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Yin-Ting Yang,1,2,* Xi-Ya Jiang,1,2,* Hong-Liang Xu,3,* Guo Chen,1,2,* Sen-Lin Wang,4 He-Ping Zhang,3 Lin Hong,1,2 Qin-Qin Jin,1,2 Hui Yao,1,2 Wei-Yu Zhang,1,2 Yu-Ting Zhu,1,2 Jie Mei,1,2 Lu Tian,1,2 Jie Ying,1,2 Jing-Jing Hu,5 Shu-Guang Zhou1,2 1Department of Gynecology and Obstetrics, Maternity and Child Healthcare Hospital Affiliated to Anhui Medical University, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Gynecology and Obstetrics, The Fifth Clinical College of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Pathology, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People’s Republic of China; 4Department of Medical Genetics Center, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People’s Republic of China; 5Department of Gynecology and Obstetrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Guang Zhou, Department of Gynecology, Anhui Medical University Affiliated Maternity and Child Healthcare Hospital, The Fifth Clinical College of Anhui Medical University, Anhui Province Maternity and Child Healthcare Hospital, No. 15, Yi-Min Street, Lu-Yang District, Hefei, Anhui, 230001, People’s Republic of China, Email zhoushuguang@ahmu.edu.cn Jing-Jing Hu, Department of Gynecology and Obstetrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email janejj55@126.comBackground: Endometriosis, a common gynecological condition, can cause symptoms such as dysmenorrhea, infertility, and abnormal bleeding, which can negatively affect a woman’s quality of life. In the current study, the pathophysiological mechanisms of endometriosis are unknown, but this study suggests that endometriosis is associated with dysregulation of the autoimmune system. This study identify hub genes involved in the prevalence, identification and diagnostic value of endometriosis and autoimmune diseases, and explore the central genes and immune infiltrates, the diagnosis of endometriosis provides a new sight of thinking about diagnosis and treatment.Methods and Results: The relevant datasets for endometriosis GSE141549, GSE7305 and autoimmune disease-related genes (AIDGs) were downloaded from online database. Using the “limma” package and WGCNA to screen out the autoimmune disease related genes and endometriosis related genes, the autoimmune disease gene-related differential genes (AID-DEGs) progressive GO, KEGG enrichment analysis, and then using the protein interaction network and Cytoscape software to select hub genes (CXCL12, PECAM1, NGF, CTGF, WNT5A), using the “pROC” package to analyze the hub genes for the diagnostic value of endometriosis. The difference in the importance of hub genes for the diagnosis of endometriosis was analyzed by machine learning random forest, and the combined diagnostic value of hub genes was analyzed by using the Support Vector Machine (SVM) algorithm. The eutopic (EU) and ectopic endometrium (EC) immune microenvironment of endometriosis was evaluated using CIBERSORT, the correlation of hub genes to the immune microenvironment was analyzed.Conclusion: The hub genes associated with AIDGs are differentially expressed in EC and EU of endometriosis and possess important value for the diagnosis of endometriosis. The hub genes have a very important impact on the immune microenvironment of endometriosis, which is important for exploring the connection between endometriosis and autoimmune diseases and provides a new insight for the subsequent study of immunotherapy and diagnosis of endometriosis.Keywords: EMT, hub genes, diagnosis, immunotherapy, immune microenvironment

Yao-Ji Wang, Qi-Qi Jin, Cheng Zheng, Jia-Xuan Lin, Yi-Fan Lin, Que Xu, Jin Li, Jia-Feng Lin Department of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jia-Feng Lin; Jin Li Email linjiafeng_wzmcfey@163.com; wdy0115@126.comObjective: Coronavirus disease 2019 (COVID-19) was associated with a higher risk of arrhythmia in infected patients. However, there are no reports about the effect of the ongoing pandemic on arrhythmias in the non-infected population. We measured the arrhythmia burden in a non-infected population with cardiac implantable devices.Methods: The arrhythmia burden during the COVID-19 pandemic was compared to a 6-month interval in the pre-COVID-19 period. The COVID-19 pandemic was divided into high-risk (17 January 2020 to 16 March 2020) and low-risk periods (17 March 2020 to 17 July 2020) according to whether there were locally infected patients. Arrhythmia burdens were compared among the pre-COVID-19, high-risk, and low-risk periods.Results: A total of 219 patients with 1859 episodes were included. We observed a larger proportion of patients with atrial fibrillation (AF) during the COVID-19 pandemic (38.36% vs 26.03%, p = 0.006). There was not significantly more ventricular arrhythmia during the COVID period than the pre-COVID-19 period (p > 0.05). During the high-risk period, daily frequency of non-sustained ventricular tachycardia (NSVT) (0.0172, 0.0475 vs 0.0109, 0.0164, p < 0.05), atrial tachycardia (AT) (0.0345, 0.0518 vs 0.0164, 0.0219 p

Remote ischemic preconditioning (RIPC) exerts a protective role on myocardial ischemia/reperfusion (I/R) injury by the release of various humoral factors. Lactate is a common metabolite in ischemic tissues. Nevertheless, little is known about the role lactate plays in myocardial I/R injury and its underlying mechanism. This investigation revealed that RIPC elevated the level of lactate in blood and myocardium. Furthermore, AZD3965, a selective monocarboxylate transporter 1 inhibitor, and 2-deoxy-d-glucose, a glycolysis inhibitor, mitigated the effects of RIPC-induced elevated lactate in the myocardium and prevented RIPC against myocardial I/R injury. In an in vitro hypoxia/reoxygenation model, lactate markedly mitigated hypoxia/reoxygenation-induced cell damage in H9c2 cells. Further studies suggested that lactate contributed to RIPC, rescuing I/R-induced autophagy deficiency by promoting transcription factor EB (TFEB) translocation to the nucleus through activating the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway without influencing the phosphatidylinositol 3-kinase-Akt pathway, thus reducing cardiomyocyte damage. Interestingly, lactate up-regulated the mRNA and protein expression of connexin 43 (CX43) by facilitating the binding of TFEB to CX43 promoter in the myocardium. Functionally, silencing of TFEB attenuated the protective effect of lactate on cell damage, which was reversed by overexpression of CX43. Further mechanistic studies suggested that lactate facilitated CX43-regulated autophagy via the AMPK-mTOR-TFEB signaling pathway. Collectively, this research demonstrates that RIPC protects against myocardial I/R injury through lactate-mediated myocardial autophagy via the AMPK-mTOR-TFEB-CX43 axis., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment., Methods: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed., Results: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated., Conclusions: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic., (© 2023. The Author(s).)

Deep vein thrombosis (DVT) affects vascular health and can even threaten life; however, its pathogenesis remains unclear. Cardiovascular disease (CVD) and DVT share common risk factors, such as dyslipidemia, aging, etc. We aimed to investigate the loci of published CVD susceptibility genes and their association with environmental factors that might be related to DVT. Genotyping by Kompetitive Allele Specific PCR (KASP), collection of lifestyle information, and determination of blood biochemical markers were performed in 165 DVT cases and 164 controls. The impact of six single nucleotide polymorphisms (SNPs) and additional potential variables on DVT morbidity was evaluated using unconditional logistic regression (ULR). To explore the high-order interactions related to genetics and the body's internal environment exposure that affect DVT, ULR, crossover analysis, and multifactor dimensionality reduction/generalized multifactor dimensionality reduction (MDR/GMDR) were employed. Sensitivity analyses were performed using the EpiR package. The polymorphisms of FGB rs1800790 and PLAT rs2020918 were significantly associated with DVT. The optimum GMDR interaction model for gene-gene (G × G) consisted of THBD rs1042579, PLAT rs2020918, and PON1 rs662. The PLAT rs2020918 and MTHFR rs1801133 polymorphisms together eliminated the maximum entropy by the MDR method. The optimum GMDR interaction model for gene-environment (G × E) consisted of MTHFR rs1801133, FGB rs1800790, PLAT rs2020918, PON1 rs662, and total homocysteine (tHcy). Those with high tHcy levels and three risk genotypes significantly increased the DVT risk. In conclusion, certain CVD-related SNPs and their interactions with tHcy may contribute to DVT. These have implications for investigating DVT etiology and developing preventive treatment plans., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Deep vein thrombosis (DVT) is a serious health issue that often leads to considerable morbidity and mortality. Diagnosis of DVT in a clinical setting, however, presents considerable challenges. The fusion of metabolomics techniques and machine learning methods has led to high diagnostic and prognostic accuracy for various pathological conditions. This study explored the synergistic potential of dual-platform metabolomics (specifically, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)) to expand the detection of metabolites and improve the precision of DVT diagnosis. Sixty-one differential metabolites were identified in serum from DVT patients: 22 from GC-MS and 39 from LC-MS. Among these, five key metabolites were highlighted by SHapley Additive exPlanations (SHAP)-guided feature engineering and then used to develop a stacking diagnostic model. Additionally, a user-friendly interface application system was developed to streamline and automate the application of the diagnostic model, enhancing its practicality and accessibility for clinical use. This work showed that the integration of dual-platform metabolomics with a stacking machine learning model enables faster and more accurate diagnosis of DVT in clinical environments.

Objective: To investigate gene mutation characteristics of primary central nervous system lymphoma (PCNSL) through whole exome sequencing (WES) to 18 patients with PCNSL., Methods: Tumor tissues from 18 patients with diffuse large B-cell lymphoma who were diagnosed with PCNSL in Department of Hematology, Lanzhou University Second Hospital from September 2018 to December 2020 and had normal immune function, no history of HIV or immunosuppressant therapy were collected. High-throughput-based WES was performed on the tumor tissues, with an average sequencing depth of >100×. After data processing and bioinformatics analysis of sequencing results, the mutation maps and mutation characteristics of 18 PCNSL patients were obtained., Results: Obvious somatic mutations were detected in all 18 patients. The median number of somatic mutations was 321. Missense mutations were most prominent (accounting for about 90%), and the mutation type was dominated by C>T (50.2%), reflecting the age-related mutation pattern. Among the top 15 frequently mutated genes, PSD3, DUSP5, MAGEB16, TELO2, FMO2, TRMT13, AOC1, PIGZ, SVEP1, IP6K3 , and TIAM1 were the driver genes. The enrichment results of driver gene pathways showed that RTK-RAS, Wnt, NOTCH, Hippo and Cell-Cycle pathways were significantly enriched. The tumor mutation burden was between 3.558 48/Mb and 8.780 89/Mb, and the average was 4.953 32/Mb, which was significantly higher than other cancer research cohorts in the TCGA database., Conclusions: PCNSL occurs somatic missense mutations frequently, mainly point mutations, and the mutation type is mainly C>T. The driver genes are mainly involved in RTK-RAS, Wnt, NOTCH and Hippo pathways, indicating that the above pathways may be related to the pathogenesis of PCNSL. PCNSL has a significantly high tumor mutation burden, which may explain the efficacy of PD-1 inhibitors in PCNSL.

Objective: To explore the clinical features and prognosis of patients with primary central nervous system lymphoma（PCNSL）., Methods: A retrospective analysis was performed on the relationship between clinical features, treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022. Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups. Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments, and the factors influencing survival were analyzed., Results: Among 46 patients with PCNSL, which pathological type were diffuse large B-cell lymphoma（DLBCL）. There were 26(56.5%) cases of male and 20(43.5%) of female, with a median age of 54(17-71) years. In Hans subtypes, 14 cases (30.4%) of GCB subtype, 32 cases (69.6%) of non-GCB subtype. 32 cases (69.6%) of Ki-67≥80%. Among 36 patients who completed at least 2 cycles of treatment with follow-up data, the efficacy evaluation was as follows: overall response rate(ORR) was 63.9%, complete response(CR) rate was 47.2%, 17 cases of CR, 6 cases of PR. The 1-year progression-free survival rate and 1-year overall survival rate was 73.6% and 84.9%, respectively. The 2-year progression-free survival rate and 2-year overall survival rate was 52.2% and 68.9%, respectively. The ORR and CR rate of 17 patients treated with RMT regimen was 76.5% and 52.9% (9 cases CR and 4 cases PR), respectively. Univariate analysis of 3 groups of patients treated with RMT regimen, RM-BTKi regimen, and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS( P =0.032), and treatment regimen was associated with adverse OS in PCNSL patients（ P =0.025）., Conclusion: Different treatment modalities were independent prognosis predictors for OS, the deep brain infiltration of PCNSL is a poor predictive factor for PFS. Patients with relapse/refractory (R/R) PCNSL have a longer overall survival time because to the novel medication BTKi. They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients. With further research, a treatment algorithm can be developed to potentially identify patients at high risk of preoperative mortality., Introduction: Red blood cell distribution width (RDW) is an independent predictor of various disease states in elderly individuals, but its association with the prognosis of elderly hip fracture patients is controversial. This study aimed to evaluate the prognostic value of RDW in such patients, construct a prediction model containing RDW using random survival forest (RSF) and Cox regression analysis, and compare RDW in patients with and without anemia., Methods: We retrospectively analyzed the data of elderly patients who underwent hip fracture surgery, selected the best variables using RSF, stratified the independent variables by Cox regression analysis, constructed a 1-year mortality prediction model of elderly hip fracture with RDW, and conducted internal validation and external validation., Results: Two thousand one hundred six patients were included in this study. The RSF algorithm selects 12 important influencing factors, and Cox regression analysis showed that eight variables including preoperative RDW (pre-RDW) were independent risk factors for death within 1-year after hip fracture surgery in elderly patients. Stratified analysis showed that pre-RDW was still independently associated with 1-year mortality in the non-anemia group and not in the anemia group. The nomogram prediction model had high differentiation and fit, and the prediction model constructed by the total cohort of patients was also used for validation of patients in the anemia patients and obtained good clinical benefits., Conclusion: An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Short-chain fatty acids are metabolites of the intestinal flora and serve as the main energy source for intestinal epithelial cells. At the same time, as important signaling molecules, it regulate a variety of cellular inflammatory responses and homeostatic proliferation through receptor-dependent and independent pathways. Short-chain fatty acids regulate the gut-liver axis and thereby directly act on the liver, participating in the pathogenesis and transformation of various liver diseases, including alcoholic liver disease, metabolic dysfunction-related liver disease, autoimmune liver disease, liver fibrosis, and hepatocellular carcinoma. In addition, short-chain fatty acids can inhibit HBV DNA replication. This article reviews the research progress on the role of short-chain fatty acids in aspects of the pathogenesis and transformation of chronic liver diseases.

Chemical constituents of 70% ethanol extract of Alangium chinense subsp. pauciflorum were investigated. The 70% ethanol extract of A. chinense subsp. pauciflorum was isolated and purified by D-101 macroporous resins, silica gel, Sephadex LH-20 and other methods. As a result, nineteen compounds were isolated and identified as 4-cyclohexene-1α,2α,3α-triol-1-O-β-D-glucoside(1), 1β,4α,6α,13-tetrahydroxy-eudesm-11(12)-ene(2), sucrose(3), 1'-O-benzyl-α-L-rhamnopyranosyl-(1″→6')-β-D-glucopyranoside(4), bis(2-ethylhexyl)benzene-1,2-dicarboxylate(5),(Z)-10-heneicosenoic acid(6), di-O-methylcrenati(7), methyl-α-D-fructofuranoside(8), β-daucosterol(9), syringic acid(10), vanillicacid(11), octacosanol(12), isoarborinol(13), 2,7-dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthalenecarboxylate(14),vanillin(15), coniferyl aldehyde(16), 9(11)-dehydroergosterolperoxide(17), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol(18), β-sitosterol(19), respectively. Compounds 1 and 2 were new compounds, compounds 5-11, 13, 15-18 were isolated from Alangium for the first time.The anti-inflammatory activity of compourd 1 was determinded by the LPS-induced RAW264.7 macrophage inflammation model. The results showed that the new compound 1 has a certain inhibitory effect on LPS-induced NO production of RAW264.7 cells, and the inhibitory rate was 54.57%.

Given that combination with multiple biomarkers may well raise the predictive value of wound age, it appears critically essential to identify new features under the limited cost. For this purpose, the present study explored whether the gene expression ratios provide unique time information as an additional indicator for wound age estimation not requiring the detection of new biomarkers and allowing full use of the available data. The expression levels of four wound-healing genes (Arid5a, Ier3, Stom, and Lcp1) were detected by real-time polymerase chain reaction, and a total of six expression ratios were calculated among these four genes. The results showed that the expression levels of four genes and six ratios of expression changed time-dependent during wound repair. The six expression ratios provided additional temporal information, distinct from the four genes analyzed separately by principal component analysis. The overall performance metrics for cross-validation and external validation of four typical prediction models were improved when six ratios of expression were added as additional input variables. Overall, expression ratios among genes provide temporal information and have excellent potential as predictive markers for wound age estimation. Combining the expression levels of genes with ratio-expression of genes may allow for more accurate estimates of the time of injury., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P < 0.05). When stratified by estrogen receptor (ER) status, the OR for patients with ER (+) breast cancer ranged from 0.782 to 0.844 (95% CI, 0.616-0.994, P < 0.05) and that for those with ER (-) breast cancer ranged from 0.663 to 0.789 (95% CI, 0.498-0.991, P < 0.05). Additionally, ORs were as follows for cancer types: 1.577-1.908 (95% CI, 1.049-2.371, P < 0.05) for endometrial carcinoma; 1.216-1.303 (95% CI, 1.021-1.591, P < 0.05) for high-grade serous ovarian cancer; 1.217 (95% CI, 1.034-1.432, P < 0.05) for low-grade malignant serous ovarian cancer; and 1.502 (95% CI, 1.112-2.029, P < 0.05) for endometrioid ovarian carcinoma. Furthermore, our findings indicated that genetic predisposition towards BMI did not exhibit a causal association with uterine fibroids, cervical precancerous lesions, or cervical cancer itself. Conclusion: A genetic association was established between a high BMI and high risk of developing multiple tumors of the female reproductive system and their associated subtypes. This underscores the significance of taking measures to prevent reproductive system tumors in women who have a high BMI., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To explore the effects of prognostic nutritional index (PNI) combined with D-dimer on the prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL)., Methods: The clinical data of 73 DLBCL patients at initial diagnosis were retrospectively evaluated, and the optimal cut-off point of PNI and D-dimer were determined by ROC curve. The overall survival (OS) rate and progression-free survival (PFS) rate in different subgroups were compared using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis was performed to identify the factors associated with OS., Results: Compared with the low PNI group (PNI<44.775), the high PNI group (PNI≥44.775) had better OS ( P =0.022) and PFS ( P =0.029), the 2-year OS rates of the two groups were 55.6% and 78.3% respectively ( P =0.041). Compared with the high D-dimer group (D-dimer≥0.835), the low D-dimer group (D-dimer<0.835) had better OS ( P <0.001) and PFS ( P <0.001), the 2-year OS rates of the two groups were 51.4% and 86.8% respectively ( P =0.001). Meanwhile, patients in the high PNI+ low D-dimer group had better OS ( P =0.003) and PFS ( P <0.001) than the other three groups, the 2-year OS rate was statistically different from the other three groups ( P <0.05). The multivariate analysis revealed that NCCN-IPI ( HR =2.083, 95% CI : 1.034-4.196, P =0.040), PNI ( HR =0.267, 95% CI : 0.076-0.940, P =0.040) and PNI+D-dimer ( HR =9.082, 95% CI : 1.329-62.079, P =0.024) were the independent risk factors affecting OS in patients with DLBCL. Subgroup analysis showed that PNI, D-dimer, and PNI combined with D-dimer could improve the prognostic stratification in low and low-intermediate risk DLBCL patients., Conclusion: High PNI, low D-dimer and combination of high PNI and low D-dimer at initial diagnosis suggest a better prognosis in DLBCL patients.

The microbial communities may undergo a meaningful successional change during the progress of decay and decomposition that could aid in determining the post-mortem interval (PMI). However, there are still challenges to applying microbiome-based evidence in law enforcement practice. In this study, we attempted to investigate the principles governing microbial community succession during decomposition of rat and human corpse, and explore their potential use for PMI of human cadavers. A controlled experiment was conducted to characterize temporal changes in microbial communities associated with rat corpses as they decomposed for 30 days. Obvious differences of microbial community structures were observed among different stages of decomposition, especially between decomposition of 0-7d and 9-30d. Thus, a two-layer model for PMI prediction was developed based on the succession of bacteria by combining classification and regression models using machine learning algorithms. Our results achieved 90.48% accuracy for discriminating groups of PMI 0-7d and 9-30d, and yielded a mean absolute error of 0.580d within 7d decomposition and 3.165d within 9-30d decomposition. Furthermore, samples from human cadavers were collected to gain the common succession of microbial community between rats and humans. Based on the 44 shared genera of rats and humans, a two-layer model of PMI was rebuilt to be applied for PMI prediction of human cadavers. Accurate estimates indicated a reproducible succession of gut microbes across rats and humans. Together these results suggest that microbial succession was predictable and can be developed into a forensic tool for estimating PMI., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Ovarian serous cystadenocarcinoma (OSC) is the most prevalent histological subtype of ovarian cancer (OV) and presents a serious threat to women's health. Anoikis is an essential component of metastasis, and tumor cells can get beyond it to become viable. The impact of anoikis on OSC, however, has only been the topic of a few studies., Methods: The mRNA sequencing and clinical information of OSC came from The Cancer Genome Atlas Target Genotype-Tissue Expression (TCGA TARGET GTEx) dataset. Anoikis-related genes (ARGs) were collected by Harmonizome and GeneCards websites. Centered on these ARGs, we used unsupervised consensus clustering to explore potential tumor typing and filtered hub ARGs to create a model of predictive signature for OSC patients. Furthermore, we presented clinical specialists with a novel nomogram based on ARGs, revealing the underlying clinical relevance of this signature. Finally, we explored the immune microenvironment among various risk groups., Results: We identified 24 ARGs associated with the prognosis of OSC and classified OSC patients into three subtypes, and the subtype with the best prognosis was more enriched in immune-related pathways. Seven ARGs (ARHGEF7, NOTCH4, CASP2, SKP2, PAK4, LCK, CCDC80) were chosen to establish a risk model and a nomogram that can provide practical clinical decision support. Risk scores were found to be an independent and significant prognostic factor in OSC patients. The CIBERSORTx result revealed an inflammatory microenvironment is different for risk groups, and the proportion of immune infiltrates of Macrophages M1 is negatively correlated with risk score ( r s  = -0.21, P  < 0.05). Ultimately, quantitative reverse transcription polymerase chain reaction (RT-PCR) was utilized to validate the expression of the seven pivotal ARGs., Conclusion: In this study, based on seven ARGs, a risk model and nomogram established can be used for risk stratification and prediction of survival outcomes in patients with OSC, providing a reliable reference for individualized therapy of OSC patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Objectives: To estimate postmortem interval (PMI) by analyzing the protein changes in skeletal muscle tissues with the protein chip technology combined with multivariate analysis methods., Methods: Rats were sacrificed for cervical dislocation and placed at 16 ℃. Water-soluble proteins in skeletal muscles were extracted at 10 time points (0 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d, 7 d, 8 d and 9 d) after death. Protein expression profile data with relative molecular mass of 14 000-230 000 were obtained. Principal component analysis (PCA) and orthogonal partial least squares (OPLS) were used for data analysis. Fisher discriminant model and back propagation (BP) neural network model were constructed to classify and preliminarily estimate the PMI. In addition, the protein expression profiles data of human skeletal muscles at different time points after death were collected, and the relationship between them and PMI was analyzed by heat map and cluster analysis., Results: The protein peak of rat skeletal muscle changed with PMI. The result of PCA combined with OPLS discriminant analysis showed statistical significance in groups with different time points ( P <0.05) except 6 d, 7 d and 8 d after death. By Fisher discriminant analysis, the accuracy of internal cross-validation was 71.4% and the accuracy of external validation was 66.7%. The BP neural network model classification and preliminary estimation results showed the accuracy of internal cross-validation was 98.2%, and the accuracy of external validation was 95.8%. There was a significant difference in protein expression between 4 d and 25 h after death by the cluster analysis of the human skeletal muscle samples., Conclusions: The protein chip technology can quickly, accurately and repeatedly obtain water-soluble protein expression profiles in rats' and human skeletal muscles with the relative molecular mass of 14 000-230 000 at different time points postmortem. The establishment of multiple PMI estimation models based on multivariate analysis can provide a new idea and method for PMI estimation.

Background and Objectives : Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are malignant disorders with adverse prognoses for advanced patients. Anoikis, which is involved in tumor metastasis, facilitates the survival and separation of tumor cells from their initial site. Unfortunately, it is rarely studied, and in the literature, studies have only addressed the prognosis character of anoikis for patients with CESC. Materials and Methods : We utilized anoikis-related genes (ANRGs) to construct a prognostic signature in CESC patients that were selected from the Genecards and Harmonizome portals. Furthermore, we revealed the underlying clinical value of this signature for clinical maneuvers by providing clinical specialists with an innovative nomogram on the basis of ANRGs. Finally, we investigated the immune microenvironment and drug sensitivity in different risk groups. Results : We screened six genes from fifty-eight anoikis-related differentially expressed genes in the TCGA-CESC cohort, and we constructed a prognostic signature. Then, we built a nomogram combined with CESC clinicopathological traits and risk scores, which demonstrated that this model may improve the prognosis of CESC patients in clinical therapy. Next, the prognostic risk scores were confirmed to be an independent prognostic indicator. Additionally, we programmed a series of analyses, which included immune infiltration analysis, therapy-related analysis, and GSVA enrichment analysis, to identify the functions and mechanisms of the prognostic models during the progression of cancer in CESC patients. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the six ANRGs. Conclusions : The present discovery verified that the predictive 6-anoikis-related gene (6-ANRG) signature and nomogram serve as imperative factors that might notably impact a CESC patient's prognosis, and they may be able to provide new clinical evidence to assume the role of underlying biological biomarkers and thus become indispensable indicators for prospective diagnoses and advancing therapy.

Background: The estimation of post-mortem interval (PMI) is one of the most important problems in forensic pathology all the time. Although many classical methods can be used to estimate time since death, accurate and rapid estimation of PMI is still a difficult task in forensic practice, so the estimation of PMI requires a faster, more accurate, and more convenient method., Materials and Methods: In this study, an experimental method, lab-on-chip, is used to analyze the characterizations of polypeptide fragments of the lung, liver, kidney, and skeletal muscle of rats at defined time points after death (0, 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, 27, and 30 days). Then, machine learning algorithms (base model: LR, SVM, RF, GBDT, and MLPC; ensemble model: stacking, soft voting, and soft-weighted voting) are applied to predict PMI with single organ. Multi-organ fusion strategy is designed to predict PMI based on multiple organs. Then, the ensemble pruning algorithm determines the best combination of multi-organ., Results: The kidney is the best single organ for predicting the time of death, and its internal and external accuracy is 0.808 and 0.714, respectively. Multi-organ fusion strategy dramatically improves the performance of PMI estimation, and its internal and external accuracy is 0.962 and 0.893, respectively. Finally, the best organ combination determined by the ensemble pruning algorithm is all organs, such as lung, liver, kidney, and skeletal muscle., Conclusion: Lab-on-chip is feasible to detect polypeptide fragments and multi-organ fusion is more accurate than single organ for PMI estimation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Zhang, Long, Lu, Wang, Cao, Jin, Ren, Zhang, Huang and Sun.)

Acute myocardial ischemia (AMI) remains the leading cause of death worldwide, and the post-mortem diagnosis of AMI represents a current challenge for both clinical and forensic pathologists. In the present study, the untargeted metabolomics based on ultra-performance liquid chromatography combined with high-resolution mass spectrometry was applied to analyze serum metabolic signatures from AMI in a rat model (n = 10 per group). A total of 28 endogenous metabolites in serum were significantly altered in AMI group relative to control and sham groups. A set of machine learning algorithms, namely gradient tree boosting (GTB), support vector machine (SVM), random forest (RF), logistic regression (LR), and multilayer perceptron (MLP) models, was used to screen the more valuable metabolites from 28 metabolites to optimize the biomarker panel. The results showed that classification accuracy and performance of MLP model were better than other algorithms when the metabolites consisting of L-threonic acid, N-acetyl-L-cysteine, CMPF, glycocholic acid, L-tyrosine, cholic acid, and glycoursodeoxycholic acid. Finally, 17 blood samples from autopsy cases were applied to validate the classification model's value in human samples. The MLP model constructed based on rat dataset achieved accuracy of 88.23%, and ROC of 0.89 for predicting AMI type II in autopsy cases of sudden cardiac death. The results demonstrated that MLP model based on 7 molecular biomarkers had a good diagnostic performance for both AMI rats and autopsy-based blood samples. Thus, the combination of metabolomics and machine learning algorithms provides a novel strategy for AMI diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Determining postmortem interval (PMI) is one of the most challenging and essential endeavors in forensic science. Developments in PMI estimation can take advantage of machine learning techniques. Currently, applying an algorithm to obtain information on multiple organs and conducting joint analysis to accurately estimate PMI are still in the early stages. This study aimed to establish a multi-organ stacking model that estimates PMI by analyzing differential compounds of four organs in rats. In a total of 140 rats, skeletal muscle, liver, lung, and kidney tissue samples were collected at each time point after death. Ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was used to determine the compound profiles of the samples. The original data were preprocessed using multivariate statistical analysis to determine discriminant compounds. In addition, three interrelated and increasingly complex patterns (single organ optimal model, single organ stacking model, multi-organ stacking model) were established to estimate PMI. The accuracy and generalized area under the receiver operating characteristic curve of the multi-organ stacking model were the highest at 93% and 0.96, respectively. Only 1 of the 14 external validation samples was misclassified by the multi-organ stacking model. The results demonstrate that the application of the multi-organ combination to the stacking algorithm is a potential forensic tool for the accurate estimation of PMI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the significance of a new risk stratification model (R2-ISS) in evaluating the prognosis of newly diagnosed multiple myeloma (MM)., Methods: Clinical data of 116 newly diagnosed MM patients admitted to Lanzhou University Second Hospital from June 2012 to March 2021 were retrospectively analyzed. According to R2-ISS, these patients were divided into four groups: low risk, low-intermediate risk, intermediate-high risk, and high risk. The significance of R2-ISS on prognosis of the patients was analyzed., Results: Survival analysis showed that R2-ISS was associated with progression-free survival (PFS) ( P =0.042) and overall survival (OS) ( P =0.014). Cox univariate analysis showed that lactate dehydrogenase, serum calcium, serum creatinine, β 2 -microglobulin, ISS, R-ISS, R2-ISS, t(4;14), and autologous hematopoietic stem cell transplantation (ASCT) were the influencing factors of OS in newly diagnosed MM patients (all P <0.05). Cox multivariate analysis showed that R-ISS, R2-ISS, and ASCT were independent risk factors affecting OS (all P <0.05). In addition, survival analysis of patients with different R2-ISS showed that ASCT improved PFS and OS., Conclusion: R2-ISS has prognostic value for newly diagnosed MM patients, while ASCT can improve the prognosis of patients with different R2-ISS.

Insulin desensitization has been observed in the brains of patients with Parkinson's disease (PD), which is a progressive neurodegenerative disorder for which there is no cure. Semaglutide is a novel long-actingglucagon-likepeptide-1 (GLP-1) receptor agonist that is on the market as a treatment for type 2 diabetes. It is in a phase II clinical trial in patients with PD. Two previous phase II trials in PD patients showed good effects with the older GLP-1 receptor agonists, exendin-4 and liraglutide. We have developed a dual GLP-1/GIP receptor agonist (DA5-CH) that can cross the blood-brain barrier (BBB) at a higher rate than semaglutide. We tested semaglutide and DA5-CH in the 6-OHDA-lesion rat model of PD. Treatment was semaglutide or DA5-CH (25 nmol/kg, i.p.) daily for 30 days postlesion. Both drugs reduced the apomorphine-induced rotational behavior and alleviated dopamine depletion and the inflammation response in the lesioned striatum as shown in reduced IL-1 β and TNF- α levels, with DA5-CH being more effective. In addition, both drugs protected dopaminergic neurons and increased TH expression in the substantia nigra. Furthermore, the level of monomer and aggregated α -synuclein was reduced by the drugs, and insulin resistance as shown in reduced pIRS-1 ser312 phosphorylation was also attenuated after drug treatment, with DA5-CH being more effective. Therefore, while semaglutide showed good effects in this PD model, DA5-CH was superior and may be a better therapeutic drug for neurodegenerative disorders such as PD than GLP-1 receptor agonists that do not easily cross the BBB., Competing Interests: CH is a named inventor on patents that cover the use of GLP-1/GIP receptor agonists in treating neurodegenerative disorders. He is the CSO of the biotech company Kariya Pharmaceuticals. The authors declare that they have no conflicts of interest., (Copyright © 2022 Lingyu Zhang et al.)

Background: Pacemaker implantation combined with atrioventricular node ablation (AVNA) could be a practical choice for atrial fibrillation (AF) patients with heart failure (HF). Left bundle branch area pacing (LBBaP) has been widely reported., Objectives: To explore the safety and efficacy of LBBaP combined with AVNA in AF patients with HF., Methods and Results: Fifty-six AF patients with HF attempted LBBaP and AVNA from January 2019 to December 2020. Standard LBBaP was achieved in forty-six patients, and another ten received left ventricular septal pacing (LVSP). The cardiac function indexes and pacemaker parameters were evaluated at baseline, and we conducted a 1-month and 1-year follow-up., Result: At the time of implantation and 1-month and 1-year follow-up, QRS duration of LVSP group was longer than that of LBBaP group. The pacemaker parameters remained stable in both the LBBaP and LVSP groups. At 1-month and 1-year follow-up after LBBaP and AVNA, left ventricular ejection fraction, left ventricular end-diastolic diameter, and NYHA classification continued to improve. Baseline left ventricular ejection fraction and QRS duration change at implantation can predict the magnitude of improvement of left ventricular ejection fraction at 1-year after LBBaP. Baseline right atrial left-right diameter, the degree of tricuspid regurgitation, and interventricular septum thickness may be the factors affecting the success of LBBaP., Conclusion: LBBaP combined with AVNA is safe and effective for patients with AF and HF. Baseline right atrial left-right diameter, the degree of tricuspid regurgitation, and interventricular septum thickness may be the factors affecting the success of LBBaP.

Objectives: To investigate the effects of injury time, postmortem interval (PMI) and postmortem storage temperature on mRNA expression of glycoprotein non-metastatic melanoma protein B (Gpnmb), and to establish a linear regression model between Gpnmb mRNA expression and injury time, to provide aimed at providing potential indexes for injury time estimation., Methods: Test group SD rats were anesthetized and subjected to blunt contusion and randomly divided into 0 h, 4 h, 8 h, 12 h, 16 h, 20 h and 24 h groups after injury, with 18 rats in each group. After cervical dislocation, 6 rats in each group were collected and stored at 0 ℃, 16 ℃ and 26 ℃, respectively. The muscle tissue samples of quadriceps femoris injury were collected at 0 h, 12 h and 24 h postmortem at the same temperature. The grouping method and treatment method of the rats in the validation group were the same as above. The expression of Gpnmb mRNA in rat skeletal muscle was detected by RT-qPCR. The Pearson correlation coefficient was used to evaluate the correlation between Gpnmb mRNA expression and injury time, PMI, and postmortem storage temperature. SPSS 25.0 software was used to construct a linear regression model, and the validation group data was used for the back-substitution test., Results: The expression of Gpnmb mRNA continued to increase with the prolongation of injury time, and the expression level was highly correlated with injury time ( P <0.05), but had little correlation with PMI and postmortem storage temperature ( P >0.05). The linear regression equation between injury time ( y ) and Gpnmb mRNA relative expression ( x ) was y =0.611 x +4.489. The back-substitution test proved that the prediction of the model was accurate., Conclusions: The expression of Gpnmb mRNA is almost not affected by the PMI and postmortem storage temperature, but is mainly related to the time of injury. Therefore, a linear regression model can be established to infer the time of injury.

Purpose: To analyze the correlation between microbiome of supragingival plaque and host blood lipid levels., Methods: Samples of supragingival plaques from 68 volunteers aged 45-60 years were collected. The total DNA was extracted, and 16S rDNA V3-V4 regions were amplified via PCR. The amplified products were sequenced by Illumina MiSeq PE300. After that, OTU clustering and species annotation were carried out. Then, the correlation of annotated species (genus level) and host blood lipid level were calculated with Spearman correlation analysis. SPSS 16.0 software package was used for statistical analysis., Results: The average number of sequences obtained from the supragingival plaque samples was 41 929, and the number of OTUs obtained by clustering was 1 037. A total of 25 phyla, 45 classes, 92 orders, 155 families and 330 genera were annotated. Species heat maps showed a high degree of consistency in the species composition abundance of 68 samples. Spearman correlation analysis showed that among the supragingival microorganisms, Alloprevotella spp., Dialister spp., Peptostreptococcus spp. and Prevotella 7 spp., were negatively correlated with the host serum total cholesterol/low density lipoprotein cholesterol level. Neisseria spp. was positively correlated with host serum high-density lipoprotein cholesterol, but negatively correlated with Prevotella 2 spp.., Conclusions: The compositional structure of the supragingival microbiome is relatively stable and has a correlation with the host blood lipid levels. Profiles of supragingival microbiome can be promising biomarkers of the lipid metabolism of the host.

Aims: This study aimed to investigate an appropriate catheter manipulation approach for ventricular arrhythmias (VAs) originating from the left ventricular epicardium adjacent to the transitional area from the great cardiac vein to the anterior interventricular vein (DGCV-AIV). Methods: A total of 123 patients with DGCV-AIV VAs were retrospectively analyzed. All these patients underwent routine mapping and ablation by conventional approach [Non-Swartz sheath support (NS) approach] firstly. In the situation of the distal portion of the coronary venous system (CVS) not being accessed or a good target site not being obtained, the Swartz sheath support (SS) approach was attempted alternatively. If this still failed, the hydrophilic coated guidewire and left coronary angiographic catheter-guided deep engagement of Swartz sheath in GCV to support ablation catheter was performed. Results: A total of 103 VAs (103/123, 83.74%) were successfully eliminated in DGCV-AIV. By NS approach, the tip of the catheter reached DGCV in 39.84% VAs (49/123), reached target sites in 35.87% VAs (44/123), and achieved successful ablation in 30.89% VAs (38/123), which was significantly lower than by SS approach (88.61% (70/79), 84.81 % (67/79), and 75.95% (60/79), P < 0.05). There were no significant differences in complication occurrence between the NS approach and the SS approach (4/123, 3.25% vs. 7/79, 8.86%, p > 0.05). The angle between DGCV and AIV <83° indicated an inaccessible AIV by catheter tip with a predictive value of 94.5%. Width/height of coronary venous system>0.69 more favored a SS approach with a predictive value of 87%. Conclusion: For radiofrequency catheter ablation (RFCA) of VAs arising from DGCV-AIV, the SS approach facilitates the catheter tip to achieve target sites and contributes to a successful ablation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Lin, Wang, Lv, Jin, Li and Lin.)

Wound age estimation is still one of the most important and significant challenges in forensic practice. The extent of wound damage greatly affects the accuracy and reliability of wound age estimation, so it is important to find effective biomarkers to help diagnose wound degree and wound age. In the present study, the gene expression profiles of both mild and severe injuries in 33 rats were assayed at 0, 1, 3, 24, 48, and 168 hours using the Affymetrix microarray system to provide biomarkers for the evaluation of wound age and the extent of the wound. After obtaining thousands of differentially expressed genes, a principal component analysis, the least absolute shrinkage and selection operator, and a time-series analysis were used to select the most predictive prognostic genes. Finally, 15 genes were screened for evaluating the extent of wound damage, and the top 60 genes were also screened for wound age estimation in mild and severe injury. Selected indicators showed good diagnostic performance for identifying the extent of the wound and wound age in a Fisher discriminant analysis. A function analysis showed that the candidate genes were mainly related to cell proliferation and the inflammatory response, primarily IL-17 and the Hematopoietic cell lineage signalling pathway. The results revealed that these genes play an essential role in wound-healing and yield helpful and valuable potential biomarkers for further targeted studies., Competing Interests: The authors declare there are no competing interests., (©2021 Li et al.)

Patients with Parkinson's disease (PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), can re-sensitize insulin signaling. In a recent phase II clinical trial, the first GLP-1 mimic, exendin-4, has shown reliable curative effect in patients with PD. DA-CH5 is a novel GLP-1/GIP receptor unimolecular co-agonist with a novel peptide sequence added to cross the blood-brain barrier. Here we showed that both exendin-4 and DA-CH5 protected against 6-hydroxydopamine (6-OHDA) cytotoxicity, inhibited apoptosis, improved mitogenesis and induced autophagy flux in SH-SY5Y cells via activation of the insulin receptor substrate-1 (IRS-1)/alpha serine/threonine-protein kinase (Akt)/cAMP response element-binding protein (CREB) pathway. We also found that DA-CH5 (10 nmol/kg) daily intraperitoneal administration for 30 days post-lesion alleviated motor dysfunction in rats and prevented stereotactic unilateral administration of 6-OHDA induced dopaminergic neurons loss in the substantia nigra pars compacta. However, DA-CH5 showed curative effects in reducing the levels of α-synuclein and the levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β). It was also more effective than exendin-4 in inhibiting apoptotic process and protecting mitochondrial functions. In addition, insulin resistance was largely alleviated and the expression of autophagy-related proteins was up-regulated in PD model rats after DA-CH5 treatment. These results in this study indicate DA-CH5 plays a therapeutic role in the 6-OHDA-unilaterally lesioned PD rat model and is superior to GLP-1 analogue exendin-4. The study was approved by the Animal Ethics Committee of Shanxi Medical University of China., Competing Interests: None

Abstract: In cases of sudden death, the prevention of sudden cardiac death and the analysis of the cause of death after sudden cardiac death have always been a difficult problem. Therefore, clinical research and forensic pathological identification of sudden cardiac death are of great significance. In recent years, metabolomics has gradually developed into a popular field of life science research. The detection of "metabolic fingerprints" of biological fluids can provide an important basis for early diagnosis of diseases and the discovery of potential biomarkers. This article reviews the current research status of sudden cardiac death and the research on metabolomics of cardiovascular diseases that is closely related to sudden cardiac death and analyzes the application prospects of metabolomics in the identification of the cause of sudden cardiac death., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Abstract: Objective To investigate the correlation between the polymorphism of 4 coagulation-related genes, rs1799963 （coagulation factor V gene Leiden）, rs6025 （prothrombin gene G20210A）, rs1042579 （thrombomodulin protein gene c.1418C>T） and rs1801131 （methylenetetrahydroflate reductase gene） and lower extremity deep venous thrombosis （LEDVT）. Methods The 4 genotypes mentioned above of 150 LEDVT patients and 153 healthy controls were detected by the kompetitive allele specific polymerase chain reaction （KASP）, then related blood biochemical indicators were collected, binary Logistic regression was established to screen the independent risk factors of LEDVT, and the correlation between polymorphism of 4 coagulation-related genes and LEDVT and its indicators under different genetic modes after adjusting confounding factors were analyzed. Results Five variables, D-dimer, fibrinogen degradation product, homocysteine, sex and age might be the risk factors of LEDVT. These variables were put into 4 genetic inheritance models, and adjusted in binary Logistic regression. The results suggested that the mutations of rs1042579 were correlated with LEDVT under dominant inheritance mode. Conclusion The gene polymorphism of rs1799963, rs6025 and rs1801131 has no significant correlation with the formation of LEDVT. The gene polymorphism of rs1042579 plays a role under dominant inheritance mode, and might be an independent risk factor for formation of LEDVT., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Background: The pathological diagnosis of sudden cardiac death caused by myocardial ischemia is a difficult problem. Relevant evidence shows that the expression of Egr-1 and c-fos undergo changes in the early stage of myocardial ischemia, but the detailed temporal variation of them is not clear. Therefore, the aim of this study was to observe the temporal changes in mRNA and protein expression of Egr-1 and c-fos in ischemic myocardium in rats., Methods: Sixty-six Sprague-Dawley rats were divided into the control group, the early myocardial ischemia (EMI) group, the sham operated group and the allergy group. The EMI rats were further divided into eight subgroups according to the different time points (30 min and 1, 2, 4, 8, 12, 24, and 48 h) after modeling. The mRNA and protein of Egr-1 and c-fos of each group were detected by real-time quantitative polymerase chain reaction and immunohistochemistry, respectively., Results: In the EMI group, Egr-1 mRNA in ischemic myocardium rose 30 min after ischemia and peaked at 2 h; the plateau was maintained up to 8 h after ischemia, and then returned to the baseline level at 12 h. The c-fos mRNA in ischemic myocardium demonstrated a consistent changing curve with that of Egr-1. The mRNA of Egr-1 and c-fos showed no significant changes in the control group, the sham operated group and the allergy group. Immunohistochemistry showed that Egr-1 protein in the myocardial ischemic area was slightly positive 30 min after ischemia, and then strongly positive at 4 and 8 h, decreased at 12 h, and was negative at 24 h. The changing trends of c-fos protein were almost the same as that of Egr-1. Immunohistochemistry of Egr-1 and c-fos protein were all negative in the control group, the sham operated group and the allergy group., Conclusions: The mRNA and protein expression of Egr-1 and c-fos presented rapid and temporal changes after myocardial ischemia, and this may be helpful in distinguishing sudden death induced by myocardial ischemia from that of allergy.

Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. The present study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process. A total of 33 rats were divided randomly into control (n=3), mild contusion (n=15), and severe contusion (n=15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n=3 per subgroup). A total of 2844 and 2298 differentially expressed genes (DEGs) were identified using microarray analyses in the mild and severe contusions, respectively. From the analysis of the 1620 coexpressed genes in mildly and severely contused muscle, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. The functional analyses of genes in the functional modules and temporal clusters were performed, and the hub genes in each module-cluster pair were identified. Interestingly, we found that genes down-regulated at 24-48 h were largely associated with metabolic processes, especially of the oxidative phosphorylation (OXPHOS), which has been rarely reported. These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation., (© 2021 The Author(s).)

The rhesus macaque (Macaca mulatta) is the most widely distributed nonhuman primate species, and captive populations play an important role in biomedical research due to close phylogenetic and physiological similarity to human beings. However, to our best knowledge, the spondyloarthritis (SpA) in rhesus macaques has been exclusively reported in captive or semicaptive populations rather than wild counterparts. In the present study, we report 2 cases of SpA observed in Taihangshan macaques (Macaca mulatta tcheliensis) inhabiting the Taihangshan Macaque National Nature Reserve, Henan Province, China. Among these 2 cases, one can be diagnosed as ankylosing spondylitis (AS) following accepted medical criteria, and another case showed evident fusion at the pubic symphysis which could be specific to rhesus macaque AS. We discuss the potential causes leading directly or indirectly to the development of SpA., (© 2021 S. Karger AG, Basel.)

Gene regulatory networks play pivotal roles in our understanding of biological processes/mechanisms at the molecular level. Many studies have developed sample-specific or cell-type-specific gene regulatory networks from single-cell transcriptomic data based on a large amount of cell samples. Here, we review the state-of-the-art computational algorithms and describe various applications of gene regulatory networks in biological studies.

Wound age estimation is a complex, multifactorial issue. It is considered to have great practical significance that combining multi-biomarkers and multi-methods for injury time estimation. We optimized our earlier "up, no change, or down" model by adding data on the expression levels of mRNAs encoding ABHD2, MAD2L2, and ARID5A, and we converted the relative quantitative expression levels of seven genes into a vector rather than a color model. We used Python to derive the cosine similarity (CS) between a test set and the vector matrix; the highest similarity most accurately reflected the injury time. For the optimized model, the internal and external verifications were approximately 0.71 and 0.66, respectively. The good double-blinded results indicated that the model was stable and reliable. In summary, we used a vector matrix and cosine similarities derived by Python to mine the levels of genes expressed in contused skeletal muscle. We are the first to combine several biomarkers and methods for wound age estimation.

Abstract: Objective To obtain the protein expression profile of rat liver tissue after death by the 2100 bioanalyzer combined with protein chip, and infer the relationship between protein expression profile and postmortem interval. Methods Rats were killed by abdominal anesthesia and placed at 16 ℃. Water-soluble proteins in liver tissues were extracted at 14 time points after death. The expression profile data of proteins with relative molecular weight of 14 000-230 000 were obtained using protein chip, and principal component analysis （PCA）, partial least squares-discriminant analysis （PLS-DA） and Fisher discriminant were used to analyze the data. Results According to the changes of protein expression profile, the postmortem interval was divided into group A （0 d）, group B （1-9 d）, group C （12-30 d） according to the result of PLS-DA. The prediction accuracy of the training set and test set of the model were all 100.0%, and the internal cross-validation of the training set was 100.0% according to Fisher discriminant. The Fisher discriminant model at each time point of group B and C was established to narrow the time window of postmortem interval estimation. The prediction accuracy of the training set and test set were all 100.0%, and the internal cross-validation accuracy of the training set was 100.0% in group B. The prediction accuracy of the training set and test set were respectively 95.2% and 78.6% in group C, and the internal cross-validation of the training set was 88.1%. Conclusion Protein chip detection technology can quickly and easily obtain the expression profile of water-soluble proteins of rat liver tissue with a relative molecular weight of 14 000-230 000 at different time points after death. PLS-DA and Fisher discriminant models are established to classify and predict the postmortem interval, in order to provide new ideas and methods for postmortem interval estimation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

In this mini-review, we highlighted the recent progresses in the controlled synthesis of metal sulfides hollow nanostructures via hard template technique. After a brief introduction about the formation mechanism of the inorganic hollow nanostructures via hard template technique, the discussions primarily focused on the emerging development of metal sulfides hollow nanostructures. Various synthetic strategies were summarized concerning the use of the hard template engaged strategies to fabricate various metal sulfides hollow nanostructures, such as hydrothermal method, solvothermal method, ion-exchange, sulfidation or calcination etc. Finally, the perspectives and summaries have been presented to demonstrate that a facile synthetic technique would be widely used to fabricate metal sulfides hollow nanostructures with multi-shells and components., (© 2020 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Although many time-dependent parameters involved in wound healing have been exhaustively investigated, establishing an objective and reliable means for estimating wound age remains a challenge. In this study, 78 Sprague-Dawley rats were divided randomly into a control group and contusion groups at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 h post-injury (n = 6 per group). The expression of 35 wound healing-related genes was explored in contused skeletal muscle by real-time polymerase chain reaction. Differences between the groups were assessed by partial least squares discriminant analysis (PLS-DA). The results show that the samples were classified into three groups by wound age (4-12, 16-24, and 28-48 h). A Fisher discriminant analysis model of 14 selected genes was constructed, and 94.9% cross-validated grouped cases were correctly classified. A PLS regression analysis using 14 genes showed reasonable internal predictive validity, with a root mean squared error of cross-validation of approximately 8 h. To examine whether the prediction models were capable of analyzing new (ungrouped) cases, an external validation was carried out using the expression data from an additional 30 rats. Approximately 76.7% of ungrouped cases were correctly classified, which was a lower proportion than that for cross-validation. Similarly, the prediction results of the PLS model showed lower relatively external predictive validity (root mean squared error of prediction = 11 h) than internal predictive validity. Although the prediction results were less accurate than expected, the gene expression modeling and multivariate analyses showed great potential for estimating injury time. These multivariate methods may be valuable when devising future wound time estimation strategies.

Nasopharyngeal carcinoma (NPC) is a prevalent head and neck tumor which has a high mortality rate in Southeast Asia, especially in Southern China. Cancer susceptibility candidate 2 (CASC2) is a newly identified long non‑coding RNA (lncRNA) that has been found to play a suppressive role in several types of tumors. However, the expression and functional role of CASC2 in NPC are still unclear. In the present study, using NPC tissues, cells and transplanted mice, we investigated the mechanism of CASC2‑mediated regulation of NPC. We showed that the CASC2 level is reduced in NPC tissues and cells. CASC2 downregulation promoted proliferation and inhibited apoptotic cell death in NPC cells. In contrast, CASC2 upregulation inhibited proliferation and increased apoptosis. There were putative binding sites of microRNA (miR)‑18a‑5p in the promoter of CASC2. The level of miR‑18a‑5p was upregulated in NPC tissues and cells. We further confirmed that CASC2 could directly bind with miR‑18a‑5p and inhibit miR‑18a‑5p expression, using reporter gene and RNA immunoprecipitation assays. miR‑18a‑5p suppressed CASC2 upregulation‑mediated decrease in proliferation and increase in apoptotic cell death. Bioinformatics predicted the putative binding site of miR‑18a‑5p in the 3' untranslated region of C‑terminal binding protein interacting protein (CtIP)/RBBP8. It was further confirmed that miR‑18a‑5p could directly bind with RBBP8 and inhibit RBBP8 expression. Downregulation of RBBP8 inhibited the anti‑miR‑18a‑5p‑mediated increase in apoptosis and decrease in proliferation. Downregulation of CASC2 increased tumor growth, increased the level of miR‑18a‑5p and decreased RBBP8 expression in vivo. In summary, CASC2 regulates NPC malignancy through modulation of RBBP8 via sponging miR‑18a‑5p. Our findings highlight the CASC2/miR‑18a‑5p/RBBP8 axis in NPC pathogenesis and provide new biomarkers and potential targets for the therapy of NPC.

There is now compelling evidence that selective stimulation of Aδ nociceptors eliciting first pain evokes robust responses in the primary somatosensory cortex (S1). In contrast, whether the C-fiber nociceptive input eliciting second pain has an organized projection to S1 remains an open question. Here, we recorded the electrocortical responses elicited by nociceptive-specific laser stimulation of the four limbs in 202 humans (both males and females, using EEG) and 12 freely moving rats (all males, using ECoG). Topographical analysis and source modeling revealed in both species, a clear gross somatotopy of the unmyelinated C-fiber input within the S1 contralateral to the stimulated side. In the human EEG, S1 activity could be isolated as an early-latency negative deflection (C-N1 wave peaking at 710-730 ms) after hand stimulation, but not after foot stimulation because of the spatiotemporal overlap with the subsequent large-amplitude supramodal vertex waves (C-N2/P2). In contrast, because of the across-species difference in the representation of the body surface within S1, S1 activity could be isolated in rat ECoG as a C-N1 after both forepaw and hindpaw stimulation. Finally, we observed a functional dissociation between the generators of the somatosensory-specific lateralized waves (C-N1) and those of the supramodal vertex waves (C-N2/P2), indicating that C-fiber unmyelinated input is processed in functionally distinct somatosensory and multimodal cortical areas. These findings demonstrated that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire. SIGNIFICANCE STATEMENT Unmyelinated C-fibers are the evolutionarily oldest peripheral afferents responding to noxious environmental stimuli. Whether C-fiber input conveys information about the spatial location of the noxious stimulation to the primary somatosensory cortex (S1) remains an open issue. In this study, C-fibers were activated by radiant heat stimuli delivered to different parts of the body in both humans and rodents while electrical brain activity was recorded. In both species, the C-fiber peripheral input projects to different parts of the contralateral S1, coherently with the representation of the body surface within this brain region. These findings demonstrate that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire., (Copyright © 2018 Jin, Wu et al.)

Objectives: To study the urinary metabolic profile in rats with deep venous thrombosis （DVT） based on metabolomics and to screen out small molecular biomarkers for the diagnosis and forensic identification of DVT., Methods: Inferior vena cava of rats was ligated to construct DVT models. The rats were randomly divided into three groups： DVT, sham, and control groups, 10 in each group. The urine of DVT and sham rats was collected during 24 hours in the metabolic cage at 48 hours after operating, meanwhile, 24 hours urine was collected in control group. The metabolic profile was analyzed by nuclear magnetic resonance. SIMCA-P 14.1 software was used for pattern recognition. The variable importance in projection （VIP） value from orthogonal PLS-DA （OPLS-DA） model combined with Mann-Whitney U test were used to search the different metabolites in the urine., Results: The metabolic profiles of urine from DVT, sham, and control groups had significant differences. The DVT, sham, and control groups could be distinguished by the partial least squares method-discriminant analysis （PLS-DA） model. Compared with the urine of the rats in control groups, the levels of leucine, glutamine, creatine, creatinine and sucrose in the urine of DVT rats were up-regulated, and the levels of 3-hydroxybutyrate, lactate, acetone, α-oxoglutarate, citrate and hippurate were down-regulated., Conclusions: The different metabolites in the urine of DVT rats are expected to become its candidate biomarkers. The results can provide a research basis for the diagnosis, treatment and forensic identification of DVT., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Deep vein thrombosis (DVT) and pulmonary embolism (PE) have high morbidity, reduce quality of life, and can cause death. Biomarkers or genetic risk factors have not been identified in patients with DVT. In present study, serum of 61 patients suffering from DVT and a rat DVT model (n = 10) were assayed by a proton nuclear magnetic resonance ( 1 H NMR) metabolomics technique combing with multivariate statistical analysis to identify the metabolites. The MetPA platform was used to identify differences in the metabolic pathways between the rat model and patients. The metabolomics results discovered that 11 different metabolites in rats and 20 different metabolites in DVT patients. Seven metabolites both altered in the rats and patients. Moreover, we observed changes in the metabolic pathways, including carbohydrate metabolism, lipid metabolism, and amino acid metabolism that were induced immediately by the thrombosis. Pathway of aminoacyl-tRNA biosynthesis perturbed only in the patients which was associated with the genetic risk factor of DVT. The study demonstrated that serum 1 H NMR metabolomics can be used to diagnose DVT in the clinic. The altered pathways related to thrombosis and genetics will provide a foundation and new strategies for understanding the pathological mechanism and pharmacological targets of DVT.

Deep vein thrombosis (DVT) is a disease involving multiple genes and systems. MicroRNAs (miRNAs) represent a class of non-coding small RNAs that post-transcriptionally suppress their target genes. The expression patterns of miRNA and messenger RNA (mRNA) in DVT remain poorly characterized. The aim of the present study was to evaluate miRNA and mRNA expression profiles in a stasis-induced DVT rat model. Male SD rats were randomly divided into three groups as follows: DVT, sham and control. The inferior vena cava (IVC) of rats was ligated to construct stasis-induced DVT models. Rats were sacrificed three days after ligation, and morphological changes in the vein tissues were observed by hematoxylin and eosin and Masson staining. The miRNA and mRNA expression profiles were evaluated by microarrays, followed by bioinformatics analysis. The microarray analysis identified 22 miRNAs and 487 mRNAs that were significantly differentially expressed between the experimental and control groups, and between the experimental and sham groups, but not between the control and sham groups (P≤0.05; ≥2.0‑fold change). By subsequent bioinformatics analysis, a 19 miRNA-98 mRNAs network was constructed in the stasis-induced DVT rat model. Notably, the majority of these miRNAs and mRNAs are reported to be expressed by endothelial cells (ECs) and are associated with the function of ECs. The results provide evidence indicating that the regulatory association of miRNA and mRNA points to key roles played by ECs in thrombosis. These findings advance our understanding of the molecular regulatory mechanisms underlying the pathophysiology of DVT.

Background: Post-herpetic neuralgia (PHN), which develops after the resolution of a herpes zoster eruption, is an exceptionally drug-resistant neuropathic pain. The unsatisfactory management of PHN partly results from the difficulty in dissecting out its contributing factors due to the complexity of PHN mechanism., Methods: Here, to elaborate our understanding of the PHN mechanism and to establish a basis for effective therapeutic strategies, we comprehensively investigated the contributions of multiple factors to PHN severity., Results: Based on the comparison of somatosensory detection thresholds (C, Aδ and Aβ fibre thresholds) between affected and unaffected sides, 16 PHN patients with significant sensory deficits and 13 PHN patients without significant sensory deficits were identified and assigned to different groups. The different extents of lesions in the nociceptive system between patients with and without sensory deficits were confirmed using laser-evoked brain responses. Moreover, patients with sensory deficits had more severe pain and psychological disorders, e.g. anxiety and depression. Importantly, chronic pain severity was significantly influenced by various psychophysiological factors (sleep disturbances, psychological disorders and hypothalamic-pituitary-adrenal axis dysfunction) for patients with sensory deficits., Conclusions: Our findings demonstrated the contribution of multiple patho-psychophysiological factors to PHN severity, which could help establish a basis for the development of a rational, patient-centred therapeutic strategy., Significance: This study revealed the contribution of multiple patho-psychophysiological factors to PHN severity, which expanded our understanding of the underlying PHN mechanism, and helped develop a rational, patient-centred therapeutic strategy targeting towards the corresponding etiology and psychophysiological disorders for individual patient., (© 2016 European Pain Federation - EFIC®.)

The high hardness or yield strength of an alloy is known to benefit from the presence of small-scale precipitation, whose hardening effect is extensively applied in various engineering materials. Stability of the precipitates is of critical importance in maintaining the high performance of a material under mechanical loading. The long period stacking ordered (LPSO) structures play an important role in tuning the mechanical properties of an Mg-alloy. Here, we report deformation twinning induces decomposition of lamellar LPSO structures and their re-precipitation in an Mg-Zn-Y alloy. Using atomic resolution scanning transmission electron microscopy (STEM), we directly illustrate that the misfit dislocations at the interface between the lamellar LPSO structure and the deformation twin is corresponding to the decomposition and re-precipitation of LPSO structure, owing to dislocation effects on redistribution of Zn/Y atoms. This finding demonstrates that deformation twinning could destabilize complex precipitates. An occurrence of decomposition and re-precipitation, leading to a variant spatial distribution of the precipitates under plastic loading, may significantly affect the precipitation strengthening.

Aim: To investigate the expression of mast cell tryptase and carboxypeptidase A in drug-related fatal anaphylaxis., Methods: The expression of mast cell tryptase and carboxypeptidase A in 15 autopsy cases of drug-related fatal anaphylaxis and 20 normal autopsy cases were detected. First, the expression of mast cell tryptase was determined in stomach, jejunum, lung, heart, and larynx by immunofluorescence. Different tissues were removed and fixed in paraformaldehyde solution, then paraffin sections were prepared for immunofluorescence. Using specific mast cell tryptase and carboxypeptidase A antibodies, the expression of tryptase and carboxypeptidase A in gastroenterology tract and other tissues were observed using fluorescent microscopy. The postmortem serum and pericardial fluid were collected from drug-related fatal anaphylaxis and normal autopsy cases. The level of mast cell tryptase and carboxypeptidase A in postmortem serum and pericardial fluid were measured using fluor enzyme linked immunosorbent assay (FEIA) and enzyme linked immunosorbent assay (ELISA) assay. The expression of mast cell tryptase and carboxypeptidase A was analyzed in drug-related fatal anaphylaxis cases and compared to normal autopsy cases., Results: The expression of carboxypeptidase A was less in the gastroenterology tract and other tissues from anaphylaxis-related death cadavers than normal controls. Immunofluorescence revealed that tryptase expression was significantly increased in multiple organs, especially the gastrointestinal tract, from anaphylaxis-related death cadavers compared to normal autopsy cases (46.67 ± 11.11 vs 4.88 ± 1.56 in stomach, 48.89 ± 11.02 vs 5.21 ± 1.34 in jejunum, 33.72 ± 5.76 vs 1.30 ± 1.02 in lung, 40.08 ± 7.56 vs 1.67 ± 1.03 in larynx, 7.11 ± 5.67 vs 1.10 ± 0.77 in heart, P < 0.05). Tryptase levels, as measured with FEIA, were significantly increased in both sera (43.50 ± 0.48 μg/L vs 5.40 ± 0.36 μg/L, P < 0.05) and pericardial fluid (28.64 ± 0.32 μg/L vs 4.60 ± 0.48 μg/L, P < 0.05) from the anaphylaxis group in comparison with the control group. As measured by ELISA, the concentration of carboxypeptidase A was also increased more than 2-fold in the anaphylaxis group compared to control (8.99 ± 3.91 ng/mL vs 3.25 ± 2.30 ng/mL in serum, 4.34 ± 2.41 ng/mL vs 1.43 ± 0.58 ng/mL in pericardial fluid, P < 0.05)., Conclusion: Detection of both mast cell tryptase and carboxypeptidase A could improve the forensic identification of drug-related fatal anaphylaxis.

Phantom limb pain (PLP) is a hallucination that the patient feels the existence off the limb after its loss and experiences somewhat pain of the missing limb. Such a pain normally appears in the distal end of the missing limb. Currently, the pathomechanism of PLP is still unclear, and the clinical research of PLP mainly relies on the subjective report of the patients and the psychophysical measurements. In this paper, we discuss extensively the pathomechanism of PLP, and summarize comprehensively the advanced methods for studying the pathomechanism of PLP. In short, the paper could deepen our understanding of the pathomechanism of PLP, and could serve as an effective instruction basis for researchers and doctors to diagnose and treat the PLP.

Objectives: Psychotic symptoms are commonly observed among heroin users. Low serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the relationship between serum BDNF levels and psychotic symptoms in heroin dependence are lacking., Method: A total of 31 heroin-dependent patients who had never experienced psychotic symptoms during heroin consumption and 21 patients with a history of psychotic symptoms were consecutively recruited. We measured by enzyme-linked immunosorbent assay (ELISA) serum BDNF levels during early abstinence. A gender- and age-matched sample of healthy controls was also recruited and underwent measurement of BDNF., Results: BDNF levels were significantly lower in patients with psychotic symptoms than in those without psychotic symptoms (P<0.001). BDNF levels were not found to be correlated with sex, age, age of onset, duration of heroin use, average daily dose of heroin use, frequency of heroin use, SDS scores, BAI scores and BDI scores in the psychotic subsamples (all P>0.05)., Conclusions: Our findings suggest that heroin-dependent patients with psychotic symptoms share some of the neurotrophic insult that characterizes schizophrenia and psychosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)