Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 682
Filtrar
1.
Zhonghua Wai Ke Za Zhi ; 60(1): 57-62, 2022 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-34954948

RESUMO

Objective: To examine the effective and safe outcomes of drug-coated balloon (DCB) angioplasty for the treatment of femoropopliteal long lesions in mid-term and long-term follow-up. Methods: The clinical data of 114 patients with symptomatic (Rutherford 2 to 6) femoropopliteal long lesions who underwent angioplasty with DCB between June 2016 and May 2021 at Department of Vascular Surgery,Beijing Tsinghua Changgung Hospital were retrospectively analyzed. A total of 75 males and 39 females patients were enrolled, aged (71.9±8.4)years (range: 49 to 89 years). Among 138 lesions in 114 patients, there were 111 de nove lesions (80.4%, 111/138). Total occlusions were recanalized in 116 limbs (84.1%, 116/138). The lesion length was (280.9±78.7)mm (range: 150 to 520 mm). DCB angioplasty combined with debulking devices was used in 59 lesions (42.8%, 59/138).The bail-out stent implantation was performed in 27 limbs (19.6%, 27/138). The Kaplan-Meier method was used to evaluate cumulative primary patency rate, freedom from the clinically driven target lesion revascularization (CD-TLR) rate and accumulate survival rate. Univariate and multivariate analyses with Cox proportional hazards models were performed to determine the significant prognostic factors for primary patency. Results: DCB angioplasty was completed in 114 patients. The technical success rate was 98.2%(112/114). The mean follow-up time was 18 months (range: 3 to 54 months).The results showed that primary patency rates at 12, 24 and 36 months postoperatively were 87.5%, 75.2% and 55.1%, respectively. Freedom from CD-TLR rate at 12, 24 and 36 months postoperatively were 92.4%, 81.8% and 68.7%, respectively. Accumulate survival rate at 12, 24 and 36 months postoperatively were 96.2%, 94.0% and 80.2%. Multivariate Cox's regression analyses showed that chronic limb-threatening ischemia(CLTI) (HR=2.629, 95%CI:1.519 to 4.547, P<0.01) and hyperlipidemia (HR=2.228, 95%CI: 1.004 to 4.948, P=0.026) were independent prognosis factors for primary patency in DCB treatment of femoropopliteal long lesions. Conclusions: DCB provided favorable outcomes for the treatment of femoropopliteal long lesions. CLTI and hyperlipidemia are independent prognosis factors for restenosis after DCB angioplasty.

2.
J Dent Res ; : 220345211054744, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34875910

RESUMO

Porphyromonas gingivalis is responsible for the destruction of cementum in patients with periodontitis and periapical periodontitis. However, research about the effects of P. gingivalis on cementoblast mineralization and the underlying mechanism is still lacking. Casein kinase 2 interacting protein 1 (Ckip-1) is a scaffold protein that interacts with various proteins and signals to regulate different cell functions, such as cell morphology, apoptosis, and differentiation. In this study, we verified the suppressive effects of P. gingivalis and lipopolysaccharide (Pg-LPS) on OCCM-30 mineralization. We also showed that Ckip-1 gradually decreased during OCCM-30 mineralization but increased with the aggravation of Pg-induced inflammation. However, it remained unchanged when cells were stimulated with Pg-LPS, regardless of the concentration and incubation time. Then, more cellular cementum and enhanced Osterix expression were observed in Ckip-1 knockout mice when compared with the wild-type mice. Meanwhile, Ckip-1 silencing significantly enhanced cementoblast mineralization with or without P. gingivalis-associated inflammation. The trend was opposite when Ckip-1 was overexpressed. Finally, we found that the p38, Akt, and Wnt pathways were activated, while the Erk1/2 pathway was inhibited when Ckip-1 was silenced. The opposite results were also observed in the Ckip-1 overexpression group. Furthermore, we proved that cell mineralization was weakened when p38, Akt inhibitors were applied and strengthened when the Erk1/2 pathway was inhibited. In summary, Ckip-1 is upregulated underP. gingivalis-induced inflammation and negatively regulates cementoblast mineralization partially through mitogen-activated protein kinases and Akt signaling pathways, which may contribute to the restoration of cementum destroyed by P. gingivalis.

3.
Clin Cancer Res ; 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34965943

RESUMO

PURPOSE: To explore relationships between biological gene expression signatures and pembrolizumab response. EXPERIMENTAL DESIGN: RNA sequencing data on baseline tumor tissue from 1188 patients across seven tumor types treated with pembrolizumab monotherapy in nine clinical trials were used. A total of eleven prespecified gene expression signatures (18-gene T-cell-inflamed gene expression profile [TcellinfGEP], angiogenesis, hypoxia, glycolysis, proliferation, MYC, RAS, granulocytic myeloid-derived suppressor cell, monocytic myeloid-derived suppressor cell [mMDSC], stroma/EMT/TGF-ß, WNT) were evaluated for their relationship to objective response rate (per Response Evaluation Criteria in Solid Tumors, version 1.1). Logistic regression analysis of response for consensus signatures was adjusted for tumor type, Eastern Cooperative Oncology Group performance status, and TcellinfGEP, an approach equivalent to evaluating the association between response and the residuals of consensus signatures after detrending them for their relationship with the TcellinfGEP (previously identified as a determinant of pembrolizumab response) and tumor type. Testing of the 10 prespecified non-TcellinfGEP consensus signatures for negative association (except proliferation [hypothesized positive association]) with response was adjusted for multiplicity RESULTS: Covariance patterns of the 11 signatures (including TcellinfGEP) identified in Merck-Moffitt and The Cancer Genome Atlas datasets showed highly concordant coexpression patterns in the RNA sequencing data from pembrolizumab trials. TcellinfGEP was positively associated with response; signatures for angiogenesis, mMDSC, and stroma/EMT/TGF-ß were negatively associated with response to pembrolizumab monotherapy. CONCLUSIONS: These findings suggest that features beyond interferon-γ-related T-cell inflammation may be relevant to anti-programmed death 1 monotherapy response and may define other axes of tumor biology as candidates for pembrolizumab combinations.

4.
Zhonghua Wai Ke Za Zhi ; 59(12): 965-968, 2021 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-34839609

RESUMO

Chronic limb threatening ischemia (CLTI) is a severe condition of peripheral artery disease with high amputation and mortality. Pain and infection cause insufficient nutrient intake and protein loss in CLTI patients,while malnutrition is very prevalent in patients with CLTI and associated with poor prognosis.More and more studies have shown that malnutrition increases the risk of amputation and mortality,delays the time of wound healing.Moderate and severe malnutrition are independent risk factors for amputation and mortality in CLTI patients undergoing surgical or endovascular revascularization.Nutritional screening tools such as Geriatric nutritional risk index,Mini Nutritional Assessment and Controlling nutritional status can help to stratify patients with nutritional risk.Identification of patients with nutritional risk and nutritional intervention can improve the prognosis of CLTI patients.

5.
Zhonghua Bing Li Xue Za Zhi ; 50(10): 1134-1138, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34619866

RESUMO

Objective: To investigate the expression and diagnostic values of CD200 and insulinoma associated protein 1 (INSM1) in gastrointestinal and pancreatic neuroendocrine neoplasm (GIP-NEN). Methods: The expression of CD200, INSM1, Syn and CgA was detected in 69 cases of GIP-NEN, 66 cases of gastrointestinal and pancreatic non-neuroendocrine neoplasm (GIP-nonNEN) and 16 cases of metastatic neuroendocrine neoplasm by immunohistochemistry, to compare the values of CD200, INSM1, Syn, CgA and their combinations in diagnosing GIP-NEN. Receiver operating characteristics (ROC) curve was used. Results: The immunoreactivity of CD200 was present in the cytoplasma and/or membrane of the neoplasms cells, the positive expression rates in GIP-NEN and GIP-nonNEN were significantly different (P<0.01). The sensitivity and specificity of CD200 for diagnosing GIP-NEN were 95.7% and 78.8%, respectively. There was significant difference of the positive rates of CD200 between neuroendocrine tumor and neuroendocrine carcinoma (P=0.05). The immunoreactivity of INSM1 was present in the nuclei of neoplasms cells. The positive expression rates in GIP-NEN and GIP-nonNEN were significantly different (P<0.01). The sensitivity and specificity of INSM1 for diagnosis of GIP-NEN were 85.5% and 95.5%, respectively. There were also significantly different positive rates of INSM1 between neuroendocrine tumor and neuroendocrine carcinoma, as well as between G1 and G3 neuroendocrine tumors (P<0.05). There was no difference in the area under ROC curve (AUC) of single stain of CD200, INSM1, Syn or CgA (0.857, 0.907, 0.890 and 0.833, respectively, P>0.05). The sensitivity of combined CD200+INSM1 stains for diagnosing GIP-NEN was significantly higher than that of Syn+CgA (85.5% vs. 63.8%, P<0.05). The AUC of two combinations were 0.962 and 0.925, respectively, which were not statistically different (P>0.05). Conclusions: CD200 and INSM1 are two novel markers of neuroendocrine neoplasm, which aid to diagnosis for GIP-NEN and exclude its mimickers. They are associated with tumor grades. Combining both as an immunohistochemical panel shows high sensitivity and specificity. Thus, the combined panel can be utilized as useful supplement for Syn and CgA.


Assuntos
Antígenos CD/genética , Carcinoma Neuroendócrino , Tumores Neuroendócrinos , Proteínas Repressoras , Biomarcadores Tumorais , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/genética , Humanos , Imuno-Histoquímica , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/genética
6.
Poult Sci ; 100(11): 101452, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34601444

RESUMO

This study was conducted to investigate the potential effects of active immunization against recombinant-derived goose inhibin-α (INH-α), anti-Müllerian hormone (AMH), and prolactin (PRL) fusion protein on broodiness onset and egg production in geese. The purified fusion proteins (INH-α, AMH, and PRL) were prepared using a prokaryotic expression system. Female Zhedong geese (10 mo old) were randomly assigned to one of 4 treatments and raised in separate pens. The geese were actively immunized with the recombinant goose INH-α, AMH, or PRL, respectively, and phosphate-buffered saline as control. The results showed the corresponding antibodies were produced when the geese were immune INH-α, AMH-, and PRL-recombinant proteins. The significantly higher luteinizing hormone contents were observed in the INH-α, AMH, and PRL recombinant protein-immunized geese, while the lower AMH hormone content only in PRL-immunized birds. AMH recombinant protein immunized geese had more large yellow follicles of ovary, while the INHα-treated birds with more other follicles compared with control geese. In addition, the geese receiving INH-α recombinant protein, the broodiness onset was about 6 d, which significantly shorter than did PBS immunization (16 d). The INHα- and PRL-immunization also resulted in 12.5 and 8.5 d shorter broody duration intervals compared to the control birds. Moreover, the lower new broodiness rate was observed in three recombinant proteins treated birds. Finally, the PRL recombinant protein-immunization resulted in an average increase of 1.34 eggs during a 40-d observation. Collectively, the data demonstrated that active immunization against recombinant proteins INH-α or AMH could promote LH hormone secretion, regulate follicle development and decrease the broodiness rate. Also, active immunization with a recombinant-derived goose PRL protein might improve egg laying performance.


Assuntos
Gansos , Prolactina , Animais , Hormônio Antimülleriano , Galinhas , Feminino , Inibinas , Óvulo , Proteínas Recombinantes , Vacinação/veterinária
7.
J Dairy Sci ; 104(12): 12496-12507, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34593232

RESUMO

This study evaluated the effects of incremental tributyrin supplementation in pasteurized waste milk on growth performance, health, and blood metabolism of dairy calves before and after weaning. Forty-eight newborn female Holstein dairy calves (39.6 ± 2.75 kg; mean ± standard deviation) were blocked by age and randomly assigned to 3 treatments: pasteurized waste milk (1) without supplementation, (2) with 1 g/L of tributyrin products (unprotected solid powder; containing 35% tributyrin), or (3) with 2 g/L of tributyrin products. The calves were weaned on d 56 and were raised until d 77. Data were analyzed for the preweaning, postweaning, and overall periods. The results showed that starter intake and hay intake were not different among treatments in any period of the trial, but the crude protein intake tended to increase linearly with tributyrin supplementation during the overall period. Although tributyrin supplementation had no effects on body weight during preweaning and overall periods, body weight increased linearly with tributyrin supplementation postweaning. The average daily gain tended to increase linearly during postweaning and overall periods. No effects were observed on feed efficiency in any period. A positive linear relationship between body length and tributyrin supplementation was observed during the postweaning period, but no differences were found for the other body structural measurements in any period. The results of diarrhea showed that tributyrin concentration had a negative linear relationship with diarrhea frequency during preweaning and overall periods. The rectal temperature did not differ among treatments in any period, but a treatment × week effect for rectal body temperature was observed. For blood metabolism, tributyrin supplementation had no effects on insulin, growth hormone, total protein, albumin, or globulin. No differences were found in serum amyloid A concentration in any of the periods, yet haptoglobin concentration decreased linearly with increasing tributyrin concentration during postweaning and overall periods. Endothelin concentration showed a tendency to decrease linearly during preweaning and postweaning periods and decreased linearly with tributyrin supplementation during the overall period. An increasing tributyrin concentration was associated with a negative linear relationship with IL-1ß concentration during the preweaning period, and no differences were found in the other periods. The concentration of IL-6 and tumor necrosis factor α were not different among treatments in any of the periods. These data suggest that increasing the concentration of tributyrin in pasteurized waste milk could increase growth performance and health of dairy calves, and incremental tributyrin supplementation could linearly reduce haptoglobin, endothelin, and IL-1ß concentrations, indicating a positive effect of tributyrin on alleviating oxidative stress and inflammatory status of dairy calves. Calves fed pasteurized waste milk supplemented with tributyrin products (containing 35% tributyrin) at 2 g/L compared with 1 g/L of milk had more improved growth and health.


Assuntos
Ração Animal , Leite , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta , Suplementos Nutricionais , Feminino , Triglicerídeos , Desmame
8.
Br Poult Sci ; : 1-8, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34558366

RESUMO

1. NOD1 is a significant member of the NOD-like receptor (NLR) family. Its main role is to identify microorganisms that invade the body, transmit immune signals and regulate innate immune responses. However, the expression and role of the NOD1 in immune defence against infection in geese remain unknown.2. The RT-PCR method and rapid amplification of cDNA ends (RACE) was used to obtain the full-length goose NOD1 (gNOD1) cDNA series. The cDNA for gNOD1 contains 2856-bp nucleotides, i.e. 47-bp 5' UTR, 135-bp 3' UTR, and 1275-bp ORF region, and encodes a 951-amino-acids (AAs) polypeptide chain. The nucleotide sequence of gNOD1 was found more than 90% similar to its homologs from other avian organisms.3. The qRT-PCR results showed that gNOD1 mRNA was widely distributed in different tissues, but highly expressed in liver, spleen, lung and caecum tissues.4. Following stimulation of goose embryo fibroblasts (GEFs) with lipopolysaccharide (LPS) and polyriboinosinic polyribocytidylic acid (poly(I:C)), the expression of gNOD1 and cytokines, such as IL-1ß, IL-6, IL-18, and TNF-α, changed with the response-efficacy correlation at 24 and 48 h post-infection (hpi).5. When the goslings were challenged with Salmonella entertidis (SE) and LPS, the expression of gNOD1 was up-regulated at 3 and 6 hpi in the spleen and caecum tissues, respectively. However, after SE infection, the expression level of gNOD1 fluctuated, while in the LPS group, gNOD1 mRNA increased immediately at a peak time of 6 hpi and then steadily declined. These results indicated that NOD1 was associated with the potency to resist bacterial and viral infections in the goose, both in vivo and in vitro.

9.
Eur J Cancer ; 157: 493-510, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34561127

RESUMO

Immunotherapy has revolutionised cancer treatment through restoration of host antitumour immune response. Immune checkpoint inhibitors (ICIs) confer durable responses in only a subset of patients. Mechanisms of ICI resistance to improve durable response rates and overall survival are an area of intense clinical research. Robust clinical development is ongoing to evaluate novel combination therapies to overcome ICI resistance, including targeting immunoregulatory pathways in the tumour microenvironment. Intratumoural (IT) immunotherapies such as toll-like receptor agonists, stimulator of interferon-induced gene agonists, retinoic-inducible gene I-like receptor agonists and oncolytic viruses may represent potential combination treatment options to overcome ICI resistance. Use of IT immunotherapies in combination with ICIs may alter the tumour microenvironment to address resistance mechanisms and improve antitumour response. Optimisation of IT immunotherapy clinical trials will elucidate resistance mechanisms, facilitate clinical trial design, define pharmacodynamic predictors that identify patients who may most benefit and inform clinical development of combination immunotherapy regimens. Here we provide an overview of IT immunotherapy principles, mechanisms of action, categories of IT immunotherapeutics, emerging data, clinical development strategies, response assessment, dose and schedule determination, clinical trial design and translational study design.

10.
Mitochondrion ; 61: 44-53, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34571250

RESUMO

Excessive autophagy-induced follicular atresia of ovarian granulosa cells might be one of the pathogenesis of Premature Ovarian Insufficiency (POI), and melatonin (MT) exerted many beneficial effects on mitochondria. However, there was little report regarding the beneficial effects of MT on excessive autophagy-induced mitochondrial and ovarian reserve function deficiency, and the mechanisms have not been clearly identified. Autophagy played a protective role in cells survival, however, high level of autophagy could lead to cell death. In this report, firstly, Chinese hamster ovary cell damage model stably expressing EGFP-LC3 was established. Next, we systematically investigated the protective effects of MT on mitochondrial and ovarian reserve function and molecular mechanisms using this cell damage model. Our results revealed that 10-9 M MT not only protected against the decline of anti-mullerian hormone (AMH) expression induced by excessive autophagy, but also rescued excessive autophagy-induced impairment of mitochondrial expression and mitochondrial membrane potential. Furthermore, MT protected against excessive autophagy-induced decrease of nucleus-encoded proteins including SDHA and mitofilin, and mitochondrial dynamic-related proteins including OPA1, MFN2, and DRP1. MT also decreased mitochondrial oxidative stress, increased antioxidant enzyme superoxide dismutase 2 (SOD2) expression and ameliorated the G2/M cell cycle arrest induced by excessive autophagy. Finally, MT inhibited excessive autophagy-induced activation of extracellular signal regulated kinase (ERK) signaling pathway. In conclusion, our study showed that MT rescued impairment of mitochondrial and ovarian reserve function, and production of mitochondrial ROS and cell cycle arrest induced by excessive autophagy through down-regulated ERK pathway, implying the potential therapeutic drug target for POI.

11.
Zhonghua Yi Xue Za Zhi ; 101(32): 2508-2513, 2021 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-34407575

RESUMO

Objective: To evaluate the clinical efficacy of dietary supplement Licofor in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: This was a prospective, randomized controlled clinical trial. Sixty patients [25 males, 35 females, aged (42±13) years] who had dry eye associated with MGD were recruited in Xiangya Hospital of Central South University from December 2018 to October 2019. The patients were equally divided into two groups: 30 cases (60 eyes) in the experimental group and 30 cases (60 eyes) in the control group. All subjects were treated with eye hot compress, artificial tears and antibiotic ointment. After that, the experimental group and control group were received dietary supplementary Licofor or placebo daily for 12 weeks. The symptoms and signs of dry eye, morphology and function of meibomian gland, and inflammatory response were assessed at the beginning, 4th, 8th and 12th week of treatment. Results: After 12 weeks of treatment, statistically significant improvements in ocular surface disease index (OSDI) scores, tear break-up time (TBUT), corneal fluorescein staining (CFS), the morphology of eyelid margin, meibomian gland orifice, meibomian gland expressibility, meibum quality, and periglandular inflammatory cell density were determined in both groups (all P<0.05). In the Licofor group, the improvement of OSDI scores [16.7 (12.5, 20.8) vs 20.8 (18.8, 22.9), P<0.001], the morphology of eyelid margin, meibomian gland orifice and periglandular inflammatory cell density [443 (318, 513) vs 553 (415, 676)/mm2, P=0.002] were more significant (all P<0.05). Conclusion: The combined treatment of licofor and conventional treatment can significantly improve symptoms of dry eye, the morphology of eyelid margin, meibomian gland orifice, meibum quality, and eyelid inflammation response of dry eye associated with MGD.


Assuntos
Síndromes do Olho Seco , Doenças Palpebrais , Disfunção da Glândula Tarsal , Suplementos Nutricionais , Síndromes do Olho Seco/tratamento farmacológico , Doenças Palpebrais/tratamento farmacológico , Feminino , Humanos , Masculino , Glândulas Tarsais , Estudos Prospectivos , Lágrimas , Resultado do Tratamento
12.
Zhonghua Yi Xue Za Zhi ; 101(29): 2310-2315, 2021 Aug 03.
Artigo em Chinês | MEDLINE | ID: mdl-34333947

RESUMO

Objective: To investigate the seasonal changes of benign paroxysmal positional vertigo (BPPV) onset, and explore the relationship between vascular risk factors and the seasonal patterns of BPPV. Methods: Data of 3 886 patients subjected to vestibular function examination and diagnosed with BPPV who underwent manipulation or instrumental repositioning from January 1, 2016 to December 31, 2019 in the Department of Neurology, Beijing Tiantan Hospital were retrospectively analyzed. Demographic information and medical history of the patients were recorded. Weather temperature data of Beijing were obtained and monthly averages were calculated. The relationship between the BPPV onset and temperature and seasonality was investigated. Meanwhile, the influence of vascular risk factors on the seasonal patterns of BPPV was determined. Results: BPPV is more common in women (n=2 667). The male to female ratio of patients was approximately 1∶2, with a mean age of (55±13) years. The cases of BPPV in spring (March-May), summer (June-August), autumn (September-November) and winter (December-February) were 1 000 (25.7%), 911 (23.4%), 808 (20.8%) and 1 167 (30.0%), respectively. The peak incidence of BPPV occurred in December (n=491) and the lowest occurred in September (n=251). The number of BPPV cases diagnosed monthly was inversely correlated with mean temperature (R2=0.317; P<0.001). Patients with ≥2 vascular risk factors were at higher risk of developing BPPV in spring or winter than those without risk factors (OR=1.32, 95%CI: 1.13-1.53,P<0.001). Proportion of onset in spring or winter increased with each additional risk factor (P trend<0.001). Conclusions: BPPV often occurs in the months with low temperature (spring and winter) and the number of cases is inversely correlated with temperature. Compared with those with no vascular risk factors, patients with more vascular risk factors are more likely to develop BPPV in spring and winter.


Assuntos
Vertigem Posicional Paroxística Benigna , Vestíbulo do Labirinto , Adulto , Idoso , Vertigem Posicional Paroxística Benigna/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
13.
Zhonghua Gan Zang Bing Za Zhi ; 29(7): 673-678, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34371538

RESUMO

Objective: To explore the possibility of hepatitis B core antibody (anti-HBc) in predicting hepatitis B virus surface antigen (HBsAg) clearance. Methods: Sixty cases with chronic hepatitis B who were previously treated with peginterferon α-2a combined with nucleos(t)ide analogues (NAs) antiviral therapy were divided according to the HBsAg clearance or non-clearance; 41 cases in the clearance group and 19 cases in the non-clearance group. Double antigen sandwich method was used to detect patients anti-HBc quantitative levels during the course of treatment and at baseline, 24, 48, 72 and 96 weeks. Logistic regression analysis and receiver operating characteristic curve (ROC) were used to evaluate the predictive ability of related influencing factors for HBsAg clearance. Results: With antiviral treatment prolongation, anti-HBC quantitative levels in the overall population showed a progressive downward trend in the clearance group and the non-clearance group, but the anti-HBC level in the clearance group was significantly higher than non-clearance group at the baseline and successive detection time points during the antiviral treatment (P < 0.05). Multivariate logistic regression showed that baseline quantitative anti-HBC level, HBsAg decline at week 24 (log10 IU / ml), and alanine aminotransferase (ALT) > 1.5 times the upper limit of normal value (ULN) were all influencing factors for HBsAg clearance during the treatment (OR = 0.156, P = 0.026; OR = 0.134, P = 0.023; OR = 0.239, P = 0.028). Among them, the baseline quantitative anti-HBc level was the best independent predictor for HBsAg clearance (OR = 0.235; P = 0.004), and the sensitivity and specificity for predicting HBsAg clearance at > 3.40 log10 IU/ mL were 56.1% and 89.5%, respectively. Logistic regression model was used as a reference to construct combined predictors in order to improve the prediction accuracy. Among them, the combined factor 3 had the highest predictive value (the area under the ROC curve had reached up to 0.870; 95%CI was 0.781 ~ 0.960; P < 0.001). The cut-off value of combined factor 3 was > 0.386, and the sensitivity and specificity were 80.5% and 78.9%, respectively. In addition, the combined index had further improved the predictive value, which is the combination of any two or more indexes based on the baseline quantitative anti-HBC level, and HBsAg clearance predictive rate had reached 94.12% ~ 100%. Conclusion: The baseline quantitative anti-HBC level has the highest predictive value for HBsAg clearance. The combination of ALT > 1.5×ULN and HBsAg decline at 24 weeks during the treatment can more precisely predict HBsAg clearance. Therefore, it is a reliable non-invasive biomarker.


Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Alanina Transaminase , Antivirais/uso terapêutico , DNA Viral , Anticorpos Anti-Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Resultado do Tratamento
14.
Geohealth ; 5(7): e2021GH000438, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34296051

RESUMO

Due to the specific hydrothermal conditions of dry-hot valleys, temperature changes caused by the development of large-scale hydropower projects may be more extreme than they are in other regions. In this study, we analyzed these temperature changes at four hydropower stations in both dry-hot and non-dry-hot valleys. Based on the calculated relative temperatures of the downstream river and the areas surrounding the reservoirs, we employed two indices to quantify the influence of the reservoirs on the temperatures of these two regions: the downstream river temperature change and the reservoir effect change intensity. Our results are as follows: (a) In the downstream rivers, the temperature regulation effect was more pronounced in the wet season; in the regions surrounding the reservoirs, the temperature regulation effect was more pronounced in the dry season. (b) The downstream river temperature in both the dry-hot and wet-hot valleys exhibited noticeable warming in both the wet and dry seasons, while the cold-dry valley was characterized by cooling in the dry season and warming in the wet season. With the exception of the Liyuan station (where the influence of the reservoir on the downstream temperatures only extended to a distance of 9 km from the dam) during the dry season, the existence of the hydropower stations affected the temperatures of the entire downstream region. (c) For the areas surrounding the reservoir, the presence of a hydropower station mainly caused the temperatures in the dry-hot valleys to rise and the temperatures in the non-dry-hot valleys to decrease.

15.
Animal ; 15(8): 100322, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34311193

RESUMO

The bones of chicken play an important role in supporting and protecting the body. The growth and development of bones have a substantial influence on the health and production performance in chickens. However, genetic architecture underlying chicken bone traits is not well understood. The objectives of this study are to dissect the genetic basis of bone traits in chickens and to identify valuable genes and genetic markers for chicken breeding. We performed a combination of genome-wide association study (GWAS) and selection signature analysis (fixation index values and nucleotide diversity ratios) in an F2 crossbred experimental population with different genetic backgrounds (broiler × layer) to identify candidate genes and significant variants related to femur, shank, keel length, chest width, metatarsal claw weight, metatarsal length, and metatarsal circumference. A total of 545 individuals were genotyped based on the whole genome re-sequencing method (26 F0 individuals were re-sequenced at 10 × coverage; 519 F2 individuals were re-sequenced at 3 × coverage). A total of 2 028 112 single-nucleotide polymorphisms (SNPs) remained to carry out analysis after quality control and imputation. The integration of GWAS and selection signature analysis indicated that all significant SNPs responsible for bone traits were mainly localized on chicken chromosomes 1, 4, and 27. Finally, we identified 21 positional candidate genes that might regulate chicken bone growth and development, including LRCH1, RB1, FNDC3A, MLNR, CAB39L, FOXO1, LHFP, TRPC4, POSTN, SMAD9, RBPJ, PPARGC1A, SLIT2, NCAPG, NKX3-2, CPZ, SPOP, NGFR, SOST, ZNF652, and HOXB3. Additionally, an array of uncharacterized genes was identified. The findings provide an in-depth understanding of the genetic architecture of chicken bone traits and offer a molecular basis for applying genomics in practical chicken breeding.


Assuntos
Osso e Ossos/fisiologia , Galinhas , Estudo de Associação Genômica Ampla , Seleção Genética , Animais , Galinhas/genética , Marcadores Genéticos , Estudo de Associação Genômica Ampla/veterinária , Fenótipo , Polimorfismo de Nucleotídeo Único
16.
Zhonghua Yi Xue Za Zhi ; 101(26): 2060-2065, 2021 Jul 13.
Artigo em Chinês | MEDLINE | ID: mdl-34275239

RESUMO

Objective: To investigate the Helicobacter pylori (H. pylori) eradication rate and improvement of dyspepsia in patients who were newly diagnosed with H. pylori infection and dyspepsia and treated by bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang(JHWK). Methods: Patients who were newly diagnosed with dyspepsia and H. pylori infection and treated in 16 medical centers in China between December 1, 2017 and September 30, 2019 were randomly divided into two groups. The experimental group received bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days), followed by JHWK (30 days), and the course of treatment was 44 days in total. In the control group, the administration regimen was bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days). The main outcome measure was H. pylori eradication rate, while the secondary outcome measures were dyspepsia symptom changes and adverse events during the treatment and the 1st month after treatment. Results: A total of 1 054 patients were included in the study. There were 522 cases enrolled in the experimental group, including 224(42.91%) men and 298(57.09%) women, and the age was 53(26, 73) years old; 532 cases enrolled in the control group, including 221(41.54%) men and 311(58.46%) women, and the age was 46(22, 71) years old. Based on PP analysis, it was found that the H. pylori eradication rate in the experimental group was significantly higher than those in the control group (93.85% vs 87.88%, P=0.001). In the group of all enrolled patients, the symptom dyspepsia after H. pylori eradication was significantly improved compared with that before treatment [4(4, 7) vs 15(10, 22), P<0.001], so was the superior and middle abdominal pain [1(1, 4) vs 4(1, 8), P<0.001], the postprandial fullness [1(1, 4) vs 4(4, 9), P<0.001], the early satiety [1(1, 1) vs 4(1, 4), P<0.001], and the heartburn [1(1, 1) vs 1(1, 4), P<0.001]. The symptom dyspepsia after treatment was significantly improved compared with that before treatment in the experimental, the control groups, the successful and the unsuccessful H. pylori eradication groups. The superior and middle abdominal pain after treatment was signifcantly improved than that before treatment [1(1, 2) vs 1(1, 4), P<0.001], so were the postprandial fullness [1(1, 3) vs 1(1, 4), P=0.002] and the dyspepsia[4(4, 7) VS 7(4, 10), P<0.001]. There was no statistically significant difference in the incidence of adverse events between the experimental group and the control group (1.34% vs 0.38%, P=0.09). Conclusions: Compared with bismuth-containing quadruple therapy, bismuth-containing quadruple therapy followed by JHWK significantly improves the H. pylori eradication rate without increasing the incidence of adverse events. H. pylori eradication therapy can improve symptoms of patients with H. pylori infection and dyspepsia.


Assuntos
Dispepsia , Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , China , Quimioterapia Combinada , Dispepsia/tratamento farmacológico , Feminino , Infecções por Helicobacter/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Phys Rev Lett ; 126(24): 241103, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34213924

RESUMO

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25 TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17_{stat}±0.02_{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160 TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

18.
Zhonghua Yi Xue Za Zhi ; 101: 1921-1928, 2021 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-34139825

RESUMO

Objective: To analyze the association of the cadmium internal exposure with chronic kidney disease (CKD) in Chinese adults aged 18 and older. Methods: A total of 9 821 adults aged 18-79 from the China National Human Biomonitoring (CNHBM) from 2017 to 2018 were included. Blood and urine cadmium exposure levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), and urine cadmium levels were adjusted with urine creatinine; CKD were defined by estimated glomerular filtration (eGFR) using the chronic kidney disease epidemiology collaboration (CKD-EPI). Weights were considered due to complex sampling process for in statistical analysis. Logistic regression is used to analyze the association of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine exposure levels with CKD, and restricted cube spline (RCS) was used to assess the exposure-response curve of blood cadmium, urine cadmium and urine cadmium adjusted with creatinine with CKD. Results: The weighted age was 44.75 and males accounted for 61.1%. The prevalence rate of CKD was 12.7%. The geometric mean values of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine were 0.96 µg/L, 0.61 µg/L, and 0.58 µg/g. After adjusting for confounding factors, the weighted logistic regression showed that the lowest quintile (Q1) was compared with the odds ratio (OR) of the highest quintile (Q5) of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine and the 95% confidence interval (CI) was 1.80 (1.02-3.20), 1.77 (0.94-3.31) and 1.94 (1.11-3.37) respectively. In the restricted cubic spline regression model, non-linear association of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine with CKD were observed after adjusting for related confounding factors (P<0.001, 0.018, 0.031 respectively). The risk of CKD increased with the increment of cadmium exposure without risk threshold, and the exposure response curve was steeper at low cadmium exposure. Conclusions: Among Chinese adults aged 18 and older, cadmium exposure is positively associated with the risk of chronic kidney disease.

19.
Ann Oncol ; 32(9): 1127-1136, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34082019

RESUMO

BACKGROUND: In the phase III KEYNOTE-061 trial (NCT02370498), pembrolizumab did not significantly improve overall survival versus paclitaxel as second-line therapy for gastric/gastroesophageal junction (GEJ) adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 tumors. The association of tissue tumor mutational burden (tTMB) status and clinical outcomes was determined, including the relationship with CPS and microsatellite instability-high (MSI-H) status. PATIENTS AND METHODS: In patients with whole exome sequencing (WES) data [420/592 (71%); pembrolizumab, 218; paclitaxel, 202], the association of tTMB with objective response rate (ORR; logistic regression), progression-free survival (PFS; Cox proportional hazards regression), and overall survival (OS; Cox proportional hazards regression) were measured using one-sided (pembrolizumab) and two-sided [paclitaxel] P values. tTMB was also evaluated using FoundationOne®CDx [205/592 (35%)]. Prespecified equivalent cut-offs of 175 mut/exome for WES and 10 mut/Mb for FoundationOne®CDx were used. RESULTS: WES-tTMB was significantly associated with ORR, PFS, and OS in pembrolizumab-treated (all P < 0.001) but not paclitaxel-treated patients (all P > 0.6) in univariate analysis. The area under the receiver operating characteristics curve for WES-tTMB and response was 0.68 [95% confidence interval (CI) 0.56-0.81] for pembrolizumab and 0.51 (95% CI 0.39-0.63) for paclitaxel in univariate analysis. There was low correlation between WES-tTMB and CPS in both treatment groups (r ≤ 0.16). WES-tTMB remained significantly associated with all clinical endpoints with pembrolizumab after adjusting for CPS and with PFS and OS after excluding known MSI-H tumors (n = 26). FoundationOne®CDx-tTMB demonstrated a positive association with ORR, PFS, and OS in pembrolizumab-treated patients (all P ≤ 0.003) but not PFS or OS in paclitaxel-treated patients (P > 0.1). CONCLUSION: This exploratory analysis from KEYNOTE-061 is the first to demonstrate a strong association between tTMB and efficacy with pembrolizumab but not paclitaxel in patients with gastric/GEJ adenocarcinoma in a randomized setting. Data further suggest tTMB is a significant and independent predictor beyond PD-L1 status.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Humanos , Paclitaxel/uso terapêutico
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(4): 607-612, 2021 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-33963723

RESUMO

OBJECTIVE: To establish a risk prediction model of chemotherapy-induced nausea and vomiting based on naive Bayes classifier. OBJECTIVE: We collected the basic information, treatment protocols and follow-up data from 300 patients receiving chemotherapy in the Oncology Department of Second Xiangya Hospital from July to September, 2020. Correlation analysis was carried out between the potential factors related to nausea and vomiting in the treatment plan and the individual characteristics of the patients. For the two characteristics with a correlation coefficient greater than 0.8, their contribution to the area under curve (AUC) was calculated, and the characteristic with a smaller contribution was removed. The naive Bayes classifier in the machine learning library scikit-learn was used as the prediction model of chemotherapy-induced nausea and vomiting, and 10-fold stratified-shuffled-split cross-validation was used to obtain the final result of the model. The machine learning model was trained using 70% of the samples, and 30% of the samples were used as the test set to assess the performance of the model. OBJECTIVE: The sensitivity of the model for predicting the risk of nausea and vomiting due to acute chemotherapy was 0.83±0.04 (95%CI: 0.80-0.86) with a specificity of 0.45±0.03 (95%CI: 0.42-0.47) and an AUC of 0.72±0.04 (95% CI: 0.69-0.75). The sensitivity of the model for predicting the risk of delayed chemotherapy-induced nausea and vomiting was 0.84±0.01 (95%CI: 0.83-0.86) with a specificity of 0.48±0.03 (95%CI: 0.45-0.52) and an AUC of 0.74±0.02 (95%CI: 0.72-0.77). OBJECTIVE: The naive Bayes classifier model has a good performance in predicting the risk of chemotherapy-induced nausea and vomiting in Chinese cancer patients.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/efeitos adversos , Teorema de Bayes , Humanos , Aprendizado de Máquina , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...