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Objective: To investigate the risk factors for organoid culture failure in colorectal cancer. Methods: This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples. Results: The median (range) duration of organoid culture was 7 (3-12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant (P=0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P>0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ2=10.773, P=0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ2=7.134, P=0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335-0.924, P=0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285-0.820, P=0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154-63.131,P=0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112-61.882, P=0.039) were identified as independent protective factors. Conclusions: The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.
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Neoplasias Colorrectales , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/secundario , Ascitis , Quimioradioterapia , Estudios Retrospectivos , Neoplasias Colorrectales/patología , Organoides , PronósticoRESUMEN
Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.
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Antineoplásicos Inmunológicos , Inhibidores de Puntos de Control Inmunológico , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios Retrospectivos , Antineoplásicos Inmunológicos/efectos adversos , Hígado , Glucocorticoides/uso terapéuticoRESUMEN
In a joint effort of both experiments and first-principles calculations, we resolve a hotly debated controversy and provide a coherent picture on the pure spin transport between Ag/Bi and ferromagnets. We demonstrate a strong inverse Rashba-Edelstein effect (IREE) at the interface in between Ag/Bi with a ferromagnetic metal (FM) but not with a ferromagnetic insulator. This is in sharp contrast to the previously claimed IREE at Ag/Bi interface or inverse spin Hall effect dominated spin transport. A more than one order of magnitude modulation of IREE signal is realized for different Ag/Bi-FM interfaces, casting strong tunability and a new direction for searching efficient spintronics materials.
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Objective: To explore the protective effect of vitamin D in acute liver failure through a mouse model. Methods: Acute liver failure was induced by combining D-galactosamine (D-GalN) lipopolysaccharide (LPS) to observe the effect of long-term vitamin D deficiency on liver injury and inflammatory signals in a mouse model. Acute liver failure was induced by thioacetamide (TAA) to observe the effect of vitamin D deficiency on the survival rate, and further high-dose of vitamin D supplementation protective effect was determined in a mouse model. Liver function was evaluated by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver inflammation by hematoxylin-eosin staining. The expressions of tumor necrosis factor (TNF-α), interleukin (IL) -1ß, NOD-like receptor family, pyrin domain containing 3 (NLRP-3), chemokines (CCL2, CXCL1 and CXCL2), etc. in liver tissues were detected by RT-qPCR. The quantitation of macrophages in liver tissue was detected by immunohistochemistry. The comparison between groups were performed by t-test. The survival curve was analyzed by log-rank (Mantel-Cox) test. Results: Long-term vitamin D deficiency had increased acute liver failure sensitivity in mice, which was manifested by increased blood cell extravasation, massive necrosis of parenchymal cells, up-regulation of TNF-α, IL-1ß, and NLRP-3 mRNA expression (P < 0.05), and increased macrophages quantitation (P < 0.05) in liver tissues. At the same time, vitamin D deficiency had increased the mice mortality rate because of liver injury (P < 0.01). On the contrary, pre-administration of high dose of vitamin D (100 IU/g) had significantly reduced liver injury, inhibited ALT and AST rise (P < 0.01), alleviated liver necrosis, and down-regulated the mRNA expression of inflammatory factors in liver tissues (P < 0.05). Conclusion: Mouse model shows that long-term vitamin D deficiency can aggravate drug-induced acute liver failure and reduce survival rates. Furthermore, high-dose of vitamin D has a certain hepatoprotective effect, which can significantly improve liver necrosis condition and inhibit inflammation. Therefore, adequate vitamin D can retain liver physiological balance to resist liver injury.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Fallo Hepático Agudo , Vitamina D/uso terapéutico , Alanina Transaminasa , Animales , Aspartato Aminotransferasas , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Galactosamina , Interleucina-1beta , Lipopolisacáridos , Hígado , Fallo Hepático Agudo/tratamiento farmacológico , Fallo Hepático Agudo/prevención & control , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). METHODS: A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. RESULTS: Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (rs = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (rs = 0.97, P < 0.01) and in placental (rs = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (rs = 0.81, P < 0.01). CONCLUSIONS: Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.
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Toxoplasma , Animales , Antígeno B7-H1/genética , Femenino , Interferón gamma/genética , Ratones , Placenta , Embarazo , Receptor de Muerte Celular Programada 1RESUMEN
Objective: To study the use of preS1-tp fusion protein as a novel vector to mediate the entry of small interfering RNA (siRNA) targeting the carboxy-terminal nuclear localization signal (NLS) region of hepatitis B virus (HBV) core protein into HBV-infected hepatocytes, and to further explore the HBV replication inhibition and covalently closed circular DNA synthesis. Methods: HepG2.2.15 cells expressing the human sodium taurocholate co-transporting polypeptide were established on the basis of lentivirus infection system. siRNA against HBV NLS region was designed and synthesized. PreS1-tp fusion protein expression and purification was observed to test its ability to cell entry and DNA binding. NLS siRNA were delivered into HepG2.2.15- sodium taurocholate co-transporting polypeptide cells by preS1-tp fusion protein as a vector to observe the effects of NLS siRNA on HBV replication and covalently closed circular DNA levels. Analysis of variance was used for comparison between multiple groups, and the measurement data differences between groups were analyzed by t-test. Results: HepG2.2.15-sodium taurocholate co-transporting polypeptide cell line was successfully constructed. Screened synthetic HBV NLS siRNA had significantly inhibited HBV replication. The preS1-tp fusion protein was expressed and purified on a large-scale. The fusion protein as a vector for HBV NLS siRNA had targeted delivery. The result showed that the fusion protein had effectively targeted siRNA to Hepg2.2.15-sodium taurocholate co-transporting polypeptide cell, which not only had effectively inhibited the expression of HBV mRNA, HBsAg and HBeAg, but also had significantly reduced the levels of HBV DNA and covalently closed circular DNA. Conclusion: The preS1-tp fusion protein constructed in this study uses the dual functional characteristics of preS1 binding to hepatocyte HBV receptor, and tp binding to nucleic acids, and targets HBV NLS siRNA against HBV-infected cells and block rcDNA from being transported to nucleus. siRNA plays a role in inhibiting HBV replication and covalently close circular DNA synthesis, providing a new strategy for the treatment of chronic hepatitis B caused by HBV infection, and a new research perspective for the complete elimination of HBV from the body.
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Virus de la Hepatitis B , Hepatitis B , ADN Circular/genética , ADN Viral/genética , Células Hep G2 , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Humanos , ARN Interferente Pequeño/genética , Replicación ViralRESUMEN
OBJECTIVE: To investigate the expression and possible role of hypoxia-inducible factor-1 (HIF-1) at the maternal-fetal interface following Toxoplasma gondii infection during early pregnancy. METHODS: Twenty pregnant C57BL/6 mice, each weighing 16 to 20 g, were randomly divided into 4 groups, including the 12-d control group, 12-d infection group, 18-d control group and 18-d infection group. Mice in the 12-d and 18-d infection groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain on day 6 of pregnancy, while mice in the 12-d control and 18-d control groups were injected with the same volume of phosphate buffered saline (PBS). Mice in the control and infection groups were sacrificed on days 12 and 18 of pregnancy, and the placental and uterine specimens of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of HIF-1α, HIF-1ß and vascular endothelial growth factor (VEGF) was quantified using quantitative fluorescent real-time PCR (qPCR) assay in the placental and uterine specimens, and the correlation between HIF-1α and VEGF mRNA expression was examined. In addition, and the HIF-1α expression was detected using immunohistochemical staining in the placental and uterine specimens of pregnant mice. RESULTS: Compared with the 12-d and 18-d control groups, adverse pregnant outcomes were observed in mice in 12-d and 18-d infection groups, such as teratism and placental dysplasia. HE staining showed swelling and blood stasis of cells, sinusoid reduction and inflammatory cell infiltration in the labyrinth area of the placenta specimens of mice in 12-d and 18-d infection groups relative to 12-d and 18-d control groups, and columnar epithelial cell injury and inflammatory cell infiltration were seen in the mouse uterine specimens in both infection groups. qPCR assay detected significantly higher HIF-1α (F = 132.6, P < 0.05) and HIF-1ß mRNA expression (F = 286.9, P < 0.05) in the placental specimens and lower HIF-1α (F = 111.5, P < 0.05) and HIF-1ß mRNA expression (F = 55.2, P < 0.05) in the uterine specimens in the 12-d infection group than in the 12-day control group, and significantly lower HIF-1α and HIF-1ß mRNA expression was detected in the placental and uterine specimens in the 18-d infection group than in the 18-day control group (F = 215.8, 418.9, 156.8 and 200.1; all P values < 0.05). Significantly lower VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the placental specimens and higher VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the uterine specimens were detected in the 12-d infection group than in the 12-d control group, and higher VEGF-A, VEGF-B and VEGF-C mRNA expression was found in the placental and uterine specimens in the 18-d infection group than in the 18-d control group (F = 521.9, 100.6, 275.9, 224.6, 108.2 and 333.4; all P values < 0.05). Immunohistochemical staining showed strongly and mildly positive HIF-1α expression in the mouse placental labyrinth area in the 12-d and 18-d infection groups relative to 12-d and 18-d control groups, while no HIF-1α expression was detected in mouse uterine specimens. CONCLUSIONS: HIF-1α expression appears a tendency towards a rise in the second trimester and a reduction in the third trimester in mice following T. gondii infection during early pregnancy, which is contrary to the changing tendency of VEGF-A, VEGF-B, and VEGF-C expression. It is hypothesized that HIF-1α inhibits placental angiogenesis in mice during pregnancy through suppressing VEGF expression, resulting in adverse pregnant outcomes.
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Toxoplasma , Factor A de Crecimiento Endotelial Vascular , Animales , Femenino , Hipoxia , Ratones , Ratones Endogámicos C57BL , Placenta , EmbarazoRESUMEN
Objective: To investigate the risk of occupational hearing loss caused by noise exposure in an automobile parts manufacturing enterprise. Methods: In June 2019, an automobile parts manufacturing enterprise in Huizhou City was selected to conduct occupational hygiene field investigation, and occupational health investigation and occupational hazards detection were carried out in the workplace. 395 workers with 8-hour working day equivalent sound level (L(ex·8 h)) ≥85 dB (a) were selected as the research objects. The occupational noise exposure risk assessment method was used to assess the noise exposure risk of L(ex·8 h)≥85 dB (a) , and the risk of high-frequency hearing loss and occupational noise deafness caused by noise exposure were evaluated when the working years were 10, 20, 30, 35 and 40. Results: When the exposure years were less than or equal to 30 years, the risk of high-frequency hearing loss of bearing pedestal final examiners was medium risk, and the risk of other positions was acceptable; the highest risk of noise deafness was the bearing pedestal final examiner, and the risk classification was higher, and the other types of work were negligible risk and acceptable risk. When the exposure years are more than 30 years, the risk classification of high-frequency hearing loss of bearing pedestal final inspection workers is high-risk, and the risk classification of other types of work is medium risk; the highest risk of noise deafness is the bearing pedestal final inspection workers, and the risk classification is higher risk, and the other types of work are medium risk. Conclusion: The enterprise should pay attention to the risk of occupational hearing loss caused by noise exposure, especially the bearing pedestal final inspection workers, and strengthen the hearing protection of noise exposed people.
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Pérdida Auditiva Provocada por Ruido , Ruido en el Ambiente de Trabajo , Enfermedades Profesionales , Exposición Profesional , Automóviles , Pérdida Auditiva Provocada por Ruido/epidemiología , Pérdida Auditiva Provocada por Ruido/etiología , Humanos , Ruido en el Ambiente de Trabajo/efectos adversos , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Exposición Profesional/efectos adversos , Medición de RiesgoRESUMEN
Objective: To analyze the epidemiological and clinical characteristics, and imaging features of patients with COVID-19 in Henan Province People's Hospital. Methods: The epidemiology, clinical symptoms, laboratory and radiologic data of 49 patients with COVID-19 infection admitted to the department of infectious disease in our hospital from January 23, 2020 to February 22, 2020 were retrospectively analyzed. All analyses were performed with SPSS software, version 22.0. Results: A total of 49 patients with COVID-19 were enrolled, of which 28 were ordinary, 16 were severe, and 5 were critical in disease severity. The average ages of the 3 groups were (46±19) , (60±16) and (68±20) years, with statistical differences (P=0.015). Common symptoms at the onset were fever (41 patients), dry cough (35 patients), and fatigue (21 patients). Epidemiological investigations found that 31 (63%) patients had direct or indirect contact with confirmed cases, and 14 cases were family clustered. Laboratory test results showed that the lymphocyte counts progressively decreased [0.85 (0.5-1.6) ×10(9)/L,0.51 (0.4-0.9) ×10(9)/L and 0.43 (0.47-0.61) ×10(9)/L, respectively], while LDH [162 (145.1-203.5) U/L,265 (195.3-288.4) U/L and 387 (312.3-415.5) U/L, respectively] and D-dimer [0.15 (0.09-0.40) mg/L,0.4 (0.2-0.6) mg/L and 0.9 (0.5-1.4) mg/L, respectively] were significantly increased (P<0.05), in all the 3 groups. The levels of IL-6 [(43.2±15.4) µg/L, (78.5±31.2) µg/L and (132.4±47.9) µg/L, respectively] and IL-10 [(3.5±3.2) µg/L, (7.6±6.4) µg/L and (9.4±7.2) µg/L respectively] increased significantly with disease severity. Pulmonary imaging of ordinary patients mainly showed unilateral or bilateral multiple infiltrates, while severe and critically ill patients showed diffuse exudation and consolidation of both lungs, and a few patients showed signs of "white lungs". Conclusions: Patients with COVID-19 has a definite history of contact with diagnosed patients, and has family aggregation. The clinical symptoms were mainly fever and dry cough. Laboratory results showed that lymphocyte count, LDH, D-dimer, interleukin-6 and interleukin-10 levels had a significant correlation with the severity of the disease, which could be used as markers for disease progression and prognosis. Pulmonary imaging showed unilateral or bilateral ground glass infiltration. In severe and critically ill patients, diffuse infiltration and consolidation or even "white lung" were present.
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Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , China , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVE: To investigate the clinical significance of detecting serum level of miR-17 in patients with hepatitis B virus (HBV) induced liver fibrosis. PATIENTS AND METHODS: A total of 200 HBV patients undergoing liver biopsy in Henan Provincial People's Hospital from June 2016 to December 2018, and 200 healthy subjects during the same period were included. Serum miR-17 level was detected by qRT-PCR. Multivariate Logistic regression analysis was conducted to evaluate independent risk factors of liver fibrosis in HBV patients. Meanwhile, ROC curves were used to assess the value of miR-17 in determining liver fibrosis severity of HBV patients. RESULTS: 200 HBV patients were classified into 4 groups based on the severity of liver fibrosis, including 52 cases in S0-1, 47 cases in S2, 53 cases in S3, and 48 cases in S4. Serum level of miR-17 was lower in healthy subjects than that in HBV patients. In addition, the serum level of miR-17 was negatively correlated with liver fibrosis severity. The relative levels of aspartate aminotransferase (AST), HBV-DNA, albumin (ALB), platelets (PLT), aspartate aminotransferase-to-platelet ratio index (APRI) and miR-17 were the independent factors of advanced liver fibrosis in HBV patients. Serum level of miR-17 exerted a predictive potential in diagnosis of the severity of HBV-induced liver fibrosis. CONCLUSIONS: Serum miR-17 level is highly expressed in HBV patients, and negatively correlated with liver fibrosis severity, which could be utilized as a non-invasive hallmark assessing liver fibrosis severity in HBV patients.
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Virus de la Hepatitis B/aislamiento & purificación , Cirrosis Hepática/sangre , MicroARNs/sangre , Adulto , Anciano , Femenino , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Curva ROC , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Long non-coding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of lncRNA SNHG7 in cervical cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of lncRNA SNHG7 in cervical cancer and to explore the possible underlying mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA SNHG7 in 60 cervical cancer tissues and adjacent normal tissues. Cell Counting Kit-8 (CCK-8) and transwell assays were used to study the effects of lncRNA SNHG7 on the proliferation and invasion of cervical cancer cells, respectively. Furthermore, Western blot was used to detect the expression levels of proteins in the epithelial-mesenchymal transition (EMT) process. RESULTS: LncRNA SNHG7 expression increased significantly in cervical cancer tissues. The inhibition of lncRNA SNHG7 expression markedly inhibited cervical cell proliferation and invasion. Meanwhile, the inhibition of lncRNA SNHG7 resulted in the increased protein expression level of E-cadherin, and decreased protein expressions of N-cadherin and Vimentin. In addition, the survival time of patients with high expression of lncRNA SNHG7 was remarkably shortened. CONCLUSIONS: LncRNA SNHG7 contributes to cell proliferation and invasion of cervical cancer. Moreover, SNHG7 has emerged as an independent and significant factor associated with poor survival of cervical cancer patients.
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Proliferación Celular/fisiología , Invasividad Neoplásica/fisiopatología , ARN Largo no Codificante/fisiología , Neoplasias del Cuello Uterino/fisiopatología , Cadherinas/biosíntesis , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/fisiología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Pronóstico , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/biosíntesis , Tasa de Supervivencia , Neoplasias del Cuello Uterino/diagnóstico , Vimentina/biosíntesisRESUMEN
Objective: To analyze the survival time of people living with HIV/AIDS and related influencing factors in Sichuan province during 1991-2017. Methods: A retrospective cohort study was conducted to analyze the data of 143 988 HIV/AIDS cases. The data were collected from Chinese HIV/AIDS Comprehensive Information Management System. Life table method was used to calculate the survival proportion of the cases, and Cox proportion hazard regression model was used to identify the factors related with survival time. Results: Among 143 988 HIV/AIDS cases a total of 30 420 cases died of AIDS related diseases (21.1%) and the average survival time was 11.51 years (95%CI: 11.39-11.64). Multivariate Cox regression analysis showed that the influencing factors for the survival of HIV/AIDS cases were gender (male vs. female, HR=1.35, 95%CI: 1.32-1.40), education level (primary school or below vs. junior middle school: HR=1.15, 95%CI: 1.12-1.18), ethnic group (Han vs. other ethnic groups, HR=1.46, 95%CI: 1.41-1.52), occupation (farmer vs. other occupations: HR=1.26, 95%CI: 1.22-1.29), age (≥55 years old vs. 15-24 years old: HR=3.18, 95%CI: 3.02- 3.36), disease phase (AIDS vs. HIV infection: HR=1.44, 95%CI: 1.39-1.48), antiretroviral therapy (ART) (receiving ART vs. receiving no ART: HR=0.20, 95%CI: 0.19-0.20), and CD(4)(+)T cell counts at diagnosis (>500 cells/µl vs.<200 cells/µl: HR=0.42, 95%CI: 0.40-0.45). Conclusions: The average survival time of HIV/AIDS cases was 11.51 years in Sichuan during 1991- 2017. The risk factors for the survival of the cases were male, education level of primary school or below, Han ethnic group, farmer, old age at diagnosis, disease phase, The protective factors for the survival of HIV/AIDS cases were receiving ART and higher CD(4)(+) T cell counts at diagnosis.
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Infecciones por VIH/epidemiología , Adolescente , China/epidemiología , Femenino , Infecciones por VIH/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Adulto JovenRESUMEN
The aim of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of the interleukin 22 (IL-22) gene and systemic lupus erythematosus (SLE) in a Chinese population. Three IL-22 SNPs (rs2227485, rs2227513 and rs2227491) were genotyped using SNaPshot SNP genotyping assays and identified by sequencing in 314 SLE patients and 411 healthy controls. The IL-22 level of serum was assessed by enzyme-linked immunosorbent assay (ELISA) kits. Data were analysed by spss version 17.0 software. We found that rs2227513 was associated with an increased risk of SLE [AG versus AA: adjusted odds ratio (aOR) = 2·24, 95% confidence interval (CI) = 1·22-4·12, P = 0·010; G versus· A: adjusted OR = 2·18, 95% CI = 1·20-3·97, P = 0·011]. Further analysis in patients with SLE showed that the AG genotype and G allele were associated with an increased risk of renal disorder in SLE (G versus A: aOR = 3·09, 95% CI = 1·30-7·33, P = 0·011; AG versus· AA: aOR = 3·25, 95% CI = 1·35-7·85, P = 0·009). In addition, the concentration of IL-22 was significantly lower in the rs2227513 AG genotype compared with AA genotype (P = 0·028). These results suggest that rs2227513 polymorphism might contribute to SLE susceptibility, probably by decreasing the expression of IL-22.
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Genotipo , Interleucinas/genética , Enfermedades Renales/epidemiología , Lupus Eritematoso Sistémico/genética , Adulto , Estudios de Casos y Controles , China/epidemiología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Interleucinas/sangre , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Riesgo , Adulto Joven , Interleucina-22RESUMEN
Objective: to compared with clinical data between nonalcoholic fatty liver disease (NAFLD) and Chronic HBV infection with NAFLD, and to explore the relationship between HBV infection and hepatic steatosis. Methods: A total of 81 patients with clinical data in the Department of Infectious Diseases in Henan Provincial People's Hospital from June 2013 to June 2016 were enrolled and divided into NAFLD group and HBV combined NAFLD group.Comparison of The levels of liver function (ALT, AST, ALP, GGT), blood lipid (TC, TG, HDL, LDL), blood glucose (GLU), uric acid (UA), hepatic fibrosis (S) and inflammation (G) And hepatic steatosis (F), and to explore the relationship between HBV infection and hepatic steatosis. The independent samples t-test or Wilcoxon two -sample test was used for comparison of continuous data,and the chi-square test was used for comparison of categorical data. Multinomial Logistic regression was used to analyze The risk factors of hepatic steatosis, P < 0.05 was considered statistically significant. Results: A total of 81 subjects were enrolled, with 31 in the NAFLD group and 36 in the HBV with NAFLD group. Baseline level comparison: ALT (t = -4.379, P < 0.01)ãAST (t = -3.847, P < 0.01) ãGGT (t = -2.763, P < 0.01) and F (χ(2) = 20.341, P < 0.01), There were significant difference (P < 0.05); There were no significant differences in the levels of blood lipids, blood glucose, uric acid, inflammation and fibrosis. e antigen status of liver steatosis is a risk factor, hepatitis B viral load and liver steatosis has nothing to do. Conclusion: In addition to HBV infection-related indicators, it is difficult to distinguish between NAFLD and NAFLD combined with HBV differences; HBV infection and hepatic steatosis have a certain relationship.
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Hígado Graso/patología , Hepatitis B Crónica/patología , Enfermedad del Hígado Graso no Alcohólico/patología , Glucemia , Hígado Graso/sangre , Hígado Graso/complicaciones , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática , Pruebas de Función Hepática , Modelos Logísticos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
Objective: To investigate the influence of hepatitis B virus X gene (HBx) on apoptosis of hepatic cells mediated by Fas in HePG2 cells. Methods: HBx eukaryotic vector pcDNA3.1(+)-X was transfected into HEPG2 cells with lipofectamine, and the null vector pcDNA3.1(+) and untransfected HEPG2 were used as normal controls. The cells were collected 72 h after transfection, and the expression of HBx mRNA and protein was determined using RT-PCR and Western blot, respectively. The mRNA expression of apoptosis-related genes Bcl-2 and Bax mRNA was also determined using RT-PCR. Cytotoxicity and apoptosis were evaluated using CCK-8 and flow cytometry, respectively, after HepG2-HBx and HepG2-3.1 cells were treated with stimulatory monoclonal antibody anti-Fas CH11. The t test was used for pairwise comparison. Results: The cell line HepG2-HBx was successfully established, as confirmed by RT-PCR and Western blot, and RT-PCR results showed that HepG2-HBx cells had significantly higher expression of Bcl-2 mRNA than HepG2-3.1 and HepG2 cells (P < 0.05), but had significantly lower expression of Bax mRNA than HepG2-3.1 and HepG2 cells (P < 0.05); CCK-8 and flow cytometry showed that anti-Fas CH11 had a lower cytotoxicity to HepG2-HBx cells and allowed for a lower apoptosis rate of HepG2-HBx cells compared with HepG2-3.1 and HepG2 cells. Conclusions: HBx can inhibit apoptosis of hepatic cells mediated by the Fas pathway.
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Apoptosis/genética , Carcinoma Hepatocelular/metabolismo , Virus de la Hepatitis B/genética , Hepatocitos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatología , Transactivadores/genética , Carcinoma Hepatocelular/virología , Acido Graso Sintasa Tipo I , Células Hep G2 , Humanos , Neoplasias Hepáticas/virología , Receptores X del Hígado , TransfecciónRESUMEN
Objective: To investigate the coagulation function in patients with acute-on-chronic liver failure (ACLF) patients using thromboelastography (TEG), and to comprehensively and dynamically evaluate patients' bleeding and coagulation status. Methods: The clinical data of ACLF patients were collected, and TEG was used to evaluate whole blood clotting kinetics in these patients. Routine biochemical parameters were measured, and complications were evaluated. The t-test was used for comparison of continuous data, the chi-square test was used for comparison of categorical data, and the Pearson correlation coefficient was used for correlation analysis. P < 0.05 was considered statistically significant. Results: A total of 60 patients (39 male and 21 female patients) were enrolled, with a mean age of 47.20±16.20 years. The TEG results showed that all patients had normal thrombokinetics, but TEG parameters were correlated with coagulation function, markers of systemic inflammatory response syndrome, laboratory markers, and prognosis. The patients with a higher R value had higher risks of infection (6.23±2.91 vs 4.74±1.12, P = 0.009), hepatorenal syndrome (5.64±2.54 vs 3.21±1.43 P < 0.01), and bleeding (6.71±3.51 vs 4.80±1.63, P = 0.01), and the patients with a lower K value (0.72±1.36 vs 1.64±1.43, P = 0.02), an increased α-angle (63.33°±10.02° vs 56.62°±12.13°, P = 0.03), and an increased MA (56.83±11.07 vs 50.40±10.81, P = 0.03) had increased risks of hepatic encephalopathy. Conclusion: ACLF patients have low coagulation function, and TEG truly reflects the "rebalance" status of this low level. Abnormal TEG parameters suggest increased risk of complications in these patients, indicating a poor prognosis.
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Insuficiencia Hepática Crónica Agudizada/diagnóstico , Tromboelastografía , Adulto , Coagulación Sanguínea , Femenino , Hemorragia , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Objective: To investigate the effect of hepatitis B core antigen (HBcAg) in promoting the invasion of hepatitis B virus (HBV)-related hepatocellular carcinoma cell line HepG2.2.15 and the role of Toll-like receptor 4 (TLR4) in the mechanism. Methods: TLR4 mRNA and protein expression in HepG2 cells and HepG2.2.15 cells was measured by reverse transcription real-time PCR and Western blot analysis, respectively. HepG2.2.15 cells were transfected with TLR4 specific small interfering RNA (siRNA) to silence TLR4 expression, and stimulated by recombinant HBcAg in culture. The invasion of cells was measured by Transwell invasion assay. The expression of TLR4 signaling pathway-related proteins in the cultured cells and proinflammatory cytokines in the supernatant was also determined. The student's t-test, one-way ANOVA, and SNK-q test were used for statistical analysis. Results: TLR4 mRNA and protein expression in HepG2.2.15 cells was significantly higher than that in HepG2 cells. TLR4 siRNA transfection remarkably down-regulated TLR4 expression in HepG2.2.15 cells. Inhibiting TLR4 expression and/or HBcAg stimulation did not affect the proliferation of HepG2.2.15 cells. However, HBcAg stimulation significantly increased the invasion ability of HepG2.2.15 cells and the secretion of proinflammatory cytokines [including interferon (IFN)-γ, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α]. Inhibiting TLR4 expression significantly reduced HBcAg-induced cellular invasion. Meanwhile, HBcAg stimulation elevated the expression of MyD88 and TRIF in HepG2.2.15 cells. TLR4 silencing inhibited HBcAg-induced increase in the expression of MyD88, while it showed no significant impact on TRIF expression. Conclusion: HBcAg can promote the invasion of HepG2.2.15 cells. The TLR4/MyD88 signaling pathway may be involved in this process by inducing the expression of proinflammatory cytokines.
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Antígenos del Núcleo de la Hepatitis B/farmacología , Antígenos de Superficie de la Hepatitis B/metabolismo , Neoplasias Hepáticas/metabolismo , Receptor Toll-Like 4/metabolismo , Carcinoma Hepatocelular , Línea Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Receptor Toll-Like 4/genéticaRESUMEN
Objective: To investigate the dynamic changes in serum ß2-microglobulin, retinol-binding protein, and cystatin C in chronic hepatitis B(CHB)patients treated with tenofovir or entecavir alone as the anti-HBV therapy, as well as their value in identifying early renal dysfunction. Methods: A total of 61 previously untreated CHB patients who were diagnosed and treated in the Department of Infectious Diseases in Henan Provincial People's Hospital from June 2013 to August 2015 were enrolled and divided into tenofovir group and entecavir group. The serum levels of ß2-microglobulin, retinol-binding protein, cystatin C, and creatinine and estimated glomerular filtration rate(eGFR)were compared between the two groups at baseline and 4, 8, 39, 52, 78, and 104 weeks after antiviral therapy. The independent samples t-test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. P < 0.05 was considered statistically significant. Results: A total of 61 CHB patients were enrolled, with 31 in the tenofovir group and 30 in the entecavir group. The two groups had comparable serum levels of ß2-microglobulin, retinol-binding protein, and cystatin C at baseline, but there were significant differences in ß2-microglobulin and retinol-binding protein over time(both P < 0.05). There was a significant difference in cystatin C at 78 weeks(t = -2.062, P = 0.044), but there was no significant difference at 104 weeks(t = -1.544, P = 0.128). There were no significant differences in serum creatinine or eGFR at any time point between the two groups(P > 0.05). At 104 weeks, there were no significant differences in HBV-DNA clearance rate or the level of virologic breakthrough between the two groups(P > 0.05). Conclusion: Serum ß2-microglobulin, retinol binding protein, and cystatin C are more sensitive than eGFR in the monitoring of early renal dysfunction during the anti-HBV therapy with tenofovir or entecavir alone.
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Antivirales/efectos adversos , Cistatina C/efectos de los fármacos , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Insuficiencia Renal/inducido químicamente , Proteínas de Unión al Retinol/efectos de los fármacos , Tenofovir/efectos adversos , Microglobulina beta-2/efectos de los fármacos , Adulto , Antivirales/uso terapéutico , Creatinina/sangre , Cistatina C/sangre , Femenino , Guanina/efectos adversos , Guanina/uso terapéutico , Hepatitis B Crónica/sangre , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/complicaciones , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Insuficiencia Renal/sangre , Proteínas de Unión al Retinol/metabolismo , Albúmina Sérica/metabolismo , Tenofovir/uso terapéutico , Resultado del Tratamiento , Microglobulina beta-2/sangreRESUMEN
ß-Hydroxybutyric acid (BHBA) has recently been shown to regulate hormone synthesis and secretion in the hypothalamus. However, little is known about the effects of BHBA-mediated hormone regulation or the detailed mechanisms by which BHBA regulates growth hormone-releasing hormone (GHRH) synthesis and secretion. In the present study, we examined the expression of the BHBA receptor GPR109A in primary hypothalamic cell cultures. We hypothesised that BHBA regulates GHRH via GPR109A and its downstream signals. Initial in vivo studies conducted in rats demonstrated that GHRH mRNA expression in the hypothalamus was strongly inversely correlated with BHBA levels in the cerebrospinal fluid during postnatal development (r = -0.89, P < 0.01). Furthermore, i.c.v. administration of BHBA acutely decreased GHRH mRNA expression in rats. Further in vitro studies revealed a decrease in GHRH synthesis and secretion in primary hypothalamic cells after treatment with BHBA; this effect was inhibited when hypothalamic cells were pretreated with pertussis toxin (PTX). BHBA had no effect on GHRH synthesis and secretion in GT1-7 cells, which do not exhibit cell surface expression of GPR109A. Furthermore, BHBA acutely decreased the transcription of the homeobox gene for Gsh-1 in the hypothalamus in both in vivo and in vitro, and this effect was also inhibited by PTX in vitro. In primary hypothalamic cells, BHBA activated the extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal kinase mitogen-activated protein kinase (MAPK) kinases, as shown by western blot analysis. Moreover, inhibition of ERK1/2 with U0126 attenuated the BHBA-mediated reduction in Gsh-1 expression and GHRH synthesis and secretion. These results strongly suggest that BHBA directly regulates GHRH synthesis and secretion via the GPR109A/ERK1/2 MAPK pathway, and also that Gsh-1 is essential for this function.
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Ácido 3-Hidroxibutírico/fisiología , Hormona Liberadora de Hormona del Crecimiento/biosíntesis , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Hipotálamo/metabolismo , Receptores Acoplados a Proteínas G/biosíntesis , Receptores Nicotínicos/biosíntesis , Transducción de Señal , Ácido 3-Hidroxibutírico/antagonistas & inhibidores , Ácido 3-Hidroxibutírico/líquido cefalorraquídeo , Ácido 3-Hidroxibutírico/farmacología , Animales , Butadienos/farmacología , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Proteínas de Homeodominio/biosíntesis , Humanos , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Nitrilos/farmacología , Toxina del Pertussis/farmacología , Cultivo Primario de Células , Ratas , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Egg allergy is associated with diarrhoeal symptoms. However, the mechanism underlying allergic diarrhoea remains unclear. OBJECTIVE: To determine whether egg white-specific IgE antibodies coexist with egg white-specific IgG antibodies in patients with egg allergy featuring diarrhoeal symptoms, and whether there is any relationship between these two antibody types. METHODS: A total of 89 patients with egg allergy featuring diarrhoeal symptoms (average age, 23.2 years; range, 1-78 years), all of whom tested positive for egg white-specific IgG, were enrolled in this study. The concentration of total IgE, egg white-specific IgE and number of eosinophils in the serum were determined. RESULTS: Among the 89 egg white allergic patients tested, 49 (55.1%) patients showed high reactivity to egg white-specific IgG, 48 (53.9%) patients had elevated serum total IgE levels, and 25 (28.1%) patients had elevated absolute eosinophil numbers. Out of the 89 egg white allergic patients, 25 showed elevated egg white-specific IgE antibody levels. Of the 25 patients who were positive for egg white-specific IgE antibody, 21 presented high sensitive reaction to egg white-specific IgG, three presented moderate sensitive reaction to egg white-specific IgG, and one presented mild sensitive reaction to egg white-specific IgG. A moderate correlation between egg white-specific IgG and egg white-specific IgE, egg white-specific IgG and absolute eosinophil number was found in the egg white allergic patients (r=0.438, P=0.000; r=0.322, P=0.002). Egg white-specific IgE levels varied in different age groups; the egg white-specific IgE concentration of younger patients (age≤18 years, mean rank 54.29) was significantly higher than that of the adult patients (age>18 years, mean rank 34.61) (Z=-3.629, P=0.000). CONCLUSION: Egg white-specific IgE antibody could coexist with egg white-specific IgG antibody in patients suffering from egg white allergy. Aberrant changes in the concentration of egg white-specific IgE antibody were associated with the presence of egg white-specific IgG antibody.