Effects and mechanism of Setaria italica extract on improving sleep in insomnia mice / 中国药房

OBJECTIVE To investigate the effects of Setaria italica extract on improving insomnia model mice and to explore its potential mechanisms. METHODS The mice were randomly assigned into blank group， model group， positive control group （diazepam， 2.6 mg/kg）， and S. italica extract low-dose， medium-dose and high-dose groups （1.2， 2.4， 4.8 g/kg）， with 10 mice in each group. Except for the blank group， all other groups received intraperitoneal injection of para-chlorophenylalanine （PCPA） to establish the insomnia model. After modeling， the blank group and model group were given a constant volume of normal saline intragastrically， and administration groups were given relevant medicine intragastrically， with a volume of 0.01 mL/g， once a day， for 7 consecutive days. After the administration， the open-field test was conducted to observe the praxiological changes of mice， and to determine the levels of 5-hydroxytryptamine （5-HT） and 5-hydroxyindoleacetic acid （5-HTAA） in the hippocampal tissue， as well as the contents of 5-HT， brain-derived neurotrophic factor （BDNF）， interleukin-2 （IL-2）， IL-6， B-cell lymphoma-2 （Bcl- 2）， and Bcl-2-associated X protein （Bax） in the serum. The expression of phosphoinositide 3-kinase/protein kinase B/nuclear factor- κB （PI3K/Akt/NF-κB） signaling pathway related protein was determined in the hippocampus of mice. RESULTS Compared with the model group， the total exercise time of mice in S. italica extract high-dose group was significantly prolonged， but the total rest time was significantly shortened （P＜0.01）； the number of standing times and modification times were significantly reduced （P＜ 0.01）. The contents of 5-HT， BDNF， and Bcl-2 in serum， and Bcl-2/Bax were significantly increased， while the contents of IL-2， IL-6， and Bax were significantly reduced （P＜0.05 or P＜ 0.01）. The content of 5-HTAA in the hippocampal tissue and 202104010910029）；the phosphorylation levels of PI3K and Akt proteins were increased significantly， while the phosphorylation level of NF-κB p65 protein was decreased significantly （P＜0.05）.CONCLUSIONS High-dose of S. italica extract demonstrates significant therapeutic effects on insomnia in mice， and the mechanism of which may be associated with the regulation of PI3K/Akt/NF-κB signaling pathway.

The relationship between COVID-19, depressive disorder, and anxiety: a bidirectional Mendelian randomization study.

Background: Previous clinical studies have found that negative mental states such as depression and anxiety are closely related to COVID-19 infection. We used Mendelian randomization (MR) to explore the relationship between depression, anxiety, and COVID-19 infection. Methods: Our data were based on publicly available GWAS databases. The COVID-19 samples were obtained from the COVID-19 Host Genetics Initiative (HGI). The depression samples were obtained from the Psychiatric Genomics Consortium (PGC). The anxiety samples were derived from the Finngen database. We used inverse-variance weighting (IVW) as the primary analysis method, with weighted median, MR Egger, and multivariate MRI adjustment. Results: There was no causal effect of different COVID-19 infection statuses on depression and anxiety as determined by MR analysis. In addition, in the reverse MR analysis, we found a significant causal effect of anxiety on severe symptoms after COVID-19 infection. The results of the MR Egger regression, weighted median, and weighted mode methods were consistent with the IVW method. Based on sensitivity analyses, horizontal pleiotropy was unlikely to influence the final results. Conclusion: Our findings indicate that anxiety is a risk factor for severe symptoms following COVID-19 infection. However, the mechanism of interaction between the two needs further investigation.

Genetically-Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage.

Background The evidence linking vitamin D (VitD) levels and spontaneous intracerebral hemorrhage (ICH) remains inconclusive. We tested the hypothesis that lower genetically determined VitD levels are associated with higher risk of ICH. Methods and Results We conducted a 2 sample Mendelian Randomization (MR) study using publicly available summary statistics from published genome-wide association studies of VitD levels (417 580 study participants) and ICH (1545 ICH cases and 1481 matched controls). We used the inverse-variance weighted approach to generate causal estimates and the MR Pleiotropy Residual Sum and Outlier and MR-Egger approaches to assess for horizontal pleiotropy. To account for known differences in their underlying mechanism, we implemented stratified analysis based on the location of the hemorrhage within the brain (lobar or nonlobar). Our primary analysis indicated that each SD decrease in genetically instrumented VitD levels was associated with a 60% increased risk of ICH (odds ratio [OR], 1.60; [95% CI, 1.05-2.43]; P=0.029). We found no evidence of horizontal pleiotropy (MR-Egger intercept and MR Pleiotropy Residual Sum and Outlier global test with P>0.05). Stratified analyses indicated that the association was stronger for nonlobar ICH (OR, 1.87; [95% CI, 1.18-2.97]; P=0.007) compared with lobar ICH (OR, 1.43; [95% CI, 0.86-2.38]; P=0.17). Conclusions Lower levels of genetically proxied VitD levels are associated with higher ICH risk. These results provide evidence for a causal role of VitD metabolism in ICH.

Simultaneous and sequential multi-species coronavirus vaccination

Although successful COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging for development of multi-species coronavirus vaccines. Here we developed prototype LNP-mRNA vaccine candidates against SARS-CoV-2 (Delta variant), SARS-CoV and MERS-CoV, and test how multiplexing of these LNP-mRNAs can induce effective immune responses in animal models. A triplex scheme of LNP-mRNA vaccination induced antigen-specific antibody responses against SARS-CoV-2, SARS-CoV and MERS-CoV, with a relatively weaker MERS-CoV response in this setting. Single cell RNA-seq profiled the global systemic immune repertoires and the respective transcriptome signatures of multiplexed vaccinated animals, which revealed a systemic increase in activated B cells, as well as differential gene expression signatures across major adaptive immune cells. Sequential vaccination showed potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrated the feasibility, antibody responses and single cell immune profiles of multi-species coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights on optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species. One sentence summaryMultiplexed mRNA vaccination in simultaneous and sequential modes provide broad and potent immunity against pathogenic coronavirus species.

Characteristic of medication compliance behavior in renal transplantation patients / 中南大学学报(医学版)

OBJECTIVES@#After renal transplantation, patients need to take various immunosuppressant, but the drug compliance is poor. The theory of planned behavior suggests that the past medication behavior and subjective norms of individuals are closely related to medication compliance. This study aims to explore the change of medication compliance behavior and its influenting factors for renal transplantation patients at different stages.@*METHODS@#This study was a prospective longitudinal study. The Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS), Medication Belief Scale, Social Support Scale and Quality of Life Scale were used to dynamically follow up renal transplantation patients at pre-operation and 1-month, 6-month, and 12-month after transplantation.@*RESULTS@#A total of 300 patients completed the whole follow-up. The percentage of patients with good medication compliance was 97.60%, 87.30% and 84.30% at 1-month, 6-month and 12-month after transplantation respectively. The life quality of the patients was decreased at 6 months after the operation, and the patients with better self-reported life quality had poor medication compliance. After adjusting for demographic data, the risk of medication incompliance in patients with poor medication compliance before operation was 37.646 times than those with good compliance. Patients who did not use medication reminders had high risk (odds ratio=2.467) of drug non-adherence. The risk of drug non-adherence in patients with more postoperative misgivings was 1.265 times compared with that in patients with less postoperative misgivings.@*CONCLUSIONS@#The medication compliance decreases with the time of transplantation, but the medication compliance of patients with good self-reported life quality is poor. Medication concerns reduce the compliance behavior. Preoperative medication behavior has a significant predictive effect on postoperative behavior. Medication reminder is a protective factor for promoting compliance. Medical staff should pay more attention to preoperative medication belief, behaviors and reminder of using drug so as to provide precise intervention in the renal transplantation patients.

Functions of key genes involved in TGF-β/Smad signaling pathway in progression of pulmonary fibrosis / 环境与职业医学

Background Although transforming growth factor-β (TGF-β)/Smad signaling pathway is important in regulating the occurrence and development of pulmonary fibrosis, the pathogenesis of pulmonary fibrosis remains elusive. Objective To explore the functions of genes associated with TGF-β/Smad signaling pathway in the progression of pulmonary fibrosis. Methods A NIH-3T3 fibroblast model induced by TGF-β1 was established. The experiment samples were divided into a control group and a TGF-β1 treatment group. The control group was exposed to normal saline, while the TGF-β1 treatment group was exposed to 10 ng·mL−1 TGF-β1 for 12 h. The RNAs of the two groups were extracted, sequenced, and analyzed by bioinformatics methods to identify seven key genes in TGF-β pathway, including Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3. The gene expression levels of five markers [Collagen1α1, Collagen1α2, α-smooth muscle actin (α-SMA), TGF-β1, and TGF-β3] and the seven key genes were detected by quantitative real-time PCR (qRT-PCR). The proteins of the two groups were extracted. The important marker protein expression levels of Smad3, the phosphorylation of Smad3 (P-Smad3), and α-SMA were detected by Western blotting. At the same time, 30 healthy SPF-grade C57BL/6 mice were randomly divided into three groups, with 10 mice in each group: a control group, a SiO2 inhalation exposure group for 28 d (10 mice), and a SiO2 inhalation exposure group for 56 d (10 mice). The mice in the two treatment groups were exposed to a natural SiO2 environment for 4 h per day with a 10-min pause for breathing fresh air at 2 h intervals. The lung tissues of the mice were taken after execution. The changes of pulmonary fibrosis were detected by Masson staining, and mRNAs and proteins were extracted to detect the expression of the above key genes and proteins. Results The expression levels of the five marker genes Collagen1α1, Collagen1α2, α-SMA, TGF-β1, and TGF-β3 were significantly increased in the TGF-β1-induced NIH-3T3 fibroblasts than those in the control group (P < 0.01); the expression levels of P-Smad3 and α-SMA proteins increased significantly (P < 0.01); the expression results of the seven key genes screened in the TGF pathway were that Dcn and Smad3 were obviously down-regulated (P < 0.01), and Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 were obviously up-regulated (P < 0.01). The changes in gene expression levels of the transcriptome sequencing showed the same trend. The results of Masson staining showed that the content of collagen fibers in the lung tissues also increased in the SiO2 inhalation exposure groups over time. In the mouse experiment, five marker genes were obviously up-regulated compared with the control group (P < 0.01); no obvious change was found in the expression of Smad3 protein, and the expression levels of P-Smad3 and α-SMA were obviously higher in the SiO2 exposure groups than those in the control group (P < 0.01); the expression levels of Dcn and Smad3 showed a down-regulated trend, while the expression levels of Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 showed an up-regulated trend with the increase of SiO2 inhalation exposure days (P < 0.01). The expression levels of the above five marker genes, three important marker proteins, and seven key genes were consistent with the expression trends of TGF-β1-induced NIH-3T3 fibroblasts. Conclusion The expression levels of pulmonary fibrosis-related marker genes and proteins change significantly in TGF-β1-induced fibroblast cells, and the lung tissues of mice under natural SiO2 inhalation exposure has obvious fibrosis characteristics. Seven genes (Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3) may be involved in the regulation of pulmonary fibrosis by the TGF-β/Smad signaling pathway.

A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program

The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n=35) or hospitalization (n=42) due to severe COVID-19 using genome-wide association summary from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (nrs495828= 53 and nrs505922=59); strongest association with venous embolism, odds ratio (ORrs495828 1.33 (p=1.32 x 10-199), and thrombosis ORrs505922 1.33, p=2.2 x10-265. Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p=4.12 x 10-191; CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p=2.26x 10-12. The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p=6.48 x10-23, lupus OR 0.84, p=3.97 x 10-06. PheWAS stratified by genetic ancestry demonstrated differences in genotype-phenotype associations across ancestry. LMNA (rs581342) associated with neutropenia OR 1.29 p=4.1 x 10-13 among Veterans of African ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.

Application of percutaneous intervention in the treatment of benign biliary-enteric anastomosis stricture / 国际外科学杂志

Choledochojejunostomy is a common surgical method for the treatment of organ diseases such as hepatobiliary, gastrointestinal and pancreatic diseases, but there are many complications related to the operation. Benign biliary-enteric anastomosis stricture (BBES) is the most common long-term complication after operation, which seriously affects the quality of life of patients. At present, bile duct reconstruction and endoscopic treatment are the main methods to deal with BBES, but there are some limitations. The new interventional therapy has the advantages of small trauma, good repeatability, high success rate and few complications. It has been applied in many medical centers. The main treatment methods include percutaneous transhepatic biliary balloon dilatation, percutaneous temporary stent placement, percutaneous transhepatic choledochoscopy, magnetic compression anastomosis and intrabiliary ablation. Up to now, there is no uniform standard for the choice of interventional therapy for BBES at home and abroad, so it is of great clinical significance to establish a standardized interventional therapy strategy.

Single-Cell Omics Reveals Dyssynchrony of the Innate and Adaptive Immune System in Progressive COVID-19

A dysregulated immune response against the SARS-CoV-2 virus plays a critical role in severe COVID-19. However, the molecular and cellular mechanisms by which the virus causes lethal immunopathology are poorly understood. Here, we utilize multiomics single-cell analysis to probe dynamic immune responses in patients with stable or progressive manifestations of COVID-19, and assess the effects of tocilizumab, an anti-IL-6 receptor monoclonal antibody. Coordinated profiling of gene expression and cell lineage protein markers reveals a prominent type-1 interferon response across all immune cells, especially in progressive patients. An anti-inflammatory innate immune response and a pre-exhaustion phenotype in activated T cells are hallmarks of progressive disease. Skewed T cell receptor repertoires in CD8+ T cells and uniquely enriched V(D)J sequences are also identified in COVID-19 patients. B cell repertoire and somatic hypermutation analysis are consistent with a primary immune response, with possible contribution from memory B cells. Our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19, which may contribute to delayed virus clearance and has implications for therapeutic intervention.

Androgen regulates SARS-CoV-2 receptor levels and is associated with severe COVID-19 symptoms in men

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a global health crisis, and yet our understanding of the disease pathophysiology and potential treatment options remains limited. SARS-CoV-2 infection occurs through binding and internalization of the viral spike protein to angiotensin converting enzyme 2 (ACE2) on the host cell membrane. Lethal complications are caused by damage and failure of vital organs that express high levels of ACE2, including the lungs, the heart and the kidneys. Here, we established a high-throughput drug screening strategy to identify therapeutic candidates that reduce ACE2 levels in human embryonic stem cell (hESC) derived cardiac cells. Drug target analysis of validated hit compounds, including 5 alpha reductase inhibitors, revealed androgen signaling as a key modulator of ACE2 levels. Treatment with the 5 alpha reductase inhibitor dutasteride reduced ACE2 levels and internalization of recombinant spike receptor binding domain (Spike-RBD) in hESC-derived cardiac cells and human alveolar epithelial cells. Finally, clinical data on coronavirus disease 2019 (COVID-19) patients demonstrated that abnormal androgen states are significantly associated with severe disease complications and cardiac injury as measured by blood troponin T levels. These findings provide important insights on the mechanism of increased disease susceptibility in male COVID-19 patients and identify androgen receptor inhibition as a potential therapeutic strategy.

Research progress of valproic acid genomics / 药学实践杂志

Valproic acid is a commonly used and broad-spectrum antiepileptic drug in clinical practice with a narrow therapeutic window. Valproic acid has a great individual difference in its metabolism which is influenced by many factors. The gene polymorphism of drug metabolic enzymes is one of the critical factors. Through consulting relevant articles, the affection of genomics and clinical treatment on valproic acid clinical application were reviewed in this paper, which provided a reference for clinical individualized treatment.

Circular RNA hsa_circ_0005556 Accelerates Gastric Cancer Progression by Sponging miR-4270 to Increase MMP19 Expression

Purpose@#Circular RNAs (circRNAs) are a new class of RNA molecules whose function is largely unknown. There is a growing evidence that circRNAs play an important regulatory role in the progression of a variety of human cancers. However, the exact roles and the mechanisms of circRNAs in gastric cancer are not clear. In this study, we aimed to elucidate the mechanism of hsa_circ_0005556. @*Materials and Methods@#Real-time quantitative polymerase chain reaction was used to detect the expression of hsa_circ_0005556, miR-4270, and matrix metalloproteinase-19 (MMP19) in gastric cancer tissues and cell lines. The expression of hsa_circ_0005556 in gastric cancer cells was silenced by lentivirus, and cell proliferation, invasion, migration, and tumorigenesis in nude mice were assessed to evaluate the function of hsa_circ_0005556 in gastric cancer. @*Results@#The expression of hsa_circ_0005556 in gastric cancer tissues and gastric cancer cell lines was higher compared to normal controls. In vitro, the downregulation of hsa_ circ_0005556 significantly inhibited proliferation, migration, and invasion of gastric cancer cells. In vivo, the downregulation of hsa_circ_0005556 suppressed tumor growth in nude mice. @*Conclusions@#Our study shows that the hsa_circ_0005556/miR-4270/MMP19 axis is involved in proliferation, migration, and invasion of gastric cancer cells through the competing endogenous RNA (ceRNA) mechanism.

Establishment and characterization of patient derived xenograft model of malignant peritoneal mesothelioma in nude mice / 中华病理学杂志

Objective@#To establish patient derived xenograft (PDX) model of malignant peritoneal mesothelioma (MPM), and to identify the key characteristics of tumor biology of the model, so as to provide an experiment platform for studying the pathologic mechanisms and new therapeutic strategies for MPM.@*Methods@#Surgically excised MPM tumor tissues were inoculated subcutaneously in BALB/c-nu/nu mice for 3 stable passages. In the 4th passage, the subcutaneous tumors were harvested under aseptic conditions, cleaned and made into MPM tumor cell homogenate. Four nude mice (two males and two females) were selected and one male and one female nude mouse were inoculated in the abdominal cavity at the dose of 100 μL, others were inoculated at a dose of 200 μL. The PDX model of MPM was established. The changes of body mass in nude mice were measured regularly, the extent of abdominal and pelvic tumors was judged by experimental peritoneal cancer index (ePCI) score, and the pathologic characteristics of tumors were analyzed.@*Results@#The subcutaneous and abdominal animal models of MPM were successfully established. The subcutaneous tumor model grew into tumor on the 20th day, followed by a slow growth stage between the 20th and 29th day, then a rapid growth stage between the 30th and 57th day. According to the dose of tumor cells (100, 200 μL) and timing (14th and 69th days after grafting), the abdominal tumor model successfully simulated the early and late clinical stages of MPM. The HE staining results of the MPM nude mice model showed that the tumor was epithelial mesothelioma and invaded most of the organs, including liver, spleen, pancreas, mesentery. Immunohistochemical staining for calretinin, cytokeratin 5/6, WT1 and Ki-67 were positive. Whole-genome exon sequencing identified 26 and 36 high frequency gene mutations in tumors derived from the PDX model and clinical sample from patients, including 21 common gene mutations.@*Conclusions@#The PDX model of MPM is established. The model is characterized by highly malignant tumor with rapid growth and high invasiveness.

Clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma / 中华肿瘤杂志

Objective@#To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma (FDCS).@*Methods@#We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real-time PCR and EBER in situ hybridization was performed on 4 cases.@*Results@#Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low-grade FDCS and 3 cases of high-grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2-40, EGFR and CXCL13, but negative for S-100, CD68, HMB45, SMA, Desmin, CD117, Dog-1, CD34, CD30, EMA and CK.Five cases were positive for PD-L1 and the its expression in high-grade FDCS were higher than that in low-grade FDCS.Two cases of low-grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren′t detected in all of 7 cases. The result of EBER in-situ hybridization showed that only the nasopharynx FDCS was positive.The follow-up information of 5 patients were available (7~43 months), 4 patients died and 1 still alive with rectum metastasis.@*Conclusions@#FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first-line antibodies including CD21, CD23, CD35 and second-line antibodies including D2-40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD-L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.

Pathological prognostic factors of pseudomyxoma peritonei / 中华病理学杂志

Objective@#To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors.@*Methods@#One-hundred and fifty-five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki-67, p53, MMR-related protein, MUC2 and MUC5AC were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis.@*Results@#Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low-grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high-grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high-grade mucinous carcinoma peritonei with signet ring cells; only 15 cases (9.7%) with lymph node metastasis; 18 cases (11.6%) with tumor emboli in the blood and lymph vessels; 8/126 (6.3%) were positive dMMR; 100 cases (64.5%) had Ki-67 label index <50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival-related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki-67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01).@*Conclusions@#Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.

Influencing factors of no seeking medical treatment among pneumoconiosis patients / 中华劳动卫生职业病杂志

Objective@#To study the causes and influencing factors of no seeking medical treatment among pneumoconiosis patients.@*Methods@#Using stratified sampling method and typical survey method, we carried out the questionnaire survey in nine provinces in China including the east, the medium and the western region using a questionnaire on the seeking medical behavior pf pneumoconiosis patients and the influencing factors. The subjects include occupational pneumoconiosis cases and clinically diagnosed cases and the response rate is 94.3 percent. The data was entered twice with epidate3.1 and error detection and statistical analysis was completed with SPSS 20.0. Chi-square test was used for univariate analysis, and multivariate logistic regression was used for multivariate analysis.@*Results@#One thousand and thirty-seven subjects were investigated with average age 55.9±11.2 years. Seventy percent of them were silicosis and 21.9 percent were coal worker’s pneumoconiosis with 67.5 percent of them residing permanently in the countryside, and 37.9 percent of their education background were primary school culture and 33.1 percent of them had junior high school culture. Thirty two point six percent of respondents had no personal income with a median monthly income of 1 200 yuan. Four hundred and thirty four of subjects hadn't seek medical treatment since they got the pneumoconiosis accounting for 41.9 percent with three hundred and thirty seven of them hospitalized directly. The reasons of no seeking medical treatment for the respondents mainly include the self-induction symptoms lighter, the high cost of treatment and cannot claiming the payment of the medical expenses, buying drugs in drugstore, thinking that no medicine can cure pneumoconiosis or no effect, complex procedures, too far away from medical institutions, no unaccompanied, needing a long time or no time, communication disorders, etc. accounting for 44.4 percent, 24.6 percent, 10.9 percent, 9.1 percent, 6.9 percent, 4.4percent, 3.2 percent, 2.9 percent, 1.9 percent, 1.5 percent, respectively. The results of multivariate analysis showed the main characteristics of subjects with restrictions to the outpatient health service utilization are as follows: demographic sociological indicators such as registered permanent residence area is western (ORwestern=2.18, 95%CI:1.38-3.43) , more than seventy five years old (ORover 75=6.82, 95%CI:2.04-22.9) , unemployment, temporary or permanent employment (OR unemployment=1.90, 95%CI:1.17-3.08; ORtemporary employment=3.11, 95%CI:1.57-6.14; ORpermanent employment=2.10, 95%CI:1.18-3.74) , self-rated health score of 50 or above (ORself-rated-70=2.04, 95%CI:1.18-3.51; ORself-rated-90=3.00, 95%CI:1.97-5.37; ORself-rated 90=2.95, 95%CI:1.74-8.07) ; with increase to the outpatient health service utilization are breath with difficulty (OR=0.57, 95%CI:0.41-0.78) , emphysema (OR=0.48, 95%CI:0.26-0.90) , hospitalized with pneumo-coniosis (OR=0.12, 95%CI:0.07-0.20) .@*Conclusion@#Pneumoconiosis patients no covered by injury insurance should be orderly included in the basic medical security system, and be given the medical treatment actively; It should be strengthened the health management for the pneumoconiosis patients and correctly guided the utilization of medical services.

Significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma of the larynx / 中华病理学杂志

Objective@#To study the significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma (BSCC) of the larynx.@*Methods@#Twenty-nine cases of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December 2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR-RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry were performed. The relationship between these indicators, various pathologic parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status was analyzed.@*Results@#There were 27 male and 2 female patients. The median age was 62 years. Lymph node metastasis and supraglottic tumor location were slightly higher than that of "usual" SCC, but not statistically significant (P>0.05). HPV DNA was detected in 27.6% (8/29) of the laryngeal BSCC, and all were HPV16. The expression of HPV was not related to age, alcohol consumption, tumor stage and tumor size. p53 was expressed in 31.0%(9/29) of laryngeal BSCC, and these cases were more likely supraglottic and had lymph node metastases (P<0.05). p16 staining was seen in 24.1% (7/29) of laryngeal BSCC, and these cases showed slightly higher rate of lymph node metastasis compared to p16 negative cases. The expression rates of p21 and cyclinD1 were 27.6% (8/29) and 69.0%(20/29), respectively, which were not related to age, tumor size, stage, lymph node metastasis, smoking and drinking. There were only 3 p16+ /HPV+ cases, which showed higher p21 and Ki-67 index compared to the HPV negative group (P<0.05).@*Conclusion@#Some laryngeal BSCC expresses HPV DNA, possibly indicating an association with HPV; but p16 expression is not a reliable indicator for HPV infection.

Comparison of whole blood indium and the serum indium of the population exposed to the indium / 中华劳动卫生职业病杂志

Objective@#The method was established for the detection of whole blood indium and serum indium. By comparing the results of two samples, it is possible to explore the significance of whole blood indium and serum indium in the population exposed to indium compounds.@*Methods@#According to GBZ/T 295-2017 and GBZ 294-2017, the whole blood and serum samples were diluted 20 times by 0.5% nitric acid solution (including 0.05% Triton X-100) . Under the standard mode of inductively coupled plasma mass spectrometry (ICP-MS) , whole blood indium and serum indium of indirect exposure group, low exposure group and high exposure group in an indium mine were detected with 20 μg/L rhodium standard solution as internal standard.@*Results@#This method has a working range of 0.00~5.00 μg/L and a correlation coefficien t>0.999. The detection limit and quantitative lower limit of whole blood indium were 0.076 μg/L and 0.26 μg/L respectively. Those of serum indium were 0.06 μg/L and 0.20 μg/L accordingly. The recovery rates of serum and whole blood samples were 88.5%~95.6% and 93.0%~101%. Intra batch precisions were 1.3%~4.4% and 1.9%~3.5% and inter batch precision were 2.4%~6.1% and 2.1%~4.6% in two samples. There were no significant differences between whole blood indium and serum indium in indirect exposure group. The serum indium level was lower than the detection limit in 3 cases, while their whole blood indium was only below the quantitative lower limit. However, in other groups whole blood indium level was significantly higher than serum indium level (P<0.05) and even was two-fold in the high exposure group.@*Conclusion@#The detection of whole blood indium is more sensitive than that of serum indium, which can reflect the internal exposure level more accurately in exposure population. Therefore, the whole blood indium is of more important referential value to health examination and poisoning diagnosis in the population exposed to indium and its compounds.

Clinicopathologic characteristics of pseudomyxoma peritonei / 中华病理学杂志

Objective@#To analyze the relationship between clinicopathologic characteristics of pseudomyxoma peritonei (PMP) and its prognosis.@*Methods@#Fifty-two cases of PMP collected from 2012 to 2017 at Beijing Shijitan Hospital, Capital Medical University were reviewed using the diagnostic criteria of WHO 2010. The histopathologic features, including original location, neural invasion and calcification were observed; and the relationship with prognosis was analyzed. Immunohistochemical staining for CK7, CK20 and CDX2 was performed on all cases. ER, PR, and p16 were additionally performed on those without clear origin.@*Results@#Patients′ mean age was 52.0 years, and included 29 males and 23 females. Thirty-two cases were derived from appendix; among them, 23 were low grade and 29 were high grade. Signet ring-cells, neural invasion and calcification were detected in 15, 12 and 9 cases respectively. Neural invasion was associated with adverse prognosis (P=0.025) and signet ring cell morphology (P<0.01). Prognosis was not related to gender, age, original location or grade.@*Conclusion@#Neural invasion is not uncommon in PMP and predicts a bad prognosis.

Efficacy observation of DA-EPOCH-R protocol for patients with B-cell non-Hodgkin lymphoma / 白血病·淋巴瘤

Objective To evaluate the efficacy and safety of DA-EPOCH-R protocol for patients with B-cell non-hodgkin lymphoma (NHL). Methods 43 patients with B-cell NHL received DA-EPOCH-R protocol, and their efficacy and adverse reactions were analyzed. Results 43 patients received a total of 203 cycles of chemotherapy and the median chemotherapy cycle was 6 (2ˉ8 cycles). 32 patients (74.4%) achieved complete remission (CR) after 2ˉ4 cycles of chemotherapy. A further analysis found that age ≤60 years and>60 years, stageⅠ/Ⅱand stageⅢ/Ⅳ, germinal center B-cell (GCB), non-GCB, double expression lymphoma (DEL) and non-DEL patients had no significant differences (P> 0.05). With a median follow-up of 40 months (9ˉ62 mouths), the overall survival (OS) rate of 1-year and 3-year was 97.6 % and 92.8 % respectively. The major toxicity of DA-EPOCH-R protocol was hematologic toxicity. Other toxicities were mild, and no treatment-related deaths occurred. At the end of follow-up, no secondary tumors were found. Conclusions DA-EPOCH-R protocol is an effective and safe protocol for patients with NHL. The result shows that the curative effect of patients in stageⅢandⅣis similar to the patients in stageⅠandⅡ.