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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

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.)

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.

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.)

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.

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

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).)

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.

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.)

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.

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.