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.

Predictive value of vascular health indicators on newly cardiovascular events: Preliminary validation of Beijing vascular health stratification system / 北京大学学报(医学版)

OBJECTIVE@#To explore the predictive value of carotid femoral artery pulse wave velocity (CF-PWV), carotid radial artery pulse wave velocity (CR-PWV), cardio-ankle vascular index (CAVI), and ankle brachial index (ABI) on coronary heart disease (CHD) and cerebral infarction (CI), and the preliminary validation of Beijing vascular health stratification (BVHS).@*METHODS@#Subjects with at least 2 in-patient records were included into the study between 2010 and 2017 from Vascular Medicine Center of Peking University Shougang Hospital. Subjects with CHD or CI, and without data of vascular function at baseline were excluded. Eventually, 467 subjects free of CHD [cohort 1, mean age: (63.4±12.3) years, female 42.2%] and 658 subjects free of CI [cohort 2, mean age: (64.3±12.2) years, female 48.7%] at baseline were included. The first in-patient records were as the baseline data, the second in-patient records were as a following-up data. Cox proportional hazard regression was used to establish the predictive models of CHD or CI derived from BVHS by multivariable-adjusted analysis.@*RESULTS@#The median follow-up time of cohort 1 and cohort 2 was 1.9 years and 2.1 years, respectively. During the follow-up, 164 first CHD events occurred in cohort 1 and 117 first CI events occurred in cohort 2. Four indicators were assessed as continuous variables simultaneously by multivariable-adjusted analysis. In cohort 1, CF-PWV, CR-PWV, ABI, and CAVI reached statistical significance in the multivariable-adjusted models (P<0.05). In cohort 2, only CAVI (P<0.05) was of statistical significance. In addition, the higher CF-PWV became a protector of CHD or CI (P<0.05). The prediction value of BVHS reached the statistical significance for CHD and CI in the unadjusted models (all P<0.05), however, BVHS could only predict the incidence of CHD (P<0.05), but not the incidence of CI (P>0.05) in the multivariable-adjusted models. CF-PWV, CR-PWV, ABI, and CAVI were associated factors of CHD independent of each other (P<0.05), only CAVI (P<0.05) was the risk factor of CI independent of the other three.@*CONCLUSION@#The different vascular indicators might have different effect on CHD or CI. CAVI might be a stable predictor of both CHD and CI. Higher baseline CF-PWV was not necessarily a risk factor of CHD or CI because of proper vascular health management. BVHS was a potential factor for the prediction of CHD, and further research is needed to explore the prediction value for CI.

Espression and significance of TMSG-1 expression in primary and liver metastases of colorectal cancer tissues / 临床与实验病理学杂志

Purpose To investigate the expression of tumor metastasis suppressor gene-1 (TMSG-1) in colorectal cancer tissues and liver metastases,and to analyses the relationship between expression of TMSG-1 and clinicopathologic characteristics. Methods Immunohistochemical SP methods was used to detect the expression of TMSG-1 protein in 200 cases of colorectal cancer and 52 cases of liver metastases. Results The ratio of high,moderate and negative of TMSG-1 expression in primary colorectal carcinoma were 42. 5％ (85/200) ,29. 5％ (59/200) and 28. 0％ (56/200) respectively. The expression of TMSG-1 was significantly associated with tumor differentiation, invasion depth,lymph node metastasis,distant metastasis and TNM stages (P < 0. 05) ,but unrelate to age,gender and tumor size. The high, moderate and negative expression ratio of TMSG-1 in liver metastases were 17. 3％ (9/52) ,50. 0％ (26/52) ,32. 7％(17/52) ,respectively. The expression of TMSG-1 in liver metastases was significantly lower than that in primary lesion (P < 0. 05) . The expression of TMSG-1 in liver metastases, and there was no significant correlation between the expression of TMSG-1 in liver metastases and clinicopathologic characteristics. Conclusion The expression of TMSG-1 is significantly down-regulated in the liver metastases,which is associated with the development and progression of colorectal cancer. TMSG-1 will be used as a new tumor marker for predicting the prognosis of colorectal cancer.

Impact of High-salt Diet on Plasma Level of Vascular Endothelial Growth Factor C and Its Relationship to Blood Pressure in Healthy Subjects and Hypertension Patients / 中国循环杂志

Objectives: To investigate the impact of high-salt diet on plasma level of vascular endothelial growth factor C (VEGF-C) in healthy subjects and hypertension patients; to explore the relationship between VEGF-C level and blood pressure (BP). Methods: Our research included in 2 groups: Essential hypertension (EH) group, 75 patients treated in our hospital from 2013 to 2014 and Control group, 98 healthy subjects at the same period. Using salt-intake 6 g/day as the borderline, both groups were respectively divided into High-sodium diet (HS) subgroups and Low-sodium diet (LS) subgroups. The age, gender, creatinine clearance (CCr), UA, fast blood glucose (FBG), body mass index (BMI), blood lipids (TC, TG, HDL-C, LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), heart rate (HR) and CF-PWV were compared between EH group and Control group, HS subgroups and LS subgroups. Results: Compared with Control group, EH group had increased plasma level of VEGF-C, (3 940.8±1 141.1) pg/ml vs (2 938.0±987.0) pg/ml, P<0.001; the age, BMI, SPB, DBP, PP, MAP and CF-PWV were different between 2 group, all P<0.005. In ES group, compared with LS subgroup, HS subgroup showed the higher VEGF-C (4 208.8±113.1) pg/ml vs (3 515.8±1 070.1) pg/ml, P=0.009; the age, SBP, DBP and PP were different between 2 group, all P<0.005. In Control group, compared with LS subgroup, HS subgroup showed the higher VEGF-C (3 158.7±917.2) pg/ml vs (2 655.7±1 011.3) pg/ml, P=0.012; the age BMI and CCr were different between 2 group, all P<0.005, while BP was similar between 2 subgroups. Spearman correlation study presented that with adjusted confounding factors, no matter in all participates and in EH group or Control group, MAP were positively related to plasma levels of VEGF-C (r=0.536, P<0.001 and r=0.546, P=0.002 or r=0.291, P=0.006) respectively. Conclusions: High-sodium diet could increase plasma VEGF-C level in either healthy subjects or hypertension patients, VEGF-C level was positively related to BP.

Study on model of tree shrew induced by chronic corticosterone injection in anxious depression / 中国药理学通报

Aim To investigate the effects of chronic corticos-terone injection on anxiety and depression-like behavior of tree shrews, evaluate the predictability of drug and establish a novel animal model of anxious depression .Methods Twelve Chinese and Burma tree shrews were randomly divided into normal group, model group and venlafaxine group .The anxious depres-sion model of tree shrew was established by chronic corticoster-one injection ( ih, 27 mg· kg-1 , 21 d) .The venlafaxine group received intragastric administration (6 mg· kg-1).Autonomous activity score, sugar water preference test and Morris water maze test were used to evaluate the anxiety and depression-like behav-ior of tree shrews .The expressions of CRH , ACTH and COR in the tree shrew plasma were determined by Elisa kit .The con-tents of monoamine neurotransmitters of tree shrews in the hippo-campus , amygdala and prefrontal cortex were detected by HPLC-ECD.Results Compared with the normal group , the autono-mous activity score , sugar water partial eclipse degree and the learning and memory ability significantly decreased (P<0.01), while the contents of CRH , ACTH and COR significantly in-creased ( P<0.05) , and the contents of 5-HT, NE and DA in the hippocampus , amygdala and prefrontal cortex declined in the model group(P<0.05).In the venlafaxine group, the learning and memory abilities of the tree shrews were improved , the lev-els of CRH and COR in plasma were significantly decreased ( P<0.05), and the contents of 5-HT, NE and DA were increased (P<0.05).Conclusions The tree shrews of anxious depres-sion have obvious HPA axis hyperactivity and monoamine neuro-transmitter disorder , and venlafaxine can reverse this phenome-non, indicating that the tree shrews model of anxious depression has drug predictability , which is a kind of novel animal model of anxious depression closer to human in clinic .

Effects of S100 B, AQP4 and CX43 expressions on the function of the blood brain barrier in hippocampus of diabetic rats with depression / 基础医学与临床

Objective To investigate the effects of S 100B, AQP4, and CX43 on the function of the blood brain barrier in the hippocampus of diabetic rats with depression .Methods Rats were divided into the diabetic group [ two weeks of high-fat diet and injection of Streptozotocin (STZ, 38 mg/kg)], depression group(chronic unpredictable stress for 28 days) , the diabetes mellitus with depression group ( combined with the above two methods ) , and the control group .The behavior of rats was evaluated with open-field test and Morris test .The expressions of AQP 4 and CX43 in rat hippocampus blood-brain barrier were detected by immunocytochemistry .Serum S100B level was detected by ELISA.Results Compared with control group, the number of autonomic activity and the space exploration times were decreased, the escape latencies were significantly longer in the Morris water maze test(P<0.05 or P<0.01) of the diabetes group and depression group; Serum S100B levels increased significantly ( P<0.01);the expressions of AQP4 and CX43 were decreased(P<0.01).Compared with diabetic group, the number of auto-nomic activity and the space exploration times were decreased , the escape latencies were significantly longer in the Morris water maze test( P<0.05 or P<0.01) of the diabetes group and depression group;Serum S 100B lev-els increased significantly( P<0.05);the expressions of AQP4 and CX43 were decreased(P<0.05 or P<0.01). Conclusions S100B, AQP4 and CX43 expression disorder may be one of the mechanisms of diabetes mellitus complicated with depression.

Preparation and properties of thermosensitive in situ gel for ophthalmic formulation containing pearl hydrolyzate / 药学学报

The study was designed to generate an ophthalmic thermosensitive in situ gel with improved mechanical and mucoadhesive properties that may prolong the retention time to enhance the bioavalability of pearl hydrolyzate. The gene was comprised of poloxamer 407, poloxamer188 and Carbopol 934, which were optimized by central composite design and response surface methodology. The rheological properties, transcorneal permeability, retention time and in vitro release behaviors of the optimal gel formulation were investigated. The gel was Newtonian liquid at 25℃ and performed as a semisolid gel with non-Newtonian liquid property with a gelation time of 13 s at 35℃. Compared with a conventional eye drops, the ophthalmic in situ gel exhibited a sevenfold increase in retention with a sustained release behavior, which was observed with suitable permeability coefficient at 5.58 cm·s-1. In conclusion, the new gel of pearl hydrolyzate prolonged the release duration of drug, which may decrease the frequency of administration of pearl hydrolyzate. kilometers with ecological similarity between 20% and 40%, mainly in Yunnan, Guangxi, Guangdong, Guizhou, Hainan, Sichuan, Fujian and Chongqing. The climate factors mainly affecting the distribution of Panax notoginseng (Burk.) F. H. Chen were precipitation of warmest quarter, SD of temperature seasonality, altitude, isothermality, coefficient of variation of precipitation seasonality, mean temperature of monthly, precipitation of driest month, reference bulk density of soil and soil texture.

Mechanism of anti-aging therapy on Parkinson's disease / 中国中药杂志

Many studies have shown that anti-aging treatment has value to prevention and treatment of some diseases. For the treatment of Parkinson' s disease, clinical and experimental researches have proved the potential value of anti-aging treatment, yet the mechanism remains unclear. For this reason, this work used the anti-aging prescriptions of Buyang Huanwu decoction in traditional Chinese medicines example to discover the anti-aging treatment mechanism on Parkinson's disease. The results showed that the mechanism of mitochondrial damage, apoptosis, free radicals and oxidative stress could contribute to the treatment of Parkinson' s disease. Buyang Huanwu decoction is more than as the carrier in this article, the discovered anti-aging treatment mechanism Parkinson's disease is not confined to Buyang Huanwu decoction, could also be used to understand the anti-aging treatment mechanism using other prescription. The main contribution of this paper is to clarify the mechanism of anti-aging treatment of Parkinson's disease, and provide a new strategy for the treatment and prevention of Parkinson's disease.

Effect of Bear Bile Powder and Its Succedaneum on Peripheral Blood and Bone Marrow Megakaryocytes in Mouse Model with Thrombocytopenia Induced by Cytosine Arabinoside / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of bear bile powder and ursodesxy cholic acid (UDCA) on peripheral blood, bone marrow megakaryocyte and immune organs in mouse model with thrombocytopenia, so as to provide a reference for studying the curative effects of bear bile powder and its succedaneum on thrombocytopenic purpura (TP).</p><p><b>METHODS</b>The mouse model with thrombocytopenia indued by cytosine arabinoside (Ara-C) was established, a total of 70 mice were randomly divided into normal group, model group, prednisone group, bear bile (middle and high dose) powder group and UDCA (middle and high dose) group. From the first day of making model mice in the each group, 0.4 ml/(20 g·d) corresponding drug was administered by infusion. At day 10 after treatment the peripheral blood, spleen and thymus organ index, the number of bone marrow megakaryocyte in each group were compared.</p><p><b>RESULTS</b>compared with the normal group, the Plt, WBC and megakaryocyte counts in model group decreased, the spleen index increased obviously (P<0.05), but the WBC count returned to normal by 10 days; after treatment, compared with model group, the Plt, WBC and megakaryocyte counts of treated groups increased, spleen index decreased significantly (P<0.05), but the WBC count in prednisone group decreased, which in bear bile powder (high) group and UDCA (high) group were particularly significant.</p><p><b>CONCLUSION</b>The bear bile powder and UDCA have been confirmed to have therapeutical effect on thrombocytopenia models induced by Ara-C, UDCA can substitute bear bile powder as a treatment drug for thrombocytopenic purpura.</p>

The effects of Tianqijiangtang capsule combined with Metformin on the levels of interleukin-6,tumor necrosis factorαand C-reactive protein in patients with type 2 diabetes mellitus / 中国糖尿病杂志

Objective To explore the effects of Tianqijiangtang capsule combined with Metformin on the levels of IL‐6 ,TNF‐α and C‐RP protein in patients with T2DM. Methods 80 T2DM were randomized into control group (treatment with Metformin ,n= 40) and treatment group (treatment with Tianqijiangtang in combination with Metformin ,n=40). The changes of levels of IL‐6 ,TNF‐α and C‐RP were observed before and after the treatment. Results Compared to the pretreatment in the same group and after treatment in control group ,IL‐6 ,TNF‐αand C‐RP of treatment group were reduced significantly [(6.79 ± 0.60) ,(7.15 ± 0.62) vs (5.08 ± 0.43)pg/ml;(8.94 ± 0.55) ,(8.61 ± 0.66) vs (5.18 ± 0.45) pg/ml;(6.79 ± 0.60) ,(6.58 ± 0.59) vs (5.56 ± 0.30) mg/L ,P<0.01]. Conclusion Tianqijiangtang capsule combined with Metformin can decrease the levels of IL‐6 ,TNF‐αand C‐RP in T2DM patients.