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1.
Zhonghua Liu Xing Bing Xue Za Zhi ; 44(7): 1027-1036, 2023 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-37482703

RESUMO

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age2, sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Neoplasias Pulmonares , Neoplasias Gástricas , Humanos , Feminino , Neoplasias Gástricas/epidemiologia , Análise da Randomização Mendeliana/métodos , Chá , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(9): 1200-1205, 2018 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-30293310

RESUMO

Objective: To prospectively explore the association between tea drinking and incidence of stroke of adults of Zhejiang province. Methods: After excluding participants with heart disease, stroke, cancer and diabetes at baseline study, 53 916 participants aged 30-79 years in the China Kadoorie Biobank (CKB) study from Tongxiang were included for final analysis. Cox regression model was used to estimate the hazard ratio (HR) for the association of tea drinking with incident stroke. Results: The main type of drinking tea was black tea (79.78%), followed by green tea (20.08%). Of the 53 916 participants, the proportion of participants who drank tea at least once per week was 31.27%. The corresponding proportions for men and women were 60.24% and 10.30%, respectively. Among 391 512 person-years of the follow-up program (median 7.26 years), a total of 1 487 men and 1 769 women were diagnosed with stroke. After adjusting for socio-demographic status, lifestyle, BMI, waist circumference, and systolic blood pressure, HR for incident stroke decreased with the increase of daily average tea consumption amount (P=0.000 6). Compared with participants who did not drink tea weekly, the HRs for incident stroke in those consuming tea 0.1-, 3.0- and ≥5.0 g/d were 0.93 (95%CI: 0.85-1.00), 0.88 (95%CI: 0.77-0.99) and 0.79 (95%CI: 0.69-0.89), respectively. The HRs for incident stroke in smokers and non-smokers who consumed tea ≥5.0 g/d were 0.71 (95%CI: 0.59-0.86) and 0.97 (95%CI: 0.77-1.21), respectively, compared with current smokers and non-smokers who did not drink tea weekly (P=0.040 0). The corresponding HRs for alcohol drinkers and non-drinkers were 0.96 (95%CI: 0.76-1.22) and 0.70 (95%CI: 0.58-0.84), respectively (P=0.040 0). The corresponding HRs for central obese persons and non-central obese persons were 0.60 (95%CI: 0.44-0.81) and 0.86 (95%CI: 0.73-1.01), respectively (P=0.040 0). Conclusion: Tea drinking had an effect on reducing the possibility of incident stroke, especially among those who were current smokers, non-alcohol drinkers and central obese.


Assuntos
Medição de Risco/métodos , Acidente Vascular Cerebral/epidemiologia , Chá , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/etnologia , Chá/efeitos adversos
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(7): 867-872, 2018 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-30060295

RESUMO

As a national strategy, the goal of Build a Healthy China is of significant importance on forming a well-off society, in which Public Health endeavor always stands an epi-center role. In developing the Healthy China strategy, we need to prioritize the people's health and recognize that Healthy China requires both brilliant health guidance and the belief of One Health. In addition, we must adhere to public welfare of health and health development. We should also take continuous reforming process and innovation as the fundamental motive force for promoting the construction of healthy China, with building up strong professional teams as one of the core elements. The development of Healthy China should adhere to the following strategies as Prevention First, Improving people's health, Strengthening control and prevention on chronic diseases, Improving health education, Building self-awareness on healthy behavior, Improving physical quality of the people, Increasing the accessibility on public health service, promoting the fully use of unique advantages provided by traditional Chinese medicine, Strengthening the health service of the key crowd, etc. We should also carry out the Patriotic Health Campaign and improve the governance of environmental problems that affecting health status of the people. In the process of building up Healthy China, the following points should stick to at all times, which are: leadership of the government and Prevention first policy' should be emphasized and adhere to the basic functions of the public health concept and providing health for all in the nation, practising the mass ecological health model which would promote the integrated development of medicine. We should also adhere to the talent strategy in improving the capacity building of the public health team, recognizing research as essential importance. The strategy should also scientifically and orderly adhere to the routine public health practices to ensure the coordination between routine and emergency services and adhere to the evidence-based decision-making models to make sure the equalization of public health services provided at an early date. Both Healthy China and Healthy life need healthy environment as well. We should work together to tackle the global public health problems. In the new era of Healthy China development, we should provide Chinese people with comprehensive and full life-cycle health services. We will make all efforts to step out the development of health-related endeavor under China's own characteristics, to contribute to the great practice of socialism in the new era.


Assuntos
Atenção à Saúde , Saúde Pública , China , Humanos
4.
Andrologia ; 46(3): 283-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23465132

RESUMO

This study is to explore whether YGW has an impact on sperm fertilising ability in mice. Twenty male mice were randomly divided into two groups. In vivo experiments, one group of animals were orally administrated with YGW decoction and another group administered with saline for 14 days. Afterwards, the animals were mated with their female partners. Percentages of retrieved zygotes were then compared. In vitro experiments, in vitro fertilisation (IVF) assay, sperm acrosome reaction and acrosin activity were used to compare sperm fertilising ability between the two groups. The YGW-treated group had a significantly higher percentage of zygotes than the saline controls (P = 0.005). The IVF rates induced by spermatozoa from the herb-treated mice were also significantly higher than those from the control animals (P = 0.015). The sperm acrosin activity of the herb-treated group was significantly higher than that of the saline-treated group (P = 0.048), although there was no significant difference in testicular weight, sperm count and sperm motility. These data suggest that YGW decoction has a significant effect on normal sperm fertilising ability both in vivo and in vitro, which may be due to, at least in part, increments in the sperm acrosin activity.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fertilização/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Acrosina/metabolismo , Reação Acrossômica/efeitos dos fármacos , Animais , Feminino , Fertilização/fisiologia , Fertilização in vitro , Infertilidade Masculina/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Tamanho do Órgão/efeitos dos fármacos , Fitoterapia , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Testículo/anatomia & histologia , Testículo/efeitos dos fármacos
5.
Public Health ; 125(1): 20-24, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21168177

RESUMO

Since the foundation of the People's Republic of China in 1949, there has been remarkable developments in public health in the country. These achievements are primarily attributed to the public health services and patriotic public health campaigns, although the contribution of high-technology medical applications is also recognized. However, along with the recent socio-economic developments and scientific and technological progress, medical disciplines have become more and more specialized, and clinical and preventive medicine have become further separated from each other. Conventional Chinese wisdom says 'when long divided they must unite, when long united they must divide'. At the onset of the new round of reforms of health care in China, it seems important to revisit the discussions on the urgency for integration of health sciences in medicine in China. Several issues and viewpoints on integrating medicine are discussed in this paper. The biopsychosocial model for health calls for broad integration. Primary care development in China requires integration in education and practice, and in treatment and prevention. Control of chronic diseases requires integrated and united action. Integration of traditional Chinese medicine with Western medicine requires creativity. The integration perspective should be instilled in the minds of medical students. Integration also entails integrated practice. After all, integration entails integrated education and practice in public health education. Changing the current public health education system still has a long way to go. True integration requires integration of concepts, policies, resources and measures, as well as changes in the organization of health care including public health, prevention and treatment. This needs to be a systematic process. Finally, success of integration relies on social mobilization, advocacy, promotion and attention of the entire society.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Educação Profissional em Saúde Pública/organização & administração , Saúde Pública/normas , China , Doença Crônica/prevenção & controle , Reforma dos Serviços de Saúde/normas , Humanos , Medicina Tradicional Chinesa , Especialização/normas
6.
Eye (Lond) ; 20(6): 712-9, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16021194

RESUMO

PURPOSE: To evaluate the efficacy of pain relief by oral diazepam, acetaminophen, mefenamic acid, intramuscular ketorolac tromethamine, and peribulbar anaesthesia in panretinal photocoagulation (PRP). METHODS: A total of 220 patients with proliferative diabetic retinopathy requiring PRP treatment were enrolled in this study. Before laser treatment, the patients were allocated randomly to one of eight groups: group 1: diazepam (n=22), group 2: acetaminophen (n=21), group 3: mefenamic acid (n=21), group 4: diazepam and acetaminophen (n=22), group 5: diazepam and mefenamic acid (n=22), group 6: peribulbar anaesthesia with lidocaine (n=23), group 7: intramuscular injection of ketorolac tromethamine (n=22), group 8: placebo (n=67). Pain after the laser treatment was assessed by a verbal descriptive scale. Blood pressure and heart rate were measured before and after laser treatment. RESULTS: Patients receiving peribulbar anaesthesia had a significantly lower pain score than the control group (P<0.0001). Additionally, the peribulbar anaesthesia-treated group had the significantly least PRP-associated rise in either systolic (P=0.043) or diastolic blood pressure rates (P=0.030). There were no significant differences in pain score using other anesthetic agents when compared with the control group. There were no significant changes in heart rate after PRP treatment. CONCLUSION: Peribulbar anaesthesia is effective in reducing pain and blood pressure increase after PRP treatment. Oral diazepam, mefenamic acid, and acetaminophen (either alone or in combination with each other) are not effective in preventing PRP treatment-associated pain. Intramuscular injection of ketorolac tromethamine is also not effective in reducing PRP-associated pain.


Assuntos
Analgesia/métodos , Retinopatia Diabética/cirurgia , Fotocoagulação a Laser/efeitos adversos , Dor Pós-Operatória/terapia , Acetaminofen , Idoso , Anestesia Local , Anestésicos Locais , Anti-Inflamatórios não Esteroides , Pressão Sanguínea , Diazepam , Feminino , Frequência Cardíaca , Humanos , Cetorolaco de Trometamina , Lidocaína , Masculino , Ácido Mefenâmico , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos
7.
Epilepsia ; 40(12): 1821-7, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10612351

RESUMO

PURPOSE: Whereas EEG spiking and decreases of the neuronal marker N-acetyl-aspartate (NAA) both localize well the epileptic focus, the significance of the intensity of these variables is unclear. Therefore we investigated whether the frequency of interictal surface spikes is related to the degree of N-acetyl-aspartate/creatine (NAA/Cr) ratio decrease as measured by proton magnetic resonance (MR) spectroscopic imaging (1H-MRSI) in patients with intractable partial epilepsy. METHODS: We retrospectively studied 14 patients, nine with temporal lobe epilepsy and five with frontal lobe epilepsy. Spikes that occurred during prolonged video-EEG monitoring from electrodes placed according to the International 10-20 system were counted blinded to the 1H-MRSI results. Eight electrode positions (F3/4, C3/4, T3/4, T5/6) were assigned to underlying brain subregions in the 1H-MRSI volume of interest. We converted NAA/Cr ratios into z-scores (NAA/Cr(z)) to compared NAA/Cr values directly across subregions. We calculated Spearman rank-order (p) and Pearson product-moment (r) correlations between spike frequency and NAA/Cr(z) values overall, as well as within each brain subregion. RESULTS: We found an overall negative relation between spike-frequency data and NAA/Cr(z) data (p = -0.341). When analyzing only spiking subregions, this negative relation became slightly stronger (p = -0.442; r = -0.338). When data from the eight sites were considered separately, this negative relation remained in most instances. CONCLUSIONS: Our results reveal a trend toward higher interictal spike frequencies on surface EEG in regions of pronounced neuronal metabolic damage or dysfunction. This suggests that both variables parallel an underlying pathologic substrate, although the pathophysiologic processes may be distinct.


Assuntos
Ácido Aspártico/análogos & derivados , Creatina/análise , Eletroencefalografia/estatística & dados numéricos , Epilepsias Parciais/diagnóstico , Lobo Frontal/química , Espectroscopia de Ressonância Magnética , Lobo Temporal/química , Adolescente , Adulto , Ácido Aspártico/análise , Ácido Aspártico/metabolismo , Creatina/metabolismo , Epilepsias Parciais/metabolismo , Epilepsia do Lobo Frontal/diagnóstico , Epilepsia do Lobo Frontal/metabolismo , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/metabolismo , Feminino , Lobo Frontal/metabolismo , Humanos , Masculino , Estudos Retrospectivos , Lobo Temporal/metabolismo
8.
Neurology ; 51(4): 1046-50, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9781527

RESUMO

BACKGROUND: Patients with hypothalamic hamartomas present with epileptic attacks of laughter and later experience multiple seizure types and cognitive decline, suggestive of secondary generalized epilepsy. It has been suggested in the past that gelastic seizures originate in the temporal lobes rather than in the hamartoma, but temporal resections have been ineffective. Recent electrophysiologic evidence suggests that the epileptogenic discharges may originate in the hamartoma itself. METHODS: We used proton magnetic resonance spectroscopic imaging to quantify the amount of neuronal damage in the temporal lobes and hamartomas of patients with hypothalamic hamartomas and gelastic seizures. Five patients were studied and the relative intensity of N-acetylaspartate to creatine (NAA/Cr) was determined for both temporal lobes as well as for the hamartoma. These values were compared with signals from the temporal lobes and hypothalami of normal control subjects. RESULTS: NAA/Cr was not significantly different from normal control subjects for either temporal lobe, nor was there a significant asymmetry between the two temporal lobes for any of the patients. NAA resonance signals were present in the hamartomas, and the ratio of NAA to Cr was decreased in the hamartomas compared with the hypothalami of normal control subjects (t = 4.5, p = 0.005). CONCLUSIONS: We found no detectable neuronal damage in the temporal lobes of patients with hypothalamic hamartomas and gelastic epilepsy. This is further evidence that gelastic seizures do not originate in the temporal lobes of these patients.


Assuntos
Epilepsia/diagnóstico por imagem , Hamartoma/diagnóstico por imagem , Doenças Hipotalâmicas/diagnóstico por imagem , Riso/fisiologia , Adolescente , Adulto , Criança , Eletroencefalografia , Epilepsia/etiologia , Epilepsia/fisiopatologia , Feminino , Hamartoma/complicações , Hamartoma/fisiopatologia , Humanos , Doenças Hipotalâmicas/complicações , Doenças Hipotalâmicas/fisiopatologia , Hipotálamo , Imageamento por Ressonância Magnética/métodos , Masculino , Tomografia Computadorizada de Emissão de Fóton Único
9.
Brain ; 121 ( Pt 8): 1507-12, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9712012

RESUMO

We used proton magnetic resonance spectroscopic imaging (MRSI) to assess in vivo cortical neuronal involvement in hyperekplexia. Cerebral neuronal function was measured using proton MRSI in four unrelated patients with hyperekplexia and 20 healthy controls. All patients had the major form of hyperekplexia, with additional atypical clinical features in two of them. Family history was positive in three patients and absent in one. The neuronal marker N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine (Cr) were measured in frontal, central and parietal areas. The MRSI showed a reduction of the relative resonance intensity of NAA/(Cr + Cho) in frontal and central regions in three patients, and in the right frontal region of the fourth. In one patient a second MRSI showed normal relative NAA resonance intensities over both temporal lobes as well as in the brainstem. In two subjects the topography of EEG abnormalities in the frontal lobes coincided with the MRSI findings. This proton MRSI study indicates the presence of frontal neuronal dysfunction in hyperekplexia. Whether this represents cortical dysfunction or an epiphenomenon of diencephalic or brainstem abnormalities remains open. However, the observation of normal proton MRSI in the temporal regions and brainstem in one of the patients seems to concur with the hypothesis of a facilitatory role of cortical dysfunction within areas of sensorimotor representation in the generation of the pathological startle reaction in hyperekplexia.


Assuntos
Lobo Frontal/fisiopatologia , Rigidez Muscular/fisiopatologia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/fisiopatologia , Neurônios/fisiologia , Reflexo Anormal/fisiologia , Reflexo de Sobressalto/fisiologia , Adolescente , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/metabolismo , Colina/metabolismo , Creatina/metabolismo , Feminino , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças do Sistema Nervoso/patologia , Valores de Referência
10.
Zhonghua Fu Chan Ke Za Zhi ; 28(7): 389-91, 440, 1993 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-8287719

RESUMO

The concentration of serum calcium (Ca), phosphorus (P), alkaline phosphatase (AKP), parathyroid hormone (PTH) and calcitonin (CT) of 66 healthy pregnant women were measured at 2nd trimester, full term, 3 days and 6 weeks postpartum. These parameters were also measured in 56 patients with moderate or severe PIH in late pregnancy. The results showed that in spite of the obvious changes observed in these parameters at various periods, regulatory system of calcium metabolism in normal pregnancy was not affected. By contrast, calcium metabolism imbalance was seen in patients with moderate and severe PIH. The occurrence of PIH between two groups of pregnant women (50 each) with or without calcium supplement was compared. The pattern of calcium metabolism in normal pregnancy was summarized, and the pathogenesis of PIH related to calcium metabolism was discussed. The study provides an important basis for calcium supplementation during pregnancy and for using calcium antagonists to treat PIH patient.


Assuntos
Cálcio/sangue , Pré-Eclâmpsia/sangue , Gravidez/sangue , Fosfatase Alcalina/sangue , Calcitonina/sangue , Feminino , Humanos , Hormônio Paratireóideo/sangue , Período Pós-Parto/sangue
11.
Contraception ; 45(6): 523-32, 1992 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1535580

RESUMO

A randomised cross-over trial was performed to compare the pharmacodynamic actions of three low-dose oral contraceptives (OCs): Marvelon (150 micrograms desogestrel (DSG)+ 30 micrograms ethinyloestradiol (EE)), Mercilon (150 micrograms DSG + 20 micrograms EE) and Microgynon (150 micrograms levonorgestrel (LNG) + 30 micrograms EE). None of the OCs produced any significant changes in serum cholesterol, LDL-C and apoprotein B. Triglycerides were increased by the desogestrel OCs but not by Microgynon. The latter however increased the glucose and insulin responses to a glucose tolerance test whereas Marvelon and Mercilon had no effect. HDL-C increased with Marvelon, was unchanged with Mercilon and was decreased with Microgynon. Apoprotein AII was increased by all three OCs but only the DSG OCs increased apoprotein AI. All OCs produced similar increases in caeruloplasmin but the increase in SHBG was much greater with Marvelon and Mercilon than with Microgynon. Testosterone was reduced more with Microgynon than with the DSG OCs. Many of the changes reflect the strong anti-oestrogenic action of LNG on metabolic parameters compared to DSG. Except for the effect on HDL-C, there was little difference between Marvelon and Mercilon on metabolic parameters and this complements the findings from large-scale clinical trials of the two OCs. Mercilon, therefore provides a very satisfactory alternative to Marvelon.


PIP: 12 healthy volunteers attending the family planning clinic at Shanghai, First Maternity and Infant China, Hospital, enrolled in the study, Oral contraceptives (OCs) were prescribed: Marvelon (150 mcg of desogestrel--DSG), Mercilon (150 mcg of DSG), and Microgynon (150 mcg of levonorgestrel--LNG). The patients were divided into 6 groups of 2 persons each in a randomized cross-over study. OCs were taken on day 6 of the cycle up to day 21, then stopping for 7 days. Each OC was used for 3 months. During the pretreatment cycle between days 6 and 9 of the follicular phase and 21 and 22 of the luteal phase a blood sample was taken after fasting for determination of lipids, sex hormone binding globulin (SHGB), ceruloplasmin, and testosterone. After glucose loading, significant increases of glucose and insulin occurred at 1, 2, and 3 hours during treatment with Microgynon only. The ratio for total areas of insulin to glucose did not change significantly nor did glycosilated hemoglobin A1 levels. Serum triglyceride concentrations increased significantly for both Marvelon (27%-43%) and Mercilon (29-40%). Serum high density lipoprotein (HDL) cholesterol concentrations were significantly elevated with Marvelon but less so with Mercilon, while HDL-C decreased significantly with Microgynon. The serum low density lipoprotein (LDL) cholesterol changes were not significant, but LDL-C concentrations declined with DSG formulations and increased with Microgynon. Apoprotein A1 and A2 increased significantly for both Marvelon and Mercilon. Apoprotein A2 increased with Microgynon. Serum SHBG increased markedly with Marvelon (335-380%). Serum testosterone concentrations decreased significantly (33.2-40.4% with Microgynon) and so did ceruloplasmin values. The antiestrogenic effect of strong LNG in Microgynon produced significant metabolic changes. The effect of 30 mcg EE in Marvelon and 20 mcg EE of Mercilon was equal.


Assuntos
Glicemia/metabolismo , Anticoncepcionais Orais Combinados , Etinilestradiol , Insulina/sangue , Levanogestrel , Lipídeos/sangue , Norgestrel , Norpregnenos , Pancurônio/análogos & derivados , Congêneres da Progesterona , Adulto , Apolipoproteínas/sangue , Ceruloplasmina/análise , Colesterol/sangue , Desogestrel , Combinação Etinil Estradiol e Norgestrel , Feminino , Teste de Tolerância a Glucose , Humanos , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Triglicerídeos/sangue
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