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1.
Materials (Basel) ; 15(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35683084

RESUMO

This paper analyses the characteristics of the mechanical behavior of a trussed steel and concrete box beam under bending conditions based on the structural stressing state theory and the numerical shape function method. Firstly, the parametric generalized strain energy density was introduced to characterize the structural stressing state of trussed steel stud concrete box girders, and the strain energy density sum was plotted. Then the Mann-Kendall criterion was used to discriminate the leap point of the curve change and to redefine the structural failure load. By analyzing the strain and displacement, the existence of a sudden change in the structural response during the load-bearing process was again demonstrated. Afterwards, the numerical shape function method was used to extend the strain data, and further in-depth analyses of strain/stress fields and internal forces were carried out to show in detail the working characteristics of each under load. Through an in-depth analysis from different angles, the rationality of updating the failure load was verified. Finally, the effects of different structure parameters on the evolution of the structural stresses of the members were analyzed in a transversal comparison. The analysis results of the stress state of a steel-concrete truss structure reveal the working behavior characteristics of a steel-concrete truss structure from a new angle, which provides a reference for the design of a steel-concrete truss structure in the future.

2.
Zhongguo Zhong Yao Za Zhi ; 47(11): 3038-3048, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35718528

RESUMO

Based on the brain-gut axis, the present study investigated the effect of Huanglian Houpo Decoction(HLHPD) in the treatment of ulcerative colitis(UC) and explored the mechanism in the regulation of 5-hydroxytryptamine(5-HT), substance P(SP), and vasoactive intestinal peptide(VIP) using modern technologies and molecular docking. Sixty male C57 BL/6 J mice were randomly divided into a blank control group, a model group, a sulfasalazine(SASP) group, and high-(5.00 g·kg~(-1)), medium-(2.50 g·kg~(-1)), and low-dose(1.25 g·kg~(-1)) HLHPD groups. The UC model was induced by oral administration of water containing 3% dextran sulfate sodium salt(DSS) in mice except those in the blank control group. After HLHPD was administered for 10 days, the mice were sacrificed for sample collection. Morphological changes of colon tissues were observed by HE staining. The expression of 5-HT, SP, VIP, tumor necrosis factor α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in the hypothalamus, serum, and colon was determined by the enzyme-linked immunosorbent assay(ELISA). The expression of tryptophan hydroxylase 1(TPH1), SP, and VIP in colon tissues was evaluated by immunohistochemistry. The expression of brain-gut peptide receptors, such as 5-HT3 A, neurokinin receptor 1(NK-1 R), and VIP receptor 1(VPAC1) in colon tissues was investigated by Western blot. The binding affinity of the brain-gut peptide receptors to the main components of HLHPD was analyzed by molecular docking. After HLHPD intervention, UC mice showed increased body weight, reduced DAI score and occult blood, prolonged colon, down-regulated levels of TNF-α, IL-1ß, and IL-6 in colon tissues, and relieved pathological damage in the colon. The VIP levels in the colon were significantly up-regulated in the HLHPD groups. The high-and medium-dose HLHPD could significantly down-regulated SP and 5-HT in colon tissues and 5-HT in the serum, and up-regulated the VIP in the serum. The high-dose HLHPD group could down-regulate 5-HT and up-regulate VIP in the hypothalamus. It is suggested that HLHPD can reverse the levels of brain-gut peptides in UC mice to varying degrees. Correlation analysis results suggested that the expression levels of brain-gut peptides in the hypothalamus, serum, and colon tissues were related to inflammatory factors. Molecular docking results showed that berberine, coptisine, and epiberberine were presumedly the material basis for HLHPD in regulating the levels of 5-HT3 A, NK-1 R, and VPAC1. The main components of HLHPD may reduce colonic inflammation and pathological damage of colon tissues by regulating the activity of brain-gut peptides and their receptors, thereby reducing DSS-induced colitis in mice.


Assuntos
Colite Ulcerativa , Animais , Colite Ulcerativa/tratamento farmacológico , Colo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Serotonina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
JAMA Netw Open ; 5(5): e2214181, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35639382

RESUMO

Importance: Marital status has been shown to be associated with mortality, but evidence in Asian populations is limited. Objective: To examine the association of marital status with total and cause-specific mortality. Design, Setting, and Participants: This cohort study included individual participant data from 16 prospective studies in the Asia Cohort Consortium conducted between 1963 and 2015. Asian participants with complete information on marital and vital status were included. Study-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards model and then pooled using a random-effects meta-analysis. The analysis began in February 2021 and ended in August 2021. Exposures: Marital status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 623 140 participants (326 397 women [52.4%] and 296 743 men [47.6%]; mean [SD] age, 53.7 [10.2] years; mean [SD] follow-up time, 15.5 [6.1] years), 123 264 deaths were ascertained. Compared with married individuals, those who were unmarried had pooled HRs of 1.15 (95% CI, 1.07-1.24) for total mortality, 1.12 (95% CI, 1.03-1.22) for cerebrovascular disease mortality, 1.20 (95% CI, 1.09-1.31) for coronary heart disease mortality, 1.17 (95% CI, 1.07-1.28) for circulatory system diseases mortality, 1.06 (95% CI, 1.01-1.11) for cancer mortality, 1.14 (95% CI, 1.05-1.23) for respiratory diseases mortality, and 1.19 (95% CI, 1.05-1.34) for external causes of death. Positive associations with total mortality were also observed for those who were single (HR, 1.62; 95% CI, 1.41-1.86), separated (HR, 1.35; 95% CI, 1.13-1.61), divorced (HR, 1.38; 95% CI, 1.13-1.69), and widowed (HR, 1.09; 95% CI, 1.04-1.13). In subgroup analyses, the positive association persisted across baseline health conditions, and the risk of death was more pronounced among men or people younger than 65 years. Conclusions and Relevance: This large pooled cohort study of individual participant data provides strong evidence that being unmarried, as well as belonging to the unmarried subcategories, was positively associated with total and cause-specific mortality. Investment of targeted social support services might need to be considered in light of the mortality differences between married and unmarried individuals.


Assuntos
Estudos de Coortes , Ásia/epidemiologia , Causas de Morte , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Estudos Prospectivos
4.
Int J Gen Med ; 15: 4807-4816, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592537

RESUMO

Introduction: The aim of this study was to explore the association between sagittal spinopelvic alignment and persistent low back pain (PLBP) following posterior decompression and instrumented fusion for mild L5-S1 spondylolisthesis. Methods: By retrieving medical records from January 2015 to April 2020, 200 patients following PLIF for mild L5-S1 spondylolisthesis were retrospectively reviewed. Patients were divided into two groups: PLBP group and non-PLBP group. The baseline characteristics and radiographic parameters were analyzed and compared between groups. Results: The PLBP group comprised 26 patients, and the non-PLBP group comprised 174 patients. No significant differences in preoperative spinopelvic parameters were found between the two groups (p > 0.05). There were statistically significant differences between the preoperative and postoperative variations of LL, SL, LSA, SD, and HOD spinopelvic parameters, regardless of group (p < 0.05). Postoperative PT and SS differed significantly between the PLBP group and non-PLBP group (p < 0.05). In the PLBP group, there were no significant differences between preoperative and postoperative PT; the same applied to SS. However, significant differences were found for the variations in preoperative and postoperative PT and SS between the two groups. The ΔPT was found as an independent risk factor for postoperative PLBP. Conclusion: Patients with mild L5-S1 spondylolisthesis with PLBP after posterior lumbar spinal fusion had decreased SS and increased PT.

5.
Am J Clin Nutr ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551603

RESUMO

BACKGROUND: Understanding the genetic predisposition to cardiovascular disease (CVD), may help to improve clinical intervention strategies. Lifestyle factors such as diet may differ among ethnic groups and may, in turn, modify individuals' risks to diseases. OBJECTIVE: We examined genetic predisposition to ever smoking in relation to CVD mortality and assessed whether such association could be modified by dietary intakes. METHODS: A total of 23,760 Chinese adults from the Singapore Chinese Heath Study (SCHS) who were free of cancer and CVD at recruitment (1993-1998) were included in the study. A weighted genetic risk score (wGRS) was calculated to define the genetically determined regular smoking behavior (never/ever). Multivariable-adjusted Cox regression models were used to assess the association between the wGRS and CVD mortality. We also conducted a one-sample Mendelian randomization analysis for ever smoking and CVD mortality. RESULTS: Over a mean 22.6 years of follow-up, 2,301 CVD deaths were identified. Genetic predisposition to ever smoking was significantly associated with CVD mortality; the multivariable-adjusted HR (95% CI) of CVD mortality was 1.07 (1.03,1.12) with per-SD increment in the wGRS. However, the Mendelian randomization analysis did not support a causal relationship between ever smoking and CVD mortality (OR [95% CI] 1.13 [0.87,1.45]). Additionally, the DASH score significantly modified the association between the smoking wGRS and CVD mortality, the association between genetic predisposition to smoking and CVD mortality was only observed among individuals with a low DASH score (P-interaction = 0.004). CONCLUSIONS: Genetic predisposition to smoking was associated with CVD mortality in the Chinese population. In addition, we detected a significant interaction showing higher genetically determined smoking related CVD mortality among those with lower DASH score.

6.
Zhongguo Zhen Jiu ; 42(5): 481-5, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35543936

RESUMO

OBJECTIVE: To observe the therapeutic effect of scalp-nape acupuncture for pharyngeal dysphagia of stroke at recovery stage on the basis of neuromuscular electrical stimulation (NMES) and rehabilitation training. METHODS: A total of 42 patients with pharyngeal dysphagia of stroke at recovery stage were randomized into an observation group and a control group, 21 cases in each group. Conventional medical symptomatic treatment was given in both groups. NMES and rehabilitation training were adopted in the control group, 30 min for each one. On the basis of the treatment in the control group, scalp-nape acupuncture was given in the observation group, scalp acupuncture was applied at lower 2/5 of anterior and posterior oblique lines of parietal and temporal, nape acupuncture was applied at Fengchi (GB 20), Yiming (EX-HN 14), Gongxue (Extra), Zhiqiang (Extra), Tunyan (Extra), etc. The treatment was given once a day, 5 days a week for 3 weeks in both groups. Before and after treatment, the videofluoroscopic dysphagia scale (VDS) score, the Kubota water swallowing test grade, the functional oral intake scale (FOIS) grade and the swallowing quality of life (SWAL-QOL) score were observed in both groups. RESULTS: After treatment, the VDS scores were decreased and the SWAL-QOL scores were increased compared before treatment (P<0.05), the Kubota water swallowing test grade and FOIS grade were improved compared before treatment (P<0.05) in both groups. The changes of VDS score and SWAL-QOL score, Kubota water swallowing test grade and FOIS grade in the observation group were superior to those in the control group (P<0.05). CONCLUSION: Based on NMES and rehabilitation training, scalp-nape acupuncture can enhance the therapeutic effect on pharyngeal dysphagia of stroke at recovery stage, and improve the patients' swallowing function and quality of life.


Assuntos
Terapia por Acupuntura , Transtornos de Deglutição , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Pontos de Acupuntura , Deglutição , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Humanos , Qualidade de Vida , Couro Cabeludo , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Resultado do Tratamento , Água
7.
Cancers (Basel) ; 14(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35565328

RESUMO

BACKGROUND: Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine and glycine with pancreatic cancer risk. METHODS: We conducted a nested case-control study involved 129 incident pancreatic cancer cases and 258 individually matched controls within a prospective cohort study of 18,244 male residents in Shanghai, China. Glycine and serine and related metabolites in pre-diagnostic serum were quantified using gas chromatography-tandem mass spectrometry. A conditional logistic regression method was used to evaluate the associations for serine, glycine, and related metabolites with pancreatic cancer risk with adjustment for potential confounders. RESULTS: Odds ratios (95% confidence intervals) of pancreatic cancer for the highest quartile of serine and glycine were 0.33 (0.14-0.75) and 0.25 (0.11-0.58), respectively, compared with their respective lowest quartiles (both p's < 0.01). No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. CONCLUSION: The risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of glycine and serine in serum collected, on average, more than 10 years prior to cancer diagnosis in a prospectively designed case-control study. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for cancer prevention.

8.
Sci Rep ; 12(1): 8533, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35595843

RESUMO

This paper addresses the mean square consensus-based formation control for multiple agent system (MAS) with input and output delays under network attacks, process noise, and measurement noise in MAS. Firstly, a time delay-free transformation approach for a multi-agent system with input and output delays is presented. The MAS is transformed into a formal delay-free discrete-time system using the delay-free transformation method. Then a state observer based on Kalman filter is presented to estimate the states of agents. A distributed predictive consensus protocol based on the estimated states of each MAS is proposed for the leader-following MAS. The sufficient and necessary conditions of mean square consensus for MAS under DoS attacks are derived. Finally, a numerical example of consensus-based formation control for multi-agent systems is provided to verify the correctness and effectiveness of the proposed consensus control protocol.

9.
Materials (Basel) ; 15(9)2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35591713

RESUMO

This paper analyzes the flexural behavior of a partially prestressed steel high-strength reinforced concrete beams based on the structural stress state theory and the numerical shape function method. First, the generalized strain energy density is formed by the measured strain data of the test beam to reflect the structural stress state of the beams, and then the Mann-Kendall criterion is used to judge characteristic points of the generalized strain energy density curve. Two characteristic points, namely, post-elastic boundary load and failure load, are detected, so that the whole loading process is divided into three structural stressing state stages. Unlike the ultimate load, failure load is defined according to the general law from quantitative to qualitative change, which represents the starting point of the failure stage of the beam. Then, experimental strains and deflections, strain/stress fields interpolated by the numerical shape function method, and internal forces calculated by integration are respectively analyzed to obtain their changing characteristics and working behavior around the characteristic points, which can also verify the correction and effectiveness of the Mann-Kendall criterion. In addition, through the analysis above, it can be known that the failure loads of the test beams can be effectively improved by increasing the prestressed reinforcement ratio or concrete strength.

10.
Orthop Surg ; 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585657

RESUMO

OBJECTIVE: To describe our experience with the combined use of pedicled neurotrophic flap and distraction osteogenesis in the management of complex lower extremity injuries with composite bone and soft tissue defects and assess the functional and cosmetic results of this method. METHODS: A pedicled flap with a marked perforator artery was applied for soft tissue coverage after radical debridement and temporary external fixation. In the second stage, the Ilizarov external fixator was used in place of the temporary external fixator for reconstruction of the segmental bone defect by distraction osteogenesis. Twenty-five patients (16 men and nine women; mean age, 39.2 years) were treated by using this combined technique between 2008 and 2016. All cases were graded initially as Gustilo-Anderson grade IIIB open fractures. The soft tissue defect after radical debridement ranged from 9 cm × 5 cm to 14 cm × 11 cm, and the average size of segmental defect was 5.2 (Range, 2.5-8.5) cm. Seventeen of these patients had a history of local infection. The bone structure and function were evaluated by two independent evaluators using Paley's criteria. RESULTS: Twenty-five patients were followed up for an average of 28.96 (Range, 15-48) months. The distally based sural neurovascular flap was applied in 13 patients, and the greater saphenous neurocutaneous perforator flap in 12 patients. The flap area ranged from 10 cm × 5 cm to 14 cm × 12 cm. Sufficient coverage of soft tissue defect was achieved in all cases. All flaps survived completely without complications. The bone defects were corrected by a mean lengthening of 6.94 (Range, 4.5-9.5) cm. The residual discrepancy was <1 cm in all cases, which was not clinically significant. The function was evaluated as excellent in 12 patients and good in 13 patients. Bone results were graded as excellent in 18 patients and good in seven patients. Complications during treatment included pain, pin tract infections, ankle midfoot joint stiffness, and docking site nonunion. No recurrence of infection was observed in infected patients. All cases achieved successful limb salvage and satisfactory function recovery without recurrence of infection. CONCLUSIONS: The combined technique of a perforator artery pedicled neurotrophic flap and distraction osteogenesis is an effective alternative approach in the salvage treatment of massively traumatized and chronically infected lower extremities.

11.
Hepatol Commun ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503778

RESUMO

It is difficult to identify people with nonalcoholic fatty liver disease (NAFLD) who are at high risk for developing hepatocellular carcinoma (HCC). A polygenic risk score (PRS) for hepatic fat (HFC-PRS) derived from non-Asians has been reported to be associated with HCC risk in European populations. However, population-level data of this risk in Asian populations are lacking. Utilizing resources from 24,333 participants of the Singapore Chinese Health Study (SCHS), we examined the relationship between the HFC-PRS and HCC risk. In addition, we constructed and evaluated a NAFLD-related PRS (NAFLD-PRS) with HCC risk in the SCHS. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence with both HFC-PRS and NAFLD-PRS. The HFC-PRS and NAFLD-PRS were highly correlated (Spearman r = 0.79, p < 0.001). The highest quartiles of both the HFC-PRS and the NAFLD-PRS were associated with significantly increased risk of HCC with HR of 2.39 (95% CI 1.51, 3.78) and 1.77 (95% CI 1.15, 2.73), respectively, compared with their respective lowest quartile. Conclusion: The PRS for hepatic fat content or NAFLD may be useful for assessing HCC risk in both Asian and European populations. The findings of this and prior studies support a potential causal role of genetically determined NAFLD in HCC development.

12.
Ann Epidemiol ; 71: 9-14, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35462044

RESUMO

PURPOSE: The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia. METHODS: Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n = 126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors. RESULTS: The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR = 2.22, 95% CI 1.26-3.92), while later age at menarche was associated with decreased EC risk (HR = 0.14, 95% CI 0.04-0.46). In postmenopausal women, later age at menopause was associated with increased EC risk (HR = 2.82, 95% CI 1.24-6.43). Lifestyle and nutritional factors were not associated with risk of EC in this cohort. CONCLUSIONS: This study is one of the largest cohort studies exploring EC risk factors in Asian populations. Our study identified similarities in EC risk factors for European and Asian populations, which potentially suggests that strategies developed for EC prevention in Western populations can be potentially appropriate for the Singapore Chinese population due to risk factor similarities.


Assuntos
Neoplasias do Endométrio , China/epidemiologia , Estudos de Coortes , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco , Singapura/epidemiologia
13.
Hum Reprod ; 37(6): 1351-1359, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-35413122

RESUMO

STUDY QUESTION: Are there genetic variants that interact with smoking to reduce reproductive lifespan in East-Asian women? SUMMARY ANSWER: Our study corroborates several recently identified genetic loci associated with reproductive lifespan and highlights specific genetic predispositions that may interact with smoking status to adversely affect reproductive lifespan in East-Asian women. WHAT IS KNOWN ALREADY: Epidemiological data as well as evaluations on genetic predisposition to smoke indicate on the importance of smoking in adverse effects on reproductive lifespan in women. However, there are no previous smoking and gene interaction studies for reproductive traits in East-Asian women. STUDY DESIGN, SIZE, DURATION: This population-based prospective cohort study comprised 11 643 East-Asian Chinese women with overlapping genome-wide genotyping and reproductive data. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a genome-wide association study for reproductive lifespan in women (n = 11 643) from the Singapore Chinese Health Study (SCHS) and carried out a genome-wide interaction study to identify loci that interacted with smoking status to affect age of natural menopause and reproductive-time. MAIN RESULTS AND THE ROLE OF CHANCE: Two known loci associated with menopause, rs113430717 (near HMCES, chromosome 3, Pmeta = 5.72 × 10-15) and rs3020136 (near RAD21, chromosome 8, Pmeta = 1.38 × 10-8) were observed beyond genome-wide levels of association with age at menopause in this study. For reproductive lifespan, the genome-wide association observed at rs79784106 (chromosome 3, Pmeta = 5.05 × 10-12) was in linkage disequilibrium with the menopause lead single-nucleotide polymorphism (SNP) (rs113430717). Four additional loci, first reported to be associated with menopause, were also associated with reproductive lifespan in our study (PAdj between 7.42 × 10-5 to 4.51 × 10-3). A significant interaction was observed between smoking and an East-Asian specific SNP, rs140146885, for reduced reproductive lifespan, per copy of the minor C allele (beta = -1.417 years, Pinteraction = 2.31 × 10-10). This interaction was successfully replicated in additional independent samples (beta = -1.389 years, Pinteraction = 6.78 × 10-3). Another known variant associated with menopause, rs11031006 (near FSHB), was also observed to interact with smoking status to reduce age at menopause in our dataset (beta = -0.450 years, Padj = 0.042). LIMITATIONS, REASONS FOR CAUTION: The modest sample size of the replication datasets used likely affected the statistical power to firmly replicate all identified novel loci observed in our smoking interaction analyses. WIDER IMPLICATIONS OF THE FINDINGS: Age of natural menopause and reproductive lifespan have clear genetic predispositions with distinct ethnic differences, and they may be adversely truncated by lifestyle factors such as smoking, which can pose a significant impact on the reproductive lifespan and future health outcomes in women. STUDY FUNDING/COMPETING INTEREST(S): The Singapore Chinese Health Study is funded by the National Medical Research Council, Singapore (NMRC/CIRG/1456/2016), National Institutes of Health (R01 CA144034 and UM1 CA182876) and National Research Foundation, Singapore (Project Number 370062002). W.-P.K. is supported by the National Medical Research Council, Singapore (MOH-CSASI19nov-0001). The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Fumar Cigarros , Predisposição Genética para Doença , China , Feminino , Estudo de Associação Genômica Ampla , Humanos , Longevidade , Menopausa/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Singapura/epidemiologia
14.
BMC Med ; 20(1): 150, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35468796

RESUMO

BACKGROUND: Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear. METHODS: In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%. RESULTS: Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history. CONCLUSIONS: Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Medição de Risco
15.
JMIR Res Protoc ; 11(4): e37171, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35380544

RESUMO

BACKGROUND: Fifth metatarsal fractures are one of the most common foot fractures, and 11% to 25% of such fractures are Dancer's fractures (distal spiral fractures). Conservative therapy while wearing a cast and operative treatment have been used as preferred modes of treatment in the limited literature available. However, we often see healing problems, such as delayed union and nonunion, when Dancer's fractures are treated nonoperatively, resulting in a need for secondary intervention. In our institution, treatment has changed over the years from predominantly conservative treatment to mostly operative treatment. To investigate whether our hypothesis holds true that primary surgical treatment is beneficial, a retrospective study was designed. OBJECTIVE: The objective of the study is to compare differences between outcomes (delayed union and nonunion) of conservative and operative treatments for Dancer's fractures. METHODS: A retrospective comparative cohort study will be conducted in a level II trauma center (Zaandam Medical Center). Patients who experienced a Dancer's fracture in the period of 2012 to 2021 will be included and divided into 2 cohorts-the conservative (2012-2015) and operative (2016-2021) treatment cohorts. The primary outcome will be the differences in percentages of delayed union and nonunion between the two groups. The secondary outcomes will be the percentage of primary conservative treatment failure, the need for secondary operative treatment, complications (infection and hardware failure), and functional outcomes. If 118 patients are included in each group, sufficient power is expected to be reached, depending on the age distribution of patients. The percentages of delayed union and nonunion among the two groups will be calculated and statistically compared via chi-square statistics. A logistic regression analysis will be used to investigate possible associations between patient characteristics and failed conservative treatment. A Mann-Whitney U test will be used to compare functional outcomes between groups. An independent, 2-tailed t test will be used to compare mean 12-Item Short Form Survey scores if they are normally distributed, and a Wilcoxon rank sum test will be used if they are nonnormally distributed. RESULTS: In total, 2134 potentially relevant health insurance codes have been extracted from the hospital's register. We expect to find a total of 236 Dancer's fractures in this data set. CONCLUSIONS: Our study has limitations due to it being a single-center study and data collection being performed retrospectively. However, it covers a large time period and may provide the possibility to show treatment outcome differences (delayed union and nonunion, complications, and functional outcomes) in 2 reasonably large cohorts (conservative and operative treatment cohorts), which has not been done before in literature on Dancer's fractures. If our hypothesis that surgery is beneficial for Dancer's fractures is proven true by our study, we plan to further corroborate it by conducting a prospective randomized controlled trial. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37171.

16.
Cell Death Discov ; 8(1): 166, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383144

RESUMO

This study aimed to investigate the role of deubiquitinating enzyme 3 (DUB3) in the regulation of Krüppel-like factor 4 (KLF4) expression in hepatocellular carcinoma (HCC). Gain- and loss-of-function assay, luciferase reporter assay, co-immunoprecipitation, and intracellular and extracellular deubiquitination assays were conducted in vitro. A tumor xenograft mouse model was established. The expression of DUB3 and KLF4 was examined in HCC patient specimens. The results showed that DUB3 upregulated KLF4 expression by deubiquitinating and stabilizing KLF4 protein in HCC cells through binding with KLF4. DUB3 inhibited HCC cell proliferation in vitro and tumor growth in vivo while enhancing the chemosensitivity of HCC cells in a KLF4-dependent manner. Furthermore, KLF4 promoted DUB3 transcription by binding to the DUB3 promoter. In HCC patients, DUB3 expression positively correlated with KLF4 expression in HCC tissues. Low DUB3 expression predicted worse overall survival and recurrence in HCC patients. In conclusion, this study revealed a positive DUB3/KLF4 feedback loop that inhibits tumor growth and chemoresistance in HCC. These results suggest that DUB3/KLF4 activation might be a potential therapeutic approach for HCC treatment.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35449449

RESUMO

Klotho is a life extension factor that has the ability to regulate the function of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs), whose dysfunction in the nucleus accumbens (NAc) underlies critical aspects of the pathophysiology of major depression. Here, we study the functional relevance of klotho in the pathogenesis of depression. A chronic social defeat stress paradigm, in which mice are categorized as either susceptible or unsusceptible based on their performance in a social interaction test, was used in this study. We found that the expression of klotho was largely decreased in the NAc of susceptible mice compared to control or unsusceptible mice. Genetic knockdown of klotho in the NAc induced behavioral alterations relevant to depression in naive mice, while overexpression of klotho produced an antidepressive effect in normal mice and ameliorated the behavioral responses to stress in susceptible mice. Molecularly, knockdown of klotho in the NAc resulted in selective decreases in total and synaptic GluN2B expression that were identical to those in susceptible mice. Elevation of klotho in the NAc reversed the reductions in GluN2B expressions and altered synaptic transmission and spine density in the NAc of susceptible mice. Furthermore, blockade of GluN2B with a specific antagonist abolished the beneficial effects of klotho elevation in susceptible mice. Collectively, we demonstrated that klotho in the NAc modulates behavioral responses to stress by regulating the function of GluN2B-containing NMDARs. These results reveal a novel role for klotho in the pathogenesis of depression, providing new insights into the molecular basis of major depression.

18.
RSC Adv ; 12(10): 5910-5918, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35424579

RESUMO

NiCo metal-organic framework (MOF) electrodes were prepared by a simple hydrothermal method. The flower-like NiCo MOF electrode exhibited an exciting potential window of 1.2 V and an excellent specific capacitance of 927.1 F g-1 at 1 A g-1. The flower-like NiCo MOF//activated carbon (AC) device delivered a high energy density of 28.5 W hkg-1 at a power density of 400.5 W kg-1 and good cycle stability (95.4% after 5000 cycles at 10 A g-1). Based on the flower-like NiCo MOF electrode, the asymmetric quasi-solid-state flexible supercapacitor (AFSC) was prepared and exhibited good capacitance retention after bending (79% after 100 bends and 64.4% after 200 bends). Furthermore, two AFSCs in series successfully lit up ten parallel red LED lights, showing great application potential in flexible and wearable energy storage devices.

19.
Int J Epidemiol ; 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35229874

RESUMO

BACKGROUND: The association between body mass index (BMI) and oesophageal cancer (OC) has been consistently negative among Asians, whereas different associations based on histological OC subtypes have been observed in Europeans and North Americans. We examined the association between BMI and OC mortality in the Asia Cohort Consortium. METHODS: We performed a pooled analysis to evaluate the association between BMI and OC mortality among 842 630 Asians from 18 cohort studies. Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A wide J-shaped association between BMI and overall OC mortality was observed. The OC mortality risk was increased for underweight (BMI <18.5 kg/m2: HR = 2.20, 95% CI 1.80-2.70) and extreme obesity (BMI ≥35 kg/m2: HR = 4.38, 95% CI 2.25-8.52) relative to the reference BMI (23-25 kg/m2). This association pattern was confirmed by several alternative analyses based on OC incidence and meta-analysis. A similar wide J-shaped association was observed in oesophageal squamous cell carcinoma (OSCC). Smoking and alcohol synergistically increased the OC mortality risk in underweight participants (HR = 6.96, 95% CI 4.54-10.67) relative to that in reference BMI participants not exposed to smoking and alcohol. CONCLUSION: Extreme obesity and being underweight were associated with an OC mortality risk among Asians. OC mortality and BMI formed a wide J-shaped association mirrored by OSCC mortality. Although the effect of BMI on OSCC and oesophageal adenocarcinoma mortality can be different in Asians, further research based on a large case-control study is recommended.

20.
Int J Gen Med ; 15: 913-926, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35115817

RESUMO

OBJECTIVES: To identify the molecular subtypes of glioblastoma multiforme (GBM) related to M2 macrophage-based prognostic genes, then to preliminarily explore their biological functions and construct immunotherapy response gene models. MATERIAL AND METHODS: We used R language to analyze GBM microarray data, and other tools, including xCell and CIBERSORTx, to identify subtypes of GBM that related to M2 macrophages. The process started with the exploration of biological functions of the two subtypes by pathway analyses and GSEA, and continued with a combined procedure of constructing an M2 macrophage-related prognostic gene model and exploring the immune treatment response for GBM. RESULTS: A high abundance of M2 macrophages in GBM was associated with poor prognosis. According to M2 macrophage-related prognostic genes, GBM was divided into two subtypes (cluster A and cluster B). The differential gene enrichment analysis of the two clusters showed that cluster A was less enriched in M2 macrophages and had immunopotential. The M2score, which was constructed based on M2 macrophage-related prognostic genes, was not only related to the survival and prognosis of patients with GBM, but also predictive of the effectiveness of immunotherapy in these patients. This result has been effectively verified in an external data set. CONCLUSION: GBM was successfully divided into two subtypes according to M2-macrophage-related prognostic genes. In GBM, a high M2score may indicate better clinical outcome and enhancement of the immunotherapy response.

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