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1.
Leuk Res ; 110: 106710, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34619433

RESUMO

In order to investigate the efficacy of lenalidomide, bortezomib and dexamethasone (VRD) induction chemotherapy regimen combined with tandem autologous stem cell transplantation (ASCT) in treating multi-hit multiple myeloma (MM), we analyzed 252 cases of newly diagnosed MM treated with the bortezomib-containing induction chemotherapy from June 2016 to June 2019. According to the fluorescence in situ hybridization (FISH) results on diagnosis, the patients were divided into multi-hit MM group (47 cases), single-hit MM group (81 cases), and standard-risk group (124 cases). Our analysis showed that R-ISS stageⅢ in transplantation group and R-ISS stageⅢ, multi-hit and VGPR or above was not achieved at the fourth cycle of chemotherapy in non-transplantation group were independent factors for poor prognosis by univariate and multivariate analyses. Moreover, the overall response rate (ORR) of VRD induction chemotherapy group was significantly higher than that of the non-VRD group in the single-hit and multi-hit groups (P = 0.021, P = 0.032); In terms of ASCT, tandem-ASCT can significantly improve the 2-year PFS (77.8 ± 3.9 %) and OS (83.3 ± 5.6 %) of multi-hit MM (P = 0.024, P = 0.037), while single-ASCT only has a limited effect on PFS (61.5 ± 3.0 %) and OS (71.9 ± 4.5 %) (P = 0.115, P = 0.155).

2.
Medicine (Baltimore) ; 100(39): e27392, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596165

RESUMO

RATIONALE: Hepatic inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a very rare disease. Till now, only 19 cases were reported in the English literature. However, the coexistence of IPT-like sarcoma and non-Hodgkin lymphoma (NHL) in the same patient has never been reported. In this report, we presented a case of hepatic IPT-like FDC with hepatic NHL history of which both were successfully resected. PATIENT CONCERNS: We reported a case of a 47-year-old male patient who presented with right upper abdominal discomfort. Nineteen years ago, he underwent liver resection of segment VII for hepatic NHL (B-cell lymphoma). He had a history of chronic hepatitis B virus infection. Serum alpha fetoprotein level was normal. However, imaging studies revealed a well-circumscribed, solid mass in the right hepatic lobe, he came back to the clinic because he was worried about a recurrence of the B-cell lymphoma. DIAGNOSES: Based on the patient's past medical history and magnetic resonance imaging results, and he was diagnosed as hepatocellular carcinoma or hepatic NHL preoperatively. INTERVENTIONS: Right hemi-hepatectomy was performed on this patient. OUTCOMES: Histological report showed features of a mixture of chronic inflammatory cells and variable amounts of spindle cells. Also, immuno-histo-chemical studies demonstrated that all the tumor cells showed strong nuclear in situ labeling for EBV-encoded small RNAs and strongly positive stainings with CD21 and CD35. The patient tolerated the surgery well, recovered smoothly and he was discharged on postoperative day 7 (day 7). The patient is still disease free after a follow-up of over 50 months. CONCLUSIONS: To our knowledge, this is the first report demonstrating hepatic IPT-like FDC sarcoma in a patient with primary hepatic NHL history. In regards to treatment, complete surgical resection should be performed and would acquire excellent long-term outcomes.


Assuntos
Sarcoma de Células Dendríticas Foliculares/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Sarcoma de Células Dendríticas Foliculares/diagnóstico por imagem , Sarcoma de Células Dendríticas Foliculares/cirurgia , Diagnóstico Diferencial , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Linfoma não Hodgkin/diagnóstico , Masculino , Pessoa de Meia-Idade
3.
Front Neurol ; 12: 715317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594296

RESUMO

Pure thalamic infarct is a rare lacunar stroke type, with little known about long-term outcomes. This 8-year, single-center, retrospective study evaluated the clinical background, etiology, Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification, and 8-year follow-up results in 27 patients with pure thalamic infarcts identified by MR diffusion-weighted imaging in Dalian, China. All patients presented chief complaints of limb weakness or sensory disturbances. Hypertension (24/27, 88.9%), diabetes (12/27, 44.4%), atrial fibrillation (1/27, 3.7%), hyperlipidemia (10/27, 37%), hyperhomocysteinemia (6/27, 22.2%), smoking history (10/27, 37%; 9/15, 60% for men; 1/12, 8.3% for women), and excessive alcohol consumption history (7/27, 25.9%; 7/15, 46.7% for men; 0 for women) were observed in our patient population. Based on TOAST classification, 1 patient had large artery atherosclerosis (7.14%), 23 had small vessel occlusion (SVO; 85.2%), and 3 patients were unidentified due to lack of cerebral angiography. The thalamic blood supply classification were as follows: 23 (85.2%), inferolateral territory; 1 (3.7%), tuberothalamic territory; 2 (7.4%), combination of tuberothalamic and paramedian arteries; 1 (3.7%), combination of inferolateral and paramedian arteries; 0, posterior choroidal arteries. During the 8-year follow-up, 3 patients died of colon cancer, multi-organ failure, and kidney failure, respectively; 7 presented with a recurrent stroke; while 10 recovered well with their risk factors under control. In conclusion, our cohort of pure thalamic infarcts were mainly due to SVO (TOAST), with hypertension as the main risk factor, and the inferolateral artery as the most implicated arterial territory. Less severe outcome or stroke recurrence are identified in long-term follow-up of pure thalamic infarcts. Other comorbidities would be cause of death in aged patients.

4.
ACS Chem Neurosci ; 12(20): 3838-3854, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34595918

RESUMO

Prion disease (PrD) and Parkinson's disease (PD) are neurodegenerative diseases characterized by aggregation of misfolded proteins in brain tissues, including protease-resistant prion protein (PrPSc) in PrD and α-synuclein in PD. In recent years, overlap of these two proteins has attracted increased attention, and cross-seeding of prion proteins by aggregated α-synuclein has been proposed. However, the changes in α-synuclein after prion infection are still unclear. In this study, we showed that α-synuclein expression was significantly decreased in the brains of prion-infected rodent models, in the SMB-S15 cell line, which exhibits persistent prion replication, and in the brains of humans with PrDs. Meanwhile, α-synuclein phosphorylated at serine 129(p(S129)-α-synuclein) was significantly increased in the brains of scrapie-infected mice and prion-infected SMB-S15 cells. The increased p(S129)-α-synuclein colocalized with GFAP- and NeuN-positive cells in the brains of scrapie-infected mice. p(S129)-α-synuclein was also observed in the cytoplasm of SMB-S15 and HEK-293 cells transiently expressing an abnormal form of prion protein (Cyto-PrP). Molecular interactions between PrP and α-synuclein were detected in recombinant proteins, normal and prion-infected brain tissues, and cultured cells. The increased p(S129)-α-synuclein colocalized with PrP signals from prion-infected SMB-S15 and HEK-293 cells expressing Cyto-PrP. Moreover, increased morphological colocalization of p(S129)-α-synuclein with mitochondrial markers was also detected in the two cell types. Our results indicate that prion replication and accumulation in cells and brains induce hyperphosphorylation of α-synuclein, particularly at S129, which may aggravate mitochondrial damage and facilitate α-synuclein aggregation in the central nervous system tissues from PrDs.

5.
Steroids ; : 108929, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653443

RESUMO

One new cevanine isosteroidal alkaloid named 5,6-anhydrohupehenine (1), together with five known alkaloids (2-6) were isolated from Fritillaria hupehensis Hsiao et K.C.Hsia, among which 5,6-anhydrohupehenine (1) exhibited strong inhibitory activity against HepG2 (IC50 = 12.21 µM) and MCF-7 (IC50 = 22.05 µM) cancer cells. Therefore, a total of 33 5,6-anhydrohupehenine derivatives (9a-9s, 10a-10f, 11a-11b, and 12a-12f) were synthesized and evaluated for their cytotoxic activity. The cytotoxicity evaluation of all 5,6-anhydrohupehenine derivatives against HepG2 and MCF-7 human cancer cells revealed that 9s displayed best activity against HepG2 cells with IC50 at 1.27 µM. Further biological evaluations on 9s showed that it inhibited the proliferation of HepG2 cells and induced apoptosis of the HepG2 cells by activating cleaved caspase-3. Moreover, 9s exhibited strong antimetastatic potential. These results suggest that 5,6-anhydrohupehenine is a promising compound to be designed as novel cytotoxic agents.

6.
Zhongguo Zhen Jiu ; 41(10): 1095-102, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34628741

RESUMO

OBJECTIVE: To observe the effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy. METHODS: Twenty children with cerebral palsy (cerebral palsy group) were randomly divided into an acupuncture and rehabilitation group (11 cases) and a rehabilitation group (9 cases), and 10 healthy children were included as the normal group. The rehabilitation group was treated with rehabilitation training, 30 min each time; on the basis of rehabilitation training, the acupuncture and rehabilitation group was treated with acupuncture at Sishenzhen, Zhisanzhen, Naosanzhen, Niesanzhen, Dazhui (GV 14), Shenzhu (GV 12), Mingmen (GV 4), etc. The Sishenzhen (left and right points) and the ipsilateral Niesanzhen were respectively connected with a group of electrodes, intermittent wave, frequency of 2 Hz for 30 min. Both groups were treated once every other day, three times a week, totaling for 3 months. The Gesell developmental diagnostic scale (GESELL) was used to evaluate the developmental quotient (DQ) scores before and after treatment, and the blood samples of children with cerebral palsy before and after treatment and normal children were collected for amino acid metabolomics. RESULTS: Compared before treatment, the DQ scores of adaptation, fine motor and social in the acupuncture and rehabilitation group was increased after treatment (P<0.05), and the DQ score of fine motor in the rehabilitation group was increased after treatment (P<0.05). Compared with the normal group, the serum L-glutamate, L-ornithine, L-tyrosine, L-methionine and L-arginine in the cerebral palsy group were down-regulated, and L-histidine, L-citrulline, 5-hydroxylysine and L-glutamine were up-regulated before treatment. The functional pathways mapped by different metabolites between the cerebral palsy group and the normal group included arginine biosynthesis, arginine and proline metabolism, etc. Compared with the cerebral palsy group, the serum L-histidine was decreased, and L-citrulline showed decreasing trend in the acupuncture and rehabilitation group after treatment. CONCLUSION: Acupuncture combined with rehabilitation training could improve cognitive function in children with cerebral palsy, and the effect may be related to the down-regulation of L-histidine and L-citrulline metabolism.


Assuntos
Terapia por Acupuntura , Paralisia Cerebral , Pontos de Acupuntura , Aminoácidos , Paralisia Cerebral/terapia , Criança , Cognição , Humanos
7.
Artigo em Inglês | MEDLINE | ID: mdl-34676106

RESUMO

Accurate theoretical predictions of desired properties of materials play an important role in materials research and development. Machine learning (ML) can accelerate the materials design by building a model from input data. For complex datasets, such as those of crystalline compounds, a vital issue is how to construct low-dimensional representations for input crystal structures with chemical insights. In this work, we introduce an algebraic topology-based method, called atom-specific persistent homology (ASPH), as a unique representation of crystal structures. The ASPH can capture both pairwise and many-body interactions and reveal the topology-property relationship of a group of atoms at various scales. Combined with composition-based attributes, ASPH-based ML model provides a highly accurate prediction of the formation energy calculated by density functional theory (DFT). After training with more than 30,000 different structure types and compositions, our model achieves a mean absolute error of 61 meV/atom in cross-validation, which outperforms previous work such as Voronoi tessellations and Coulomb matrix method using the same ML algorithm and datasets. Our results indicate that the proposed topology-based method provides a powerful computational tool for predicting materials properties compared to previous works.

8.
Front Oncol ; 11: 715799, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604052

RESUMO

Objectives: To evaluate the relationship between deep inguinal lymph node metastasis (ILNM) and pelvic lymph node metastasis (PLNM) and explore the prognostic value of deep ILNM in penile squamous cell carcinoma (PSCC). Materials and Methods: The records of 189 patients with ILNM treated for PSCC were analysed retrospectively. Logistic regression models were used to test for predictors of PLNM. Cox regression was performed in univariable and multivariable analyses of cancer-specific survival (CSS). CSS was compared using Kaplan-Meier analyses and log rank tests. Results: PLNM were observed in 53 cases (28.0%). According to logistic regression models, only deep ILNM (OR 9.72, p<0.001) and number (≥3) of metastatic inguinal lymph nodes (ILNs) (OR 2.36, p=0.03) were independent predictors of PLNM. The incidences of PLNM were 18% and 19% with negative deep ILNM and extranodal extension (ENE); and 76% and 42% with positive deep ILNM and ENE, respectively. The accuracy of deep ILNM, ENE, bilateral involvement and number (≥3) of ILNMs for predicting PLNM were 81.0%, 65.6%, 63.5% and 67.2%, respectively. The CSS was significantly different in patients with positive and negative deep ILNM (median 1.7 years vs not reached, p<0.01). Patients who presented with deep ILNM had worse CSS (median 3.8 years vs not reached, p<0.01) in those with negative PLNs. Conclusions: Deep ILNM is the most accurate factor for predicting PLNM in PSCC according to our data. We recommend that patients with deep ILNM should be referred for pelvic lymph node dissection. Involvement of deep ILNs indicates poor prognosis. We propose that patients with metastases of deep ILNs may be staged as pN3.

10.
Clin Lab ; 67(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655202

RESUMO

BACKGROUND: Alzheimer's disease (AD) is clinically characterized as a progressive cognitive impairment and behavioral disorder. Pathological hallmarks of AD include extracellular senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and massive neuronal loss. Although the exact cause of AD is not well understood, a mounting body of evidence has demonstrated that the pathogenesis of AD is associated with oxidative stress, neu-roinflammation, and amyloid beta (Aß) induced neural apoptosis. Moreover, overexpression of ß-secretase 1 (BACE1), Aß, mammalian target of rapamycin (mTOR), and Tau proteins are closely related to cognitive symptoms in AD. Studies have demonstrated that artemether, an antimalarial drug with acceptable side effects, possesses protective effects against neuroinflammation and oxidative stress. Importantly, artemether can easily penetrate the blood brain barrier, thereby representing an ideal drug candidate for AD treatment. METHODS: The effect of artemether on memory protection and the associated molecular mechanisms were investigated in an Aß25-35 induced cognitive impairments rat model. RESULTS: Results of the in vivo study showed that oral administration of artemether significantly attenuated Aß25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly downregulated the endogenous expression of Aß, BACE1, mTOR, and Tau proteins in N2a cells. CONCLUSIONS: The beneficial effect of artemether against Aß 25-35-induced cognitive impairments was attributable to the downregulation of the expression of Aß, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides , Animais , Artemeter , Ácido Aspártico Endopeptidases/genética , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Fragmentos de Peptídeos , Ratos , Serina-Treonina Quinases TOR , Proteínas tau
11.
Biomolecules ; 11(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34572480

RESUMO

The prognostic heterogeneity in patients with BRAF V600E metastatic colorectal cancer (mCRC) remains poorly defined. Real-world data of 93 BRAF V600E mCRC patients from Sun Yat-sen University Cancer Center were evaluated using the prognostic factors affecting overall survival (OS). Treatment of metastases served as an independent prognosticator, where curative locoregional interventions (LRIs) were associated with superior clinical outcomes (adjusted hazard ratio (HR): 0.46, 95% confidence interval (CI): 0.22-0.98; p = 0.044). The LRIs group showed an improved median OS of 49.4 months versus 18.3 months for the palliative treatments (PTs) group. The median OS of patients with colorectal liver metastasis (CRLM) was significantly prolonged after undergoing LRIs (42.4 vs. 23.7 months; HR: 0.11, 95% CI: 0.01-1.22; p = 0.030), and patients in the LRIs plus liver-limited or lung-limited metastasis (LLM) group benefited more than those in the LRIs plus non-LLM group when compared to the PTs group (LLM from LRIs vs. PTs, HR: 0.16, 95% CI: 0.04-0.68; p = 0.006. Non-LLM from LRIs vs. PTs, HR: 0.47, 95% CI: 0.21-1.05; p = 0.074). In conclusion, we confirmed the positive prognostic value of LRIs in BRAF V600E mCRC, particularly in patients with CRLM or LLM.

12.
Pharm Biol ; 59(1): 1314-1325, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34569428

RESUMO

CONTEXT: Lycium barbarum L. (Solanaceae) seed oil (LBSO) exerts LBSO exerts protective effects in the testis in vivo and in vitro via upregulating SIRT3. OBJECTIVE: This study evaluates the effects and mechanism of LBSO in the d-galactose (d-gal)-induced ageing testis. MATERIALS AND METHODS: Male Sprague Dawley (SD) rats (n = 30, 8-week-old) were randomly divided into three groups: LBSO group (n = 10) where rats received subcutaneous injection of d-gal at 125 mg/kg/day for 8 weeks and intragastric administration of LBSO at 1000 mg/kg/day for 4 weeks, ageing model group (n = 10) received 8-week-sunbcutaneous injection of d-gal, and control group (n = 10) with same administration of normal saline. Lentivirus had established TM4 cells with SIRT3 overexpression or silencing before LBSO intervened in vitro. RESULTS: Treatment with LBSO, the levels of INHB and testosterone both increased, compared to ageing model. In vitro, we found the ED50 of LBSO was 86.72 ± 1.49 and when the concentration of LBSO at 100 µg/mL to intervene TM4 cells, the number of cells increased from 8120 ± 676.2 to 15251 ± 1119, and the expression of SIRT3, HO-1, and SOD upregulated. However, HO-1 and SOD were dysregulated by silencing SIRT3. On the other hand, the expression of AMPK and PGC-1α upregulated as an effect of SIRT3 overexpression by lentivirus, meanwhile the same increasing trend of that being found in cells treated with LBSO, compared to control group. DISCUSSION AND CONCLUSIONS: LBSO alleviated oxidative stress in d-gal-induced sub-acutely ageing testis and TM4 cells by suppressing the oxidative stress to mitochondria via SIRT3/AMPK/PGC-1α.

13.
Bioengineered ; 12(1): 5620-5631, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34515615

RESUMO

Numerous differentially expressed circular RNAs (circRNAs) have been identified; however, their roles have not been fully elucidated. Since dysregulated circRNAs may have clinical applications, it is vital to study their expression characteristics, function, and mechanism in prostate cancer cells. The role, regulatory mechanism, and expression of hsa_circ_0075542 were analyzed using quantitative reverse transcription polymerase chain reaction. The results indicated that the expression of hsa_circ_0075542 was downregulated in prostate tumor tissues. The functions of prostate cancer cell lines LNCaP and PC3 cells were assessed using cell counting kit-8 and transwell assays and flow cytometry analysis. The results of the functional experiments showed that overexpression of hsa_circ_0075542 suppressed cell proliferation, reduced migration and invasiveness capabilities, and promoted apoptosis. Moreover, hsa_circ_0075542 targeted the microRNA-1197 (miR-1197) homeobox C11 (HOXC11) axis by sponging miR-1197. Overexpression of miR-1197 played a tumor-promoting role. Overexpression of hsa_circ_0075542 alleviated the tumor-promoting effect of miR-1197 overexpression In conclusion, hsa_circ_0075542 suppressed malignant characteristics and promoted apoptosis in LNCaP and PC3 cells by acting as a competing endogenous RNA of miR-1197. The hsa_circ_0075542/miR-1197 axis might play a role via HOXC11.

14.
Infect Drug Resist ; 14: 3667-3671, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526786

RESUMO

Objective: To observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis. Methods: We retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups. Results: Among the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ 2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ 2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury. Conclusion: Non-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.

15.
Ann Transl Med ; 9(16): 1313, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532450

RESUMO

Background: The prognostic value of hypertension remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). In this study, we aimed to develop hypertension as a prognostic signature for improving the clinical outcome of non-metastatic NPC patients treated with IMRT. Methods: A clinical cohort, comprising 1,057 patients with non-metastatic, histologically proven, NPC who were treated with IMRT were retrospectively reviewed. Associations between hypertension and overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were estimated by Cox regression. A subgroup analysis of the relationship between hypertension grade and NPC prognosis was also conducted. Results: Among the 1057 patients, 94 (8.9%) had hypertension. Significant differences were observed between patients with hypertension and patients without hypertension in relation to OS (66.6% vs. 85.4%; P<0.0001), PFS (60.8% vs. 76.3%; P=0.001), LRRFS (85.3% vs. 90.5%; P=0.024), and DMFS (77.4% vs. 85.1%; P=0.048), and patients without hypertension had greater treatment success rates. The Cox analysis showed that hypertension was an independent unfavorable prognostic factor for OS [hazards ratio (HR), 2.056; P=0.001], PFS (HR, 1.716; P=0.005), and DMFS (HR, 1.658; P=0.049). The patients with more severe levels of hypertension had worse OS and LRRFS. Specifically, the 5-year OS and LRRFS for grades 1, 2, and 3 were 70.6%, 64.3%, and 62.4% (P=0.712), and 89.5%, 86.4%, and 76.1% (P=0.376), respectively. Conclusions: Hypertension is an independent adverse prognostic factor in NPC patients treated with IMRT. The question of whether the severity of hypertension affects prognosis needs to be further verified by large sample data.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34583911

RESUMO

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

17.
Front Pharmacol ; 12: 678256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483898

RESUMO

Sepsis is a highly heterogeneous syndrome that is caused by an unbalanced host response to an infection. Long noncoding RNAs (lncRNAs) have been reported to exert regulatory roles in a variety of biological processes, and became potential biomarkers and therapeutic targets for diverse diseases. However, current understanding on the roles of lncRNAs in sepsis is extremely limited. Herein, to decipher the underlying functions of lncRNAs, we reexplored the 83 transcriptome datasets from specimens with sepsis, no_sepsis by final diagnosis, and control. The results of differentially expressed genes (DEGs), differentially expressed lncRNA (DElncRNA) analysis, and co-expression analysis of lncRNA-mRNA pairs were obtained. We found that the expression pattern of lncRNAs was significantly activated in sepsis specimens, which was clearly distinguished in sepsis from no_sepsis and control specimens. By performing co-expression analysis, we found DElncRNAs were closely related to T-cell activation and immune response-related terms in sepsis by regulating mRNA expression in the trans manner. The lncRNA-mRNA network and the qRT-PCR test revealed that lncRNAs LINC00861, RP11-284N8.3, and CTB-61M7.2 were significantly correlated with the pathogenesis of sepsis. In addition, weighted gene co-expression analysis (WGCNA) and cis-regulation analysis also revealed sepsis-specific lncRNAs were highly associated with important biological processes correlated with sepsis. In summary, the systematic dysregulation of lncRNAs is tightly involved in the remodeling of gene expression regulatory network in sepsis, and the lncRNA-mRNA expression network may be used to refine biomarker predictions for developing novel therapeutic approaches in sepsis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34484410

RESUMO

Vitis amurensis Rupr. "Beibinghong" is abundant in anthocyanins, including malvidin (Mv), malvidin-3-glucoside (Mv3G), and malvidin-3,5-diglucoside (Mv35 G). Anthocyanins offer nutritional and pharmacological effects, but their stability is poor. Interaction of malvid anthocyanins with caffeic acid through ultrahigh pressure technology produces stable anthocyanin derivatives. This study aims to identify the structure of stable mallow-like anthocyanins and to determine the effect of these stable anthocyanins on human umbilical vein endothelial cells (HUVECs) with H2O2-induced oxidative damage and the signaling pathway involved. The products of malvid anthocyanins and caffeic acid bonding were identified and analyzed using ultra-high performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS/MS). The bonding products were malvidin-3-O-guaiacol (Mv3C), malvidin-3-O-(6″-O-caffeoyl)-glucoside (Mv3CG), and malvidin-3-O-(6″-O-caffeoyl)-5-diglucoside (Mv3C5G). An oxidative stress injury model in HUVECs was established using H2O2 and treated with Mv, Mv3G, Mv35 G, Mv3C, Mv3CG, and Mv3C5G at different concentrations (10, 50, and 100 µmol/L). Results showed that the above compound concentrations can significantly increase cell proliferation rate and reduce intracellular reactive oxygen species at 100 µmol/L. The effects of the most active products Mv and Mv3C on the AMP-activated protein (AMPK)/silencing information regulator-1 (SIRT1) pathway were analyzed. Results showed that Mv and Mv3C significantly increased SOD activity in the cells and significantly upregulated the expression of SIRT1 mRNA, SIRT1, and p-AMPK protein. However, they did not significantly change the expression of AMPK protein. After the silent intervention of siRNA in SIRT1 gene expression, the upregulation of SIRT1 and p-AMPK protein by Mv and Mv3C was significantly inhibited. These results indicate that stabilization malvid anthocyanins exerts an antioxidant activity via the AMPK/SIRT1 signaling pathway.

19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 531-535, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494522

RESUMO

Objective To explore the factors related to tympanic membrane perforation in children with acute suppurative otitis media,and to provide reference for clinical practice. Methods We reviewed the clinical data of 1274 children with acute suppurative otitis media from February 2017 to May 2020,and analyzed the factors related to tympanic membrane perforation. Results Tympanic membrane perforation occurred in 67 out of the 1274 children with acute suppurative otitis media,with the incidence of 5.27%.The univariate analysis showed that 11 factors including the duration of onset(t=2.381,P=0.017),upper respiratory tract infection(χ2=12.228,P=0.000),pulmonary infection(χ2=5.242, P=0.022),chronic sinusitis(χ2=12.715,P=0.000),adenoid hypertrophy(χ2=4.783,P=0.029),tympanic empyema(χ2=16.020,P=0.000),the duration of using antibiotics(t=-2.277,P=0.025),combined use of antibiotics(χ2=5.587,P=0.018),the time from onset to selection of antibiotics according to drug sensitivity(t=3.716,P=0.000),procalcitonin(t=2.599,P=0.009),and white blood cell count in peripheral blood(t=2.196,P=0.031)were related to tympanic membrane perforation in children with acute suppurative otitis media.The multivariate logistic analysis showed that the duration of onset(OR=4.854,95% CI=2.675-8.806,P=0.000),upper respiratory tract infection(OR=6.506,95% CI=3.213-13.171,P=0.000),chronic sinusitis(OR=7.866,95% CI=3.780-16.370,P=0.000),tympanic empyema(OR=2.625,95% CI=1.442-4.777,P=0.002),and time from onset to selection of antibiotics according to drug sensitivity(OR=5.107,95% CI=2.129-12.248,P=0.000)were independent risk factors for tympanic membrane perforation in children with acute suppurative otitis media. Conclusion The incidence of tympanic membrane perforation in children with acute suppurative otitis media can be reduced by early treatment,keeping the Eustachian tube unobstructed,draining the tympanic cavity,preventing chronic sinusitis and upper respiratory tract infection,early drug sensitivity test,and selection of antibiotics based on the test results.


Assuntos
Otite Média Supurativa , Perfuração da Membrana Timpânica , Criança , Doença Crônica , Humanos , Otite Média Supurativa/complicações , Pró-Calcitonina , Fatores de Risco , Perfuração da Membrana Timpânica/etiologia
20.
Oncotarget ; 12(18): 1859-1860, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34504658

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.11877.].

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