S-methyl-L-cysteine sulfoxide (SMCO) is a non-protein sulfur-containing amino acid with a variety of functions. There are few reports on the enzymes catalyzing the biosynthesis of SMCO from S-methyl-L-cysteine (SMC). In this study, the flavin-containing monooxygenase gene derived from Schizosaccharomyces pombe (spfmo) was heterologously expressed in Escherichia coli BL21(DE3) and the enzymatic properties of the expressed protein were analyzed. The optimum catalytic conditions of the recombinant SpFMO were 30 ℃ and pH 8.0, under which the enzyme activity reached 72.77 U/g. An appropriate amount of Mg²⁺ improved the enzyme activity. The enzyme kinetic analysis showed that the K_m and k_cat/K_m of SpFMO on the substrate SMC were 23.89 μmol/L and 61.71 L/(min·mmol), respectively. Under the optimal reaction conditions, the yield of SMCO synthesized from SMC catalyzed by SpFMO was 12.31% within 9 h. This study provides reference for the enzymatic synthesis of SMCO.
Schizosaccharomyces/genetics* ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Cysteine/biosynthesis* ; Mixed Function Oxygenases/metabolism* ; Schizosaccharomyces pombe Proteins/metabolism* ; Oxygenases/metabolism* ; Kinetics

As a novel neuromodulation technology,the application of deep brain stimulation(DBS)in treatment-resistant psychiatric disorders has received widespread attention in recent years.Based on the current research frontiers,this review puts forward several unique and insightful issues of DBS in psychiatric disorders,including therapeutic targets,stimulation modes,closed-loop modulation,and long-term efficacy in order to provide suggestions and perspectives for future research directions.

Objective To investigate the value of X-ray guided desmopressin (DDAVP) stimulated bilateral inferior petrosal sinus sampling (IPSS) in diagnosing the recurrence of ACTH dependent Cushing disease or ineffectiveness after surgery or radiotherapy. Methods Retrospective analyses of patients with recurrent ACTH dependent Cushing disease (31 cases) or ineffective (3 cases) treatment after surgery or radiotherapy from January 2013 to October 2014 in our hospital was conducted. Bilateral inferior petrosal sinus angiography showed the same side of the cavernous sinus to prove successful intubation. The cases with discontinuous of the inferior petrosal sinus and cavernous sinus were excluded by this study. Finally, there were 34 cases of the patients in this study. Diagnosis was based on the ratio of ACTH level in IPS to peripheral vein after desmopressin test.The gradient≥2 at baseline or gradient≥3 after desmopressin test suggested the sources were in the pituitary. Diagnosis was confirmed by gold standard to investigate the value of X-ray guided desmopressin (DDAVP) stimulated bilateral IPSS. Results The IPS gradient≥2 at baseline or gradient≥3 after desmopressin test suggested the sources were in the pituitary in 30 patients. A total of 22 (22/30) patients underwent surgery with a final diagnosis of ACTH adenoma. The symptoms were obviously relieved in 8 (8/30) cases after sellar area gamma knife treatment and lesions were confirmed in the pituitary. IPS gradient<2 at baseline or gradient<3 after desmopressin test was found in 4 cases. One case (1/4) was found to have for ACTH adenoma after pituitary surgery. The other 3 cases (3/4) were confirmed to have lung carcinoid and clinical symptom alleviated after surgery. The sensitivity of desmopressin stimulated IPSS was 96.8%, the specificity was 100%, and the accuracy was 97.1%. Conclusion Desmopressin stimulated IPSS is an effective diagnostic procedure in diagnosing ACTH dependent Cushing disease recurrence or ineffectiveness after surgery or radiotherapy.

To investigate the academic features of Waizheng-YiAn-Huibian and provide references for research and application of it. With research approach in bibliography, the academic features of the book were studied from source of medical cases, writing characteristic, academic thought, etc. The academic features of Waizheng-YiAn-Huibian were summarized into the following 5 points, including multiple chosen medical cases but all with unique individual features, precious discussion after each case, named external symptoms, but covered internal symptoms, encouraging mild treatment and against being broad and complicated, emphasis on veins and arteries, positioning and nature determination. Waizheng-YiAn-Huibian is a wonderful masterpiece in medical cases research and worth learning and studying.

To discuss the academic features of Ding-Ganren’s medical records and to provide the references for learning and applying the theories in the book. With bibliography research method, the academic features of Ding-Ganren’s medical records were investigated in academic thoughts, medication characteristic and clinic experience, etc. The academic features of Ding-Ganren’s medical records were summarized into 4 pointes, which are ①good at classical prescription and determination of treatment based in pathogenesis obtained through differentiation of symptoms and signs of typhus and complicated diseases. ②Focusing on six meridians and proposing the combination of cold and warm treatment. ③Mild treatment and claiming gentle application of the medicine. ④Determination of treatment based in pathogenesis obtained through differentiation of symptoms and signs of scarlet fever and emphasizing to distinguish Qi from Ying. Ding-Ganren YiAn has high academic value in research and clinic application and worth further study.

Objective To summarize the clinical characteristics of primary pigmented nodular adrenocortical disease (PPNAD).Methods Eight patients with PPNAD from 2001 to 2009 in PUMC Hospital were reviewed,their clinical data were collected.Results PPNAD often occurred in adolescents.62.5% of patients with PPNAD were complicated with Carney complex(CNC).In addition to general features of Cushing's syndrome,amenorrhea and growth retardation in stature were very frequent in clinical manifestations of PPNAD.Plasma ACTH was undetectable,circadian rhythm of plasma cortisol was disappeared,glucocorticoid excretion was increased paradoxically during the dexamethasone suppression test in 50% patients with PPNAD.Adrenal imaging from 75% patients revealed normal-sized adrenal glands or suspectable micronodular changes.Adrenal pathologic analysis revealed numerous brown cortical nodules containing lipofuscin pigmentation.Unilateral adrenalectomy may relieve symptoms of Cushing's syndrome,but plasma ACTH and circadian rhythm of plasma cortisol were difficult to recovere.Hypercorticoidism might re-occure after unilateral adrenalectomy.Conclusion PPNAD should be bewared in ACTH independent Cushing's syndrome patients without apparent adrenal mass,and CNC should be screened and followed up.

Objective To evaluate the correlation between hyperlipidemia and lower limb arterial disease in eldedy diabetic patients with color Doppler uhrasonography.Methods Two hundred and sixty elderly diabetic patients and 206 normal subjects were enrolled in the study.Doppler uhrasonographic manifestations of lower limb arterial disease,blood pressure and blood biochemistry parameters including fasting plasma glucose(FPG),postprandial plasma glucose(PPG),TC,TG,HLD-C,LDL-C,apoprotein B (apoB),very low density lipoprotein cholesterol(VLDL-C),apoprotein Al(apoA1)and fibrinogen(Fb)were compared between the 2 groups.Results (1)The blood biochemistry parameters,including the levels of FPG,PPG,TC,TG,VLDL-C,LDL-C,apoB and Fb were higher in diabetic patients t11an in normal subiects.while HDL-C was lower(all P＜0.05).(2)The thickness of intima-media(IMT)in the lower limb arterial disease group was significantly increased and the presence of arterial stenosis and wall plaques more in diabetic patients[IMT in 205 cases(78.85%),atherosclerotic plaque in 241 cases(92.69%),muhivessel disease(more than 2 vessels)in 60 cases(23.08%)and arterial stenosis in 89 cases (34.23%)]than in normal subjects[IMT in 37 cases(17.96%),atherosclerotic plaque in 51 cases (24.76%),muhivessel disease in 27 cases(13.11%)and arterial stenosis in 3 cases(0.01%)],all P＜0.01.(3)Regression analysis showed that lower limb arterial disease was correlated with high level of LDLC and low level of HDL-C.Conclusions Arteriosclerotic plaque is one of the early manifestations in elderly diabetic patients and hyperlipidemia may provide the basis of its formation.Doppler uhrasonographic examination of lower limbarterial discloses the early arteriosclerotic changes of lower limb arterial disease in elderly patients and offers the basic data of indication for clinical treatment.

Through analyzing the academic ideas in Shanghan Zhinan written by Wei-Ju ZHU, a modern famous physician, it is pointed out that ZHU's achievement on integrative medicine has been overlooked. Taking the theory of syndrome differentiation of six channels from Shanghan Lun as an example, ZHU presumed that the essence of therapeutic theory of traditional Chinese medicine was to conform to or strengthen human body's self-healing and self-regulating abilities. Since Yangqi is the major force in the body to help heal disease when it occurred, ZHU often took measures to strengthen Yang first in treating disease and also was good at using hot-natured herbs, such as Radix aconiti lateralis preparata. ZHU's thoughts on integrative medicine were concerned with etiology, pathology and therapeutics. In addition, ZHU generalized the syndrome differentiation into the theory of five phases and eight principles, and made important contributions to the history of integrative medicine. His thinking will provide valuable revelation for clinical practice and modern research on traditional Chinese medicine.

Objective To understand the correlation between insulin resistance(IR) and adrenal androgen excess in adolescents with polycystic ovary syndrome (PCOS). Methods According to BMI, 90 adolescents with PCOS were divided to groups of normal weight PCOS(NW-PCOS,33 cases,BMI<25.0 kg/m2) and obesity PCOS(OB-PCOS,57 cases, BMI≥ 25.0 kg/m2),and 15 normal weight healthy girls matched for age as controls.All patients had normal OGTT.Acute ACTH stimulating test was performed on patients, and cortisol (F), 17-hydroxyprogesterone(17-OHP), dehydroepiandrosterone(DHEA) during ACTH testing at 0 and 60 minute (steroid0 and steroid60) were determined. Results Compared with controls, NW-and OB-PCOS patients showed significantly greater levels of total testosterone (T), Luteotropic hormone(LH), FIns, 2 hIns, and HOMA-IR(P<0.01).The freqnencies of hirsuties and acne, and serum level of FIns, 2 hIns, and HOMA-IR were significantly higher and LH levels were much lower in the group of OB-PCOS than those in NW-PCOS(P<0.05 and P<0.01).ACTH stimulating test showed that PCOS patients had significantly higher levels of basal 17-OHP0, DHEA0, as well as 60-minute ACTH-stimulated levels (Steroid60) of 17-OHP60、DHEA60, and net increase of 17-OHP(Δ17-OHP)as compared with normal controls(P<0.05 and P<0.01).The 60-minute ACTH-stimulated levels of 17-OHP60, DHEA60,Δ17-OHP, and ΔDHEA were also higher in group of OB-PCOS than those in group of NW-PCOS(P<0.05 and P<0.01), and there were no obvious discrepancies in basal 17-OHP0, DHEA0 between OB-PCOS and NW-PCOS groups.Spearman correlation analysis showed that in group of OB-PCOS, HOMA-IR value was significantly associated with BMI, 17-OHP60, Δ17-OHP, DHEA60, ΔDHEA(P<0.05 and P<0.01); whereas in group of NW-PCOS, HOMA-IR was associated only with BMI(P<0.01). Conclusions The significantly higher basal and ACTH-stimulated levels of 17-OHP and DHEA indicates adrenal hyperresponsiveness in adolescents with PCOS.Adrenal androgen excess appears to be closely associated with insulin resistance in obese adolescents with PCOS

OBJECTIVETo gain a primary understanding of the prevalence of 21-hydroxylase deficiency(21-OHD) heterozygote (carrier) among androgen excess women of Chinese Han nationality, compare the molecular genetic changes therein revealed with the results of adrenocorticotropic hormone (ACTH) stimulating test, and assess the carriers' phenotype-genotype correlation.

METHODSEighty-two androgen excess cases and 14 healthy women underwent ACTH stimulating test during the follicular phase. Molecular genetic analysis of CYP21 for 9 common mutations was performed with the method of amplification-created restriction sites.

RESULTSIn androgen excess group, the basal level of F0 (P<0.01), as well as basal 17-OHP0 and the ACTH stimulated concentrations of 17-OHP60 were much higher than controls (P<0.01), and there was no obvious discrepancy in F60 (P>0.05). The net increase of 17-OHP and the ratio of net increase of 17-OHP to net increase of F were also higher than controls (P<0.01). No CYP21 gene mutations were found in control group. Four patients of the androgen excess group were identified as heterozygous carriers of CYP21 mutations. The ACTH stimulating test results from gene normal patients and from carriers overlapped to a certain extent.

CONCLUSIONAmong 82 patients of Chinese Han nationality androgen excess women, 4.9% were 21-OHD heterozygous. The response of serum 17-OHP is not useful for predicting CYP21 gene mutation carrier status. Genotyping is the most reliable method to detect carrier.

Adolescent ; Adrenal Hyperplasia, Congenital ; diagnosis ; ethnology ; genetics ; Adrenocorticotropic Hormone ; Adult ; Asian Continental Ancestry Group ; genetics ; Child ; China ; Female ; Genetic Carrier Screening ; methods ; Genotype ; Humans ; Mutation ; Polymerase Chain Reaction ; Steroid 21-Hydroxylase ; genetics ; metabolism