At present,there is not a clear guideline for residual solvents in the new drugs in our country. In practice,the ICH Q3C is our important reference in general,but in practical research and evaluation of new drugs,some adjustment should be made on principles of ICH Q3C,making it suitable for the reality of the pharmaceutical industry in our country. In this article, we put forward some suggestions to improve the quality control of residual solvents in our country,and some initial ideas were provided to solve the question in practice.

OBJECTIVETo explore the clinical value of the neonatal hearing combined with deafness gene screening.METHODSFrom February 2014 to August 2015, 1933 newborns were included in the study. We analyzed the effects of combined screening of hearing and deafness gene.RESULTSAmong all the 1933 neonates, 71.34% (1379/1933) passed and 28.66% (554/1933) failed the initial hearing screening.The hearing impairment rate was 4.14‰ (8/1933). Genetic screening mutation rate was counted. GJB2 mutation rate was 28.97‰ (56/1933). SLC26A4 mutation rate was 13.97‰ (27/1933). GJB3 mutation rate was 6.21‰ (12/1933). Mitochondrial 12 S rRNA gene mutation rate was 1.03‰ (2/1933). 1 case of 235 delc homozygous mutation did not pass the initial hearing screening and lost to follow-up rescreening. 2 cases of 12 S rRNA 1555A>G homogeneous mutations passed early hearing screening. 8 cases of auditory handicaps were all normal.CONCLUSIONDeafness gene screening can make up for the deficiencies of the universal newborn hearing screening. Joint use of both of them should complement each other and play the biggest role.

Objective To evaluate the effect of pepliteal artery endovascular angioplasty for the treatment of diabetic foot. Methods 65 cases (69 limbs) of diabetic foot were treated by long bloon endovascular angioplasty. Results No death occured. 60 cases (64 limbs) were successfully treated and 5 cases (5 limbs) failed. The imme-diately success rate was 92.75%. The pain relieved, the temperature was improved and the ankle brachial index (ABI) was up to 0.84±0.11. Anterior tibial artery or posterior tibial artery of 39 limbs could be touched. 21 limbs were cured by debride and change dressings. 10 limbs were cured after the gangrene was ablated. 6 limbs were cured after the gangrene was debrided. 22 limbs were cured after toe amputation. Half of the foot was amputated. No limb was amputated. Every month was further consulted by Doppler and the rate of follow upwas 100%. 6 limbs of 6 cases were reobliterated (1,1,2,2 cases occurred after 1,6,12,18 month respectively.) and treated by endovascular an-gioplasty again. Conclusion Endovascular angioplasty below the knees for the treatment of diabetic foot is an effec-tive method for the limbs saving, with minimal invasive, safety, less complication and retreatment. It can be used as a first choice for the artery obliteration of diabetic foots.

Objective To establish a population pharmacokinetic ( PPK) model of metformin in healthy Chinese subjects , and evaluate the effect of different physiological factors on pharmacokinetic parameters of metformin .Methods The preparation of pericar-dial fixation liquid is divided into solution A ( buffer solution ) and solution B ( glutaraldehyde solution ) , which were reserved in the re-frigerator before used .Before the experiment , solution A and B were mixed evenly to make fresh pericardial fixation fluid .Stability of solution A and B before and after disinfection , solution B, pericardial fixation fluid at room temperature and 4℃in the refrigerator were studied using pH meter and hydroxylamine salt method with pH value and the content as indexes .Results The decline of pH value and the content was slight after disinfection for both solution A and B within the prescribed scope .when glutaraldehyde was in alkaline con-dition after the mix of solution A and B , it was with strong bactericidal activity and pericardial fixation ability;stability study showed that pericardial fixation fluid was more stable in cold storage than at room temperature within one year .Conclusion The improved preparation process of pericardial fixation fluid is reasonable and feasible .The pericardial fixation fluid has good stability , and the quality guarantee period could be extended to one year .

Objective To observe the effect of PIF1 knockdown on cell growth and cell cycle arrest induced by ionizing radiation.Methods HeLa cell lines that consistently down-regulated PIF1 were prepared by the lentivirus granules interfering technology and confirmed by real-time PCR and Western blotting.The effect of down-regulation of PIF1 on cell growth and cell cycle arrest induced by ionizing radiation was evaluated by cell counting and flow cytometry.Results HeLa cell lines consistently down-regulating PIF1 were established.The growth of HeLa that down-regulated PIF1 was inhibited greatly after 4 Gy of γ-ray irradiation.There was little cell proliferation until the 5th day post 4 Gy γ-ray.Moreover, the S phase block and G2/M phase block of PIF1 knock-downed cell lines were significantly delayed after 8 Gy γ-ray irradiation.Conclusion Knockdown of PIF1 can significantly enhance the radiation sensitivity and delayes the S phase block and G 2 /M phase block induced by ionizing radiation.

OBJECTIVE: To explore the genetic basis for a child featuring delayed intellectual development. METHODS: The child and his parents were subjected to conventional G-banding karyotyping and single nucleotide polymorphism array (SNP-array) analysis. Suspected copy number variations (CNVs) were verified in both parents. RESULTS: No karyotypic abnormality was found with the child and his parents. SNP-array results for both parents were normal. The child was found to harbor a de novo 172 kb deletion at 18q21.2 with a physical position of 52 957 042-53 129 237. The deletion only involved one OMIM gene, namely TCF4, resulting in removal of its exons 6 to 8. CONCLUSION The SNP-array assay has facilitated with the diagnosis of this child. Deletion of 18q21.2 region probably accounts for the Pitt-Hopkins syndrome (PTHS) in this patient.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 18 ; genetics ; DNA Copy Number Variations ; Developmental Disabilities ; genetics ; Facies ; Humans ; Hyperventilation ; genetics ; Intellectual Disability ; genetics ; Phenotype ; Transcription Factor 4 ; genetics

OBJECTIVETo deepen the understanding of clinical manifestations and treatment of patients with positive lupus anticoagulant (LAC).

METHODSThe clinical data of 2 patients were analyzed and related literature were reviewed.

RESULTSCase 1, a 31-year-old female, diagnosed as lupus anticoagulant positive, secondary to undifferentiated connective tissue disease, was presented with menorrhagia and thrombocytopenia. Anti-nuclear antibody (ANA) was positive 1:1000 (homogeneous type) with anti-double stranded DNA positive, and dRVVT LA1/LA2 was 3.4. Coagulation function was alleviated after treatment with glucocorticoid and total glucosides of paeony. Case 2, a 59-year-old female was presented with gingival bleeding, hematuria with the level of F II:C 13%. dRVVT LA1/LA2 was 2.0. Anti-nuclear antibody (ANA) was positive 1:1000 (type of cytoplasmic granule), anti-double stranded DNA was positive. The patient was diagnosed as hypoprothrombinemia-lupus anticoagulant syndrome (LAHS) and acquired coagulation factor deficiency. The signs of hemorrhage were alleviated after treatment with methylprednisolone 40 mg/day and cyclophosphamide, while the level of F II:C was below normal.

CONCLUSIONSymptoms of patients with positive LAC are variable. The diagnosis relies on history of disease and laboratory test. Currently, there is no standardized treatment. Cases of LAHS should be thoroughly investigated for any known causes and related disorder.

Adult ; Blood Coagulation ; Cyclophosphamide ; therapeutic use ; Female ; Glucocorticoids ; therapeutic use ; Hematologic Tests ; Hemorrhage ; Humans ; Hypoprothrombinemias ; diagnosis ; Lupus Coagulation Inhibitor ; blood ; Methylprednisolone ; therapeutic use ; Middle Aged

Objective To investigate the prevalence of dyslipidemia in subjects with type 2 diabetes mellitus in Beijing urban communities.Methods Total 3316 subjects with type 2 diabetes (age 20-80 years) were recruited from 15 urban community health centers in Beijing using a multi-stage random sampling approach.Dyslipidemia was diagnosed according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults:2007 version.Results Among 3316 diabetic subjects (1329 malesand 1987 females),75.6％ (2506/3316) had dyslipidemia,the prevalence was 72.5％ (964/1329)in men and 77.6％ (1542/1987) in women.The prevalence of hypertriglyceridemia and hypercholesterolemia was 41.9％ (1388/3316) and 48.1％ (1595/3316),respectively.31.5％ (1043/3316) subjects had high levels of low-density lipoprotein cholesterol (LDL-C) and 21.2％ (703/3316) had low high-density lipoprotein cholesterol (HDL-C).Among all subjects with dyslipidemia only 22.9％ (575/2506) took hypolipid agents.The overall blood lipid control rates of triglyceride (TG),total cholesterol (TC),LDL-C and HDL-C in 1393 subjects with dyslipidemia history were 48.0％ (669/1393),17.4％ (242/1393),30.9％ (430/1393) and 75.8％ (1056/1393),respectively.Diabetics with dyslipidemia had higher body mass index,waist circumference,blood pressure,plasma glucose and hemoglobin A1c.The prevalence of dyslipidemia in the overweight and uncontrolled-glucose group were 79.0％ (1678/2125),78.9％ (1756/2227),respectively.Logistic regression analysis showed that gender,age,body mass index and hemoglobin A1c were associated with dyslipidemia.Conclusions The prevalence of dyslipidemia in diabetic subjects in Beijing urban communities is high and less than one quarter patients take hypolipid agents.Age,body mass index and hemoglobin A1c are the risk factors of dyslipidemia in type 2 diabetic patients.

Objective To investigate current status of use of oral hypoglycemic drugs and insulin among adult patients with type 2 diabetes mellitus (T2DM) in urban community of Beijing.Methods In total,3297 T2DM patients aged more than 20 years from 15 urban communities of Beijing were studied.Their body weight,height,fasting plasma glucose level and glycosylated hemoglobin Alc (HbAlc) were measured.A door-to-door questionnaire survey on use of oral hypoglycemic drugs and insulin was conducted for them.All the T2DM patients surveyed were divided into four groups based on their received intervention.Results ①Of 3279 T2DM patients,454 (13.8％) received lifestyle intervention,971 (29.5％) used only one oral hypoglycemic drug,1179 (35.7％) with combined oral hypoglycemic drugs,and 693(21.0％) with insulin.②There was significant difference in average HbAlc among the four groups of T2DM patients with lifestyle intervention,only one oral hypoglycemic drug,combined oral hypoglycemic drugs,and insulin,with HbAI c of (7.0 ± 1.9) ％,(7.1 ± 1.5) ％,(7.4 ± 1.5 ) ％,and (7.5 ± 1.5 ) ％for them,respectively ( F =15.1,P ＜ 0.01 ).Proportions of the T2DM patients with HbAlc equal to or higher than 7.0％ were 32.2％,39.4％,52.1％ and 59.5％ for the four groups,respectively ( x2 =117.7,P ＜ 0.01 ).③In the T2DM patients with lifestyle intervention,32.2％ (146/454) of them with HbA1 c equal to or higher than 7.0％ were untreated with any oral hypoglycemic drug.In those with only one oral hypoglycemic drug,39.4％ (383/971) of them with HbAlc equal to or higher than 7.0％ were not treated with combined oral hypoglycemic drugs and/or insulin.In those with combined oral hypoglycemic drugs,52.1％ (614/1079) of them with HbAlc equal to or higher than 7.0％ were not received combined insulin treatment.④ Fasting plasma glucose level,treatment strategies,postprandial 2-h blood glucose level and length of the illness were independent risk factors for HbAlc level equal to or higher than 7.0％,with odds ratio (OR) of 1.757,1.256,1.175 and 1.031,respectively.⑤ In 2843 T2DM patients with oral hypoglycemie drugs and/or insulin treatment,1494 (52.6％ ) received biguanides and 693 received (24.4％ )insulin,respectively.Conclusions More than half of adult patients with T2DM do not meet the target of glycemic control of HbAlc less than 7.0％ in urban communities of Beijing,due to not active use of oral hypoglycemic drugs,and not timely adoption of combined use of oral hypoglycemic drugs and insulin therapy.

Objective To study clinical characteristics of type 2 diabetic(T2D)patients with metabolic syndrome(MS)and its components in Beijing urban communities.Methods Totally,3295 T2D patients involved in a combined prospective diabetic management study from 15 urban communities in Beijing were classified as four groups, according to 2004 Chinese Diabetes Society's definition of MS, i. e, isolated T2D, T2D with one component of MS, T2D with two components of MS and T2D with three components of MS. Their clinical characteristics were analyzed. Results ( 1 ) Among 3295 T2D patients, 155 (4. 7% )were isolated T2D, 107 (32.6%) T2D with one component of MS, 1386 (42.1%) T2D with two components of MS and 679 (20.6%) T2D with three components of MS, with an overall 62.7% (2065/3295) of T2D patients complicated with MS. (2) In these T2D patients, the more components of MS they had, the higher body mass index (BMI), waist circumference, waist to hip circumference ratio (WHR),systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting serum levels of insulin and triglyceride (TG) and the lower level of high-density lipoprotein-cholesterol (HDL) were presented (P <0. 01 ). (3) Percentage of isolated T2D in women increased from 49. 0% (76/155) to 61.9% (420/679)of those with three components of MS ( P < 0 01 ), with increasing of components of MS. (4) Multiple logistic regression analysis showed that BMI, history of hypertension, decreased HDL, increased TG,increased blood pressure, all were risk factors for T2D patients complicated with MS. Conclusions Among T2D patients in urban communities of Beijing, 95.3% (3140/3295) of them complicated with one or more components of MS, and 61.9% (420/679) of them complicated with MS. So, community diabetic management must be implemented in an all-round way, including control of blood pressure, blood lipids,body weight and so on, in addition to control of blood sugar.