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OBJECTIVE: Our study aims to prospectively compare an autologous duraplasty in situ technique (IS group) with the synthetic dural graft duraplasty (SDG group) to clarify the effectiveness and superiority of the former in the treatment of patients with Chiari malformation type 1 (CM-I). METHOD: 29 patients with CM-I were randomly assigned to either IS or SDG group. In both groups, a dissection from the occipital bone was performed. All procedures were performed by the same surgeon. The two duraplasty methods were compared in terms of surgical factors and complications. Data analysis was done for the baseline material, the neurological outcome and MRI-documented syrinx size at the 6 month follow-up. RESULT: 29 patients were enrolled in this study, 14 in the IS group and 15 in the SDG group. The results showed no significant difference in operation time (P = 0.916), amount of bleeding (P = 0.120), operation complications, hospitalization time (P = 0.854) and prognosis between the two groups. The hospitalization cost of IS group was 15,125 yuan less than that of SDG group (P < 0.05). CONCLUSION: The autogenous duraplasty in situ technique is a novel, simple, effective and economical surgical management for patients with CM-I.
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Malformação de Arnold-Chiari , Dura-Máter , Humanos , Malformação de Arnold-Chiari/cirurgia , Malformação de Arnold-Chiari/diagnóstico por imagem , Masculino , Feminino , Adulto , Dura-Máter/cirurgia , Dura-Máter/diagnóstico por imagem , Estudos Prospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem , Transplante Autólogo/métodos , Adolescente , Procedimentos Neurocirúrgicos/métodos , Imageamento por Ressonância MagnéticaRESUMO
Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a posttranslational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolismrelated genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, nonalcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.
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Ácido Láctico , Hepatopatias , Humanos , Ácido Láctico/metabolismo , Hepatopatias/metabolismo , Animais , Fígado/metabolismo , Fígado/patologiaRESUMO
Colorectal cancer (CRC) is a malignancy that is widely prevalent worldwide. Due to its unsatisfactory treatment outcome and extremely poor prognosis, many studies on the molecular mechanisms and pathological mechanisms of CRC have been published in recent years. The tumor microenvironment (TME) is an extremely important feature of tumorigenesis and one of the hallmarks of tumor development. Metabolic reprogramming is currently a hot topic in tumor research, and studies on this topic have provided important insights into CRC development. In particular, metabolic reprogramming in cancer causes changes in the composition of energy and nutrients in the TME. Furthermore, it can alter the complex crosstalk between immune cells and associated immune factors, such as associated macrophages and T cells, which play important immune roles in the TME, in turn affecting the immune escape of tumors by altering immune surveillance. In this review, we summarize several metabolism-related processes affecting the immune microenvironment of CRC tumors. Our results showed that the immune microenvironment is regulated by metabolic reprogramming and influences the development of CRC.
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Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with ß-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/ß-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the ß-catenin inhibitor XAV-939, ß-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/ß-catenin signaling pathway.
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Two-dimensional (2D) materials, such as tungsten disulfide (WS2), have attracted considerable attention for their potential in gas sensing applications, primarily due to their distinctive electrical properties and layer-dependent characteristics. This research explores the impact of the number of WS2 layers on the ability to detect gases by examining the layer-dependent sensing performance of WS2-based gas sensors. We fabricated gas sensors based on WS2 in both monolayer and multilayer configurations and methodically evaluated their response to various gases, including NO2, CO, NH3, and CH4 at room temperature and 50 degrees Celsius. In contrast to the monolayer counterpart, the multilayer WS2 sensor exhibits enhanced gas sensing performance at higher temperatures. Furthermore, a comprehensive gas monitoring system was constructed employing these WS2-based sensors, integrated with additional electronic components. To facilitate user access to data and receive alerts, sensor data were transmitted to a cloud-based platform for processing and storage. This investigation not only advances our understanding of 2D WS2-based gas sensors but also underscores the importance of layer engineering in tailoring their sensing capabilities for diverse applications. Additionally, the development of a gas monitoring system employing 2D WS2 within this study holds significant promise for future implementation in intelligent, efficient, and cost-effective sensor technologies.
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INTRODUCTION: This study aimed to evaluate recent trends in physical inactivity prevalence by sociodemographic characteristics and the province of China's residence between 2013 and 2019. METHODS: The study included 4,229,616 participants 40 yr or older from 414 geographically defined localities in China during the 7-yr period. Self-reported total physical inactivity was collected to determine the standardized prevalence of physical inactivity. Logistic regression analysis was used to examine the association between physical inactivity and stroke risk, obtaining odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Results showed that the standardized prevalence of physical inactivity increased from 22.12% (95% CI = 21.99%-22.45%) in 2013 to 28.79% (95% CI = 28.48%-29.19%) in 2019, with an absolute difference of 6.67% (95% CI = 6.15% to 7.16%) and a yearly increase rate of 5.03% (95% CI = 4.85% to 5.21%). In 2019, physical inactivity was higher in female and rural participants (female = 29.55%, rural = 29.46%) than in male and urban participants (male = 28.03%, urban = 28.26%). The prevalence of physical inactivity also varied by race/ethnic groups, with the highest prevalence observed among Uyghur (47.21%) and the lowest among Yizu (14.84%). Additionally, the prevalence of physical inactivity differed by province, ranging from 14.44% in Beijing to 50.09% in Tianjin in 2019. Multivariate analyses showed that physical inactivity was associated with a higher risk of stroke (OR = 1.17, 95% CI = 1.12-1.21, P < 0.001). CONCLUSIONS: In conclusion, our study found an overall increase in physical inactivity prevalence among Chinese adults ≥40 yr old from 2013 to 2019, with significant variation across regions, sex, ages, and race/ethnic groups.
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Comportamento Sedentário , Acidente Vascular Cerebral , Adulto , Humanos , Masculino , Feminino , Exercício Físico , China/epidemiologia , PrevalênciaRESUMO
Spasmolytic polypeptide-expressing metaplasia (SPEM) is a trefoil factor 2-expressing metaplasia in the fundic glands that resembles the fundic metaplasia of deep antral glandular cells and arises mainly from transdifferentiation of mature chief cells as well as mucous neck cells or isthmic stem cells. SPEM participates in the regulation of gastric mucosal injury, including focal and diffuse injury. This review focuses on the origin, models, and regulatory mechanisms of SPEM and on its role in the development of gastric mucosal injury. We hope to provide new prospects for the prevention and treatment of gastric mucosal diseases from the perspective of cell differentiation and transformation.
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Background: Tic disorders (TD) are a kind of neuropsychiatric disease that frequently occur among preschool and school-age children, mainly characterized by motor tics or sometimes accompanied by vocal tics, and its pathogenesis is still unclear. The clinical manifestations are mainly characterized by chronic multiple movements, rapid muscle twitching, involuntary occurrence, and language disorder. Acupuncture, tuina, traditional Chinese medicine, and other methods are commonly used in clinical treatments, which have unique therapeutic advantages but have not been recognized and accepted by the international community. This study conducted a quality evaluation and meta-analysis of the currently published randomized controlled trials (RCTs) of acupuncture for TD in children in order to provide reliable evidence-based medical evidence for acupuncture for TD. Methods: All the randomized controlled trials (RCTs) using the intervention methods acupuncture + traditional Chinese medical herbs, acupuncture + tuina, and acupuncture, and the control group using Western medicine were included in the analysis. The main outcomes were obtained by using the Yale Global Tic Severity Scale (YGTSS), the Traditional Chinese medicine (TCM) syndrome score scale, and clinical treatment efficiency. Secondary outcomes included adverse events. The risk of bias in the included studies was assessed according to the tool recommended by Cochrane 5.3. The risk of bias assessment chart, risk of bias summary chart, and evidence chart in this study will be produced using R and Stata software. Results: There were 39 studies that met the inclusion criteria, including 3,038 patients. In terms of YGTSS, the TCM syndrome score scale changes and shows a clinically effective rate, and we found that acupuncture combined with Chinese medicine is the best treatment. Conclusion: Acupuncture + traditional Chinese medical herbs may be the best therapy to improve TD in children. At the same time, compared with Western medicine commonly used in clinical practice, acupuncture and acupuncture combined with tuina therapy have better effects on improving TD in children.
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Hepatocellular carcinoma is the most common type of liver cancer and associated with a high fatality rate. This disease poses a major threat to human health worldwide. A considerable number of genetic and epigenetic factors are involved in the development of hepatocellular carcinoma. However, the molecular mechanism underlying the progression of hepatocellular carcinoma remains unclear. Karyopherin subunit alpha 2 (KPNA2), also termed importin α1, is a member of the nuclear transporter family. In recent years, KPNA2 has been gradually linked to the nuclear transport pathway for a variety of tumor-associated proteins. Furthermore, it promotes tumor development by participating in various pathophysiological processes such as cell proliferation, apoptosis, immune response, and viral infection. In hepatocellular carcinoma, it has been found that KPNA2 expression is significantly higher in liver cancer tissues versus paracancerous tissues. Moreover, it has been identified as a marker of poor prognosis and early recurrence in patients with hepatocellular carcinoma. Nevertheless, the role of KPNA2 in the development of hepatocellular carcinoma remains to be determined. This review summarizes the current knowledge on the pathogenesis and role of KPNA2 in hepatocellular carcinoma, and provides new directions and strategies for the diagnosis, treatment, and prediction of prognosis of this disease.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Transporte Ativo do Núcleo Celular , alfa Carioferinas/genética , alfa Carioferinas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carioferinas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologiaRESUMO
Diffuse gastric mucosal injury is a chronic injury with altered cell differentiation, including spasmolytic polypeptide expression metaplasia (SPEM) and intestinal metaplasia (IM), which are considered precancerous lesions of gastric cancer (GC). Previously, most studies have focused on how parietal cell loss causes SPEM through transdifferentiation of chief cells. In theory, alteration or loss of chief cells seems to be a secondary phenomenon due to initial partial cell loss. However, whether initial chief cell loss causes SPEM needs to be further investigated. Currently, increasing evidence shows that initial chief cell loss is sufficient to induce gastric mucosal injury, including SPEM and IM, and ultimately lead to GC. Therefore, we summarized the two main types of models that explain the development of gastric mucosal injury due to initial chief cell loss. We hope to provide a novel perspective for the prevention and treatment of diffuse gastric mucosal injury.
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Liver cancer is one of the most common cancers in the world, and the rate of liver cancer is high due to the of its illness. The main risk factor for liver cancer is infection with the hepatitis B virus (HBV), but a considerable number of genetic and epigenetic factors are also directly or indirectly involved in the underlying pathogenesis of liver cancer. In particular, the apolipoprotein B mRNA editing enzyme, catalytic peptide-like protein (APOBEC) family (DNA or mRNA editor family), which has been the focus of virology research for more than a decade, has been found to play a significant role in the occurrence and development of various cancers, providing a new direction for the research of liver cancer. APOBEC3B is a cytosine deaminase that controls a variety of biological processes, such as protein expression, innate immunity, and embryonic development, by participating in the process of cytidine deamination to uridine in DNA and RNA. In humans, APOBEC3B has long been known as a DNA editor for limiting viral replication and transcription. APOBEC3B is widely expressed at low levels in a variety of normal tissues and organs, but it is significantly upregulated in different types of tumor tissues and tumor lines. Thus, APOBEC3B has received increasing attention in various cancers, but the role of APOBEC3B in the occurrence and development of liver cancer due to infection with HBV remains unclear. This review provides a brief introduction to the pathogenesis of hepatocellular carcinoma induced by HBV, and it further explores the latest results of APOBEC3B research in the development of HBV and liver cancer, thereby providing new directions and strategies for the treatment and prevention of liver cancer.
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BACKGROUND: Loss of motor function in the trapezius muscle is one complication of radical neck dissection after cutting the accessory nerve (AN) during surgery. Nerve repair is an effective method to restore trapezius muscle function, and includes neurolysis, direct suture, and nerve grafting. The suprascapular nerve (SCN) and AN are next to each other in position. The function of the AN and SCN in shoulder elevation and abduction movement is synergistic. SCN might be considered by surgeons for AN reanimation. AIM: To obtain anatomical and clinical data for partial suprascapular nerve-to-AN transfer. METHODS: Ten sides of cadavers perfused with formalin were obtained from the Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center. The SCN (n = 10) and AN (n = 10) were carefully dissected in the posterior triangle of the neck, and the trapezius muscle was dissected to fully display the accessory nerve. The length of the SCN from the origin of the brachial plexus (a point) to the scapular notch (b point) and the distance of the SCN from the origin point (a point) to the point (c point) where the AN entered the border of the trapezius muscle were measured. The length and branches of the AN in the trapezius muscle were measured. A female patient aged 55 years underwent surgery for partial SCN to AN transfer at Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The patient suffered from recurrent upper gingival cancer. Radical neck dissection was performed on the right side, and the right AN was removed at the intersection between the nerve and the posterior border of the SCM muscle. One-third of the diameter of the SCN was cut off, and combined epineurial and perineurial sutures were applied between the distal end of the cut-off fascicles of the SCN and the proximal end of the AN without tension. Both subjective and objective evaluations were performed before, three months after, and nine months after surgery. For the subjective evaluation, the questionnaire included the Neck Dissection Impairment Index (NDII) and the Constant Shoulder Scale. Electromyography was used for the objective examination. Data were analyzed using t tests with SPSS 19.0 software to determine the relationship between the length of the SCN and the linear distance. A P value of < 0.05 was considered as statistically significant. RESULTS: The whole length of the AN in the trapezius muscle was 16.89 cm. The average numbers of branches distributed in the descending, horizontal and ascending portions were 3.8, 2.6 and 2.2, respectively. The diameter of the AN was 1.94 mm at the anterior border of the trapezius. The length of the suprascapular nerve from the origin of the brachial plexus to the scapular notch was longer than the distance of the suprascapular nerve from the origin point to the point where the accessory nerve entered the upper edge of the trapezius muscle. The amplitude of trapezius muscle electromyography indicated that both the horizontal and ascending portions of the trapezius muscle on the right side had better function than the left side nine months after surgery. The results showed that the right-sided supraspinatus and infraspinatus muscles did not lose more function than the left side. CONCLUSION: Based on anatomical data and clinical application, partial suprascapular nerve-to-AN transfer could be achieved and may improve innervation of the affected trapezius muscle after radical neck dissection.
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Integrins allow cells to adhere to the extracellular matrix and promote the recruitment of other integrins, resulting in the formation of focal adhesion sites at the binding sites. Focal adhesion sites play essential roles in the assembly of the cytoskeleton and are vital in shaping the structure of cells. They also play other regulatory roles by influencing numerous biological functions, such as cell proliferation and apoptosis. Hydrogen peroxideinducible clone 5 (Hic5) is a member of the Paxillin family of proteins and is an adhesive plaque scaffolding protein. Its expression can be detected in both vascular and smooth muscle cells. Thus, it plays an essential role in vascular remodeling, as well as in fibrotic diseases. Hic5 functions as a coactivator of steroid receptors, thus playing a role in steroid hormonedependent diseases. It also plays a vital role in the invasive metastasis of various types of cancer. Moreover, several studies have demonstrated that Hic5 plays a critical role in transcriptional regulation, as well as in numerous signaling pathways. Therefore, the inhibition of the functions of Hic5 may prevent the development or halt the progression of several diseases. Its use as a therapeutic target in future investigations may thus aid in the treatment of several diseases, including various types of cancer. The present review article focused on the expression and functions of Hic5 in different organs, with the aim of highlighting novel possibilities for future research.
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Peróxido de Hidrogênio , Integrinas , Adesão Celular/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Hormônios , Peróxido de Hidrogênio/metabolismo , Integrinas/metabolismo , Paxilina/metabolismo , FosforilaçãoRESUMO
Deep brain stimulation (DBS) is an effective treatment for dyskinesia in patients with Parkinson's disease (PD), among which the therapeutic targets commonly used include the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Levodopa-induced dyskinesia (LID) is one of the common motor complications arising in PD patients on chronic treatment with levodopa. In this article, we retrospectively evaluated the outcomes of LID with the Unified Dyskinesia Rating Scale (UDysRS) in patients who underwent DBS in multiple centers with a GPi or an STN target. Meanwhile, the Med off MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-â ¢) and the levodopa equivalent daily dose (LEDD) were also observed as secondary indicators. PD patients with a GPi target showed a more significant improvement in the UDysRS compared with an STN target (92.9 ± 16.7% vs. 66.0 ± 33.6%, p < 0.0001). Both the GPi and the STN showed similar improvement in Med off UPDRS-III scores (49.8 ± 22.6% vs. 52.3 ± 29.5%, p = 0.5458). However, the LEDD was obviously reduced with the STN target compared with the GPi target (44.6 ± 28.1% vs. 12.2 ± 45.8%, p = 0.006).
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BACKGROUND: Listeria monocytogenes (L. monocytogenes) is an opportunistic facultative anaerobic pathogen that is widely distributed in nature. Brain infection (meningitis and meningoencephalitis) and bacteremia are common clinical manifestations of listeriosis in elderly and immunocompromised individuals. Brain abscesses caused by L. monocytogenes are extremely rare. In this study, we describe a case of an older male who with a brain abscess caused by Listeria infection. CASE DESCRIPTION: We report a case of a 59-year-old male who was once diagnosed with acute cerebral infarction. The diagnose was changed after needle biopsy of the abscess and culture of L. monocytogenes. The patient was first empirically used the broad-spectrum antibiotic meropenem for 12 days (2 g Q8 h) until culture results were available, and then switched to oral trimethoprim/sulfamethoxazole 160/800 mg/12 h for further 2 weeks. The symptoms of slurred speech, numbness and impaired muscle strength of the right leg improved. Computed tomography (CT) and magnetic resonance imaging (MRI) examination were performed 2 weeks after operation showed smaller abscess and reduced perifocal edema. The patient was continued oral trimethoprim/sulfamethoxazole for 8 weeks. The remaining right arm dysfunction recovered. After six months, the patient had returned to normal daily activities and only exhibited weakness of the right fingers. CONCLUSIONS: Brain abscess caused by L. monocytogenes should be considered in patients who have risk factors for listeriosis. Pathogen infection, including with Listeria monocytogenes, should be taken into account when patients with impaired immune function exhibit hemiplegia and aphasia. Listeria infection should also be considered in immunocompetent patients. Performing needle biopsy or lesion resection and starting antibiotic therapy according to drug susceptibility testing in the early stage is key to treating this kind of disease.
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Abscesso Encefálico , Listeria monocytogenes , Listeriose , Mycobacterium tuberculosis , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Testes de Sensibilidade Microbiana , Listeriose/complicações , Listeriose/diagnóstico , Listeriose/tratamento farmacológico , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVE: This study aims to present the clinical characteristics and surgical treatment in patients with intracranial hemangioblastomas and to investigate risk factors for postoperative functional outcomes. METHODS: Patients with intracranial hemangioblastomas who received surgical treatment in our institute between 2011 and 2020 were included. We retrospectively reviewed and analyzed the clinical characteristics, surgical treatment, and postoperative functional status. Risk factors for postoperative functional outcomes were further analyzed using univariate and multivariate analysis. RESULTS: We identified 48 patients with 82 intracranial hemangioblastomas resected in this study. There were 22 females and 26 males, and the mean age was 39.3 ± 15.3 years. Total resection was achieved in all the cases. After primary surgery, immediate functional status was improved in 20 patients (41.7%), stable in 9 patients (18.8%), and worsened in 19 patients (39.6%). Forty-two patients (89.4%) had favorable functional status (Karnofsky Performance Scale ≥80) at long-term follow-up. Through univariate and multivariate analysis, body mass index, number of resected tumors per operation, and intraoperative blood loss were independent risk factors for the immediate functional outcome (P = 0.006, P = 0.023, P = 0.038, respectively). Preoperative hydrocephalus was significantly associated with unfavorable long-term functional status (P = 0.047). CONCLUSIONS: Generally, patients can benefit from surgical removal of intracranial hemangioblastomas with favorable functional outcomes. Body mass index, number of resected tumors per operation, and intraoperative blood loss can be used as risk factors for immediate functional outcomes after surgery, and preoperative hydrocephalus for long-term functional status.
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Hemangioblastoma , Hidrocefalia , Adulto , Perda Sanguínea Cirúrgica , Análise Fatorial , Feminino , Hemangioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Upper gastrointestinal (GI) bleeding is a severe acute disease of gastroenterology department. Fish bone is the most common food-related foreign body. However, fish bone piercing the esophagus, causing the mediastinal abscess that corroded the left subclavian artery, resulting delayed but high-risk massive upper gastrointestinal bleeding is very rare. CASE PRESENTATION: We report a 54-year-old man who was diagnosed with delayed but high-risk massive upper GI bleeding that was the result of a fish bone piercing the esophagus, causing a mediastinal abscess that corroded the left subclavian artery. He was saved effectively by early and timely multidisciplinary collaboration. CONCLUSION: A fish bone-caused mediastinal abscess that corrodes the left subclavian artery and induces delayed but high-risk massive upper GI bleeding is very rare. In addition to routine consideration of upper GI bleeding, medical history, endoscopy and CT are helpful for achieving a diagnosis. Importantly, early and timely multidisciplinary collaboration can effectively save critically ill patients.
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Corpos Estranhos , Hemorragia Gastrointestinal , Doença Aguda , Endoscopia Gastrointestinal , Esôfago , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Fungal azaphilones have attracted considerable interest as they exhibit great potential in food and pharmacological industries. However, there is a severe bottleneck in the low production in wild strains and the ability to genetically engineer azaphilone-producing fungi. Using Monascus azaphilones (MAs) as an example, we demonstrate a systematic metabolic engineering strategy for improving the production of MAs. In this study, Monascus purpureus HJ11 was systematically engineered through a combination of promoter engineering, gene knockout, rate-limiting enzyme overexpression, repression of the competing pathway, enzyme engineering, and metabolic rebalance. The maximum yield and titer of MAs successfully increased to 906 mg/g dry cell weight (DCW) and 14.6 g/L, respectively, 2.6 and 3.7 times higher than those reported in the literature. Our successful model not only offers a practical and efficient way to improve the azaphilone production but also sheds light on the potential of systematic metabolic engineering in nonmodel fungi as a chassis for the production of high-value chemicals.
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Monascus , Benzopiranos , Engenharia Metabólica , Monascus/genética , Pigmentos BiológicosRESUMO
The incidence of gastrointestinal (GI) mucosal diseases, including various types of gastritis, ulcers, inflammatory bowel disease and GI cancer, is increasing. Therefore, it is necessary to identify new therapeutic targets. Ion channels/transporters are located on cell membranes, and tight junctions (TJs) affect acid-base balance, the mucus layer, permeability, the microbiota and mucosal blood flow, which are essential for maintaining GI mucosal integrity. As ion channel/transporter dysfunction results in various GI mucosal diseases, this review focuses on understanding the contribution of ion channels/transporters to protecting the GI mucosal barrier and the relationship between GI mucosal disease and ion channels/transporters, including Cl-/HCO3- exchangers, Cl- channels, aquaporins, Na+/H+ exchangers, and K+ channels. Here, we provide novel prospects for the treatment of GI mucosal diseases.
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Membrana Celular/metabolismo , Mucosa Gástrica/patologia , Gastroenteropatias/patologia , Mucosa Intestinal/patologia , Canais Iônicos/metabolismo , Animais , Mucosa Gástrica/metabolismo , Gastroenteropatias/metabolismo , Humanos , Mucosa Intestinal/metabolismoRESUMO
Portal hypertensive gastropathy (PHG) is a complication of cirrhotic or noncirrhotic portal hypertension. PHG is very important in the clinic because it can cause acute or even massive blood loss, and its treatment efficacy and prognosis are poor. Currently, the incidence of PHG in patients with cirrhosis is 20-80%, but its pathogenesis is complicated and poorly understood. Studies have shown that portal hypertension can cause changes in gastric mucosal microcirculation hemodynamics, leading to changes in gastric mucosal histology and function and thereby weakening the mucosal defense barrier. However, no specific drug treatment plans are currently available. This article reviews the current literature to further our understanding of the mechanism underlying PHG and the relationship between PHG and the posterior mucosal defense barrier and to explore new therapeutic targets.