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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 849-854, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622604

RESUMO

Objective: To explore the clinical efficacy and influencing factors of children receiving mite-specific subcutaneous immunotherapy (SCIT). Methods: We retrospectively analyzed the data of children who had received mite SCIT for 3 years at the Desensitization Center of our hospital. We used the daily medication score (DMS) to evaluate the medication use status (the higher the score, the higher the amount of medications given and the less satisfactorily was the primary disease controlled) and we used the visual analogue scale (VAS) to evaluate clinical symptoms (the higher the score, the more severe the symptoms). Evaluation was performed after the first SCIT treatment and after treatment was given for 3 months, 4 months, 12 months, and 3 years. According to whether medication for the primary disease was stopped after 3 years, the patients were divided into two groups, the discontinued medication group (discontinued group) and the continued medication group (continued group). The general data, DMS, VAS and the decline rate of the two groups were compared, and logistic regression was performed to analyze the influencing factors of the outcome. Results: A total of 711 children were enrolled in the study, with an average age of 8.38 years at the time of the first visit to the hospital. There were 442 males and 269 females. Skin prick test showed that 445 cases only had mite allergy, and 266 cases had mite allergy combined with other allergies. 360 cases have discontinued the medication for the primary disease after 3 years, and 351 cases had relieved symptoms, but still needed to continue with the medication. At the beginning of SCIT treatment, the DMS and VAS of the discontinued group were lower than those of the continued group ( P<0.05). Evaluations from 3 months to 3 years showed that both DMS and VAS continued to decrease compared with those from the beginning, and the decline rate of DMS and VAS of the discontinued group was higher than that of the continued group after 3 years of SCIT ( P<0.05). After 3 months of SCIT, the positive rates of nasal and ocular symptoms in the discontinued group were lower than those in the continued group ( P<0.05). After 3 years of SCIT, the positive rates of nasal, ocular, and chest symptoms in the discontinued group were lower than those in the continued group ( P<0.05). Univariate analysis combined with multivariate logistic regression showed that initial DMS>4 points and initial VAS>3.5 points were protective factors for the discontinuation of the medication for the primary disease at the end of 3 years of SCIT, while the female sex and DMS reduction rate after 12 months of treatment>50% were risk factors for discontinuation. Conclusions: Mite SCIT can help relieve clinical symptoms and reduce the use of medication for symptomatic treatment. Symptoms can be improved after 3 months of SCIT, with the fastest improvement shown in nasal and eye symptoms. It is not recommended to discontinue the medication for the primary disease for too much after 1 year of treatment.


Assuntos
Asma , Ácaros , Animais , Criança , Feminino , Humanos , Imunoterapia , Injeções Subcutâneas , Masculino , Estudos Retrospectivos
2.
iScience ; 24(10): 103133, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34632332

RESUMO

Immune transcripts are essential for depicting onco-immunologic interactions. However, whether cancer cells mimic immune transcripts to reprogram onco-immunologic interaction remains unclear. Here, single-cell transcriptomic analyses of 7,737 normal and 37,476 cancer cells reveal increased immune transcripts in cancer cells. Cells gradually acquire immune transcripts in malignant transformation. Notably, cancer cell-derived immune transcripts contribute to distinct prognoses of immune gene signatures. Optimized immune response signature (oIRS), obtained by excluding cancer-related immune genes from immune gene signatures, and offers a more reliable prognostic value. oIRS reveals that antigen presentation, NK cell killing and T cell signaling are associated with favorable prognosis. Patients with higher oIRS expression are associated with favorable responses to immunotherapy. Indeed, CD83+ cell infiltration, which indicates antigen presentation activity, predicts favorable prognosis in breast cancer. These findings unveil that immune mimicry is a distinct cancer hallmark, providing an example of cancer cell plasticity and a refined view of tumor microenvironment.

3.
Platelets ; : 1-8, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34634980

RESUMO

This study aimed to evaluate the predictive performance of the REACH, PARIS, BleeMACS, and PRECISE-DAPT scores in Chinese patients undergoing coronary drug-eluting stent (DES) implantation. A total of 1911 patients undergoing coronary DES implantation were consecutively recruited and followed up for 1 year. The primary endpoints were BARC type 3 or 5 bleeding and BARC type 2,3, or 5 bleeding. The BleeMACS score and the PRECISE-DAPT score were significantly associated with 1-year incidence of BARC type 3 or 5 bleeding, but not BARC type 2, 3, or 5 bleeding. The discrimination of the PRECISE-DAPT score was moderate for BARC type 3 or 5 bleeding (c-statistic = 0.633), while those of the REACH (c-statistic = 0.533), PARIS (c-statistic = 0.553), and BleeMACS scores (c-statistic = 0.613) were relatively low. However, the analysis of c-statistic, NRI, and IDI detected no significant discrimination improvement of the PRECISE-DAPT score for BARC type 3 or 5 bleeding compared to the other three scores. The calibrations of the PRECISE-DAPT and BleeMACS scores were modest (Hosmer-Lemeshow test p > .05). Decision curve analysis indicated net benefit of the PRECISE-DAPT score in bleeding risk evaluation. In conclusion, the PRECISE-DAPT score performed moderately in predicting BARC type 3 or 5 bleeding, while the discriminative capacities of the REACH, PARIS, BleeMACS scores were relatively low in patients undergoing DES implantation. But no significant discrimination improvement of the PRECISE-DAPT score compared to the other scores could be detected. Further studies are required to develop standardized bleeding risk scores for this population.

4.
Mol Neurobiol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618330

RESUMO

We recently reported that intraperitoneal injection of 7,8-dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor-mimicking small compound, could attenuate alcohol-related behaviors in a two-bottle choice ethanol consumption procedure (IA2BC) in rats via tropomyosin receptor kinase B in the ventral tegmental area (VTA), which is closely related to alcohol use disorder. However, the detailed mechanisms underlying the regulation of 7,8-DHF on alcohol drinking behavior remain elusive. In this study, we determined the role of nitric oxide (NO), a pleiotropic signaling molecule, in the VTA in the action of 7,8-DHF upon alcohol drinking behavior. Intermittent alcohol exposure led to the overexpression of NO in the VTA, especially 72 h after withdrawal from four weeks of ethanol exposure in IA2BC rats. A higher amount of alcohol intake was also found at the same time point, consistent with the overexpression of NO in the VTA. Microinjection of NG-Nitro-l-Arginine Methyl Ester, (NO synthase inhibitor) or 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (NO scavenger) into the VTA inhibited alcohol intake, whereas application of S-Nitroso-N-acetyl-DL-penicillamine (SNAP, the NO donor) in the VTA further enhanced alcohol consumption in IA2BC rats. Interestingly, either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (a sGC inhibitor) or KT5823 [a selective protein kinase G (PKG) inhibitor] blocked NO's enhancing effect on ethanol intake. Intraperitoneal injection of 7,8-DHF reduced the overexpression of NO; SNAP microinjected into the VTA reversed the inhibitory effects of 7,8-DHF on alcohol consumption. Our findings suggest that NO-cGMP-PKG might be involved in regulation of 7,8-DHF on alcohol consumption in IA2BC rats.

5.
Sci Rep ; 11(1): 20523, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654871

RESUMO

Few studies have investigated the relationship between sarcopenia and mild to moderate renal decline. This study aimed to investigate the relationship between chronic kidney disease (CKD) and sarcopenia. In total, 123 patients hospitalized with CKD and 57 healthy volunteers who underwent physical examination during the same period (control group) were analyzed. Body compositions were measured by dual-energy X-ray absorptiometry, and the relative appendicular skeletal muscle index (RASMI) was calculated. Muscular strength was evaluated using hydraulic hand dynamometer. Walking speed within 6 m was measured for muscular function assessment. Single-photon emission computed tomography was performed to measure the glomerular filtration rate of CKD patients, who were then divided into CKD1 (55 patients in CKD stages 1 and 2) and CKD2 (68 patients in CKD stages 3-5). RASMI showed a downward trend with CKD progression (P = 0.001). Multivariate logistic regression analysis showed that age and CKD progression were independent risk factors for sarcopenia. The morbidity of sarcopenia was significantly greater in CKD patients than in healthy volunteers, and the degree of muscle loss was closely related to CKD progression.

6.
J Am Chem Soc ; 143(40): 16768-16776, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34607434

RESUMO

Solid-state Li-metal batteries offer a great opportunity for high-security and high-energy-density energy storage systems. However, redundant interfacial modification layers, intended to lead to an overall satisfactory interfacial stability, dramatically debase the actual energy density. Herein, a dual-interface amorphous cathode electrolyte interphase/solid electrolyte interphase CEI/SEI protection (DACP) strategy is proposed to conquer the main challenges of electrochemical side reactions and Li dendrites in hybrid solid-liquid batteries without sacrificing energy density via LiDFOB and LiBF4 in situ synergistic conversion. The amorphous CEI/SEI products have an ultralow mass proportion and act as a dynamic shield to cooperatively enforce dual electrodes with a well-preserved structure. Thus, this in situ DACP layer subtly reconciles multiple interfacial compatibilities and a high energy density, endowing the hybrid solid-liquid Li-metal battery with a sustainably brilliant cycling stability even at practical conditions, including high cathode loading, high voltage (4.5 V), and high temperature (45 °C) conditions, and enables a high-energy-density (456 Wh kg-1) pouch cell (11.2 Ah, 5 mA h cm-2) with a lean electrolyte (0.92 g Ah-1, containing solid and liquid phases). The compatible modification strategy points out a promising approach for the design of practical interfaces in future solid-state battery systems.

7.
Eur J Clin Pharmacol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636928

RESUMO

PURPOSES: The POPular Risk Score (PRiS), a pharmacogenetic-driven algorithm consisting of CYP2C19 genotype, platelet reactivity, and clinical risk factors, is developed to evaluate ischemic risk and guide dual antiplatelet therapy (DAPT). This study aimed to evaluate the efficacy and safety of DAPT in accordance with the PRiS in patients undergoing drug-eluting stent (DES) implantation. METHODS: A total of 1757 patients recruited in this cohort study were divided into four groups according to the PRiS and type of P2Y12 receptor inhibitor treatment at discharge. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and target vessel revascularization) during 1-year follow-up. The safety endpoints were defined by Bleeding Academic Research Consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5) and clinically relevant bleeding (BARC 2, 3a, 3b, 3c, and 5). RESULTS: Among 1046 patients with PRiS < 2 and 711 patients with PRiS ≥ 2, 34.2% and 38.3% of them were treated with ticagrelor, respectively. The PRiS ≥ 2 was an independent predictor for the 1-year incidence of MACE (HR(95%CI): 2.09 (1.37-3.20), p = 0.001). Multivariable Cox regression indicated that in the PRiS ≥ 2 group, ticagrelor was superior to clopidogrel in reducing the risk of MACE (HR(95%CI): 0.53 (0.29-0.98), p = 0.042), without increasing the bleeding risk. On the other hand, in the PRiS < 2 group, clopidogrel treatment was related to a remarkably lower rate of BARC class ≥ 2 bleeding (HR(95%CI): 0.39 (0.20-0.72), p = 0.003), but comparable incidences of MACE and BARC class ≥ 3 bleeding during 1-year follow-up. Similar associations between P2Y12 receptor inhibitors and 1-year endpoints in the PRiS < 2 and PRiS ≥ 2 group could also be identified in propensity score-weighted analysis and propensity score-matched analysis. CONCLUSION: Tailored DAPT based on the PRiS could assist in improving the prognosis of patients undergoing DES implantation. Further randomized controlled trials are required to provide more evidence for PRiS-guided DAPT.

8.
Cell Death Dis ; 12(10): 893, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593753

RESUMO

Uncontrolled mitosis is one of the most important features of cancer, and mitotic kinases are thought to be ideal targets for anticancer therapeutics. However, despite numerous clinical attempts spanning decades, clinical trials for mitotic kinase-targeting agents have generally stalled in the late stages due to limited therapeutic effectiveness. Alisertib (MLN8237) is a promising oral mitotic aurora kinase A (AURKA, Aurora-A) selective inhibitor, which is currently under several clinical evaluations but has failed in its first Phase III trial due to inadequate efficacy. In this study, we performed genome-wide CRISPR/Cas9-based screening to identify vulnerable biological processes associated with alisertib in breast cancer MDA-MB-231 cells. The result indicated that alisertib treated cancer cells are more sensitive to the genetic perturbation of oxidative phosphorylation (OXPHOS). Mechanistic investigation indicated that alisertib treatment, as well as other mitotic kinase inhibitors, rapidly reduces the intracellular ATP level to generate a status that is highly addictive to OXPHOS. Furthermore, the combinational inhibition of mitotic kinase and OXPHOS by alisertib, and metformin respectively, generates severe energy exhaustion in mitotic cells that consequently triggers cell death. The combination regimen also enhanced tumor regression significantly in vivo. This suggests that targeting OXPHOS by metformin is a potential strategy for promoting the therapeutic effects of mitotic kinase inhibitors through the joint targeting of mitosis and cellular energy homeostasis.

9.
Front Oncol ; 11: 712857, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552871

RESUMO

Objective: To determine the characteristics and spatiotemporal distribution of major gastrointestinal (GI) neoplasms in inpatients from 1995 to 2016 in Wuwei city, northwestern China. Method: Data from all paper and electronic medical records entered between 1995 and 2016 at 12 major public hospitals in Wuwei city were retrospectively collected. Patients with GI neoplasms were identified and classified according to the International Classification of Diseases (ICD)-10. Trends in the incidence of major GI neoplasms were expressed as an annual percentage change (APC), and the Z test was used to assess the time fluctuation trends. Age-standardized incidence rates (ASIRs) were also calculated and the corresponding APC was estimated by the Joinpoint software for long-term trend analysis. Thematic maps of annual incidence at the township level were produced. Results: Among the 19,137 new inpatients identified with GI neoplasms in Wuwei, gastric cancer was the leading cause of morbidity, followed by cancers of the esophagus, colorectum, gastric cardia, liver, and pancreas with ASIRs of 21.8, 11.0, 5.8, 5.7, 4.4, and 1.7 per 100,000 person-years, respectively. Overall, there was a steady increase in the ASIR for all GI neoplasms, and male cases were 2.1 times more frequent than female cases. The ASIR significantly increased by 12.2% per year from 1995 to 2009 for all GI neoplasms, and the increase rates ranged 9.4%-16.7% per year for the individual GI neoplasm. Despite an increase by 1.4% per year from 2009 to 2016, the ASIR decreased for esophageal and gastric cardia cancers by 4.6% and 17.3% per year, respectively. The annual incidence of all GI neoplasms showed significantly differential geographic distributions among different townships of the city during the study period.

10.
Ann Transl Med ; 9(16): 1331, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532468

RESUMO

Background: This study involved a retrospective analysis of 559 metastatic breast cancer (MBC) patients with brain metastasis (BM). We aimed to establish the effectiveness of different preferred treatment methods and factors affecting overall survival following BM diagnosis (BMOS) and explore the feasibility of systemic treatment for MBC patients with BM. Methods: Univariate and multivariate analyses were used to assess the efficacy of different preferred treatments and other factors associated with BMOS, and a nomogram was then established based on the results of the univariate analysis. Results: Patients that initially received systemic drug therapy exhibited a clinical benefit rate (CBR) of 43.9% and an intracranial disease control rate (DCR) of 80.6%. The median time between BM diagnosis and the requirement for local intracranial treatment due to worsening disease status was 10.0 months for these patients (95% CI: 7.811-12.189 months). The median follow-up was 28.0 months, and the median BMOS was 16.0 months. Following BM diagnosis, the systemic drug treatment group had a better outcome than the local brain treatment group, with a respective median BMOS of 22.0 and 16.0 months (χ2=7.743, P=0.005). At the time of BM diagnosis, the median BMOS for patients without neurological symptoms diagnosed by regular screen was significantly longer than that of patients with neurological symptoms (18.0 vs. 13.0 months, respectively; χ2=11.371, P=0.001). Based on these analyses, a nomogram was constructed that incorporated disease-free survival (DFS), Karnofsky performance status (KPS), molecular subtype, number of extracranial metastases, BM location, number of BMs, neurological symptoms, and the preferred treatment approach, with a prediction probability (c-index) value of 0.76. Conclusions: Systemic drug treatment has a beneficial effect on brain lesions, and effective treatment delays the need for local intracranial treatment. Cranial magnetic resonance imaging (MRI) screening can detect asymptomatic BM in MBC patients (particularly those with HER2-positive or triple-negative disease), offering these patients an opportunity to undergo systemic drug therapy, thereby prolonging their survival. To our knowledge, this is a well-fitted nomogram including current treatment and medical examination strategies to predict BMOS probability that offers value as an adjunct for the prognostic evaluation of MBC-BM patients.

11.
J Comp Neurol ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34585379

RESUMO

The medial prefrontal cortex (mPFC) is thought to be closely associated with emotional processes, decision making and memory. Previous studies have identified the prefrontal cortex (PFC) as one of the most vulnerable brain regions in Alzheimer's disease (AD). Running exercise has widely been recognized as a simple and effective method of physical activity that enhances brain function and slows the progression of AD. However, the effect of exercise on the mPFC of AD is unclear. To address these issues, we investigated the effects of four months of exercise on the numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of 12-month-old APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice using stereological methods. The spatial learning and memory abilities of mice were tested using the Morris water maze. Four months of running exercise delayed declines in spatial learning and memory abilities. The stereological results showed significantly lower numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of APP/PS1 mice than in the wild-type (WT) control group. The numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of running APP/PS1 mice were significantly greater than those in the APP/PS1 control mice. In addition, running-induced improvements in spatial learning and memory were significantly associated with running-induced increases in spinophilin-immunoreactive puncta and neurons numbers in the mPFC. Running exercise could delay the loss of spinophilin-immunoreactive puncta and neurons in the mPFC of APP/PS1 mice. This finding might provide an important structural basis for exercise-induced improvements in the spatial learning and memory abilities of individuals with AD. This article is protected by copyright. All rights reserved.

12.
BMC Med ; 19(1): 190, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465315

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthracycline, cyclophosphamide and taxane (ACT), and whether the combination of HRD and tumour immunity can improve the recognition of ACT responders are still unknown. METHODS: Data from 83 TNBC patients in The Cancer Genome Atlas (TCGA) was used as a discovery cohort to analyse the association between HRD and ACT chemotherapy benefits. The combined effects of HRD and immune activation on ACT chemotherapy were explored at both the genome and the transcriptome levels. Independent cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) were adopted to validate our findings. RESULTS: HRD was associated with a longer ACT chemotherapy failure-free interval (FFI) with a hazard ratio of 0.16 (P = 0.004) and improved patient prognosis (P = 0.0063). By analysing both HRD status and ACT response, we identified patients with a distinct TNBC subtype (ACT-S&HR-P) that showed higher tumour lymphocyte infiltration, IFN-γ activity and NK cell levels. Patients with ACT-S&HR-P had significantly elevated immune inhibitor levels and presented immune activation associated with the increased activities of both innate immune cells and adaptive immune cells, which suggested treatment with immune checkpoint blockade as an option for this subtype. Our analysis revealed that the combination of HRD and immune activation enhanced the efficiency of identifying responders to ACT chemotherapy (AUC = 0.91, P = 1.06e-04) and synergistically contributed to the clinical benefits of TNBC patients. A transcriptional HRD signature of ACT response-related prognostic factors was identified and independently validated to be significantly associated with improved survival in the GEO cohort (P = 0.0038) and the METABRIC dataset (P < 0.0001). CONCLUSIONS: These findings highlight that HR deficiency prolongs FFI and predicts intensified responses in TNBC patients by combining HRD and immune activation, which provides a molecular basis for identifying ACT responders.


Assuntos
Neoplasias de Mama Triplo Negativas , Antraciclinas , Ciclofosfamida , Humanos , Reparo de DNA por Recombinação , Taxoides , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética
13.
Front Oncol ; 11: 718556, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497768

RESUMO

Background: For locally advanced gastric cancer (LAGC) with serosal invasion (cT4NxM0), adjuvant chemotherapy (AC) after D2 gastrectomy is the standard therapy in Asia. However, perioperative chemotherapy (PCT) combined with D2 gastrectomy is mostly suggested in Europe and America. As a part of PCT, the value of neoadjuvant chemotherapy (NAC) is unclear. We investigated whether NAC could further improve survival and other outcomes for these patients. Methods: Patients with cT4NxM0 gastric cancer who underwent D2 gastrectomy were analyzed. The patients were divided into two groups based on whether they received NAC: the neoadjuvant chemotherapy (NAC) and direct surgery (S) groups. After propensity score matching (1:1 ratio), survival and perioperative outcomes were analyzed between the two groups. Results: A total of 902 patients met all the eligibility criteria and were enrolled. After propensity score matching, 221 matched pairs of patients were identified. The median overall survival (OS) and disease-free survival (DFS) of all patients were 75.10 and 43.67 months, respectively. The median OS of patients in the NAC and S groups were undefined and 29.80 months, respectively (P<0.0001). The median DFS of patients in the NAC and S groups were undefined and 22.60 months (P<0.0001). There were no significant differences in the radical degrees of operation between the two groups (P=0.07). However, there were significant differences in postoperative hospital stay (P<0.001) and complications (P=0.037) between the two groups. Conclusion: This study suggested NAC can further improve prognosis and prevent recurrence in LAGC (cT4NxM0) patients. NAC is feasible and safe for LAGC (cT4NxM0) patients, and does not increase the risk of perioperative surgery.

14.
Brain Imaging Behav ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34549378

RESUMO

Neuroimaging studies have displayed aberrant brain activities in individual sensory- and emotional-linked regions in postherpetic neuralgia (PHN) patients. However, multi-dimensional dysfunction in chronic pain may rely on the interplay between networks. Little is known about the changes in the functional architecture of resting state networks (RSNs) in PHN. In this cross-sectional study, we recruited 31 PHN patients, 33 RHZ patients and 34 HCs; all participants underwent resting-state functional magnetic resonance imaging scans. We investigated the differences of within- and cross-network connectivities between different outcomes of HZ patients [including PHN and recuperation from herpes zoster (RHZ)] and healthy controls (HCs) so as to extract a characteristic network pattern of PHN. The abnormal network connectivities were then correlated with clinical variables in respective groups. PHN and RHZ patients could be similarly characterized by abnormal within-default mode network (DMN), DMN-salience network (SN) and SN-basal ganglia network (BGN) connectivity relative to HCs. Of note, compared with RHZ patients, PHN patients could be characterized by abnormal DMN-BGN and within-BGN connectivity. Furthermore, the within-DMN connectivity was associated with pain-induced emotional scores among PHN patients. Our study presented that network-level imbalance could account for the pain-related dysfunctions in different outcomes of herpes zoster patients. These insights are potentially useful for understanding neuromechanism of PHN and providing central therapeutic targets for PHN.

15.
Signal Transduct Target Ther ; 6(1): 333, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34482361

RESUMO

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor differentiation and high prevalence of Epstein-Barr virus (EBV) infection. Here, we show that the expression of EBV latent protein LMP1 induces dedifferentiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA. Mechanistically, LMP1 upregulates STAT5A and recruits HDAC1/2 to the CEBPA locus to reduce its histone acetylation. HDAC inhibition restored CEBPA expression, reversing cellular dedifferentiation and stem-like status in mouse xenograft models. These findings provide a novel mechanistic epigenetic-based insight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.

16.
Cancer Med ; 10(19): 6744-6761, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34472719

RESUMO

BACKGROUND: Anthracycline-based chemotherapy (ABC) is one of the standard therapies against breast cancer. However, few guidelines are currently available to optimize the use of ABC. Therefore, the present analysis aimed at determining the profile and treatment patterns of ABC and the association of clinicopathological characteristics with ABC selection. METHODS: We retrospectively analyzed the data of a nation-wide multicenter epidemiological study, which collected the medical records of breast cancer patients receiving chemotherapy in different settings from seven geographic regions in China (NCT03047889). RESULTS: In total, 3393 patients were included, with 2917 treated with ABC. Among them, 553 (89.8%), 2165 (81.7%), and 814 (25.7%) were subjected to ABC as neoadjuvant, adjuvant, and advanced chemotherapy, respectively. The most frequently used regimens were anthracycline-taxane-based combinations for neo- and adjuvant chemotherapy, along with taxanes and oral fluorouracils for the palliative stages. In the overall cohort, patients aged < 40 or 40-65 (p < 0.001), in premenopause (p < 0.001), without comorbidities (p = 0.016), with invasive ductal carcinoma (p= 0.001), high lymph node involvement (p < 0.001), in the pTNM stage II, III, or IV versus stage I (p < 0.001), subjected to mastectomy (p < 0.001) or subjected to sentinel lymph node biopsy combined with axillary lymph node dissection (p = 0.044), or with a decreased disease-free survival (p < 0.001) were more likely to be recommended to ABC. CONCLUSION: Taken together, ABC remained the mainstay of breast cancer treatment, especially in neo and adjuvant therapy. ABC was mainly used as a combination therapy, and the correlation between influencing factors and ABC choice varied during different settings, indicating the preference and different perspectives of medication considered by medical oncologists regarding the use ABC in China.

17.
Front Oncol ; 11: 709617, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540676

RESUMO

Background: For gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT. Methods: We retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study. Results: From May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%). Conclusion: The results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT.

18.
J Oncol ; 2021: 6621722, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567118

RESUMO

Objective: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. Methods: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. Results: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, P < 0.0001), while no prohibitive variables among clinical characteristics were detected. Conclusion: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.

20.
Zhongguo Zhong Yao Za Zhi ; 46(12): 2900-2911, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467680

RESUMO

Paridis Rhizoma(PR) is prepared from the dried rhizome of Paris polyphylla var. yunnanensis(PPY) or P. polyphylla var. chinensis(PPC) in Liliaceae family. The rapid development of PPY or PPC planting industry resulted from resource shortage has caused the waste of a large number of non-medicinal resources. To clarify the chemical compositions in rhizomes, fibrous roots, stems, leaves, seeds and pericarps of PPC, and explore the comprehensive application value and development prospect of these parts, the qualitative and quantitative analyses on the different parts of PPC were carried out by ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) and high performance liquid chromatography(HPLC). A total of 136 compounds were identified, including 112 steroidal saponins, 6 flavonoids, 11 nitrogen-containing compounds and 7 phytosterols. Rhizomes, fibrous roots, and seeds mainly contained protopennogenyl glycosides and pennogenyl glycosides; leaves and stems mainly contained protodiosgenyl glycosides and diosgenyl glycosides; pericarps mainly contained pennogenyl glycosides, followed by diosgenyl glycosides. The total level of four saponins was the highest in fibrous roots and rhizomes, followed by those in the pericarps and arillate seeds, and the lowest in the stems and exarillate seeds. This study can provide data support for the comprehensive development and rational application of non-medicinal parts of PPC.


Assuntos
Liliaceae , Melanthiaceae , Saponinas , Cromatografia Líquida de Alta Pressão , Rizoma , Espectrometria de Massas em Tandem
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