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ObjectiveTo investigate the antidepressant effect of Sinisan (SNS) by regulating glycogen aynthase kinase-3β (GSK-3β)/tumor necrosis factor alpha-induced protein 3(A20)/CCAAT enhancer binding protein β(C/EBPβ) to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group, model group, fluoxetine group (5.0 mg·kg-1), low-dose Sinisan group (4.9 g·kg-1), medium-dose Sinisan group (9.8 g·kg-1), and high-dose Sinisan group (19.6 g·kg-1), with 12 mice in each group. After one week of adaptive feeding, chronic unpredictable mild stress (CUMS) was performed to establish the depression model. In the fifth week, drug treatment was conducted for four weeks. In the ninth week, behavioral tests were performed, including sucrose preference test (SPT), open field test (OPT), elevated plus maze (EPM) test, and forced swimming test (FST). Western blot was used to detect the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), nitric oxide synthase (iNOS), GSK-3β, A20, and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation 68 (CD68) in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS, compared with the normal group, the mice in the model group had a significantly reduced sucrose preference rate (P<0.01), and the activity in the central area of the OPT was significantly reduced (P<0.01). The activity in the open arm area of the EPM test was significantly reduced (P<0.05), and the immobility time of FST was increased (P<0.01). The expression levels of inflammatory proteins IL-1β, IL-6, and iNOS were increased (P<0.01), and the fluorescence co-localization index of Iba1 and CD68 was increased (P<0.05). The protein expression levels of GSK-3β and C/EBPβ were significantly increased (P<0.05, P<0.01). After four weeks of SNS intervention, compared with the model group, the mice in the SNS group had significantly increased sucrose preference rate (P<0.01), significantly increased activities in the central area and the open arm area in the OPT and the EPM test (P<0.05), and significantly reduced immobility time in the FST (P< 0.01). The protein expression levels of IL-1β, IL-6, and iNOS were significantly decreased (P<0.05), and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group (P<0.05). The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased (P<0.01), and that of A20 was significantly increased (P<0.01). ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.
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Objective:To investigate the feasibility, efficacy and adverse reactions of programmed death-1(PD-1) inhibitors in patients with acquired immunodeficiency syndrome (AIDS) complicated with malignant tumor.Methods:From September 2020 to August 2021, patients with AIDS complicated with malignant tumor in Zhongnan Hospital of Wuhan University were enrolled. Data including basic information, laboratory test results, CD4 + T cell count, human immunodeficiency virus (HIV) viral load were collected. Patients were continuously administered intravenously PD-1 monoclonal antibody until disease progression or intolerant toxicity reaction occurred. Adverse reactions during treatment were recorded.And treatment outcomes were assessed once every 12 weeks after treatment. HIV viral load was measured after treatment once a week for four consecutive times, then once four weeks for two consecutive times, and then once every 12 weeks. Results:Ten patients were included in the study, including seven males and three females, three cases of Hodgkin′s lymphoma, two cases of cervical cancer and hepatocellular carcinoma respectively, one case of non-Hodgkin′s lymphoma, non-small cell lung cancer and anal cancer respectively. There were four patients with CD4 + T cell count of 100 to 200 cells/μL and two patients with CD4 + T cell count lower than 100 cells/μL. All patients had completed at least three cycles of treatment with PD-1 monoclonal antibody, HIV viral load remained lower than 20 copies /mL. Three cases achieved complete response and three cases achieved partial response. Adverse reactions were cutaneous capillary endothelial proliferation (CCEP) (seven cases), major bleeding (three cases), and hearing impairment (one case). Conclusions:PD-1 inhibitor has no adverse effect on the continuous suppression of HIV viral load and has an effect on tumor control, so it is a viable choice in AIDS patients complicated with tumor. However, due to its considerable adverse reactions, multidisciplinary cooperation is needed to reduce the risk of complications and deal with serious complications.
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Global warming has induced higher frequencies of excessively high-temperature weather episodes, which pose damage risk to rice growth and production. Past studies seldom specified how high temperature-induced carbohydrate metabolism disturbances from both source and sink affect rice fertilization and production. Here we discuss the mechanism of heat-triggered damage to rice quality and production through disturbance of carbohydrate generation and consumption under high temperatures. Furthermore, we provide strong evidence from past studies that rice varieties that maintain high photosynthesis and carbohydrate usage efficiencies under high temperatures will suffer less heat-induced damage during reproductive developmental stages. We also discuss the complexity of expressional regulation of rice genes in response to high temperatures, while highlighting the important roles of heat-inducible post-transcriptional regulations of gene expression. Lastly, we predict future directions in heat-tolerant rice breeding and also propose challenges that need to be conquered in the future.
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Carbohydrate Metabolism/genetics , Gene Expression Regulation, Plant , Hot Temperature , Oryza/genetics , Oryza/metabolism , Energy Metabolism/genetics , Transcription Factors/metabolismABSTRACT
Objective:To investigate the epidemic trend and risk change of acquired immunodeficiency syndrome (AIDS) complicated with malignant tumors after combination antiretroviral therapy (cART).Methods:The types of malignant tumors in patients with AIDS at different stages of cART were analyzed among anti-human immunodeficiency virus (HIV)-positive population in Hubei Province screened in National AIDS/HIV prevention and control information system from 1st January, 2004 to 31st December, 2018. The standardized incidence ratios(SIR) of malignant tumors in AIDS patients was analyzed based on the incidence of malignant tumors in the general population in Hubei Province or China in 2013. The changes in risks for development of malignant tumors in AIDS patients at different cART stages from 2004 to 2013 and 2014 to 2018 were compared.Chi-square test was used for statistical analysis.Results:Three hundred and twenty-three out of 22 994 AIDS patients were diagnosed with malignant tumors. Non-Hodgkin lymphoma(NHL) and cervical cancer were most common types in acquired immunodeficiency syndrome-defining cancers (ADC), while liver cancers and lung cancers were the most common types in non-acquired immunodeficiency syndrome-defining cancers (NADC). The overall risk of malignancy in AIDS patients was similar to that in the general population (SIR=1.06, χ2=0.62, P=0.426). However, the risks of Kaposi sarcoma, NHL, Hodgkin lymphoma, cervical cancer, and head and face cancers (excepting nasopharyngeal cancer) in AIDS patients were significantly higher than those in the general population (SIR=834.09, 9.65, 13.33, 5.22 and 2.94, respectively, χ2=11 747.27, 625.54, 56.65, 184.21 and 13.66, respectively, all P<0.01). The risks of lung cancer, colorectal anal cancer, stomach cancer and breast cancer in AIDS patients were significantly lower than those in the general population (SIR=0.33, 0.36, 0.43 and 0.45, respectively, χ2=33.43, 12.84, 9.01 and 7.21, respectively, all P<0.05). The SIR of cervical cancer, liver cancer and colorectal anal cancer from 2014 to 2018 were 4.06, 0.43 and 0.10, respectively, which were significantly lower than those from 2004 to 2013 (7.42, 1.96 and 0.84, respectively). The differences were all statistically significant ( χ2=5.39, 19.52 and 10.86, respectively, all P<0.05). Conclusions:At present, there are no significant differences of the incidences of malignant tumors between AIDS patients and general population, but the tumor types are different. The most common malignant tumors in this region are NHL and cervical cancer, which should be noted that HIV screening among patients with such tumors is conducive to comprehensive treatment to improve the efficacy.
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The data of patients with HIV/AIDS from Hubei Province during 2004 to 2018 were obtained from the National AIDS Comprehensive Prevention and Control Information System. A total of 22 980 HIV-positive or AIDS patients were followed up for 113 164 person-years and 323 malignant tumors were diagnosed. Non-Hodgkin′s lymphoma (NHL), cervical cancer, liver cancer, lung cancer, and Kaposi sarcoma (KS) accounted for 70.0% (226/323) of all malignant tumors in this population. The average crude incidence and mortality of malignant tumors in HIV-infected patients were 285.43/100 000(269.11/100 000 in males and 325.87/100 000 in females), and 169.67/100 000(184.78/100 000 in males and 132.19/100 000 in females), respectively. The result indicates that the overall cancer incidence and mortality in HIV/AIDS population under widely implementation of combination anti-retroviral therapy (cART) are similar to those in the general population of the region. But the incidence and mortality of AIDS-related tumors such as KS, NHL, HD and cervical cancer are higher than those in general population, and attention should be given to screening of these malignancies in HIV/AIDS population.
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Substance dependence is a pervasive worldwide problem, of which the mechanism remains unclear, and there is no effective intervention. In recent years, it has been showed that the gut microbiota is closely related to substance dependence. As discussed in this review, gut microbiota is significantly affected by the substances of abuse, and may serve as an important regulator in the development of substance dependence. This article reviews the research progress of gut microbiota in the most widely used substances, in order to provide ideas for future studies on underlying mechanisms and further interventions in substance dependence.
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@#Choroid neovascularization is the characteristic pathological change of many fundus diseases and is the most common cause for severe vision loss and metamorphopsia. Among the pathogenic factors, VEGF is considered to be the most important and treatment targeting VEGF showed promising results. However, anti-VEGF agents need to be administrated frequently and they are usually expensive. Also, some patients got no response to this treatment. These facts force us to find other pathway that involves in the formation of CNV. This article reviews the latest research on CNV-related signaling pathways so as to provide a deeper look into CNV and hopefully point out new directions for treating diseases that share similar pathogenesis.
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Objective:To compare the efficacy of morphine with intravenous injection and subcutaneous injection in the treatment of advanced cancer,and explore the indications of different drug delivery methods for high-dose morphine. Methods: A prospective study was performed,and 46 cases of patients with advanced cancer pain were collected and divided into intravenous group and subcutaneous group according to the administration route. Pain was assessed during the administration,and the analgesic efficiency and the incidence of adverse reactions were observed to compare the efficacy and safety of two different ways to give high-dose morphine. Results:No statisti-cally significant differences were found in the number of outbreaks needed to be rescued,the frequency of morphine-induced drug deliver-y,the efficiency of analgesia after opioid transfer,and the incidence of opioid-related side effects between the groups (P>0.05). The dose of morphine in the subcutaneous group was higher than that of the intravenous group(P<0.05). Conclusion:The continuous ad-ministration of morphine with intravenous injection and subcutaneous injection can quickly,safely and effectively relieve pain. With the same analgesic efficacy,patients can choose appropriate administration route according to the dose of morphine, the influence degree of primary diseases and the individual will.
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Objective To explore the clinical characteristics, pathological features and prognostic factors of patients with acquired immune deficiency syndrome (AIDS) related lymphoma (ARL).Methods The clinical characteristics, treatment regimen and survival status were retrospectively analyzed.At a ratio of 1∶2, 106 general non-Hodgkin lymphoma (NHL) cases were included after matching for demography and clinical characteristics with 53 ARL patients.Chi-square test was used for statistical analysis.Overall survival was analyzed using Kaplan-Meier curves.Cox regression was used for multivariant analysis.Results The predominant pathologic type of ARL was diffuse large B cell lymphoma (60.4%, 32/53).B cell lymphoma accounted for 88.7% (47/53) and T cell lymphoma accounted for 11.3% (6/53).Patients in ARL group (62.3%, 33/53) had lower proportion of receiving radiotherapy or chemotherapy compared with patients in general NHL group (94.3%, 100/106) (χ2=26.58, P<0.05).ARL group had lower hepatitis B surface antigen (HBsAg) positivity rate compared with general NHL group (1.9% vs 26.4%, χ2=14.26, P<0.05).No other characteristic was found significantly different between these two groups.The survival time of ARL and general NHL patients was (6.0±1.3) months and (48.0±10.0) months, respectively (t=8.13, P<0.01).The 1-year, 2-year, 3-year and 5-year survival rates of ARL patients were 39.6%, 32.7%, 27.7% and 20.1%, respectively, while those of general NHL patients were 79.2%, 56.8%, 42.4% and 25.0%, respectively.Of the 33 ARL patients and 100 general NHL patients who received anti-NHL treatment, the 1-year survival rates were 60.6% and 83.0%, respectively (χ2=4.040, P=0.043), the 2-year survival rates were 53.5% and 60.5%, respectively (χ2=0.003, P=0.096), the 3-year survival rates were 48.1% and 45.9%, respectively (χ2=0.288, P=0.59), the 5-year survival rates were 39.1% and 27.5%, respectively (χ2=0.798, P=0.372).Multivariate analysis revealed that anti-NHL therapy and international prognostic index score were independent predictors for prognosis (both P<0.05).Conclusions Diffuse large B cell lymphoma is the predominant pathologic type of ARL.ARL patients has significantly lower survival rate compared with general NHL patients.Combination of anti-HIV therapy and anti-lymphoma therapy in individuals with ARL can prolong their survival time.
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Objective@#To analyze the clinical characteristics, pathological features and survival of patients with AIDS related non-Hodgkin’s lymphoma (ARL) .@*Methods@#The clinical data of 53 ARL cases diagnosed and received care at Zhongnan hospital of Wuhan University were retrospectively studied, and 106 controls were enrolled as control group according to 1∶2 for paired cases and control. SPSS 13.0 package was used for statistical analysis. Kaplan-Meier was applied to assess the survival probability.@*Results@#The mean age of patients with ARL was 43 (11-67) years. Male versus female was approximately 4∶1. The median CD4+ T cell count was (146±20) /ml. The Ann Arbor clinical classification showed that 52.8% of the cases were of stage Ⅲ and Ⅳ. Approximately 54.7% of the patients had elevated serum lactate dehydrogenase (LDH) . According to international prognosis index score, 64.2% of the patients were in high risk group. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype. Among 53 cases, 33 cases (62.3%) received combination of anti-HIV therapy and anti-NHL (CHOP) chemotherapy regimen, 8 cases (15.1%) only received anti-HIV therapy, and 12 cases (22.6%) asked for alleviative treatment. Median survival time was (6.0±1.3) months for ARL cases versus (48.0±10.0) months for controls (P<0.05) . After eliminating cases who did not receive anti-lymphoma treatment, ARL cases showed a lower 1-year OS rates than control group (60.6% versus 83.0%) , but no difference about 2-, 3- and 5-year OS rates (53.5% versus 60.5%, 48.1% versus 45.9%, and 39.1% versus 27.5%, respectively) .@*Conclusions@#ARL is more common in young adults; one-year mortality rate is high. Anti-HIV therapy combined with anti-NHL therapy could significantly improve the prognosis of ARL patients. CHOP regimen may be more suitable for ARL patients.
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Objective: To discuss the conversion coefficient of morphine injection with continuous intravenous pump delivery or subcutaneous injection for the patients with advanced cancer pain demanding high dose of opioids.Methods: Using a retrospective survey, the patients with advanced cancer pain demanding high dose of opioids with poor efficacy were divided into 3∶1 group and 2.5∶1 group, and the conversion coefficient of 3∶1 or 2.5∶1 was used for the opioids equivalently conversed to intravenous or subcutaneous injection of morphine.After the conversion, the degree of pain relief, the analgesic efficiency in the conversion process, titration time, daily oral morphine equivalent amount at stable pain, morphine related adverse reactions and the other indicators were studied to evaluate the analgesic effect of morphine injection with different conversion coefficient.Results: There was no statistical significant difference between the two groups in the degree of pain relief, the effective rate of analgesia and the daily oral akministration amount of morphine at sable pain(P>0.05).The adjustment times for morphine in the two groups was (1.57±0.93) and (1.0±0.00), respectively, and the difference was statistically significant (P0.05).Conclusion: Giving morphine injection to the patients with terminal cancer pain demanding high dose of opioids with poor effect, the use of PCA pump through intravenous or subcutaneous injection can effectively relieve pain.Using the conversion coefficient of 2.5:1 can quickly complete the titration process, and safely achieve the effective analgesia.
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Objective To evaluate the effect of home-made immobilization device with KV-CBCT in lung-SBRT and investigate its clinical use value.Methods Choosing 10 lung tumor patients (half centre type tumor;half peripheral type) random analysis the interfractional and intrafractional setup errors in the SBRT process by this fixed device with KV-CBCT.The concrete method is using Varian's KV-CBCT scans the patients before and after the SBRT each time,then make the registration between the reconstructed 3 d image and the planned CT image (both based on bone landmark),we then obtain the average setup errors in LR,AP and SI directions.Simultaneously,this research make contrastive analysis of setup errors among this fixed device and other fixed devices such as vacuum pad,phantom in body IMRT.All data make one-factor analysis of variance by SSPS 17.0.Results All the setup errors data was gaussian distribution,the centre type interfraction was at (0.01 ±0.32) cm (LR),(-0.08 ±0.38) cm (AP),(0.14 ±0.36) cm (SI) of the cross section,peripheral type interfraction was at (0.01 ± 0.32) cm (LR),(-0.08 ± 0.38) cm (AP),(0.14 ± 0.36) cm (SI) of the cross section (P =0.001).We found out that the average of lung tumor's setup error at all three directions have no significant difference-the largest was the AP directions (P =0.003),the second was the SI direction (P =0.003) and the smallest was the LR direction (P =0.001).The central type has no significant difference at three directions.Compare to the other fixed device,the average setup errors of our device are (0.09 ± 0.33) cm (LR),(-0.10 ± 0.44) cm (SI),(0.17 ±0.35) cm (AP) better than the report at present paper.As the interfraction setup error was small enough by using this fixed device while it has beyond the system algorithm,the registration software of system shows (0.0 ± 0.0 cm).Conclusions The range of lung tumor motion can be cut down obviously and enhance each placement accuracy,repeatability,on SBRT with home-made immobilization device.
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ObjectiveTo investigate the CT number linearity of the cone-beam CT (CBCT) images at the different spatial locations in the scanning area.MethodsThe CatphanS04 phantom at the different locations are scanned repeatcdly using the CBCT on the Varian 23EX linear accelerator.The phantom is located the isocenter point,eccentric 3 cm,eccentric 6 cm,and different points on the z-axis successively on the accelerator.The scanned mode is the standard head mode.The reconstructive thickness is 2.5 cm.The different densities inserts of CTP404 module on the different locations are measured via Eclips treatment planning system (TPS) and computed by Matlab 7.0 and the CT linear fitting are then processed.In order to understand better the linear distribution along with the value of CT in the spatial distribution the results are compared with the fan-beam CT.ResultsPhantom studies show that:CBCT has good linearity performance not only under the standard header (body) of the scanning conditions,but also on such locations including the cross-sectional,the sagittal,the coronal plane and the eccentric position ( R2 > 0.953 ).Bowtie filtration device does not change the CT finearity but changes the value of CT.ConclusionsThe linearity of X-ray CBCT on the Varian linear accelerator is favorable.CBCT will be used in the TPS dose calculation via further correction of the CT value.
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<p><b>OBJECTIVE</b>To study the relationship between simian acquired immunodeficiency syndromn (SAIDS) and autoimmunity in simian immunodeficiency virus (SIV)-infected monkeys.</p><p><b>METHODS</b>Indirect immunofluorescence assays were performed to detect plasma or serum autoantibodies in SIV-infected monkeys. The heart, liver, spleen, lung, kidney, and lymph node of BALB/c mice, a strain of endothelial cell ECV304, and granulocytes were used as target antigens. These results were compared with HE stained slides of SIV-infected monkeys.</p><p><b>RESULTS</b>The levels of various autoantibodies, including anti-lymphocyte autoantibodies, anti-endothelial cell autoantibodies, and anti-granulocyte antibodies, increased after SIV infection in monkeys. Moreover, pathological examinations showed injuries in the lymphoid tissue and vascular pathological changes in cerebral cortex, submucosa of gastrointestinal tract, interstitial capillaries of myocardium, nephron of the kidney, and sinusoid cell of liver.</p><p><b>CONCLUSION</b>The increased autoantibodies and the pathological changes of tissues and organs confirm the existence of autoimmunity in SIV-infected monkeys.</p>