Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice / 中国生物制品学杂志

Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice@#Objective To investigate the effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 crown protein vaccine in mice.Methods The amantadine dimer was synthesized by substitution reaction ligation,hydrolytic acidification reaction ligation and amide condensation reaction ligation,with which as adjuvant,female BALB/c mice were immunized with the receptor-binding domain(RBD).The mice were randomly divided into five groups,six for each as follows:R6A+RBD group[21 μg(0.033 μmol)amantadine dimer+10 μg RBD],Ada+RBD group[10 μg(0.066 μmol)amantadine+10 μg RBD],Alu+RBD group(35 μg aluminum adjuvant+10 μg RBD),RBD group(10 μg RBD)and Blank group(0.9% normal saline),which were immunized i.m.on day 0,14 and 28 respectively.Serum samples were collected from tail vein of mice 7 d after the second dose and 14 d after the last dose and determined for specific IgG antibody levels by ELISA.Results The amantadine dimer was purified by thin layer chromatography(TLC)and identified by electrospray ionization-MS(ESI-MS)positive/negative ion mode.After two times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all higher than those of Ada+RBD group,while lower than those of Alu+RBD group.However,after three times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all significantly higher than those of Ada+RBD and Alu+RBD groups(each F > 30,each P < 0.000 1 and each P < 0.01).Conclusion Amantadine dimer adjuvant enhanced humoral immune response induced by SARS-CoV-2 protein vaccine in mice with good adjuvant effect,which may be used as an alternative adjuvant.This strategy based on existing drug transformation provided a new idea for the development of novel adjuvants.

Analysis of anxiety and depression in patients undergoing radiotherapy during COVID-19 epidemic period / 中华放射肿瘤学杂志

Objective:To investigate the anxiety and depression of cancer patients undergoing radiotherapy during the epidemic of COVID-19.Methods:By using self-rating anxiety scale and self-rating depression scale, a cross-sectional survey was conducted during the COVID-19 epidemic period.Results:During the COVID-19 epidemic period, the incidence of anxiety and depression in cancer patients undergoing radiotherapy was 15.8% and 27.7% respectively, of which 12.9% suffered from both anxiety and depression. The average scores of anxiety and depression were 49.4(25/76) and 46.4(25/83), respectively, which were higher than those of the domestic norm. Age is a contributing factor for anxiety, and patients living in urban are more likely to experience depression.Conclusions:The prevalence of anxiety and depression of cancer patients undergoing radiotherapy are higher than healthy people during the COVID-19 outbreak. We should pay more attention to the psychological states of the cancer patients.

Analysis of quality of life and sexual quality of life in cervical cancer patients undergoing radiotherapy / 中华放射肿瘤学杂志

Objective To investigate the quality of life, sexual quality of life and its influencing factors in cervical cancer patients undergoing radiotherapy. Methods Pre-menopausal patients of 87 cases were diagnosed with cervical cancer treated with radiotherapy at Peking Union Medical College Hospital from December 2013 to December 2018 were recruited in this study. The functional assessment of cancer therapy-cervix ( FACT-Cx V4. 0) and the female sexual function index ( FSFI) were evaluated. Demographic and treatment data were collected. The influencing factors were analyzed by multiple linear regression analysis. Results The total score of quality of life was 114( 100-126) , 19( 16-21) for physiology, 21( 18-24) for social/family, 19( 17-21 ) for emotion, 19 ( 14-22 ) for function and 39 ( 34-43 ) for additional attention, respectively. The end time of radiotherapy was the influencing factor of the total score ( P= 0.034 ) , physiology ( P=0) and function ( P=0.008) . Family was the influencing factor of social family dimension ( P=0.010) . The total score of FSFI was 8.0( 5.0-20.5) , 1.8( 1.2-3.0) for sexual desire, 1.5( 0-2.7) for sexual arousal, 0.3( 0-3.6) for vaginal lubrication, 0( 0-3.6) for orgasm, 3.2( 2-4) for satisfaction and 0( 0-3.6) for sexual pain, respectively. The total score was less than 27 in 97%( 84/87) of the patients and had sexual dysfunction. Age was the influencing factor of sexual arousal ( P=0.005) and vaginal lubrication ( P=0.039) . Occupation was the influencing factor of sexual pain ( P=0.004) . Conclusions The quality of life of premenopausal patients with cervical cancer is affected by multiple factors. Radiotherapy-related complications should be actively treated to improve the quality of life and sexual life of patients.

Information Needs and Quality among Cervical Cancer Patients / 中国医学科学院学报

Objective To investigate the demand for scientific information among cervical cancer patients and to evaluate the quality of the relevant information available for these patients.Methods The demand for medical science information among patients with cervical cancer was investigated via questionnaire.The Discernn scoring system was used to score the cervical cancer science articles retrieved by Baidu and Sogou.A model was established to analyse the reading difficulty of these articles.Results Nearly half(53.6%)of the respondents searched for online science information at least weekly.The main target readings were the etiology and risk factors of diseases,symptoms,treatment options,adverse reactions of treatments,and prognosis.Most respondents(96.4%)thought that the network science information was reliable.Of the 104 search results included in the sample bank,13(12.5%)met the inclusion criteria,91(87.5%)were not selected,including 32 duplicates(30.8%),6 non-text webpages(5.8%),18 short texts(less than 300 Chinese characters)(17.3%),7 advertisements(6.7%),3 news articles(2.9%),22 forum posts(21.2%),and 3 academic articles(2.9%).According to the Discern scoring system,the reliability(=0.728, <0.001),the quality of treatment-related information(=0.431, <0.001),and the overall scores(=0.559,<0.001)of the enrolled 13 publications were consistent,as evaluated by two professional physicians.The mean overall score was 3.A lower score(less than 3)in the reliability assessment was due to the source of the content,generation methods,sponsors,citations,and the undefined parts.During the evaluation of treatment information,the average score was below 3 for each item.Analysis of the reading difficulty showed that,among these 13 articles,4 were at postgraduate thesis level(level 5),4 at undergraduate thesis level(level 4),0 at high school textbook level(level 3),and 8 was higher than middle school level(≥level 3).Eight articles(61.5%)were suitable for readers with an education background of higher middle school and only 5 articles(38.5%)were suitable for readers with an education background of middle school or lower(≤ level 2).Conclusions The vast majority of patients with cervical cancer search for clinical information through the Internet and trust their reliability.Chinese search engines have lower detection rates for high-quality medical science articles.The currently available high-quality medical science articles are small in number and difficult to read.More physicians are urged to write easy-to-read high-quality articles for these patients.

Sexual Quality of Life in Patients with Cervical Cancer Undergoing Radiotherapy / 中国医学科学院学报

To investigate the sexual quality of life and its influencing factors in patients with cervical cancer undergoing radiotherapy. Methods Totally 205 patients with cervical cancer who received radiotherapy in Peking Union Medical College Hospital from December 2013 to December 2018 were enrolled in this study.The Female Sexual Function Index(FSFI)scale was used to assess the sexual quality of life of these patients.The demographic data(including age,education level,marital status,family status,and occupation)and clinical data(including tumor stage and treatment method)were collected.Mann-Whitney test and Kruskal-Wallis test were used to analyze the influence of various factors on the sexual quality of life. Results Female sexual dysfunction was common among patients with cervical cancer undergoing radiotherapy.The total FSFI score was 5.5(3.6,16.3),and the scores of subscales were as follows:desire,1.20(0,1.80);sexual arousal,0.90(0,1.80);vaginal lubrication,0.30(0,3.30);orgasm,0(0,2.80);satisfaction,2.40(1.60,3.60);and sexual pain,0(0,2.80).Age(=0.010),duration of radiotherapy(=0.008),marital status(=0.020),family status(=0.010),and occupation(=0.024)were influential factors of sexual quality of life in cervical cancer patients undergoing radiotherapy. Conclusions The sexual quality of life of patients with cervical cancer undergoing radiotherapy is affected by multiple factors.Instructions on treatment,mental status,and post-treatment sexual life should be offered in an individualized way to improve the sexual quality of life of these patients.

Assessment of anxiety and analysis risk factors in 646 patients receiving radiotherapy and their relatives S / 中华放射肿瘤学杂志

Objective To evaluate the anxiety and explore relevant risk factors in patients receiving radiotherapy and their relatives,aiming to provide evidence for improving the quality of life. Methods Before radiotherapy,the self-rating anxiety scale (SAS) was utilized to evaluate the anxiety of patients and their relatives. The incidence rate of anxiety was analyzed under the influence from different risk factors. Results A total of 646 participants (463 patients and 183 relatives) were included in this study. The average SAS scores of all participants,patients and family relatives were 41.52±10. 08,41.02±19. 37 and 42.79±11. 56, significantly higher than 37.23±12. 58 for the healthy population in China (P= 0. 000. 0.000,0. 000).For patients aged 11-30,31-50 and 51-90 years,the incidence rate of anxiety was 26％(7/ 26),11. 0％(20/ 182) and 19. 1％(47/ 246),respectively (P= 0. 026).The incidence rate of anxiety for patients with and without tumor recurrence was 27％ (13/ 48) and 15. 4％ (64/ 415) (P= 0. 040).Seventeen of 63 patients (27％) with metastases experienced anxiety,whereas 60 of 396 patients (15. 2％) without metastases suffered from anxiety (P= 0. 020).The incidence rate of anxiety in patients with three or more chronic diseases was 26％(19/ 74),significantly higher compared with 15. 0％(58/ 387) in those with less comorbidities (P= 0. 024). Multivariate binary logistic regression analysis demonstrated that three or more chronic diseases or serious diseases were high risk factors of anxiety (OR= 1. 92,95％CI:1. 03-3. 567). Conclusions Patients who receive radiotherapy and their relatives are prone to anxiety. Young age,tumor recurrence or metastasis and≥ three comorbidities or severe diseases are the high risk factors of anxiety. It is necessary to evaluate the anxiety of patients and their family relatives before radiotherapy and deliver psychological counseling.

Imaging analysis of rectal cancer patients with clinical and pathological complete remission after concurrent chemoradiotherapy / 中华放射肿瘤学杂志

Objective To analyze the imaging data of patients with complete clinical remission ( cCR ) and postoperative pathological complete remission ( pCR ) after concurrent chemoradiotherapy, aiming to evaluate the values of MRI and rectal ultrasound in predicting pCR. Methods Clinical data of 42 patients with locally advanced rectal cancer treated with concurrent chemoradiotherapy combined with operation were retrospectively analyzed. The magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and pathological data were statistically compared between patients with cCR and pCR. Results After concurrent chemoradiotherapy,12 patients obtained cCR and 7 patients achieved pCR.The consistency rate of cCR between MRI and EUS was 3/12(25％), and 4/12(33％) for pCR.The consistency rate of pCR of MRI combined with EUS was 5/12 ( 42％) . Conclusion Rectal ultrasound combined with MRI cannot fully predict pCR. More accurate detection approach remains to be explored to evaluate the clinical outcomes of watch-and-wait patients.

Anti-inflammatory effect of Qingwen Baidu Decoction (清瘟败毒饮) in sepsis rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the pharmacological anti-inflammatory mechanism of Chinese formula Qingwen Baidu Decoction (清瘟败毒饮, QBD) from the view of holistic biology.</p><p><b>METHODS</b>The rats were randomly divided into a normal conrol group, a lipopolysaccharide (LPS) group, the low- and high-dose QBD groups, and a dexamethasone (DXM) group. NR8383 cells were treated with culture fluid containing 6% serum from rats of each group respectively. Inflammatory mediators were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting hybridization, enzyme linked immunosorbent assay (ELISA), polymerase chain reaction (PCR) gene array and antibody array.</p><p><b>RESULTS</b>It is showed that the levels of interleukin (IL)-1α, IL-4 and IL-12 were enhanced in the low-dose QBD group; levels of IL-1α, IL-12 and IL-18 were augmented in the high-dose QBD group, compared with the LPS group after ELISA detection. Western blot showed that IL-1β and tumor necrosis factor (TNF)-α expression of the control group were lower than other groups. IL-1β level of the low-dose and high-dose QBD groups detected by RT-PCR was higher in early stage but lower after 24 h than that of the control group (P<0.01). Expression of 84 main inflammatory cytokines and receptors was detected by rat inflammatory cytokines and receptors PCR array. Up-regulation genes were 22 in both the LPS group and the low-dose QBD group, among which 16 up-regulating genes were the same. In these 16 genes, the up-regulating amplitude of 9 genes in the low-dose QBD group was less than that in the LPS group, 4 were similar to and 3 were more. Twenty-nine main cytokines were inspected by rat cytokine antibody array. Intergroup gray value differences were found in 7 expressed cytokines. The levels of these 7 cytokines in the low-dose QBD group were all lower than those in the the LPS group.</p><p><b>CONCLUSIONS</b>QBD has anti-inflammatory effect on sepsis by changing the level of inflammatory mediators.</p>

Up-regulation of T-lymphoma and metastasis gene 1 in gastric cancer and its involvement in cell invasion and migration / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>T-lymphoma and metastasis gene 1 (Tiam1) produces a guanine nucleotide exchange factor (GNEF) that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiam1 was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiam1 in gastric carcinoma.</p><p><b>METHODS</b>We analyzed the expression of Tiam1 in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiam1 expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiam1 over-expression were analyzed with stable-expression Tiam1 plasmid in human gastric cancer cell lines.</p><p><b>RESULTS</b>Tiam1 expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiam1 mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues. Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiam1 expression had significantly shorter overall survival time than those with negative Tiam1 expression. Ectopic expression of Tiam1 promoted cell growth, migration and invasion of gastric cancer cells in vitro.</p><p><b>CONCLUSIONS</b>In gastric cancer cells, Tiam1 affects multiple properties associated with acquisition of the metastatic phenotype, and may be a marker of gastric cancer progression and metastasis in a subset of cancer.</p>

Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>One effect of solid tumors is severe hypoxia of local tissues. Heme oxygenase-1 (HO-1) is highly expressed in a variety of human tumor tissues; its induction and activity are closely related to growth of solid tumors. Hypoxia inducible factor-1 (HIF-1) is a transcription factor that regulates hypoxia signal transduction and plays a central role in tumor hypoxia regulation. However, whether and how changes in HO-1 activity affect HIF-1 gene expression has not been reported previously.</p><p><b>METHODS</b>Hypoxia-inducible models were established using gastric cancer cell lines (SGC-7901) in a hypoxia incubator. Cells were placed in four groups: Group A, transfected by plasmid harboring HO-1 shRNA; Group B, transfected with scrambled shRNA vector; Group C, treated with hemin; and Group D, exposed to hypoxia only. Expressions of HO-1 and HIF-1 mRNAs were quantified by reverse transcription-polymerase chain reaction. Expressions of HO-1 and HIF-1 proteins were determined by immunohistochemistry and Western blotting.</p><p><b>RESULTS</b>mRNA and protein levels of HO-1 and HIF-1 in the control group were significantly higher than in Group A (P < 0.01), but lower than in Group C (P < 0.01). Chromatin immunoprecipitation analysis showed that HIF-1 was identified as the direct HO-1 target gene.</p><p><b>CONCLUSION</b>While affected by HIF-1, HO-1 up-regulation promotes the expression of HIF-1 and the down-regulation of HO-1 suppresses the expression of HIF-1 gene.</p>

Proliferation and Apoptosis of Bone Marrow CD4+ T Cells in Patients with Aplastic Anemia and Impacts of the Secreted Cytokines on Hematopoietic Stem Cells from Umbilical Cord Blood / 华中科技大学学报（医学）（英德文版）

Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy controls with immunomagnetic beads sorting,and proliferation capability,apoptosis features and the impacts of their secreted cytokines on hematopoiesis stem/progenitor cells were compared between them.By 3H-TdR method,CD4+ T cells in AA group presented more enhanced proliferative activity.The stimulation index in control group and AA group was 1.47±0.24,and 2.51±0.34 respectively(P<0.01).After BM CD4+ T cells were induced by high concentration of CD3 monoclonal antibody for 18h,evident apoptosis cells could be seen under the electron microscope in both control group and AA group.Flow cytometry revealed that apoptosis rates in the early and late stages of AA group were significantly higher than in control group(P<0.01).Early-stage apoptosis rate in control and AA groups was(6.85±1.48)% and(16.98±4.40)%,and late-stage apoptosis rate in control group and AA group was(2.654±1.57)% and(7.74±0.83)%,respectively(P<0.01).The CFU-GM count in AA group and control group was(74.50±9.50)/104 cells and(124.25±19.80)/104 cells respectively under an inverted microscope(P<0.01),and the expression levels of CyclinD3 mRNA and protein in cord blood CD34+ cells were both down-regulated induced by BM CD4+ T cell culture supernatant in AA patients.These results indicate that BM CD4+ T cells of AA patients are likely in an abnormally proliferative,and activated state which can correlate intimately with AA hematopoiesis damage.BM CD4+ T cells in AA patients can secret some soluble cytokines that can inhibit proliferation of hematopoietic stem cells by suppressing the expression of Cyclin D3,resulting in hematopoiesis failure.

Expression and clinical significance of matrix metalloproteinase in gastric stromal tumor / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the expression and clinical significance of matrix metalloproteinase (MMP) in gastric stromal tumor (GST).</p><p><b>METHODS</b>MMP-2 and MMP-9 expression were determined by immunohistochemistry in tumor tissues in 44 patients with GST, and their relationship with clinicopathologic factors of the neoplasm was also investigated.</p><p><b>RESULTS</b>MMP-2 and MMP-9 were expressed in the cytoplasm in 84.1% (37/44) and 81.8% (36/44) of tumors, respectively. The positive rates of MMP-2 and MMP-9 increased significantly in parallel to the increase in tumor malignancy (P < 0.05) and associated with pattern of tumor growth, tumor size, and centre necrosis (P < 0.05). In addition, there was a statistically significant positive correlation between the expression of the two markers in GST (r = 0.6523, P < 0.05). Furthermore, the 5-year postoperative survival rates of patients with positive expressions of MMP-2 and MMP-9 were significantly lower than those of patients with negative expressions of the two markers (P < 0.05).</p><p><b>CONCLUSION</b>Over expression of MMP-2 and MMP-9 can be served as objective markers to judge the malignant degree and, to predict the prognosis of patients with GST.</p>

Field demonstration of reduction of lead availability in soil and cabbage (Brassica Chinensis L.) contaminated by mining tailings using phosphorus fertilizers / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

A field demonstration of reduction of lead availability in a soil and cabbage (Brassica Chinensis L.) contaminated by mining tailings, located in Shaoxing, China was carried out to evaluate the effects of applications of phosphorus fertilizers on Pb fractionation and Pb phyto-availability in the soil. It was found that the addition of all three P fertilizers including single super phosphate (SSP), phosphate rock (PR), and calcium magnesium phosphate (CMP) significantly decreased the percentage of water-soluble and exchangeable (WE) soil Pb and then reduced the uptake of Pb, Cd, and Zn by the cabbage compared to the control (CK). The results showed that the level of 300 g P/m(2) soil was the most cost-effective application rate of P fertilizers for reducing Pb availability at the first stage of remediation, and that at this P level, the effect of WE fraction of Pb in the soil decreased by three phosphorus fertilizers followed the order: CMP (79%)>SSP (41%)>PR (23%); Effectiveness on the reduction of Pb uptake by cabbage was in the order: CMP (53%)>SSP (41%)>PR (30%). Therefore our field trial demonstrated that it was effective and feasible to reduce Pb availability in soil and cabbage contaminated by mining tailings using P fertilizers in China and PR would be a most cost-effective amendment.