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Reflective mirrors are the key imaging components of space-borne telescopes, which require a high lightweight ratio integrated with excellent optical properties. In this context, a novel, to our knowledge, 2.5D centroidal Voronoi tessellation (CVT) generation methodology is proposed for designing and optimizing a lightweight mirror structure. Firstly, the initial designs are obtained combining global sensitivity factor mapping and local distribution optimization. Then, the optimal model is selected through multi-objective optimization and decision making. Subsequently, the FEA (finite element analysis) results indicate that, under the same mass, the proposed design exhibits better optomechanical performance. Finally, in practical applications, the approach presented in this paper outperforms the traditional design for each technological requirement, including a 62% reduction in RMS and a higher lightweight ratio. This method offers a kind of novel design and optimization process for space-based optomechanical lightweight structures.
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The objective of this study is to assess the potential impact of tefluthrin and guadipyr on the gut microbial composition and metabolism in adult Apis mellifera ligustica, thereby elucidating the underlying mechanisms of insecticide action and its practical implications for bee protection. In this investigation, A. mellifera were subjected to one of three dietary conditions: (1) control sugar water, (2) tefluthrin-infused sugar water, or (3) guadipyr-infused sugar water. After a 10-day exposure period, genomic DNA from the gut bacteria was extracted. High-throughput sequencing was employed to evaluate the potential influence of tefluthrin and guadipyr treatments on the diversity and abundance of gut bacteria. Among the A. mellifera specimens, a total of twenty species of gut bacteria were identified, spanning across five phyla, six classes, eleven orders, eleven families, and fifteen genera. The dominant phyla within the gut bacterial community were Proteobacteria and Bacteroidetes. In comparison to the control group, both the tefluthrin-treated and deltamethrin-treated groups exhibited alterations in the composition of their gut bacterial flora. At the phylum level, there was a significant decrease in the relative abundance of Cyanobacteria (P < 0.05). On the genus level, the tefluthrin group displayed a significant increase in the relative abundance of Bartonella and Serratia (P < 0.05). In the guadipyr-treated group, the relative abundance of Gilliamella and Frischella increased significantly (P < 0.05), while the relative abundance of norank_o_Chloroplast and Enterobacter decreased significantly (P < 0.05). Further analysis of cluster of orthologous genes predicted functional changes in gut microbial metabolism following tefluthrin exposure but no significant changes after guadipyr exposure. Consequently, exposure to tefluthrin and guadipyr can induce shifts in both the composition and metabolic activity of the gut bacteria in A. mellifera. Notably, the impact of tefluthrin on the gut bacteria of A. mellifera appears to be more pronounced compared to that of guadipyr.
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Bactérias , Microbioma Gastrointestinal , Inseticidas , Piretrinas , Animais , Abelhas/microbiologia , Abelhas/efeitos dos fármacos , Piretrinas/farmacologia , Inseticidas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/classificaçãoRESUMO
OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.
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Síndrome da Imunodeficiência Adquirida , Coinfecção , Tuberculose , Humanos , Vacina BCG , Coinfecção/epidemiologia , Prevalência , Fatores de Risco , Tuberculose/epidemiologia , China/epidemiologiaRESUMO
BACKGROUND: The aim of this retrospective matched-paired cohort study was to clarify the effectiveness of preserving the vagus nerve in totally laparoscopic radical distal gastrectomy (TLDG). METHODS: One hundred eighty-three patients with gastric cancer who underwent TLDG between February 2020 and March 2022 were included and followed up. Sixty-one patients with preservation of the vagal nerve (VPG) in the same period were matched (1:2) to conventional sacrificed (CG) cases for demographics, tumor characteristics, and tumor node metastasis stage. The evaluated variables included intraoperative and postoperative indices, symptoms, nutritional status, and gallstone formation at 1 year after gastrectomy between the two groups. RESULTS: Although the operation time was significantly increased in the VPG compared with the CG (198.0 ± 35.2 vs. 176.2 ± 35.2 min, P < 0.001), the mean time of gas passage in the VPG was significantly lower than that in the CG (68.1 ± 21.7 h vs. 75.4 ± 22.6 h, P = 0.038). The overall postoperative complication rate was similar between the two groups (P = 0.794). There was no statistically significant difference between the two groups hospital stay, total number of harvested lymph nodes, and mean number of examined lymph nodes at each station. During follow-up, the morbidity of gallstones or cholecystitis (8.2% vs. 20.5%, P = 0.036), chronic diarrhea (3.3% vs. 14.8%, P = 0.022), and constipation (4.9% vs. 16.4%, P = 0.032) were significantly lower in the VPG than in the CG in this study. Moreover, injury to the vagus nerve was found to be an independent risk factor for gallstone formation or cholecystitis and chronic diarrhea in univariate analysis and multivariate analysis. CONCLUSION: The vagus nerve plays an imperative role in gastrointestinal motility, and hepatic and celiac branch preservation mainly exerts efficacy and safety in patients who undergo TLDG.
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Colecistite , Cálculos Biliares , Laparoscopia , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Estudos de Coortes , Cálculos Biliares/cirurgia , Gastrectomia/efeitos adversos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Laparoscopia/efeitos adversos , Nervo Vago/patologia , Colecistite/cirurgia , Diarreia/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Roux-en-Y (R-Y) anastomoses have been widely used in distal gastrectomy, while the incidence of Roux stasis syndrome remains common. Uncut R-Y anastomosis maintains the neuromuscular continuity, thus avoiding the ectopic pacemaker of the Roux limb and reducing the occurrence of Roux stasis. However, retrospective studies of Uncut R-Y anastomosis remain scarce and randomized controlled trials have not been reported. METHODS: We conducted a randomized controlled trial to compare the surgical safety, nutritional status, and postoperative quality of life (QOL) between uncut and classic Roux-en-Y (R-Y) reconstruction patients. Patients with Stage I gastric cancer were randomly enrolled and underwent laparoscopic distal gastrectomy followed by uncut or classic R-Y reconstruction. Body mass index and blood test were used to evaluate the nutritional status. QOL was evaluated using European Organization for Research and Treatment of Cancer QOL Questionnaire (STO22) and laboratory examinations at postoperative month (POM) 3, 6, 9, and 12. Computed tomography scanning was used to evaluate the skeletal muscle index (SMI) at POM 6 and 12. Endoscopy was performed at POM 12. RESULTS: Operation time, blood loss, time to recovery, complication morbidities, and overall survival were similar between the two groups. Compared with the classic R-Y group, the uncut R-Y group displayed a significantly decreased QOL at POM 9, possibly due to loop recanalization, determined to be occupied 34.2% of the uncut R-Y group. Post-exclusion of recanalization, the QOL was still higher in the classic R-Y group than in the uncut R-Y group, despite their hemoglobin and total protein levels being better than those in the classic R-Y group. Preoperative pre-albumin level and impaired fasting glycemia significantly correlated with the postoperative recanalization. CONCLUSION: We found no significant benefit of uncut over classic R-Y reconstruction which challenges the superiority of the uncut R-Y reconstruction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02644148.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Qualidade de Vida , Gastrectomia/métodos , Estudos Retrospectivos , Estudos Prospectivos , Resultado do Tratamento , Anastomose em-Y de Roux/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The cotton bollworm, Helicoverpa armigera is one of the worldwide pests. Electrophysiological properties of voltage-gated sodium channels in central neurons of sensitive and pyrethroid resistant H. armigera were investigated using whole-cell patch clamp technique. The modification effects of pyrethroid insecticides deltamethrin and tefluthrin on sodium channels were also compared. The V0.5 of voltage dependence of activation of resistant H. armigera sodium channels (resistant channels) exhibited an obvious depolarizing shift by 13.52 mV compared to that of sensitive H. armigera sodium channels (sensitive channels). In contrast, the V0.5 of the voltage dependence of steady-state inactivation of the resistant channels showed a significant hyperpolarizing shift by 7.59 mV in comparison with that of the sensitive channels. The time course of recovery from inactivation for the resistant channels was prolonged significantly, by 0.17 ms, compared with that for the sensitive channels. We also assessed the use-dependent effects of deltamethrin and tefluthrin on sensitive sodium channels. Repetitive depolarization remarkably increased the extent of the sensitive channel modification by 10 µM deltamethrin by ~4.61-fold but had no effect on the extent of sensitive channel modifications by 10 µM tefluthrin. These results provide more direct evidence for the presence of nerve insensitivity in resistant H. armigera strains in North of China. The sodium channels of the resistant H. armigera differ from those of the sensitive H. armigera in the fundamental electrophysiological properties, and correspondingly, have a different response to the modification of pyrethroids. Both deltamethrin and tefluthrin have effects on the closed state of the sensitive sodium channels, but deltamethrin has higher affinity to the open state of these channels.
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Inseticidas , Mariposas , Piretrinas , Animais , China , Ciclopropanos , Hidrocarbonetos Fluorados , Inseticidas/toxicidade , Neurônios , Nitrilas , Piretrinas/toxicidadeRESUMO
Two pairs of polymer donor materials based on indacenodithiophene (IDT) and indacenodithieno[3,2-b]thiophene (IDTT) as the donor units are synthesized. Thiophene or selenophene is introduced as the π-bridge units and electron-deficient fluorine-substituted quinoxaline is used as acceptor unit. Selenophene-containing polymers PIDT-DFQ-Se and PIDTT-DFQ-Se show redshifted absorption and narrower bandgaps. Combined with IDTT donor unit, PIDTT-DFQ-Se shows the highest absorption coefficient. Both the IDTT unit and selenophene unit have positive effects on the hole mobilities, making PIDTT-DFQ-Se the highest one. The best power conversion efficiency of 7.4% is obtained from devices based on PIDTT-DFQ-Se:[6,6]-phenyl C71 butyric acid methyl ester (PC71 BM) with a Jsc of 12.6 mA cm-2 , a Voc of 0.89 V, and a fill factor (FF) of 0.66.
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Compostos Organosselênicos/química , Polímeros/química , Energia Solar , Tiofenos/química , Estrutura Molecular , Polímeros/síntese químicaRESUMO
HIV/AIDS is a severe infectious disease with ineffective drug or method found till now. Highly active antiretroviral therapy (HAART) is a treatment method widely internationalized. Its coverage populations are continually expanding due to its definite clinical effect. AIDS prevented and treated by Chinese medicine and pharmacy has ever been reported. Especially early intervention of Chinese medicine syndrome differentiation based treatment can delay the process of HIV-infected subjects' entry into AIDS in AIDS asymptomatic phase. However, it has great significance of clinical and basic researches in the following 4 aspects: (1) attenuating toxic/adverse reactions of HAART; (2) improving clinical effects of HAART; (3) lowering resistance rate of HAART; and (4) treating common opportunistic infections of AIDS in the post-HAART period.
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Síndrome da Imunodeficiência Adquirida , Terapia Antirretroviral de Alta Atividade , Infecções por HIV , Medicina Tradicional Chinesa , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Medicamentos de Ervas Chinesas , HIV , Infecções por HIV/prevenção & controle , HumanosRESUMO
BACKGROUND: Collagen-related cell adhesion molecules (CAMs) are a major component of the extracellular matrix (ECM) and often accumulate in the liver during chronic liver disease or hepatocellular carcinoma (HCC). In this study we identified several promising collagens related to CAMs that may be of clinical use for the diagnosis and prognosis of HCC. METHODS: We obtained multi-omics data including RNA sequencing (RNA-Seq) data, microarray data, proteomic data from the TCGA, GEO databases, GTEx, and NODE. Bioinformatics analyses were then performed to investigate correlations between the expression patterns of significant genes and HCC. Tumor tissue and para-cancerous tissue samples from HCC patients were also used to validate the results using RT-PCR. RESULTS: A literature research and LASSO-COX analysis identified three significant collagen-related CAM genes: SERPINH1, DCN, and ITGB1. Immunohistochemistry images in the Human Protein Atlas Project database showed that SERPINH1 and ITGB1 proteins were moderately or highly expressed in HCC tumor tissues compared to para-cancerous tissue, whereas DCN expression was lower in HCC tumor tissue. These results were validated by RT-PCR. Low- and high-risk groups of HCC patients were distinguished by the logistic panel in the TCGA database. These showed significantly different prognosis, clinicopathological features, and immune cell infiltration. Logistic regression was used to construct predictive models based on the individual expression levels of DCN, SERPINH1, and ITGB1. These showed highly accurate diagnostic ability (AUC = 0.987). CONCLUSIONS: The current findings suggest that the collagen-related CAMs DCN, SERPINH1, and ITGB1 may be potential therapeutic targets in HCC. Logistic panels of DCN, SERPINH1 and ITGB1 could serve as non-invasive and effective diagnostic biomarkers for HCC. CLINICAL TRIAL REGISTRATION: Identifier: NCT03189992. Registered on June 4, 2017. Retrospectively registered (https://clinicaltrials.gov/).
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Proteômica , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , ColágenoRESUMO
Background: We aimed to distinguish the different Chinese medicine (CM) syndromes of acquired immune deficiency syndrome (AIDS) patients at the proteomics level. Methods: We collected AIDS patients diagnosed with different CM syndromes from Weishi County, Kaifeng City, Henan Province, China, including Qi-deficiency syndrome (named QD group) and dampness-heat syndrome (named DH group). Healthy people were collected as controls from Weishi County, Kaifeng city, Henan Province, China. The plasma from three groups were labeled with ITRAQ, LC/MC was used for protein quantitative analysis. Finally, sequence search and cluster analysis were performed. Results: Overall, 27 different proteins were found. Three proteins were up-regulated and 2 proteins down-regulated in the QD group, 11 proteins up-regulated and 13 proteins down-regulated in the DH group. Compared with DH group, there were 7 different proteins in QD group, among which 5 proteins were down-regulated and 2 proteins were up-regulated. When the target protein of DH group was up-regulated, the protein of HC group was down-regulated correspondingly. Conclusion: The significance analysis and clustering of protein results showed that DH group was significantly different from QD group and HC group at the protein level (P<0.05). However, the QD group could not be effectively distinguished from the HC group. AAT, PF4, C-reactive protein and c4bp may be used as potential biomarkers in DH group. Mass spectrometry based on feature selection can be used to classify different CM syndromes.
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Background: The short-term and long-term outcomes of laparoscopic-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) have been subject to controversy with various reconstruction techniques of Billroth-I, Billroth-II, Roux-en-Y, and Uncut. This study aims to compare the short-term and long-term outcomes of LADG and TLDG as well as the outcomes of different anastomoses. Methods: This study enrolled patients with gastric cancer at the First Affiliated Hospital of Nanjing Medical University (NMUH) between 2017 and 2021. Postoperative complications were classified according to the Clavien-Dindo grade. Exclusion criteria included metachronous and synchronous malignancy and palliative surgery. The Kaplan-Meier analysis was applied to assess 5-year prognosis between two groups. Results: This study included 1221 cases with an overall complication rate of 17.37% for LADG, which was significantly higher than TLDG's 10.72%. The incidence of anastomosis-related complications was 4.79% for LADG and 1.13% lower for TLDG. LADG and TLDG did not show significant difference for Grade III-V complications and resected lymph nodes. The postoperative stay was shorter for TLDG than LADG, and R-Y had a longer postoperative stay than B-II and Uncut after combining LADG and TLDG. The operation time was shorter in TLDG cases than that in LADG cases. The 5-year OS of the TLDG group was not significantly better than that of the LADG group. Conclusion: TLDG is superior in overall complication rate, anastomosis-related complication rate, postoperative stay and operation time to LADG. No difference of OS was observed between LADG and TLDG. Four anastomoses had no convincing evidence of being superior in complications rates, post-op stay, and harvested lymph nodes to each other.
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Background: Gastric cancer (GC) continues to be one of the leading causes of cancer-related deaths globally. Diet significantly influences the incidence and progression of GC. However, the relationship between dietary intake and GC is inconsistent. Methods: A study was conducted with adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2016 to investigate possible associations between 32 dietary factors and GC. To further detect potential causal relationships between these dietary factors and the risk of GC, a two-sample Mendelian randomization (MR) analysis was conducted. The primary method employed was the inverse variance weighted (IVW) analysis, and its results were further validated by four other methods. Results: Of the 35,098 participants surveyed, 20 had a history of GC. Based on the results of weighted logistic multivariate analysis, it was observed that there was a positive correlation between total fat intake [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.01-1.17), p = 0.03] and GC as well as negative association of dietary monounsaturated fatty acids (MUFAs) intake [OR = 0.83, 95% CI: (0.76-0.92), p < 0.001]. Further evaluations of the odds of GC across the quartiles of dietary MUFAs showed that the top quartile of total MUFA intake was associated with a lower likelihood of GC in three different models [model1: OR = 0.03, 95% CI: (0.00-0.25), p < 0.01; model2: OR = 0.04, 95% CI: (0.00-0.38), p = 0.01; model3: OR = 0.04, 95% CI: (0.00-0.40), p = 0.01]. For the MR analyses, genetic instruments were selected from the IEU Open GWAS project; IVW analysis showed that GC risk was not associated with MUFAs [OR = 0.82, 95% CI: (0.59-1.14), p = 0.23] or the ratio of MUFAs to total fatty acids [OR = 1.00, 95% CI: (0.75-1.35), p = 0.98]. Similar results were observed when using the other MR methods. Conclusion: The NHANES study revealed that consuming MUFAs was linked to a lower risk of GC, although the results of MR analyses do not provide evidence of a causal relationship. Additional research is therefore necessary to clarify these findings.
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Hepatocellular carcinoma (HCC) is a malignant tumor with high mortality. This study aimed to build a prognostic signature for HCC patients based on immune-related genes (IRGs) and epigenetics-related genes (EPGs). RNA-seq data from Gene Expression Omnibus were used for dynamic network biomarker (DNB) analysis to identify 56 candidate IRG-EPG-DNBs and their first-neighbor genes. These genes were screened using LASSO-Cox regression analysis to finally obtain five candidate genes-RNF2, YBX1, EZH2, CAD, and PSMD1-which constituted the prognostic signature panel. According to this panel, patients in The Cancer Genome Atlas and International Cancer Genome Consortium were divided into high- and low-risk groups. The prognosis, clinicopathological features, and immune cell infiltration significantly differed between the two risk groups. The prognostic ability of the signature panel and expression profiling were further validated using online databases. We used an independent cohort of patients to validate the expression profiles of the five genes using reverse transcription-PCR. CMap and CellMiner predicted four small molecule drug-protein pairs based on the five prognostic genes. Of them, two market drugs approved by the Food and Drug Administration (AT-13387 and KU-55933) have emerged as candidates for HCC study. This new signature panel may serve as a potential prognostic marker, engendering the possibility of novel personalized therapy with classification of HCC patients.
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BACKGROUND: Previous studies have revealed the critical role of transglutaminase 2 (TGM2) as a potential therapeutic target in cancers, but the oncogenic roles and underlying mechanisms of TGM2 in gastric cancer (GC) are not fully understood. In this study, we examined the role and potential mechanism of TGM2 in GC. METHODS: Western blotting, immunohistochemistry, CCK8, colony formation and transwell assays were used to measure TGM2 expression in the GC cells and tissues and to examine the in vitro role of TGM2 in GC. Xenograft and in vivo metastasis experiments were performed to examine the in vivo role of TGM2 in GC. Gene set enrichment analysis, quantitative PCR and western blotting were conducted to screen for potential TGM2 targets involved in GC. Gain/loss-of-function and rescue experiments were conducted to detect the biological roles of STAT1 in GC cells in the context of TGM2. Co-immunoprecipitation, mass spectrometry, quantitative PCR and western blotting were conducted to identify STAT1-interacting proteins and elucidate their regulatory mechanisms. Mutations in TGM2 and two molecules (ZM39923 and A23187) were used to identify the enzymatic activity of TGM2 involved in the malignant progression of GC and elucidate the underlying mechanism. RESULTS: In this study, we demonstrated elevated TGM2 expression in the GC tissues, which closely related to pathological grade, and predicted poor survival in patients with GC. TGM2 overexpression or knockdown promoted (and inhibited) cell proliferation, migration, and invasion, which were reversed by STAT1 knockdown or overexpression. Further studies showed that TGM2 promoted GC progression by inhibiting STAT1 ubiquitination/degradation. Then, tripartite motif-containing protein 21 (TRIM21) was identified as a ubiquitin E3 ligase of STAT1 in GC. TGM2 maintained STAT1 stability by facilitating the dissociation of TRIM21 and STAT1 with GTP-binding enzymatic activity. A23187 abolished the role of TGM2 in STAT1 and reversed the pro-tumor role of TGM2 in vitro and in vivo. CONCLUSIONS: This study revealed a critical role and regulatory mechanism of TGM2 on STAT1 in GC and highlighted the potential of TGM2 as a therapeutic target, which elucidates the development of medicine or strategies by regulating the GTP-binding activity of TGM2 in GC.
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Proteína 2 Glutamina gama-Glutamiltransferase , Fator de Transcrição STAT1 , Neoplasias Gástricas , Humanos , Calcimicina , Linhagem Celular Tumoral , Guanosina Trifosfato/metabolismo , Proteína 2 Glutamina gama-Glutamiltransferase/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Neoplasias Gástricas/patologia , UbiquitinaçãoRESUMO
Background: Anastomotic leakage (AL) after gastrectomy is one of the severest postoperative complications and is related to increasing mortality. In addition, no consensus guidelines about strategies of AL treatment have been established. This large cohort study aimed to inspect the risk factors and efficacy of the conservative treatment for AL in patients with gastric cancer. Methods: We reviewed the clinicopathological data of 3,926 gastric cancer patients undergoing gastrectomy between 2014 and 2021. Results contained the rate, risk factors, and conservative therapy outcomes of AL. Results: In total, 80 patients (2.03%, 80/3,926) were diagnosed with AL, and esophagojejunostomy was the most frequent AL site (73.8%, 59/80). Among them, one patient (2.5%, 1/80) died. Multivariate analysis indicated that low albumin concentration (P = 0.001), presence of diabetes (P = 0.025), laparoscopic method (P < 0.001), total gastrectomy (P = 0.003), and proximal gastrectomy (P = 0.002) were predicting factors for AL. The closure rate for the conservative treatment of AL in the first month after AL diagnosis was 83.54% (66/79), and the median time from leakage diagnosis to the closure of leakage was 17 days (interquartile range 11-26 days). Low level of plasma albumin (P = 0.004) was associated with late leakage closures. In terms of 5-year overall survival, no significant difference was observed between patients with and without AL. Conclusion: The incidence of AL after gastrectomy is associated with low albumin concentration, diabetes, the laparoscopic method, and extent of resection. The conservative treatment is relatively safe and effective for the AL management in patients after gastric cancer surgery.
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Accurate differentiation between pulmonary arteries and veins (A/V) holds pivotal importance in the realm of diagnosing and treating pulmonary ailments. This study presents a new approach that leverages grayscale differences between A/V. Distinctions are measured using median and mean grayscale values within the vessel area. Initially, adherent regions are removed based on vessel structure. The trunk regions are segmented using gray level information near the heart region of the lung boundary. Incorrectly segmented vessels are corrected based on connectivity. For distal lung vessels, a similar distance field is established using a graph-cut method. Experimental results show the algorithm's superior segmentation accuracy, achieving 97.26% compared to the CNN-based average accuracy of 91.67%. Error branches are more concentrated, aiding subsequent manual and automatic correction. This demonstrates the algorithm's effective segmentation of pulmonary A/V.
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HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin's inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of [Formula: see text]9.8[Formula: see text]kcal/mol and [Formula: see text]9.3[Formula: see text]kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin's anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP-FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.
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Curcumina , Infecções por HIV , HIV-1 , Humanos , Curcumina/farmacologia , Curcumina/química , Curcuma/química , HIV-1/genética , HIV-1/metabolismo , Células HEK293 , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Quimiocinas , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Luciferases , Ribonuclease H/farmacologia , Fatores de Transcrição Forkhead/farmacologia , Receptores CCR5/genética , Receptores CCR5/metabolismoRESUMO
Background: For gastric cancer (GC) patients with pylorus outlet obstruction (POO), whether laparoscopic surgery has advantages over open surgery remains unclear. This study aims to investigate the differences between patients with and without POO in open and laparoscopic groups and to determine the differences between laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) in GC patients with POO. Methods: A total of 241 GC patients with POO who underwent distal gastrectomy at the Department of Gastric Surgery of the First Affiliated Hospital of Nanjing Medical University between 2016 and 2021 were included in this study. A total of 1,121 non-POO patients who underwent laparoscopic surgery and 948 non-POO patients who underwent open surgery from 2016 to 2021 were also enrolled in the study. We compared complication rates and hospital stays between open and laparoscopic groups. Results: There was no significant difference for LDG between GC patients with and without POO regarding the overall complication rates (P = 0.063), the Grade III-V complication rate (P = 0.673), and the anastomotic complication rate (P = 0.497) from 2016 to 2021. The patients with POO had longer preoperative hospital stay (P = 0.001) and postoperative hospital stay (P=0.007) compared to patients without POO. No significant difference was observed for open patients between POO and non-POO patients regarding the overall complication rate (P = 0.357), grade III-V complication rate (P = 1.000), and anastomosis-related complication rate (P = 0.766). Compared with open surgery in GC patients with POO (n = 111), the total complication rate of the LDG group was 16.2%, which was significantly lower than that of the open group (26.1%, P = 0.041). No significant differences in the Grade III-V complication rate (P = 0.574) and anastomotic complication rate (P = 0.587) were observed between laparoscopic and open groups. Patients receiving laparoscopic surgery had shorter postoperative hospital stay than open surgery (P = 0.001). More resected lymph nodes (LNs) were also observed in the laparoscopic group (P = 0.0145). Conclusion: The comorbidity of GC with POO does not increase the complication rate after laparoscopic or open distal gastrectomy. In GC patients with POO, laparoscopic surgery shows advantages over open surgery with a lower overall complication rate, shorter postoperative hospital stay, and more harvested lymph nodes. Laparoscopic surgery is a safe, feasible, and effective treatment for GC with POO.
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Traditional Chinese medicine (TCM) syndrome is an important basis for TCM diagnosis and treatment. As Child-Pugh classification as well as compensation and decompensation phase in liver cirrhosis, it is also an underlying clinical classification. In this paper, we investigated the correlation between single nucleotide polymorphisms (SNPs) of Interleukin-10 (IL-10) and TCM syndromes in patients with hepatitis B cirrhosis (HBC). Samples were obtained from 343 HBC patients in China. Three SNPs of IL-10 (-592A/C, -819C/T, and -1082A/G) were detected with polymerase chain-reaction-ligase detection reaction (PCR-LDR). The result showed the SNP-819C/T was significantly correlated with Deficiency syndrome (P = 0.031), but none of the 3 loci showed correlation either with Child-Pugh classification and phase in HBC patients. The logistic regression analysis showed that the Excess syndrome was associated with dizzy and spider nevus, and the Deficiency syndrome was associated with dry eyes, aversion to cold, IL-10-819C/T loci, and IL-10-1082A/G loci. The odds ratio (OR) value at IL-10-819C/T was 4.022. The research results suggested that IL-10-819C/T locus (TC plus CC genotype) is probably a risk factor in the occurrence of Deficiency syndrome in HBC patients.
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ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan is a traditional Chinese herbal formula that has long been used to treat liver cirrhosis, liver failure, and hepatocarcinoma (HCC). However, little is known about its mechanism of action and targets in treating chronic liver disease. AIM OF THE STUDY: This study aimed to detect the critical transition of HCC progression and to explore the regulatory mechanism and targets of Xiaoyaosan treating liver cirrhosis (cirrhosis) using integrative medicinal research involving system biology and pharmacology. MATERIALS AND METHODS: We recruited chronic liver disease participants to obtain gene expression data and applied the dynamic network biomarker (DNB) method to identify molecular markers and the critical transition. We combined network pharmacology and DNB analysis to locate the potential DNBs (targets). Then we validated the DNBs in the liver cirrhosis rat models using Xiaoyaosan treatment. The expression of genes encoding the four DNBs, including Cebpa, Csf1, Egfr, and Il7r, were further validated in rat liver tissue using Western blot analysis. RESULTS: We found EGFR, CEBPA, Csf1, Ccnb1, Rrmm2, C3, Il7r, Ccna2, and Peg10 overlap in the DNB list and Xiaoyaosan-Target-Disease (XTD) network constructed using network pharmacology databases. We investigated the diagnostic ability of each member in the DNB cluster and found EGFR, CEBPA, CSF1, and IL7R had high diagnostic abilities with AUC >0.7 and P-value < 0.05. We validated these findings in rats and found that liver function improved significantly and fibrotic changes were relieved in the Xiaoyaosan treatment group. The expression levels of CSF1 and IL7R in the Xiaoyaosan group were significantly lower than those in the cirrhosis model group. In contrast, CEBPA expression in the Xiaoyaosan group was significantly higher than that in the cirrhosis model group. The expression of EGFR in the Xiaoyaosan group was slightly decreased than in the model group but not significantly. CONCLUSION: Using the DNB method and network pharmacology approach, this study revealed that CEBPA, IL7R, EGFR, and CSF1 expression was remarkably altered in chronic liver disease and thus, may play an important role in driving the progression of cirrhosis. Therefore, CEBPA, IL7R, EGFR, and CSF1 may be important targets of Xiaoyaosan in treating cirrhosis and can be considered for developing novel therapeutics.