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.

Surveillance of antibody level of influenza among physical examination population of Shenzhen City from 2014 to 2018 / 上海预防医学

Objective To provide the basis for influenza epidemic prevention and control by monitoring the antibody level of influenza among the general population in Dapeng New District of Shenzhen City. Methods A total of 1 350 serum samples of people were collected ten times from 2014 to 2018, and the antibody level was tested by hemagglutination-inhibition test. Results During 2014-2018 years, only the positive rate of antibody to H3N2 was above 60%.The positive rates of H1N1, H3N2, BV and BY were 50.0%, 85.6%, 35.4% and 45.6%, respectively, and the geometric mean titers (GMT) of antibody were 8.2, 81.5, 3.9 and 6.4, respectively.Influenza antibody titers of 1 : 160 and 1 : 320 were mainly distributed in influenza H3N2.The antibody level of BV and BY in age group 0~4 years was 29.0% and 30.4% separately. Conclusion It is imperative to enhance the surveillance of antibody level of influenza among general population in Dapeng New District, to investigate the epidemic development trend of influenza constantly, and to prevent and control the outbreak of influenza epidemics.

Construction and analysis of a breast cancer gene-drug network model / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a breast cancer gene-drug network model for extracting and predicting the correlations between breast cancer-related genes and drugs.</p><p><b>METHODS</b>We developed an algorithm based on the ABC principle and the association rules to obtain the correlations between the biological entities. For breast cancer, we constructed 3 different correlations (gene-gene, drug-drug and gene-drug) and used the R language to implement the associated network model. The reliability of the algorithm was verified by ROC curve.</p><p><b>RESULTS</b>We identified 185 breast cancer-associated genes and 98 associations between them, 97 drugs and 170 associations between them. The breast cancer genes-drugs network contained 127 genes and 77 drugs with 384 associations between them.</p><p><b>CONCLUSIONS</b>We identified a large number of different correlations between the breast cancer-related genes and drugs and close correlations between some biological entity pairs that have not yet been reported, which may provide a new strategy for experimental design for testing personalized breast cancer treatment.</p>

Comparative study of DSC-PWI and 3D-ASL in ischemic stroke patients / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to quantitatively analyze the relationship between three dimensional arterial spin labeling (3D-ASL) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) in ischemic stroke patients. Thirty patients with ischemic stroke were included in this study. All subjects underwent routine magnetic resonance imaging scanning, diffusion weighted imaging (DWI), magnetic resonance angiography (MRA), 3D-ASL and DSC-PWI on a 3.0T MR scanner. Regions of interest (ROIs) were drawn on the cerebral blood flow (CBF) maps (derived from ASL) and multi-parametric DSC perfusion maps, and then, the absolute and relative values of ASL-CBF, DSC-derived CBF, and DSC-derived mean transit time (MTT) were calculated. The relationships between ASL and DSC parameters were analyzed using Pearson's correlation analysis. Receiver operative characteristic (ROC) curves were performed to define the thresholds of relative value of ASL-CBF (rASL) that could best predict DSC-CBF reduction and MTT prolongation. Relative ASL better correlated with CBF and MTT in the anterior circulation with the Pearson correlation coefficients (R) values being 0.611 (P<0.001) and-0.610 (P<0.001) respectively. ROC curves demonstrated that when rASL ≤0.585, the sensitivity, specificity and accuracy for predicting ROIs with rCBF<0.9 were 92.3%, 63.6% and 76.6% respectively. When rASL ≤0.952, the sensitivity, specificity and accuracy for predicting ROIs rMTT>1.0 were 75.7%, 89.2% and 87.8% respectively. ASL-CBF map has better linear correlations with DSC-derived parameters (DSC-CBF and MTT) in anterior circulation in ischemic stroke patients. Additionally, when rASL is lower than 0.585, it could predict DSC-CBF decrease with moderate accuracy. If rASL values range from 0.585 to 0.952, we just speculate the prolonged MTT.

The synthesis of purine derivatives and its inhibitory activity on CD38 NADase / 药学学报

CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38.

Expression of uncoupling protein 2 on macrophages and its relation to interleukin-10/interferon ratio in patients with unexplained recurrent spontaneous abortion / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between the expression of uncoupling protein 2 (UCP2) and ratio of interleukin-10/interferon-gamma (IL10/IFNgamma) in the macrophages from patients with unexplained recurrent spontaneous abortion (URSA).</p><p><b>METHODS</b>Twelve women undergoing selective termination of normal early pregnancy (control) and 11 having URSA were included in this study. Magnetic cell sorting (MACS) was used to isolate the macrophages in the decidua, and the expression of UCP2 was detected with flow cytometry. Cytokine (IL10 and IFNgamma) secretion by the macrophages was detected by enzyme-linked immunosorbent spot-forming (ELISPOT) cell assay.</p><p><b>RESULTS</b>Compared to the control group, the women with URSA showed significantly decreased expression of UCP2 on decidual macrophage (136-/+25 vs 201-/+31, P<0.01), and the expression of UCP2 was positively correlated to the ratio of IL10/IFNgamma(r=0.73, P<0.01).</p><p><b>CONCLUSION</b>UCP2 may play an important role in the regulation of macrophage activity and cytokine secretion to contribute to spontaneous abortion.</p>

Uncoupling protein 2 combats oxidative damage to human sperm / 中华男科学杂志

<p><b>OBJECTIVE</b>Germ cells are much more susceptible to oxidative stress than somatic cells. Accumulating evidence indicates that uncoupling protein 2 (UCP2) prevents the apoptosis of multiple types of cells induced by reactive oxygen species (ROS). The present study aimed to evaluate the protective effect of uncoupling protein 2 (UCP2) against oxidative damage to human sperm.</p><p><b>METHODS</b>Semen parameters were obtained from 97 semen samples by computer assisted sperm analysis (CASA), and the samples, based on the percentage of grade a + b sperm, allotted to Groups I (n = 25, grade a + b sperm > 50%), II (n = 24, grade a + b sperm 25%-50%), III (n = 24, grade a + b sperm 10-25%) and IV (n = 24, grade a + b sperm < 10%). The expressions of sperm UCP2 mRNA was detected by RT-PCR, and the malonaldehyde (MDA) content in ROS was determined in the sperm suspension.</p><p><b>RESULTS</b>The expressions of UCP2 mRNA in sperm were 1.51 +/- 0.24, 1.28 +/- 0.15, 1.17 +/- 0.20 and 0.69 +/- 0.18, and the MDA contents were (14.66 +/- 2.55), (16.00 +/- 2.09), (17.44 +/- 1.40) and (21.20 +/- 3.50) nmol/10(8) sperm in Groups I, II, III and lV, respectively. There was a significant negative correlation between the expression of UCP2 mRNA and the content of MDA (r = -0.633, P < 0.01), the former obviously reduced while the latter remarkably increased in the groups of lower sperm motility (P < 0.01).</p><p><b>CONCLUSION</b>UCP2 plays an important protective role against oxidative stress damage to human sperm by diminishing ROS production.</p>

Uncoupling protein-2 expression in granular cells and embryo development in in vitro fertilization-embryo transfer cycle / 南方医科大学学报

<p><b>OBJECTIVE</b>To examine the expression of uncoupling protein-2 (UCP2) in the granular cell of women undergoing in vitro fertilization (IVF) and explore its role in embryo development.</p><p><b>METHODS</b>In this prospective study, the levels of UCP2 and reactive oxygen species (ROS) were measured by the chemiluminescence method in the granular cell of 53 women.</p><p><b>RESULTS</b>Women with low UCP2 level had higher ROS level, suggesting an inverse relationship between them (r=-0.578, P<0.01), and their oocyte development was impaired. Granular cells of elder women exhibited lowered UCP2 expression.</p><p><b>CONCLUSION</b>The granular cells increase UCP2 expression to suppress the elevation of intracellular ROS level through a feedback mechanism and therefore protect the oocytes against oxidative stress.</p>

Effect of low-dose triptorelin on pituitary down-regulation for patients undergoing in vitro fertilization and embryo transfer / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the effect of low-dose triptorelin in later luteal phase on pituitary down-regulation for patients undergoing IVF-ET.</p><p><b>METHODS</b>One hundred and twenty patients were randomly divided into 2 groups(A and B). In group A, the patients were treated with triptorelin of 0.1 mg subcutaneously daily started on day 21 of menstrual cycle for 7 days. In group B, the patients were treated with long protocol of Buserelin intranasal spray. Comparisons were made between the groups in serum concentrations of FSH, LH, E2, T, PRL and P on the third day (D3) of superovulation cycle and on the day of hCG administration, highly purified follicle-stimulating hormone (HP) dosages, and so on.</p><p><b>RESULTS</b>In group A, mean serum LH level on D3 and the day of hCG was (1.55 +/- 0.99) U/L and (2.70 +/- 1.45) U/L, E2 was (85.66 +/- 13.13) pmol/L and (5,451.31 +/- 1,900.61) pmol/L, respectively, significantly lower than those of group B (P < 0.001; P < 0.01; P < 0.05; P < 0.001). Mean HP(75 IU/Amp) dosage per treatment cycle in group A was 28.20 +/- 11.03 ampoules, significantly higher than 22.30 +/- 6.40 ampoules in group B(P < 0.001).</p><p><b>CONCLUSIONS</b>Low-dose triptorelin in later luteal phase is effective for down-regulation of pituitary and produces more suppression on endogenous LH in pituitary than Buserelin long protocol.</p>

Effects of catheter depth and infused semen volume on the pregnancy of intrauterine insemination / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the effects of catheter depth and infused semen volume on the pregnancy rate of intrauterine insemination(IUI) with the husband's semen.</p><p><b>METHODS</b>According to different catheterizing distances from the fundus and infused semen volumes, 330 patients undergoing intrauterine insemination were randomly divided into 6 groups: A, 1 cm/0.5 ml; B, 1 cm/0.3 ml; C, 2 cm/0.5 ml; D, 2 cm/0.3 ml; E, 3 cm/0.5 ml and F, 3 cm/0.3 ml. The pregnancy rate was investigated in each group.</p><p><b>RESULTS</b>The pregnancy rates from group A to group E were 9.09% (5/55), 12.73% (7/55), 10.91% (6/55), 29.09% (16/55), 9.09% (5/55) and 12.73% (7/55), respectively. It was significantly higher in group D than in groups A, B, C, E and F(P < 0.05).</p><p><b>CONCLUSIONS</b>Catheterizing distance of 2 cm from the fundus with infused semen volume of 0.3 ml can significantly improve pregnancy rate in patients undergoing IUI with the husband's semen.</p>