Secondary endoscopic submucosal dissection for locally recurrent or incompletely resected gastric neoplasms

AIM To investigate the feasibility and safety of secondary endoscopic submucosal dissection(ESD) for residual or locally recurrent gastric tumors. METHODS Between 2010 and 2017, 1623 consecutive patients underwent ESD for gastric neoplasms at a single tertiary referral center. Among these, 28 patients underwent secondary ESD for a residual or locally recurrent tumor. Our analysis compared clinicopathologic factors between primary ESD and secondary ESD groups. RESULTS The en bloc resection and curative rate of resection of secondary ESD were 92.9% and 89.3%, respectively. The average procedure time of secondary ESD was significantly longer than primary ESD(78.2 min vs 55.1 min, P = 0.004), and the adverse events rate was not significantly different but trended slightly higher in the secondary ESD group compared to the primary ESD group(10.7% vs 3.8%, P = 0.095). Patients who received secondary ESD had favorable outcomes without severe adverse events. During a mean follow-up period, no local recurrence occurred in patients who received secondary ESD. CONCLUSION Secondary ESD of residual or locally recurrent gastric tumors appears to be a feasible and curative treatment though it requires greater technical efficiency and longer procedure time.

Reproducibility of perfusion CT derived CBV and rCBV measurements with different slice thickness in patients with brain neoplasms

Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brain neoplasms. Meth- ods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms. The results of the measurements with different slice thickness were compared. Calculation of coefficient of variation (CV), and relative paired difference of the measurements were used to determine the levels of inter- and intraobserver reproducibility. Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant (P < 0.05) respectively in observer 2, and were not significant in the other two observers (P > 0.05). For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant. Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group. Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group. The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively. No other intraobserver differences of measurements were statistically significant. CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers. Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness. Suitable training may be helpful to maintain a high level of consistency for measurements.

Inhibition of endoplasmic reticulum stress alleviates secondary injury after traumatic brain injury

Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal（1 mg/kg）, by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.

Extrapancreatic malignancies and intraductal papillary mucinous neoplasms of the pancreas

Over the last two decades multiple studies have demonstrated an increased incidence of additional malignancies in patients with intraductal papillary mucinous neoplasms(IPMNs).Additional malignancies have been identified in 10%-52% of patients with IPMNs.The majority of these additional cancers occur before or concurrent with the diagnosis of IPMN.The gastrointestinal tract is most commonly involved in secondary malignancies,with benign colon polyps and colon cancer commonly seen in western countries and gastric cancer commonly seen in Asian countries.Other extrapancreatic malignancies associated with IPMNs include benign and malignant esophageal neoplasms,gastrointestinal stromal tumors,carcinoid tumors,hepatobiliary cancers,breast cancers,prostate cancers,and lung cancers.There is no clear etiology for the development of secondary malignancies in patients with IPMN.Although population-based studies have shown different results from single institution studies regarding the exact incidence of additional primary cancers in IPMN patients,both have reached the same conclusion:there is a higher incidence of extrapancreatic malignancies in patients with IPMNs than in the general population.This f inding has signif icant clinical implications for both the initial evaluation and the subsequent long-term followup of patients with IPMNs.If a patient has not had recent colonoscopy,this should be performed during the evaluation of a newly diagnosed IPMN.Upper endoscopy should be performed in patients from Asian countries or for those who present with symptoms suggestive of upper gastrointestinal disease.Routine screening studies(breast and prostate) should be carried out as currently recommended for patient's age both before and after the diagnosis of IPMN.

Changes in circulating inflammatory cells and the relationship to secondary brain injury in patients with craniocerebral injury

BACKGROUND：Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE： To observe changes in white blood cells （WBC） and polymorphonuclear neutrophils （PMN） in peripheral blood, and to determine their role in secondary brain insult in patients with craniocerebral injury. DESIGN, TIME AND SETTING： A case-control study at the Department of Neurosurgery of the Affiliated Hospital North Sichuan University of Medical Sciences between August 2007 and May 2008. PARTICIPANTS： Sixty-three patients, admitted within 24 hours after craniocerebral injury and who received no surgery, were included in the study. The cohort consisted of 41 males and 22 females, aged 9–72 years, with an average age of 42 years. Ten healthy volunteers, selected from the Department of Neurosurgery, were designated as the control group. METHODS： WBC and PMN from the peripheral blood were measured 0, 24, 48, 72, and 168 hours after admission to hospital. The Glasgow coma scale, area of cerebral hemorrhage, and degree of brain edema were simultaneously determined. The Glasgow outcome scale was evaluated six months after injury. The relationship between changes in WBC and PMN were analyzed. Sixty-three patients were divided into 0, 24, 48, 72, and 168 hours groups, with admission time to hospital as the determining factor. As controls, WBC and PMN of peripheral blood were also detected in 10 healthy volunteers. MAIN OUTCOME MEASURES： The main outcome measures were WBC and PMN counts in the peripheral blood at 0, 24, 48, 72, and 168 hours after admission to hospital, the mutual relationship between GCS, WBC and PMN, and changes in brain hemorrhage volume and edema size. RESULTS： WBC peaked at 24 hours after injury, and PMN peaked at 48 hours after injury （P 〈 0.01）. These measures negatively correlated to the Glasgow coma scale （r = -0.657, -0.541, respectively, P 〈 0.05）. In patients with Glasgow coma sale 〈 8, WBC and PMN were significantly higher than in the patients with GCS ≥ 8 （P 〈 0.05）. Cerebral hemorrhage reached a peak at 24 hours after injury, and the degree of brain edema was maximal at 168 hours after injury. WBC and PMN counts were positively correlated to cerebral hemorrhage volume and brain edema size （P 〈 0.05）. CONCLUSION： WBC and PMN counts significantly increased after craniocerebral injury and exhibited a correlation with the GCS score, volume of hemorrhage and edema, and Glasgow outcome scale.

Changes in platelet parameters and secondary brain injury in acute craniocerebral trauma

Changes in platelet parameters are important in secondary brain injury in acute craniocerebral trauma We selected 163 patients with craniocerebral trauma who were admitted within 24 hours with nonoperative therapy. Platelet parameters of 40 healthy subjects served as controls. Platelet number was decreased, while mean platelet volume and platelet distribution width values were increased, at 1 and 3 days after injury. Platelet number was lower and mean platelet volume and platelet distribution width were larger in patients with traumatic cerebral infarction and those in Glasgow Coma Scale score 〈 8 group. Platelet number was negatively correlated to volume of cerebral edema, but positively correlated to Glasgow Outcome Scale score. These data indicate that changes in platelet parameters may be utilized to indicate the state of central nervous system injury and patient prognosis .

创伤性脑损伤大鼠皮质神经元中Lnx1表达及参与继发性脑损伤的机制

背景:细胞凋亡在继发性脑损伤中发挥重要作用。探究创伤性脑损伤后促进神经细胞存活的病理生理机制,将为防治创伤性脑损伤提供新的方向和理论依据。目的:探究Lnx1分子在哺乳动物脑损伤后皮质神经元中的表达变化及参与继发性脑损伤的可能机制。方法:80只成年SD大鼠平均分成假手术组和创伤性脑损伤组,每组雌雄各20只。采用重物坠落方法建立创伤性脑损伤大鼠模型,分别在脑损伤后6,12,24,48,72 h,通过RT-qPCR、Western blot和免疫荧光染色等技术分析相关分子在受损皮质神经元中的表达情况。结果与结论:(1)创伤性脑损伤组大鼠损伤部位脑组织出血,可观察到明显的组织损伤,脑组织含水量升高;(2)与假手术组相比,创伤性脑损伤组皮质神经元中Lnx1表达在损伤24 h开始显著升高;(3)创伤性脑损伤后与Lnx1相结合的PBK和BCR蛋白表达降低,促存活因子ctgf的表达升高;(4)结果表明:脑损伤后神经元中Lnx1表达上调,其通过降低靶分子PBK和BCR的表达,进一步上调促成活因子ctgf的表达,对受损神经元具有保护作用。

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

Relationship between HER-2 overexpression and brain metastasis in esophageal cancer patients

AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010.Data analyzed consisted of demographic and clinical variables.The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test.RESULTS:One hundred and forty two patients were reviewed.Median age was 64 years(36-86 years).Eighty eight patients(62%) received neoadjuvant chemoradiotherapy.Pathological complete and partial responses were achieved in 17(19%) and 71(81%) patients.Cancer relapsed in 43/142(30%) patients.The brain was the first site of relapse in 9/43 patients(21%,95% CI:10%-36%).HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9(56%) cases overexpressed HER-2(3+ staining).CONCLUSION:HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy.Further studies will be required to validate this observation.

Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury

Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n=0, stomach: n=10, colorectal: n=47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray (Gy) or 3Gy to a total dose of 50Gy or 30Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6mo vs 8.0mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n=916) was 3.4mo and 3.2mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n=57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70 was 5.5mo vs 2.1mo for patients with KPS <70 (P<0.01, log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.

Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.

Brain metastasis of hepatocellular carcinoma:A case report and review of the literature

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. It is more common in far eastern countries and relatively rare in the United States and western European countries where at autopsy it accounts for only 1-2% of malignant rumors, The disease is usually manifested in the the 6^th and 7^th decade of life. HCC is one of the highly malignant neoplasms, Extrahepatic metastases are seen in 64% of patients with HCC. The lungs, regional lymph nodes, kidney, bone marrow and adrenals are common sites of HCC metastasis^[1-3], But, metastasis to brain and skull is extremely rare. Table I shows some of the reported cases of HCC with brain metastasis. These case reports reaffirms the complex and multidisciplinary care of these patients^[4-5].

Comparative transcriptomic analysis of rat versus mouse cerebral cortex after traumatic brain injury

The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.

Genome-wide interrogation of transfer RNA-derived small RNAs in a mouse model of traumatic brain injury

Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether ts RNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated ts RNA and messenger RNA(m RNA) transcriptome sequencing were used. The results revealed that 103 ts RNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 ts RNAs were upregulated and 47 ts RNAs were downregulated. Based on micro RNA-like seed matching and Pearson correlation analysis, 57 differentially expressed ts RNA-m RNA interaction pairs were identified, including 29 ts RNAs and 26 m RNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that ts RNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No. 20190411) on April 11, 2019.

Tandem Mass Tag-based proteomics analysis reveals the vital role of inflammation in traumatic brain injury in a mouse model

Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers.Therefore,it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury(TBI).In this study,we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of TBI.Our results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after injury.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses,including complement and coagulation cascades,as well as chemokine signaling pathways.Subsequent transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1,RelA,IRF1,STAT1,and Spi1 play pivotal roles in the secondary injury that occurs after TBI,which further corroborates the functional enrichment for inflammatory factors.Our results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI.

Quantitative proteomic and phosphoproteomic analyses of the hippocampus reveal the involvement of NMDAR1 signaling in repetitive mild traumatic brain injury

The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.

A Phase Ⅰ trial of dose escalation of topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer

Objective The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer.

Research progress on the mechanism of acupuncture in the treatment of secondary brain injury after intracerebral hemorrhage

Intracerebral hemorrhage is a major cause of death in humans,with high morbidity,mortality,and disability rates.Secondary brain injury after intracerebral hemorrhage is a consequence of brain edema and neurological dysfunction.Acupuncture is markedly effective against secondary brain injury,and various mechanisms are involved in its action,such as inhibition of inflammatory cascades,inhibition of oxidative stress,attenuation of brain edema,inhibition of nerve cell death,and regulation of neural plasticity.This paper summarizes the mechanism underlying the effects of acupuncture on secondary brain injury after intracerebral hemorrhage in recent years to provide new ideas for subsequent research.

Secondary Parkinson disease caused by breast cancer during pregnancy: A case report

BACKGROUND Paraneoplastic neurological syndrome manifesting as secondary Parkinson disease caused by breast cancer is extremely rare.CASE SUMMARY We report a 39-year-old primipara of 31 gestational weeks,who presented with worsening tremors,facial stiffness and speech disfluencies,and decreased limb strength.Thorough physical examinations and auxiliary tests suggested secondary Parkinson’s disease,but the pathogenesis was unknown.During the cesarean section at the 31 weeks plus 6 d,an exploration and liver biopsy revealed a metastatic,poorly differentiated adenocarcinoma.The positron emission tomography and immunohistochemical analysis confirmed a breast ductal carcinoma of stage IV.To our knowledge,only two reports have documented the association between the breast cancer and the Parkinson disease,and neither occurred in pregnant women.CONCLUSION Our case alerts the secondary Parkinson disease as the possible presentation of breast cancer,the most common malignancy during pregnancy.