[Correlations between plaque characteristics and cerebral blood flow in patients with moderate to severe carotid stenosis using magnetic resonance vessel wall imaging].

OBJECTIVE: To investigate the correlations between carotid plaque characteristics and cerebral blood flow (CBF) in patients with unilateral moderate to severe carotid stenosis using high-resolution magnetic resonance imaging (HR-MRI) and 3D pseudo-continuous arterial spin labeling (3D pcASL). METHODS: A total of 43 patients with unilateral moderate to severe carotid stenosis were recruited. The degree of carotid stenosis, maximum wall thickness (Max WT) and normalized wall index (NWI) were measured using HR-MRI. The plaque characteristics were analyzed. Presence or absence of plaque components including intraplaque hemorrhage (IPH), lipid-rich necrotic nucleus (LRNC), calcification and ulcer were identified, and the grades of calcification and LRNC were recorded. CBF values within the region of interest representing the bilateral middle cerebral artery distribution were acquired using 3D pcASL. Paired sample t test was used to compare the differences of CBF values between the index side and the contralateral side. Spearman correlation analysis was conducted to evaluate the correlations of CBF values with the degree of carotid stenosis, Max WT and NWI. The differences of CBF values between the patients with or without IPH and ulcer were compared using Mann-Whitney U test. Different levels of calcification and LRNC were compared by Kruskal-Wallis test, respectively. RESULTS: The ave-rage degree of carotid stenosis at the index side was 77.30%±11.79%. The mean CBF value of the index side was (46.77±11.65) mL/(100 g·min), and that of the contralateral side was (49.92±9.95) mL/(100 g·min), and the difference was statistically significant (t=-2.474, P=0.017). The mean Max WT and NWI of the carotid plaques at the index side was (6.40±1.87) mm and 62.91%±8.87%, respectively. There were no significant correlations of CBF values with the degrees of stenosis, Max WT and NMI (P>0.05). Plaque composition analysis showed that the CBF values of the index side were different when there was calcification or not and the degrees of calcification were different (P=0.030), but there were no differences between the CBF values on the index sides with or without IPH, ulcer and LRNC. CONCLUSION: In patients with unilateral moderate to severe carotid stenosis, calcification might affect CBF perfusion. When there is no calcification, the plaque components need attention.

[Application and evaluation of artificial intelligence TPS-assisted cytologic screening system in urine exfoliative cytology].

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.

[Advances in clinical diagnosis and treatment of drug-induced liver injury in children].

Drug-induced liver injury (DILI) is one of the most common adverse drug reactions that may seriously threaten the health of children and is receiving increasing clinical attention day by day. There is still no independent diagnosis and treatment guideline for DILI in children, but its clinical features are not completely similar to those in adults. This article reviews the epidemiology, clinical features, diagnosis, and treatment progress in order to provide a reference for the management of DILI in children.

[Clinicopathological features and prognosis of high-grade B-cell lymphoma with MYC and bcl-2 and/or bcl-6 rearrangements].

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma ß2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.

[Clinical effect and influencing factors of pegylated interferon alfa-2a and entecavir monotherapy among children with HBeAg-positive chronic hepatitis B based on a real-world study].

Objective: To compare the efficacy, safety, and influencing factors among children with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B (CHB) who received short-term therapy with pegylated interferon alfa-2a (Peg-IFNα-2a) or continuous therapy with entecavir (ETV). Methods: Quantitative data were compared using analysis of variance to compare the differences between groups. Enumeration data were compared by χ2 test (or Fisher's exact test). Univariate and multivariate logistic regressions were used to analyze the influencing factors. Results: Peg-IFNα-2a, ETV, and untreated group had HBsAg clearance rates of 46.2%, 5.3%, and 0 after 52 weeks of therapy, respectively. HBsAg clearance in the patients' group with Peg-IFNα-2a and ETV was all accompanied by anti-HBS positive conversion, and the difference was statistically significant (χ2=13.616, P=0.001). Peg-IFNα-2a group was followed-up for 104 weeks. Peg-IFNα-2a, ETV, and the untreated group had HBsAg clearance rates of 46.2%, 10.5%, and 0%, respectively, and the differences were statistically significant (χ2=11.056, P=0.004). Only one of the two children with HBsAg clearance in the ETV group had achieved anti-HBs antibodies, and the difference was statistically significant (χ2=13.616, P=0.001). Univariate and multivariate logistic regression analysis showed that HBsAg clearance was associated with age and antiviral therapy. During treatment, adverse events such as fever (n=4, 30.8%), rash (n=4, 30.8%), fatigue (n=1, 7.7%), leukopenia (n=7, 53.8%), arthritis (n=1, 7.7%), and alopecia (n=3, 23.1%) were observed in the Peg-IFNα-2a group, while none were observed in the ETV group. Conclusion: Peg-IFNα-2a antiviral therapy produced higher HBsAg clearance than ETV in five-year-old and younger children with HBeAg-positive CHB, while ETV had fewer adverse events and was safer than Peg-IFNα-2a.

[Random survival forest: applying machine learning algorithm in survival analysis of biomedical data].

Traditional survival methods have a wide application in the field of biomedical research. However, applying traditional survival methods requires data to meet a set of special assumptions while the Random Survival Forest model can overcome this inconvenience. Herein, we used the clinical data of Primary Biliary Cholangitis (PBC) from Mayo Clinic to introduce and demonstrate Random Survival Forest model from mathematical principles, model building, practical example and attentions, aiming to provide a novel method for doing survival analysis.

[Expressions of MPV, P-LCR and NLR in patients with novel coronavirus disease 2019].

To provide new ideas for clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19), this study explore the expression level and prognostic value of platelet parameters in mild, moderate and severe COVID-19. This is a retrospective analysis. From January to May 2020, a total of 69 patients who were diagnosed with COVID-19 in the Third Central Hospital and the Jinnan Hospital (both situated in Tianjin) were enrolled in the disease group. According to the severity, these patients were divided into mild group (15 cases), moderate group (46 cases), and severe group (8 cases). In the same period, 70 non-infected patients were enrolled in control group. The level of white blood cell count (WBC), absolute neutrophil count (NEU#), absolute lymphocyte count (LY#), neutrophil-lymphocyte ratio (NLR), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large contrast ratio (P-LCR) before and after treatment were analyzed. Binary logistic regression analysis is used to establish a mathematical model of the relationship between these indexes and the outcome of severe COVID-19 patients. The receiver operating characteristic(ROC) curve is used to further explore the prognosis value of MPV, P-LCR, NLR separately and jointly in COVID-19 patients. Compare to the control group, WBC and NE# increase (Z=-5.63, P<0.01;Z=-9.19,P<0.01) and LY# decrease (Z=-9.34, P<0.01) in the severe group; NLR increase with the aggravation of the disease, there is significant difference between groups (Z=17.61, P<0.01); PLT, PDW, MPV and P-LCR decrease with the aggravation of the disease, there is significant difference between groups (Z=9.47, P<0.01; Z=11.41, P<0.01; Z =16.76, P<0.01; Z=13.97, P<0.01). Binary logistic regression analysis shows MPV, P-LCR and NLR have predictive value for severe COVID-19 patients. There is a negative correlation between MPV, P-LCR and severe COVID-19 patients (OR=1.004, P=0.034; OR=1.097, P=0.046). There is a positive correlation between NLR and severe COVID-19 patients (OR=1.052, P=0.016). MPV and P-LCR of patients with good prognosis after treatment were significantly higher than those before treatment (Z=-6.47, P<0.01; Z=-5.36, P<0.01). NLR was significantly lower than that before treatment (Z=-8.13, P<0.01). MPV and P-LCR in poor prognosis group were significantly lower than those before treatment (Z=-9.46, P<0.01; Z=-6.81, P<0.01). NLR was significantly higher than that before treatment (Z=-3.24, P<0.01). There were significant differences between good and poor prognosis groups before and after treatment in MPV, P-LCR and NLR (P<0.01). Combination of these three indexes, ROC shows the AUC is 0.931, the sensitivity is 91.5%, the specificity is 94.1%, the positive predictive value is 88.9%, and the negative predictive value is 87.4%, which is better than any of these indexes separately. Changes in these parameters are closely related to clinical stage of COVID-19 patients. MPV, P-LCR and NLR are of great value in the prediction and prognosis of severe COVID-19 patients.

[Progress in diagnosis and treatment of viral hepatitis in children].

Hepatitis B and C virus infections are major global public health problem and economic burden. Most children with vertical infection have asymptomatic hepatitis, but the risk of chronic viral hepatitis and further development of liver cirrhosis or hepatocellular carcinoma is higher. Over the past two to three decades, with the rapid development of detection technology and the continuous research and development of antiviral drugs, great progress has been made in the diagnosis and treatment of viral hepatitis caused by hepatitis B and C infection. However, due to the particularity of its characteristics, it is still necessary to carefully judge and evaluate the diagnosis and antiviral treatment of children. This article focuses on the difficulties in the diagnosis and treatment of viral hepatitis in children, and summarizes its progress.

[Correlation of qAnti-HBc with antiviral efficacy in children with chronic hepatitis B and exploration of its possible immune mechanism].

Objective: To compare the baseline difference in the quantitative hepatitis B core antibody levels (qAnti-HBc) between non-response and response group in children with HBeAg-positive chronic hepatitis B (CHB) who received antiviral therapy, and further explore the proportion and functional activity of CD8 + memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children. Methods: The baseline anti-HBc quantification (qAnti-HBc) levels of 85 children with HBeAg-positive CHB who visited the Department of Infectious Diseases, Children's Hospital of Chongqing Medical University from June 2018 to December 2020 were detected retrospectively. The relationship between the baseline qAnti-HBc level and HBeAg serological response in 37 children who received antiviral therapy was analyzed. The proportion of CD8(+) memory T lymphocyte subsets and the secretion levels of interferon (IFN) γ, and tumor necrosis factor (TNF) α in peripheral blood of 59 children at baseline were detected by flow cytometry. The relationship between qAnti-HBc level and the proportion and functional activity of CD8(+) memory T lymphocyte subsets was analyzed. Pearson's Chi-square test was used to compare the count data. Mann-Whitney U test or Kruskal-Wallis test was used to compare measurement data between two or more groups, and Spearman's rank correlation analysis was used for the correlation between continuous variables. Results: Among 37 children who received entecavir (ETV, 21/37 cases) or pegylated interferon (Peg-IFN, 16/37 cases), 18 cases had developed HBeAg seroconversion (10/ 21 cases in the ETV group, 8/16 cases in the Peg-IFN group). The baseline qAnti-HBc level was significantly higher in the response group [4.71 (4.64~4.81) log(10)IU/ml] than the non-response group children [4.54 (4.45~4.64) log(10)IU/ml, Z = -3.316, P = 0.001]. The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes were significantly higher in the high-qAnti-HBc group than the low-qAnti-HBc group (P < 0.05). The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem and CD38(+)CD8(+) Temra cells was significantly higher in ALT > 1× upper limit of normal value (ULN) group than ALT≤1×ULN group (P < 0.05). However, there were no significant differences in the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes between the two groups (P > 0.05). Spearman's correlation analysis showed that qAnti-HBc was positively correlated with the proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the level of IFNγ secreted by CD8(+)T lymphocytes (P < 0.05). Additionally, ALT was only positively correlated with the proportion of CD38(+)CD8(+) TEM and CD38(+) CD8(+) Temra cells (P < 0.05). Conclusion: Raised baseline qAnti-HBc level is related to the HBeAg serological response to antiviral therapy in children with CHB. Peripheral blood effector CD8+ T lymphocytes of CHB children with higher qAnti-HBc show stronger phenotype and functional activation characteristics, which may shed some light on the underlying immune mechanism related to antiviral therapy efficacy in children with CHB.

[Analysis of liver pathological characteristics and exploration of noninvasive markers of liver fibrosis in children with chronic hepatitis B].

Objective: To analyze and summarize the characteristics of liver pathology and their relation to clinical markers and further explore noninvasive markers of liver fibrosis in children with chronic hepatitis B. Methods: Data of 80 hospitalized children with chronic hepatitis B who underwent liver biopsy without antiviral treatment from 2011 to 2020 were retrospectively analyzed. Inflammation and liver fibrosis characteristics were analyzed in children of different ages and genders. Variables with good correlation with liver fibrosis stage were selected to establish a non-invasive diagnostic score of liver fibrosis in children. Measurement data was used to compare the t-test or rank sum test. Mantel-Haenszel χ (2) test was used for bidirectional ordered grouping data. Spearman's rank correlation test was used for rank correlation analysis. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of the newly established diagnostic score in children with liver fibrosis. Results: The median age of the children was 6.4 years. HBV DNA level was high (P50 = 7.6 log(10) IU/ml), and serum alanine aminotransferase (ALT) in P50 was 171 U/L (< ULN: 5 cases, ULN-2ULN: 10 cases, > 2 ULN: 65 cases). Pathological analysis showed that the incidence of liver tissue inflammation was 97.5%, and the proportion of patients with G≥2 was 42.5%, while S≥2 was 36.3%. The incidence rate of liver fibrosis and liver cirrhosis was 81.3%, and 1.3%, respectively. The changes in liver tissue inflammation and fibrosis were gradually aggravated with the increase of age, and the proportion of high-grade inflammation and liver fibrosis in male children was higher than that in female children. Serum levels of glutamyl transpeptidase (GGT), γ-glutamyltransferase/platelet ratio (GPR) and HBeAg had a good correlation with fibrosis stage (r(s) = 0.397, 0.389, and - 0.311) in children with chronic hepatitis B. The combination of GGT, GPR and HBeAg can establish a non-invasive diagnostic score for evaluating liver fibrosis in children. When the score is less than 1.5, it can be diagnosed as S0, and 1.5 ≤ score < 3.5, it can be diagnosed as S1; 3.5 ≤ score < 5.5, the diagnosis of fibrosis is S2; score≥ 5.5, the diagnosis of fibrosis is S≥3. The sensitivity and specificity were 80%, 83%, 86%, and 53%, 55%, 67%, respectively. Conclusion: The incidence of liver tissue inflammation in children with chronic hepatitis B with elevated and fluctuating transaminase levels is high, and the pathological changes of liver tissue aggravate with the age of the children. GGT, GPR and HBeAg have a good correlation with liver fibrosis in children with chronic hepatitis B. Therefore, combining the above-mentioned markers to establish a new noninvasive diagnostic score has certain diagnostic value for liver fibrosis stage S0-S3 in children with chronic hepatitis B.

[Analysis of the feasibility and prognostic value of circulating tumor DNA in detecting gene mutations in small cell lung cancer].

Objective: To investigate the feasibility of circulating tumor DNA (ctDNA) in detecting small cell lung cancer (SCLC) gene mutations and its prognostic value in chemotherapy and/or radiotherapy for SCLC patients. Methods: A total of 77 SCLC patients who were admitted to the Department of Thoracic Medical Oncology and the Department of Thoracic Radiation Oncology of Zhejiang Cancer Hospital from July 2016 to November 2019 were included. There were 66 males and 11 females, with a median age of 60 years. Among them, 42 cases were in limited stage (LS) and 35 cases were in extensive stage (ES). Next-generation sequencing (NGS) of patients' plasma ctDNA was performed before treatment. The differences of mutated genes and signaling pathways between LS and ES patients were analyzed and compared. Blood-based tumor mutation burden (bTMB) was calculated according to detected somatic cell mutations. Patients were divided into the high bTMB and the low bTMB groups according to the optimal threshold calculated by R software. Log-rank tests were used to compare progression-free survival (PFS) between the high bTMB and the low bTMB groups. Results: Among the 77 patients, 76 patients had gene mutations detected in their plasma, and the positive rate of ctDNA test was 98%. Among the 76 patients, the genes with the highest mutation frequency were TP53 (89%), RB1 (70%), LRP1B (34%), CREBBP (21%), MLL3 (21%), MLL2 (16%), NOTCH1 (13%), ROS1 (13%), BRCA2 (12%), and PTPRD (12%). The most common mutated genes in LS patients were TP53 (90%), RB1 (68%), LRP1B (24%), MLL2 (22%), and BRCA2 (17%); the most common mutated genes in ES patients were TP53 (89%), RB1 (71%), LRP1B (46%), CREBBP (31%), and MLL3 (29%). The mutation rates of NOTCH1 and CREBBP genes were significantly higher in ES patients (31.4% and 22.9%) than those in LS patients (11.9% and 4.8%) (both P<0.05). Signaling pathway analysis showed that there were more NOTCH pathway gene variations in ES patients. Among LS patients, patients in the high bTMB group (≥ 6.96 mutations/Mb) had a longer PFS than that in the low bTMB group (<6.96 mutations/Mb) (P=0.033); but no such difference was noted in ES patients. Conclusion: Plasma ctDNA sequencing detected SCLC gene mutation profiles similar to those reported in previous literature, thus ctDNA could be used as a tool to study SCLC genomics; the mutation spectra of ES-SCLC and LS-SCLC were different. bTMB has potential prognostic value in LS-SCLCs treated with chemoradiotherapy.

[Clinicopathological features of de novo CD5-positive diffuse large B-cell lymphoma].

Objective: To investigate the relationship between the protein expression of C-MYC, bcl-2 and bcl-6 and the clinicopathological characteristics in patients with de novo CD5-positive diffuse large B cell lymphoma (CD5(+)DLBCL). Methods: Fifty seven cases of de novo CD5(+)DLBCL were collected at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2013 to September 2018. The hematoxylin-eosin stained slides were reviewed, and immunohistochemical (IHC) staining and FISH were used to analyze the relationship between C-MYC, bcl-2, bcl-6 expression and the clinicopathologic characteristics of patients. Results: Among these 57 cases, 27 were male and 30 were female. The age of onset was 35-99 years old. The IHC expression rates of C-MYC, bcl-2 and bcl-6 were 50.9% (29/57), 84.2% (48/57), and 75.4% (43/57) respectively; and co-expression rate of C-MYC and bcl-2 proteins was 40.4 (23/57). There was no significant correlation between protein expression and patients' genders, clinical stage, the level of serum LDH,ß2 microglobulin, IPI,B symptoms, bone marrow involvement and central nervous system recurrence (P>0.05). Univariate analysis showed that the median OS of C-MYC negative patients was significantly longer than C-MYC positive patients (P<0.05); and the median OS of patients without double expression was significantly longer than that of patients with positive expression (P<0.05), and bcl-6 positive patients had longer median OS than bcl-6 negative patients (P<0.05). There was no significant correlation between prognosis and bcl-2 protein expression (P>0.05) . Cox multivariate analysis showed C-MYC protein expression was an independent predictor of OS in de novo CD5(+)DLBCL (P<0.05). Conclusions: Bcl-2 protein expression has no effect on the prognosis in de novo CD5(+)DLBCL whereas bcl-6 expression is correlated with good prognosis. C-MYC protein expression could be used as an independent and effective index to predict the prognosis of patients with de novo CD5(+)DLBCL.However, the relationship between protein expression and gene rearrangement of C-MYC, bcl-2 and bcl-6 needs to be further explored.

[Problems for the conversion therapy in advanced gastric cancer].

Patients with advanced gastric cancer have a poor prognosis, which remains the clinical concerned hot topic. The main previous treatments for advanced gastric cancer were adjuvant chemotherapy and palliative surgery, however, the application of conversion therapy has improved the survival in recent years. There are still many problems and challenges for conversion therapy because of its initial stage, such as the definition of advanced gastric cancer and conversion therapy, the selection of suitable population for conversion therapy, and the role of surgery in conversion therapy. Precision medicine will be applied to conversion therapy for advanced gastric cancer in the future, which would benefit more patients.

Proteomics and Its Application in Forensic Pathology.

Proteomics has become one of the hot topics in modern life sciences. Its application prospects have been confirmed in clinical medical research, such as the discovery of new disease biomarkers, identification of disease-related proteins, and development of new drug targets. However, in the field of forensic science, especially in forensic pathology, it is still in the stage of exploration. This paper reviews the research techniques and the use of proteomics in forensic pathology in domestic and foreign scholars, in order to provide new ideas for the research and application of forensic pathology.

Sperm cystic fibrosis transmembrane conductance regulator expression level is relevant to fecundity of healthy couples.

Cystic fibrosis transmembrane conductance regulator (CFTR) is relevant to sperm quality, sperm capacitation and male fertility. However, it is still unknown whether CFTR can be a potential parameter for fecundity prediction in healthy couples. In this study, 135 healthy couples were divided into groups according to their fertility. We demonstrated that the sperm CFTR expression level of healthy males who never impregnated their partners (49 cases, 38.68 ± 2.71%) was significantly lower than that of fertile men (86 cases, 46.35 ± 2.32%). Sperm CFTR expression level accurately corresponded with fertility through the logistic regression model. Receiver operating characteristic (ROC) curve analysis showed that the cut-off value of sperm CFTR expression level for fecundity prediction was 43.75%. Furthermore, cumulative pregnancy rates (CPRs) of CFTR > 43.75% group and CFTR ≤ 43.75% group during the follow-up periods were 80.6% and 49.3% respectively. Meanwhile, the mean time to pregnancy (TTP) of CFTR ≤ 43.75% group (26.79 ± 2.35) was significantly longer than that of CFTR > 43.75% group (16.46 ± 2.42). Therefore, sperm CFTR expression level is relevant to fecundity of healthy couples and shows potential predictive capacity of fecundity.

Protective effect of necrostatin-1 on myocardial tissue in rats with acute myocardial infarction.

The aim of this study was to investigate the protective effect of necrostatin-1 on myocardial tissue of acute myocardial infarction (AMI) rats and to provide a basis for necrostatin-1 for the treatment of acute myocardial infarction. AMI rats (45) were established by ligating the anterior descending branch of the left coronary artery. The rats were randomly divided into the model group and necrostatin-1 low-dose and high-dose groups. The control group rats (15) underwent the sham operation. The rats in the necrostatin-1 low-dose and high-dose groups were injected with 1 and 4 mg/kg necrostatin-1, respectively, via the tail vein. The rats in the control and model groups were injected with isometric dimethyl sulfoxide, once daily, for 3 consecutive days. The levels of RIP1 and RIP3 mRNA and phosphorylated protein in the myocardial tissue of rats were detected by real time polymerase chain reaction and western blot. The myocardial infarct size was detected by tetrazolium chloride. Compared with that in the control group, the levels of RIP1 and RIP3 mRNA and phosphorylated protein significantly increased in the myocardial tissue of model group rats, necrostatin-1 low-dose group, and high-dose group. The levels of RIP1 and RIP3 mRNA and phosphorylated protein in the myocardial tissue of rats in the necrostatin-1 low-dose and high-dose groups decreased significantly compared with that in the model group (P < 0.05). The levels of RIP1 and RIP3 mRNA in the myocardium of the high-dose group rats were significantly lower than those of the low-dose group rats (P < 0.05). The myocardial infarct sizes significantly increased in model, low-dose, and high-dose group rats. The apoptotic level of myocardial cells significantly decreased in the low-dose group and high-dose group after treatment with necrostatin-1 but was still higher than that of the control group (P < 0.05). In conclusion, necrostatin-1 can inhibit myocardial tissue apoptosis and necrosis in acute myocardial infarct rats and has a protective effect on myocardial tissue.

Expression and clinical significance of obesity-associated gene STEAP4 in obese children.

The aim of this study was to investigate the expression and clinical significance of the obesity-associated gene STEAP4 in obese children. Fifty-three obese children and 33 children with a standard body weight (control) from our hospital were recruited to this study. The expression of STEAP4 mRNA and protein in the adipose tissue were detected by reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in order to analyze the relationship between STEAP4 mRNA and protein levels and blood pressure, blood lipid profile, blood glucose levels, and inflammation in obese children. Obese children showed significantly lower levels of STEAP4 mRNA and protein in the adipose tissue compared to the control subjects (P < 0.05). The obese subjects exhibited significantly higher diastolic blood pressure (DBP), systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), fasting plasma glucose (FPG), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels, and a significantly lower high-density lipoprotein (HDL) level, compared to the control subjects (P < 0.05). Correlation analysis revealed that STEAP4 expression was negatively correlated with the DBP, SBP, TC, TG, LDL, FPG, IL-6, and TNF-α levels, and was positively correlated with the HDL level (P < 0.05). In conclusion, the expression of STEAP4 was significantly downregulated in the adipose tissue of obese children and was closely related to the blood pressure, blood lipid, blood glucose, and inflammation in these patients; therefore, these results could provide a theoretical basis for the treatment of childhood obesity.

Role of interleukin-10 gene polymorphisms in the development of coronary artery disease in Chinese population.

The aim of this study was to investigate the association between three common SNPs (-1082A/G, -819T/C, and -592A/C) in the interleukin 10 (IL-10) gene, and the development of coronary artery disease. Between January 2013 and December 2014, 272 patients with coronary artery disease and control subjects (each) were recruited for this study from the Huaihe Hospital of Henan University. The IL-10-1082A/G, -819T/C and -592A/C gene polymorphisms were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Logistic regression analyses revealed an association between the AA and GA+AA genotypes of IL-10-1082G/A and an elevated risk of coronary artery disease, compared to the GG genotype [adjusted odds ratio (OR) = 2.31 and 1.49; 95% confidence interval (CI) = 1.29-4.19 and 1.04-2.12, respectively]. The AG+GG genotype was associated with a moderately increased risk of coronary artery disease in smokers (adjusted OR = 2.74; 95% CI = 1.01-3.01). In conclusion, the AA and GA+AA genotypes of IL-10-1082G/A were associated with an elevated risk of coronary artery disease; the IL-10-1082G/A gene polymorphism also interacted with the tobacco smoking habits, contributing to the development of coronary artery disease.

Association between the epithelial cadherin -160C/A gene polymorphism and diffuse gastric cancer risk: a meta-analysis.

Several previous studies have investigated whether the -160C/A epithelial cadherin promoter polymorphism confers an increased risk of diffuse gastric cancer (DGC), but conflicting results have been reported. To explore further the association of this polymorphism with DGC susceptibility, we performed an extensive search of relevant studies and conducted a meta-analysis to obtain a more precise estimate. We conducted a systematic literature search using the databases EMBASE, PubMed, and Web of Knowledge for reports published before August 2012 that met certain criteria. Information was carefully and independently extracted from all eligible publications by 2 of the authors. Twelve distinct data sets from 10 case-control studies were analyzed. They included 1115 cases of DGC and 2965 controls. Although none of the genotypes was associated with DGC risk, a slight trend of increased risk was found among A allele carriers [odds ratio (OR) = 1.237, 95% confidence interval (95%CI), 0.940-1.627], CA heterozygotes (OR = 1.229, 95%CI = 0.938-1.610), and AA homozygotes (OR = 1.146, 95%CI = 0.684-1.918). However, when the cases were stratified by ethnicity, a diverging trend occurred in AA homozygotes between the Asian group (OR = 0.710, 95%CI = 0.328-1.536) and its Caucasian counterpart (OR = 1.434, 95%CI = 0.657-3.131). Taken together, the summarized analyses of these case-control studies demonstrated that the -160A of the epithelial cadherin gene exhibited no significant association with susceptibility for DGC; however, the results suggested that it is a potential genetic risk factor in both Asians and Caucasians. Additional large-scale, well-designed studies are necessary to confirm whether AA homozygosity is a protective factor in Asians.