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Fu Jin,1 Huan-Li Luo,1 Juan Zhou,2 Ya-Nan He,1 Xian-Feng Liu,1 Ming-Song Zhong,1 Han Yang,1 Chao Li,1 Qi-Cheng Li,1 Xia Huang,1 Xiu-Mei Tian,1 Da Qiu,1 Guang-Lei He,1 Li Yin,1 Ying Wang1 1Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing, People’s Republic of China; 2Forensic Identification Center, College of Criminal Investigation, Southwest University of Political Science and Law, Chongqing, People’s Republic of China Abstract: Modern radiotherapy (RT) is being enriched by big digital data and intensive technology. Multimodality image registration, intelligence-guided planning, real-time tracking, image-guided RT (IGRT), and automatic follow-up surveys are the products of the digital era. Enormous digital data are created in the process of treatment, including benefits and risks. Generally, decision making in RT tries to balance these two aspects, which is based on the archival and retrieving of data from various platforms. However, modern risk-based analysis shows that many errors that occur in radiation oncology are due to failures in workflow. These errors can lead to imbalance between benefits and risks. In addition, the exact mechanism and dose–response relationship for radiation-induced malignancy are not well understood. The cancer risk in modern RT workflow continues to be a problem. Therefore, in this review, we develop risk assessments based on our current knowledge of IGRT and provide strategies for cancer risk reduction. Artificial intelligence (AI) such as machine learning is also discussed because big data are transforming RT via AI. Keywords: cancer risk, radiotherapy, workflow, big data

With the release of large-scale genomic resources from ancient and modern populations, advancements in computational biology tools, and the enhancement of data mining capabilities, the field of genomics is undergoing a revolutionary transformation. These advancements and changes have not only significantly deepened our understanding of the complex evolutionary processes of human origins, migration, and admixture but have also unveiled the impact of these processes on human health and disease. They have accelerated research into the genetic basis of human health and disease and provided new avenues for uncovering the evolutionary trajectories recorded in the human genome related to population history and disease genetics. The ancestral recombination graph (ARG) reconstructs the evolutionary relationships between genomic segments by analyzing recombination events and coalescence patterns across different regions of the genome. An ARG provides a record of all coalescence and recombination events since the divergence of the sequences under study and specifies a complete genealogy at each genomic position, which is the ideal data structure for genomic analysis. Here, we review the theoretical foundations and research advancements of the ARG, and explore its translational applications and future prospects across various disciplines, including forensic genomics, population genetics, evolutionary medicine, and medical genomics. Our goal is to promote the application of this technique in genomic research, thereby deepening our understanding of the human genome.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.

Background: Osteoporosis is a prevalent bone metabolic disease in menopause, and long-term medication is accompanied by serious side effects. Estrogen deficiency-mediated hyperactivated osteoclasts is the initiating factor for bone loss, which is regulated by nuclear factor-κB (NF-κB) signaling. Safranal (Saf) is a monoterpene aldehyde produced from Saffron (Crocus sativus L.) and possesses multiple biological properties, particularly the anti-inflammatory property. However, Saf's role in osteoporosis remains unknown., Purpose: This study aims to validate the role of Saf in osteoporosis and explore the potential mechanism., Study Design: The RANKL-exposed mouse BMM (bone marrow monocytes) and the castration-mediated osteoporosis model were applied to explore the effect and mechanism of Saf in vitro and in vivo., Method: The effect of Saf on osteoclast formation and function were assessed by TRAcP staining, bone-resorptive experiment, qPCR, immunoblotting and immunofluorescence, etc. Micro-CT, HE, TRAcP and immunohistochemical staining were performed to estimate the effects of Saf administration on OVX-mediated osteoporosis in mice at imaging and histological levels., Results: Saf concentration-dependently inhibited RANKL-mediated osteoclast differentiation without affecting cellular viability. Meanwhile, Saf-mediated anti-osteolytic capacity and Sirt1 upregulation were also found in ovariectomized mice. Mechanistically, Saf interfered with NF-κB signaling by activating Sirt1 to increase p65 deacetylation and inactivating IKK to decrease IκBα degradation., Conclusion: Our results support the potential application of Saf as a therapeutic agent for osteoporosis., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objectives: To survey the development status and actual needs of virtual autopsy technology in China and to clarify the applicability of forensic virtual autopsy laboratory accreditation., Methods: The questionnaire was set up included three aspects：(1) the current status of virtual autopsy technology development; (2) the accreditation elements such as personnel, equipment, entrustment and acceptance, methods, environmental facilities; (3) the needs and suggestions of practicing institutions. A total of 130 forensic pathology institutions were surveyed by online participation through the Questionnaire Star platform., Results: Among the 130 institutions, 43.08% were familiar with the characteristics of virtual autopsy technology, 35.38% conducted or received training in virtual autopsy, and 70.77% have establishment needs (including maintenance). Relevant elements were suitable for laboratory accreditation., Conclusions: Virtual autopsy identification has gained social recognition. There is a demand for accreditation of forensic virtual autopsy laboratory. After the preliminary assessment, considering the characteristics and current situation of this technology, China National Accreditation Service for Conformity Assessment (CNAS) can first carry out the accreditation pilot of virtual autopsy project at large comprehensive forensic institutions with higher identification capability, and then CNAS can popularize the accreditation in a wide range when the conditions are suitable.

Osteoporosis is a prevalent bone metabolic disease in menopause, and long-term medication is accompanied by serious side effects. Ginger, a food spice and traditional medicine with ancient history, exhibits the potential to alleviate osteoporosis in preclinical experiments, whereas its complex composition leads to ambiguous pharmacological mechanisms. The purpose of this study was to investigate the effect and mechanism of Ced in estrogen-deficient osteoporosis, a sesquiterpene alcohol recently discovered from Ginger with multiple pharmacological properties. RANKL was stimulated BMM (bone marrow macrophages) differentiation into osteoclasts in vitro. And the osteoclast activity and number were assessed by TRAcP and SEM. We found that Ced mitigated RANKL-induced osteoclastogenesis by descending the ROS content and obstructing NFATc1, NF-κB, and MAPK signaling. Also, Ced-mediated anti-osteolytic property was found in ovariectomized mice by Micro-CT scanning and histological staining. Summarily, our works demonstrated the anti-osteoporotic potential of Cedrol in Ginger for the first time, which also offered more pharmacological evidence for Ginger as food or medicine used for bone metabolic disease., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant ( P <0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P <0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P >0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups ( P >0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant ( P <0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

Among the lymphatic system in the human body, the spleen is the most extensive one and has hematopoietic, hemofiltration, blood storage, and immune functions. As a new method of preserving the spleen, laparoscopic partial splenectomy (LPS) has been increasingly applied in clinical practice with people's deeper insights into minimally invasive treatment and the development of technical equipment. Compared with conventional open splenectomy, LPS can preserve normal spleen tissue as much as possible, decrease the occurrence of complications after total splenectomy, and reduce postoperative hospital stay. The bipolar radiofrequency excision hemostatic device used for LPS can solidify the splenic tissue and close the small blood vessels, which reduces the hemorrhage of the spleen cross-section and clears the operative field, thus achieving the ideal effect of "bloodless partial splenectomy". Therefore, under the premise of strictly mastering the indications and fully understanding the vascular anatomy of the spleen, the application of the bipolar radiofrequency excision hemostatic device in LPS is worthy of clinical promotion.

Preeclampsia-eclampsia is a common obstetric critical disease and obstetricians have studied it assiduously for hundreds of years. We have attempted to explore the etiology, pathology, prevention, intervention, and treatment of preeclampsia-eclampsia, but we still have not arrived at a thorough understanding of its causes, and it is difficult to find effective prevention and treatment methods. Although the research process has been fraught with difficulties and frustrations, we are nonetheless gradually gaining a better understanding of the disease. Perhaps, in the near future, we will be able to acquire a full understanding of the disease and find better ways to ensure the health and safety of mothers and fetuses., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Preeclampsia gravely threatens the health of mothers and infants. At present, treatment based on the relevant mechanisms of pathogenesis is still not available, and there is no independent reliable clinical index for early prediction of preeclampsia. According to recent studies, analysis of the cell-free RNA in the peripheral blood of pregnant women has shown that testing certain cell-free RNA levels can help predict in advance the occurrence of preeclampsia before clinical symptoms appear. In this paper, we described the status of research and progress in using maternal cell-free RNA analysis in predicting preeclampsia. In addition, we stated that cell-free RNA in peripheral blood may become a promising, real-time and non-invasive monitoring method that can be used to explore the mechanisms of pathogenesis and pathophysiology of preeclampsia and to identify different subtypes of preeclampsia., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs., Results: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo., Conclusions: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP., (© 2022. The Author(s).)

Objectives: To analyze and predict the striking velocity range of stick blunt instruments in different populations, and to provide basic data for the biomechanical analysis of blunt force injuries in forensic identification., Methods: Based on the Photron FASTCAM SA3 high-speed camera, Photron FASTCAM Viewer 4.0 and SPSS 26.0 software, the tester's maximum striking velocity of stick blunt instruments and related factors were calculated and analyzed, and inputed to the backpropagation (BP) neural network for training. The trained and verified BP neural network was used as the prediction model., Results: A total of 180 cases were tested and 470 pieces of data were measured. The maximum striking velocity range was 11.30-35.99 m/s. Among them, there were 122 female data, the maximum striking velocity range was 11.63-29.14 m/s; there were 348 male data, the maximum striking velocity range was 20.11-35.99 m/s. The maximum striking velocity of stick blunt instruments increased with the increase of weight and height, but there was no obvious increase trend in the male group; the maximum striking velocity decreased with age, but there was no obvious downward trend in the female group. The maximum striking velocity of stick blunt instruments has no significant correlation with the material and strike posture. The root mean square error (RMSE), the mean absolute error (MAE) and the coefficient of determination ( R 2 ) of the prediction results by using BP neural network were 2.16, 1.63 and 0.92, respectively., Conclusions: The prediction model of BP neural network can meet the demand of predicting the maximum striking velocity of different populations.

Objective: The study aimed to understand multimorbidity among adults in a high-tech city in southern coastal China that has undergone rapid economic development and to investigate its relationship with lifestyle status., Methods: A population-based survey was conducted among 24 community centers in the Nanshan District of Shenzhen from February to December of 2018. Participants were recruited using a stratified random sampling approach. A self-administered questionnaire on typical chronic diseases, lifestyle factors, body composition, and social demographics was used to collect data. Multimorbidity was defined as two or more chronic diseases coexisting in a single person. An algorithm on body mass index, physical activity, drinking, smoking, and sleep quality was used to calculate lifestyle scores (0-9), with higher scores predicting a healthier lifestyle., Results: A total of 2,905 participants were included in the analysis, with men accounting for 52.4%, and single for 25%. The prevalence of multimorbidity was 4.8%, and the mean lifestyle score was 4.79 ± 1.55. People who were old, retired, married, and had less education were more likely to have multimorbidity (all P < .05). A higher prevalence of multimorbidity was found among those who were obese, less engaged in physical activity, consumed more alcohol, and had poorer sleep quality (all p < .05). After adjusting for age, employment, education, and marital status, one unit increase in lifestyle score was associated with 0.74 times lower to have multimorbidity (OR: 0.74; 95% CI: 0.63-0.87, p < .05)., Conclusion: The prevalence of multimorbidity was relatively low in economically developed Shenzhen. Keeping a healthy lifestyle was related to the lower possibility of suffering from multiple chronic diseases., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objectives: To reconstruct the cases of acceleration craniocerebral injury caused by blunt in forensic cases by finite element method (FEM), and to study the biomechanical mechanism and quantitative evaluation method of blunt craniocerebral injury., Methods: Based on the established and validated finite element head model of Chinese people, the finite element model of common injury tool was established with reference to practical cases in the forensic identification, and the blunt craniocerebral injury cases were reconstructed by simulation software. The cases were evaluated quantitatively by analyzing the biomechanical parameters such as intracranial pressure, von Mises stress and the maximum principal strain of brain tissue., Results: In case 1, when the left temporal parietal was hit with a round wooden stick for the first time, the maximum intracranial pressure was 359 kPa; the maximum von Mises stress of brain tissue was 3.03 kPa at the left temporal parietal; the maximum principal strain of brain tissue was 0.016 at the left temporal parietal. When the right temporal was hit with a square wooden stick for the second time, the maximum intracranial pressure was 890 kPa; the maximum von Mises stress of brain tissue was 14.79 kPa at the bottom of right temporal lobe; the maximum principal strain of brain tissue was 0.103 at the bottom of the right temporal lobe. The linear fractures occurred at the right temporal parietal skull and the right middle cranial fossa. In case 2, when the forehead and left temporal parietal were hit with a round wooden stick, the maximum intracranial pressure was 370 kPa and 1 241 kPa respectively, the maximum von Mises stress of brain tissue was 3.66 kPa and 26.73 kPa respectively at the frontal lobe and left temporal parietal lobe, and the maximum principal strain of brain tissue was 0.021 and 0.116 respectively at the frontal lobe and left temporal parietal lobe. The linear fracture occurred at the left posterior skull of the coronary suture. The damage evaluation indicators of the simulation results of the two cases exceeded their damage threshold, and the predicted craniocerebral injury sites and fractures were basically consistent with the results of the autopsy., Conclusions: The FEM can quantitatively evaluate the degree of blunt craniocerebral injury. The FEM combined with traditional method will become a powerful tool in forensic craniocerebral injury identification and will also become an effective means to realize the visualization of forensic evidence in court.

Background: Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1β/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown., Purpose: This study aims to validate the role of Ory in IVDD and explore the potential mechanism., Study Design: Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory., Method: The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1β-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels., Results: Ory treatment inhibited IL-1β-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1β/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development., Conclusion: Our results support the potential application of Ory as a therapeutic compound for IVDD., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Sleep disorder is a commonly reported complication in patients who have undergone a hysterectomy, which increases perioperative complications and delays patient recovery. Several pharmacological and non-pharmacological approaches have been employed to improve the quality of sleep of patients during the postoperative period, but these strategies have certain limitations. Intradermal needle therapy is now among the most common treatments for insomnia in traditional Chinese medicine (TCM). The present study was developed to explore the effects of intradermal needle therapy (as an adjunct to physiotherapy-based treatments for postoperative sleep impairment) on the postoperative sleep quality of patients who have undergone a laparoscopic hysterectomy., Methods: This is a prospective, single-center, single-blind, randomized controlled trial. In total, 80 eligible patients will be randomly allocated to the control and experimental groups at a 1:1 ratio. Random numbers and grouping schemes will be generated using the SPSS 25.0 software package. Following the completion of the laparoscopic hysterectomy procedure, the patients will be returned to the medical ward and undergo authentic or sham intradermal needle therapy as appropriate. For patients in the experimental group, following sterilization, intradermal needles will be inserted into the bilaterally "Shenmen" (HT36) and "Sanyinjiao" (SP6) acupoints; the needles will be replaced after 24 h. False intradermal needles that exhibit similar surface characteristics but lack needles will be employed in the control group. Patients will undergo a single 3-day treatment course. The primary outcome is the Pittsburgh Sleep Quality Index. The secondary outcomes are the 10-Item Short-Form Identity-Consequence Fatigue Scale, the Hospital Anxiety and Depression Scale-Anxiety, and postoperative pain scores, which will be rated using a visual analog scale. Time to postoperative defecation and the duration of hospitalization will also be recorded., Discussion: The present study seeks to examine the efficacy of the intradermal needle as a therapeutic tool for improving the sleep quality of patients after surgery who have undergone a laparoscopic hysterectomy to provide a foundation for future large-scale clinical studies., Trial Registration: Chinese Clinical Trial Registry (identifier: ChiCTR2200056890)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2980/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Heat stroke is the outcome of excessive heat stress, which results in core temperatures exceeding 40°C accompanied by a series of complications. The brain is particularly vulnerable to damage from heat stress. In our previous studies, both activated microglia and increased neuronal autophagy were found in the cortices of mice with heat stroke. However, whether activated microglia can accelerate neuronal autophagy under heat stress conditions is still unknown. In this study, we aimed to investigate the underlying mechanism that caused neuronal autophagy upregulation in heat stroke from the perspective of exosome-mediated intercellular communication., Methods: In this study, BV2 and N2a cells were used instead of microglia and neurons, respectively. Exosomes were extracted from BV2 culture supernatants by ultracentrifugation and then characterized via transmission electron microscopy, nanoparticle tracking analysis and Western blotting. N2a cells pretreated with/without miR-155 inhibitor were cocultured with microglial exosomes that were treated with/without heat stress or miR-155 overexpression and subsequently subjected to heat stress treatment. Autophagy in N2a cells was assessed by detecting autophagosomes and autophagy-related proteins through transmission electron microscopy, immunofluorescence, and Western blotting. The expression of miR-155 in BV2 and BV2 exosomes and N2a cells was measured using real-time reverse transcription polymerase chain reaction. Target binding analysis was verified via a dual-luciferase reporter assay., Results: N2a autophagy moderately increased in response to heat stress and accelerated by BV2 cells through transferring exosomes to neurons. Furthermore, we found that neuronal autophagy was positively correlated with the content of miR-155 in microglial exosomes. Inhibition of miR-155 partly abolished autophagy in N2a cells, which was increased by coculture with miR-155-upregulated exosomes. Mechanistic analysis confirmed that Rheb is a functional target of miR-155 and that microglial exosomal miR-155 accelerated heat stress-induced neuronal autophagy mainly by regulating the Rheb-mTOR signaling pathway., Conclusion: Increased miR-155 in microglial exosomes after heat stroke can induce neuronal autophagy via their transfer into neurons. miR-155 exerted these effects by targeting Rheb, thus inhibiting the activity of mTOR signaling. Therefore, miR-155 could be a promising target for interventions of neuronal autophagy after heat stroke., 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 © 2022 Li, Luo, Luo, He, Shen, Yu, Wang, Tan, Liu and Yang.)

Plasma D-dimer, a special cross-linked fibrin derivative, is produced when fibrin is degraded by plasminase. During pregnancy, D-dimer increases along with the increase of gestational age, and the reference value of plasma D-dimer (≤0.5 mg/L) traditionally used for the screening of venous thrombosis in the normal population is not applicable to the pregnant population. Due to the lack of uniform D-dimer detection methods or measurement units, there is currently no unified D-dimer reference values for pregnancy or puerperium. Each region or laboratory should establish its own pregnancy D-dimer reference value for different gestational weeks through blood coagulation function testing of large numbers of samples of different gestational periods. More and more studies have been conducted to investigate the association between D-dimer and venous thromboembolism (VTE) during pregnancy, gestational hypertensive disorders (GHD) and pregnancy outcome. We reviewed, herein, the generation and measurement of D-dimer, the reference values of D-dimer during normal pregnancy, and the association between D-dimer and some pathological pregnancies, intending to help clinicians develop a more thorough understanding of D-dimer during pregnancy., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed malignancy and the third leading cause of cancer-related deaths worldwide. A 58-year-old man visited his local hospital due to abdominal discomfort and was diagnosed with lung metastasis. After admission to our hospital in April 2020, he received two cycles of transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC-Folfox), sorafenib, and camrelizumab every 3 weeks. Due to the end of HAIC treatment, he underwent drug-eluting transcatheter arterial chemoembolization (dTACE) once, sorafenib, and camrelizumab. However, because of worsening liver function, we interrupted TACE and only gave sorafenib and camrelizumab in August 2020. Although he received systemic therapy, the tumors still rapidly progressed and we considered the possibility of tumor resistance. Subsequently, regorafenib was given. In September, the patient underwent conventional TACE (cTACE) once, regorafenib, and camrelizumab. After half a year of comprehensive treatment, the treatment effect was not satisfactory, and he returned to the local hospital to received regorafenib every day and camrelizumab once every 3 weeks. The patient found that the tumor and lung metastasis had shrunk significantly after 1 year of the initial diagnosis, then he was admitted to our hospital and received surgery treatment, and now he has survived disease-free for 6 months., 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 © 2022 Xie, Liu, Guo, Wu, He, Cai, Pan and Fu.)

Microglial CX3C chemokine receptor 1 (CX3CR1) has been implicated in numerous cellular mechanisms, including signalling pathways that regulate brain homoeostasis and adult hippocampal neurogenesis. Specific environmental conditions can impair hippocampal neurogenesis-related cognition, learning and memory. However, the role of CX3CR1 in the neurogenic alterations resulting from the cross-tolerance protection conferred by heat acclimation (HA) against the effects of electromagnetic field (EMF) exposure is less well understood. Here, we investigated the role of microglial CX3CR1 signalling in adult hippocampal neurogenesis induced by HA in EMF-exposed mice. We found that EMF exposure significantly decreased the number of proliferating and differentiating cells in the dentate gyrus (DG) of the hippocampus, resulting in a reduced neurogenesis rate. Moreover, alterations in the phenotypes of activated microglia and decreased expression levels of CX3CR1, but not sirtuin 1 (SIRT1), were observed in the brains of EMF-exposed mice. Remarkably, HA treatment improved microglial phenotypes, restored the expression of CX3CR1, and ameliorated the decrease in the adult hippocampal neurogenesis rate following EMF exposure. Moreover, pharmacological inhibition of CX3CR1 and SIRT1 failed to restore CX3CR1 expression and ameliorate hippocampal neurogenesis impairment following HA plus EMF stimulation. These results indicate that microglial CX3CR1 is involved in the cross-tolerance protective effect of HA on adult hippocampal neurogenesis upon EMF exposure., (Copyright © 2021. Published by Elsevier Inc.)

Background: The glycocalyx plays an important physiological role and may be damaged during cardiopulmonary bypass. Sevoflurane can protect the glycocalyx; however, its relevance in a clinical setting is unknown., Objective: Glycocalyx degradation during cardiopulmonary bypass in patients was investigated. On the basis of the available experimental data, we hypothesised that sevoflurane-based anaesthesia would confer additional protection against cardiopulmonary bypass-induced glycocalyx damage., Design: Randomised controlled study., Setting: Clinical study at The First Affiliated Hospital of Wenzhou Medical University between June 2018 and March 2019., Patients: Fifty-one patients., Interventions: After intubation and mechanical ventilation, patients undergoing elective heart valve surgery were maintained under general anaesthesia with either propofol or sevoflurane during surgery., Main Outcome Measures: Glycocalyx markers (such as syndecan-1, heparan sulphate and hyaluronan), sheddases responsible for the degradation of the endothelial glycocalyx (such as matrix metalloproteinase-9 and cathepsin-B), urine albumin-to-creatinine ratio and levels of lactic acid and myocardial enzymes were all measured. Postoperative mechanical ventilation time and length of stay in the cardiac care unit and hospital were also measured. Morbidity and mortality after 30 days and 1 year were evaluated., Results: The vascular endothelial glycocalyx was damaged during cardiopulmonary bypass. The glycocalyx damage in the sevoflurane group was less extensive than that in the propofol group. The urine albumin-to-creatinine ratio increased in both groups but was lower in the sevoflurane group. Enzymes including matrix metalloproteinase-9 and cathepsin-B were positively correlated with glycocalyx marker concentrations. After operation, the sevoflurane group showed lower levels of lactic acid and myocardial enzyme, as well as shorter duration of postoperative mechanical ventilation than the propofol group., Conclusion: Sevoflurane can decrease glycocalyx degradation in patients undergoing heart valve surgery under cardiopulmonary bypass., Trial Registration: Chinese Clinical Trial Registry, chictr.org.cn, identifier: ChiCTR1800016367., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Autophagy and the ubiquitin proteasome system (UPS) are two major protein degradation pathways involved in brain ischemia. Autophagy can compensate for UPS impairment‑induced cellular dysfunction. HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1 (Huwe1), an E3 ubiquitin ligase, serves critical roles in nervous system plasticity, regeneration and disease. However, the role of Huwe1 in autophagy in brain ischemia/reperfusion (I/R) injury remains unknown. The aim of the present study was to investigate the crosstalk between autophagy and the UPS in brain ischemia. The present study established an oxygen‑glucose deprivation and reperfusion (OGD/R) model in rat primary cortex neurons in vitro. Lentiviral interference was used to silence the expression of Huwe1. An autophagy promoter (rapamycin), an autophagy inhibitor (wortmannin) and a JNK pathway inhibitor (SP600125) were also used in the current study. Cellular autophagy‑related proteins, including Beclin‑1, autophagy related (ATG) 7, ATG5, ATG3 and microtubule associated protein 1 light chain 3 α, and apoptosis‑related proteins, such as P53, cleaved caspase 3, Bax and Bcl2, were detected via western blotting and immunocytochemistry. Neuronal apoptosis was evaluated using a TUNEL assay. The results demonstrated that silencing Huwe1 increased the expression levels of autophagy‑related proteins at 24 h after OGD/R. Treatment with a JNK inhibitor or cotreatment with Huwe1 shRNA significantly increased autophagy. Rapamycin increased apoptosis under OGD/R conditions. However, treatment with Huwe1 shRNA decreased the number of TUNEL‑positive cells at 24 h after OGD/R. Cotreatment with Huwe1 shRNA and wortmannin alleviated neuronal apoptosis under OGD/R conditions compared with cotreatment with DMSO. Collectively, the present results suggested that silencing Huwe1 was accompanied by a compensatory induction of autophagy under OGD/R conditions. Furthermore, the JNK pathway may be a key mediator of the interaction between Huwe1 and autophagy in response to UPS impairment.

Abstract: MicroRNA （miRNA） belongs to a class of endogenous non-coding small RNA molecules with a length of 18-24 nucleotides. The expression of miRNA is highly conservative, has time sequence and is highly tissue-specific. MiRNA could not be easily degraded by ribonuclease, and is resistant to changes in environmental factors such as temperature and pH value. Moreover, miRNA can even be detected in corrupt tissue. As a result, miRNA has broad application prospects in many fields of forensic medicine such as source identification of body fluid and estimation of cause of death. This article briefly summarizes the application of miRNA in forensic practice, such as body fluid identification, determination of postmortem interval and cause of death analysis., 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.)

Objective: To investigate the relationship between platelet-activating factor acetylhydrolase (PAF-AH) gene (PLA2G7) G994T (V279F, rs76863441) and R92H (rs1805017) polymorphisms and risk of preeclampsia (PE) in Chinese women., Study Design: This is a case-control study of 273 patients with PE and 530 healthy pregnant women., Main Outcome Measures: PLA2G7 genotypes were determined by polymerase chain reaction amplification and restriction analysis. Plasma PAF-AH, apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH), total high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH), apoE-containing HDL-associated PAF-AH (apoE-H-PAF-AH) activities, and clinical, metabolic, and oxidative stress parameters were also analyzed., Results: The frequencies of the GT + TT genotype (14.7 versus 9.2%, P = 0.019) and T allele (7.5% versus 4.6%) of PLA2G7 G994T polymorphism were significantly higher in patients with PE than in the control subjects. The GT + TT genotypes remained a significant predictor for PE in a regression model including age, body mass index (BMI), plasma PAF-AH, H-PAF-AH, apoE-H-PAF-AH and apoB-PAF-AH activities as covariates (odds ratio (OR) = 4.926, 95% confidence interval (CI): 1.707-14.219, P = 0.003). The ratio of apoB-PAF-AH to H-PAF-AH activities was significantly higher, while serum triglyceride levels were lower in patients with the GT genotype compared with patients with the GG genotype (P < 0.05). No significant differences were observed in the frequencies of the R92H genotype and allele between the PE and control groups., Conclusions: The PLA2G7 G994T, but not R92H, genetic polymorphism is associated with the risk of PE in Chinese women., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Abstract: The number of death from insulin overdose, including accidental poisoning, suicide and homicide, is increasing these years. The forensic diagnosis of death from insulin overdose is a tough task. Glucose is the main energy source of the brain. Therefore, hypoglycemic brain damage is considered to be the main reason of death from insulin overdose. Recently, research of hypoglycemic brain damage caused by insulin overdose is gradually being paid attention in the field of forensic medicine. This paper summarizes the neuropathologic changes, pathophysiologic process and potential neural molecular markers of hypoglycemic brain damage caused by insulin overdose in terms of forensic neuropathology, providing reference for the research and practice in forensic medicine related fields., 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.)

The function of triggering receptor expressed on myeloid cells-2 (TREM2) has been described within microglia with a beneficial activated phenotype. However, the role of TREM2 underlying microglial phenotypic alterations in the cross-tolerance protection of heat acclimation (HA) against the inflammatory stimuli electromagnetic field (EMF) exposure is less well known. Here, we investigated the TREM2-related signaling mechanism induced by HA in EMF-stimulated N9 microglial cells (N9 cells). We found that EMF exposure significantly increased the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α, IL-1β, and IL-6), and the expression of M1 markers (CD11b and CD86); meanwhile, decreased the levels of anti-inflammatory cytokines (IL-4 and IL-10) and the expression of M2 markers (CD206 and Arg1) in N9 cells. Clearly, HA treatment decreased the secretion of TNF-α, IL-1β and IL-6 and the expression of CD11b and CD86, and enhanced the production of IL-4 and IL-10 and the expression of CD206 and Arg1. Moreover, TREM2 esiRNA and selective inhibitor of PI3K clearly decreased anti-inflammatory cytokines production, M2 markers expression, and phosphorylation of PI3K and Akt following HA plus EMF stimulation. These results indicate that TREM2 and PI3K-Akt pathway are involved in the cross-tolerance protective effect of HA in microglial polarization towards the EMF exposure. This finding inspires future studies that aim to explore the non-drug approaches underlying EMF stimulation and other central nervous system (CNS) inflammatory diseases., (Copyright © 2020 He, Luo, Shen, Wang, Li, Luo, Yang, Tan, Wang, Gao and Yang.)

Objective: MicroRNA-361-5p (miR-361-5p) has been found to be involved in the pathogenesis of several human cancers. However, the specific role of miR-361-5p is still unclear in hepatocellular carcinoma (HCC). Therefore, this study was designed to elucidate the function of miR-361-5p in HCC., Patients and Methods: The expression levels of miR-361-5p and Wilms' tumor-1 (WT1) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Moreover, the function of miR-361-5p was examined through Cell Counting Kit-8 (CCK-8) and transwell assays. The protein expressions were examined via Western blot analysis and immunocytochemical assay. Tumor growth of HCC was observed via xenograft tumor formation assay. The relationship between miR-361-5p and WT1 was verified by the Dual-Luciferase assay., Results: Downregulation of miR-361-5p was identified in HCC, which predicted a worse prognosis in HCC patients. Furthermore, it was found that miR-361-5p suppressed cell proliferation, migration, and invasion in HCC by inhibiting WT1. MiR-361-5p also inhibited tumor growth of HCC. Besides that, miR-361-5p suppressed EMT and negatively activated the WNT/β-cadherin pathway in HCC., Conclusions: MiR-361-5p suppressed tumorigenesis of HCC by targeting WT1 and inactivating the WNT/β-cadherin pathway.

Background and Objectives: The feasibility and safety of single-port laparoscopic surgery for left lateral liver lobectomy are largely unknown. This study is aimed at comparing the effectiveness and safety between single-port laparoscopic (SPL) and conventional multiport laparoscopic (CL) surgeries for hepatic left lateral sectionectomy., Methods: A total of 65 patients receiving laparoscopic hepatic left lateral sectionectomy between January 2008 and July 2015 were included and divided into the SPL group ( n = 40) and the CL group ( n = 25)., Results: There was no significant difference in the operative time, estimated intraoperative blood loss, length of hospital stay, and incidences of postoperative complications (biliary leakage, hemorrhage, and contusion at incision) between groups (all P > 0.05). However, the SPL group had a significantly lower VAS pain score (at 24 h but not 7 days postoperation) and higher cosmetic satisfaction scores (at both 2 months and 6 months postoperation) than the CL group (all P < 0.01). Moreover, multivariate linear regression analysis further confirmed the superior pain score and cosmetic outcome in the SPL group., Conclusions: Single-port laparoscopic hepatic left lateral sectionectomy is a safe and feasible treatment for patients with lesions in the left hepatic lobe. Patients with benign lesions in the left hepatic lobe are more suitable to receive single-port laparoscopic hepatic left lateral sectionectomy than those with malignancies.

Placental hypoxia serves a role in the early stages of normal pregnancy and is involved in the pathophysiology of preeclampsia. Previously, it was suggested that p57kinase inhibitory protein (KIP)2 regulates the cell cycle during embryogenesis and apoptosis. Recent evidence has indicated that p57KIP2 is increased in preeclamptic placentas and absence of p57KIP2 induces preeclampsia‑type symptoms in rats. However, effects of p57KIP2 on apoptosis under hypoxic conditions remain to be elucidated. In the present study, HTR‑8/SVneo trophoblasts were cultured under hypoxic conditions (2% O2). Knockdown using small interfering (si)RNA and overexpression of p57KIP2 were utilized to explore the biological function of p57KIP2 in apoptosis and cell function in vitro. Furthermore, expression of p57KIP2 and apoptosis were evaluated by western blotting, flow cytometry and TUNEL assays, and the response of trophoblasts to hypoxia and the role of p57KIP2 in trophoblast migration and invasion was assessed. The role of p57KIP2 in the JNK signaling pathway in HTR‑8/SVneo trophoblasts was further studies. In vitro, protein expression of p57KIP2 was increased in HTR‑8/SVneo cells exposed to 2% O2. Exogenous p57KIP2 overexpression significantly decreased the expression of pro‑apoptosis proteins, including p53, Bax and cleaved caspase3, under hypoxic conditions for 24 h. In addition, knockdown of p57KIP2 increased the response to apoptosis following hypoxia for 24 h. The present study revealed that overexpression of p57KIP2 decreased the levels of phosphorylated‑JNK. JNK inhibitor treatment combined with the overexpression of p57KIP2 significantly decreased the levels of apoptosis and increased cell invasion and migration. Taken together, p57KIP2 knockdown significantly increased apoptosis in HTR‑8/SVneo cells exposed to 2% O2, whereas overexpression of p57KIP2 had opposite effects, mediated by the JNK/stress activated protein kinase (SAPK) signaling pathway. The results indicated that hypoxia‑induced expression of p57KIP2 promoted trophoblast migration and invasion by mediating the JNK/SAPK signaling pathway, which is crucial during placentation. These results may provide a novel molecular mechanism to understand the involvement of p57KIP2 in the pathogenesis of preeclampsia.

The abnormal expression of long noncoding RNAs (lncRNAs) is associated with human carcinoma. The present study aimed to investigate the mechanisms underlying the function of lncRNA AK002107 in the progression of hepatocellular carcinoma (HCC). The differential expression of lncRNAs between HCC and paired nontumor tissues was identified using microarrays, and the correlation between the expression of lncRNA AK002107 and the clinical prognosis of HCC was analyzed. We investigated the role of lncRNA AK002107 in HCC tumor biology in vitro using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, and Matrigel invasion assays and in vivo by assessing the growth of xenografted HCC tumors. The potential microRNAs that interact with lncRNA AK002107 were identified using online tools and were verified using PCR and luciferase reporter assay. The levels of TGFBR1, E-cadherin, and vimentin were determined using western blot assays. We then further investigated the correlation between expression of lncRNA AK002107 with miR-140-5p and TGFBR1 expression in HCC tissues. The expression of lncRNA AK002107 is frequently upregulated in HCC samples and cell lines. Patients with HCC who have elevated lncRNA AK002107 expression exhibit poorer overall survival and disease-free survival. Silencing lncRNA AK002107 expression significantly inhibited HCC cell proliferation, colony formation, and invasion both in vitro and in vivo. Furthermore, lncRNA AK002107 directly binds to miR-140-5p and significantly inhibits miR-140-5p expression. The functions of lncRNA AK002107 in cell growth and tumor invasion are mediated via miR-140-5p. lncRNA AK002107 upregulated TGFBR1 expression and then induced epithelial-mesenchymal transition (EMT) by inhibiting miR-140-5p expression. The expression of lncRNA AK002107 inversely correlated with miR-140-5p expression and positively correlated with TGFBR1 expression in HCC tissues. In summary, lncRNA AK002107 functions as an oncogene in tumors by inhibiting miR-140-5p, targeting TGFBR1, and then inducing EMT. The lncRNA AK002107/miR-140-5p/TGFBR1/EMT regulatory network may be a valuable target for the development of novel diagnostic and treatment methods for HCC., (© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Objective. To evaluate the efficacy and safety of traditional Chinese medicine in preventing kidney damage caused by Henoch-Schonlein Purpura (HSP) in Children by meta-analysis. Methods. We systematically searched the main Chinese and English electronic databases and collected randomized controlled trials of Chinese herbs in children with HSP until July 2018. Then we used the bias risk assessment tool in Cochrane Handbook 5. 1. 0 to complete the risk assessment of the included studies. We utilized STATA12.0 and RevMan 5.3 for meta-analysis and GRADE pro. for quality evaluation of evidence. Result. (1) Meta-analysis: data from 39 studies, representing 3643 individuals, were included in the analysis. Thirty-seven studies were treated with traditional Chinese medicine for clearing away heat and cooling blood, which were combined. On this basis, subgroup analysis was conducted according to the bias risk of the original study. It showed that Chinese herbs can significantly improve the treatment effect (OR: 4.31, 95% CI [3.34, 5.57], P < 0.01) and reduce the risk of renal damage (RR: 0.36; 95% CI [0.21, 0.61], P < 0.01) and the risk of recurrence (RR: 0.43, 95% CI [0.34, 0.54], P <0.01). (2) Side effect: a total of 7 studies described adverse reactions, and 12 of 319 patients in therapy group had adverse events and 20 of 263 patients in control group. (3) Publication bias: the bias risk Egger's test for the incidence of kidney injury was P =0.572, the relapse rate Egger's test was P =0.175, the efficiency was combined with the low-risk original study, and the bias risk Egger's test was P =0.175. There was not any significant publication bias based on the funnel plot and Egger's test. (4) GRADE evaluation: GRADE evaluation showed that the quality of evidence in the risk of renal damage and recurrence rate was moderate. Conclusion. Chinese medicine treatment can prevent the occurrence of renal damage in children with HSP and can reduce the recurrence rate, the incidence of adverse reactions, and the effect in terms of efficiency. However, the quality of the included studies in the meta-analysis and the quality of the evidence of outcomes were not high; the clinical use of the evidence needs to be cautious.

Background: The neuroinflammatory responses of microglial cells play an important role in the process of brain dysfunction caused by heat stroke. MicroRNAs are reportedly involved in a complex signaling network and have been identified as neuroinflammatory regulators. In this study, we determined the biological roles of microRNA-155 in the inflammatory responses in heat-stressed microglia and explored the underlying mechanisms. Methods: MicroRNA-155 mimic and inhibitor were used to separately upregulate or downregulate microRNA-155 expression. The activation state of BV-2 microglial cells (BV-2 cells) was assessed via immunoreactions using the microglial marker CD11b and CD68. Levels of induced interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured using real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assays (ELISAs). The activation of nuclear factor kappa B (NF-κB) signaling proteins was evaluated by Western blotting for inhibitory kappa B alpha (IκBα) and NF-κB p65 phosphorylation and indirect immunofluorescence analysis using a p65 phosphorylation antibody. A luciferase reporter assay was used to verify liver X receptor α (LXRα) as a target gene of microRNA-155. Results: Heat stress significantly induced IL-1β, IL-6, and TNF-α release and increased the expression of CD11b and CD68. In addition, IκBα and NF-κB p65 phosphorylation were dramatically increased by heat stress, and microRNA-155 expression was also elevated. High expression of microRNA-155 in heat-stressed microglial cells was inversely correlated with LXRα expression. We then determined the role of microRNA-155 in the heat stress-induced inflammatory responses. The results revealed that by targeting LXRα, microRNA-155 enhanced NF-κB signaling activation and facilitated immune inflammation in heat stress-treated BV-2 cells. Conclusion: MicroRNA-155 promotes heat stress-induced inflammatory responses in microglia. The underlying mechanisms may include facilitating inflammatory factors expression by increasing NF-κB pathway activation via targeting LXRα.

Mixed stains is the common biological sample in sexual crime cases. Its analysis and DNA profiles interpretation are one of the difficulties in forensic examination. The current genetic marking of mixed stain detection mainly rely on capillary electrophoresis （CE） separation technology, and the analysis methods of the results are mainly inclusion rate and likelihood methods. Because CE has limited resolution and is not able to exploit the efficacy of each genetic marker, its ability to split mixed stain is limited. In recent years, the emerging massively parallel sequencing （MPS） technique not only can obtain the base sequence information of genetic markers, but also is capable of detecting multiple genetic markers simultaneously, and thus derives new analytical methods, bringing new opportunities for forensic detection and analysis of mixed stain. This paper intends to review the application prospects of conventional mixed stain analyses and MPS technique, therefore to provide references for later research and practice., 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.)

Objectives: To investigate the value of optical coherence tomography （OCT） in the diagnosis of coronary atherosclerosis and myocardial infarction in forensic identification., Methods: OCT and hematoxylin-eosin （HE） examination were performed to examine the pathological samples of coronary artery and myocardial infarction in 5 cases of sudden coronary death. The morphological and local measurement indexes were compared., Results: In the OCT images, the layers of coronary artery could be distinguishably featured, and the atheroma plaques had a good morphological correspondence with HE slices. The normal myocardia in the OCT image showed weak light signals with high absorbance, while the fiber scar tissues in the myocardial infarction areas showed strong light signals with low absorbance. There were no significant differences on the fibrous cap thickness in coronary atherosclerotic plaques or intima-media thickness between the OCT images and the HE slices （ P >0.05）. In the OCT images, the optical densities of the old myocardial infarction areas （1 226.24±622.66） and those of normal myocardia （3 707.90±962.98） were significantly different （ P <0.05）., Conclusions: The OCT image has a good morphological consistency with HE slice, thus is expected to be the primary screening method for the forensic pathology examination of coronary artery atherosclerosis and myocardial infarction, which can help to improve the diagnostic accuracy., 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.)

Although microglial reaction to heat shock is considered to be protective, heat shock is still a potential hazard caused by high temperatures. Recent studies indicate that the inhibition of the 90-kDa heat shock protein (HSP90) increasing the protective heat shock response and suppressing inflammatory signalling pathways in several diseases. Nevertheless, the effects of heat shock on microglial pro-inflammatory responses are not completely identical. Here, we aim to investigate the effect of the HSP90 inhibitor ganetespib on microglial pro-inflammatory responses following heat shock. HSP90 isoforms were determined by transfecting N9 microglial cells (N9 cells) with enzymatically prepared siRNA (esiRNAs). We found that heat shock significantly increased the secretion of tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO), and the phosphorylation of extracellular signal-regulated kinase (ERK), Janus-activated kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκB-α) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (p65 NF-κB) in N9 cells. These increases, except for phospho-p65, were attenuated efficiently in a dose-dependent manner by ganetespib pretreatment. Furthermore, the suppression of heat shock-evoked cytokines and NO production, and the phosphorylation of ERK, JAK2 and STAT3 in cytosols and/or nuclei were also observed by administering esiRNA HSP90β, but not HSP90α, in heat shock-treated N9 cells. Taken together, our findings demonstrate that the HSP90 inhibitor ganetespib blocks pro-inflammatory responses in heat shock-treated N9 cells via a signalling mechanism involving HSP90β and STAT3., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To investigate the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in pregnant women in urban areas of China. Methods: The study was a national cross-sectional survey conducted from September 19th, 2016 to November 20th, 2016. According to the classification of the National Bureau of Statistics, all survey sites were set up in 6 regions of the country.Pregnant women were continuously selected using multistage stratified sampling. A total of 12 403 pregnant women were collected and examined for serum ferritin and hemoglobin levels. Results: The median serum ferritin level during pregnancy was 20.60 μg/L (11.78-36.98 μg/L) , the hemoglobin level was (118±12) g/L. With the progress of pregnancy, the levels of serum ferritin and hemoglobin decreased gradually. The median serum ferritin levels in the first, second trimester and third trimester were 54.30 μg/L (34.48-94.01 μg/L) , 28.60 μg/L (16.40-50.52 μg/L) , and 16.70 μg/L (10.20-27.00 μg/L) respectively ( P< 0.01) . The mean hemoglobin levels were (127±10) g/L, (119±11) g/L and (117±11) g/L respectively ( P< 0.01) . The prevalence of ID in urban pregnant women was 48.16% (5 973/12 403) , and IDA prevalence was 13.87% (1 720/12 403) . The prevalence of IDA in the first, second trimester and third trimester were 1.96% (20/1 019) , 8.40% (293/3 487) and 17.82% (1 407/7 897) ,respectively ( P< 0.01) . The prevalence of standardized ID and IDA were significantly different in various regions of China ( P< 0.01) . The standardized prevalence of ID were relatively higher in East China and Northeast China, 57.37% and 53.41% respectively, while it was the lowest in Southwest China, 30.51%. The standardized prevalence of IDA in South Central, Northwest, and East China were relatively high, 21.30%, 16.97% and 17.53% respectively, and the standardized prevalence of IDA in Southwest China was the lowest, 5.44%, the differents in various regions were significant (all P< 0.01) . Conclusion: The current phenomenon of ID and IDA in pregnant women is still very common, and nutrition and health care during pregnancy should be strengthened.

The VAD (vincristine-doxorubicin-dexamethasone) regimen has been used for decades to treat multiple myeloma (MM). Based on reports that vascular endothelial growth factor- (VEGF-) mediated angiogenesis is critical for MM pathogenesis, the antiangiogenic compound thalidomide has been added to VAD (T-VAD). However, it remains unclear whether T-VAD is more efficacious than VAD for serum VEGF reduction or if the difference influences clinical outcome. Pubmed, Cochrane library, China Biomedical Literature (CBM) database, China National Knowledge Infrastructure (CNKI) database, Vip database, and Wanfang database were searched for relevant studies published up to June 2017. RevMan5.2 was used for methodological quality evaluation and data extraction. Thirteen trials (five randomized, seven nonrandomized, and one historically controlled) involving 815 cases were included. Serum VEGF was significantly higher in MM cases than non-MM controls (MD=353.01, [95%CI 187.52-518.51], P<0.01), and the overall efficacy of T-VAD was higher than that of VAD (RR=1.36, [1.21-1.53], P <0.01). Further, T-VAD reduced VEGF to a greater extent than VAD does ([MD=-49.85, [-66.28- -33.42], P<0.01). The T-VAD regimen also reduced VEGF to a greater extent in newly diagnosed MM patients than it did in recurrent patients ([MD=-120.20, [-164.60--39.80], P<0.01). There was no significant difference in VEGF between T-VAD patients (2 courses) and nontumor controls (MD=175.94, [-26.08-377.95], P=0.09). Greater serum VEGF reduction may be responsible for the superior efficacy of T-VAD compared to VAD.

Background: The effect of maternal weights on the risk of iron deficiency anemia (IDA) during pregnancy remains unclear. The study aimed to investigate the association between maternal weight indicators and IDA during pregnancy., Methods: We conducted a cohort study to examine the association between maternal weight indicators, including prepregnancy body mass index and the rate of gestational weight gain (GWG), and the risk of IDA among Chinese pregnant women. Data about new-onset IDA at different trimesters from a national cross-sectional survey were collected; information regarding baseline variables and rate of GWG from women participating in the survey were retrospectively collected. Tested IDA and reported IDA were documented. Multilevel logistic regression to examine the association between maternal weight indicators and the risk of IDA after adjusting for potential confounders was conducted., Results: This study enrolled 11,782 pregnant women from 24 hospitals from September 19, 2016, to November 20, 2016. Among those, 1515 (12.9%) IDA events were diagnosed through test (test IDA); 3915 (33.3%) were identified through test and patient reporting (composite IDA). After adjusting for confounders and cluster effect of hospitals, underweight pregnant women, compared with normal women, were associated with higher risk of test IDA (adjusted odds ratio [aOR]: 1.35, 95% confidence interval [CI]: 1.17-1.57 and composite IDA (aOR: 1.35, 95% CI: 1.21-1.51); on the contrary, overweight and obese women had lower risk of test IDA (aOR: 0.68, 95% CI: 0.54-0.86 overweight; aOR: 0.30, 95% CI: 0.13-0.69 obese) and composite IDA (aOR: 0.77, 95% CI: 0.67-0.90 overweight; aOR: 0.34, 95% CI: 0.21-0.55 obese). The higher rate of GWG was associated with higher risk of IDA (test aOR: 1.86 95% CI: 1.26-2.76; composite aOR: 1.54, 95% CI: 1.16-2.03)., Conclusions: Pregnant women who are underweight before pregnancy and who have faster GWG are more likely to develop IDA. Enforced weight control during pregnancy and use of iron supplements, particularly among underweight women, may be warranted., Competing Interests: There are no conflicts of interest

Objective: To determine factors associated with adverse outcomes of preeclampsia and develop a predictive model., Methods: Clinical data of 2 532 patients with preeclampsia who were admitted to our hospital from 2005 to 2014 were extracted for the study. The patients were divided into two groups, including 990 (39.1%) with adverse outcomes and 1 542 (60.9%) without adverse outcomes. Factors associated with adverse outcomes were identified through univariate analyses. The predictive model was developed through multivariate logistic regression analyses using a randomly selected sample containing 80% of the cases. The remaining 20% of cases served for the purpose of validation and the establishment of the ROC curve., Results: Primiparas, educational attainments, prenatal care, multiple births, edema, chest pain, dyspnea, dizziness, headache, blurred vision, intrahepatic cholestasis of pregnancy, gestational diabetes, cardiovascular disease, blood pressure, urine protein, liver and kidney functions were found to be associated with adverse outcomes of preeclampsia. Multiple births, edema, dyspnea, blurred vision, cardiovascular disease, liver and kidney functions entered into the logistic regression model ( P <0.05). The Logit( P ) model had a good fitness of data and 77.1% accuracy in predicting adverse outcomes. The area under the curve ( AUC ) of the ROC curve was 0.804 [ P <0.01, 95% confidence interval CI ): 0.758 to 0.849]. The highest sensitivity was achieved when the cut-off point set risk value at 0.300, [CM(155mm]with 58.6% patients having adverse outcomes representing 83.8% true positive rate and 46.8% false positive rate., Conclusion: Adverse outcomes of preeclampsia can be predicted through multiple births, edema, dyspnea, blurred vision, cardiovascular disease, liver and kidney functions. Risk value ≥0.300 is recommended., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

NiS/g-C 3 N 4 /SrTiO 3 (NS/CN/STO) composites were prepared using a facile hydrothermal method. The synergistic effect of g-C 3 N 4 /SrTiO 3 (CN/STO) heterojunction and NiS cocatalyst enhanced the photocatalytic hydrogen evolution activity of NS/CN/STO. A hydrogen production rate of 1722.7 μmol h -1  g -1 was obtained when the 2%NiS/20%g-C 3 N 4 /SrTiO 3 (2NS/20CN/STO) was used for the photocatalytic hydrogen evolution in the presence of methanol used as a sacrificial agent under UV-vis light irradiation; the photocatalytic hydrogen production rate of 2NS/20CN/STO is 32.8, 8.9 and 4.2 times the value of that obtained with pure g-C 3 N 4 , SrTiO 3 and 20%g-C 3 N 4 /SrTiO 3 (20CN/STO), respectively. Moreover, in photoelectrochemical investigations when compared with 20CN/STO, SrTiO 3 and g-C 3 N 4 , 2NS/20CN/STO exhibited significant photocurrent enhancement. The heterojunction and cocatalyst in NS/CN/STO improved the charge separation efficiency and the lifetime of the charge carriers, leading to the enhanced generation of electrons for photocatalytic hydrogen production., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To establish a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure having an appropriate treatment window., Methods: Sixteen cynomolgus monkeys were randomly divided into four groups (A, B, C and D) after intracranial pressure (ICP) sensor implantation. D-galactosamine at 0.3, 0.25, 0.20 + 0.05 (24 h interval), and 0.20 g/kg body weight, respectively, was injected via the small saphenous vein. Vital signs, ICP, biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48, 72, 96, and 120 h after D-galactosamine administration. Progression of clinical manifestations, survival times, and results of H&E staining, TUNEL, and Masson staining were recorded., Results: Cynomolgus monkeys developed different degrees of debilitation, loss of appetite, and jaundice after D-galactosamine administration. Survival times of groups A, B, and C were 56 ± 8.7 h, 95 ± 5.5 h, and 99 ± 2.2 h, respectively, and in group D all monkeys survived the 144-h observation period except for one, which died at 136 h. Blood levels of ALT, AST, CK, LDH, TBiL, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin, and inflammatory markers [(tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6)] significantly increased compared with baseline values in different groups ( P < 0.05). Pathological results showed obvious liver cell necrosis that was positively correlated with the dose of D-galactosamine., Conclusion: We successfully established a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure, and the single or divided dosage of 0.25 g/kg is optimal for creating this model., Competing Interests: Conflict-of-interest statement: No conflict of interest exists.

Objective: To investigate the risk factors for increased red blood cells (RBCs) transfusion ratio in the women with postpartum hemorrhage (PPH)., Methods: This case-control study obtained the inpatient medical records of 112 441 pregnant women from 37 hospitals in 2011. There were 4 131 women diagnosed with PPH,record data of those patients were analyzed,including basic characteristics of patients,the level of hospital,pregnancy related complications,prenatal hemoglobin (Hb),mode of delivery,details of postpartum blood loss and blood transfusion,and maternal and neonatal outcomes. Multiple logistic regression analysis was used to identify risk factors for increased RBCs transfusion ratio., Results: There were 61 339 (54.6%) out of 112 441 women received with Cesarean section and 637 (15.4%) out of 4 131 women with PPH had blood transfusion,one to four units of RBCs were sufficient for a majority of those patients. It demonstrated that level of hospital,multiple,placenta preiva,abruptio placenta,pre-eclampsia or eclampsia,pre-delivery hemoglobin,gestational age and labor method were independent risk factors for RBCs transfusion., Conclusion: Cesarean section and pregnant complications are important risk factors for blood transfusion in women with PPH .

Diabetic neuropathic pain (DNP) plays a major role in decreased life quality of diabetes patients, however, the neural mechanisms underlying DNP remain unclear. Endomorphins are the endogenous ligands for mu-opioid receptor. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, using a streptozotocin induced diabetic rat model that displayed obvious mechanical allodynia, it was found that the expression of spinal EM2 was significantly decreased in DNP rats. While intrathecal administration of exogenous EM2 attenuated mechanical allodynia in DNP rats, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. It was found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of diabetes-induced oxidative stress. Taken together, our results provide the first evidence that the reduction in the level of an endogenous opioid in primary afferents was significantly associated with DNP. This indicates that the chronic pain associated with DNP might be due to the loss of an inhibitory effect on pain signal transmission., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To investigate the severe adverse pregnancy outcomes in pregnancies with placenta previa and prior cesarean delivery and its risk factors., Methods: This retrospective casecontrol study reviewed all pregnancies with placenta previa and prior cesarean delivery delivered by repeat cesarean section in our institution between January 2005 and June 2015,and investigated the incidence of severe adverse pregnancy outcome. A composite of severe adverse pregnancy outcomes (including transfusion of 10 units or more red blood cells,maternal ICU admission,unanticipated injuries,repeat operation,hysterectomy,and maternal death) and other maternal and neonatal outcomes were described. Univariate and multivariable logistic regression analysis were used to quantify the effects of risk factors on severe adverse pregnancy outcomes., Results: There were 478 women with placenta previa and prior cesarean delivery in our hospital over the last decade. The average age of them was 32.5±4.8 years old,most women were beyond 30 years old,the average gravidity and parity were 4 and 1,131 cases (27.4%) had severe adverse pregnancy outcomes. Transfusion of 10 units or more red blood cells happened in 75 cases (15.7%,75/478); 44 cases (9.2%,44/478) necessitated maternal ICU admission; unanticipated bladder injury occurred in 11 cases,but non ureter or bowel injury happened; All 4 repeat operations were due to delayed hemorrhage after conservative management during cesarean delivery,and an emergent hysterectomy was performed for all of the 4 cases. Hysterectomy (107 cases,22.4%) was the most common severe adverse pregnancy outcome. Among all 311 morbidly adherent placenta cases finally confirmed by pathological or surgical findings or both,only 172 (55.3%) were suspected before delivery. Multivariable logistic regression analysis showed that the risk of severe adverse pregnancy outcomes was significantly increased by pernicious placenta previa (i.e. anterior placenta overlying the prior cesarean scar),suspicion of morbidly adherent placenta before delivery and hemoglobin before delivery lower than 100 g/L,and the corresponding odds ratios and 95% confidence intervals were 2.4 (1.5-3.8),3.6 (2.3-5.6) and 2.5 (1.6-3.9),respectively., Conclusion: Pernicious placenta previa,suspicion of morbidly adherent placenta before delivery and hemoglobin before delivery lower than 100 g/L were associated with severe adverse pregnancy outcomes in women with placenta previa and prior cesarean delivery .

Aim: To establish a reversible porcine model of acute liver failure (ALF) and treat it with an artificial liver system., Methods: Sixteen pigs weighing 30-35 kg were chosen and administered with acetaminophen (APAP) to induce ALF. ALF pigs were then randomly assigned to either an experimental group ( n = 11), in which a treatment procedure was performed, or a control group ( n = 5). Treatment was started 20 h after APAP administration and continued for 8 h. Clinical manifestations of all animals, including liver and kidney functions, serum biochemical parameters and survival times were analyzed., Results: Twenty hours after APAP administration, the levels of serum aspartate aminotransferase, total bilirubin, creatinine and ammonia were significantly increased, while albumin levels were decreased ( P < 0.05). Prothrombin time was found to be extended with progression of ALF. After continuous treatment for 8 h (at 28 h), aspartate aminotransferase, total bilirubin, creatinine, and ammonia showed a decrease in comparison with the control group ( P < 0.05). A cross-section of livers revealed signs of vacuolar degeneration, nuclear fragmentation and dissolution. Concerning survival, porcine models in the treatment group survived for longer times with artificial liver system treatment ( P < 0.05)., Conclusion: This model is reproducible and allows for quantitative evaluation of new liver systems, such as a bioartificial liver. The artificial liver system (ZHJ-3) is safe and effective for the APAP-induced porcine ALF model., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.

Forty-nine patients with stage II b cervical cancer were included to investigate the changes in bladder volume in response to different approaches to maintaining consistent bladder filling. The impacts of age (P age ), water consumption (P wat ), and body mass index (BMI, P bmi ) on the mean urinary inflow rate (v tot ) were analysed. The bladder volume (BV) increased linearly over time. A large variation in v tot among individuals was observed, ranging from 0.19 to 5.13 ml/min. The v tot was correlated with P age (R = -0.53, p = 0.01) and P wat (R = 0.84, p = 0.00), and no correlation between v tot and P bmi was found (p > 0.05). Therefore, v tot could be parameterized using two methods: multivariable linear regression and iterative fitting. There was no statistically significant difference between the two methods. The model accuracy was successfully assessed with several validation tests for patients with good compliance (79.2% of all patients), and the proportion of radiotherapy (RT) fractions with zero wait time (one ultrasound (US) scan) increased from 6.5% to 41.2%. The optimal US scanning number and RT time could be provided using this model. This adaptive RT approach could reduce patient discomfort caused by holding onto urine and reduce technician labour as well as cost.