Activation of PXR causes drug interactions with Paxlovid in transgenic mice

Paxlovid is a nirmatrelvir (NMV) and ritonavir (RTV) co-packaged medication used for the treatment of coronavirus disease 2019 (COVID-19). The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster. Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid. By using recombinant human cytochrome P450s (CYPs), we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism. The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice, which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV. Pregnane X receptor (PXR) is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression. We next explored the impact of drug- and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5. We found that PXR activation increased CYP3A4/5 expression, accelerated NMV metabolism, and reduced the systemic exposure of NMV. In summary, our work demonstrated that PXR activation can cause drug interactions with Paxlovid, suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.

Skin Ultrastructure and the Changes of HIF-2α, H-FABP Expression in the Myocardium of Electric Shock Death Rats / 法医学杂志

Objective To observe the skin ultrastructure change of electric shock death rats and to test the expression changes of hypoxia-inducible factor-2α （HIF-2α） and heart type-fatty acid-binding protein （H-FABP） of myocardial cells, in order to provide basis for forensic identification of electric shock death. Methods The electric shock model of rats was established. The 72 rats were randomly divided into control group, electric shock death group and postmortem electric shock group. Each group was divided into three subgroups, immediate （0 min）, 30 min and 60 min after death. The skin changes of rats were observed by HE staining, the changes of skin ultrastructure were observed by scanning electron microscopy, and the expression of HIF-2α and H-FABP in rats myocardium was tested by immunohistochemical staining. Results The skin in the electric shock death group and postmortem electric shock group had no significant difference through the naked eye or by HE staining. Under the scanning electron microscope, a large number of cellular debris, cells with unclear boundaries, withered cracks, circular or elliptical holes scattered on the cell surface and irregular edges were observed. A large number of spherical foreign body particles were observed. Compared with the control group, the expression of HIF-2α in all electric shock death subgroups increased, reaching the peak immediately after death. In the postmortem electric shock group, HIF-2α expression only increased immediately after death, but was lower than that of electric shock death group （P<0.05）. Compared with the control group, the expression of H-FABP in all subgroups of electric shock death group and postmortem electric shock group significantly decreased. The expression of H-FABP in all subgroups of electric shock death group was lower than that of the postmortem electric shock group （P<0.05）. Conclusion Electric shock can increase HIF-2α expression and decrease H-FABP expression in the myocardium, which may be of forensic significance for the determination of electric shock death and identification of antemortem and postmortem electric shock.

Clinical Significance of Pretransplant Serum Ferritin Level in Patients with Prolonged Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between pretransplant serum ferritin (SF) level and prolonged or prolonged isolated thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 35 patients with PT after allo-HSCT were retrospectively analyzed, and 35 patients were matched according to age and sex as a controls from 424 allo-HSCT patients with normal platelet count. The serum ferritin level before the transplantation was analyzed. The potential risk factors were analyzed by chi-square test and Fisher's exact test as well as univariate and multivariate logistic regression. The survival curve was estimated by the Kaplan-Meier model to explore its clinical significance. In addition, ROC curve was used to verify the predictive power of SF.@*RESULTS@#Compared with control group, the SF level in the PT group before transplantation significantly increased (P=0.001). Multivariate analysis results showed that SF level before transplantation was a risk factor for prolonged thrombocytopenia after HSCT, and patients with SF≥1000 ng / ml showed a higher risk of death (P=0.014). ROC curve showed that SF level could be used as a predictor of prolonged thrombocytopenia after allo-HSCT.@*CONCLUSION@#The SF level before allo-HSCT relates with occurrence and prognosis of PT in patients after allo-HSCT. Detection of SF level can provide guidance for the intervention of prolonged thrombocytopenia after HSCT.

Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation in Treatment of Intermediate Risk Acute Myeloid Leukemia with Negative for FLT3-ITD, NPM1 or Biallelic CEBPA Mutation / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and post-remission chemotherapy (PR-CT) in treatment of intermediate risk acute myeloid leukemia with negative for FLT3-ITD, NPM1 or biallelic CEBPA mutation.@*METHODS@#The clinical data of patients with intermediate risk NPM1/non-CEBPA/FLT3-ITD AML from October 2009 to May 2016 were retrospectively analyzed.@*RESULTS@#The overall survival rate of the patients treated with PR-CT, MSD-HSCT or hi-HSCT was 63.7%, 71.7%, 75.5%, respectively (P＜0.05); the disease-free survival (DFS) rate was 52.8%, 67.1%, 71.3% respectively (P＜0.001); the cumulative incidence of relapse was 24.7%, 16.9%, 14.4% respectively (P＜0.05); the non-relapse mortality was 26.2%, 17.3%, 14.4% reapectively (P＞0.05). The analysis of transplantation, related adverse events showed that II-IV grade of aGVHD in the MSD-HSCT group and hi-HSCT group was 48.9% and 45.6% respectively (P＞0.05); the extensive cGVHD event was 21.6% and 8.8% (P＜0.05) respectively.@*CONCLUSION@#The efficiency of hi-HSCT and MSD-HSCT is superior to that of PR-CT for treatment of patients with intermediate risk NPM1/non-CEBPA/FLT3-ITD AML after CR1, there is no statistically significant difference in the efficiency of consolidatorg treatment and the transplantation-related mortality between hi-HSCT and MSD-HSCT.

Correlation between subconcave choroid thickness and family history of myopia in children with myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the subfoveal choroidal thickness(SFCT)and its influencing factors in children with different degree of myopia.<p>METHODS: This is prospective cohort study. Eighty-nine eyes of 45 school-age children aged 5-14 years old were studied, and according to the equivalent sphericity(SE)into different refractive groups. Mild, moderate and high myopia groups had 27, 42 and 20 eyes respectively, apply the enhanced depth scanning mode(EDI-OCT)of an optical coherence tomography(OCT)scanner to measure SFCT to compare choroid thickness differences among myopia groups, to find out the change rule of SFCT between myopia groups, and Pearson correlation analysis was used to analyze the related influencing factors.<p>RESULTS:SFCT of mild myopia, moderate myopia and high myopia respectively were(253.22±43.56)μm,(223.19±54.93)μm,(185.90±50.99)μm, SFCT differences between different refractive groups were statistically significant(<i>P</i><0.05), Pearson correlation analysis found that there was a significant correlation between SFCT and SE and axial length(<i>r</i>=0.430, -0.499, 0.425, all <i>P</i><0.001); slightly related to K1 and K2, and the correlation of AL, retinal nerve fiber layer(RNFL)thickness were better than that of SE. There were statistically significant differences in family history of myopia among the myopic groups(χ2=7.44, <i>P</i><0.05). <p>CONCLUSION: The degree of myopia in children was deepened and SFCT became thinner. The degree of myopia in children is related to the family history of myopia.

Estimation on Formation Time of Thrombus / 法医学杂志

OBJECTIVES@#To observe the changes of the formation time of venous thrombus in rats, and to provide new ideas and methods for the estimation on thrombus formation time of the forensic cases died from thrombosis.@*METHODS@#Totally 80 rats were randomly divided into 10 groups （0 h, 3 h, 6 h, 12 h, 1 d, 3 d, 1 week, 2 weeks, 3 weeks and 4 weeks after operation）. A vein thrombosis model was established by the "narrow" method. The processes of thrombosis, organization, recanalization and the features of change on hemosiderin and calcium salt were observed by HE stain, Perls stain and Von Kossa stain. The expression changes of CD61, α-SMA and CD34 were observed by immunohistochemical staining technique.@*RESULTS@#Platelets adhered to the exposed blood vessel intima 3 h after operation, and platelet trabeculae were formed by the repeated accumulation of platelets 1 d after operation. The thrombus organization formed through the fibroblasts from vessel wall that grew into the interior of the thrombus 3 d after operation. Endothelial cells covered the surface of thrombus and then the new blood vessels were reformed, and the vessels were reconstructed. The expression of CD61 upregulated at the stages of the thrombus formation （3 h） and thrombus reformation （4 weeks）, and reached the peak 1 d after thrombus formation. The release of hemosiderin and the initial expression of α-SMA were detected 3 d later. Calcium deposit and expression of CD34 were observed 1 week later.@*CONCLUSIONS@#The hemosiderin, calcium salt, CD61, α-SMA and CD34 show time-dependent changing characteristics, which is expected to provide a reference for the estimation on thrombus formation time of the forensic cases died from thrombosis.

Study on role of TIGIT signal in Th1/Th2 balance in Schistosoma japonicum-infected mice / 中国血吸虫病防治杂志

Objective To investigate the role of TIGIT signal in Th1/Th2 balance in the process of Schistosoma japonicum in-fection.Methods Male C57BL/6 mice were infected with cercariae of S.japonicum,and normal uninfected mice served as the controls.The percentages of TIGIT+cells,Ki67+CD3+CD4+TIGIT+cells,Ki67+CD3+CD4+TIGIT-cells,IFN-γ+CD3+CD4+TIGIT+cells,IFN-γ+CD3+CD4+TIGIT- cells,IL-4+CD3+CD4+TIGIT+cells and IL-4+CD3+CD4+TIGIT- cells were evaluated in mouse spleen by flow cytometry.Results The proportion of TIGIT+CD4+T cells was higher in the spleen of S.japonicum-infected mice than in the normal uninfected mice(29.30%±0.70% vs.3.09%±0.50%;t=8.834,P<0.01).However,no significant differ-ence in the percentages of TIGIT+CD8+T cells between the infection group and normal controls(3.61% ± 0.26% vs. 3.58% ± 0.16%;t=0.108,P>0.05),and no significant difference was detected in the percentages of TIGIT+cells in non-T cells be-tween the infection group and controls(1.86%±0.19% vs.1.37%±0.17%;t=1.931,P>0.05).In addition,the proportion of Ki67 in the TIGIT+cells was higher than that in the TIGIT-cells(17.03%±0.64% vs.6.59%±0.37%;t=14.09,P<0.01).The Th2/Th1 ratio was higher in the TIGIT+CD4+T cells than in the TIGIT-CD4+T cells(39.28%±3.75% vs.11.79%±1.64%;t=6.721,P<0.01).Conclusion The TIGIT signaling may be involved in the development of Th2 responses in the mice infected with S.japonicum.

Effects of glycolytic pathway on generation of regulatory T cells during Schistosoma japonicum infection / 中国血吸虫病防治杂志

Objective To assess the influence of glycolytic pathway on the proportion and numbers of regulatory T cells dur-ing Schistosoma japonicum infection. Methods A S. japonicum-infected mouse model was established,and C57/BL6 male mice infected with S.japonicum were subjected to intraperitoneal injections of with the glycolytic inhibitor 2-Deoxy-D-glucose (2DG)or PBS for 6 times,and then the cells from spleen or mesenteric lymph nodes(LNs)were isolated and analyzed by flow cytometry(FCM)to detect the percentage of Glut1+CD4+T cells and Treg cells. Results The proportions of Glut1+CD4+T cells in the spleen(43.58%±2.50% vs.21.15%±0.96%;t=8.834,P<0.01)and mesenteric LNs(38.97%±1.97% vs.28.40%± 2.11%;t=3.662,P<0.05)were higher in the normal mice than those in the infected mice,and the percentages of Treg cells in the spleen(6.83% ± 0.21% vs. 13.30% ± 0.35%;t = 15.65,P < 0.01)and LNs(8.26% ± 0.15% vs. 14.37% ± 0.44%;t =13.14,P<0.01)were lower in the normal mice than those in the infected mice.In addition,the proportions of Treg cells in the spleen(15.50%±0.76% vs.13.07%±0.15%;t=3.130,P<0.05)and LNs(17.00% ± 0.41% vs.13.83% ± 0.18%;t=6.947, P<0.01)were higher in the infected mice injected intraperitoneally with 2DG than those in the infected mice injected intraperi-toneally with PBS. Conclusion Glycolytic pathway inhibits Treg differentiation in the spleen and mesenteric LNs of S.japoni-cum-infected mice.

Schistosoma japonicum heat shock protein 60 enhances regulatory T cell im-munosuppressive function by promoting the expressions of IL-10 and TGF-β / 中国血吸虫病防治杂志

Objective To explore the possible mechanisms by which Schistosoma japonicum heat shock protein 60(SjH-SP60)enhances CD4+CD25+regulatory T cell(Treg)immunosuppressive function.Methods An in vitro method was used to investigate the effect of SjHSP60 on Treg immunosuppressive activity.Co-cultures in transwells and in vitro suppression assay were performed to investigate how SjHSP60 enhanced the immunosuppressive function of Tregs.Intracellular cytokine staining combined with flow cytometry was used to detect Treg-expressing IL-10 and TGF-β,and flow cytometry was also used to analyze the expressions of Foxp3 and CTLA-4 in Tregs.Results SjHSP60 enhanced the immunosuppressive function of Tregs.Soluble cytokines IL-10 and TGF-β mediated inhibitory activity of SjHSP60-triggered Tregs.SjHSP60 induced significant increases in both IL-10 and TGF-β expressions of Tregs.Further investigation showed significant increased Foxp3 and CTLA-4 in SjHSP60-trggered Tregs.Conclusion SjHSP60 enhances Treg immunosuppressive function by promoting the expressions of IL-10 and TGF-β,possibly due to SjHSP60-mediated induction of Foxp3 and CTLA-4 in Tregs.

Clinical Observation of Intensive Treatment with Antibiotics and Chinese Medicine Fule Tablets for Treatment of Pelvic Inflammatory Disease / 广州中医药大学学报

Objective To investigate the short-term clinical effect of intensive treatment with antibiotics and Chinese medicine Fule Tablets for pelvic inflammatory disease (PID). Methods A total of 240 PID patients were randomly divided into observation group and control group,120 cases in each group. The observation group was given oral use of antibiotics (Cefodizime or Cefixime Granules + Ornidazole)for 14 days (d1-d14)and Fule Tablets orally for 30 days(d1-d30). The control group was only given oral use of antibiotics(Cefodizime or Cefixime Granules+Ornidazole)for 14 days (d1-d14). Visual Analogue Scale (VAS)scores for lower abdominal pain, tenderness of the uterus or adnexal region, body temperature, vaginal secretions, and ultrasonogram were observed after treatment for 7, 14 and 30 days in both groups. And the therapeutic effect was also evaluated. Results(1)After treatment,VAS scores for lower abdominal pain,tenderness of the uterus or adnexal region, fever, vaginal secretions, pelvic hydrops, adnexal thickening or adnexal mass in the two groups were much improved after treatment (P < 0.05 compared with those before treatment),and the improvement of VAS scores for lower abdominal pain,tenderness of the uterus or adnexal region,vaginal secretions,and pelvic hydrops in the observation group on day 30 was superior to that in the control group (P < 0.05). (2)After treatment for 7,14 days,the differences of the therapeutic effect between the two groups were insignificant(P>0.05). After treatment for 30 days,the therapeutic effect of the observation group was much stronger than that in the control group (P < 0.05). Conclusion The intensive treatment with antibiotics and Chinese medicine Fule Tablets has stronger effect for the treatment of PID than antibiotics alone, which is effective on relieving clinical symptoms and signs,shortening the course of disease,and reducing or preventing the occurrence of sequelae.

Comparison of five methods for the detection of fungal infections in vaginal secretions / 国际检验医学杂志

Objective To compare the similarities and differences of the five detection methods used in the detection of fungi in vaginal secretions,and find the most sensitive、the most specific、the fastest、the most cost effective and the simplest method used in the detection of fungi in vaginal secretions.Methods A total of 442 patients were selected from the Department of Gynecology of Shenzhen OCT Hospital from May 2016 to August 2016.The vaginal secretion of 442 specimens was detected by using the methods of fungi culture、saline and KOH suspension method,Gram stain,Wright''s stain and Vaginitis Multi Test Kit.In these five methods,Fungi culture were using as gold standard to evaluate the specificity,sensitivity,negative predictive value,positive predictive value and accuracy of the other four methods.Results Using the fungus culture method to detect 442 cases of vaginal secretion,we found the positive rate of mycotic infection was 34.8%(154/442).Compared with the fungi culture method,the Specificity of saline and KOH suspension method was 97.9%,the sensitivity was 64.9%,the negative predictive value was 83.9%,the positive predictive value was 94.3% and the accuracy was 86.4%;the Specificity of Gram stain was 96.5%,the Sensitivity was 83.1%,the negative predictive value was 91.4%,the positive predictive value was 92.7% and the accuracy was 91.8%;the Specificity of Vaginitis Multi Test Kit was 84.7%,the Sensitivity was 46.8%,the negative predictive value was 74.8%,the positive predictive value was 62.0% and the accuracy was 71.5%;the Specificity of Wright''s stain was 96.9%,the Sensitivity was 78.6%,the negative predictive value was 89.4%,the positive predictive value was 93.1% and the accuracy was 90.5%.Conclusion Gram stain could be the most sensitive and specific method in the four methods,with highest accuracy,and the the fastest,the most cost effective and the simplest method for the detection of fungi in vaginal secretions.The accuracy of detecting fungi in vaginal secretions could be improved by the combination of Gram stain method in clinical work.

Systematic evaluation of training effect of high-fidelity simulator (HFS) in medical training of cardiopulmonary resuscitation / 中国实用护理杂志

Objective To evaluate the effectiveness of using high-fidelity simulator (HFS) in medical training of cardiopulmonary resuscitation (CPR).Methods The randomized controlled trials (RCTs),quasi-randomized controlled trials (q-RCTs) about comparing HFS with traditional teaching methods in medical training of CPR were searched from Cochrane Library,Pubmed,Web of Knowledge,CNKI,CBM and Wanfang Data.The methodological quality of the included studies was assessed and the valid data were extracted.Meta-analysis was conducted with the Cochrane Collaboration RevMan 5.0.Results Ten q-RCTs and one RCT were included.The quality of the studies were relatively low.Meta-analysis showed that compared with the traditional teaching method,high-fidelity simulation in medical training of CPR had no statistically significant differences in mastering the theoretical knowledge,but had statistically significant differences in mastering the CPR skills.Conclusions HFS in medical training of CPR skills is positive and effective,superior to the traditional teaching methods,but in terms of theoretical knowledge and satisfaction,self-confidence,more researches still need to be further confirmed.

Dexamethasone enhances invasiveness of Aspergillus fumigatus conidia and fibronectin expression in A549 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The efficacies of current treatments for invasive aspergillus (IA) are unsatisfactory and new therapeutic targets or regimens to treat IA are urgently needed. Previous studies have indicated that the ability of conidia to invade host cells is critical in IA development and fibronectin has a hand in the conidia adherence process. In the clinical setting, many patients who receive glucocorticoid for extended periods are susceptible to Aspergillus fumigatus (A. fumigatus) infection, for this reason we investigated the effect of glucocorticoid on conidia invasiveness by comparing the invasiveness of A. fumigatus conidia in the type II human alveolar cell line (A549) cultured with different concentrations of dexamethasone. We also explored the relationships between dexamethasone and fibronectin expression.</p><p><b>METHODS</b>Following culture with anti-fibronectin antibodies and/or dexamethasone, type II human alveolar A549 cells were infected with conidia of A. fumigatus. After 4 hours, the extracellular free conidia were washed away and the remaining immobilized conidia were released using Triton-X 100 and quantified by counting the colony-forming units. The invasiveness of conidia was measured by calculating the invasion rate (%). The transcription of the fibronectin gene in cells cultured with different concentrations of dexamethasone for 24 hours was tested by fluorogenic quantitative RT-PCR while the expression of fibronectinin cells cultured for 48 hours was tested by Western blotting and immunocytochemistry.</p><p><b>RESULTS</b>A significant reduction in the invasiveness of conidia was seen in the cells cultured with anti-fibronectin antibody ((14.42 ± 1.68)% vs. (19.17 ± 2.53)%, P < 0.05), but no significant difference was observed in cells cultured with a combination of anti-fibronectin antibody and dexamethasone (6.37 ± 10(-5) mol/L). There was no correlation between the dexamethasone concentration and the invasiveness of conidia after dexamethasone pretreatment of cells for 4 hours. In contrast, after pretreated for 24 hours, the invasiveness of conidia in the presence of 6.37×10(-5) mol/L dexamethasone ((24.66 ± 2.41)%) was higher than for the control ((19.17 ± 2.53)%) and the 0.25×10(-5) mol/L group ((19.93 ± 3.06)%), and the invasiveness in the 1.27×10(-5) mol/L group ((22.47 ± 2.46)%) was also higher than in the control, P < 0.05. The relative transcripts of the fibronectin gene after exposure to 6.37×10(-5) mol/L dexamethasone (9.19×10(-3)±1.2×10(-3)) was higher than for the control (4.61×10(-3)± 1.54×10(-3)) and the 0.25×10(-5) mol/L group (6.20×10(-3)± 1.93×10(-3)), and expression in the 1.27×10(-5) mol/L group (7.94×10(-3)± 2.24×10(-3)) was also higher than for the control, P < 0.05. High concentrations of dexamethasone promoted fibronectin production after culture for 48 hours.</p><p><b>CONCLUSIONS</b>Dexamethasone can increase invasiveness of A. fumigatus conidia by promoting fibronectin expression. This may partially explain why patients who are given large doses of glucocorticoids for extended periods are more susceptible to A. fumigatus infection.</p>

Predictive factors of chronic thromboembolic pulmonary hypertension in patients with acute pulmonary thromboembolism / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the incidence and predictive factors of chronic thromboembolic pulmonary hypertension (CTEPH) in patients with acute pulmonary thromboembolism (PTE).</p><p><b>METHODS</b>Clinical data of 104 patients with CT angiography-proven PTE were collected and Wells score, revised Geneva score and ECG score were calculated. Blood gas analysis, CK-MB and D-dimer values were analyzed. Heart chamber diameters and pulmonary artery systolic pressure (PASP) were assessed by echocardiography. Qanadli obstruction index and Mastora obstruction index were evaluated according to computed tomography pulmonary angiography (CTPA). Patients were followed up by telephone or clinic visit to assess the WHO functional class and the incidence of CTEPH.</p><p><b>RESULTS</b>During the 25.47±16.94 months (4 to 62 months) follow-up, 7 out of 104 patients were lost to follow-up and data from the remaining 95 patients were analyzed. The incidence of CTEPH was 14.4% (14/97). Baseline PASP, incidence of recurrent PTE, right atrium and right ventricle diameters and CK-MB were significantly higher in CTEPH group compared to non-CTEPH group (all P<0.05). Higher CK-MB (odds ratio: 8.3) and baseline PASP (odds ratio: 5.0 per 20 mm Hg increment) were independent predictive factors for CTEPH in this cohort.</p><p><b>CONCLUSIONS</b>Higher CK-MB and baseline PASP values are independent predictive factors related to the development of CTEPH post acute pulmonary thromboembolism.</p>

Efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen in the treatment of HER2-positive advanced gastric cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen (irinotecan plus 5-FU/LV) in the treatment of HER2-positive advanced gastric cancer.</p><p><b>METHODS</b>T Thirty-four patients with pathologically confirmed advanced gastric cancer, all positive for the human epidermal growth factor receptor 2 (HER2) as identified by immunohistochemistry and fluorescence in situ hybridization, were randomized into the test group and control group to for treatment with the combined regimen and the FOLFIRI regimen alone, respectively. FOLFIRI regimen was administered every 2 weeks for 2 to 4 cycles. Trsatuzumab was given intravenously on a weekly basis with an initial dose of 4 mg/kg and a subsequent dose of 2 mg/kg. All the patients were assessed for efficacy and toxicity of the treatments.</p><p><b>RESULTS</b>The overall response rate was 58.8% in the test group and 35.3% in the control group, with disease control rates of 88.2% and 64.7%, respectively, showing significant differences between the two groups (P<0.05). The most frequent grade I/II treatment-related adverse events included diarrhea, nausea/vomiting and neutropenia.</p><p><b>CONCLUSION</b>Trsatuzumab combined with FOLFIRI regimen is effective, safe and well tolerated for treatment of HER2-positive advanced gastric cancer.</p>

Near-fatal infection following an elective ankle-fracture fixation: less risk should not mean less vigilance / 中华医学杂志(英文版)

Surgical fixation of closed ankle fracture is traditionally viewed as having low risk for post-operative infection. Only a few cases of surgical-site confined infection have been reported. Because of the low infection risk, the necessity for perioperative prophylaxis has been questioned. We report a case of fulminant methicillin-resistant Staphylococcus aureus endocarditis occurring shortly after an elective ankle fixation surgery in an elderly woman with chronic rheumatoid arthritis. Because systemic infection was unexpected, she had been given antipyretics for postoperative fever until just before rapid clinical deterioration. A nearly fatal hematogenous infection occurred after such a procedure, indicating the necessity for being on high alert and considering the possibility of bloodstream infection.

Effects of high-volume hemofiltration on alveolar-arterial oxygen exchange in patients with refractory septic shock / 世界急诊医学杂志（英文）

@#BACKGROUND: High-volume hemofiltration (HVHF) is technically possible in severe acute pancreatitis (SAP) patients complicated with multiple organ dysfunction syndrome (MODS). Continuous HVHF is expected to become a beneficial adjunct therapy for SAP complicated with MODS. In this study, we aimed to explore the effects of fluid resuscitation and HVHF on alveolar-arterial oxygen exchange, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with refractory septic shock. METHODS: A total of 89 refractory septic shock patients, who were admitted to ICU, the Provincial Hospital affiliated to Shandong University from August 2006 to December 2009, were enrolled in this retrospective study. The patients were randomly divided into two groups: fluid resuscitation (group A, n=41), and fluid resuscitation plus high-volume hemofiltration (group B, n=48). The levels of O2 content of central venous blood (CcvO2), arterial oxygen content (CaO2), alveolar-arterial oxygen pressure difference P(A-a)DO2, ratio of arterial oxygen pressure/alveolar oxygen pressure (PaO2/PAO2), respiratory index (RI) and oxygenation index (OI) were determined. The oxygen exchange levels of the two groups were examined based on the arterial blood gas analysis at different times (0, 24, 72 hours and 7 days of treatment) in the two groups. The APACHE II score was calculated before and after 7-day treatment in the two groups. RESULTS: The levels of CcvO2, CaO2 on day 7 in group A were significantly lower than those in group B (CcvO2: 0.60±0.24 vs. 0.72±0.28, P<0.05; CaO2: 0.84±0.43 vs. 0.94±0.46, P<0.05). The level of oxygen extraction rate (O2ER) in group A on the 7th day was significantly higher than that in group B ( 28.7±2.4 vs. 21.7±3.4, P<0.01). The levels of P(A-a)DO2 and RI in group B on the 7th day were significantly lower than those in group A. The levels of PaO2/PAO2 and OI in group B on 7th day were significantly higher than those in group A (P<0.05 or P<0.01). The APACHE II score in the two groups reduced gradually after 7-day treatment, and the APACHE II score on the 7th day in group B was significantly lower than that in group A (8.2±3.8 vs. 17.2±6.8, P<0.01). CONCLUSION: HVHF combined with fluid resuscitation can improve alveolar- arterial-oxygen exchange, decrease the APACHE II score in patients with refractory septic shock, and thus it increases the survival rate of patients.

Acute paraplegia following embolization of spinal dural arteriovenous fistula / 中华医学杂志(英文版)

Embolization therapy has been used as the initial treatment for spinal dural arteriovenous fistula (SDAVF) only for certain patients or in certain medical institutions due to its minimal invasiveness, but the recurrence of embolization remains a clinical challenge. The recurrent patient usually exhibits a gradual onset of symptoms and progressive deterioration of neurological function. Developing paraplegia several hours after embolization is commonly seen in patients with venous thrombosis-related complications, for which anticoagulation therapy is often administered. This article reports on a SDAVF patient who had weakness of both lower extremities before embolization and developed complete paraplegia several hours after embolization therapy, later confirmed by angiography as fistula recurrence. The symptoms were relieved gradually after second embolization. The pathophysiology of this patient is also discussed.

A lack of association between adiponectin polymorphisms and coronary artery disease in a Chinese population

We investigated the association between two single nucleotide polymorphisms (SNPs) in the adiponectin gene (rs822395 and rs266729) and coronary artery disease (CAD) in a case-control study of 198 unrelated Chinese CAD patients (with ; 70 percent coronary stenosis or previous myocardial infarction) and 237 non-CAD controls. The ligase reaction was used to detect SNPs rs822395 and rs266729, and the allelic association of these SNPs with the occurrence and severity of CAD was assessed. There were no significant differences in the genotypic or allelic frequencies of the two SNPs between control and CAD individuals. In addition, there was no association between the two SNPs and the severity of CAD based on the number of diseased vessels. The frequencies of alleles C and G at rs266729 differed significantly between females in the CAD and control groups, but not between males. Female carriers of allele G at rs266729 had a higher risk of CAD compared with allele C carriers (OR = 1.30, 95 percent CI: 1.09-2.64, p = 0.02). These results indicate a gender-specific effect of the adiponectin gene rs266729 variant in modulating the risk of CAD in women.

Effect of Insulin Pump Therapy on Type 1 Diabetes Mellitus with Diabetic Keto or Diabetic Ketoacidosis / 实用儿科临床杂志

Objective To observe the effects of insulin pump therapy on type 1 diabetes mellitus children with diabetic keto or diabetic ketoa-cidosis(DK/DKA).Methods Forty-three children with DK/DKA were randomly divided into treatment group(n=26)and control group(n=17).The patients in treatment group were treated with insulin pump,control group were received small amount insulin injravenous injection.The changs of blood sugar,urine ketone bodies,incidence of hypoglycemia and length of stay were observed.Results 1.The effect of decreasing sugar was the same between two groups.2.There was no hypoglycemia events in treatment group.But 2 cases in control group had hypoglycemia.3.There was significant difference of length of stay between two groups(P