Global optimization for light concentrators of a Geiger-mode cosmic-ray Cherenkov calorimeter.

Light concentrators are crucial devices for photon-counting instruments, the optical characteristics of which affect the photoelectric response for the sensors. The designs that only aim to the light transmission have been proved far from optimum for the Geiger-mode calorimeters due to the significant influence from the angle-dependent reflectance, versatile light trajectories, and saturation of fired avalanche photodiodes (APDs). In this paper, we took into account these coupling effects, presented a novel approach to solve the problems in global optimization for light concentrators in combination with silicon photomultiplier (SiPM). In addition, a new probability method is studied and used to restore the photon counting for precise reconstruction of cosmic-ray air showers. The Monte-Carlo experiment verified that the new system design features a high accurate energy scaling for cosmic-ray measurement. The results also indicate that the precision is able to be improved by at least one order in magnitude.

Marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques.

Marburg virus (MARV), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a mortality rate of up to 90%. Currently, there is no effective treatment or approved vaccine for MARV for human use to control disease outbreak and spread. Virus-like particles (VLPs), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and hepatitis B virus (HBV). In this study, we generated MARV virus-like particles (VLPs) by co-expressing a glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. Rhesus macaques vaccinated with MARV VLPs mixed with adjuvant Poria cocos polysaccharides (PCP-II) produced a GP-specific IgG titer of up to 1:1280 and virus-neutralizing antibody titers that reached 1:320. MARV VLPs also elicited interferon-γ (IFN-γ) and interleukin-4 (IL-4) secretion associated with T-helper 1 cell (Th1)- and T-helper 2 cell (Th2)-mediated immunity, as detected using enzyme-linked immunospot (ELISpot) assays. These data indicate that MARV VLPs mixed with adjuvant PCP-II have excellent immunogenicity in rhesus macaques and may be a promising candidate vaccine against MARV.

Long-Term Changes in Drug Craving and Nutritional Status of Opioid Addicts with Nucleus Accumbens Ablative Stereotactic Neurosurgery at Five Years Postoperatively.

BACKGROUND: The nucleus accumbens (NAcc) has been proven to be associated with drug and food craving. NAcc ablative neurosurgery has been suggested to modulate the balance of the brain reward system and thus alleviate drug dependence in patients. It has been hypothesized that it would also alleviate food craving in patients as well as altering their nutritional status. AIMS: This study aimed to estimate the effect of NAcc neurosurgery on drug craving and nutritional status in patients with drug dependence at 5 years postoperatively. METHODS: The study included 100 patients with NAcc surgery and 92 patients without surgery. Body mass index (BMI) and body fat percentage (BF%) were examined to assess nutritional status, and questionnaires were administered to assess drug craving. RESULTS: Compared with the nonsurgery group and the relapse patients from the surgery group, the nonrelapse patients from the surgery group had higher BMI and BF% but lower drug craving. There were no significant differences between the nonsurgery group and the relapse patients in BMI, but the relapse patients had higher drug craving than the nonsurgery group. CONCLUSIONS: Long-term follow-up suggested that NAcc ablative neurosurgery would alleviate drug craving and yield a better nutritional status if individuals sustained abstinence. It would increase drug craving but would not ruin the nutritional status of patients even when individuals relapsed postoperatively.

Association between brachial artery peak systolic velocity and ipsilateral radio-cephalic arteriovenous fistula maturation.

OBJECTIVE: To evaluate the association between brachial artery blood velocity by color Doppler flow imaging (CDFI) and primary maturation of radio-cephalic autologous arteriovenous fistula (RC-AVF). METHODS: Clinical data from patients who underwent end-to-side cephalic-radial anastomosis were collected from December 2015 to December 2020. The anastomosis diameter (mm), blood velocity (cm/s), and brachial artery diameters (mm) 7 cm proximal to the elbow pre- and postoperation were measured by GE LOGIC-E9 ultrasound. The AVF was mature if it could be cannulated successfully and the blood flow was >200 ml/min during dialysis. RESULTS: A total of 197 patients were included in our statistical analysis. A total of 163 patients had mature AVFs, and 34 patients had poor maturity (assisted and failed maturation). There were no significant differences in the clinical characteristics, peak systolic velocity (PSV) of the brachial artery, diameter of the radial artery or cephalic vein measured by CDFI preoperatively. The diameter of the brachial artery (5.41 ± 0.77 vs 4.89 ± 0.90, p = 0.00) and the fistula anastomosis (2.79 ± 0.78 vs 2.45 ± 0.85, p = 0.02) and PSV of the brachial artery (123.58 ± 37.11 vs 89.63 ± 28.31, p = 0.00) in the mature group were higher than those in the immature group. CONCLUSION: Brachial artery PSV and increased brachial artery PSV could be used to detect RC-AVF maturation in the early stage.

Associations between personality changes and nucleus accumbens ablation in opioid addicts.

AIM: It has been reported that nucleus accumbens (NAc) lesions can help to prevent relapse in opioid addicts. This article aimed to investigate associations between personality changes and NAc lesions. METHODS: The surgery group consisted of 78 patients who had received bilateral stereotactic lesions of the NAc to treat opioid addiction. Seventy two non-surgery opioid addicts were appropriately paired with the patients of the surgery group as the non-surgery group. All participants were interviewed in person and received urine tests, naloxone provocative tests and hair tests to determine the prevalence of relapse. Eysenck personality questionnaire (EPQ) and the health survey questionnaire (SF-36) were employed to assess personality and functional health, respectively. RESULTS: In the surgery group, 30 participants relapsed, and the non-relapse rate was 61.5% (48/78). Compared with the Chinese normative data, the neuroticism (N) and psychoticism (P) dimensions of the EPQ in the non-surgery group were significantly higher, whereas the lie (L) dimension was significantly lower. There was no significant difference in all dimensions of the EPQ between the surgery group and the Chinese normative data. The N dimension in the relapse group and the L dimension in the surgery group were significantly lower than those of the non-surgery group. The P dimension in the relapse group was significantly higher than that of the non-relapse group. The extraversion (E) dimension was relatively stable between these groups. CONCLUSION: Although the influence of other factors cannot be excluded, it is apparent that surgically induced NAc lesions are associated with lower P and N dimensions for opioid addicts, and a higher P dimension is associated with a tendency to relapse.

Growth and stress responses of the earthworm Eisenia fetida to Escherichia coli O157:H7 in an artificial soil.

Escherichia coli O157:H7 is an intestine-inhabiting bacterium associated with many severe disease outbreaks worldwide. It may enter the soil environment with the excreta of infected animals (including horses, cattle and chickens) and human. Earthworms are able to protect themselves against invading pathogens due to their efficient innate defense system. To better understand the mechanisms earthworms (Eisenia fetida) utilize to defend and eliminate Escherichia coli O157:H7, we examined the changes in the growth rate, as well as antioxidant and antimicrobial functions of earthworms in response to various concentrations of Escherichia coli O157:H7 in an artificial soil. Our results show that earthworms can inhibit the growth of Escherichia coli O157:H7. Upon exposure to Escherichia coli O157:H7 from 0 d to 24 d, coelomic cytolytic factor (CCF) in earthworms is induced, the reactive oxygen species (ROSs) and superoxide dismutase (SOD) are also elevated. Under lower bacterial concentrations (10(5)-10(6)CFU g(-1)), these ROSs can be rapidly scavenged by superoxide dismutase (SOD) to avoid peroxidation damage, but when the bacterial concentrations are high (10(7)-10(8)CFU g(-1)), excess amount of ROSs then cause accumulation of lipid peroxidation molecular malondialdehyde (MDA). In addition, exposure to Escherichia coli O157:H7 can induce the gene expression of antimicrobial peptide lumbricin I in the tissues of the earthworms. In conclusion, antioxidant systems and antimicrobial immune function may play important roles in the defense of the earthworms Eisenia fetida against Escherichia coli O157:H7.

Lung Squamous Cell Carcinoma with EML4-ALK Fusion and TP53 Co-mutation Treated with Ensartinib: A Case Report and Literature Review / 中国肺癌杂志

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Clinical features of portal biliopathy / 临床肝胆病杂志

ObjectiveThis article aims to investigate the clinical features of portal biliopathy （PB） patients， in order to improve the understanding of PB. MethodsClinical data were collected from 22 patients who were diagnosed with PB in recent years in The First Hospital of Jilin University， and an analysis was performed for their clinical manifestations， liver function， abdominal color Doppler ultrasound， abdominal CT， and hepatobiliary magnetic resonance imaging. The imaging manifestations of biliary tract abnormalities were described， as well as the type of collateral circulation and the location of thrombosis. ResultsAs for the initial symptom in these 22 patients， three were 11 patients with gastrointestinal bleeding， 5 with abdominal distension， 3 with abdominal pain， 1 with fever， 1 with abdominal discomfort， and 1 with gingival bleeding. There were 3 patients with an increase in aspartate aminotransferase， 4 with an increase in alanine aminotransferase， 4 with an increase in gamma-glutamyl transpeptidase， 7 with an increase in alkaline phosphatase， 8 with a reduction in cholinesterase， 9 with a reduction in albumin， 2 with an increase in globulin， and 5 with an increase in total bilirubin. Among the 22 patients， 20 had cavernous transformation of the portal vein， and 2 had portal vein thrombosis without cavernous transformation. All 22 patients had bile duct abnormalities， among whom 2 had extrahepatic bile duct abnormalities alone， 12 had intrahepatic bile duct dilatation alone， and 8 had dilatation of both intrahepatic and extrahepatic bile ducts. Varices at different sites were observed in 20 patients， among whom 19 had esophageal and gastric varices and 1 had peri-gallbladder varices， and no varices was observed in the superior mesenteric vein or the splenic vein. ConclusionThere are no typical clinical symptoms and changes in liver function parameters in patients with PB， but radiological examination may show dilatation， stenosis， or malformation of the bile ducts at different parts. Therefore， it is necessary to expand the sample size to further explore the diagnosis and treatment of PB.

Construction of an Analysis Model of mRNA Markers in Menstrual Blood Based on Naïve Bayes and Multivariate Logistic Regression Methods / 法医学杂志

OBJECTIVES@#To establish the menstrual blood identification model based on Naïve Bayes and multivariate logistic regression methods by using specific mRNA markers in menstrual blood detection technology combined with statistical methods, and to quantitatively distinguish menstrual blood from other body fluids.@*METHODS@#Body fluids including 86 menstrual blood, 48 peripheral blood, 48 vaginal secretions, 24 semen and 24 saliva samples were collected. RNA of the samples was extracted and cDNA was obtained by reverse transcription. Five menstrual blood-specific markers including members of the matrix metalloproteinase (MMP) family MMP3, MMP7, MMP11, progestogens associated endometrial protein (PAEP) and stanniocalcin-1 (STC1) were amplified and analyzed by electrophoresis. The results were analyzed by Naïve Bayes and multivariate logistic regression.@*RESULTS@#The accuracy of the classification model constructed was 88.37% by Naïve Bayes and 91.86% by multivariate logistic regression. In non-menstrual blood samples, the distinguishing accuracy of peripheral blood, saliva and semen was generally higher than 90%, while the distinguishing accuracy of vaginal secretions was lower, which were 16.67% and 33.33%, respectively.@*CONCLUSIONS@#The mRNA detection technology combined with statistical methods can be used to establish a classification and discrimination model for menstrual blood, which can distignuish the menstrual blood and other body fluids, and quantitative description of analysis results, which has a certain application value in body fluid stain identification.

Clinical study on the treatment of gastrointestinal neurosis with insomnia by combination of "stomach ten acupuncture" and domperidone tablets / 国际中医中药杂志

Objective:To study on the effect of "stomach ten acupuncture" combined with domperidone tablets on clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia based on the theory of "stomach harmonious leading to restless".Methods:Randomized controlled trial. From March 2020 to March 2021, 98 patients with gastrointestinal neurosis and insomnia in our hospital who met the inclusion criteria were randomly divided into two groups, with 49 patients in each group. The control group took domperidone tablets orally, and the observation group was treated with "stomach ten acupuncture" on the basis of the control group. Both groups were treated for 8 weeks. Before and after treatment, TCM syndromes were scored, the severity of gastrointestinal symptoms was assessed with Gastrointestinal Symptom Rating Scale (GSRS), anxiety and depression were assessed with Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), and sleep quality was assessed with Pittsburgh Sleep Quality Index Scale (PSQI).Results:After treatment, the scores and total scores of epigastric pain, belching, abdominal distension, anorexia, noisy acid regurgitation, tiredness and asthenia, constipation and loose stools in the observation group were significantly lower than those in the control group ( t values were 19.61, 19.30, 23.10, 22.05, 20.43, 21.81, 20.51, 16.38, respectively, P<0.01); the scores and total scores of typical symptoms, abdominal pain symptoms, reflux symptoms, diarrhea symptoms, constipation symptoms were significantly lower than those in the control group ( t values were 10.10, 11.14, 11.04, 9.31, 11.24, 5.30, respectively, P<0.01); HAMA and HAMD scores were significantly lower than those in the control group ( t values were 6.96 and 6.85, respectively, P<0.01). The scores of time to fall asleep (1.15 ± 0.56 vs. 2.11 ± 0.75, t=7.18), time to sleep (0.92 ± 0.63 vs. 1.52 ± 1.12, t=3.27), sleep quality (1.02 ± 0.66 vs. 1.96 ± 0.80, t=6.35), sleep efficiency (0.86 ± 0.62 vs. 1.68 ± 0.85, t=5.46), sleep disorders (0.92 ± 0.36 vs. 1.48 ± 0.55, t=5.96), daytime dysfunction (0.96 ± 0.42 vs. 1.97 ± 0.87, t=7.32), hypnotics (0.98 ± 0.45 vs. 1.81 ± 0.62, t=7.58) and total scores (6.85 ± 1.47 vs. 12.73 ± 2.95, t=12.49) were significantly lower than those in the control group ( P<0.01). Conclusion:The "stomach ten acupuncture" combined with domperidone tablets can improve the clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia.

Renewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferation via Jagged-1-Notch1

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX3CR1+CCR2-Ly6C-MHCII- (MP1), CX3CR1lowCCR2lowLy6C-MHCII- (MP2), CX3CR1-CCR2+Ly6C+MHCII- (MP3), and CX3CR1+CCR2-Ly6C-MHCII+ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.

Prognostic Significance of LPCAT1 in Adult Acute Myeloid Leukemia Patients with FAB Subtype M2 / 中国实验血液学杂志

OBJECTIVE@#To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML).@*METHODS@#TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors.@*RESULTS@#The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049).@*CONCLUSION@#In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.

Analysis of Clinical Features and Risk Factors for Oral Ulcers and Bloodstream Infection in Patients with Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the risk factors of oral ulcers and bloodstream infection in patients with hematopoietic stem cell transplantation.@*METHODS@#The clinical data of 401 hematopoietic stem cell transplant patients in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospective analyzed, and the risk factors of oral ulcers and bloodstream infection statistical and analyzed.@*RESULTS@#Among the 401 patients, the incidence of oral ulcers was 61.3% (246/401), and the incidence of bloodstream infection was 9.0% (36/401). A total of 40 strains of pathogenic bacteria were isolated from 36 patients, including 26 strains of Gram negative strains (65%), 13 strains of Gram positive strains (32.5%), and 1 strain of fungi (2.5%). Single-factor analysis showed that oral hygiene was associated with the occurrence of bloodstream infection, and the Multi-factor analysis showed that age ≥14 years old, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers.@*CONCLUSION@#The incidence of oral ulcers in patients with hematopoietic stem cell transplantation is high. The age ≥14 years, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers in patients, and oral hygiene was associated with the occurrence of bloodstream infection.

Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies.@*METHODS@#The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated.@*RESULTS@#A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027).@*CONCLUSION@#The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

Noninvasive Tracking of Every Individual in Unmarked Mouse Groups Using Multi-Camera Fusion and Deep Learning / 神经科学通报·英文版

Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions. Traditional tracking methods (e.g., marking each animal with dye or surgically implanting microchips) can be invasive and may have an impact on the social behavior being measured. To overcome these shortcomings, video-based methods for tracking unmarked animals, such as fruit flies and zebrafish, have been developed. However, tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns. In this study, we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network (R-CNN) deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology. The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior. The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.

A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models / 国际口腔科学杂志·英文版

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.

Effect of Toxoplasma gondii Chinese 1 genotype infections on brain iron metabolism in mice / 中国血吸虫病防治杂志

Objective To investigate the effect of Toxoplasma gondii Chinese 1 genotype infections on host brain iron metabolism and brain damages. Methods Twenty C57BL/6 mice, each weighing 15 to 17 g, were randomly divided into the control and infection groups, of 10 mice in each group. Each mouse in the infection group was injected intraperitoneally with 4 000 tachyzoites of the TgCtwh3 isolate with Chinese 1 genotype, while each mouse in the control group was injected with an equal amount of sterile phosphate-buffered saline (PBS). All mice were sacrificed 6 day post-infection and brain tissues were sampled. The iron levels were measured in mouse brain specimens using inductively coupled plasma mass spectrometry (ICP-MS). The differentially expressed genes were determined between the experimental and control groups using RNA chips and Gene Ontology (GO) term enrichment analysis of differentially expressed genes was performed. The mRNA expression of Toxoplasma gondii surface antigen 1 (TgSAG1) gene and some Zrt- and Irt-like protein (ZIP) family member coding genes was detected by quantitative real-time PCR (qPCR) assay. The ultrastructure of the hippocampus dentate gyrus in mouse brain specimens was observed using optical and electronic microscopy. The glutathione peroxidase 4 (GPx4) expression was determined using Western blotting, and malondialdehyde (MDA) level was measured using thiobarbituric acid (TBA) test. In addition, the optical density (OD) of vascular endothelial growth factor (VEGF) protein was measured using immunohistochemistry. Results Optical microscopy showed cell necrosis in the hippocampus dentate gyrus of mouse brain specimens in the infection group, and electronic microscopy cytoplasmic vacuolization, nuclear atrophy and necrosis, disruption of cristae mitochondriales and increased autophagosome levels in the mouse brain hippocampus specimens in the infection group. The iron level was significantly greater in mouse brain specimens in the infection group than in the control group [(32.92 ± 0.90) μg/g vs. (37.72 ± 1.10) μg/g; t = 3.397, P < 0.01]. RNA chips revealed 721 up-regulated genes and 276 down-regulated genes in mouse brain specimens between the infection and control groups, and the differentially expressed genes were significantly enriched in metal ion binding ability (molecular function). Elevated expression of metal element transporter ZIP2 mRNA (t = 8.659, P < 0.05), reduced GPx4 expression [(1.046 ± 0.025) vs. (0.720 ± 0.101); t = 3.129, P < 0.01], increased MDA level [(4.37 ± 0.33) nmol/mgprot vs. (5.93 ± 0.54) nmol/mgprot; t = 2.451, P < 0.05], and up-regulated mean OD of VEGF protein [(0.348 3 ± 0.017 8) vs. (0.490 6 ± 0.010 5); t = 6.641, P < 0.01] were found in mouse brain specimens in the infection group than in the control group. Conclusions Chinese 1 genotype T. gondii infection results in iron accumulation in brain tissues, reduced antioxidant ability and elevated levels of oxidative stress in mice, suggesting that T. gondii infection may cause brain damages through affecting iron metabolism in host brain tissues.

The influence of application-audit system for doctoral enrollment on scientific research ability and employment development of medical graduate students / 中华医学教育探索杂志

Objective:To investigate and analyze the differences of PhD student scientific research ability, employment and development among types of postgraduate students that admitted by various of doctoral admissions under the perspective of medical students to assess and optimize the existing applications-audit system (AAS).Methods:A self-compiled questionnaire was used to investigate the opinions of medical students at different grades and types on the AAS related issues. Excel and SPSS were used to perform frequency statistics, chi-square test and independent sample t-test. Results:The PhD enrolled from AAS tended to complete the paper-publication at first and second year (38.71%, 12/31; 35.48%, 11/31), while unified enrollment (UE) tended to complete in the second year (33.33%, 10/30) and seven-year degree (SYD) in the third year (40.54%, 15/37) ( P=0.021). In terms of the value of the materials required in the application stage to the doctoral research, 74.19%(23/31) of AAS students and 48.65%(18/37) of SYD students believed that scientific research results were the most helpful to the doctoral research process, while UE believed that English helped the most (26.67%, 8/30), with significant differences among groups ( P=0.002). In terms of fair recognition of enrollment in the application system, 71.53% (304/425) of graduate students believed that AAS for doctoral enrollment was fair. The institution ( P=0.001) and type of master's degree ( P=0.001) significantly affected graduate students' recognition of the fairness of AAS. Conclusion:The degree and speed of dissertation completion of the AAS PhD are prior, reflecting the advantages of AAS in the cultivation of medical doctors' scientific academic ability and achievements. The AAS plays a significant role in enhancing the reserve of high-level scientific researchers in China, and has a high recognition and influence in medical students. In the future, the application examination system will be optimized to create the most suitable way for doctoral enrollment in China.

Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma

Background It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. Method Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. Results The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892– 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581–27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901–21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780–0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661–0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs=–0.338, P=0.014), immunoglobulin E (rs=-0.277, P=0.047), TNF-α (rs=-0.423, P=0.002), IL-1β (rs=-0.389, P=0.004), and IL-17 (rs=-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1β (rs=-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). Conclusion DUSP1 reflects the reduced exacerbation risk, and associates with lower (AU)

[Effects of oral interventions on carotid artery in rats with chronic periodontitis for the detection of Porphyromonas gingivalis and the expression of C-reactive protein].

OBJECTIVE: This study aimed to establish a SD rat model of chronic periodontitis (CP) merged with hyperlipidemia (HL), perform periodontal treatment, detect the expression of partial C-reactive protein (CRP) and Porphyromonas gingivalis (P. gingivalis) in the rat carotid artery, and explore the relationship between periodontitis and atherosclerosis. METHODS: SD rats were randomly divided into three groups: control group (A), HL group (B), and CP+HL group (C). Group C rats were divided into natural process group (C1), scaling and root planning group (C2), and tooth extraction group (C3). Group C2 rats were randomly divided into C2-1 (scaling and root planning group) and C2-2 (scaling and root planning+minocyline+systemic antibiotics group). Group C3 rats were randomly divided into C3-1 (tooth extraction group) and C3-2 (tooth extraction+systemic antibiotic group). One rat from group B was randomly selected and sacrificed after 15 weeks. Subsequently, the carotid vascular tissue was collected for oil red O staining. Modeling was successful when foam cell formation was observed. Periodontal treatments were conducted twice, and euthanasia was performed after the experiment. Moreover, double-carotid artery bifurcation was carried out to detect the expression of CRP and P. gingivalis. Immunohistochemical and 16sRNA semiquantitative methods were used to detect the CRP expression and the relative contents of P. gingivalis, respectively. RESULTS: Immunohistochemical results showed that the CRP-positive expression in groups B and C was significantly higher than that in group A (P<0.05). The CRP-positive expression in other group C rats were significantly lower than that in group C1 (P<0.05). The CRP-positive expression in group C2-2 was the lowest among the groups (P<0.05). The relative quantity of P. gingivalis in group C1 was the highest and significantly higher than that in groups A and B (P<0.05). The relative quantities of P. gingivalis in groups C2-1, C2-2, C3-1, and C3-2 were significantly lower than that in group C1 (P<0.05), and the quantity in group C3-2 was the lowest (P<0.05). CONCLUSIONS: Rats with CP associated with HL will increase the CRP expression and oral bacteria quantity on carotid artery, and lesions will gradually aggravate. Interventions, such as periodontal basic treatment and tooth extraction, could improve carotid artery lesions. The basic treatment with local and systemic anti-inflammatory drugs exerts the most satisfactory effect on local CRP expression. Tooth extraction with antibiotics is an effective method on reducing oral bacteria in carotid artery. Periodontal basic treatment associated with local and systemic antiflammatory drugs can obviously improve the effect.
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