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.

Molecular Mechanism of Salvia miltiorrhiza Quality Formation Based on Single Nucleotide Polymorphism of Functional Genes / 中国实验方剂学杂志

Objective:To investigate the relationship between the single nucleotide polymorphism（SNP）of function genes and effective components of <italic>Salvia miltiorrhiza</italic> and the molecular mechanism of specific quality formation of <italic>S. miltiorrhiza</italic>. Method:The fingerprints of components in <italic>S. miltiorrhiza</italic> from eight different habitats and varieties were obtained by high-performance liquid chromatography （HPLC）. The full-length cDNA of three functional genes<italic> </italic>acetyl-CoA C-acetyltransferase（<italic>SmAACT</italic>），4-diphosphocytidyl-2-C-methyl-<italic>D</italic>-erythritol kinase（<italic>SmCMK</italic>） and isopentenyl diphosphate isomerase（<italic>SmIPPI</italic>） in tanshinone metabolic pathway were amplified by polymerase chain reaction（PCR），cloned， and sequenced，followed by bioinformatics analysis. Result:The full-length cDNA sequences of three functional genes <italic>SmAACT</italic>，<italic>SmCMK</italic>， and <italic>SmIPPI</italic> in tanshinone metabolic pathway were obtained from 23 strains of <italic>S. miltiorrhiza</italic> from eight different habitats and varieties. As revealed by the analysis of SNP and amino acid polymorphisms of three functional genes，18，16， and 14 SNP sites were found respectively. HPLC results showed the samples from Beijing，Hubei，Shandong （No. SDB），Shanxi，Henan， and Shandong （No. SDZ） were clustered into one branch，and those from Hebei and Inner Mongolia were clustered into another branch， which suggested that the variation trend of <italic>S. miltiorrhiza</italic> components had little correlation with geographical distance，but the variety was a critical factor for the quality. Conclusion:There was an obvious genetic differentiation trend in <italic>S. miltiorrhiza</italic> from different habitats，and different origin-specific genotypes were formed. The molecular mechanism of the formation of the specific quality of <italic>S. miltiorrhiza</italic> from different habitats was discussed，which laid a foundation for the stability and effectiveness of clinical medication，and guided the breeding of excellent varieties of <italic>S. miltiorrhiza</italic>.

Role of Counterevidence from Chinese Medicinal Prescription in Construction of Integrated Disease-syndrome Animal Model： Xiaoyaosan as Counterevidence for Depression of Liver Depression and Spleen Deficiency Syndrome / 中国实验方剂学杂志

Objective:To seed for stable time window of the integrated disease-syndrome animal model based on the counterevidence from Chinese medicinal prescriptions， and to verify syndrome stability and reliability. Method:A model of depression was established by exposing rats to chronic unpredictable mild stress （CUMS）， followed by body weight measurement， sugar water test， behavioral test， and brain 5-hydroxytryptamine（5-HT） detection. The identification of liver depression and spleen deficiency syndrome was conducted after the equivalent transformation of human clinical symptoms into macroscopic representations of rats. Based on the dynamically collected macroscopic representation scale， Xiaoyaosan was used to reversely verify the stability and reliability of the integrated disease-syndrome animal model of depression due to liver depression and spleen deficiency. Result:The sugar water consumption and the number of crossings and the total movement distance in the open field test of 16-week-old rats in the CUMS （eight weeks of CUMS） group were significantly lower than those in the normal group （<italic>P</italic><0.05）. According to the immunohistochemical results， the 5-HT content in hippocampal area CA2 of rats in the CUMS group was also significantly lowered as compared with that in the normal group（<italic>P</italic><0.05），which indicated that depression was successfully modeled. The liver depression and spleen deficiency syndrome was present in 14-week-old rats （six weeks after CUMS）of the CUMS group， and the number of rats experiencing the liver depression and spleen deficiency syndrome reached the peak in the 16th week （eight weeks after CUMS），accounting for 70% of the total number. Thereafter， the number decreased gradually. The syndrome scores of the 14-， 16-， 18-， 20-， and 22-week-old rats in the Xiaoyaosan group were reduced by 66.6%， 70.7%， 54.8%， 50.4%， and 44.8%， which were graded as effective， marked effective， effective， effective， and effective， respectively. Conclusion:The age of 14-16 weeks（six to eight weeks after CUMS） is considered the stable and reliable time window for depression due to liver depression and spleen deficiency.

Effect of mechanical environment on differentiation of mesenchymal stem cells at fracture site during early stage of fracture healing and research of related mechanisms / 中国药理学通报

Aim To explore the influence of mechani-cal environment on differentiation of mesenchymal stem cells ( MSCs) at fracture site during early stage of frac-ture healing. Methods The rat femur fracture models were established and fixed with external fixation frame of different stiffness coefficient and were divided into three groups, namely, the sham group with super-high stiffness external fixation frame, the high stiffness fixa-tion frame group and the low stiffness fixation frame group. The bone callus and the degree of fracture heal-ing after two weeks compared with the very day after surgery were observed by X-ray. And the effects were evaluated respectively by histopathology 6 weeks after operation. Callus tissues of 2 days, 6 days, 10 days, 14 days after operation were acquired. Runx2, Osterix and Sox9 expression were measured by RT-qPCR. Runx2 and Sox9 were tested by Western blot. Results X-ray showed that the amount of callus of high stiff-ness group was significantly less than that of low stiff-ness group. Histological study showed, sham group and high stiffness group achieved less callus and had lots of active bone cells while low stiffness group got cartilage ossification well. The results of RT-qPCR showed that the level of Runx2 , Osterix increased with-in 14 days. And Sox9 reached the highest level in sham group and high stiffness group 10 days after sur-gery and declined in 14 days while low stiffness group had been rising within 14 days after surgery. The ex-pression levels of Runx2 , OSX and Sox9 in 14 days af-ter operation presented statistically significant differ-ence among the three groups at the same time point, i. e. low stiffness group > high stiffness group > the sham group ( P <0.05 ) . The results of Western blot were consistent with those of RT-qPCR. Conclusion The differentiation of MSCs at fracture site is affected by the mechanical environment, and subtle movement could promote the healing of fracture sites.

Inhibition of Yuyihe Powder on Tumor Growth in Mice Models of Sarcoma 180 / 中草药·英文版

Objective To explore the antitumor effect of Yuyihe Powder (Yu Yi He San, YYHS) and its antitumor mechanism. Methods After treatment, tumor weight, immune apparatus weight, the life span of transplanted animals, spleen lymphocyte proliferation assays, and IL-2 concentration in mouse serum were recorded or detected. Results YYHS showed strong antitumor ability. Compared with control group, mid-dose YYHS (1.0 g/kg) could inhibit the tumor growth, prolong the life span of S180-bearing mice to some extent, significantly increase the thymic and splenic indices of S180 mice, and strongly promote the secretion of IL-2 in blood; The inhibitory rate on tumor growth and life prolongation rate were 37.1% and 38.37%, respectively. Conclusion YYHS could not only significantly inhibit the growth of S180 cells, but also markedly prolong the survival time of S180 bearing mice. The mechanism of antitumor effect could obviously enhance immunologic function of the S180 bearing mice to inhibit the growth of S180 cells.

Clinical features and prognostic factors in patients with leptomeningeal metastases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and prognostic factors of leptomeningeal metastases (LM) from solid tumors and to develop better treatment strategies.</p><p><b>METHODS</b>The clinical characteristics and follow-up results of 77 cases of leptomeningeal metastases (LM) from solid tumors diagnosed and treated in our hospital from 2002 to 2011 were retrospectively analyzed. Clinical characteristics, treatment methods and overall survival were analyzed using Kaplan-Meier method and Cox regression model.</p><p><b>RESULTS</b>The median survival time for all the patients was 88 days. KPS score, control of the primary tumor and systemic treatment were correlated with survival time for the patients (P < 0.05 for all). The median survival time of systemic treatment was 150 d and those without systemic treatment (chemotherapy and/or targeted therapy) after LM was 60 d (P = 0.001). Systemic therapy combined with local treatment (radiotherapy to the meninges or intrathecal chemotherapy) further improved the survival time of patients. Multivariate analysis showed that KPS and short-term therapeutic response for the LM were independent prognostic factors (P < 0.05 for both).</p><p><b>CONCLUSIONS</b>KPS and short-term therapeutic response are independent prognostic factores for leptomeningeal metastases from solid tumors. Systemic chemotherapy or targeted therapy can prolong the survival time. Systemic treatment (chemotherapy and/or targeted therapy) combined with radiation therapy or intrathecal injection may further improve the clinical outcomes.</p>

Detection of epidermal growth factor receptor gene mutations in advanced non-small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the mutations of epidermal growth factor receptor (EGFR) in tumor tissue and pleural effusion in advanced non-small cell lung cancer (NSCLC) patients, and to analyze the relationship between EGFR mutations and the clinicopathologic characteristics.</p><p><b>METHODS</b>Two-hundred and forty-one cases of formalin-fixed, paraffin-embedded tumor tissues and 14 paired pleural effusions from advanced NSCLC patients were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by scorpions and amplification refractory mutation system (scorpions ARMS) using real time PCR. The relationship between the EGFR mutations and clinical parameters was analyzed using statistical methods. EGFR mutation of 37 cases were detected with direct sequencing, and assessed the sensitivity, the specificity and the accuracy of scorpions ARMS.</p><p><b>RESULTS</b>EGFR somatic mutations were detected in 114 of 234 advanced NSCLC patients, with the mutation rate of 48.7%, including deletions in exon 19 in 65 patients and point mutation of L858R in exon 21 in 39 patients; both accounting for 91.2% (104/114) of all types of EGFR mutations. The test results of 14 paired pleural effusion specimens were entirely the same to the tissues. The concordance rate of 2 different detection methods was 94.6%. Mutation rate was higher in women (55.9%) than in men (42.2%), and there was no difference in mutation rates between smokers and non-smokers; patients in stage IIIB and stage IV; adenocarcinoma and non-adenocarcinoma.</p><p><b>CONCLUSIONS</b>EGFR somatic mutations appear to occur frequently in Chinese. Scorpions ARMS technology is a sensitive method to detect EGFR mutations and is suitable for screening patients who would likely respond to EGFR inhibitors therapy.</p>

Efficacy of erlotinib after the failure of gefitinib in patients with metastasis of non-small cell lung cancer with unknown EGFR mutation status / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of erlotinib in patients with metastasis of non-small cell lung cancer who had benefits from initial gefitinib treatment but finally demonstrated resistance, especially in those of unknown EGFR mutation status, and to compare the efficacy of erlotinib between patients who received erlotinib immediately after gefitinib failure and those who received chemotherapy before erlotinib.</p><p><b>METHODS</b>Forty Chinese patients who had been treated with erlotinib (150 mg daily) after gefitinib (250 mg daily) failure were evaluated retrospectively. All of these patients had achieved gefitinib treatment for at least three months with response of partial remission or stable disease. Among them, 16 patients shifted to erlotinib immediately after progression (Group G-E), and the other 24 patients inserted chemotherapy between gefitinib and erlotinib (Group G-C-E).</p><p><b>RESULTS</b>In the whole group, the disease control rate (DCR) of erlotinib was 52.5% (21/40) while the objective response rate (RR) was only 10.0% (4/40). The RR of the group G-E was 6.2% and the group G-C-E was 12.5%, and the DCR was 56.2% and 50.0% in the two groups, respectively, both without significant differences (P = 0.638 and P = 0.755). There was no correlation between the efficacy of erlotinib and that of initial gefitinib in both group G-E and group G-C-E (P = 0.365 and P = 0.658). The median progression-free survival (PFS) and overall survival (OS) for the erlotinib treatment were 3.0 and 12.0 months in the 40 patients. Statistically no significant difference was observed in PFS (4 months in the group G-E and 2 months in the group G-C-E, P = 0.768) and OS (12 months in both Groups, P = 0.510).</p><p><b>CONCLUSIONS</b>Erlotinib can be considered either immediately after gefitinib failure or following the insertion of chemotherapy after gefitinib failure in progressive non-small cell lung cancer patients who initially benefited from gefitinib.</p>

Factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinical factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer.</p><p><b>METHODS</b>Clinical data were retrospective analyzed to determine the clinical factors affecting the outcome of 166 patients with advanced non-small cell lung cancer who received EGFR-TKI treatment in our hospttal from January of 2005 to December of 2006.</p><p><b>RESULTS</b>One hundred and nineteen patients benefited from EGFR-TKI treatment in the total of 166 patients and the disease control rate was 71.7%. Among the factors analyzed, sex, age, smoking, pathological type, brain and bone metastasis or not when EGFR-TKI was used, the time using EGFR-TKI and the level of LDH at the time of diagnosis had no significant effect on the clinical benefit rate. Among the 126 patients with serum CEA assayed at diagnosis, 84 cases had a higher serum CEA level. Compared with the patients with normal serum CEA level, the patients with a higher serum CEA level benefited more easily from EGFR-TKI therapy, with a disease control rate of 79.8% and 59.5%, respectively (P = 0.016). Among the patients who got benefits from EGFR-TKI treatment, smoking and the CEA level at diagnosis had effects on the duration of progression-free survival. The progression free survivals were 9.57 ± 6.75 months in non-smokers, 4.86 ± 3.44 months in light-smokers and 5.25 ± 4.34 months in heavy-smokers (P = 0.007). The progression free survival was 9.45 ± 7.48 months in the group with a higher serum CEA level and 6.52 ± 4.46 months in the group with normal serum CEA level (P = 0.036).</p><p><b>CONCLUSIONS</b>In patients with advanced non-small cell lung cancer, EGFR-TKIs treatment is safe and effective. The patients with high CEA level are prone to benefit from it.</p>

Association of serum EGFR protein concentration with the efficacy of Gefitinib in the treatment of advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer (NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC.</p><p><b>METHODS</b>Ninety-nine cases were enrolled in this study. Pathological tissue specimens and paired peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene mutation were detected by direct sequencing. The concentration of plasma EGFR protein was detected by ELISA. Univariate and multivariate statistical analyses of the efficacy and survival were performed using SPSS 13.0 software.</p><p><b>RESULTS</b>The response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was 55.42 µg/L. The RR and CBR of patients with EGFR gene mutation was significantly higher than those without mutation (65.7% vs. 43.8%, P = 0.037; 94.3% vs. 71.9%, P = 0.008). The median PFS was prolonged (23 months vs. 10 months, P = 0.014). The CBR of patients with high EGFR protein expression (concentration ≥ 55.42 µg/L) was significantly higher than those with low expression (90.0% vs 64.1%, P = 0.004), and the median PFS was prolonged (21 months vs. 8 months, P = 0.016). EGFR protein level was an independent factor affecting the EGFR gene mutation status. The Correlation between EGFR gene mutation status and EGFR protein level was positive.</p><p><b>CONCLUSIONS</b>Gefitinib is effective in the treatment of advanced NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR protein level in peripheral blood may be a molecular biomarker in prediction of efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.</p>

Progress in sulfur dioxide biology: from toxicology to physiology / 生理学报

Based on our studies for more than 20 years, we review the recent advances in sulfur dioxide (SO2) biology. Three sections are involved: (1) The studies on SO2 toxicological effects and its underlying mechanisms; (2) The new investigations on SO2 donor and physiological role of SO2 as a new type-gas transmitter; (3) The observations on pathophysiologic roles of SO2.

Phase II clinical study on the modified DCF regimen for treatment of advanced gastric carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A phase III trial involving docetaxel, cisplatin, and fluorouracil (DCF) in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel (D) and cis-platinum (CDDP), and administered 5-fluorouracil (5-FU) via a continuous intravenous (CIV) infusion.</p><p><b>METHODS</b>Chemotherapy-naive patients with gastric adenocarcinomas received D (60 mg/m(2) 1 hour on day 1), CDDP (30 mg/m(2) on days 1 and 2), and 5-FU (1500 mg×m(-2)×24 h(-1) CIV on days 1 and 8 every 3 weeks). The primary endpoint was the response rate.</p><p><b>RESULTS</b>Fourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1% complete remission (CR), 71% partial remission (PR), 14% stable disease (NC/SD), and 7.1% progressive disease (PD). The median survival time was 13 months. Nine patients (64%) had grade III-IV neutropenia, and 4 patients (29%) had grade IV neutropenia, among whom 1 had grade IV neutropenia with grade III nausea and vomiting.</p><p><b>CONCLUSION</b>The modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer.</p>

Clinical study on recombinant human interleukin-2 (Proleukin) in the treatment of metastatic renal cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of subcutaneous injection of recombinant human interleukin-2 (Proleukin) in the treatment of metastatic renal cell carcinoma (RCC).</p><p><b>METHODS</b>Forty-one patients with pathologically confirmed metastatic RCC after radical nephrectomy were enrolled into this study. Two or four consecutive cycles of subcutaneous injection of rhLL-2 were given, with each cycle duration of five weeks consisting of 4 weeks of treatment and one week of rest. The rhLL-2 was injected twice daily subcutaneously at a dose of 9 MIU on D1-D5 during week one, then 9 MIU twice daily on D1-D2 and followed by 9 MIU daily on D3-D5 during week 2-4. Patients were evaluated after the second cycle of treatment. If an objective response or stable disease was observed, the patient would receive another two cycles of treeatment.</p><p><b>RESULTS</b>Of the 41 patients, the overall objective response rate was 17.1% (95% confidence interval, 5.6% to 28.6%) with a complete response (CR) rate of 0.0% and partial response rate (PR) of 17.1%. However, nineteen patients (46.3%) still had a stable disease (SD), and 15 (36.6%) had progressed disease (PD). The disease control rate was 63.4% and the median time to progression (mTTP) was 6 months. The 1-year survival rate was 71.2% with a median overall survival (mOS) rate of 22.5 months. Among 36 PP population, the overall objective response rate was 19.4% (95% confidence interval, 6.5% to 32.3%) with CR rate of 0.0% and PR rate of 19.4%. Sixteen patients(44.4%) had stable disease, and 13 (36.1%) progressed disease. The disease control rate was 63.9%. The 1-year survival rate was 66.7% with a median time to progression of 6 months. The median overall survival (mOS) had not reached yet. The follow-up data showed that the long term survival of the patient who responsed to the IL-2 therapy can be prolonged. Severe toxicity (> or = grade III) was rarely observed. Grade I or II toxicities such as fatigue (100.0%) and fever (82.9%) were frequently observed but reversible.</p><p><b>CONCLUSION</b>Subcutaneous injection of recombinant human interleukin-2 may prolong the survival of patients with a metastatic renal cell carcinoma. This regimen is tolerable with rare severe toxicities.</p>

Value of plasma tissue factor, tissue factor pathway inhibitor and factor VII assessments in patients with acute myocardial and cerebral infarction / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the clinical implications of changes in plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and factor VII (FVII) after the onset of acute myocardial infarction (AMI) and acute cerebral infarction (ACI).</p><p><b>METHODS</b>Sixty-nine patients with AMI, 71 with ACI and 50 age-matched healthy volunteers were enrolled in this study. Blood samples were obtained from the healthy subjects and from the patients at the early stage of AMI and ACI onset for examination of plasma TF and TFPI activity using chromogenic assay, and the plasma TF and TFPI antigens were measured by enzyme-linked immunosorbent assay (ELISA). The plasma FVII coagulation activity (FVII:C) was also measured, and the plasma FVIIa determined using soluble TF assay.</p><p><b>RESULTS</b>Compared with the healthy control group, AMI patients had significantly enhanced plasma TF and TFPI activities and elevated TF and TFPI antigen levels (P<0.05), with also markedly increased FVIIa (P<0.05) but comparable FVII:C (P>0.05). In ACI patients, the plasma TF activity and antigen were obviously increased in comparison with the control group (P<0.05), but plasma TFPI activity and antigen were lowered (P<0.05), and both the FVII:C and FVIIa were markedly higher (P<0.05). Significant differences were noted in plasma TF and TFPI activities and their antigen levels as well as in FVII:C, but not in FVIIa between AMI and ACI patients.</p><p><b>CONCLUSION</b>V Following the onset of AMI and ACI, TF pathway is initiated and the risk of thrombogenesis increases, and the assessment of TF pathway is therefore of value for understanding the development of the condition.</p>

Phase I/II clinical trial of weekly administration of docetaxel plus cisplatin for advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime.</p><p><b>METHODS</b>In phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial.</p><p><b>RESULTS</b>In the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia.</p><p><b>CONCLUSION</b>Weekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.</p>

Recent Progress in Research on Muscle-derived Stem Cells / 中国生物工程杂志

Muscle recently has been identified as a good source of adult stem cells that can differentiate into cells of different lineages.Researchers have identified two types of stem cells in skeletal muscle.Further research is necessary to delineate the relationship between different populations of musclederived stem cells(MDSCs)and between MDSCs and other adult stem cells.The methods used to isolate these cells appear to influence the stem cell characteristics.As these efforts continue,the potential for MDSCsbased therapy for other musculoskeletal injuries,as well as for cardiac and smooth muscle injuries,is currently being explored.The behavior,biocharacteristic,isolation,differentiation and the probability of application to regenerate lost or diseased tissue of MDSCs were summarized.

Expression of orexin A, orexin receptor-1, and Ob-R of hypothalamus in rats with chronic renal failure / 中国医学科学院学报

<p><b>OBJECTIVE</b>To examine the changes of expressions of orexin A, orexin receptor-1 (OX1R), prepro-orexin (Prepro-OX) mRNA, OX1R mRNA and ob-R of hypothalamus in rats with chronic renal failure (CRF).</p><p><b>METHODS</b>Sixty-two male Wister rats weighing 200-250 g were divided into three groups, including group 1 (normal, n = 5), group 2 (sham-operated, n = 25) and group 3 (CRF, n = 32). Hypothalamus orexin A was assayed by radioimmunoassay. Serum leptin was assayed by enzyme linked immunosorbent assay. The expression of Prepro-OX mRNA and OX1R mRNA of hypothalamus were measured by reverse transcription polymerase chain reaction, and expression of orexin A, OX1R and ob-R by immunohistochemistry. Automatic biochemical analyzer was used to measure the serum creatinine.</p><p><b>RESULTS</b>Hypothalamus orexin A levels were negatively correlated (r = -0.63, P < 0.001) with serum leptin levels in the rats. The expression of hypothalamus Prepro-OX mRNA in CRF rats was significantly lower than that of sham-operation at week 12 (P < 0.01). Hypothalamus Prepro-OX mRNA levels were negatively correlated (r = -0.81, P < 0.001) with the levels of serum leptin and serum creatinine (r = -0.68, P < 0.05) in the rats at week 12. The expression of hypothalamus OX1R mRNA in CRF rats was lower than that of sham-operation at week 12 (P > 0.05). Specific immunoreactivity for orexin A was present in perikeryon of the hypothalamus neuron. Specific OX1R-like immunoreactivity was observed in some nerve fibres. Specific immunoreactivity for ob-R was present in membranes of the hypothalamus neuron. Hypothalamus neurons of orexin A-like specific immunoreactivity in CRF rats were significantly fewer than those in shamoperated rats at week 8. Hypothalamus neurons of OX1R-like specific immunoreactivity in CRF rats were similar to those in sham-operated rat at week 8. Hypothalamus neurons of ob-R-like specific immunoreactivity in CRF rats were significantly more than those in sham-operated rats at week 8.</p><p><b>CONCLUSIONS</b>The lower hypothalamus orexin A levels may be induced by high serum leptin level in CRF rats. The lower expression of hypothalamus Prepro-OX mRNA in CRF rats may be one of the main causes inducing lower hypothalamus orexin A. The expression of OX1R in hypothalamus neurons is somewhat reduced and the expression of ob-R in hypothalamus neurons is somewhat raised in CRF rats. These remain to be studied further.</p>