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1.
J Orthop Surg Res ; 16(1): 104, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531039

RESUMO

BACKGROUND: Total hip arthroplasty (THA) for bony ankylosis is technically challenging in patients with ankylosing spondylitis (AS). This study aimed to determine the mid-term results of bilateral synchronous THA for bony ankylosis in patients with AS. METHODS: Nineteen cases of bony ankylosis in patients with AS who received bilateral synchronous THA were included in this study (17 males and 2 females, mean age 49.2 years). Disease duration was 5-38 years (mean 18 years and 6 months). All patients received cementless THA. Intraoperative blood loss, visual analog scale (VAS) score, and complications were assessed. Harris hip scores evaluated the clinical effect. RESULTS: Patients were followed up for 62-98 months (mean 82.5 months). VAS score decreased from 7.42 ± 0.92 to 2.42 ± 0.83, Harris hip score improved from 21.8 ± 7.2 to 80.3 ± 6.5, and the flexion-extension range of the hip improved from 0 to 142.3 ± 6.2°. One patient with septum bronchiale had a fracture intraoperatively and was treated with wire strapping. One patient had a traction injury of the femoral nerve postoperatively and recovered 1 year after the operation. Loosening and subsidence were not observed in all patients. Heterotopic bone formation was noted in 3 patients. No complications such as joint dislocation, acute infection, and deep vein thrombosis were found. CONCLUSION: Bilateral synchronous THA was effective for bony ankylosis of the hip in patients with AS because it improved patients' quality of life and had satisfactory mid-term outcomes.

2.
Elife ; 102021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595435

RESUMO

The kinase PDK1 is a crucial regulator for immune cell development by connecting PI3K to downstream AKT signaling. However, the roles of PDK1 in CD4+ T cell differentiation, especially in T follicular helper (Tfh) cell, remain obscure. Here we reported PDK1 intrinsically promotes the Tfh cell differentiation and germinal center responses upon acute infection by using conditional knockout mice. PDK1 deficiency in T cells caused severe defects in both early differentiation and late maintenance of Tfh cells. The expression of key Tfh regulators was remarkably downregulated in PDK1-deficient Tfh cells, including Tcf7, Bcl6, Icos, and Cxcr5. Mechanistically, ablation of PDK1 led to impaired phosphorylation of AKT and defective activation of mTORC1, resulting in substantially reduced expression of Hif1α and p-STAT3. Meanwhile, decreased p-AKT also suppresses mTORC2-associated GSK3ß activity in PDK1-deficient Tfh cells. These integrated effects contributed to the dramatical reduced expression of TCF1 and ultimately impaired the Tfh cell differentiation.

3.
Nat Commun ; 12(1): 1333, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637761

RESUMO

T follicular helper (TFH) cells are specialized effector CD4+ T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in TFH cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N6-methyladenosine (m6A) modification) in CD4+ T cells impairs TFH differentiation and germinal center responses in a cell-intrinsic manner in mice. METTL3 is necessary for expression of important TFH signature genes, including Tcf7, Bcl6, Icos and Cxcr5 and these effects depend on intact methyltransferase activity. m6A-miCLIP-seq shows the 3' UTR of Tcf7 mRNA is subjected to METTL3-dependent m6A modification. Loss of METTL3 or mutation of the Tcf7 3' UTR m6A site results in accelerated decay of Tcf7 transcripts. Importantly, ectopic expression of TCF-1 (encoded by Tcf7) rectifies TFH defects owing to METTL3 deficiency. Our findings indicate that METTL3 stabilizes Tcf7 transcripts via m6A modification to ensure activation of a TFH transcriptional program, indicating a pivotal function of post-transcriptional regulation in promoting TFH cell differentiation.

4.
Chem Commun (Camb) ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33543182

RESUMO

CoMn phosphide encapsulated in a nitrogen-doped graphene core-shell structure was successfully prepared with Prussian Blue complexes as the precursor and P atom doping at a high temperature. The core-shell heterostructure demonstrates an impressive catalytic performance of hydrogen evolution reaction over a broad pH range, i.e., the overpotentials reach 159, 190 and 279 mV at a current density of 20 mA cm-2 in the conditions of pH = 0, 14 and 7, and maintains excellent stability.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33543534

RESUMO

Pyroptosis as a lytic and inflammatory form of cell death is a powerful tool to fight against cancer. However, pyroptosis is usually activated by chemotherapeutic drugs, which limits its anti-tumor applications due to drug resistance and severe side effects. Herein, we demonstrate that membrane targeting photosensitizers can induce pyroptosis for cancer cell ablation with noninvasiveness and low side effects. A series of membrane anchoring photosensitizers (TBD-R PSs) with aggregation-induced emission (AIE) characteristics were prepared through conjugation of TBD and phenyl ring with cationic chains. Upon light irradiation, cytotoxic ROS were produced in situ, resulting in direct membrane damage and superior cancer cell ablation. Detailed study revealed that pyroptosis gradually became the dominant cell death pathway along with the increase of TBD-R PSs membrane anchoring capability. This study offers a photo-activated pyroptosis-based intervention strategy for cancer cell ablation.

6.
Support Care Cancer ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33598735

RESUMO

PURPOSE: To examine a predictive theoretical model of psychological distress based on the following variables reflected on family caregivers of patients with cancer: the unmet supportive care needs, subjective caregiving burden, social support, and the positive aspects of caregiving. METHODS: A cross-sectional descriptive study was conducted on a sample of 484 dyads of patients and their family caregivers. The caregivers completed structured questionnaires designed to measure psychological distress, unmet supportive care needs, subjective caregiving burden, positive aspects of caregiving, and social support. Patients' demographic variables and medical data were collected from a medical record review. We used a structural equation modeling to test the predictive theoretical model. RESULTS: Path analysis results partially supported the proposed model with satisfactory fit indices. Specifically, family caregivers with an increasing number of unmet needs or a heavier caregiving burden were more likely to have more severe psychological distress. Bootstrapping results supported that the caregiving burden and social support were significant mediators. Greater unmet supportive care needs predicted higher psychological distress through increasing caregiving burden. Stronger social support predicted lower psychological distress through decreasing caregiving burden. Positive aspects of caregiving predicted lower caregiving burden through the increasing perceived social support, which in turn eliminated psychological distress. CONCLUSIONS: Unmet supportive care needs could cause psychological distress through increasing caregiving burden. The positive aspects of caregiving reduced caregiving burden through increasing social support, which subsequently alleviated psychological distress. Interventions that aim to satisfy supportive care needs, to reduce caregiving burden, and to strengthen social support ties may boost the mental health of family caregivers.

7.
Eur Spine J ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616790

RESUMO

PURPOSE: Inadequate decompressions can lead to poor improvement of symptoms in patients with Chiari I malformation (CMI). In this study, the "all-factors-surgery" that including all levels decompressions was performed on symptomatic CMI patients for the snake of eliminating all possible pathogenic factors and reducing the chance of reoperation. METHODS: The "all-factors-surgery" combined operations of posterior fossa decompression, enlarged cranioplasty, duraplasty, cerebellar tonsil partial resection and adhesion release. Total 194 patients from January 2010 to December 2015. The outcome measures included improvement rate of symptoms, patients self-evaluation (improved, unchanged, worsened), Visual Analogue Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Chicago Chiari Outcome Scale (CCOS) score, the diameter of the syrinx and complications. RESULTS: Postoperative data were collected from the three stages: at discharge, the short-term follow-up (average, 9.39 months), and the long-term follow-up (average, 54.44 months). Patients self-evaluation improvement rate in the three follow-up stages was 92.27%, 90.07% and 85.93%. The VAS scores (mean, 1.49, 1.21, 1.47 vs 3.76) and JOA scores (mean, 15.66, 15.99, 16.10 vs 14.84) were significant difference between the follow-up and pre-operation (P < .05). The CCOS scores of short-term and long-term follow-up were significantly better than that at discharge (mean, 14.75, 14.87 vs 13.68) (P < .05). The diameter of syrinx in each follow-up stage was significantly less than that in pre-operation (mean, 3.39, 1.95, 1.87 vs 5.09) (P < .05). There were no serious complications, and no one asked for reoperation during the follow up. CONCLUSION: Symptomatic CMI patients undergoing "all-factors-surgery" had persistently high rates of symptom relief and rarely needed reoperation.

8.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 164-168, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627212

RESUMO

OBJECTIVE: To study the clinical features of children with recurrent medulloblastoma (MB) and treatment regimens. METHODS: A retrospective analysis was performed on 101 children with recurrent MB who were admitted to the hospital from August 1, 2011 to July 31, 2017. The children were followed up to July 31, 2020. The Kaplan-Meier method was used for survival analysis. The Cox regression model was used for multivariate regression analysis. RESULTS: Of the 101 children, 95 underwent remission induction therapy, among whom 51 had response, resulting in a response rate of 54%. The median overall survival (OS) time after recurrence was 13 months, and the 1-, 3-, and 5-year OS rates were 50.5%±5.0%, 19.8%±4.0%, and 10%±3.3% respectively. There was no significant difference in the 5-year OS rate between the children with different ages (< 3 years or 3-18 years), sexes, pathological types, or Change stages, between the children with or without radiotherapy before recurrence or re-irradiation after recurrence, and between the children with different times to recurrence (< 12 months or ≥ 12 months after surgery) (P > 0.05). There were significant differences in the 5-year OS rate between the children with or without reoperation after recurrence and between the children with different recurrence sites (P < 0.05). The children with reoperation after recurrence had a significantly longer survival time than those without reoperation (P=0.007), and the risk of death in children undergoing reoperation after recurrence was 0.389 times (95% confidence interval:0.196-0.774) that in children who did not undergo such reoperation. CONCLUSIONS: As for the recurrence of MB, although remission induction therapy again can achieve remission, such children still have a short survival time. Only reoperation can significantly prolong survival time, and therefore, early reoperation can be considered to improve the outcome of children with recurrent MB.

9.
Cell Biol Int ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527533

RESUMO

Although T cell receptors (TCRs) are related to the progression of breast cancer (BC), but their prognostic values remain unclear. We downloaded the mRNA profiles and corresponding clinical information of 1413 BC patients from the Cancer Genome Atlas and Gene Expression Omnibus database, respectively. The different expression analysis of 104 TCRs in BC samples was performed, and the consensus clustering based on 104 TCRs was performed by using the K-mean method of R language. Univariate cox regression analysis was used to screen TCRs significantly associated with the prognosis of BC, and LASSO Cox analysis was applied to optimize key TCRs. Risk Score was calculated using the prognostic model constructed based on six optimal TCRs, and Multivariate Cox regression analysis was used to determine whether it was as an independent prognostic signature. Finally, the nomogram was constructed by to predict the overall survival of BC patients. Six optimal TCRs (ZAP70, GRAP2, NFKBIE, IFNG, NFKBIA and PAK5) which were favorable for prognosis of BC patients were screened. Risk score could reliably predict the prognosis of BC patients as an independent prognostic signature. In addition, when bringing into two independent prognostic signatures age and risk score, the nomogram model could better predict the overall survival of BC patients. Our results suggested that the poor prognosis of BC patients with high risk might be due to immunosuppressive microenvironment. In summary, a risk prognostic model based on six TCRs was established and could efficiently predict the prognosis of BC patients. This article is protected by copyright. All rights reserved.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33486849

RESUMO

AIM: Levels of American Heart Association-defined cardiovascular (CV) health behaviours have not been fully reported among young adolescents in low- and middle-income countries (LMICs). We describe poor, intermediate and ideal levels of American Heart Association-defined CV health behaviours among young adolescents in LMICs. METHODS: We categorised the levels of CV health behaviours (smoking, body mass index, physical activity and diet) as poor, intermediate, or ideal and calculated the prevalence of each level and the cumulative number of ideal CV health behaviours using the latest data from the global school-based health survey during 2009-2015. The weighted prevalence and 95% confidential intervals were calculated for the whole sample and for sub-groups stratified by gender and age. Pooled overall and regional estimates were calculated using a random-effects model. This study included 153 759 young adolescents from 45 countries. RESULTS: Overall, 86.3% (95% confidence interval, 82.7-89.9), 80.1% (79.8-80.4), 15.4% (13.7-17.2) and 1.7% (1.1-2.2) of respondents reported ideal levels for smoking, body mass index, physical activity and a healthy diet score, respectively. Overall, 0.3% (0.2-0.4) of respondents had 'four' cumulative ideal CV health behaviours. This 'percentage' was lowest in the Americas (0.2%) and highest in Southeast Asia (0.5%). CONCLUSIONS: Consistently low proportions of young adolescents in LMICs met the ideal levels of physical activity and a healthy diet score or had 'four' ideal CV health behaviours. For this population, physical activity and a healthy dietary pattern should be strongly prioritised.

11.
Chem Commun (Camb) ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410450

RESUMO

A chemo- and regioselective Pd(0)-catalyzed spiroannulation has been successfully developed. The key feature of this method is the use of readily available 1,2-dihaloarenes, alkynes and 2-naphthols for the rapid assembly of spirocarbocyclic molecules. Mechanistic studies revealed that this domino reaction proceeded through a cascade of oxidative addition to Pd(0), alkyne migratory insertion, and 2-naphthol-facilitated dearomatizing [4+1] spiroannulation.

12.
Theranostics ; 11(3): 1429-1445, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391543

RESUMO

Rationale: Breast cancer preferentially develops osteolytic bone metastasis, which makes patients suffer from pain, fractures and spinal cord compression. Accumulating evidences have shown that exosomes play an irreplaceable role in pre-metastatic niche formation as a communication messenger. However, the function of exosomes secreted by breast cancer cells remains incompletely understood in bone metastasis of breast cancer. Methods: Mouse xenograft models and intravenous injection of exosomes were applied for analyzing the role of breast cancer cell-derived exosomes in vivo. Effects of exosomes secreted by the mildly metastatic MDA231 and its subline SCP28 with highly metastatic ability on osteoclasts formation were confirmed by TRAP staining, ELISA, microcomputed tomography, histomorphometric analyses, and pit formation assay. The candidate exosomal miRNAs for promoting osteoclastogenesis were globally screened by RNA-seq. qRT-PCR, western blot, confocal microscopy, and RNA interfering were performed to validate the function of exosomal miRNA. Results: Implantation of SCP28 tumor cells in situ leads to increased osteoclast activity and reduced bone density, which contributes to the formation of pre-metastatic niche for tumor cells. We found SCP28 cells-secreted exosomes are critical factors in promoting osteoclast differentiation and activation, which consequently accelerates bone lesion to reconstruct microenvironment for bone metastasis. Mechanistically, exosomal miR-21 derived from SCP28 cells facilitates osteoclastogenesis through regulating PDCD4 protein levels. Moreover, miR-21 level in serum exosomes of breast cancer patients with bone metastasis is significantly higher than that in other subpopulations. Conclusion: Our results indicate that breast cancer cell-derived exosomes play an important role in promoting breast cancer bone metastasis, which is associated with the formation of pre-metastatic niche via transferring miR-21 to osteoclasts. The data from patient samples further reflect the significance of miR-21 as a potential target for clinical diagnosis and treatment of breast cancer bone metastasis.

13.
Anal Chim Acta ; 1145: 26-36, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33453877

RESUMO

Biofilms are broadly formed by diverse microorganisms under stressful environments that are basically surrounded by an EPS matrix, which enable bacterial cells to confer the resistance to the biocides, antibiotics and other invasions. Yet, biofilms cause harmful impacts in various fields, including clinical infections, food contaminations and environmental pollution. However, the mechanism of biofilm formation remains incompletely elucidated, and currently, we lack an efficient strategy to tackle these tough problems by eradicating biofilms. In the present study, we sought to decipher the mechanism of biofilm formation in Escherichia coli from metabolic perspective. By exposing bacterial cells to various concentrations of iron, we found that iron can regulate biofilm formation, and the phenotypic changes were obviously dependent on iron concentration. A functional metabolome assay was further implemented to investigate the regulatory mechanism of iron on biofilm formation; we verified that siderophores mostly account for the transportation of iron into bacterial cells. Then, the bioavailable iron was recruited by bacterial cells to direct the levels of five functional metabolites (l-tryptophan, 5'-MTA, spermidine, CMP and L-leucine), which were identified as new effectors that directly regulate biofilm formation. Taken together, this study is the first to identify five functional metabolites to efficiently regulate biofilm formation, which can be targeted to tackle the harmful impacts associated with biofilm formation in different niches.

14.
Sci Rep ; 11(1): 181, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420301

RESUMO

Cataract surgery is the most common intraocular procedure. To decrease postsurgical inflammation, prevent infection and reduce the incidence of secondary cataract, we built a temperature-sensitive drug delivery system carrying dexamethasone, moxifloxacin and genistein nanostructured lipid carrier (GenNLC) modified by mPEG-PLA based on F127/F68 as hydrogel. Characterizations and release profiles of the drug delivery system were studied. In vitro functions were detected by CCK-8 test, immunofluorescence, wound-healing assay, real time-PCR and western blotting. The size of GenNLCs was 39.47 ± 0.69 nm in average with surface charges of - 4.32 ± 0.84 mV. The hydrogel gelation temperature and time were 32 °C, 20 s with a viscosity, hardness, adhesiveness and stringiness of 6.135 Pa.s, 54.0 g, 22.0 g, and 3.24 mm, respectively. Transmittance of the gel-release medium was above 90% (93.44 ± 0.33% to 100%) at range of 430 nm to 800 nm. Moxifloxacin released completely within 10 days. Fifty percent of dexamethasone released at a constant rate in the first week, and then released sustainably with a tapering down rate until day 30. Genistein released slowly but persistently with a cumulative release of 63% at day 40. The thermoresponsive hydrogel inhibited the proliferation, migration and epithelial-mesenchymal transition of SRA 01/04 cells, which were confirmed by testing CCK-8, wound-healing assay, western blot, real time-PCR (RT-PCR) and immunofluorescence. These results support this intracameral thermoresponsive in situ multi-drug delivery system with programmed release amounts and release profiles to cut down the need of eye drops for preventing inflammation or infection and to reduce posterior capsular opacification following cataract surgery.

15.
J Gynecol Oncol ; 32(2): e23, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33470065

RESUMO

OBJECTIVE: Familial cancer appears at a young age and its incidence is increasing. About 12% of familial ovarian cancer cases are associated with BRCA1/2 mutations (BRCAm). In this study, we investigated BRCA1 methylation may predict ovarian cancer in those with a family history of cancer (FHC) but without BRCA1/2 mutations (BRCAwt). METHODS: Using peripheral blood DNA from 55 subjects without a history of cancer [cancer(-)] and 52 ovarian cancer patients, we examined BRCA1 promoter methylation through bisulfite sequencing of the promoter and expressed the results as the cumulative methylation index. Then, we evaluated the BRCA1 promoter methylation according to BRCA1/2 germline mutations. RESULTS: BRCA1 methylation was more prevalent in the BRCAm cancer(-) group than in the BRCAwt cancer(-) group and ovarian cancer patients (p=0.031 and p=0.019, respectively). In the BRCAwt cancer(-) group, BRCA1 methylation was more prevalent in those with an FHC than in those without one and in the BRCAm cancer(-) group with an FHC (p=0.001 and p<0.001, respectively). CONCLUSION: Our data suggest a predictive role of BRCA1 methylation profile for ovarian cancer in those without a history of cancer but with an FHC. BRCA1 methylation has important implications for diagnostic and predictive testing of those with BRCAwt cancer(-) status with FHC.

16.
Adv Mater ; 33(9): e2007888, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33491820

RESUMO

Radiodynamic therapy (RDT), an emerging therapeutic approach for cancer treatment by employing ionizing irradiation to induce localized photodynamic therapy (PDT) can overcome the drawbacks of the limited penetration depth for traditional PDT and the unconcentrated energy in the tumor for traditional radiotherapy (RT). Taking advantage of aggregation-induced emission (AIE) photosensitizers with bright fluorescence and efficient singlet oxygen production in the aggregate state, Hf-AIE coordination polymer nanoparticles (CPNs), which show both strong RT and RDT effect under X-ray irradiation, are developed. Furthermore, to enhance the tumor accumulation and prolong the tumor retention of the CPNs, bioorthogonal click chemistry is applied in the system through coupling between dibenzocyclooctyne (DBCO)-modified CPNs (Hf-AIE-PEG-DBCO) (PEG: poly(ethylene glycol)) and azide groups on the cell membrane formed by metabolic glycoengineering. Thanks to the high penetration of X-ray irradiation, the bioorthogonal-assisted RT and RDT combination therapy realizes significant killing of cancer cells without showing noticeable biotoxicity after intravenous administration of CPNs.

17.
Eur J Pharmacol ; 896: 173912, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33508280

RESUMO

Ulcerative colitis (UC), as an autoimmune disease, has been troubling human health for many years. Up to now, the available treatments remain unsatisfactory. Rhizoma Coptidis has been widely applied to treat gastrointestinal diseases in China for a long time, and coptisine (COP) is identified as one of its major active components. This study aimed to evaluate the bioactivity of COP on dextran sulfate sodium (DSS)-induced mice colitis and clarify the potential mechanism of action. The results revealed that COP treatment markedly alleviated DSS-induced clinical symptoms by relieving body weight loss and the disease activity index (DAI) score. Specifically, the colon length in the COP (50 and 100 mg/kg) groups were obviously longer than that in the DSS group (7.21 ± 0.34, 8.59 ± 0.45 cm vs. 6.71 ± 0.59 cm, P < 0.01). HE staining analysis revealed that COP treatment significantly protected the integrity of intestinal barrier and alleviated inflammatory cells infiltration. Western blot assay confirmed that COP notably improved the intestinal epithelial barrier function by enhancing the expressions of colonic tight junction proteins and inhibited the expressions of apoptosis-related proteins. In addition, COP treatment remarkably suppressed the levels of colonic myeloperoxidase (MPO), adhesion molecules and pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1ß, IL-6 and IL-17), while enhanced IL-10 and TGF-ß. The mechanism anti-inflammatory of COP might be related to inhibiting the phosphorylation of IκBα, and the translocation of NF-κB p65 from cytoplasm to nucleus. In summary, the study indicated that COP ameliorated DSS-induced colitis, at least partly through maintaining the integrity of intestinal epithelial barrier, inhibiting apoptosis and inflammatory response.

18.
Exp Cell Res ; 399(2): 112465, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33385415

RESUMO

Melanoma is the most aggressive malignant tumor of skin cancer as it can grow rapidly and metastasize. Photodynamic therapy (PDT) is a promising cancer ablation method for skin tumors, although it lacks efficiency owing to factors such as tumor characteristics, delivery of photosensitizers, immune response in vivo etc. Extensive investigation of molecules that can potentially modulate treatment efficacy is required. Protein 4.1R is a cytoskeletal protein molecule. Previous studies have shown that protein 4.1R knockdown reduces PDT sensitivity in mouse embryonic fibroblast cells. However, the functional role of protein 4.1R in melanoma is unclear. In this study, we aimed to elucidate the effect of protein 4.1R on PDT for melanoma in mice and the mechanism of anti-tumor immunity. Our results indicated that CRISPR/Cas9-mediated protein 4.1R knockout promotes the proliferation, migration, and invasion of B16 cells. We further investigated the potential mechanism of protein 4.1R on tumor cell PDT sensitivity. Our results showed that protein 4.1R knockout reduced the expression of membrane transporters γ-aminobutyric acid transporter (GAT)-1 and (GAT)-2 in B16 cells, which affected 5-ALA transmembrane transport and reduced the efficiency of PDT on B16 cells. Protein 4.1R knockout downregulated the anti-tumor immune response triggered by PDT in vivo. In conclusion, our data suggest that protein 4.1R is an important regulator in PDT for tumors and may promote the progress and efficacy of melanoma treatment.

19.
Hum Reprod ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33501984

RESUMO

STUDY QUESTION: What is the current burden of polycystic ovary syndrome (PCOS) at the global, regional, and country-specific levels in 194 countries and territories according to age and socio-demographic index (SDI)? SUMMARY ANSWER: Slight increases in age-standardized incidence of PCOS and associated disability-adjusted life-years (DALYs) were evidenced among women of reproductive age (15-49 years) from 2007 to 2017 at the global level, and in most regions and countries. WHAT IS KNOWN ALREADY: No detailed quantitative estimates of the PCOS incidence and DALYs by age and SDI in these 194 countries and territories have been published previously. STUDY DESIGN, SIZE, DURATION: An age- and SDI-stratified systematic analysis of the PCOS incidence and DALYs across 194 countries and territories has been performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2017 to estimate the total and age-standard PCOS incidence rates and DALYs rates among women of reproductive age in both 2007 and 2017, and the trends in these parameters from 2007 to 2017. MAIN RESULTS AND THE ROLE OF CHANCE: Globally, women of reproductive age accounted for 1.55 million (95% uncertainty intervals (UIs): 1.19-2.08) incident cases of PCOS and 0.43 million (0.19-0.82) associated DALYs. The global age-standardized PCOS incidence rate among women of reproductive age increased to 82.44 (64.65-100.24) per 100 000 population in 2017, representing an increase of 1.45% (1.43-1.47%) from 2007 to 2017. The rate of age-standardized DALYs increased to 21.96 (12.78-31.15) per 100 000 population in 2017, representing an increase of 1.91% (1.89-1.93%) from 2007 to 2017. Over the study period, the greatest increase in the age-standardized PCOS incidence and DALYs rates were observed in the middle-SDI and high-middle SDI regions, respectively. At the GBD regional level, the highest age-standardized incidence and DALY rates in 2017 were observed in Andean Latin America, whereas the largest percentage increases in both rates from 2007 to 2017 were observed in Tropical Latin America. At the national level, Ecuador, Peru, Bolivia, Japan, and Bermuda had the highest age-standardized incidence rates and DALYs rates in both 2007 and 2017. The highest increases in both the age-standardized incidence rates and DALYs rates from 2007 to 2017 were observed in Ethiopia, Brazil, and China. LIMITATIONS, REASONS FOR CAUTION: Although the GBD (2017) study aimed to gather all published and unpublished data, the limited availability of data in some regions might have led to the estimation of wide UIs. Additionally, the PCOS phenotype is complicated and the diagnostic criteria are constantly changing. Consequently, the incidence of PCOS might have been underestimated. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge about the differences in the PCOS burden across various locations will be valuable for the allocation of resources and formulation of effective preventive strategies. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants from the Innovative Talent Support Plan of the Medical and Health Technology Project in Zhejiang Province (2021422878), Ningbo Science and Technology Project (202002N3152), Ningbo Health Branding Subject Fund (PPXK2018-02), Sanming Project of Medicine in Shen-zhen (SZSM201803080), and National Social Science Foundation (19AZD013). No potential conflicts of interest relevant to this article were reported. TRIAL REGISTRATION NUMBER: N/A.

20.
BMC Musculoskelet Disord ; 22(1): 92, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468108

RESUMO

BACKGROUND: The purpose of the study is to investigate the correlation between upper lumbar disc herniation (ULDH) and multifidus muscle degeneration via the comparison of width, the cross-sectional area and degree of fatty infiltration of the lumbar multifidus muscle. METHODS: Using the axial T2-weighted images of magnetic resonance imaging as an assessment tool, we retrospectively investigated 132 patients with ULDH and 132 healthy individuals. The total muscle cross-sectional area (TMCSA) and the pure muscle cross-sectional area (PMCSA) of the multifidus muscle at the L1/2, L2/3, and L3/4 intervertebral disc levels were measured respectively, and in the meantime, the average multifidus muscle width (AMMW) and degree of fatty infiltration of bilateral multifidus muscle were evaluated. The resulting data were analyzed to determine the presence/absence of statistical significance between the study and control groups. Multivariate logistical regression analyses were used to evaluate the correlation between ULDH and multifidus degeneration. RESULTS: The results of the analysis of the two groups showed that there were statistically significant differences (p < 0.05) between TMCSA, PMCSA, AMMW and degree of fatty infiltration. The multivariate logistic regression analysis indicated that the TMCSA, PMCSA, AMMW and the degree of fatty infiltration of multifidus muscle were correlated with ULDH, and the differences were statistically significant (P < 0.05). CONCLUSIONS: A correlation could exist between multifidus muscles degeneration and ULDH, that may be a process of mutual influence and interaction. Lumbar muscle strengthening training could prevent and improve muscle atrophy and degeneration.

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