Fetal growth, fetal development, and placental features in women with polycystic ovary syndrome: analysis based on fetal and placental magnetic resonance imaging / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#Polycystic ovary syndrome (PCOS), a common endocrine-metabolic dysfunction in reproductive-aged women, may be involved in compromised pregnancy and offspring outcomes. This study aimed to investigate whether maternal PCOS affects fetal growth, fetal development, and placental features.@*METHODS@#This retrospective case-control study included 60 pregnant women with PCOS (PCOS group) and 120 healthy pregnant women without PCOS (control group). Fetal magnetic resonance imaging (MRI) was performed followed by an ultrasound examination and indications for imaging, including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member, and concern for placenta accreta. Fetal MRI images were analyzed for head circumference (HC), abdomen circumference (AC), lung-to-liver signal intensity ratio (LLSIR, a prenatal marker of fetal lung maturity), lengths of liver and kidney diameters in fetuses, and placental relative signal intensity on T2-weighted single-shot fast spin echo (SSFSE) imaging (rSI@*RESULTS@#Compared to the control group, the PCOS group showed the following characteristics: (1) smaller biparietal diameter and femur length in fetuses (P=0.026 and P=0.005, respectively), (2) smaller HC in fetuses (evident after 32 weeks; P=0.044), (3) lower LLSIR and smaller dorsoventral length of liver in fetuses (evident before 32 weeks; P=0.005 and P=0.019, respectively), and (4) smaller placental thickness (evident before 32 weeks; P=0.017). No significant differences in placental rSI@*CONCLUSIONS@#There exist alterations of fetal growth, fetal development, and placental features from women with PCOS.

Clinical effects of Xiaoer-Chaigui-Tuire granules in the treatment of mycoplasma pneumoniae pneumonia / 国际中医中药杂志

Objective To study the effects of Xiaoer-Chaigui-Tuire granules in the treatment of mycoplasma pneumoniae pneumonia (MPP). Methods A total of 200 children with mycoplasma pneumoniae pneumonia which conformed to the standard of admission were randomly divided into the control group (n=100) and the treatment group (n=100). The control group were treated with azithromycin, and the treatment group were treated with Xiaoer-Chaigui-Tuire granules combined with azithromycin. The temperature recovery time, cough disappeared time, asthma disappeared time, lungs rale disappeared time of the two groups were observed and compared. The serum IgG, IgM and IgA levels were detected by ELISA and the CD3, CD4, CD8 cell ratio of peripheral blood were detected by flow cytometry. Results The total effect rate of the treatment group was 95.0％ (95/100), significantly higher than 80.0％ (80/100) of the control group (χ2=10.286, P=0.001). The fever disappeared time (2.5 ± 0.3 d vs. 4.2 ± 0.9 d, t=17.004), cough disappeared time (3.0 ± 0.6 d vs. 4.5 ± 0.5 d, t=19.861), asthma disappeared time (3.1 ± 1.1 d vs. 4.0 ± 1.3 d, t=5.046), lungs rale disappeared time (4.2 ± 1.0 d vs. 8.4 ± 1.5 d, t=22.988) and of the treatment group were significantly lower than those of the control group (P<0.01). After treatment, the IgG (9.47 ± 1.63 g/L vs. 7.05 ± 1.46 g/L, t=11.059), IgM (1.87 ± 0.52 g/L vs. 1.53 ± 0.48 g/L, t=4.804) and IgA (1.79 ± 0.61 g/L vs. 1.20 ± 0.53 g/L, t=7.301) of the treatment group were significantly higher than those of the control group (P<0.01). After treatment, the blood CD3 levels (78.83％ ± 5.20 ％ vs. 57.48％ ± 4.09％, t=32.271), CD4 levels (40.27％ ± 3.42％ vs. 30.54％ ± 3.27％, t=20.563) of the treatment group were significantly higher than the control group, and the blood CD8 levels (21.15％ ± 2.90％ vs. 30.14％ ± 3.85％, t=18.651) of the treatment group were significantly lower than the control group (P<0.01). There was no significant difference in the incidence of adverse events between two groups (χ2=0.649, P=0.421). Conclusions The Xiaoer-Chaigui-Tuire granules combined with azithromycin for children with MPP has a good efficacy and low adverse events. They could relieve the clinical symptoms and improve the children's immune function.

American, European, and Chinese practice guidelines or consensuses of polycystic ovary syndrome: a comparative analysis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder in women. However, there is no agreement concerning how to diagnose and treat PCOS worldwide. Three practice guidelines or consensuses, including consensus from the European Society of Human Reproduction and Embryology (ESHRE)/the American Society for Reproductive Medicine (ASRM) in Rotterdam, diagnosis criteria and consensus in China, and clinical practice guideline from the Endocrine Society (ES) in the United States are widely recognized. The present paper may provide some guidance for clinical practice based on a comparative analysis of the above three practice guidelines or consensuses.

Long-term effects of polycystic ovary syndrome on the offspring / 浙江大学学报·医学版

Polycystic ovary syndrome (PCOS) is an endocrine disorder with reproductive dysfunction and abnormal metabolic syndrome. However, its etiology is unknown yet. Androgen hypersecretion is one of the main features of PCOS. It has been found that PCOS has various effects on the offspring in reproductive, metabolic and nervous systems, including:increasing secretion of gonadotropin-releasing hormone and luteinizing hormone, ovarian morphological changes and abnormal secretion of sex hormones, leading to disorders of lipid and glucose metabolism, and increasing the risks of depression and autism. However, there is still lack of direct evidence, and more studies should be conducted on the underlying mechanism in future.

Research Status of TCM Intervention of Vascular Remodeling in Hypertension / 中国中医药信息杂志

Vascular remodeling is an important pathological link of maintaining and developing high blood pressure. TCM has the advantage of comprehensive regulation effects with multiple channels, multiple links and multiple targets. Applying TCM treatment in vascular remodeling is a good point cut in the prevention and treatment of hypertention. This article reviewed the research status of TCM treatment of vascular remodeling in hypertention, with a purpose to provide ideas for clinical application and further research.

Correlation between follicle-stimulating hormone and total procollagen I N-terminal propeptide in perimenopausal women / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the correlation between serum levels of follicle-stimulating hormone (FSH) and total procollagen I N-terminal propeptide (TP1NP) in perimenopausal women.</p><p><b>METHODS</b>Total 274 women aged 33~60 y with perimenopausal period were enrolled in this study. Serum levels of FSH and TP1NP were detected by electrochemiluminescence.</p><p><b>RESULTS</b>In 274 perimenopausal women, the average level of TP1NP was (48.99±20.31) ng/mL, which was positively correlated with FSH level (r=0.159, P=0.009). In 40-50 age group, TP1NP level in women with FSH<40 mIU/mL was lower than that in those with FSH≥40mIU/mL [(35.05±18.11) ng/mL vs (51.33±24.67) ng/mL; t=-2.954, P=0.004]. However, in <40 and 50-60 age groups, there were no significant differences in TP1NP levels between patients with FSH<40 mIU/mL and those with FSH≥40 mIU/mL (t=-0.063, P=0.950; t=1.177, P=0.242). Multiple linear regression analysis showed that standardized coefficients of age variable was 0.047 (P=0.448) and standardized coefficients of FSH variable was 0.146 (P=0.019).</p><p><b>CONCLUSION</b>TP1NP levels showed a certain correlation with FSH in perimenopausal women, especially for women aged 40-50, indicating that high FSH levels may be important factors for osteoporosis in postmenopausal women.</p>

Changes of plasma cardiotrophin-1 levels in neonates with myocardial ischemic injury / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes and significance of plasma cardiotrophin-1 (CT-1) in neonates with hypoxic-ischemic encephalopathy (HIE) complicated by myocardial ischemic injury.</p><p><b>METHODS</b>Forty-five neonates with HIE (15 mild cases, 24 moderate cases and 6 severe cases) were enrolled and divided into two subgroups based on the presence of myocardial injury (n=19) and not (n=26). Twenty healthy neonates were used as the control group. Plasma CT-1 levels were measured using double-antibody sandwich enzyme immunoassay method. Serum creatinine kinase MB (CK-MB) and cardiac troponin I (CTnI ) levels were also measured.</p><p><b>RESULTS</b>Plasma CT-1 levels in the mild HIE (169±20 pg/mL) and moderate/severe HIE subgroups (287±44 pg/mL) were significantly higher than those in the control group (30±8 pg/mL), and plasma CT-1 levels were associated with the severity of HIE (P<0.01). Plasma CT-1 levels were positively correlated with serum CK-MB and CTnI levels in neonates with HIE in the acute phase (r=0.565 and 0.621 respectively; P<0.01). Plasma CT-1 levels in neonates with myocardial injury were significantly higher than those without myocardial injury (249 ±35 pg/mL vs 177±26 pg/mL; P<0.01). Plasma CT-1 levels were significantly reduced in neonates with myocardial injury in the convalescent phase (157±19 pg/mL) compared with those in the acute phase (249±35 pg/mL; P<0.01).</p><p><b>CONCLUSIONS</b>Detection of plasma CT-1 levels may be useful in the diagnosis of myocardial ischemic injury and the severity evaluation of HIE.</p>

Management of Cesarean Scar Pregnancy: A Case Series / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To survey effective treatment strategies for cesarean scar pregnancy (CSP).</p><p><b>METHODS</b>The clinical data of 78 patients diagnosed with CSP from January 2010 to December 2013 were reviewed.</p><p><b>RESULTS</b>Among these patients, 17 patients were first treated at our hospital; of them, 2 were misdiagnosed. The other 61 patients were referred from other hospitals; of them, 21 were initially misdiagnosed. There were 9 patients who were treated with laparotomy, 50 patients with curettage after uterine artery embolization (UAE) with or without local methotrexate (MTX) infusion, 10 patients with dilatation and curettage, 6 patients with transvaginal sonographic guided local intragestational MTX injection, and 3 patients with systemic MTX injection. All patients finally recovered. Patients with excessive vaginal hemorrhage underwent either emergency UAE treatment or laparotomy. These two treatments had similar success rates (81.82% vs. 100%, χ2 =0.289, P>0.05).</p><p><b>CONCLUSIONS</b>The accurate diagnosis of CSP is important. Curettage after UAE with or without local MTX infusion is a safe and effective method.</p>

ZO-1 gene methylation status and its clinical significance in children with non-Hodgkin lymphoma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the methylation status of zonula occludens-1 (ZO-1) gene promoter and its clinical significance in children with stage IV non-Hodgkin lymphoma (NHL) and to provide a basis for further etiological study and early diagnosis of this disease.</p><p><b>METHODS</b>Fifty-five children with a confirmed diagnosis of stage IV NHL (40 cases of T-NHL and 15 cases of B-NHL) were selected as the case group, and 20 children with diseases other than hematologic malignancies were selected as the control group. Bone marrow samples were collected from these subjects. Methylation-specific PCR (MS-PCR) was applied to evaluate the methylation status of ZO-1 gene promoter, and the integrated optical density (IOD) was determined. RT-PCR was used to measure the mRNA expression of ZO-1.</p><p><b>RESULTS</b>MS-PCR showed that the methylated bands of ZO-1 gene promoter were found in 39 (70.9%) of 55 patients in the case group before treatment, while no ZO-1 gene promoter methylation was detected in the control group. With close tracking of 47 cases in the study group, consisting of 32 cases of T-NHL and 15 cases of B-NHL, the rates of ZO-1 gene promoter methylation prior to treatment were 72% and 67%, respectively, (P>0.572). The cases of T-NHL and B-NHL showed no significant changes in methylation rate in the early and middle phases of chemotherapy (P>0.05), but they showed significant changes in methylation rate in the late phase of chemotherapy (P<0.05). RT-PCR showed that the NHL cases carrying methylated ZO-1 gene had no mRNA expression of ZO-1, while all children in the control group had mRNA expression of ZO-1. There was no linear relationship between the total number of peripheral blood leukocytes and ZO-1 gene IOD (r=0.093, P=0.575); a positive correlation was found between the number of malignant cells in bone marrow and ZO-1 gene IOD (r=0.669, P<0.001).</p><p><b>CONCLUSIONS</b>ZO-1 gene shows a hypermethylation status in children with NHL, and the methylation level is positively correlated with the number of malignant cells in bone marrow. ZO-1 may be used as a novel molecular marker in early diagnosis, outcome assessment, prognostic evaluation, and detection of minimal residual disease.</p>

Detection of malignant lymphoma in children by using Id4 gene methylation indicator / 中华实用儿科临床杂志

Objective To study and discuss what part does methylated Id4 gene participate in malignant lymphoma stage Ⅳ by detecting the extent of how much Id4 gene has been methylated in afflicted children who suffer from malignant lymphoma.Methods Forty-two patients who had diagnosed with malignant lymphoma [Hodgkin's disease (HD),Non-Hodgkin's lymphoma(NHL)] were selected as study group.Their chemotherapy stages of pre-treatment,early-treatment,mid-treatment,post-treatment and clinical remissions or relapse throughout the entire treatment had been traced.At each stage the expression of methylated Id4 gene mRNA was detected by methylation-specific polymerase chain reaction (MS-PCR) and compared with the control group.The control group consisted of 20 non-neoplastic hematologic disorder affected children as sample donors.Results MS-PCR detection:in pre-treatment stage,there were 27 patients who were found methylated or partially methylated Id4 genes.Methylated ratio was thus at 64.3％ (27 patients out of a total of 42 patients).Those 27 patients were actively traced down along with different stages of treatment (21 NHL patients,6 HD patients).Before NHL there was 55.6％ methylated Id4 gene (15 cases out of 27 NHL patients).During chemotherapy treatment,there was 51.9％ of methylated Id4 gene positive (14 cases out of 27 patients).In post chemotherapy treatment,there was 48.1％ of methylated Id4 gene positive (13 cases out of 27 patients).Totally there were 9 patients showed clinical recovery after chemotherapy.There was 44.4％ of traceable methylated Id4 gene after recovered chemotherapy patients (4 recovered patients still carrying positive reading of methylated Id4 gene out of totally 9 recovered patients).There were 2 patients relapsed,with traceable methylated Id4 gene re-appeared in them afterwards.Throughout different treatment stages,there was no significant correlation in the treatment result and the appearance of methylated Id4 gene in early treatment stages (all P ＞ 0.05).But in latter treatment of chemotherapy,the correlation started to emerge (P ＜ 0.05) ; The overall statistics on NHL and HD share the same statistical pattern on different stages (all P ＞ 0.05).The control group had 20 patients,none of them had methylated Id4 gene.The study group showed noticeable difference in methylated Id4 gene before and after the experiment (P ＜ 0.001).RT-PCR result showed that before chemotherapy treatment,all of those who carried methylated Id4 gene had no expression of mRNA,by comparison to the control1 group which all had expression of mRNA.Conclusions Methylated Id4 gene is closely related in affected children who suffer from malignant lymphoma and its complications.The expression of Id4 gene is depressed when it has been methylated.The state of methylated Id4 gene is changed as patient's condition changed,so the methylated Id4 gene is thus a possible indicator of early diagnostic tool for children lymphoma.

Relationship between methylation status in promoter region of Runx3 gene and children malignant lymphoma / 白血病·淋巴瘤

Objective To study methylation status of the Runx3 gene in occurrence and development of children malignant lymphoma.Methods The bone marrow specimens of 48 children diagnosed as malignant lymphoma were included into experimental group.20 children with non-malignancy were included into control group.Methylation-specific polymerase chain reaction (MS-PCR) was used to detect methylation status of Runx3 gene in bone marrow cells.The reverse transcription-polymerase chain reaction (RT-PCR) was used to detect mRNA expression of Runx3 gene.Results MS-PCR assay results showed that 31 cases expressed Runx3 gene methylation in experimental group,the positive rate was 64.6 ％ (31/48),but no one was detected in control group (20 cases),the difference between two groups was significant (x2 =15.7,P ＜0.05).Dynamic observation of 42 cases in experimental group showed the declining of Runx3 methylation positive rate.RT-PCR assay results showed that all 20 cases in the control group expressed Runx3 gene mRNA,all cases with methylation status of the Runx3 gene in the experimental group didn’ t expressed Runx3 gene mRNA.In experimental group,9 cases of clinical remission expressed Runx3 gene mRNA,and 1 case of relapsed didn’ t expressed Runx3 gene mRNA.Conclusion Runx3 gene shows a high methylation status in bone marrow cells of malignant lymphoma children,so that blocked the expression of Runx3 gene,which is closely related to the occurrence and development of children malignant lymphoma.

Methylation of Id4 gene and inhibitive effect of arsenic trioxide on it in Raji cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To study methylation of Id4 gene and demethylation effect of arsenic trioxide (ATO) in Raji cells.</p><p><b>METHODS</b>Human Burkitt's Raji lymphoma cells were cultared and treated with ATO at different concentrations and different time points. Methylated degree of Id4 gene was detected by methylation specificity polymerase chain reaction (MS-PCR), Id4 mRNA expression in Raji cell by reverse transcription polymerase chain reaction (RT-PCR), the growth of cell by MTT assay, and cell apoptosis and cycle distribution by Flow Cytometry (FCM).</p><p><b>RESULTS</b>(1) The Id4 gene exhaustive methylation in control group, and hypermethylation in experimental group were reversed by ATO in a dose-dependent manner. (2) Id4 mRNA expression in Raji cells treated with ATO for 48 h increased gradually with ATO concentration increasing in experimental group. (3) Raji cell growth inhibited rates after different concentrations of ATO treatment for 24, 48, 72 h were 12.15% ∼ 92.17% in the experimental group (P < 0.05). (4) Apoptosis peak emerged after ATO treatment for 48 hours in experimental group, while a much lower apoptosis in control group. (5) After ATO treatment for 48 h in experiment group, the cells were arrested at G(0)/G(1) phase in a dose-dependent manner.</p><p><b>CONCLUSION</b>Id4 gene presents exhaustive methylation in Raji cells. ATO can reverse the hypermethylation of Id4 gene and recover the expression of Id4 mRNA. Hypermethylation of Id4 gene is one of the reasons of Raji cells malignant proliferations.</p>

The expressions and clinical sig nificances of p27 and proliferating cell nuclear antigen and nuclear-associated antigen in synovial sarcoma / 中国地方病学杂志

Objective To investigate the association of the expressions of p27 and proliferating cell nuclear antigen(PCNA)and nuclear-associated antigen(ki-67)proteins in synovial sarcoma,and the relationship with its prognosis.Methods The expression of p27,PCNA and ki-67 in 36 synovial sarcoma and 10 normal synovial tissue were immunohistochemically examined.The relationship between the expressions of p27,PCNA and ki-67 proteins in synovial sarcoma with its prognosis by clinical stage,tissue grades and prognosis was investigated.Results (1)In normal synovial tissue,the expressions of PCNA(0) and ki-67(0) were positive,p27 were positive100%(10/10).but the expressions of PCNA[86.1%(31/36)]and ki-67[69.4%(25/36)]in most synovial sarcoma were positive,p27 were negative[11.1%(4/36)],significant differences were found among these expressions(χ2=25.16,χ2=9.18,P＜0.05).(2) p27 positive-expression correlated significantly wiht thehistological grade of synovial sarcoma(χ2=9.19,P＜0.05)and prognosis(χ2=5.98,P＜0.05).The positive expressions of PCNA and ki-67 were positively related with the clinical stage(χ2=7.40,χ2=8.12,P＜0.05)and tissue grades(χ2=7.17,χ2=9.18,P＜0.05)and prognosis(χ2=13.03,χ2=10.66,P＜0.05)of synovial sarcina(3) There were negative correlations between p27 and PCNA(r=-0.63,P＜0.05) and between p27 and ki-67(r=-0.53,P＜0.05).But positive correlation between PCNA and ki-67(r=0.63,P＞0.05)was found.Conclusions Expressions of PCNA and ki-67 in most synovial sarcomas are positive,and that of p27 is negative,each plays an important role in the proliferation of synovial sarcoma.Combination of measuring of the p27,PCNA and ki-67 is valuble in predicting the prognosis.

Effects of Recombinant Human Erythropoietin on Immune Function of Chemotherapy Mice / 实用儿科临床杂志

Objective To observe the effects of recombinant human erythropoietin(rh-EPO) on immune function of cyclophosphamide-treated mice.Methods Six-week-old mice were randomly divided into 4 groups.Cyclophosphamide plus normal saline group(CTX(+NS));cyclophosphamide plus lower and higher dosage rh-EPO group(CTX+LDrh-EPO and CTX+HD rh-EPO);normal saline control group(NS).The changes of Hb,WBC,red blood cell immune function((C_3b)-R%),T lymphocyte proliferative responsiveness optical density index A(A score),IL-2,TNF-? of 4 groups were observed.Results The CTX + NS group showed lower levels on Hb,WBC,C_(3b)-R%,A score,IL-2 and TNF-? compared with NS normal control group(P0.05).There were positive correlation between C_(3b)-R% and Ascore,C_(3b)-R% and IL-2.Conclusions 1.Cyclophosphamide treated mice have lower Hb,WBC,C_(3b)-R%,A,IL-2 and TNF-? secretion.2.rh-EPO administration have improvements with Hb,RBC immune function,T lymphocyte proliferative responsiveness and IL2 production.

Comparative study on the efficacy of Yiweining and Gestrinone for post-operational treatment of stage III endometriosis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy and safety of Yiweining (YWN) and gestrinone (GT) in treating post-operational patients of stage III endometriosis (EM-III).</p><p><b>METHODS</b>Fifty-two patients of EM-III after operation were randomly assigned into three groups, the YWN group (20 patients) was treated through oral intake of YWN 200 ml, twice a day; the GT group (19 patients) treated with gestrinone 2.5 mg, twice every week, with the medication starting from the 7th post-operational day and lasting for 6 months. The control group (13 patients) was untreated. Six months was one therapeutic course, and follow-up study was carried out in the 6 - 30 months after the end of the medication.</p><p><b>RESULTS</b>The recurrence rate in the YWN group and the GT group were 5.0% and 5.3% respectively, showing insignificant difference between the two groups, but they were lower than that in the control group (30.7%, P < 0.05). Besides, the adverse reaction rate in the YWN group was lower than that in the GT group (10.0% vs 31.6%, P < 0.05).</p><p><b>CONCLUSION</b>Application of YWN to prevent the post-operational recurrence of endometriosis is effective and safe, and its efficacy is similar to that of GT.</p>

Effects of Yiweining recipe on expressions of metalloproteinase-2 and cyclooxygenase-2 mRNAs in ectopic endometrium of rats with endometriosis / 中西医结合学报

OBJECTIVE: To explore the effects of Yiweining Recipe (YWNR), a compound Chinese herbal medicine, on expressions of metalloproteinase-2 (MMP-2) and cyclooxygenase-2 (COX-2) mRNAs in rats with endometriosis (EM). METHODS: Operational self-transplantation was applied in establishing the rat models. Detection of MMP-2 and COX-2 mRNAs was conducted with hybridization in situ. RESULTS: There were significant differences in the expressions of MMP-2 and COX-2 mRNAs between the untreated group and the high-dose YWNR-treated group. YWNR could reduce the expressions of MMP-2 and COX-2 mRNAs. CONCLUSION: YWNR can treat EM through reducing the positive expressions of MMP-2 and COX-2 mRNAs.

Empirical study of effect of Yiwei Ning on expression of Fas/FasL in rat with endometriosis / 中华中医药杂志

Objective: To expound the effect of Yiwei Ning in treating endometriosis through measuring Fas/FasL protein expression.Method:The female Wistar rats were divided into five groups randomly.After 8 weeks of administration,expression of Fas/FasL protein were determined.Results: There were significant difference in the positive expression of Fas/FasL protein between Yiwei Ning group and the control group(P

On the Consistency of "Wu Chang" Thought in Confucian Doctrines and Doctors′ Professionalism / 中国医学伦理学

The "Wu Chang" thought is a core idea in Chinese Confucian morality system,which plays a critical role in establishing and further developing traditional Chinese medical ethical principles,doctors′ professional obligations,behavioral regulations,professional requirements,and physician-patient relationship.Therefore,it is also of positive referencing and revealing significance for fully understanding the modern doctors′ professionalism and responsibilities raised by the "Doctors′ Declaration of Doctors′ Professionalism in the New Century".