Disorders of sex development(DSD) include anomalies of sex chromosomes,gonads,reproductive ducts,and genitalia.Here,the term "intersex" is avoided because of its imprecision.The purpose of this review is to assist health care professionals in the provision of treatment,education,and support to children born with DSD and to their families.The goal of DSD treatment is to achieve the long-term physical,psychological,and sexual well-being of the patients.In the case of DSD it involves several principles.Providing medical and surgical care to deal with a complication that threatens to the patient's physical well-being;minimizing the potential for the patient and family to feel ashamed,stigmatized,or overly obsessed with genital appearance;delaying elective surgical and hormonal treatments until the patient can actively participate in decision-making;telling the truth to the family and the child and addressing psychosocial distress of the children and their parents.This approach is termed as "patient-centered".

Objective To investigate expression of glutathione S-transferase(GST) mRNA in peripheral blood of the population in coal-burning fluorosis area and to evaluate the effect of comprehensive control intervention. Methods Fifty samples of peripheral blood from patients in the coal-buring fluorosis area in Bijie county of Guizhou province were selected as fluorasis group and 50 samples of peripheral blood from patients in area with comprehensive management were selected as intervention group, respectively. Fifty samples from non-endemic fluorosis area were selected as the control group. Total RNA from blood was extracted and purified by the Trizol- Phenol-Chloroform one-step method. Expression of GST mRNA was detected by using SYBR Green I real-time fluorescence quantitative PCR. Results The data of GST mRNA in fluorosis group, intervention group and control group was 38.28±27.22,70.56±37.23 and 103.46 ± 46.62, respectively. There was a significant difference between the groups(F = 3.75, P < 0.05). Decreased expression of GST mRNA in fluorosis group and intervention group as compare to control was detected(all P < 0.05), and the expression of GST mRNA in intervention group was higher than that in fluorosis group(P < 0.05). Conclusion Coal-burning fluorosis possibly led to the decreased expression of GST mRNA in peripheral blood, and comprehensive control maybe prevent the decreased expression of GST in mRNA level.

Angina Pectoris ; drug therapy ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Phytotherapy ; Technology, Pharmaceutical

A reliable method for simultaneous determinition of eleven representative components (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, shanzhiside, geniposidic acid, genipin-1-β-D-gentiobioside, geniposide and secoxyloganin) in combination of chromatographic fingerpint analysis for Reduning injection was developed by ultra high-performance liquid chromatography (UPLC). The method was performed on an Agilent ZORBAX SB-C18 anlytical column (3. 0 mm x 100 mm, 1. 8 µm) with a guard column of Agilent UPLC Guard ZORBAX SB-C18 (3.0 mm x 5 mm) at the column temperature of 30 °C. The gradient mobile phase consisted of acetonitrile (A)-0. 1% phosphoric acid (B) with a flow rate of 0. 4 mL . min-1. The injection volumn was 2 µL. The detection wavelengths were set at 324 nm and 238 nm for quantit tive analysis and 225 nm for fingerpint chromatography. Neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, shanzhiside, geniposidic acid, genipin-1-β-D-gentiobioside, geniposide and secoxyloganin were baseline seperated with good linearity relationships (r >0. 999) between concentration and peak areas over the linear ranges. The average recoverys of the investigated compounds were 103.5%, 100. 2%, 103. 3%, 102. 8%, 101. 3%, 102. 8%, 97. 36%, 99. 62%, 98. 16%, 102. 8%, 99. 27%, respectively. Reduning injection of forty-five batches was analyzed by UPLC finge print chromatography. Thirty batches were selected to generate the reference fringerprint chromatography with fourteen common peaks. The similarity values between the reference fringerprint chromatography and the remaining fifteen batches were higher than 0. 99. The developed method was fast, accurate and sensitive. It could be used as a reference for the quality control of multiple components determination and fingerprint chromatography for Reduning injection in future.
Chlorogenic Acid ; chemistry ; isolation & purification ; standards ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; standards ; Glucosides ; chemistry ; isolation & purification ; standards ; Iridoids ; chemistry ; isolation & purification ; standards ; Quality Control ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity ; Time Factors

OBJECTIVETo investigate the effects of α3 neuronal nicotinic acetylcholine receptor (nAChR) on apoptosis and p38 signal transduction pathway in SH-SY5Y cells and to assess the roles of α3 nAChR in the pathogenesis of Alzheimer's disease (AD).

METHODSThe levels of α3 nAChR mRNA and protein were measured by real-time PCR and Western blot, respectively, in SH-SY5Y cells transfected with α3 nAChR siRNA. The mRNA level of bcl-2 and bax was measured by the real-time PCR. The siRNA transfected SH-SY5Y cells and control were then treated with 10 µmol/L Aβ25-35 for another 48 h, and the change in apoptotic rate and the levels of p-p38 and p38 were measured by flow cytometry and Western blot. Subsequently these SH-SY5Y cells were exposed to a blocker of p38 protein, and the apoptotic rate was measured again.

RESULTSCompared to the controls, the expression of α3 nAChR at mRNA and protein levels in the SH-SY5Y cells transfected with α3 nAChR siRNA decreased by 95% and 86%, respectively; the mRNA levels of bax increased 2.11 times and that for bcl-2 decreased 0.53 times. The apoptotic rate was unaffected (3.40% ± 0.20%); but it increased after Aβ25-35 treatment (24.52% ± 1.59%); the level of p-p38 protein also increased by 178% in the α3 nAChR inhibited cells treated with Aβ25-35. Compared to controls, the Aβ25-35-treated SH-SY5Y cells and the Aβ25-35-treated and siRNA-transfected cells both showed a reduction in apoptosis after treatment with p38 blocker, especially in the former.

CONCLUSIONThe siRNA silencing of α3 nAChR mRNA may enhance the effect of Aβ25-35 on the cell apoptosis by increasing the levels of p38 protein and bax mRNA and decreasing the level of bcl-2 mRNA, which may play a role in the pathogenesis of AD.

Alzheimer Disease ; etiology ; Amyloid beta-Peptides ; metabolism ; Apoptosis ; Cell Line, Tumor ; Gene Silencing ; Humans ; Neuroblastoma ; metabolism ; pathology ; Peptide Fragments ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, Nicotinic ; genetics ; metabolism ; Signal Transduction ; Transfection ; bcl-2-Associated X Protein ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To investigate the expression of c-Jun-N-terminal kinase(JNK) in rat brains with chronic fluorosis and try to reveal the molecular mechanism for the neural impairment induced by the disease.Methods The rats were randomly divided into 3 groups, normal control group(drinking water containing less than 0.5 mg/L of sodium fluoride, NaF), lower fluoride exposed group(drinking water containing 5 mg/L NaF) and higher fluoride exposed group(drinking water containing 50 mg/L NaF), 24 in every group. The rats were examined at the sixth month after feeding. The concentration of fluorine in urine and blood was detected by F-ion selective electrode. The expression of JNK in brains was investigated by using Western blotting and immunohitochemistry staining, and analyze the correlation between activating of JNK and the concentration of fluorine in blood. Results The increased concentration of fluorine in urine(control: 0.92 ± 0.30, lower fluoride exposed group: 2.56 ± 0.91,higher fluoride exposed group: 5.73 ± 3.14, P ＜ 0.05) were observed when 6 months after the beginning of the experiment, and the amount of fluorine in blood was also higher in rats with fluorosis(control: 0.12 ± 0.07, lower fluoride exposed group: 0.36 ± 0.14, higher fluoride exposed group: 0.50 ± 0.18, P ＜ 0.05). The expression of phospho-JNK at protein levels were higher in the brains of rats with fluorosis than that of controls (control: 1.00 ± 0.37, lower fluoride exposed group: 1.20 ± 0.28, higher fluoride exposed group: 1.74 ± 0.69, P ＜ 0.05), whereas no change of total-JNK was found(F = 0.046, P ＞ 0.05). Furthermore, the expression of phospho-JNK in the parietal cortex(119.3 ± 14.1), occipital cortex(112.7 ± 5.4), hippocampus CA3(100.6 ± 8.9), dorsal thalamus (117.8 ± 10.4) and olivary nucleus( 112.6 ± 5.9) of rats in higher fluoride exposed group were higher than that in control( 104.1 ± 8.9,106.6 ± 9.6,106.6 ± 9.7,108.9 ± 6.4,100.3 ± 8.4, all P ＜ 0.05) and lower fluoride exposed group(96.7 ± 17.1,102.5 ± 8.3,106.4 ± 6.5,110.2 ± 9.3,102.4 ± 4.7,102.5 ± 9.8, all P＜ 0.05). The positive stained neurons of total-JNK also distributed in the same brain regions of rats, but no difference was detected between the rats with fluorosis and controls(all P ＞ 0.05). The increased level of phospho-JNK was positively correlated with the fluoride contents in blood of the rats with fluorosis (r = 0.677). Conclusions The expression of phospho-JNK in brains of rats with fluorosis was significantly increased with a correlation to fluoride content in blood, which might be connected to the mechanism of neural impairment induced by chronic fluorosis.

Objective To investigate the expression of extraeellular signal-regulated protein kinase (ERK1/2)pathway in rat brains with fluorosis and the effects of fluoride on learning and memory of the rats,and to reveal the mechanisms of damaged nervous system resulted from the toxicity of the ion.Methods Seventy-two SD rats were divided into 3 groups and 24 rats were in each group.Three groups were fed respectively with different concentrations of fluoride(NaF)for 6 months to establish rat models with fluorosis.Controls were fed with tap water (NaF＜0.5 mg/L):lower and higher concentration group were fed with water containing NaF(5,50 ms/L).Animals are sacrificed after 6 months of treatment with fluoride and the dissected brains were kept for analysis.The protein levels of ERK1/2 in rat brains were detected by Western-blotting and the mRNA level by RT-PCR. The spatial learning and memorizing ability was measured by Morris water maze test. Results The ERK1/2 protein in control group,lower and higher concentration group was 0.944±0.10,1.253±0.02,1.953±0.07,the differece being statistieally sighificant between any two groups (P ＜ 0.05). The phospho-ERKl/2 protein in control group,lower and higher concentration group was 0.73±0.08,0.77±0.07,1.28±0.11,the differece being statistieally sighificant between any two groups(P ＜ 0.05);the activation rate of phospho-ERK1/2 in lower and higher concentration group [(68.4± 3.8)%,(64.1±3.2)%] was decreased compared to control group[ (82.3±10.7)%],the differece being significant(P ＜ 0.05). In the navigation trial,longer escape latencies of lower concentration group on the second, the third,the fifth and the sixth day were observed[ (46.0±8.0),(24.0±2.7),(8.9±5.3),(7.4±4.1 )s] compared to the control[ (39.3±6.9),(19.1±9.1 ),(8.3±3.4),(4.8±2.7)s],the differece being significant (P ＜ 0.05 or ＜ 0.01 );the similar results were also observed in the higher concentration group[ (36.9±16.8),(37.7±12.9), (19.7±7.6),(12.2±5.7 )s],and the escape latencies of the higher concentration group on the third,the fifth and the sixth day were longer than that in lower concentration group. In the probe test,the rats took more time to reach the first cross in lower and higher concentration group[(1.17±0.75),(4.18±1.10)s] than control group[ (5.89± 0.56 ) s ],the differece being significant (P ＜ 0.05 or ＜ 0.01 ) ;stayed shorter [ ( 17.05±4.25 ),(18.20±4.57 ) s ] than control [(25.37±5.65 )s ] in platform area (P ＜ 0.01 );the activation rates of ERK1/2 were directly correlated with the time taken to reach the first cross platform located in the probe test(r = 0.364,P ＜ 0.05) and the activation rates were also directly correlated with the escape latencies on the sixth day(r = 0.497,P ＜ 0.05). Conclusion Long-term exposure of excessive fluoride induces the change of expression and activating rate of the ERK1/2 in rat brains,leading to the decreased capacity of learning and memory.

Objective To investigate the changes of oxidative stress level in brain tissues and serum, and learning and memory in rats with oxidative stress level in nerve damage in chronic fluorosis. Methods The rats were randomly divided into 3 groups according to the body weight, eight rats in each group, i.e., control group, drinking water containing less than 0.5 mg/L of fluoride; lower fluoride exposure group, drinking water containing 5 mg/L of fluoride; higher fluoride exposure group, drinking water containing 50 mg/L of fluoride. The animals were examined six months after initiating the experiment. The total antioxidant capacity (T-AOC) and malondialdehyde (MDA), as well as learning and memory, were measured. Results Escape latency in higher fluoride exposed group[ (14.37±3.48)s] was significantly higher than that of controls[ (5.84±1.87)s] and exposed te lower fluoride [ (7.18±1.42)s], the difference being statistically signifieant(P<0.05). As compared with controls[ (2.17±0.11)× 103 U/L , (0.79±0.11)×103 U/g Pr] ,the rats exposed to higher fluoride and lower fluoride exhibited lower levels of T-AOC [(1.37±0.27)×103 U/L,(0.24±0.06)×103 U/g Prand (1.20±0.14) x 103 U/L,(0.41 ~ 0.10)×103 U/g Pr], the difference being statistically signifieant(P<0.05). As compared with controls[ (2.34±0.16) mmoL/L, (2.97±0.11)mmol/g Pr] and low fluoride exposed group[ (2.68±0.33)mmoL/L, (3.38±0.21)mmol/g Pr], higher level of MDA were observed in higher fluoride exposed group[ (3.72±0.59)retool/L, (4.01±0.21)mmol/g Pr], the difference being statistically significant(P<0.05). Conclusion The results indicated that higher amount of fluoride induced an increased level of oxidation, which might result in the decreased capacity of intelligence of rats with fluorosis.

Objective To analyze the examination results of external quality assessment (EQA),at all levels of iodine deficiency disorders (IDD) network laboratories in Ningxia Province and to further standardize and improve the laboratory,and to provide a reliable laboratory quality assurance for surveillance and control of IDD.Methods The examination results of EQA at all levels of IDD laboratories in Ningxia Province were statistically analyzed in accordance with the National Reference Laboratory (NRL) of IDD (2002-2011).Results Laboratory hardware equipment and technology at all levels met the testing requirements,and qualified rate of quality control increased year by year.Both of the response rate and qualification rate of urine iodine laboratories at provincial level were 100％ in the past decade.From 2005 on,the response rate of city laboratories had been 100％,and the qualification rate had been 100％ since 2007.The response rate and qualification rate of salt iodine laboratories at both the provincial level and the city level were 100％ in the past decade.The response rate of salt iodine laboratories at county level had been 100％ since 2004,and the qualification rate had been 100％ since 2009.Salt iodine and urinary iodine levels were fully qualified for the past three years at provincial,municipal and county levels.Conclusions All levels of IDD network laboratory in Ningxia Province runs good,EQA is fully qualified,and is able to provide a reliable laboratory quality assurance for surveillance and control of IDD.

Objective To evaluate the effect of transcatheter arterial chemoembolization (TACE) and delayed surgery for infant hepatoblastoma.Methods TACE was performed with the initial digital subtractive angiography (DSA) under general anesthesia 1-3 times in 8 infants with huge hepatoblastoma, whose age was 2 to 12 months. DSA was done via arterials in hepatoblastoma each time before chemoembolization. The arterials were perfused with chemodrugs and suspensions in ultrasome iodized oil , and were blocked with spring rings. DSA findings indicated that the tumor shrank without new tumorous arterials after 1 month in 6 cases, and 4 of them showed no tumorous staining, and the delayed surgery was performed successfully 1 week later in 6 infants. One boy underwent systemic chemotherapy alone during 6 months after 3 times of TACE. Results TACE therapy did not encounter any major technical problem or toxic reaction caused by chemotherapy. The following DSA test 4 weeks later did not detect any new tumorous vessels in 6 cases. Six children received TACE and surgery had been followed-up with no tumor recurrence for months averagely. The boy underwent TACE and venous chemotherapy for 6 months , without surgery , had been followed-up for 48 months until the present report. CT, AFP and DSA did not show any hints of tumor recurrence. Six cases receiving 3 times TACE combined with surgery survived without tumor recurrence. Conclusions TACE is a very effective, safe and helpful therapy for hepatoblastoma, which stressed the repeated use of spring ring to block tumor vessels lastingly if necessary. If surgery is required, DSA test is needed beforehand to detect new tumorous vessels or neoplasm. If there is any , TACE is repeated. TACE combined with surgery may provide an additional promising choice in the treatment of hepatoblastoma, and repeated TACE alone may cure hepatoblastoma in infants.