Carboplatin-loaded surface modified-PLGA nanoparticles confer sustained inhibitory effect against retinoblastoma cell in vitro / Nanopartículas de PLGA com superfície modificada carregada com carboplatina conferem efeito inibitório sustentado contra células de retinoblastoma in vitro

ABSTRACT Purpose: To investigate the antiproliferative effect of carboplatin-loaded surface-modified poly(lactide-co-glycolide) on retinoblastoma cells. Methods: Carboplatin-loaded poly(lactide-co-glycolide) with or without sodium alginate surface modification was prepared using sodium alginate-poly(lactide-co-glycolide) and poly(lactide-co-glycolide). The zeta potential and carboplatin release behavior were investigated. The cellular uptake of the released drug was observed in the retinoblastoma cell line Y79. The inhibitory effect of carboplatin-loaded nanoparticles against the Y79 cell line was evaluated using methyl thiazolyl tetrazolium assay and western blot. Native carboplatin and void nanoparticles without carboplatin loading were used as controls. Results: The zeta potential was -(26.1 ± 3.1) mV for carboplatin-loaded poly(lactide-co-glycolide) and-(43.1 ± 8.1) mV for carboplatin-loaded sodium alginate-poly(lactide-co-glycolide). The burst release percentages of carboplatin-loaded poly(lactide-co-glycolide) and sodium alginate-poly(lactide-co-glycolide) were (40.0% ± 8.2%) and (18.9% ± 4.3%) at 24 hours, respectively. A significant difference was identified regarding drug release between carboplatin-loaded sodium alginate-poly(lactide-co-glycolide) and carboplatin-loaded poly(lactide-co-glycolide). Fluorescence detection revealed that intense uptake of carboplatin into the cytoplasm of the Y79 cell line that was exposed to carboplatin-loaded sodium alginate-poly(lactide-co-glycolide). Carboplatin-loaded poly(lactide-co-glycolide) or sodium alginate-poly(lactide-co-glycolide) exposure inhibited proliferating cell nuclear antigen expression in Y79 cells on day 3. Extension of exposure to day 5 revealed that the sodium alginate-poly(lactide-co-glycolide) surface modification was superior to that of poly(lactide-co-glycolide) in terms of proliferating cell nuclear antigen inhibition. The cell viability test using methyl thiazolyl tetrazolium revealed a similar inhibitory effect. Furthermore, the carboplatin-loaded nanoparticles of lower concentration inhibited cell viability more strongly than native carboplatin of higher concentration in methyl thiazolyl tetrazolium assay. Conclusions: Carboplatin-loaded sodium alginate-poly(lactide-co-glycolide) inhibited retinoblastoma cell proliferation with superior effect as compared with poly(lactide-co-glycolide) and native carboplatin. Sodium alginate surface modification offers a potential strategy for the sustained carboplatin release system.

RESUMO Objetivo: Investigar o efeito antiproliferativo de poli (lactídeo-coglicolídeo) com superfície modificada carregada com carboplatina contra células de retinoblastoma. Métodos: Preparou-se poli (lactídeo-co-glicolídeo) carregado com carboplatina com ou sem alginato de sódio para modifição da superfície, poli com alginato de sódio (lactídeo-co-glicolídeo) e poli (lactídeo-co-glicolídeo). O potencial zeta e o comportamento de liberação de carboplatina foram investigados. A captação celular do fármaco liberado foi observada na linha celular de retinoblastoma Y79. O efeito inibitório das nanopartículas carregadas com carboplatina contra a linha celular Y79 foi avaliado através do ensaio de metiltiazol tetrazólio e Western-blot. Carboplatina nativa e nanopartículas vazias sem carga de carboplatina serviram como controles. Resultados: O potencial zeta de poli carregado com carboplatina (lactídeo-co-glicolídeo) foi - (26,1 ± 3,1) mV versus - (43,1 ± 8,1) mV em poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo). A percentagem de libertação de explosão de poli carregado com carboplatina (lactídeo-co-glicolídeo) e poli com alginato de sódio (lactídeo-co-glicolídeo) foram (40,0 ± 8,2)% e (18,9 ± 4,3)% às 24 horas, respectivamente. Uma diferença significativa foi identificada em relação à liberação de fármaco entre poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo) e poli carregado com carboplatina (lactídeo-co-glicolídeo). A detecção de fluorescência revelou que a carboplatina foi assimilada intensamente no citoplasma da linha celular Y79 que foi exposta ao poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo). A exposição de poli carregada com carboplatina (lactídeo-co-glicolídeo) ou poli com alginato de sódio (lactídeo-co-glicolídeo) inibiu a expressão de antígeno nuclear de proliferação celular em células Y79 no 3º dia. A extensão da exposição no 5º dia revelou que poli com alginato de sódio (lactídeo-co-glicolídeo) para modificação da superfície foi superior a poli (lactídeo-co-glicolídeo) em termos de inibição do antígeno nuclear de proliferação celular. O teste de viabilidade celular via metiltiazol tetrazólio mostrou um efeito inibitório semelhante. Além disso, as nanopartículas carregadas com carboplatina de concentração mais baixa inibiram a viabilidade celular mais fortemente em comparação com a carboplatina nativa de concentração mais alta no ensaio de metiltiazol tetrazólio. Conclusões: Poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo) inibiu a proliferação de células de retinoblastoma com efeito superior em contraste com poli (lactídeo-co-glicolídeo) e carboplatina nativa. O alginato de sódio para modificação da superfície oferece uma estratégia potencial para o sistema de liberação de carboplatina sustentada.

Clinical characteristics and prognosis of 83 children with newly treated hepatoblastoma / 中华儿科杂志

Objective: To investigate the clinical features, survival and prognostic risk factors of children with hepatoblastoma (HB). Methods: Clinical data of 83 children with newly treated HB at the Department of Hematology and Oncology, Children's Hospital, the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2019 were analyzed retrospectively. The sex, age, first clinical manifestations, pretreatment extent of disease (PRETEXT) stages, pathological types, initial alpha-fetoprotein (AFP), treatment methods and treatment outcome of all patients were summarized. The children diagnosed before 2018 were treated with "Wuhan Protocol", and those who diagnosed after 2018 were treated with the "Expert Consensus for Multidisciplinary Management of Hepatoblastoma"(CCCG-HB-2016) protocol. Kaplan-Meier survival analysis was used to calculate the survival rate, Log-Rank test was used in univariate analysis, and the Cox regression model was used in multivariate prognosis analysis. Results: Among 83 cases, there were 51 males and 32 females. The age of onset was 25.2 (9.0, 34.0) months old, and 64 cases (77%) were under 3 years old. The most common first clinical manifestation was abdominal mass in 45 cases (54%). There were 8 cases of PRETEXT stage Ⅰ, 43 cases of stage Ⅱ, 20 cases of stage Ⅲ and 12 cases of stage Ⅳ. During the follow-up period of 40 (17, 63) months, the 1-year overall survival (OS) rate and event-free survival (EFS) rate were (84±4) % and (79±5) %, respectively, and 5-year OS rate and EFS rate were (78±5) % and (76±5) %, respectively. Fifty-five cases were treated with "Wuhan Protocol", and the 5-year OS and EFS rate were (73±6) % and (71±6) %, respectively. Twenty-eight cases were treated with CCCG-HB-2016 protocol, and the 5-year OS and EFS rate were (88±7) % and (82±9) %, respectively. Multivariate COX regression analysis showed that AFP did not turn negative after 3 courses of postoperative chemotherapy (HR=9.228, 95%CI 1.017-83.692) and PRETEXT stage Ⅳ (HR=6.587, 95%CI 1.687-25.723) were independent risk factors affecting the prognosis of children with HB. Conclusions: The "Wuhan Protocol" and CCCG-HB-2016 protocol were effective in the treatment of children with HB. AFP did not turn negative after 3 courses of postoperative chemotherapy and PRETEXT stage Ⅳ were independent risk factors affecting the prognosis of children with HB.

Mortality trend of chronic respiratory diseases in China, 1990-2019 / 中华流行病学杂志

Objective: To analyze mortality and its trend of chronic respiratory diseases (CRD) in China from 1990 to 2019. Methods: Based on the provincial results of China from the 2019 Global Burden of Disease (GBD) study, the average annual percent change (AAPC) of standardized mortality rates of different CRDs were analyzed by using Joinpoint 4.8.0.1, and the age-standardized mortality rate of CRD was calculated by using the GBD 2019 world standard population. Based on the comparative risk assessment theory of GBD, the attributable deaths due to 12 CRD risk factors were estimated, including smoking, indoor air pollution, occupational gas exposure, particulates and smog exposure, environmental particulate pollution, low temperature, passive smoking, ozone pollution, occupational exposure to silica, occupational asthma, high body mass index, high temperature and occupational exposure to asbestos. Results: From 1990 to 2019, the number of deaths and standardized mortality of chronic obstructive pulmonary disease (COPD) showed a downward trend (P<0.001). The number of COPD deaths decreased from 1 244 000 (912 000 - 1 395 000) in 1990 to 1 037 000 (889 000 - 1 266 000) in 2019. AAPC=-0.9% (95%CI: -1.5% - -0.3%), P<0.001; The standardized mortality rate decreased from 217.9/100 000 (163.3/100 000 - 242.0/100 000) in 1990 to 65.2/100 000 (55.5/100 000 - 80.1/100 000) in 2019. AAPC= -4.2% (95%CI:-5.2% - -3.2%), P<0.001. The number of deaths from asthma decreased from 40 000 (30 000 - 58 000) in 1990 to 25 000 (20 000 - 31 000) in 2019. AAPC=-2.0% (95%CI: -2.6% - -1.4%), P<0.001; The standardized mortality rate of asthma decreased from 6.4/100 000 (4.7/100 000 - 9.5/100 000) in 1990 to 1.5/100 000 (1.2/100 000 - 1.9/100 000) in 2019. AAPC=-5.1% (95%CI: -5.8% - -4.4%), P<0.001. The number of pneumoconiosis deaths decreased from 11 000 (8 000 - 14 000) in 1990 to 10 000 (8 000 - 14 000) in 2019, AAPC=-0.2%(95%CI:-0.4% - 0.1%), P=0.200; The standardized mortality rate of pneumoconiosis decreased from 1.4/100 000 (1.0/100 000 - 1.7/100 000) in 1990 to 0.5/100 000 (0.4/100 000 - 0.7/100 000) in 2019. AAPC=-3.1% (95%CI: -3.4% - -2.8%), P<0.001. The number of deaths from pulmonary interstitial diseases and pulmonary sarcoidosis increased from 3 000 (3 000 - 6 000) in 1990 to 8 000 (6 000 - 10 000) in 2019, AAPC=3.5% (95%CI: 2.7% - 4.2%), P<0.001; The corresponding standardized mortality rate changed little from 1990 to 2019, and AAPC was not statistically significant.The age-standardized mortality rates of different CRDs were higher in men than those in women. In 1990 and 2019, the mortality rates of COPD, asthma, pneumoconiosis and interstitial pulmonary disease and pulmonary sarcoidosis increased with age. In 2019, the population attributable fractions (PAFs) for smoking, environmental particulate pollution, occupational gas exposure, particulate and smog exposure, low temperature exposure and passive smoking were 71.1% (68.0% - 74.3%), 24.7% (20.1% - 30.0%), 19.3% (13.0% - 25.4%), 15.7% (13.6% - 18.3%) and 8.8% (4.5% - 13.1%) respectively in men, and the PAFs for environmental particulate pollution, smoking, low temperature exposure, occupational gas exposure, particulate and smog exposure, and passive smoking were 24.1% (19.6% - 29.3%), 21.9% (18.7% - 25.2%), 16.4% (14.0% - 19.2%), 15.6% (10.2% - 21.1%) and 14.7% (7.9% - 21.3%) respectively in women. Conclusions: During 1990-2019, the overall death level of CRD decreased significantly in China, but it is still at high level in the world. Active prevention and control measures should be taken to reduce the death level caused by CRD.

Analysis of community intervention effects for diabetic eye diseases in Shanghai Xinjing community from 2016 to 2018 / 中华预防医学杂志

Objective: To analyze the effects of community-based interventions for diabetic eye diseases in Xinjing community, Shanghai from 2016 to 2018. Methods: Based on the project of "Establishment of Service Model for Comprehensive Prevention and Treatment of Diabetic Eye Diseases in Shanghai", the participants were not suffering diabetic retinopathy (DR) in Xinjing community in 2016 before interventions and received community-based interventions for diabetic eye diseases. The incidence of DR, visual acuity and awareness of DR were used as evaluation indicators to analyze the effects of interventions for diabetic eye diseases in the community. Results: A total of 537 patients were included in this study, the incidence of DR among diabetic patients in Xinjing community was 7.6% after interventions. The duration of diabetes (OR= 1.065) and HbA1c (OR= 1.090) were the risk factors of DR. Before and after the interventions, the patients with monocular low vision and binocular low vision were 27 cases (5.0%), 8 cases (1.5%), 19 cases (3.5%) and 7 cases (1.3%) respectively. After interventions, the awareness on the prevention and treatment of DR increased significantly, and the proportion of regular visits to ophthalmology examination, diet control and physical exercise also increased significantly. Conclusion: Community-based interventions for diabetic eye diseases are helpful to improve the awareness of DR prevention and control, reduce the incidence of DR.

Prokaryotic expression and polyclonal antibody preparation of human adenovirus type 7 DNA binding protein / 中华预防医学杂志

Objective: To express DNA-binding protein (DBP) of human adenovirus (HAdV) type 7 using the prokaryotic expression system, and product anti-HAdV-7 DBP rabbit polyclonal antibody. Methods: The HAdV-7 DBP gene was synthesized and cloned into prokaryotic expressing vector pET30a, and the recombinant plasmid was transformed into E. coli BL21 (DE3) competent cell. The recombinant protein DBP was expressed by induced Isopropyl-beta-D-thiogalactopyranoside (IPTG) and purified with Ni-NTA affinity column. The titer of anti-DBP polyclonal antibody produced in immunized rabbit was measured by indirect ELISA, and the specificity of the antibody was identified by Western blotting and indirect immunofluorescence assay (IFA). In addition, purified rDBP was used as coating antigen for indirect ELISA assay to detect specific IgM and IgG antibodies against DBP in the serum of children infected with HAdV. Results: The HAdV-7 DBP plasmid was constructed successfully. The purified recombinant DBP was more than 95% after purification. The titer of polyclonal antibody was 1∶1 024 000. The polyclonal antibody showed high specificity in vitro using Western blotting and IFA. The positive rate of specific anti-DBP IgM and IgG antibody in acute-phase serum samples collected from children infected with HAdV were 50.0% (19/38) and 63.2% (24/38), respectively, using indirect ELISA. Conclusion: In summary, the HAdV-7 rDBP is expressed using prokaryotic expression system, and the recombinant HAdV-7 DBP protein and the anti-DBP rabbit polyclonal antibody with high titer are prepared.

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.

Progress on delineation of clinical target volume of primary tumour of nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Accurate delineation of clinical target volume (CTV) of nasopharyngeal carcinoma is of significance to prevent local recurrence and improve the survival rate of patients. When intensity-modulated radiotherapy (IMRT) was first introduced, CTV was delineated based on two-dimensional radiotherapy experience. The local recurrence-free survival is high, but the adverse reactions induced by radiotherapy are severe and the patients’ quality of life is poor. How to reduce CTV to alleviate acute and late radiotherapy-induced adverse reactions without deteriorating therapeutic effect has currently become a research hotspot. Despite the 2010 Chinese Nasopharyngeal Carcinoma IMRT Target and Dose Design Guideline Expert Consensus and the International Guideline for the Delineation of the CTV for Nasopharyngeal Carcinoma as references, the optimal individualized and standardized delineation of CTV remains controversial. This review summarizes the progress on the delineation of CTV of primary tumour of nasopharyngeal carcinoma, aiming to provide practical reference for clinicians.

Development of Nursing Skill Rating Scale of Intravenous Therapy for Community Nurses and the test of its reliability and validity / 中国实用护理杂志

Objective:To develop Nursing Skill Rating Scale of Intravenous Therapy for Community Nurses and to test its reliability and validity.Methods:Refer to the 2019 Infusion Nursing Society Infusion Therapy Standards of Practice, Nursing Technical Operation Specification of Intravenous Therapy, through literature review, expert group meeting and pre-survey, the Nursing Skill Rating Scale of Intravenous Therapy for Community Nurses was formed, and 260 community nurses of 20 communities in Dalian were investigated by convenience sampling method from May to June 2020 to test the reliability and validity. Results:The Nursing Skill Rating Scale of Intravenous Therapy for Community Nurses included five dimensions (theoretical knowledge, skill operation, management ability, complication treatment, health education) with 18 items, cumulative variance contribution rate was 50.510%. The scale-content validity index was 0.92. The item-level content validity index were from 0.76 to 1.00. The total Cronbach α coefficient of questionnaire was 0.857. The test-retest reliability was 0.948. Conclusions:The Nursing Skill Rating Scale of Intravenous Therapy for Community Nurses has good reliability, validity and strong applicability. It could be applied for the nursing skill level of intravenous therapy for community nurses.

Analysis of clinical significance and prognostic impact of TET2 single nucleotide polymorphism I1762V in patients with acute myeloid leukemia / 中华血液学杂志

Objective: This study aimed to investigate the clinical and prognostic significance of TET2 single nucleotide polymorphism I1762V in patients with acute myeloid leukemia (AML) . Methods: The high-throughput sequencing method was used to sequence 58 hematological tumor-related genes in bone marrow samples from 413 patients with AML. TET2 I1762V and other somatic mutations were annotated and compared with patients' clinical information and prognosis. Results: I1762V was found in 154 patients with AML, which was significantly different from the general population in NyuWa Chinese Population Variant Database (χ(2)=72.4, P<0.001) . I1762V was not related to sex, age, and karyotype of patients with AML (P>0.05) . Patients with I1762V had a significantly higher proportion of NPM1 and KIT gene mutations than others (P<0.001) . NPM1 and KIT mutations were mutually exclusive. The survival analysis results revealed that the overall survival (OS) and progression-free survival (PFS) of patients with AML with I1762V were significantly greater than those of wild-type patients (HR=0.57, P=0.030; HR=0.55, P=0.020) , whereas the OS and PFS in patients with AML with DNMT3A mutation (with or without I1762V mutation) were lower than those of wild-type patients (HR=1.79, P=0.030; HR=1.74, P=0.040) . Conclusion: TET2 SNP I1762V has been linked to AML. I1762V is a prognostic factor of patients with AML, which can be used to guide the treatment and evaluate the prognosis of AML.

Progress on the protective effect of heme oxygenase-1 in viral infection / 药学学报

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the conversion of heme to CO, biliverdin, and iron, which together protect cells from oxidative and inflammatory damage and play an important role in maintaining cell homeostasis. In recent years, HO-1 has also been found to have antiviral biological effects, and the induced expression of HO-1 inhibits the replication of various viruses such as hepatitis C virus, hepatitis B virus, human immunodeficiency virus, dengue virus, ebolavirus, influenza A virus, Zika virus, severe acute respiratory syndrome coronavirus 2, human respiratory syncytial virus, hepatitis A virus and enterovirus 71. The inhibitory effect of HO-1 on these viruses involves three mechanisms, including direct inhibition of virus replication by HO-1 and its downstream products, enhancement of type I interferon responses in host cell, and attenuation of inflammatory damage caused by viral infection. This review focuses on the recent advances in the antiviral effect of HO-1 and its mechanism, which is expected to provide evidence for HO-1 as a potential target for antiviral therapy.

The therapeutic effect of human thioredoxin on ulcerative colitis in mice / 药学学报

This study was designed to obtain recombinant human thioredoxin (rhTXN) by gene cloning and prokaryotic expression, and evaluated its therapeutic effect in the mouse ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS). The human thioredoxin gene TXN was cloned from the cDNA of Jurkat cells. The recombinant expression plasmid pCold TF-rhTXN was constructed by restriction enzyme digestion. After expression in E. coli BL21 (DE3), recombinant human thioredoxin was purified by a nickel column. Intact rhTXN recombinant protein was obtained after removal of the fusion partner-tag by enzyme digestion and the activity of disulfide reductase was detected by the insulin reduction method. The animal experiments in this study were performed in accordance with the ethical guidelines of the Laboratory Animal Welfare Ethical Review Committee of Nanjing University. Experiment ulcerative colitis was induced by providing mice with sterilized drinking water which contained 3% DSS. rhTXN was injected intraperitoneally. The therapeutic effect was studied by weight change, colon length and HE (hematoxylin and eosin) stained sections. In vivo imaging was used to study the targeting of rhTXN to DSS mice. The GSE107499 data set of GEO database was used to screen the hub genes at the lesional sites of UC and study the correlation with TXN. The experimental results showed that rhTXN was successfully expressed and purified with disulfide reductase activity. rhTXN (100 μg·kg-1) had a significant therapeutic effect on maintaining the weight change of mice (P = 0.000 5) and reducing intestinal injury (P < 0.000 1), and had a colon targeting effect on DSS mice. In GSE107499 data set, TXN in inflammatory sites of UC patients was significantly down regulated (P < 0.01) and negatively correlated with hub gene CD40 (P < 0.01) and positively correlated with hub gene fibronectin 1 (FN1) (P < 0.01). In this study, biologically active rhTXN was successfully prepared and proved to have a promising therapeutic effect on the DSS mouse model, and TXN gene was significantly correlated with the UC hub genes CD40 and FN1.

Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Clinical effect of fetal reduction by intracranial and intrathoracic KCl injection / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the feasibility and effectiveness of fetal reduction by transabdominal intracranial KCl injection for multifetal pregnancies in the early second trimester.@*METHODS@#The data of 363 patients who underwent transabdominal fetal reduction in the Reproductive Medical Center of Peking University Third Hospital from January 2006 to December 2019 were analyzed retrospectively. According to the location of fetal reduction, they were divided into two groups: Intracranial injection group (n=196) and intrathoracic injection group (n=167). The process of fetal reduction and pregnancy outcome of the two groups were compared.@*RESULTS@#There was no significant difference between the two groups in the average age and the proportion of type of infertility before assisted reproductive technology, conception method, indication for fetal reduction, starting number of fetuses, reduced number of fetuses, and finishing number of fetuses (P>0.05). There was no significant difference between the two groups in the proportion of the number of puncture ≥ 2 times (12.1% vs. 8.6%, P=0.249) and the incidence of replacing puncture site (10.7% vs. 6.4%, P=0.161). The next day after fetal reduction, color Doppler ultrasound was rechecked. In the intracranial injection group and intrathoracic injection group, the incidence of fetal heartbeat recovery [3.6% (8/224) vs. 1.1% (2/187), P=0.188], the volumes of KCl used [(2.6±1.0) mL vs. (2.8±1.1) mL, P=0.079], and the abortion rate within 4 weeks after fetal reduction (1.0% vs. 0.6%, P=0.654) were of no significant difference. In addition, there was no significant difference in the total abortion rate after fetal reduction, premature delivery rate, cesarean section rate, delivery gestational week and neonatal birth weight between the two groups (P>0.05).@*CONCLUSION@#Intracranial KCl injection can be an effective alternative to intrathoracic KCl injection for multifetal pregancy reduction.

Research progress in the application of non-thermal atmospheric pressure plasma in dentin bonding / 中华口腔医学杂志

As a convenient and effective surface modification approach, non-thermal atmospheric pressure plasma (NTAPP)can be used to improve dentin bonding, and has recently become a research focus. Studies have shown that NTAPP can alter dentin surface properties, improve the penetration and polymerization of adhesives, stimulate the cross-linking of collagen, and change the micro-morphology and element content of dentin surface, thus improve the dentin bonding quality. This article introduces the current research progress in the application of NTAPP in the field of dentin bonding, in order to provide innovative information for future research in optimization of the quality of dentin bonding.

Study on the relationship between the pathological type of lung cancer caused by coke oven discharge and the contact type and exposure time / 中华劳动卫生职业病杂志

Objective: To study the pathological types of lung cancer caused by coke oven emissions and analyze the correlation between different exposure levels. Methods: In October 2020, the relevant data of 86 confirmed cases of lung cancer caused by coke oven emissions (including basic information of patients, relevant occupational exposure and clinical data) were collected, The workers were grouped according to the different COEs concentrations in their posts: workers in auxiliary posts were taken as the low exposure group (11 persons) , The workers at coke side and furnace bottom are the medium exposure group (14 persons) , and the workers at furnace top are the high exposure group (61 persons) , and the correlation between pathological types of lung cancer and different exposure levels was analyzed. Results: There was no significant difference in age and length of service among the groups (P>0.05) ; The number of lung cancer cases and pathological types among workers in each group were statistically significant (P=0.044) . After adjusting for interference factors, the number of undifferentiated cancers (mainly small cell lung cancer) increased with the increase of exposure level, with a statistically significant difference (P=0.001) . The incidence of lung cancer increased gradually with the length of service, and the incidence rate of lung cancer among workers of different working ages was statistically significant (P<0.05) . Conclusion: Undifferentiated small cell carcinoma is the most common pathological type of lung cancer caused by coke oven emissions, and the incidence of lung cancer tends to increase with the length of service.

Analysis of the usage of post-exposure prophylaxis and related factors among men who have sex with men / 中华预防医学杂志

A survey was conduct to analyze the usage situation of post-exposure prophylaxis(PEP) and related factors among men who have sex with men(MSM) in 6 cities of Shandong Province. Total of 2 620 subjects, the use ratio was 2.98% (78/2 620). Compared with age≤24 years,monthly income<5 000 yuan,non-commercial sex, non-DU,non-STD,role for being insert in the anal intercourse,MSM was more likely to use PEP with age≥45 years(OR=3.87, 95%CI:1.12-13.36),monthly income≥5 000 yuan(OR=1.87, 95%CI:1.07-3.28),commercial sex (OR=3.13, 95%CI:1.56-6.28), drug users (DUs) (OR=4.63, 95%CI:2.51-8.52),STD patient (OR=2.35,95%CI:1.05-5.27),the mixed sex role group(OR=2.25,95%CI:1.10-4.62).

Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain / 神经科学通报·英文版

Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (Ih), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the Ih. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.

Clinical Analysis of Salvage Treatment of Glucocorticoid Resistant Graft-Versus-Host Disease with Vedolizumab in Children / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of VDZ (Vedolizumab) in the salvage treatment of glucocorticoid resistance to gastrointestinal graft-versus-host disease (GR-GI GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children.@*METHODS@#The clinical data of 5 patients with refractory GI GVHD who received allo-HSCT in Wuhan Children's Hospital from December 2020 to December 2021 were retrospectively analyzed with VDZ salvage therapy.@*RESULTS@#Among the 5 children with refractory GI GVHD, there were 1 male and 4 female, including 2 cases of extremely severe aplastic anemia, 1 case of acute myeloid leukemia (M2, high-risk), 1 case of fanconi anemia and 1 case of myelodysplastic syndrome. The median age of transplant recipients was 54.4 (12-164) months. The median treatment time from transplantation to VDZ was 1.4 (0.6-6.8) months. On average, 3.5 (2-5) doses of VDZ were received. After receiving treatment, 2 patients achieved a complete response (CR), 2 patients achieved a very good partial response (VGPR), 1 patient was non-responsive (NR) after a short-term partial response (PR). Compared with that before VDZ treatment, the amount of diarrhea, stool color, blood and traits of the children after medication were effectively improved. The median follow-up time was 9.3 (7.23-12.83) months. No disseminated or severe bacterial/fungal infections occurred during VDZ treatment and follow-up, and 2 children died of leukemia recurrence and pulmonary bronchiolitis obliterans.@*CONCLUSION@#VDZ salvage treatment of refractory GI GVHD in children has obvious short-term efficacy and good safety.

Development and Evaluation of Biocontrol Agents Against Panax ginseng Root Rot / 中国实验方剂学杂志

ObjectiveTo develop safe and effective microbial agents against Panax ginseng root rot. MethodP. notoginseng endophytes were screened in plate confrontation tests， followed by morphological and molecular biological identification of antagonistic strains， optimization of strain fermentation conditions in a single factor test， and determination of optimal carriers and auxiliary agents of the microbial agent and their ratio using response surface methodology for formulating the production process. The prevention and control effects of the microbial agent were verified in the confrontation and pot culture experiments. ResultThe plate confrontation test yielded a strain named Fusarium pseudoanthophilum with significant resistance to root rot， and its antibacterial rate was 53.33%. According to the single factor test， the fermentation conditions of F. pseudoanthophilum were determined to be fermentation time 60 h， fermentation temperature 26 ℃， speed 120 r·min-1， and pH 6.5. The response surface optimization results showed that the number of viable bacteria reached the maximum （5.23×109 cfu·g-1） when the peat was 60.00 g， sodium carboxymethylcellulose 3.50 g， and sodium alginate 4.76 g. The influences of carriers and auxiliary agents on the number of viable bacteria were sorted by degree in a descending order as follows： peat>sodium carboxymethylcellulose >sodium alginate. The confrontation test results showed that when the microbial agent concentration was greater than 1.00 g·L-1， it had a significant inhibitory effect on the root rot pathogen F. oxysporum and the inhibitory rate was more than 42.3%. As demonstrated by the pot culture experiment， the inoculation of biocontrol agent for 28 d significantly reduced the incidence （66.99%） of root rot in P. ginseng seedlings and disease index （61.69%） and increased their leaf length （33.04%） and fresh weight （34.48%）. ConclusionF. pseudoanthophilum inoculant is efficient in preventing and controlling the root rot， making it worthy of further development and utilization.