Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors / 中华肿瘤杂志

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

Quality evaluation of fried Glycyrrhizae Radix et Rhizoma pieces by HPLC fingerprint and multicomponent quantitative analysis / 中国中药杂志

To establish the HPLC fingerprint and multi-component determination method of fried Glycyrrhizae Radix et Rhizoma pieces. HPLC analysis was performed on Thermo Acclaim ~(TM)120 C_(18) column(4.6 mm×250 mm, 5 μm). Acetonitrile-0.1% phosphoric acid aqueous solution was taken as the mobile phase for gradient elution. The flow rate was 1 mL·min~(-1),the column temperature was maintained at 30 ℃, and the detection wavelength was 237 nm and 360 nm. The similarity of 15 batches of fried Glycyrrhizae Radix et Rhizoma pieces was higher than 0.849, and 17 common peaks were identified. Liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizic acid were identified; among them, the mass fractions of Liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, glycyrrhizic acid were were 0.519%-3.058%, 0.227%-0.389%, 0.070%-0.439%, 0.038%-0.173%, 1.381%-4.252%, respectively. According to the cluster analysis, the 15 batches of decoction pieces were classified into three categories; principal component analysis screened out four principal components, with the cumulative variance contribution rate of 86.630%, indicating that the principal components contained most information of original data. Partial least squares discriminant ana-lysis marked 6 differential components in the decoction pieces. The established fingerprint and multicomponent determination are stable and reliable, and can provide a reference for the quality control of Radix Glycyrrhizae Radix et Rhizomae and fried Glycyrrhizae Radix et Rhizoma pieces.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study / 生物医学与环境科学（英文）

Objective@#The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.@*Methods@#The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.@*Results@#A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).@*Conclusion@#An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Construction of targeted cryptotanshinone liposomes and research on its in vitro anti-glioma effect / 药学学报

Cryptotanshinone (CPT), an active ingredient with the inhibitory effect on brain glioma cells, is trapped with poor solubility and low tumor permeability. Therefore, it is urgent to design nano drug delivery systems characterized with deep penetration and accurate targeting. In the present study, tLyp-1 modified liposomes loaded with CPT (tLipo/CPT) was prepared by emulsion solvent evaporation method. Peptide tLyp-1 which targeting tumor angiogenesis and neuropilin receptors (NRP) was modified on surface of CPT liposomes, with the aim of active targeting brain glioma cells and further release CPT precisely. The size and polymer dispersity index (PDI) of tLipo/CPT were (162.2 ± 14.6) nm and 0.24 ± 0.03. The optimal molar ratio of tLyp-1 modified on CPT liposomes was 0.5% determined by intracellular fluorescence parameters. The morphology displayed a smooth sphericity structure as determined by transmission electron microscope. Efficiency of CPT encapsulated in tLipo/CPT was detected by high performance liquid chromatography. The encapsulation efficiency of CPT was (70.06 ± 7.22) %. Liposomes modified with tLyp-1 peptide (tLipo) were internalized more than liposomes not modified with tLyp-1 (Lipo) by GL261 cells. Fluorescence intensity of tLipo in GL261 cells increased 40% than that of Lipo. Furthermore, we proved that the intake of tLipo/CPT in GL261 cells was mediated by NRP-1 receptor. MTT analysis indicated that tLipo/CPT significantly inhibit the proliferation of GL261 cells. The half maximal inhibitory concentration (IC50) was 5.70 μmol·L-1. In vitro blood-brain barrier (BBB) model experiment indicated that tLipo/CPT could penetration across BBB. Moreover, in vivo fluorescence biodistribution study indicated tail vein injection of DiR labeled tLipo after 0.5 h, DiR fluorescence could be observed in the brain of mice. Even after 24 h, DiR fluorescence still was observed in the brain. Our research certified that tLipo/CPT can penetrate the BBB and show effect of anti-glioma by inhibiting the proliferation of GL261 cells. The animal experiment was carried out in accordance with protocol evaluated and approved by the Ethics Committee of Nanjing University of Chinese Medicine.

Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen) / 中草药·英文版

Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.

Comparison of effects of transpedicular grafting of vertebral pedicle screw and strode over fractured vertebra of vertebral pedicle screw in the treatment of thoracolumbar fractures / 中国基层医药

Objective@#To compare the effects of transpedicular grafting of vertebral pedicle screw and strode over fractured vertebra of vertebral pedicle screw in the treatment of thoracolumbar fractures.@*Methods@#From January 2015 to December 2016, 84 cases of thoracolumbar fractures in Weihai Central Hospital were randomly divided into two groups according to the digital table, with 42 cases in each group.The control group received strode over fractured vertebra of vertebral pedicle screw, and the study group received transpedicular grafting of vertebral pedicle screw.The patients were followed up for 12 months.The bleeding loss, operation time, postoperative drainage, fracture healing time, hospitalization days and anterior compression ratio of vertebral body, kyphosis Cobb angle before and after treatment and postoperative complications were compared between the two groups.@*Results@#There were no statistically significant differences in postoperative drainage volume, fracture healing time and hospitalization days between the two groups (t=1.38, 1.79, 1.20, all P>0.05), but the intraoperative bleeding volume[(183.85±13.88)mL]and operation time[(119.74±14.85)min]in the study group were significantly higher than those in the control group[(137.97±14.24)mL, (99.46±13.42)min](t=14.95, 6.57, all P<0.01). Compared with the control group, the compression ratio of the anterior vertebral body in the study group was significantly increased after operation[(92.15±8.70)% vs.(83.75±7.04)%](t=4.86, P<0.01), and the kyphotic Cobb angle in the study group and the control group were significantly decreased compared with those before operation[(10.15±2.47)°, (14.53±4.85)°], and the postoperative kyphotic Cobb angle in the study group was significantly lower than that in the control group (t=5.21, P<0.01). The incidence rate of postoperative complications in the study group was 4.76%, which showed no statistically significant difference compared with the control group (14.29%, χ2=2.21, P=0.14).@*Conclusion@#Transpedicular grafting of vertebral pedicle screw is superior to strode over fractured vertebra of vertebral pedicle screw in promoting reduction, correcting posterior process deformity and reconstructing vertebral height in patients with thoracolumbar fractures, and it does not cause serious complications, so it has good clinical value.

Comparison of effects of transpedicular grafting of vertebral pedicle screw and strode over fractured vertebra of vertebral pedicle screw in the treatment of thoracolumbar fractures / 中国基层医药

Objective To compare the effects of transpedicular grafting of vertebral pedicle screw and strode over fractured vertebra of vertebral pedicle screw in the treatment of thoracolumbar fractures.Methods From January 2015 to December 2016,84 cases of thoracolumbar fractures in Weihai Central Hospital were randomly divided into two groups according to the digital table,with 42 cases in each group.The control group received strode over fractured vertebra of vertebral pedicle screw,and the study group received transpedicular grafting of vertebral pedicle screw.The patients were followed up for 12 months.The bleeding loss,operation time,postoperative drainage,fracture healing time,hospitalization days and anterior compression ratio of vertebral body,kyphosis Cobb angle before and after treatment and postoperative complications were compared between the two groups.Results There were no statistically significant differences in postoperative drainage volume,fracture healing time and hospitalization days between the two groups (t =1.38,1.79,1.20,all P ＞ 0.05),but the intraoperative bleeding volume [(183.85 ± 13.88) mL] and operation time[(119.74 ± 14.85) min] in the study group were significantly higher than those in the control group[(137.97 ±14.24) mL,(99.46 ± 13.42) min] (t =14.95,6.57,all P ＜ 0.01).Compared with the control group,the compression ratio of the anterior vertebral body in the study group was significantly increased after operation [(92.15 ± 8.70) ％vs.(83.75 ± 7.04)％] (t =4.86,P ＜ 0.01),and the kyphotic Cobb angle in the study group and the control group were significantly decreased compared with those before operation [(10.15 ± 2.47) °,(14.53 ± 4.85) °],and the postoperative kyphotic Cobb angle in the study group was significantly lower than that in the control group (t =5.21,P ＜0.01).The incidence rate of postoperative complications in the study group was 4.76％,which showed no statistically significant difference compared with the control group (14.29％,x2 =2.21,P =0.14).Conclusion Transpedicular grafting of vertebral pedicle screw is superior to strode over fractured vertebra of vertebral pedicle screw in promoting reduction,correcting posterior process deformity and reconstructing vertebral height in patients with thoracolumbar fractures,and it does not cause serious complications,so it has good clinical value.

Fluid structure interaction analysis of transcatheter aortic valve implantation / 中国组织工程研究

BACKGROUND: Cardiac valve replacement provides an effective therapeutic means for valvular heart disease. Compared with thoracotomy surgery, interventional treatment, typified by transcatheter aortic valve implantation, has the advantages of minor trauma and rapid recovery. At present, the transcatheter aortic valve replacement is rarely applied in clinical practice. Existing studies mainly focus on the changes of physiological conditions after surgery, while little is reported on the transcatheter aortic valve models. OBJECTIVE: To explore the deformation and stress distribution features of the transcatheter aortic valve, and to verify its working performance. METHODS: The finite element geometric model and mathematical model of the aortic valve, including the aortic valve, blood vessel wall, blood and stent, were established. The fluid structure interaction analysis was carried out by the immersion boundary method, and the effective orifice area index was calculated to verify the performance of the model. RESULTS AND CONCLUSION: During the course of blood shock, the valve leaflets were curl, and the maximum deformation occurred at 1/4 and 3/4 of the valve leaflet free edge. The largest equivalent stress of the aortic valve model was on the stent, but it is almost unformed. The stress concentration of the valve leaflets was located at the curved site of the free edge and the suture points of the leaflets and stents, where a damage easily occurred. The dynamic flow experiments show that the process of the simulation model deformation and effective orifice area index are close to the experimental results. Therefore, the simulation model is reasonable and effective.

Posaconazole as primary prevention of fungal infection in intensive immunosuppressive therapy for severe aplastic anemia / 中华血液学杂志

Objective: To Evaluate the efficacy and safety of posaconazole as primary prevention of invasive fungal disease (IFD) in patients with severe aplastic anemia (SAA) treated with anti-thymus/lymphocyte immunoglobulin (ATG/ALG) combined with cyclosporine intensive immunosuppressive therapy (IST). Methods: A retrospective analysis of clinical data of 58 SAA patients who received IST of anti-thymocyte immunoglobulin combining cyclosporine and antifungal prophylaxis during April 2013 to May 2017 in Peking Union Medical College Hospital was performed. The patients were divided into posaconazole prophylaxis group and the control group (itraconazole or fluconazole). The disease characteristics, IFD prevention effect and adverse drug reaction, curative effect and prognosis of the two groups were compared. Results: Posaconazole was used to prevent fungal infection in 20 patients. The other 38 patients were used as the control group. Retrospective analysis showed comparable characteristics (gender, age, disease severity, etiology, interval between the onset of disease to treatment, ATG/ALG type) of both groups. The incidence of IFD were 0 and 15.8% in posaconazole prophylaxis group and the control group, respectively (P=0.084). In the control group, there were 6 cases diagnosed as IFD. Of them, 2 were confirmed, 2 suspected and 2 not identified. Five of the 6 cases were pulmonary infection, 1 bloodstream infections. Of the 6 IFD cases, 5 were very severe aplastic anemia (VSAA). There was no obvious adverse reaction in posaconazole prophylaxis group. Conclusion: Posaconazole is safe and effective for primary prevention of fungal infection of SAA patients receiving IST, especially for the VSAA.

DNA Vaccines Encoding Toxoplasma gondii Cathepsin C 1 Induce Protection against Toxoplasmosis in Mice

Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant α-GalCer. As results, TgCPC1 DNA vaccine with or without adjuvant α-GalCer showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and IFN-γ in the spleen compared to controls (PBS, pEGFP-C1, and α-Galcer). Upon challenge infection with tachyzoites of T. gondii (RH), pCPC1/α-Galcer immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and α-Galcer). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.

CD200/CD200R Expression Levels and Its Significance after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>BACKGROUND</b>CD200 and its receptor CD200R are both type-1 membrane glycoproteins, which are members of the immunoglobulin superfamily (IgSF). Besides the inhibitory effect on macrophages, CD200/CD200R also play an important role in regulating the regulatory T cells, allergicreaction, autoimmune diseases, allograft, neurological diseases and other autoimmune-related diseases, etc.</p><p><b>OBJECTIVE</b>To investigate the role of CD200 and its receptor in the graft versus host disease (GVHD).</p><p><b>METHODS</b>Experimental samples were divided into aGVHD group, non-aGVHD group, cGVHD group and non-cGVHD group, the healthy persons were used as normal controls. Firstly, the expression levels of CD200 and CD200R on CD19+ cell, CD3+ cell and dendritic cell (CD19- CD14- CD1c+) surfaces in each group were detected by using flow cytometry, so as to determine whether there were expression differences among each groups. Then, the mRNA levels of each groups were tested by using real-time quantitative polymerase chain reaction for finding the differences of mRNA expression level among each group. Finally, the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1 antibody for 48 hours, and the interleukin-10 level in the co-culture system was tested by using enzyme linked immunosorbent assay for verifying the function of CD200/CD200R.</p><p><b>RESULTS</b>The CD200 expression level on CD19+ cell surface in the aGVHD group and non-aGVHD group was both lower than that in healthy control group; that in the non-aGVHD group was higher than that in the aGVHD group. The CD200 expression level on CD19+ CD200+ cells in the non-cGVHD group were higher than that in the cGVHD group and healthy control group. There were no significant differences of CD200 and CD200R expression levels on CD3 cells and dendritic cells among all groups. The CD200 mRNA expression levels in the aGVHD group and cGVHD group were both lower than the healthy control group. The CD200 mRNA expression level was lower in the aGVHD group than in the non-aGVHD group, and was lower in the cGVHD group than in the non-cGVHD group. There was no significant difference of the CD200R mRNA expression level among all groups. After the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1 antibody for 48 hours, the interleukin-10 concentration decreased with the increasing of anti-CD200R1 antibody concentrations in the co-culture system.</p><p><b>CONCLUSION</b>The CD200/CD200R may play a role in the pathogenesis of GVHD after allo-HSCT.</p>

An Interdisciplinary Nutrition Support Team Improves Clinical and Hospitalized Outcomes of Esophageal Cancer Patients with Concurrent Chemoradiotherapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prevalence of malnutrition is very high in patients with cancer. The purpose of this study was to investigate whether or not a nutrition support team (NST) could benefit esophageal cancer patients undergoing chemoradiotherapy (CRT).</p><p><b>METHODS</b>Between June 2012 and April 2014, 50 esophageal cancer patients undergoing concurrent CRT were randomly assigned into two groups: The NST group and the control group. The nutritional statuses of 25 patients in the NST group were managed by the NST. The other 25 patients in the control group underwent the supervision of radiotherapy practitioners. At the end of the CRT, nutritional status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay (LOS) and the in-patient cost were also compared between these two groups.</p><p><b>RESULTS</b>At the completion of CRF, the nutritional status in the NST group were much better than those in the control group, as evidenced by prealbumin (ALB), transferrin, and ALB parameters (P = 0.001, 0.000, and 0.000, respectively). The complication incidences, including bone marrow suppression (20% vs. 48%, P = 0.037) and complications related infections (12% vs. 44%, P = 0.012), in the NST group were lower and significantly different from the control group. In addition, only one patient in the NST group did not complete the planned radiotherapy while 6 patients in the control group had interrupted or delayed radiotherapy (96% vs. 76%, P = 0.103). Furthermore, the average LOS was decreased by 4.5 days (P = 0.001) and in-patient cost was reduced to 1.26 ± 0.75 thousand US dollars person-times (P > 0.05) in the NST group.</p><p><b>CONCLUSIONS</b>A NST could provide positive effects in esophageal cancer patients during concurrent CRT on maintaining their nutrition status and improving the compliance of CRF. Moreover, the NST could be helpful on reducing LOS and in-patient costs.</p>

Sequence Variation in Superoxide Dismutase Gene of Toxoplasma gondii among Various Isolates from Different Hosts and Geographical Regions

Toxoplasma gondii, an obligate intracellular protozoan parasite of the phylum Apicomplexa, can infect all warm-blooded vertebrates, including humans, livestock, and marine mammals. The aim of this study was to investigate whether superoxide dismutase (SOD) of T. gondii can be used as a new marker for genetic study or a potential vaccine candidate. The partial genome region of the SOD gene was amplified and sequenced from 10 different T. gondii isolates from different parts of the world, and all the sequences were examined by PCR-RFLP, sequence analysis, and phylogenetic reconstruction. The results showed that partial SOD gene sequences ranged from 1,702 bp to 1,712 bp and A + T contents varied from 50.1% to 51.1% among all examined isolates. Sequence alignment analysis identified total 43 variable nucleotide positions, and these results showed that 97.5% sequence similarity of SOD gene among all examined isolates. Phylogenetic analysis revealed that these SOD sequences were not an effective molecular marker for differential identification of T. gondii strains. The research demonstrated existence of low sequence variation in the SOD gene among T. gondii strains of different genotypes from different hosts and geographical regions.

Expression of BRCA1 and WWOX and their clinicopathologic implication in breast carcinomas occurring in young women / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the clinicopathologic characteristics and biological markers of breast carcinomas in young women.</p><p><b>METHODS</b>Immunohistochemical SP method was used to study breast cancer susceptibility gene (BRCA1) and WWOX in breast carcinomas of patient ≤ 35 years of age (107 cases) and ≥ 60 years of age (112 cases). The findings were correlated with clinicopathological features. In addition, PCR amplification and direct sequencing were performed to detect the BRCA1 gene mutation of exons 2 and 20 using fresh frozen tissue samples in other 10 patients who were ≤ 35 years of age.</p><p><b>RESULTS</b>The positive rate of BRCA1 protein expression was higher in the young age group [65.4% (70/107)] than that of the old age group [35.7% (40/112)]. ER, PR, HER2, and WWOX protein expression and proliferation marker Ki-67 were no statistically different in the two groups (all P > 0.05). BRCA1 expression was significantly correlated with pTNM and axillary lymph node metastasis (both P < 0.05), but not with ER, PR, HER2 and WWOX protein expression (all P > 0.05). Ki-67 and histological grading showed no statistical correlation (P > 0.05). WWOX protein expression showed no correlation with clinicopathologic characteristics (all P > 0.05). Mutation of exons 2 and 20 of the BRCA1 gene was not detected in any of 10 cases studied.</p><p><b>CONCLUSION</b>BRCA1 cytoplasmic expression statistically correlates with the development and prognosis of breast cancer of young patients.</p>

Clinical features of invasive pulmonary fungal infection secondary to malignant blood diseases / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the clinical features of invasive pulmonary fungal infection (IPFI) secondary to malignant blood diseases (MBD).</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 52 patients with IPFI secondary to MBD admitted to Peking Union Medical College Hospital from January 1995 to December 2008.</p><p><b>RESULTS</b>The incidences of IPFI secondary to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL), and aplastic anemia (AA) were 4.6%, 3.2%, 2.8%, and 2.5%, respectively. In patients with IPFI secondary to AML, 88.5% (23/26) of the patients suffered from the infections during the non-remission (NR) period (including relapse), and 11.5% (3/26) in the complete-remission (CR) period. In all the patients with IPFI secondary to malignant blood diseases, 86.5% (45/52) of MBD were neutropenic or agranulocytic, and 67.3% (35/52) had been treated with broad-spectrum antibiotics for more than 96 hours before anti-fungal therapy. The total mortality after anti-fungal therapy was 13.7% (7/51). More than half of patients with fluconazole or itraconazole as the first-line therapy had to switch to other medicines because of poor infection control.</p><p><b>CONCLUSIONS</b>IPFI secondary to MBD is most common in AML patients. Patients with NR of AML, neutropenia or agranulocytosis, and long-term broad-spectrum antibiotics usage are susceptible to IPFI. Fluconazole and itraconazole have low efficacy, and other more potent anti-fungal medicines should be considered.</p>

Study on the effect and mechanism of ascorbic acid on renal podocytes in diabetes / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect and mechanism of ascorbic acid on podocyte, last barrier of glomerular filtration, in diabetic rats.</p><p><b>METHODS</b>Diabetic rats induced by streptozotocin injection intraperitoneally were treated by ascorbic acid for 5 weeks. The levels of blood glucose (BG), HbA1c, urinary albumin excretion rate (UAER) and superoxide diamutase (SOD), catalase (CAT) and malondialdehyde (MDA) in renal cortex were measured. The podocyte ultrastructure was observed while the expression of desmin protein, a marker of podocyte injury, was examined.</p><p><b>RESULTS</b>Compared with control group, BG and HbA1c were increased markedly in diabetic group. The activities of SOD and CAT were decreased and the concentrations of MDA were increased significantly in diabetic renal cortex. There were the increased proteinic expression of desmin, foot process effacement in podocytes and UAER markedly in diabetic rats. Compared with diabetic rats, foot process effacement and the changes of UAER were ameliorated markedly while the activities of SOD were increased, the levels of MDA and proteinic expression of desmin were decreased markedly although BG, HbA1c and the activities of CAT were no significant difference in the diabetic rats by ascorbic acid treatment.</p><p><b>CONCLUSION</b>The findings suggest that there are marked injury in podocyte, last barrier of glomerular filtration, in diabetic rats and administration of ascorbic acid can protect podocyte by increasing antioxidative capacity and ameliorating the renal oxidative stress.</p>

Evaluation of therapeutic effects of synthetic auricular point therapy for treatment of common migraine at the attack stage / 中国针灸

<p><b>OBJECTIVE</b>To observe and evaluate the short-term and long-term curative effects of the synthetic auricular point therapy on the common migraine in attack stage.</p><p><b>METHODS</b>With the study method of randomized controlled trial, 108 cases of common migraine at the attack stage were randomly assigned to a treatment group of 72 cases treated with synthetic auricular point therapy (blood-letting on the ear back, point injection of own blood, pricking ear point), and a control group of 36 cases treated with Western medicine. Their short-term and long-term curative effects were observed and evaluated.</p><p><b>RESULTS</b>The total short-term effective rate and the total long-term effective rate were respectively 98.6% and 79. 6% in the treatment group with less adverse effects, and with a very significant difference as compared with the control group (P < 0.01).</p><p><b>CONCLUSION</b>The synthetic auricular point therapy has obvious short-term and long-term curative effects on common migraine at the attack stage with safety.</p>

Effects of recombinant adenovirus encoding human apM1 gene on proliferation and nitric oxide synthase activity in human umbilical vein endothelial cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of recombinant adenovirus encoding human apM1 gene on proliferation and nitric oxide synthase (NOS) activity in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>Protein expression of apM1 in cell culture supernatant of HUVECs transfected with human Ad-apM1 was detected by double antibody sandwich ELISA. The effect of human adiponectin on cell proliferation was assessed by MTT assay. The total NOS and iNOS expressions were measured by chromatometre.</p><p><b>RESULTS</b>Human adiponectin protein level and total NOS and eNOS expressions were significant increased and iNOS expression significantly reduced in culture supernatant of HUVECs infected with Ad-apM1 compared to that in control HUVECs. The recombinant adenovirus had no influence on HUVECs growth as determined by MTT assay.</p><p><b>CONCLUSIONS</b>Human Ad-apM1 can be effectively expressed in HUVECs and do not influence HUVECs growth. Increased total NOS and eNOS expressions and decreased iNOS expression in HUVECs transfected with Ad-apM1 gene suggest a potential role of Ad-apM1 gene transfer for the prevention and treatment of arteriosclerosis.</p>

Research on the modeling of biological valves poppet / 生物医学工程学杂志

In this paper are described the construction of biological valves poppet and the establishment of mathematical model according to cardiac valves hydrokinetics and the theory of membrane. Finite elements of biological valves leaflets connected with biological valves poppet are analyzed. The method of constructing geometric model is reasonable. CAD of biological valves poppet is realized by structured programming and parameterization.

Renal protective effect and its mechanism of sodium ferulate in diabetic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the renal protective effect of sodium ferulate (SF) and its mechanism in rats with diabetic mellitus (DM).</p><p><b>METHODS</b>DM rats induced by streptozotocin were treated with SF 110 mg/kg per day for 8 weeks. The ratio of kidney weight/body weight (KW/BW), serum triglyceride (TG) and total cholesterol (TC), creatinine clearance rate (Ccr), urinary protein/24 hrs, levels of endothelin-1 (ET-1) and nitric oxide (NO) in renal cortex in rats were measured, the pathological change of kidney were observed and the expression of transforming growth factor-beta 1 (TGF-beta 1) and collagen IV (C-IV) in kidney were examined using immunohistochemical assay. The data obtained were compared with those obtained from untreated DM rats and normal rats respectively.</p><p><b>RESULTS</b>Compared with the normal rats, in DM rats, Ccr, urinary protein/24 hrs, ET-1, expressions of TGF-beta 1 and C-IV were significantly increased in DM model rats (all P < 0.01), and significantly abnormal pathological change in kidney was found. While in the SF treated DM rats, the above-mentioned abnormal changes were all significantly improved.</p><p><b>CONCLUSION</b>SF has effect in protecting kidney of DM rats, the mechanism might be related with its actions of reducing ET-1 production in kidney and inhibiting the expressions of TGF-beta 1 and C-IV.</p>