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Objective: Unusual clinical course. Background: Rapidly involuting congenital hemangioma (RICH) of the fetal skull is an extremely rare vascular disease which undergoes proliferation only in utero and progresses with maximal size at birth. RICH can be detected by prenatal imaging but is easily misdiagnose. Case Report: A 28-year-old nulliparous woman was referred at 38 weeks of gestation for routine screening with obstetric ultrasonography. The ultrasonography revealed a female fetus with a previously undetected head tumor (32×22 mm). Certain unusual sonographic features were observed: the lesion was fusiform, with a wide base adjacent to the frontal bone. Tumor growth appeared to be toward the brain parenchyma rather than outwards (ie, toward the skull), which suggested that the mass may have been derived from the skull. The mass may have remained undiagnosed due to its small size or due to the superimposition of the skull in poor quality ultrasound images. On the basis of ultrasound findings, the lesion was diagnosed as an intracranial tumor, but fetal MRI findings led to the suspicion of RICH of the fetal skull. Finally, the patient was followed up until 1 year after birth, by which time the lesion had completely disappeared. Conclusions: Careful evaluation of prenatal ultrasound is necessary to ensure detection of any mass adjacent to the skull, and the ultrasonography technician should carefully examine the features of any suspected mass to diagnose it correctly to avoid affecting the treatment strategy. [ABSTRACT FROM AUTHOR]

People that the author would like to thank for their assistance in the creation of the book are mentioned, icluding Hongmei Dong of the Shantou University Medical School and Kent HayGlass of the University of Manitoba.

Background: Ethics teaching is a relatively new area of medical education in China, with ethics curricula at different levels of development. This study examined ethics education at three medical schools in China to understand their curricular content, teaching and learning methods, forms of assessments, changes over time, and what changes are needed for further improvement. Methods: We used student and faculty surveys to obtain information about the ethics courses’ content, teaching methods, and revisions over time. The surveys also included five realistic cases and asked participants whether each would be appropriate to use for discussion in ethics courses. Students rated the cases on a scale and gave written comments. Finally, participants were asked to indicate how much they would agree with the statement that medical professionalism is about putting the interests of patients and society above one’s own. Results: There were both similarities and differences among these schools with regard to course topics, teaching and assessment methods, and course faculty compositions, suggesting their courses are at different levels of development. Areas of improvement for the schools’ courses were identified based on this study’s findings and available literature. A model of the evolution of medical ethics education in China was proposed to guide reform in medical ethics instruction in China. Analysis identified characteristics of appropriate cases and participants’ attitudes toward the ideal of professionalism. Discussion: We conclude that the development of medical ethics education in China is promising while much improvement is needed. In addition, ethics education is not confined to the walls of medical schools; the society at large can have significant influence on the formation of students’ professional values. [ABSTRACT FROM AUTHOR]

The aim of the study was to prepare an active recombinant human perforin by comparing 5 candidate segments of human perforin. Full-length perforin, MAC1 (28–349 aa), MAC2 (166–369 aa), C-100, and N-60 of human perforin were selected as candidate active segments and designated, respectively, HP1, HP2, HP3, HP4, and HP5. The target genes were amplified by PCR and the products were individually subcloned into pGEM-T. The genes for HP1, HP2, HP3, and HP5 were subcloned into pET-DsbA, whereas pET-41a (+) was used as the expression vector of HP4. The fusion proteins were expressed in Escherichia coli BL21pLysS(DE3) and purified using nickel nitrilotriacetic acid (NTA) agarose affinity chromatography. The hemolysis microassay was used as an activity assay of fusion protein. From this study, we obtained the recombinant plasmids pGEM-T-HP1, -HP2, -HP3, -HP4 and -HP5, consisting of 1600, 960, 600, 300bp, and 180, respectively. From these recombinant plasmids, expression plasmids were successfully constructed and expressed in E. coli BL21pLysS(DE3). The resultant fusion proteins, affinity purified using Ni–NTA, were ~80, 58, 45, 44, and 30 kDa, respectively. The recombinant proteins were assayed for activity on hemolysis. HP2 and HP5 were the only recombinant proteins that were active in hemolysis, and the hemolytic function was concentration dependent. These results demonstrate that active recombinant forms of perforin can be synthesized in a prokaryote model. The recombinant N-60 and MAC1 (28–349 aa) of human perforin have the function of forming pores. Our study provides the experimental basis for further investigation on the application of perforin. [ABSTRACT FROM AUTHOR]

Aconitum species are commonly used in traditional Chinese medicine, and they have a narrow therapy window due to the possibility of aconitine poisoning. Aconitine poisoning deaths appear infrequently in forensic practice. It is important to collect valuable body samples in time due to the rapid absorption and excretion of aconitine. However, it is unknown whether postmortem samples have value for toxicological analysis if the deceased has experienced long-term treatment before death. Herein, we present a case of a woman who died after 12 days of failed active treatment for aconitine poisoning. Aconitine was detected in the liver tissue. To our knowledge, this is the first case report describing the detection of aconitine in a decedent after long-term active treatment. The findings indicated that the aconitine concentration in liver tissue can be maintained after long-term treatment; this information may therefore serve as a reference in forensic practice. [ABSTRACT FROM AUTHOR]

The article focuses on recent efforts by China to standardize residency training programs. Topics discussed include the mandatory residency training standards released in 2012 by the Chinese Medical Association under the commission of the Ministry of Health, and a survey of residents at a teaching hospital in China about program organization, quality of clinical teaching, and teaching of competencies.

Cefuoxime, a second-generation cephalosporin, is used in the treatment of Gram-positive infections. Here, we report a case cefuroxime-induced disulfiram-like reaction which led to sudden death of the patient. [ABSTRACT FROM AUTHOR]

Traumatic axonal injury (TAI) accounts for a large proportion of the mortality of traumatic brain injury (TBI). The diagnosis of TAI is currently of limited use for medicolegal purposes. It is known that axons in TAI are diffusely damaged by secondary processes other than direct head injury. However, the physiopathological mechanism of TAI is still elusive. The present study used RGD peptide, an antagonist of the mechanotransduction protein integrin, to explore the role of integrin-transmitted mechanical signalling in the pathogenesis of rat TAI. The rats were subjected to a linearly accelerating load, and changes in beta-amyloid precursor protein (β-APP) expression, skeleton ultrastructure, skeleton protein neurofilament light (NF-L), and α-tubulin in the brainstem were observed, indicating that RGD could relieve the severity of axonal injury in TAI rats. In addition, the expression of β-integrin was stronger and centralized in the brainstem of the deceased died from TAI compared to other nonviolent causes. This study examined the pathophysiology and biomechanics of TAI and assessed the role of integrin in the injury of microtubules and neurofilaments in TAI. Thus, we propose that integrin-mediated cytoskeletal injury plays an important role in TAI and that integrin has the potential as a biomarker for TAI. [ABSTRACT FROM AUTHOR]

The article presents a case study of the impact of integrating histology and physiology teaching to a traditional curriculum at the Medical School of Wuhan University in China. Topics include the use of an attitude survey to measure students' attitudes regarding the curriculum change and a knowledge test to measure students' proficiency in the subject areas, efforts to promote the subjects' connection to clinical medicine, and the application of new pedagogies and assessment methods.

A 27-year-old woman, gravida 1 para 0, died 30 min after intercourse at the 16th week of gestation. The prenatal medical history indicated the placental implantation position at the cervix. The autopsy revealed massive hemoperitoneum and a tumor in the placenta and myometrium on the anterior right side of the cervix. A transmural perforation was found from the tumor to the serosal surface of the cervix. The autopsy, histopathology, and medical history indicated that her death was ascribed to the rupture of the cervix due to intraplacental choriocarcinoma (IC) after intercourse. The case indicated that placental implantation and tumor invasion might lead to the rupture of the uterus triggered by external forces in daily life. This case study might increase the awareness and recognition of IC. [ABSTRACT FROM AUTHOR]

Chorioangioma is a rare kind of benign placental tumor. Generally, patients have no clinical symptoms if tumors are small. The giant chorioangiomas would trigger multiple complications, which result in adverse outcome of fetus. However, the fetus sudden death caused by the large tumor with no complications was really less reported. We herein present a case of intrauterine fetal death due to a giant placental chorioangioma to remind the clinicians that the treatment should be performed as soon as possible to avoid this kind of tragedy. [ABSTRACT FROM AUTHOR]

Friedreich's ataxia (FRDA), the most common inherited ataxia, is caused by recessive mutations that reduce the levels of frataxin (FXN), a mitochondrial iron binding protein. We developed an inducible mouse model of Fxn deficiency that enabled us to control the onset and progression of disease phenotypes by the modulation of Fxn levels. Systemic knockdown of Fxn in adult mice led to multiple phenotypes paralleling those observed in human patients across multiple organ systems. By reversing knockdown after clinical features appear, we were able to determine to what extent observed phenotypes represent reversible cellular dysfunction. Remarkably, upon restoration of near wild-type FXN levels, we observed significant recovery of function, associated pathology and transcriptomic dysregulation even after substantial motor dysfunction and pathology were observed. This model will be of broad utility in therapeutic development and in refining our understanding of the relative contribution of reversible cellular dysfunction at different stages in disease. [ABSTRACT FROM AUTHOR]

Traumatic axonal injury (TAI) is a progressive and secondary injury following traumatic brain injury (TBI). Despite extensive investigations in the field of forensic science and neurology, no effective methods are available to estimate TAI interval between injury and death. In the present study, Fourier transform IR (FTIR) spectroscopy with IR microscopy was applied to collect IR spectra in the corpus callosum (CC) of rats subjected to TAI at 12, 24, and 72 h post-injury compared with control animals. The classification amongst different groups was visualized based on the acquired dataset using hierarchical cluster analysis (HCA) and partial least square (PLS). Furthermore, the established PLS models were used to predict injury interval of TAI in the unknown sample dataset. The results showed that samples at different time points post-injury were distinguishable from each other, and biochemical changes in protein, lipid, and carbohydrate contributed to the differences. Then, the established PLS models provided a satisfactory prediction of injury periods between different sample groups in the external validation. The present study demonstrated the great potential of FTIR-based PLS algorithm as an objective tool for estimating injury intervals of TAI in the field of forensic science and neurology. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) ranks as the fourth most frequent in incidence and second in mortality among all cancers worldwide. The development of effective treatment approaches is an urgent requirement. Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) have been found to be present in a variety of tumoral tissues and cell lines. Therefore the inhibition of GHRH-Rwas proposed as a promising approach for the treatment of these cancers. However, little is known about GHRH-R and the relevant therapy in human GC. By survival analyses of multiple cohorts of GC patients, we identified that increased GHRH-R in tumor specimens correlates with poor survival and is an independent predictor of patient prognosis. We next showed that MIA-602, a highly potent GHRH-R antagonist, effectively inhibited GC growth in cultured cells. Further, this inhibitory effect was verified in multiple models of human GC cell lines xenografted into nude mice. Mechanistically, GHRH-R antagonists target GHRH-R and down-regulate the p21-activated kinase 1 (PAK1)-mediated signal transducer and activator of transcription 3 (STAT3)/nuclear factor-κB (NF-κB) inflammatory pathway. Overall, our studies establish GHRH-R as a potential molecular target in human GC and suggest treatment with GHRH-R antagonist as a promising therapeutic intervention for this cancer. [ABSTRACT FROM AUTHOR]

Background: Postpartum hemolytic uremic syndrome (PHUS) is a severe thrombotic microangiopathy (TMA) that is clinically characterized by hemolytic anemia, renal dysfunction, and low platelet levels after childbirth. Here, we report a rare case of unexpected death due to PHUS. Case Presentation: A 23-year-old parturient had an uncomplicated cesarean section at 40 weeks gestation. The immediate postpartum course was uneventful. However, eight days post delivery, the patient developed severe nausea and vomiting followed by hematuria, spontaneous bruising, marked pallor, icteric sclera, and lethargy. Laboratory findings revealed that the patient had hemolytic anemia, thrombocytopenia, and acute renal failure. This patient died approximately 29 h after the onset of symptoms. Post-mortem examination confirmed that the patient had PHUS. Conclusions: This paper addresses the need for a renal histological examination in addition to a thorough clinical history and appropriate laboratory tests for the rapid and accurate diagnosis of PHUS. Early detection and diagnosis can significantly improve the prognosis and optimize maternal outcomes. [ABSTRACT FROM AUTHOR]

Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC. [ABSTRACT FROM AUTHOR]

Background: Postpartum hemolytic uremic syndrome (PHUS) is a severe thrombotic microangiopathy (TMA) that is clinically characterized by hemolytic anemia, renal dysfunction, and low platelet levels after childbirth. Here, we report a rare case of unexpected death due to PHUS. Case Presentation: A 23-year-old parturient had an uncomplicated cesarean section at 40 weeks gestation. The immediate postpartum course was uneventful. However, eight days post delivery, the patient developed severe nausea and vomiting followed by hematuria, spontaneous bruising, marked pallor, icteric sclera, and lethargy. Laboratory findings revealed that the patient had hemolytic anemia, thrombocytopenia, and acute renal failure. This patient died approximately 29 h after the onset of symptoms. Post-mortem examination confirmed that the patient had PHUS. Conclusions: This paper addresses the need for a renal histological examination in addition to a thorough clinical history and appropriate laboratory tests for the rapid and accurate diagnosis of PHUS. Early detection and diagnosis can significantly improve the prognosis and optimize maternal outcomes. [ABSTRACT FROM AUTHOR]

• We report an extremely rare case of sudden death due to acute necrotizing encephalopathy(ANE) caused by influena A infection. • The expression of influenza A virus antigen in the brain by immuno-histochemistry is helpful for diagnosis of ANE due to influenza virus A virus. • The present case emphasizes the neuropathological features of ANE. Influenza occasionally causes central nervous system disorders. Acute necrotizing encephalopathy (ANE) is one of the most severe influenza-associated complications, predominantly affecting infants and young children under 5 years of age. We present this case as it involves a very rare complication of influenza infection that is known to have a high rate of mortality. A 5-year-old girl presented with a high fever and convulsions. Her condition deteriorated rapidly, and she died within 24 h. Autopsy revealed extensive brain edema, multifocal perivascular hemorrhage, and necrosis of neurons without inflammatory cell infiltration in the pons and bilateral thalamus. Tests for influenza virus A and antibodies to it were positive. The girl's death was attributed to ANE associated with influenza A infection based on the clinical presentation, the postmortem neuropathology, and identification of the virus. The goal of this report is to draw attention to the potentially serious complications of influenza A infection. We hope that the lethal outcome of this disease will be fully recognized by medical personnel. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a highly heritable, behaviorally defined, heterogeneous disorder of unknown pathogenesis. Several genetic risk genes have been identified, including the gene encoding the receptor tyrosine kinase MET, which regulates neuronal differentiation and growth. An ASD-associated polymorphism disrupts MET gene transcription, and there are reduced levels of MET protein expression in the mature temporal cortex of subjects with ASD. To address the possible neurodevelopmental contribution ofMETto ASD pathogenesis, we examined the expression and transcriptional regulation ofMETby a transcription factor, FOXP2, which is implicated in regulation of cognition and language, two functions altered in ASD. MET mRNA expression in the midgestation human fetal cerebral cortex is strikingly restricted, localized to portions of the temporal and occipital lobes. Within the cortical plate of the temporal lobe, the pattern ofMETexpression is highly complementary to the expression pattern of FOXP2, suggesting the lattermayplay a role in repression of gene expression. Consistent with this, MET and FOXP2 also are reciprocally expressed by differentiating normal human neuronal progenitor cells (NHNPs) in vitro, leading us to assess whether FOXP2 transcriptionally regulates MET. Indeed, FOXP2 binds directly to the 5′ regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET. The expression of MET in restricted human neocortical regions, and its regulation in part by FOXP2, is consistent with genetic evidence for MET contributing to ASD risk. [ABSTRACT FROM AUTHOR]

The neuropeptide vasoactive intestinal peptide (VIP) has been shown to inhibit macrophage proinflammatory actions, promote a positive Th2/Thl balance, and stimulate regulatory T-cell production. The fact that this peptide is highly efficacious in animal models of inflammatory diseases such as collagen-induced arthritis and experimental autoimmune encephalomyelitis (EAE) suggests that the endogenous peptide might normally provide protection against such pathologies. We thus studied the response of VIP-deficient (i.e., VIP KO) mice to myelin oligodendrocyte protein-induced EAE. Surprisingly, VIP KO mice were almost completely resistant to EAE, with delayed onset and mild or absent clinical profile. Despite this, flow cytometric analyses and antigen-rechallenge experiments indicated that myelin oligodendrocyte protein-treated VIP KO mice exhibited robust Thu Th17 cell inductions and antigen-specific proliferation and cytokine responses. Moreover, adoptive transfer of lymphocytes from immunized VIP KO mice to WT recipients resulted in full-blown EAE, supporting their encephalitogenic potential. In contrast, transfer of encephalitogenic WT cells to VIP KO hosts did not produce EAE, suggesting that loss of VIP specifically affected the effector phase of the disease. Histological analyses indicated that CD4 T cells entered the meningeal and perivascular areas of VIP-deficient mice, but that parenchymal infiltration was strongly impaired. Finally, VIP pre- treatment of VIP KO mice before immunization was able to restore their sensitivity to EAE. These results indicate that VIP plays an unanticipated permissive and/or proinflammatory role in the propagation of the inflammatory response in the CNS, a finding with potential therapeutic relevance in autoimmune neuroinflammatory diseases such as multiple sclerosis. [ABSTRACT FROM AUTHOR]

Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a widely expressed neuropeptide originally discovered in the hypothalamus. It closely resembles vasoactive intestinal peptide (VIP), a neuropeptide well known to inhibit macrophage activity, promote Th2-type responses, and enhance regulatory T cell (Treg) production. Recent studies have shown that administration of PACAP, like VIP, can attenuate dramatically the clinical and pathological features of murine models of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis. However, specific roles (if any) of endogenous VIP and PACAP in the protection against autoimmune diseases have not been explored. Here, we subjected PACAP-deficient mice to myelin oligodendrocyte glycoprotein (MOG35-55)-induced EAE. MOG immunization of PACAPdeficient mice triggered heightened clinical and pathological manifestations of EAE compared to wild-type mice. The increased sensitivity was accompanied by enhanced mRNA expression of proinflammatory cytokines (TNFα, IL-6, IFN-γ. IL-12p35, IL-23p19, and IL-17), chemokines (MCP-1/CCL2, MIP-1α/CCL3, and RANTES/CCL5), and chemotactic factor receptors (CCR1, CCR2, and CCR5), but downregulation of the antiinflammatory cytokines (IL-4, IL-10, and TGF-β) in the spinal cord. Moreover, the abundance of CD4+CD25+FoxP3+ Tregs in lymph nodes and levels of FoxP3 .mRNA in the spinal cord were also diminished. The reduction in Tregs was associated with increased proliferation and decreased TGF-β secretion in lymph node cultures stimulated with MOG. These results demonstrate that endogenous PACAP provides protection in EAE and identify PACAP as an intrinsic regulator of Treg abundance after inflammation. [ABSTRACT FROM AUTHOR]