To explore the relationship between KLF2 and Nrf2 protein,we utilize the method of co-immunoprecipitation (CO-IP).</p><p><b>RESULTS</b>IHC and Western blot showed that protein expressions of KLF2, Nrf2, gamma-GCS were higher in the lung tissues from rats with COPD than those in the control groups (all P < 0.05). The levels of KLF2, gamma-GCS mRNA were markedly increased in the COPD group (all P < 0.01) while Nrf2 mRNA expression in COPD group had no significant difference with that in control group ( P > 0.05). CO-IP result showed that KLF2 were obviously present in immunoprecipitates of Nrf2 (P < 0.01) . Linear correlation analysis showed that the level of KLF2 protein was positively correlated with the level of Nrf2 protein (P < 0.05), and KLF2, Nrf2 proteins were positively correlated with gamma-GCS mRNA and protein (all P < 0.05).</p><p><b>CONCLUSION</b>The expression of KLF2 is significantly up-regulated in COPD, which maybe up-regulate gamma-GCS mRNA expression by increasing Nrf2 expression and nuclear translocation against oxidative stress.</p>

The expression of hypoxia-inducible factor-1alpha and its hydroxylases in pulmonary arteries of patient with chronic obstructive pulmonary disease / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the expression of hypoxia-inducible factor-lalpha subunit (HIF-1alpha), HIF prolyl hydroxylase domain-containing protein(PHDs) and factor inhibiting HIF-1(FIH) in pulmonary arteries of patient with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Pulmonary specimens were obtained from patients undergoing lobectomy for lung cancer, 12 had concurrent COPD (COPD group) and 14 without COPD (control group). The ratio of vascular wall area to total vascular area (WA%) and pulmonary artery media thickness (PAMT) was observed, and HIF-1alpha and its hydroxylases(PHD1, PHD2, PHD3, FIH) mRNA and protein were detected by in situ hybridization and immunohistochemistry respectively.</p><p><b>RESULTS</b>WA% and PAMT of COPD patients(50 microm +/- 9 microm, 40% +/- 5%, were statistically different from those of the control subjects (39 microm +/- 6 microm, 31% +/- 4%, P < 0.01). Relative quantification of mRNA and protein levels (absorbance, A) showed that HIF-lalpha mRNA and protein levels in COPD group (0.230 +/- 0.036,0.275 +/- 0.039) were statistically higher than those of the control subjects (0.174 +/- 0.029, 0.102 +/- 0.015, P < 0.01 ), and that the protein level increased more markedly. PHD1 mRNA in COPD subjects (0.180 +/- 0.030) was comparable to that in control group (0.191 +/- 0.029, P > 0.05); PHD2 and PHD3 mRNA levels in COPD (0.245 +/- 0.044, 0.252 +/- 0.023) were significantly higher than those in control group(0.182 +/- 0.028, 0.127 +/- 0.017, P < 0.01). On the other hand, in COPD subjects PHD1 protein (0.104 +/- 0.015) was significantly lower(P < 0.01), whereas PHD2 protein (0.274 +/- 0.044) was significantly higher(P < 0.01) than those in control group(0.209 +/- 0.023, 0.219+/- 0.043). As for PHD3 protein, no significant changes were observed between the two groups (0.161+/- 0.023 in COPD, 0.146 +/- 0.021 in control, P > 0.05). FIH mRNA and protein both showed no differences between the two groups. Linear correlation analysis showed that HIF1alpha protein was positively correlated with WA%, PAMT, PHD2 mRNA and protein, PHD3 mRNA, and that HIF1alpha protein was negatively correlated with PHD1 protein.</p><p><b>CONCLUSION</b>PHDs may be involved in the process of hypoxic pulmonary vascular remodeling in COPD via regulation of HIF-1alpha gene expression</p>

The roles of PPAR-gamma/PGC-1alpha to Nrf2/gamma-GCS-h in lung of guinea pigs with bronchial asthma / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h in lung of guinea pigs with bronchial asthma, and to explore the roles of them.</p><p><b>METHODS</b>Forty adult male guinea pigs were randomly divided into 4 groups: the control group (group A), asthmatic group ( group B), dexamethasone group (group C) and rogridone group (group D), 10 guinea pigs in each group. The asthmatic model was established by the ovalbumin challenge method. Expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h mRNA in lung tissue were assayed by in situ hybridization. Expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h protein were detected by immunohischemistry and by Western blot.</p><p><b>RESULTS</b>In situ hybridization showed that the expressions of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h mRNA in lung tissue were the lowest in group B and the comparison among groups showed statistical significant (all P < 0.01). Immunohistochemistry and Western blot indicated that the value of PPAR-gamma/PGC-1alpha and Nrf2/gamma-GCS-h protein in lung tissue were the lowest in group B, and expressed primarily in nucleus, the differences being statistically significant (all P < 0.01). There was positive correlation between PPAR-gamma and PGC-1. gamma-GCS-h mRNA also positively correlated between PPAR-gamma/PGC-1alpha and Nrf2 in nucleus, and the expression of Nrf2 was also positively correlated with PPAR-gamma/ PGC-1alpha.</p><p><b>CONCLUSION</b>In acute asthmatic models induced by ovalbumin, the expressions of PPAR-alpha/PGC-1alpha and Nrf2/gamma-GCS-h were decreased, and PPARgamma/PGC-1alpha could up-regulate the expressions of Nrf2/gamma-GCS-h to increase the antioxidant defense of tissues, thus being implicated that PPARgamma/PGC-1alpha might play important roles in the pathogenesis and prevention of asthma.</p>

The pathway of PI3k/Akt-aPKCiota/zeta-Nrf2 regulating the expression of gamma-glutamylcysteine synthetase in the bronchial epithelial cells of rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effect of the signal pathway of phosphoinositol-3-kinase (PI3K)/Akt-antypical protein kinase C(iotazeta) (aPKC(iotazeta))-Nuclear factor-E2 related factor (Nrf2) on gamma-glutamylcysteine synthetase (gamma-GCS) of the bronchial epithelial cells of rats after exposure to cigarette smoke extracts (CSE).</p><p><b>METHODS</b>gamma-GCS, Nrf2, p-Akt and p-aPKC(iotazeta) proteins were semi-quantified by Western blot. gamma-GCS protein expression was assessed by immunocytochemistry. gamma-GCS mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). Nrf2 protein was observed by immunofluorescence. The rate of the cells expressed p-Akt were analyzed by flow cytometry. GSH content and gamma-GCS activity were measured.</p><p><b>RESULTS</b>GSH content, Nrf2 protein of nucleus, p-aPKC(iotazeta) protein, p-Akt protein and positive cells, gamma-GCS protein and mRNA and activity were significantly increased after exposure to CSE for 3 hours. aPK(iotazeta) inhibitor RO813220 significantly reduced the expression of p-aPKC(iotazeta) protein, gamma-GCS protein and mRNA and activity, but enhanced Nrf2 protein of cytoplasm expression, had no effect on p-Akt. p-Akt inhibitor LY294002 and RO813220 + LY294002 decreased p-aPKC(iotazeta) protein, p-Akt protein and positive cells, gamma-GCS protein and mRNA and activity expression, increased Nrf2 protein of cytoplasm expression. The correlation analysises demonstrated that there were a positive correlation between Nrf2 and gamma-GCS, p-Akt, p-aPKC(iotazeta), between p-Akt and Nrf2, p-aPKC(iotazeta), gamma-GCS, between p-aPKC(iotazeta) and Nrf2, p-Akt, gamma-GCS.</p><p><b>CONCLUSION</b>CSE might upregulate gamma-GCS expression through PI3K/Akt-aPKC(iotazeta)-Nrf2 signaling pathway in the bronchial epithelial cells of rats.</p>

Hippocampal cAMP response element binding protein and antidepressant treatments / 生理学报

With the deepening research on pathogenesis of depression, the focus has diverted from the mechanism of regulating monoamines to the basic pathophysiology of depression and the long-term mechanism of antidepressant treatments. cAMP response element binding protein (CREB) in the brain, especially in the hippocampi, as a converging agent of many intracellular signaling transduction pathways is getting increasing attention. To better understand the basic pathophysiology of depression and the long-term mechanism of antidepressant treatments, it is significant to make clear the correlation between hippocampal CREB and antidepressant treatments. This review mainly refers to the formation of CREB and its distribution in hippocampi, the upstream signaling transduction pathways of hippocampal CREB and antidepressant treatments, and the possible antidepressant mechanisms by regulating hippocampal CREB.

The cooperation of OS-9 and PHDs in hypoxia-induced pulmonary hypertension of rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the dynamic expression of hypoxia-inducible factor 1alpha, PHDs and OS-9 in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.</p><p><b>METHODS</b>SD rats were randomly divided into 5 groups (n = 8) and exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively. RT-PCR and in situ hybridization were used to determine the expression of mRNA. Immunohistochemistry and Western blot were used to determine the expression of protein.</p><p><b>RESULTS</b>HIF-1alpha protein was poorly positive in control, markedly up-regulated after 3 d and 7 d of hypoxia (P < 0.05, vs group C), and then declined slightly after 14 d and 21 d of hypoxia. HIF-1alpha mRNA increased dramatically after 14 d of hypoxia (P < 0.05, vs group C). PHD1, PHD2 mRNA and protein was positive in group C. PHD2 mRNA and protein were up-regulated after 3 d of hypoxia (P < 0.05, vs group C), reaching its peak after 14 d of hypoxia while PHD1 protein declined after 14 d of hypoxia (P < 0.05, vs group C) without statistic mRNA changing. PHD3 mRNA and protein were detected at low level in control, markedly up-regulated after 3 d of hypoxia (P < 0.05, vs group C), and then PHD3 mRNA kept at high level while PHD3 protein declined after 14 d of hypoxia (P < 0.05, vs 7 d). OS-9 mRNA was positively in control, markedly decreased after 3 d of hypoxia (P < 0.05, vs group C), reaching its lowest lever after 14 d of hypoxia. Linear correlation analysis showed that OS-9 protein was positively correlated with OS-9 mRNA (r = 0.82, P < 0.01) and HIF-1alpha protein (r = 0.57, P < 0.01).</p><p><b>CONCLUSION</b>HIF-1alpha, PHDs and OS-9 are all involved in the pathogenesis of hypoxic pulmonary hypertension in rats. OS-9 may interact with both HIF-1alpha and PHDs to promote PHD-mediated hydroxylation of HIF-1alpha.</p>

The preventative effects of protein tyrosine kinase on the inflammation and airway remondeling in lung of guinea pigs with bronchial asthma / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of protein tyrosine kinase on the inflammation and airway remodeling in lung of guinea pigs with bronchial asthma.</p><p><b>METHODS</b>30 adult male guinea pigs were randomly divided into 3 groups (n=3): control group (C group), asthmatic group(A group)and genistein group (B group). Asthmatic model was established by ovalbumin intraperitoneal injection and ovalbumin inhalation. The total cell and the proportion of inflammatory cell in bronchial alveolar lavage fluid(BALF), inflammatory cell infiltration and index of remodeling of bronchiole were measured, respectively. The expression of p-tyrosine in lung tissue was examined by immunohistochemistry.</p><p><b>RESULTS</b>The total cell and proportion of eosinophil in BALF of A group were significantly higher than that of C group (P < 0.01), but compared with A group, the total cell and proportion of eosinophil in BALF of B group were much lower (P < 0.01). The number of eosinophile and lymphocyte of bronchiole in A group were significantly higher than that of C group (P < 0.01), but compared with A group, the number of eosinophile and lymphocyte in bronchiole of B group were much lower (P < 0.01). Compared with A group, the remodeling of bronchiole of B group was significantly relieved (P <0.01), there was no difference between B and C group (P > 0.05). Immunohistochemistry indicated that in A group the p-tyrosine was more positively expressed at the bronchial smooth muscle, bronchial epithelium, smooth muscle of vessel and inflammatory cell, especially at smooth muscle of bronchi and vessel and inflammatory cell than that of C group (P <0.01), there was no difference between B group and C group (P > 0.05).</p><p><b>CONCLUSION</b>PTK played a key role in inflammation and bronchial remodeling in lung of guinea pigs with bronchial asthma. The Protein tyrosine kinase inhibitor genistein could prevent and inhibit the inflammation and bronchial remodeling in lung of guinea pigs with bronchial asthma.</p>

Roles of NRF2 regulating gamma-glutamylcysteine synthetase in lung of rats with chronic obstructive pulmonary disease / 中国应用生理学杂志

<p><b>AIM</b>To investigate the expression and relationship of gamma-glutamylcysteine synthetase (gamma-GCS) and NF-E2-related factor2 (NRR2) in lung of rat with chronic obstructive pulmonary disease (COPD)in order to elucidate the possible important role of gamma-GCS and NRF2 in pathogenesis of COPD.</p><p><b>METHODS</b>The rat COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposed to cigarette smoke daily. The gamma-GCS activity was measured, the expression of gamma-GCS mRNA in lung was examined by in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR), the protein expressions of NRF2, gamma-GCS in lung were detected by immunohistochemical (IH) and Western blot respectively.</p><p><b>RESULTS</b>The gamma-GCS activity was higher in COPD group than that in control group. The expressions of gamma-GCS mRNA in COPD group was stronger than those in control group. ISH showed that the gamma-GCS mRNA was expressed in alveolar epithelium and bronchial smooth muscle cell in COPD. The protein expressions of NRF2, gamma-GCS were significantly higher than the control group. IH showed that NRF2, gamma-GCS proteins were expressed in alveolar and bronchial epithelium in the COPD group. There was a positive correlation between NRF2 and gamma-GCS and gamma-GCS mRNA.</p><p><b>CONCLUSION</b>NRF2 may play an important role in the mechanism of COPD oxidative stress vis up-regulation of gamma-GCS.</p>

Treatment of floating knee injury / 中国骨伤

<p><b>OBJECTIVE</b>To explore the clinical outcome of floating knee injury treated by open reduction and internal fixation.</p><p><b>METHODS</b>The course of treatment of floating knee in 78 cases by open reduction and internal fixation were reviewed. There were 59 males and 19 females, aged from 17 to 58 years old, with an average age of 37.5 years. Intramedullary nail, pressure plate hollow screw, multi-function single side external fixation holder and other internal fixature were used in the operation. Early exercises were followed postoperatively.</p><p><b>RESULTS</b>All patients were followed-up for 8 to 35 months (mean 18.6 months). According to the criterion of Karlström, of the 48 cases with femoral shaft fracture, 45 were excellent and 3 were good. In the 11 cases of bimalleolar fracture, 5 were excellent, 3 good, 1 fair and 2 bad. Of the 19 cases of mixed fracture, 9 were excellent,6 good, 3 fair and 1 bad.</p><p><b>CONCLUSION</b>Strict sterilization, non-invasion and standard internal and external fixation could make the fracture anatomical reduction and firm fixation. It is beneficial to early rehabilitation exercise. Complications such as malunion, and stiff joint could be avoided. The clinical outcome were satisfactory.</p>