Resistance of C57BL/6 Mice to Different Artemisinin-sensitive Strains of PbK173 / 中国实验方剂学杂志

ObjectiveThe tolerance of C57BL/6 mice to artemisinin-sensitive and -resistant strains of Plasmodium berghei （Pb） K173 and the differences in blood parameters， spleen coefficient and spleen structure during infection were compared to explore whether the artemisinin resistance of Pb would aggravate malaria infection. MethodPbK173 artemisinin-sensitive and -resistant strains were tested in parallel. C57BL/6 mice were randomly divided into 1 control group， 4 artemisinin-sensitive strain groups and 4 artemisinin-resistant strain groups by body weight. Each infection group was simultaneously inoculated （ip） with 1×107 infected red blood cells （iRBCs） of sensitive/resistant strain. For the mice in the survival test group， the body weight was recorded every day post infection， and the tail vein blood smear was collected to calculate the Pb infection rate. In the other infection groups， peripheral blood and spleen were collected on 2， 5 and 9 d after infection. Peripheral blood parameters， spleen coefficient， pathological section of spleen and spleen cells were detected in each group. ResultOn 1-3 d after infection， the infection rate of the resistant strain （0.4±0.0， 0.8±0.1， 1.9±0.4）% was always higher than that of the sensitive strain （0.2±0.1， 0.4±0.1， 1.1±0.3）% （P<0.01）. From the 4th d of infection， the infection rate of the two groups gradually approached. The survival period of the sensitive strain group （20.5±1.2） d was shorter than that of the resistant strain group （23.3±1.4） d （P<0.01）. On the 9th d， the white blood cell count of the sensitive strain group （16.2±1.1）×109 cells/L was higher than that of the resistant strain group （10.6±1.8）×109 cells/L （P<0.01）. Flow cytometry analysis of spleen cells showed that the sensitive strain group （3.6±0.4） demonstrated a higher CD4+/CD8+ value than the resistant strain group （2.3±0.2） on the 9th d （P<0.01）. The spleen of C57BL/6 infected mice was gradually enlarged during infection， and on the 9th d， the resistant strain group （3.1±0.1）% showed a higher spleen coefficient than the sensitive strain group （2.7±0.2）% （P<0.01）. In the early stage of C57BL/6 infected mice， the red pulp of spleen was hyperemic and swollen. On the 9th d， the marginal area of the spleen disappeared and the structure of the red and white pulp was destroyed. ConclusionWithout drug treatment， the protective immune responses of peripheral blood and spleen of C57BL/6 mice were more sensitive to PbK173 artemisinin-sensitive strain. The artemisinin-resistant strain of PbK173 bred with mouse-to-mouse blood transmission and increased artemisinin dose exhibited shortened growth period and reduced toxicity.

Effect of Dihydroartemisinin on Oxidative Damage and Energy Metabolism of HepG2 Cells and Its Synergistic Effect with Sorafenib / 中国实验方剂学杂志

Objective:To explore the inhibitory effect of dihydroartemisinin （DHA） on the proliferation of HepG2 cells， elucidate the mechanism from the perspectives of oxidative damage and energy metabolism， and discuss the possibility of combined use of DHA with sorafenib （Sora）. Method:Cell counting kit-8 （CCK-8） assay was used to obtain the 50% inhibitory concentration （IC₅₀） of DHA and Sora on HepG2 and SW480 cells and Chou-Talalay method was used to obtain the combination index （CI） of DHA and Sora. HepG2 cells were classified into the control group， DHA group （10 µmol·L^-1）， Sora group （5 µmol·L^-1）， and DHA + Sora group （DHA 10 µmol·L^-1， Sora 5 µmol·L^-1） and then incubated with corresponding drugs for 8-12 h. Seahorse XF glycolytic rate assay kit and cell mito stress test kit were employed to respectively detect the glycolysis function of cells and oxidative phosphorylation function of mitochondria. DCFH-DA and lipid peroxidation MDA assay kit were separately used to analyze the intracellular levels of reactive oxygen species （ROS） and malondialdehyde （MDA）. Western blot was applied to determine the intracellular levels of heme oxygenase-1 （HO-1） and glutamate-cysteine ligase catalytic subunit （GCLC）. Result:Compared with the control group， DHA alone inhibited the ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （<italic>P</italic><0.01）， increased the levels of intracellular ROS and MDA （<italic>P<</italic>0.05）， and decreased the levels of HO-1 and GCLC （<italic>P<</italic>0.05） in HepG2 cells. DHA and Sora had synergistic inhibitory effect on proliferation of HepG2 and SW480 cells， with CI < 0.90. The DHA + Sora group showed stronger suppression of ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （<italic>P</italic><0.01）， higher levels of intracellular ROS and MDA （<italic>P<</italic>0.01）， and lower levels of intracellular antioxidation-related proteins HO-1 and GCLC in HepG2 cells （<italic>P<</italic>0.01） than the DHA group. Conclusion:DHA may increase the level of MDA by reducing HO-1 and GCLC and increasing ROS in HepG2 cells， which results in mitochondria oxidative damage， restricts cell glycolysis and mitochondrial oxidative phosphorylation， and thus finally inhibits the proliferation of HepG2 cells. DHA and Sora have synergistic inhibitory effect on the proliferation of HepG2 and SW480 cells， and the mechanism may be related to the synergistic oxidative damage that affects the mitochondrial electron transport chain and suppresses cell energy metabolism.

Efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of OSAHS with soft palate oropharyngeal obstruction / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Seventy-three patients(including 60 males and 13 females) with OSAHS admitted to the department of otorhinolaryngology of our hospital in recent two years were retrospectively analyzed. All the patients had velopharyngeal obstructionevaluated by electronic endoscopic Müller test and were divided into control group (34 cases) and observation group (39 cases). The patients in the control group were performed modified uvulopalatopharyngoplasty, while those in the observation group were performed relocation and expansion pharyngoplasty by suspension sutures.The scores of ESS, AHI and LSaO2 before and after treatment were collected and compared. Results: The total effective rate of the observation group was 94.87%, which was significantly higher than 79.41% of the control group. The AHI was lower and LSaO2 value was higher (χ2=-1. 896,-1. 968,P<0.05)in the observation group. The sleeping symptoms and quality of life of the two groups were significantly improved. The ESS score of the observation group was decreased more significantly than that of the control group after treatment, and the difference was statistically significant (χ2=-1.451,P<0.05). The incidence of foreign body sensation in pharynx of the observation group (89.74%) was higher than that of the control group (55.88%), and the postoperative bleeding and postoperative recurrence rate (0.00%, 2.56%) was lower than that of the control group (8.82%, 14.70%)with statistical significance (χ2=4.738,4.249,4.119,P<0.05).The incidence of transient nasopharyngeal reflux in both groups was low and statistically insignificant (χ2=0.629,P>0.05). Conclusions: Preoperative strict screening of indications plays an important role in the selection of palatopharyngeal surgery methods and curative effect. Relocation and expansion pharyngoplasty by suspension sutures can improve the clinical efficacy of OSAHS with better safety and less recurrence.

Clinical Significance of EBV-DNA Copy Number in EBV Positive Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of EBV-DNA copy number on the prognosis of patients with EBV positive lymphoma.@*METHODS@#Clinical data of 109 patients diagnosed as EBV positive lymphoma in Tianjin Medical University Cancer Institute and Hospital from January 2010 to January 2020 were enrolled and analyzed retrospectively. Kaplan-Meier analysis was used for survival analysis, Log-rank was used to compare the clinical characteristics between the patients in different groups, and Cox regression was used for multivariate analysis.@*RESULTS@#Among the 109 patients with EBV-positive lymphoma, the medium age were 56 (range 15 to 83) years old. 29 patients at Ann Arbor stage I-II while 80 patients at stage III-IV. The average value of EBV-DNA was 1 023 510 IU/ml, 7 patients were higher than the average value, while 102 patients were lower. KM survival analysis showed that OS and PFS in patients with EBV-DNA above average level were shorter than those in patients with EBV-DNA below average level (OS: P=0.048, PFS: P=0.001), EBV-DNA copy number was a factor affecting the prognosis of patients. In addition, LDH level showed positive correlation with EBV-DNA copy number (r=0.650), which was also one of the factors affecting OS (P=0.053).@*CONCLUSION@#EBV-DNA copy number and LDH level can influence the prognosis of EBV positive lymphoma patients. Therefore, detection of EBV-DNA copy number in peripheral blood is important for evaluate the prognosis the patients.

Bushen Huoxue Recipe Inhibited Vascular Calcification in Chronic Renal Failure Rats by Regulating BMP-2/Runx2/Osterix Signal Pathway / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Bushen Huoxue Recipe (BHR) on inhibiting vascular calcification (VC) in chronic renal failure (CRF) rats by regulating BMP-2/Runx2/Osterix signal pathway, and to explore its possible mechanism.</p><p><b>METHODS</b>Thirty SD rats were randomly divided into the normal group, the model group, and the BHR group, 10 in each group. Rats in the model group and the BHR group were administered with 250 mg/kg adenine suspension by gastroagavage and fed with 1.8% high phosphorus forage, once per day in the first 4 weeks, and then gastric administration of adenine suspension was changed to once per two days in the following 5-8 weeks. Rats in the BHR group were administered with BHR at the daily dose of 55 g/kg by gastrogavage in the first 8 weeks, once per day. Equal volume of normal saline was given to rats in the normal group by gastrogavage for 8 weeks. Histological changes in renal tissue and aorta VC were observed by HE staining and alizarin red staining respectively. Levels of calcium (Ca), phosphorus (P), serum creatinine (Cr), blood urea nitrogen (BUN), and intact parathyroid hormone (iPTH) in serum were detected. Protein expression levels of bone morphogenetic protein (BMP-2), Runt related transcription factor (Runx2) , and Osterix were detected by Western blot.</p><p><b>RESULTS</b>HE staining showed that compared with the normal group, disordered glomerular structure, tubular ectasia and dropsy, intracavitary inflammatory cell infiltration, dark brown crystal deposition in kidney tubules, renal interstitial fibrosis, and decreased number of renal blood vessels in the model group. Compared with the model group, normal glomerular numbers increased more, reduced degree of tubular ectasia, decreased number of inflammatory cells, and reduced adenine crystal deposition in the BHR group. Alizarin red staining showed that compared with the normal group, calcified nodes could be found in the model group, with extensive deposition of red particle in aorta. Compared with the model group, calcified nodes were reduced in the BHR group. Compared with normal group, serum levels of P, SCr, BUN, and iPTH significantly increased, serum Ca level significantly decreased, protein expressions of BMP-2, Runx2, Osterix also increased in the model group (P < 0.05, P < 0.01). Compared with the model group, serum levels of P, SCr, BUN, and iPTH levels significantly decreased, serum Ca level significantly increased, protein expressions of BMP-2, Runx2, Osterix also decreased in the BHD group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>BHD could improve renal function, Ca-P metabolism, and renal histological changes in CHF rats, down-regulate the expression level of BMP-2/Runx2/Osterix signal pathway in vascular calcification of CRF, which might be one of the mechanisms for inhibiting VC in CHF.</p>

Reciprocal effects of Guizhi decoction to the Guizhi decoction syndrome by toll-like receptor mRNA expression and cytokines secretion / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the pathological mechanisms of Guizhi Decoction () syndrome and the therapeutic molecular mechanisms of the Guizhi Decoction, Mahuang Decoction (), Sangju Decoction ( ) and Yinqiao Powder (), as well as the potentially biological basis that Guizhi Decoction is most effective only for the patients with Guizhi Decoction syndrome in clinical practice.</p><p><b>METHODS</b>We first got serum samples from the patients suffering from both upper respiratory tract infection and Guizhi Decoction syndrome identified by the doctors of Chinese medicine (CM) in the clinic. Four formulas with therapeutic actions of pungent warmth or pungent coolness for superficial syndromes were chosen and four kinds of rat serum samples each containing one of the above-mentioned herbal formulas were collected, then the effects of Guizhi Decoction syndromes' patient serum as well as the effects of sera containing the formulas after being stimulated by the patient serum samples on both the mRNA expression of certain toll-like receptor (TLR) subtypes and the release of some inflammatory cytokines in RAW264.7 cells were tested and analyzed in vitro.</p><p><b>RESULTS</b>The expression of TLR-3, TLR-4 and TLR-9 mRNA among the 9 tested TLR subforms were up-regulated in the macrophages stimulated by the sera from untreated upper respiratory infection patients with the Guizhi Decoction syndrome (symptomcomplex). The products such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-β from stimulated macrophages through TLR signaling pathways were also increased correspondingly. Interestingly, the changes induced by the Guizhi Decoction syndrome patients' sera were masked significantly after the macrophages were incubated with the sera from donors treated with Guizhi Decoction. Similarly, the three other exterior-releasing formulas were all effective in reversing the up-regulated changes of certain TLR subforms to different degrees, but both the number of targeted TLRs and efficacy of them seemed to be inferior to that of Guizhi Decoction.</p><p><b>CONCLUSION</b>Evidence from these experiments might contribute to the scientific explanation of both the pharmacological mechanisms of Guizhi Decoction and also the CM theory that Guizhi Decoction is specifically prescribed for the treatment of Guizhi Decoction syndrome (The gearing formula to the symptom-complex).</p>

Effect of L-arginine on pulmonary surfactant and alveolar macrophages in rats with pulmonary injury induced by lipopolysaccharide / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of L-Arginine (L-Arg) on pulmonary surfactant (PS) expression and alveolar macrophage (AM) in rats with pulmonary injury induced by lipopolysaccharide (LPS).</p><p><b>METHODS</b>Model of acute lung injury (ALI) was made by injection (iv) with LPS 5 mg/kg in rats. Fourty-eight male SD rats were randomly divided into 3 groups(n = 16): control, model (LPS) and L-Arg groups. L-Arg (500 mg/kg ip ,L-Arg group) or saline (control and LPS group) was administrated at 3 h or 6 h after LPS injection respectively for 3 h. The expression of surfactant protein A (SP-A) mRNA in the lung tissue was detected by ISH. The total protein (TP) in the bronchoalveolar lavage fluid (BALF) was detected. Rat AM were isolated from the bronchial alveolar lavage fluid of SD rats and harvested by selective plating technique. LPS and L-Arg were added to the culture medium. The concentration of nitric oxide (NO),the activity of lactate dehydrogenase (LDH), the contents of tumor necrosis factor alpha (TNF-alpha) and interleukin- 6 (IL-6) in the culture supernatants were respectively measured.</p><p><b>RESULTS</b>Compared with the control group, the expression of SP-A mRNA was significantly decreased, the TP concentration was significantly increased in LPS group. Compared with LPS group at the same time points, treatment with L-Arg at 3 h after LPS, the expression of SP-A mRNA in lung tissue was increased markedly, whereas TP concentration was decreased significantly. In cultured rat AM, LDH activity, NO, TNF-alpha and IL-6 contents in culture medium were significantly increased in LPS group to compared with those of control group. LDH activity, TNF-alpha and IL-6 contents were decreased in L-Arg group compared with those of LPS group.</p><p><b>CONCLUSION</b>L-Arg can protect the lung against LPS-induced pulmonary injury by up-regulating the expression of PS and inhibiting inflammatory transmitters from AM.</p>

Efficacy and survival status of retuximab-NCE regimen treatment in patients with relapsed or refractory B cell non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to analyze the efficacy and toxicity of RNCE regimen in the treatment of relapsed or refractory B cell non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>From January 2000 to December 2005, 46 patients with relapsed or refractory B cell NHL were treated by RNCE regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analyzed retrospectively.</p><p><b>RESULTS</b>A total of 46 patients were eligible. The complete response rate of second-line therapy was 52.17% (24/46), and the overall response rate was 82.61% (38/46). The median follow-up duration in this series was 69 months (range:6 to 102 months). The overall 1, 3, 5-year survival rate was 74.8%, 48.3%, 40.1%, respectively, with a median survival time of 30.2 months (5 to 65 months), and median progression free survival time of 10.9 months (2 to 31 months). The major toxicities were myelosuppression, GI toxicity, fatigue, fever and alopecia.</p><p><b>CONCLUSION</b>Our data show that RNCE regimen treatment is effective and well tolerated in patients with relapsed or refractory B cell non-Hodgkin's lymphoma.</p>

Nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The clinical data of 37 NSCLC patients who received nimotuzumab in combination with chemotherapy in Tianjin Medical University Cancer Hospital from January 2009 to October 2010 were retrospectively reviewed. Of the thirty-seven patients, 12 patients were in stage III B, 25 patients in stage IV. Twenty-four patients recived platinum-based chemotherapy in combination with nimotuzumab, 13 patients recived nonplatinum-based chemotherapy in combination with nimotuzumab. Ten patients received nimotuzumab in combination with chemotherapy as first-line regimen, 23 patients as second-line regimen, 4 patients as third-line regimen.</p><p><b>RESULTS</b>Of the 37 advanced NSCLC patients who received nimotuzumab in combination with chemotherapy, the total number of chemotherapy were 137 cycles, the mean number was 3.7 cycles. One patient had complete remission (CR), 9 patients had partial remission (PR), 16 cases had stable disease (SD), and 11 patients had progressive disease (PD). The response rate (RR) was 27% and clinical benefit rate (CBR) was 70.3%. The main side effects were bone marrow suppression and gastrointestinal reactions. Grade I acneiform rash was found in one patient.</p><p><b>CONCLUSION</b>The regimen of nimotuzumab in combination with chemotherapy can improve the response rate and was well tolerated in patients with advanced non-small cell lung cancer.</p>

Expression of Cdc7 and mcm2 as a marker for proliferation and prognosis in diffuse large B cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to assess the expression of cell division cycle 7 (Cdc7) kinase and minichromosome maintenance protein 2 (MCM2) in diffuse large B cell lymphoma (DLBCL) and explore their relationship with prognosis of DLBCL patients.</p><p><b>METHODS</b>Clinical data of 60 DLBCL patients treated in our hospital from 2008.1 to 2010.1 were collected. The expression levels of Cdc7 and MCM2 in peripheral blood and bone marrow were determined by real-time PCR. A statistical analysis was carried out to evaluate their association with prognosis in DLBCL patients.</p><p><b>RESULTS</b>The 2-year survival rate of patients with high expression of peripheral blood Cdc7 was 38.3% and those with low expression 65.4% (P = 0.001). The 2-year survival rate of patients with high expression of bone marrow Cdc7 was 37.2% and those with low expression was 75.5% (P = 0.032). The 2-year survival rate of patients with high expression of MCM2 in peripheral blood was 44.0% and those with low expression was 68.2% (P = 0.025). The 2-year survival rate of patients with high expression of MCM2 in bone marrow was 39.0% and those with low expression was 63.4% (P = 0.007). A poor disease specific survival was observed in DLBCL patients with high level expression of Cdc7 and MCM2.</p><p><b>CONCLUSIONS</b>Cdc7 and MCM2 expression can be used to assess tumor proliferation and may be useful as an additional marker in combination with conventional markers in prediction of the outcome of DLBCL patients. Moreover, the Cdc7 and MCM2 signal pathway might be useful as a new approach in the treatment of refractory DLBCL lymphoma patients.</p>

Effects of hydrogen sulfide on pulmonary surfactant in rats with acute lung injury induced by lipopolysccharide / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the changes of pulmonary surfactant (PS) in rats with acute lung injury(ALI) induced by lipopolysaccharide (LPS) and to explore the effects of hydrogen sulfide (H2S) on PS.</p><p><b>METHODS</b>Fourty- eight male rats were randomly divided into six groups (n = 8). They were control group, LPS group, LPS+ NaHS low, middle, high dose groups and LPS+ PPG group. Saline was administrated in Control group. LPS was administrated in LPS group. In LPS + NaHS low, middle, high dose groups or LPS + PPG group, sodium hydrosulfide (NaHS) of different doses or DL-propargylglycine (PPG) were respectively administrated when the rats were administrated of LPS after 3 hours. All the rats were killed at 6 hours after administration of Saline or LPS. The morphological changes of alveolar epithelial type II cells (AEC-II) were respectively observed by transmission electron microscopes. The content of H2S in plasma and activity of cystathionine-gamma-lyase (CSE) in lung tissues were respectively detected. The contents of total protein (TP) and total phospholipids (TPL) in bronchoalveolar lavage fluid (BLAF) were respectively measured. The pulmonary surfactant protein A (SP-A), surfactant protein B (SP-B) and surfactant protein-C (SP-C) mRNA expressions in lung tissues were analysed.</p><p><b>RESULTS</b>(1) Compared with control group, the content of H2S in plasma, activity of CSE, content of TPL, and SP-A, SP-B and SP-C mRNA expressions were respectively decreased in LPS group (P < 0.05 or P < 0.01). But the content of TP was increased in LPS group (P < 0.01); (2) Compared with LPS group, the content of H2S, activity of CSE and SP-A mRNA expression were significantly increased in LPS + NaHS low, middle and high dose groups (P < 0.05). The SP-B mRNA expression and content of TPL were significantly increased in LPS + NaHS Middle and High dose groups (P < 0.05). The content of TP was decreased in LPS + NaHS High dose group (P < 0.05). The SP-C mRNA expression was not altered in LPS+ NaHS low, middle and high dose groups (P > 0.05); (3) Compared with LPS group, the content of H2S, activity of CSE, content of TPL, and SP-A, SP-B and SP-C mRNA expressions were respectively decreased, but content of TP was increased in LPS + PPG group (P < 0.05).</p><p><b>CONCUSION</b>The decrease of PS is the important physiopathologic process of ALI induced by LPS. Exogenously applied H2S could attenuate the process of ALI that possibly because H2S could adjust the compose and secretion of PS.</p>

Effects of hydrogen sulfide on myocardial mitochondrial injury during acute myocardial ischemia in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of hydrogen sulfide (H2S) on mitochondrial function in acute myocardial ischemia in rats.</p><p><b>METHODS</b>Acute myocardial ischemia models were established by ligating the left anterior descending coronary artery (LADC) of rats. Fourty-eight male SD rats were randomly divided into 6 groups (n = 8): sham operation group, ischemia group, ischemia + sodium hydrosulfide (NaHS) low, middle and high dose groups and ischemia + DL-proparglycine(PPG) group. The ultrastructures of myocardial mitochondria were observed with electron microscope. The content of H2S in plasma and the activity of cystathionine-gamma-lyase (CSE) in myocardial tissue of rats were respectively detected. The swelling and activity of myocardial mitochondria were determined. The activities of ATPase, GSH-Px, SOD and the content of malondial-dehyde (MDA) in myocardial mitochondria of rats were also measured.</p><p><b>RESULTS</b>Compared with those of the sham operation group, the content of H2S in plasma, the activity of CSE in myocardial tissue and the activity of myocardium mitochondria were significantly decreased. The activities of ATPase, SOD, GSH-Px in myocardial mitochondria were significantly decreased, The content of malondial dehyde(MDA) in myocardial mitochondria and the swelling of mitochondria were distinctly increased in the ischemia group (P < 0.01). Compared with those of the ischemia group, the content of H2S in plasma and the activity of CSE in myocardial tissue were increased, and the activities of mitochondria, ATPase, SOD, and GSH-Px in myocardial mitochondria were significantly increased in ischemia + NaHS low, middle and high-dose groups; the swelling of mitochondria and the content of MDA in myocardial mitochondria were significantly decreased in ischemia + NaHS middle and high-dose groups (P < 0.05 or P < 0.01). The administration of PPG could partially reduce the myocardial protection of hydrogen sulfide (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>It could be concluded that the administration of hydrogen sulfide could enhance the activities of mitochondrial ATPase, SOD, GSH-Px, decrease the level of mitochondrial lipid peroxidation, and play a protective effect against acute myocardial ischemia.</p>

Capecitabine combined with weekly docetaxel in Chinese patients > 65 years with anthracycline-resistant metastatic breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients.</p><p><b>METHODS</b>MBC patients aged > 65 years pretreated with 1 - 5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m(2) twice daily, days 1 - 14, plus docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles (median 4, range 2 - 8) and were evaluable for efficacy.</p><p><b>RESULTS</b>The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia (12%), alopecia (7%), grade 3 nausea and vomiting (2%) and grade 3 nail toxicity (2%).</p><p><b>CONCLUSIONS</b>Capecitabine 825 mg/m(2) twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women > 65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.</p>

Effects of propofol on the activation of nuclear factor-kappaB and cardiomyocytes apoptosis during myocardial ischemia/reperfusion injury in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the molecular mechanisms of propofol in myocardial protection, the activation of nuclear factor-kappaB (NF-kappaB) and the apoptosis of cardiomyocytes were examined.</p><p><b>METHODS</b>Rat myocardium I/R injury was induced by occluding the left main coronary artery for 30 min and reperfusion for 2 h. Propofol was intravenously given 15 min before ischemia. The pathological changes of myocardium were examined by light and electron microscopy. The translocation of NF-kappaB in the cardiomyocytes was detected by immunohistochemistry. The expressions of NF-kappaB and caspase-3 were determined by Western blot. The incidence of cardiomyocyte apoptosis was detected by the TdT-mediated dUTP nick end labeling (TUNEL) staining.</p><p><b>RESULTS</b>The pathological changes of myocardium induced by I/R injury, such as cardiomyocyte swelling, myofibrillar lysis, disorganized, mitochondrial membrane swelling, and the cristae disruption were significantly alleviated by 6, 12 mg/(kg x h) propofol. Compared with the sham control group, NF-kappaB significantly translocated from the cytoplasm into the nucleus in the I/R group. And the expression of NF-kappaB in the nuclei markedly increased (P < 0.05). In addition, the expression of caspase-3 and the apoptosis index were significantly increased in the I/R group (P < 0.05). Compared with those of I/R group, administration of propofol at 6, 12 mg/(kg x h) significantly inhibited the NF-kappaB translocation into nucleus and attenuated the expression of NF-kappaB in the nuclei (P < 0.05), decreased the expression of caspase-3 in myocardium (P < 0.05) and inhibited the occurrence of cardiomyocytes apoptosis.</p><p><b>CONCLUSION</b>Propofol could inhibit NF-kappaB activation and down-regulate the expression of caspase-3 and as a result suppress cardiomyocytes apoptotic initiation during the myocardium I/R injury, which may be one of the molecular mechanisms of its cardioprotection.</p>

Effect of L-Arg on inflammatory reaction and nuclear factor-kappa B signal pathway in the acute lung injury in rats induced by lipopolysaccaride / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects and the mechanisms of L-Arginine (L-Arg), the critical substrate for nitric oxide (NO) production, on pulmonary inflammatory cytokine expression and Nuclear Factor-kappa B signal pathway in a model of lipopolysaccharide (LPS) induced acute lung injury (ALI).</p><p><b>METHODS</b>Model of ALI was induced by injection (iv) with LPS 5 mg/kg in male SD rats. L-Arg (500 mg/kg ip) was administrated at 3 h or 6 h after LPS injection respectively for 3 h, and the rats were killed at 6 h or 9 h after saline (control) or LPS injection. The expression and the translocation of NF-kappa B P65 in lung tissue were detected with immunohistochemisty (IHC). The gene expression of intercellular adhesion molecule-1 (ICAM-1) was examined by RT-PCR. The concentrations of TNF-alpha and IL-6 in lung tissue were respectively evaluated by radioimmunoassay. The pathological changes of lung tissue were observed by light microscope.</p><p><b>RESULTS</b>Compared with LPS group, treatment with L-Arg at 3 h after LPS significantly decreased the expression of NF-kappa B protein. The concentrations of TNF-alpha and IL-6 in lung tissue were significantly decreased and the lung damage was inproved respectively compared with that of the LPS (3 h + 3 h) group. The lung damage was alleviated in L-Arg (3 h + 3 h) group.</p><p><b>CONCLUSION</b>Relatively early administration of L-Arg might protect lung from LPS-induced injury by inhibiting NF-kappa B activation and subsequently inhibiting the NF-kappa B-mediated release of inflammatory factors.</p>

Effects of propofol on cardiomyocytes apoptosis and its mechanism after ischemia/reperfusion injury in isolated rat hearts / 中国应用生理学杂志

<p><b>AIM</b>To investigate the protective effect of propofol on ischemia/reperfusion (I/R) injury in isolated rat hearts and clarify the possible molecular mechanism from oxidative stress and the apoptosis initiated by mitochondria pathway.</p><p><b>METHODS</b>The Langendorff model of ischemia/reperfusion was used. Forty isolated perfused rat hearts were randomly divided into control, I/R, propofol 15, 30, 60 micromol x L(-1) groups. Hearts were suffered globally ischemia for 25 min and 30 min with reperfusion. The cardiac function indexes such as the left ventricular developed pressure (LVDP), the left ventricular end diastolic pressure (LVDEP), heart rate (HR), coronary arterial flow (CF) were recorded at the time of equilibration, before ischemia, the end of reperfusion respectively. The lactate dehydrogenase (LDH), creatine kinase (CK) activities in the flow were measured. The swelling and activity of mitochondria, the activity of manganese superoxide dismutase (Mn-SOD) and content of malondialdehyde (MDA) in myocardium mitochondria were also determined. The incidence of cardiomyocyte of apoptosis and the expression of Bcl-2 and Bax were evaluated by Flow Cytometry (FCM). The expression of caspase-3, 8, 9 was detected by immunohistochemistry.</p><p><b>RESULTS</b>Compared with I/R group, administration of propofol at the concentration of 30 and 60 micromol x L(-1) markedly ameliorated the cardiac function in CF, LVDP and LVDEP (P < 0.05), distinctly reduced the activities of the LDH and CK in the flow (P < 0.05) and the mitochondrial swelling, the content of MDA in myocardium mitochondria (P < 0.05), and significantly enhanced the activity of Mn-SOD in myocardium mitochondria (P < 0.05). The apoptotic index in propofol 30, 60 micromol x L(-1) group was markedly lower than that of I/R group. The expression of Bcl-2 protein in 30, 60 micromol x L(-1) propofol was higher than that of I/R group (P < 0.05). The expressions of Bax, caspase-9, 3 protein in 30, 60 micromol x L(-1) propofol were obviously lower than those of I/R group( P < 0.05). There was no significant difference in expression of caspase-8 between propofol administrated groups and I/R group.</p><p><b>CONCLUSION</b>It could be concluded that propofol administrated before ischemia and during reperfusion has cardioprotective effects on ischemia/reperfusion injury in the isolated rat heart. The effect is associated with diminishing oxidative stress, protecting mitochondria from peroxidative injury, thus interfering with the mitochondria-dependent apoptotic pathway might be one of the major mechanisms of its cardioprotection.</p>

DNCE regimen for treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of DNCE [DXM, navelbine (NVB), DDP and Vp-16] regimen and DICE [dexamethasone (DXM), ifosfamide (IFO), cisplatin (DDP) and etoposide (Vp-16)] regimen in the treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma (NHL).</p><p><b>METHODS</b>A total of 69 patients with histopathologically proved advanced aggressive and highly aggressive NHL were randomized into trial group (32 patients treated with DNCE regimen) and control group (37 patients treated with DICE regimen). The control group was given DICE regimen: DXM 20 mg, iv d1 approximately d4; IFO 1 g/m2), iv d1 approximately d4; Mesna 400 mg, iv q8h, d1 approximately d4; DDP 25 mg/m2, iv d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28 days. The trial group was given DNCE regimen: DXM 20 mg, iv d1 approximately d4; NVB 25 mg/m2, iv d1 and d5; DDP 25 mg/m2, iv d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28 days. Each patient completed at least 2 cycles of treatment.</p><p><b>RESULTS</b>A better efficacy was shown in the complete response rate, partial response rate, and total response rate between DNCE and DICE groups (18.8% vs. 10.8%, 37.5% vs. 35.1%, and 56.3% vs. 45.9%, respectively), but the differences were statistically non-significant (P > 0.05). The 1-, 3-, and 5-year survival rates were not significantly increased in DNCE group compared with that in DICE group (86.5% vs. 87.5%, 58.3% vs. 63.2%, 42.9% vs.38.5%, respectively, P > 0.05). The major side effects were leucopenia, thrombocytopenia, and nausea in both groups. The bone marrow depression in DNCE group was significantly slighter than that in the DICE group (P < 0.05).</p><p><b>CONCLUSION</b>The efficacy of DNCE regimen is as good as DICE regimen, and the bone marrow toxicity is less severe in DNCE group than that in DICE regimen. Therefore, the DNCE regimen is an effective second-line salvage regimen for the treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma.</p>

Effects of Fufang Xiaojingtong capsules on uterine activity of animals / 中国中药杂志

<p><b>OBJECTIVE</b>To observe effects of Fufang Xiaojingtong capsules (FXJTC) on activities of the uterine smooth muscle of the rat in vitro and the uterus of the rabbit in vivo.</p><p><b>METHOD</b>The isolated rat uterine smooth muscle strips were mounted in a Magnus bath containing Locke's solution with a final content of 12.48, 6.24 or 3.12 mg x mL(-1) of FXJTC at 37 degrees C; and 2.0, 1.0 and 0.5 g x kg(-1) of FXJTC and 2.0 g x kg(-1) of Tianqi Tongjing capsules were respectively given to the rabbits through the duodenum, respectively. Their effects on frequency, amplitude and activity of contraction of the rat uterus in vitro and the rabbit uterus in vivo were investigated.</p><p><b>RESULT</b>FXJTC could significantly inhibit the frequency, amplitude and activity of contraction of the normal rat uterus in vitro and decrease the oxytocin-induced increase of contraction of the rabbit uterus in vitro; lowered the frequency, amplitude and activity of contraction of the rabbit uterus in vivo and inhibit the oxytocin-induced the strengthening of contraction of the rabbit uterus in vivo.</p><p><b>CONCLUSION</b>Fufang Xiaojingtong capsules maybe used for treatment of dysmenorrhea induced by spasm of uterine smooth muscle.</p>

Effect of Shensu Yin on the expression of toll-like receptors and the downstream signaling components on RAW 264.7 cells / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the influences of Shensu Yin to RAW 264.7 on the expression of TLR3, TLR4 and the factors of the downstream in RAW 264. 7 cells.</p><p><b>METHOD</b>RAW 264.7 cell line was stimulated with Lipopolysaccharide and POLY I: C, respectively, and treated with the drug serum of Shensuyin simultaneously. 24 hours later, collected the supernatant and measured the inflammatory factors TNF-alpha and IFN-beta, extracted mRNA and measured the expression of TLR3, TLR4 and other correlated indexes of the downstream, analyzed and evaluated Shensu Yin's substance basis of pharmacodynamic actions.</p><p><b>RESULT</b>Shensu Yin drug serum depressed the expression of TLR4, MyD88, TRAF-6, TRAM and TRIF mRNA, as a result, it decreased the amount of TNF-alpha and IFN-beta.</p><p><b>CONCLUSION</b>Depressing the expression of TLR3, MyD88, TRAM and TRIF mRNA may be the elementary basis of Shensu Yin to play heat-clearing and detoxicating effect.</p>

Effect of N(G)-nitro-L-arginine on inflammatory factor and neuronal apoptosis after focal cerebral ischemic injury in rats / 中国应用生理学杂志

<p><b>AIM</b>To evaluate the effect of NG-nitro-L-arginine (L-NA) on inflammatory factor and neuronal apoptosis after focal cerebral ischemic injury in rats and the possible mechanism of protective effect of L-NA against cerebral ischemic injury.</p><p><b>METHODS</b>Thirty male SD rats weighing 250-280 g were randomly divided into three groups (n=10): (1) Sham operated group (SH), (2) Ischemic group (IS), (3) L-NA group. In L-NA group L-NA 20 mg/kg was given intraperitoneally twice a day for 3 consecutive days. In IS group normal saline was given instead of L-NA. Focal cerebral ischemia was produced by middle cerebral artery occlusion (MCAO) for 12 h. A nylon thread with rounded tip which was inserted into left internal carotid artery cranially until resistance was felt. The distance from bifurcation of common carotid artery to the tip of the thread was about 18-19 mm. Focal cerebral ischemia was confirmed by left Horner's syndrome and right side hemiplegia. In SH group the carotid artery was exposed but no thread was inserted. The expression of TNF-alpha was determined by immunochemistry and the content of IL-1beta was measured by radio immunity. The Bcl-2 and Bax protein expression were detected by flow cytometry.</p><p><b>RESULTS</b>The expression of TNF-alpha and the content of IL-1 beta were markedly increased after MCAO. Significantly increased DNA fragmentation indication of apoptosis was detected after MCAO. The expression of TNF-alpha and the content of IL-1 beta was significantly lower in L-NA group than in IS group. The percentage of apoptosis cells and expression of Bax protein were markedly lower in L-NA group than in IS group but still significantly higher than in SH group. The expression of Bcl-2 protein was markedly higher in L-NA group than in IS group. There was no significant difference in the expression of Bcl-2 protein between IS and SH group.</p><p><b>CONCLUSION</b>L-NA could inhibit the increase in the expression of TNF-alpha and the content of IL-1beta, and protect neurons from apoptosis induced by focal cerebral ischemia through increasing the Bcl-2 protein expression and inhibiting the Bax protein expression.</p>