Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 927
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33068196

RESUMO

BACKGROUND: The management of high-risk breast lesions diagnosed on image-guided core biopsy remains controversial. We implemented a high-risk breast conference attended by breast pathologists, imagers, and surgeons to prospectively review all contemporary cases in order to provide a consensus recommendation to either surgically excise or follow on imaging at 6-month intervals for a minimum of 2 years. METHODS: Between May, 2015 and June, 2019, 127 high-risk lesions were discussed. Of these 127 cases, 116 had concordant radiology-pathology (rad-path) findings. The remaining 11 patients had discordant rad-path findings. Of the 116 concordant cases, 6 were excluded due to lack of the first imaging follow-up until analysis. Of the remaining 110 patients, 43 had atypical ductal hyperplasia (ADH), 12 had lobular carcinoma in situ (LCIS), 19 had atypical lobular hyperplasia (ALH), 33 had radial scar (RS), 2 had flat epithelial atypia (FEA), and 1 had mucocele-like lesion (ML). We recommended excision for ADH if there were > 2 ADH foci or < 90% of the associated calcifications were removed. For patients with LCIS or ALH, we recommended excision if the LCIS or ALH was associated with microcalcifications or the LCIS was extensive. We recommended excision of RS when < 1/2 of the lesion was biopsied. We recommended all patients with FEA and ML for 6-month follow-up. RESULTS: Following conference-derived consensus for excision, of the 27 ADH excised, 9 were upgraded to invasive carcinoma or ductal carcinoma in situ. Of the six LCIS cases recommended for excision, none were upgraded. Nine excised radial scars revealed no upgrades. Additionally, 3 patients with ADH, 2 with ALH, 1 with LCIS, and 2 with RS underwent voluntary excision, and none were upgraded. All other patients (13 with ADH, 5 LCIS, 17 ALH, 22 RS, 2 FEA and 1 ML) were followed with imaging, and none revealed evidence of disease progression during follow-up (187-1389 days). All 11 rad-path discordant cases were excised with 2 upgraded to carcinoma. CONCLUSIONS: The results of this prospective study indicate that high-risk breast lesions can be successfully triaged to surgery versus observation following establishment of predefined firm guidelines and performance of rigorous rad-path correlation.

2.
Nucleic Acids Res ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045734

RESUMO

In this report, we investigated the molecular mechanism underlying a deafness-associated m.7516delA mutation affecting the 5' end processing sites of mitochondrial tRNAAsp and tRNASer(UCN). An in vitro processing experiment demonstrated that m.7516delA mutation caused the aberrant 5' end processing of tRNASer(UCN) and tRNAAsp precursors, catalyzed by RNase P. Using cytoplasmic hybrids (cybrids) derived from one hearing-impaired Chinese family bearing the m.7516delA mutation and control, we demonstrated the asymmetrical effects of m.7516delA mutation on the processing of tRNAs in the heavy (H)-strand and light (L)-strand polycistronic transcripts. Specially, the m.7516delA mutation caused the decreased levels of tRNASer(UCN) and downstream five tRNAs, including tRNATyr from the L-strand transcripts and tRNAAsp from the H-strand transcripts. Strikingly, mutant cybrids exhibited the lower level of COX2 mRNA and accumulation of longer and uncleaved precursors of COX2 from the H-strand transcripts. Aberrant RNA metabolisms yielded variable reductions in the mitochondrial proteins, especially marked reductions in the levels of ND4, ND5, CO1, CO2 and CO3. The impairment of mitochondrial translation caused the proteostasis stress and respiratory deficiency, diminished ATP production and membrane potential, increased production of reactive oxygen species and promoted apoptosis. Our findings provide new insights into the pathophysiology of deafness arising from mitochondrial tRNA processing defects.

3.
Environ Pollut ; 268(Pt B): 115838, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33099195

RESUMO

The effects of biological activated carbon treatment using Fe2O3 modified coconut shell-based activated carbon (Fe/CAC) were investigated on the occurrence of opportunistic pathogens (OPs) and formation of disinfection by-products (DBPs) in simulated drinking water distribution systems (DWDSs) with unmodified CAC as a reference. In the effluent of annular reactor (AR) with Fe/CAC, the OPs growth and DBPs formation were inhibited greatly. Based on the differential pulse voltammetry and dehydrogenase activity tests, it was verified that extracellular electron transfer was enhanced in the attached biofilms of Fe/CAC, hence improving the microbial metabolic activity and biological removal of organic matter especially DBPs precursors. Meanwhile, the extracellular polymeric substances (EPS) on the surface of Fe/CAC exhibited stronger viscosity, higher flocculating efficiency and better mechanical stability, avoiding bacteria or small-scale biofilms falling off into the water. Consequently, the microbial biomass and EPS substances amount decreased markedly in the effluent of Fe/CAC filter. More importantly, Fe/CAC did significantly enhance the shaping role on microbial community of downstream DWDSs, continuously excluding OPs advantage and inhibiting EPS production. The weakening of EPS in DWDSs resulted in decrease of microbial chlorine-resistance ability and EPS-derived DBPs precursors supply. Therefore, the deterioration of water quality in DWDSs was inhibited greatly, sustainably maintaining the safety of tap water. Our findings indicated that optimizing biological activated carbon treatment by interface modification is a promising method for improving water quality in DWDSs.

4.
Nat Commun ; 11(1): 5263, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067430

RESUMO

Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, blaMBL and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-ß-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of ß-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-ß-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs.

5.
Sci Rep ; 10(1): 18132, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093581

RESUMO

Stage IV breast cancer is metastatic breast cancer (MBC). Because real-world data are lacking in China, our research attempts to explore the effect of locoregional surgery on the prognosis of patients with MBC. A total of 987 patients from 10 hospitals and 2 databases in East China (2004-2018) were included in this study. Overall, 47% of patients underwent locoregional surgery, and 53% did not. Surgeons tended to perform surgery on patients with small tumours (T1/T2), positive hormone receptor (HR) markers, and metastatic sites confined to a single organ and non-visceral sites (bone only/others) (each p < 0.05). Kaplan-Meier survival curves and the log-rank test showed that median survival was longer for patients who had locoregional surgery than for those who did not (45.00 vs. 28.00 months; p < 0.001). Patients who underwent surgery after systemic treatment had better survival than those who underwent surgery immediately (p < 0.001). In most subgroups, overall survival (OS) was significantly longer in the surgery group than in the no-surgery group (each p < 0.05), except for brain metastases and triple negative breast cancer. Therefore, we concluded that locoregional surgery for the primary tumour in MBC patients was associated with a marked reduction in risk of dying except for patients with brain metastases or triple-negative subtype.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33006191

RESUMO

This experiment was conducted to investigate the effects of dietary energy on antioxidant capacity, liver glucose-lipid-related gene expressions and meat fatty acid of Holstein bulls. Thirty-six Holstein bulls (age, 17.0 ± 0.49 months; body weight, 493.3 ± 39.7 kg) were randomly allocated to three dietary treatments. The metabolizable energy of diets was 10.12, 10.90 and 11.68 MJ/kg. Bulls in each dietary treatment were sampled at the age of 20, 23 or 26 months. Results showed that serum glutathione peroxidase and superoxide dismutase decreased with the increasing age. Dietary energy and age had interaction effects on the expressions of fatty acid synthase, peroxisome proliferator-activated receptor alpha, acyl coenzyme A oxidase 1 and carnitine palmitoyl-transferase 1 alpha. Besides, the increase of age and dietary energy increased the expression of liver phosphoenolpyruvate carboxykinase 1. The expressions of liver glucose-6-phosphatase, tumour necrosis factor alpha and sterol regulatory element binding protein 1 increased with the increasing age. The increase of age and dietary energy increased the proportions of C18:1cis-9, C18:2n-6trans and monounsaturated fatty acid. In summary, the increase of age and dietary energy enhanced the intensity of metabolic changes and inflammatory responses. Dietary energy and age affected the expressions of liver lipid metabolism-related genes, further affected meat fatty acid composition of Holstein bulls.

7.
Neural Plast ; 2020: 8851525, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029120

RESUMO

The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell (HC) mechanotransduction and hearing. Cell junctions are indispensable for the establishment of compositionally distinct fluid compartments in the inner ear. Ototoxic drug cisplatin can damage SV and cause sensorineural hearing loss; however, the underlying mechanisms behind such injury are unclear. In this study, after the intraperitoneal injection of cisplatin (3 mg/kg/day for 7 days) in mice, we determined the auditory function by EP recording and auditory brainstem response (ABR) analysis, observed the ultrastructure of SV by transmission electron microscopy (TEM), and examined the expression and distribution of cell junction proteins by western blot, PCR, and immunofluorescence staining. We discovered that the EP was significantly reduced while ABR thresholds were significantly elevated in cisplatin-treated mice; cisplatin induced ultrastructural changes in marginal cells (MCs), endothelial cells (ECs), pericytes, etc. We found that cisplatin insulted auditory function not only by reducing the expression of zonula occludens protein-1 (ZO-1) in MCs of the SV but also by decreasing the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in MCs and basal cells (BCs). More importantly, cisplatin induced activations of perivascular-resident macrophage-like melanocytes (PVM/Ms) and interleukin-1beta (IL-1ß) as well as increased expressions of profibrotic proteins such as laminin and collagen IV in SV. Thus, our results firstly showed that cisplatin induced fibrosis, inflammation, and the complex expression change of cell junctions in SV.

8.
Acta Otolaryngol ; : 1-5, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074754

RESUMO

BACKGROUND: Three semicircular canal plugging (TSCP) is an optimized treatment for intractable Meniere's disease (MD). However, 20-30% of patients experience hearing loss after TSCP, for reasons that remain unclear. OBJECTIVE: To evaluate hearing loss resulting from TSCP. SUBJECTS AND METHODS: This study included 12 patients, which were diagnosed with definite MD and consented to TSCP surgery. Intraoperative auditory brainstem response (ABR) was monitored in each surgical procedure. RESULTS: After opening the mastoid cavity, the ABR threshold increased to 77.08 ± 9.88 dB nHL. The ABR threshold almost recovered to preoperative levels, to 68.33 ± 7.78 dB nHL, after completing TSC outlining. Exposure of three semicircular canal 'blue lines' had little effect on ABR threshold. The most prominent change on hearing loss was observed after mastoid outlining, when 41.67% of patients showed hearing loss ≥10 dB nHL. None of the patients showed a threshold shift ≥10 dB nHL following the last step. CONCLUSIONS: TSCP operation itself caused little hearing damage. SIGNIFICANCE: Ruled out hearing loss as a result of the surgery itself. The reason why 20-30% of patients showed hearing loss in 2-year follow-up visit was not clear, although it may be due to serous fibrous labyrinthitis.

9.
JCO Clin Cancer Inform ; 4: 824-838, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32970484

RESUMO

PURPOSE: To examine the impact of a clinical decision support system (CDSS) on breast cancer treatment decisions and adherence to National Comprehensive Cancer Center (NCCN) guidelines. PATIENTS AND METHODS: A cross-sectional observational study was conducted involving 1,977 patients at high risk for recurrent or metastatic breast cancer from the Chinese Society of Clinical Oncology. Ten oncologists provided blinded treatment recommendations for an average of 198 patients before and after viewing therapeutic options offered by the CDSS. Univariable and bivariable analyses of treatment changes were performed, and multivariable logistic regressions were estimated to examine the effects of physician experience (years), patient age, and receptor subtype/TNM stage. RESULTS: Treatment decisions changed in 105 (5%) of 1,977 patients and were concentrated in those with hormone receptor (HR)-positive disease or stage IV disease in the first-line therapy setting (73% and 58%, respectively). Logistic regressions showed that decision changes were more likely in those with HR-positive cancer (odds ratio [OR], 1.58; P < .05) and less likely in those with stage IIA (OR, 0.29; P < .05) or IIIA cancer (OR, 0.08; P < .01). Reasons cited for changes included consideration of the CDSS therapeutic options (63% of patients), patient factors highlighted by the tool (23%), and the decision logic of the tool (13%). Patient age and oncologist experience were not associated with decision changes. Adherence to NCCN treatment guidelines increased slightly after using the CDSS (0.5%; P = .003). CONCLUSION: Use of an artificial intelligence-based CDSS had a significant impact on treatment decisions and NCCN guideline adherence in HR-positive breast cancers. Although cases of stage IV disease in the first-line therapy setting were also more likely to be changed, the effect was not statistically significant (P = .22). Additional research on decision impact, patient-physician communication, learning, and clinical outcomes is needed to establish the overall value of the technology.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32951585

RESUMO

BACKGROUND: This study aimed to determine the effect and mechanism of Xiaoaiping (XAP) injection combined with S-1 in inhibiting the invasion and metastasis of human GC cells. METHODS: BGC-823 and MGC-803 cells were incubated in vitro, and the effects of treatment on the cytotoxicity and proliferation of BGC-823 and MGC-803 cells were evaluated by MTT assay. Cell adhesion tests and Transwell assays were used to detect the effects of Xiaoaiping injection combined with S-1 on the metastatic ability of BGC-823 and MGC803 cells. The expression of VEGF, metalloproteinases (MMPs) and proteins related to the epithelial-mesenchymal transition (EMT) were detected by Western blotting. Meanwhile, a tumour model was established in nude mice, and the effect of XAP combined with S-1 on BGC-823 cells in vivo was studied. RESULTS: Compared with the single drug group, the combination of XAP with S-1 increased the inhibition rate (P<0.05). The adhesion test showed that the combination group significantly inhibited the adhesion of BGC-823 and MGC-803 cells (P<0.05). Combination of XAP with S-1 reduced the migration and invasion potential of human GC BGC-823 and MGC803 cells. Western blotting showed that the expression of VEGF, MMP-9, N-cadherin and vimentin was decreased and Ecadherin expression was increased in the combination group compared with these expression values in either the XAP or S-1 alone group (P<0.05). In vivo, we found that XAP combined with S-1 had a significant inhibitory effect on the growth of tumours compared with XAP or S-1 alone. Immunohistochemistry showed that XAP combined with S-1 was able to enhance the levels of E-cadherin and downregulate N-cadherin and vimentin. CONCLUSION: The combination of XAP with S-1 can enhance the inhibitory effect of a single drug on proliferation, invasion and metastasis. The mechanism may be related to the decrease in the expression of VEGF and MMP-9 proteins and the effect on EMT.

11.
Int J Nanomedicine ; 15: 6545-6560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32943867

RESUMO

Background: The metastasis, one of the biggest barriers in cancer therapy, is the leading cause of tumor deterioration and recurrence. The anti.-metastasis has been considered as a feasible strategy for clinical cancer management. It is well known that diosgenin could inhibit tumor metastasis and doxorubicin (DOX) could induce tumor apoptosis. However, their efficient delivery remains challenging. Purpose: To address these issues, a novel pH-sensitive polymer-prodrug based on diosgenin nanoparticles (NPs) platform was developed to enhance the efficiency of DOX delivery (DOX/NPs) for synergistic therapy of cutaneous melanoma, the most lethal form of skin cancer with high malignancy, early metastasis and high mortality. Methods and Results: The inhibitory effect of DOX/NPs on tumor proliferation and migration was superior to that of NPs or free DOX. What is more, DOX/NPs could combine mitochondria-associated metastasis and apoptosis with unique internalization pathway of carrier to fight tumors. In addition, biodistribution experiments proved that DOX/NPs could efficiently accumulate in tumor sites through enhancing permeation and retention (EPR) effect compared with free DOX. Importantly, the data from in vivo experiment revealed that DOX/NPs without heart toxicity significantly inhibited tumor metastasis by exerting synergistic therapeutic effect, and reduced tumor volume and weight by inducing apoptosis. Conclusion: The nanocarrier DOX/NPs with satisfying pharmaceutical characteristics based on the establishment of two different functional agents is a promising strategy for synergistically enhancing effects of cancer therapy.

12.
Neural Plast ; 2020: 8829587, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32952548

RESUMO

Aims: This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods: A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results: A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion: A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

13.
Can J Infect Dis Med Microbiol ; 2020: 9373984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963655

RESUMO

Background: Salmonella and Shigella are often associated with fecal-oral transmission and cause large-scale outbreaks in centralized catering units and, therefore, should be frequently and strictly monitored, especially among food handlers. However, no specific and sensitive on-site detection method is available until now. Methods: In this study, an insulated isothermal PCR assay for the detection of Salmonella and Shigella on a field-deployable PCR system was developed. Specificity, sensitivity, reproducibility, and clinical accuracy of the assay were characterized and evaluated. Results: The insulated isothermal PCR assay could be completed within 58 minutes with minimal pretreatment needed. The assay was specific and with good reproducibility. The limit of detection was 103 CFU/mL and 101 CFU/mL for Salmonella and Shigella, respectively, which was comparable to multiplex real-time PCR. Mock on-site clinical evaluation results showed that the analytical sensitivity and specificity of the insulated isothermal PCR assay were 100% and 96.6%, while the positive predictive value and negative predictive value were 94.1% and 100%, respectively. Conclusion: Based on our results, we believe that the assay developed herein could serve as an alternative method for preliminary screening and provide a valuable platform for the on-site detection of Salmonella and Shigella, especially in resource-limited and developing countries.

14.
Analyst ; 145(21): 7009-7017, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-32870185

RESUMO

As a class of ideal fluorescent nanomaterials, self-assembled copper nanoclusters (CuNCs) have attracted increasing interest. Unfortunately, most of these CuNCs only possessed bright luminescence in acidic solution, which limited their practical applications in a physiological environment. Retaining the strong fluorescence of these CuNCs in neutral or alkaline solution is still a challenging task. In this strategy, self-assembled CuNCs were prepared by using 4-methylthiophenol as the protecting ligand. The self-assembled CuNCs display stable and bright luminescence with excitation/emission maxima at 330/605 nm even in neutral and alkaline environments. Interestingly, with the addition of glutathione (GSH), the fluorescence intensity of CuNCs is enhanced strongly through the GSH-controlled aggregation-induced emission enhancement of self-assembled CuNCs. The turn-on fluorescence strategy can determine the GSH concentration in the range from 1 to 100 µM with a limit of detection of 300 nM. In addition, the method is employed for the determination of GSH levels in cells. Therefore, the turn-on fluorescence strategy is reliable, sensitive and suitable for the determination of cellular GSH levels.

15.
Int J Biol Macromol ; 163: 2127-2133, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32946937

RESUMO

Along with advancements in both protein and chemistry science, the chemical modification of proteins is attracting more and more attention. More specifically, the attachment of polymers or reactive moieties into collagen offers a method to add novel functions to this protein. However, the fibrillogenesis of the modified collagen with high grafting density cannot always be achieved. Here, inspired by the hybrid fibrils of xenogeneic collagen, fibrillogenesis of acrylic acid-grafted-collagen (AAc-g-Col) without self-assembly property was achieved by the induction of natural collagen (Col). The step-by-step co-assembly process of AAc-g-Col and Col was confirmed by turbidity assay. The formation of Col/AAc-g-Col hybrid fibrils was verified by TEM since the acryloyl groups of the hybrid fibrils were labelled using HS-AuNPs based on the Michael addition. Moreover, rheology, SEM, and MTT assays revealed that the fibrillary structures and biocompatibility of the Col/AAc-g-Col hydrogel were comparable to that of the Col hydrogel, although they presented a lower viscoelasticity.

16.
Chin Med J (Engl) ; 133(19): 2274-2280, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32925291

RESUMO

BACKGROUND: After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. METHODS: A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. RESULTS: Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function. CONCLUSION: A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.

17.
Int J Cancer ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32930403

RESUMO

Reasons behind the rapid increase of thyroid cancer (TC) in China are uncertain. We assessed the burden of TC and the role of access to screening and salt iodization. We analyzed two national databases in China: Hospital Quality Monitoring System (HQMS) and China Reinsurance Company (CRC) database. HQMS covered 1037 (44.3%) Class 3 hospitals and 76 263 617 Class 3 hospital inpatients in 2013 to 2017 and CRC covered 93 123 018 clients in 2000 to 2016. The proportion of TC inpatients among inpatients in HQMS and TC incidence in critical illness insurance buyers were used to evaluate the association with screening and iodine status. Between 2013 and 2017, the proportion of TC patients in HQMS with urban employee medical insurance and good access to screening increased sharply while there was little change among those with the other two forms of medical insurance. Across provinces, the proportion of TC inpatients in HQMS was positively correlated with per capita disposable income but not with median urinary iodine. Similar findings were observed in the CRC database. In 2017, approximately 1000 individuals were overdiagnosed with TC daily. We conservatively forecast that 5.1 million healthy individuals would become TC patients unnecessarily between 2019 and 2030. Our findings suggested the epidemic of TC in China was substantially underestimated. It was associated with screening but not with salt iodization.

18.
Proc Natl Acad Sci U S A ; 117(36): 22183-22192, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32826329

RESUMO

Among several reversible epigenetic changes occurring during transcriptional activation, only demethylation of histones and cytosine-phosphate-guanines (CpGs) in gene promoters and other regulatory regions by specific demethylase(s) generates reactive oxygen species (ROS), which oxidize DNA and other cellular components. Here, we show induction of oxidized bases and single-strand breaks (SSBs), but not direct double-strand breaks (DSBs), in the genome during gene activation by ligands of the nuclear receptor superfamily. We observed that these damages were preferentially repaired in promoters via the base excision repair (BER)/single-strand break repair (SSBR) pathway. Interestingly, BER/SSBR inhibition suppressed gene activation. Constitutive association of demethylases with BER/SSBR proteins in multiprotein complexes underscores the coordination of histone/DNA demethylation and genome repair during gene activation. However, ligand-independent transcriptional activation occurring during heat shock (HS) induction is associated with the generation of DSBs, the repair of which is likewise essential for the activation of HS-responsive genes. These observations suggest that the repair of distinct damages induced during diverse transcriptional activation is a universal prerequisite for transcription initiation. Because of limited investigation of demethylation-induced genome damage during transcription, this study suggests that the extent of oxidative genome damage resulting from various cellular processes is substantially underestimated.

19.
PLoS Med ; 17(8): e1003188, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760064

RESUMO

BACKGROUND: The impacts of air pollution on circulatory and respiratory systems have been extensively studied. However, the associations between air pollution exposure and the risk of noncommunicable diseases of other organ systems, including diseases of the digestive, musculoskeletal, and genitourinary systems, remain unclear or inconclusive. We aimed to systematically assess the associations between short-term exposure to main air pollutants (fine particulate matter [PM2.5] and ozone) and cause-specific risk of hospital admission in China over a wide spectrum of human diseases. METHODS AND FINDINGS: Daily data on hospital admissions for primary diagnosis of 14 major and 188 minor disease categories in 252 Chinese cities (107 cities in North China and 145 cities in South China) from January 1, 2013, to December 31, 2017, were obtained from the Hospital Quality Monitoring System of China (covering 387 hospitals in North China and 614 hospitals in South China). We applied a 2-stage analytic approach to assess the associations between air pollution and daily hospital admissions. City-specific associations were estimated with quasi-Poisson regression models and then pooled by random-effects meta-analyses. Each disease category was analyzed separately, and the P values were adjusted for multiple comparisons. A total of 117,338,867 hospital admissions were recorded in the study period. Overall, 51.7% of the hospitalized cases were male, and 71.3% were aged <65 years. Robust positive associations were found between short-term PM2.5 exposure and hospital admissions for 7 major disease categories: (1) endocrine, nutritional, and metabolic diseases; (2) nervous diseases; (3) circulatory diseases; (4) respiratory diseases; (5) digestive diseases; (6) musculoskeletal and connective tissue diseases; and (7) genitourinary diseases. For example, a 10-µg/m3 increase in PM2.5 was associated with a 0.21% (95% CI 0.15% to 0.27%; adjusted P < 0.001) increase in hospital admissions for diseases of the digestive system on the same day in 2-pollutant models (adjusting for ozone). There were 35 minor disease categories significantly positively associated with same-day PM2.5 in both single- and 2-pollutant models, including diabetes mellitus, anemia, intestinal infection, liver diseases, gastrointestinal hemorrhage, renal failure, urinary tract calculus, chronic ulcer of skin, and back problems. The association between short-term ozone exposure and respiratory diseases was robust. No safety threshold in the exposure-response relationships between PM2.5 and hospital admissions was observed. The main limitations of the present study included the unavailability of data on personal air pollution exposures. CONCLUSIONS: In the Chinese population during 2013-2017, short-term exposure to air pollution, especially PM2.5, was associated with increased risk of hospitalization for diseases of multiple organ systems, including certain diseases of the digestive, musculoskeletal, and genitourinary systems; many of these associations are important but still not fully recognized. The effect estimates and exposure-response relationships can inform policy making aimed at protecting public health from air pollution in China.


Assuntos
Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Admissão do Paciente/tendências , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Bases de Dados Factuais/tendências , Feminino , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo
20.
Invest Ophthalmol Vis Sci ; 61(10): 23, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32785675

RESUMO

Purpose: Exogenous erythropoietin (EPO) is being considered for tissue protection and angiogenesis in retinal vascular diseases. However, studies are limited by insufficient tools to address signaling effects through the EPO receptor (EPOR). We used a humanized mouse model of hypoactive EPOR signaling to test the hypothesis that EPOR signaling supports angiogenesis in retinovascular diseases. Methods: Humanized Knockin EPOR mice (hWtEPOR) with hypoactive EPOR signaling were compared to littermate wild-type mice (WT). Postnatal day (p)7 mice of each genotype were exposed to 75% oxygen for five days, followed by 21% oxygen in the oxygen-induced retinopathy model (OIR) and compared to room-air (RA)-raised pups. At time points after OIR, pups were sacrificed, and flat-mounted, lectin-stained retinas were analyzed for central avascular area or intravitreal neovascular area (IVNV). Flash-frozen retinas were analyzed for angiogenic protein (Epo, VEGF, p-Stat3) and gene (Vegfa, Kdr, Epo, Hif1α, Hif2α) expression levels. Results: In OIR, hWtEPOR mice had increased AVA compared with WT at p8, p12, and p17, but there was no difference in IVNV between hWtEPOR and WT mice at p17. Although VEGF and p-STAT3 proteins were increased in WT at p17 OIR, there were no differences in retinal angiogenic factor expression levels between hWtEPOR and WT OIR at p17 despite similar areas of IVNV. Conclusions: Our data support the hypothesis that EPOR signaling was associated with regrowth of vascularization following oxygen-induced capillary dropout and played a role in intravitreal angiogenesis. Additional study of EPOR signaling regulation on other angiogenic factor pathways may be considered.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA