In HCl medium,trace o-dinitrobenzene can sensitively inhibit the discoloration reaction of neutral red oxidized by KIO4. The optimum neagent is 0.55 mL neutral red, 0.60 mL HCl, 0.6 mL KIO4, respectively. The neaction ttmperatune is 80℃， neaction time is 6 min. The optimum condition and kinetic parameters are investigated in detail,a new method for determination of trace o-dinitrobenzene is proposed.　The　detection limit is 7.7×10-7　g/L and the linear range is 0.0～4.0　μg/L o-dinitrobenzene.　It has been　applied to the determination of trace o-dinitrobenzene in environmental water sample with　satisfactory results.

Objective To investigate the sensitivity of BIOMED-2 primer system in adult acute lymphoblastic leukemia (AIJ,) patients Ig gene rearrangement, and to analyze their frequency, corearrangement pattern, utilization of V, D and J genes and composition of junctional regions. Methods Amplification of rearranged IgH (complete and incomplete), IgK, IgK-Kde and IgL was performed in standard PCR in 29 adult ALL patients. Monoclonal PCR products were subjected directly to DNA sequencing. Sequences were identified by comparison with all known human Ig germline sequences to analyze the recombination patterns, somatic mutations and germline gene segments usage. Results IgH, incomplete IgH, IgK, igK-Kde and Igl, rearrangements were found with positive rate of 70.8%, 12.5% , 29.2% , 25.0% and 0 of B-ALL patients, respectively. All B-ALL patients displayed at least one pattern of Ig gene rearrangements. In TALL, one of five patients was found with incomplete IgH rearrangement, two patients were found with IgK rearrangements and two patients were PCR-negative. The sequence analysis showed that the most frequently used V, D, J segments in adult B-ALL patients were from VH3/VH4 families, DH3 family and JH6 family, respectively. Four of five IgK rearrangement used VκI family. 23.5% B-ALL IgH contained scattered replacement mutations with replacement to silent substitution ratio < 1 in complementarity determining regions. Conclusion BIOMED-2 multiplex PCR analysis strategy is a reliable and useful technique in the adult BALL patients.

Objective Plasma renin concentration (PRC) offers advantages in processing and standardization as compared with plasma renin activity (PRA). The aim of the study is to compare the sensitivity and specificity of plasma aldosterone concentration ( PAC)/PRA (ARR) and PAC/PRC (AARR) in screening primary aldosteronism ( PA ) in hypertensive patients and to observe the influence of different postures on PRC and AARR. Method ( 1 ) PAC and PRC in the supine position and after 1-hour and 2-hour upright posture were determined in 28 patients with PA and 51 patients with essential hypertension. The diagnostic efficacies during different postures were compared according to the ROC curve analysis. (2) 31 patients with PA, 242 patients with essential hypertension, and 145 normotensitive subjects were recruited in the study. The diagnostic efficacy of AARR in screening PA from hypertensive patients was evaluate. PAC, PRA, and PRC were measured by radioimmunoassay. Results ( 1 ) The AUC of AARR in the supine position, 1-hour and 2-hour upright posture were0.950 (95% CI0.906-0.994, P<0. 01), 0.979 (95% CI0.956-1.000, P<0.01) and 0.917 (95% CI 0. 856-0. 979, P<0. 01 ) respectively. AARR of 1 -hour upright yielded the highest screening efficiency. ( 2 ) The correlation coefficient index of Log-PRA and Log-PRC was 0. 705 ( P< 0. 01, n = 418 ), whereas the correlation coefficient index of Log-ARR and Log-AARR was 0.705 (P<0.01, n=418). The AUC of ARR and AARR were 0.998 (95% CI0. 981-1. 000, P<0.01 ) and 0.957 (95% CI0. 929-0.985, P<0.01 ) respectively according to the ROC curve. The optimal cutoff of AARR during upright 1 hour was 42.36 ng · dl-1/ng ·dl-1 ( sensitivity 87.10%, specificity 93.75% ). Conclusion The screening efficacy of AARR in screening PA in hypertensive patients was comparable with ARR. AARR measured after keeping upright 1 hour yielded the highest screening efficiency. The optimal cutoff of AARR was 42.36 ng · dl-1/ng ·dl-1.

Objective To explore the effect of dihydromyricetin (DMY) on the cholesterol efflux in macrophage derived foam cells and analyze the possible mechanisms. Methods RAW 264.7 macrophages were incubated by oxidized low densi?ty lipoprotein (ox-LDL, 50 mg/L) for 48 h to induce foam cells. Subsequently, the foam cells were subdivided into control group (RPMI1640 media) and DMY 1-4 groups (10, 20, 40 and 80μmol/L) and cultured for 24 h. Cholesterol efflux from foam cells was examined by [3H] labed cholesterol. The high performance liquid chromatography assay was used to test the cellular contents of free cholesterol (FC), cholesteryl ester (CE) and total cholesterol (TC). The expression of ATP-binding cassette transporter A1 (ABCA1) was measured by Western blot assay. Results Compared with control group, cholesterol efflux was significantly increased, the content of FC, TC CE and CE/TC ratio were significantly decreased and expression of ABCA1 was significantly up-regulated in dose dependent manner in DMY (20, 40 and 80μmol/L) groups (P<0.05). There were no significant differences in cholesterol efflux, the content of FC, TC and CE, and expression of ABCA 1 between control group and DMY (10μmol/L) group of foam cells (P>0.05). Conclusion DMY promotes the cholesterol efflux in the macro?phage derived foam cells, which may be related with the increase of ABCA1 induced by DMY.

Objective: To investigate the effect of clopidogrel on antiplatelet therapy in patients with coronary artery disease (CAD) combining chronic kidney disease (CKD) in order to provide a medication reference in clinical practice. Methods: We retrospectively investigated 423 CAD patients with coronary angiography (CAG) conifrmed diagnosis in our hospital from 2014-01 to 2014-09. According to the value of eGFR, the patients were classiifed into 2 groups:CAD+ CKD- group,n=257 patients with eGFR ≥ 90 ml/(min?1.73 m2), including 182 male and 75 female at the mean age of (60.39 ± 11.09) years, and CAD+CKD+ group,n=166 patients with eGFR < 90 ml/(min?1.73 m2), including 107 male and 59 female at the mean age of (65.80 ± 10.84) years. The patients were treated either by aspirin 0.1 g/d with clopidogrel 75 mg/d for at least 7 days, or by PCI operation with the load of aspirin 0.3g and clopidogrel 300 mg. The thrombelastography was conducted to examine and compare the inhibitory rates of ADP receptor and arachidonic acid (AA) pathway in platelet between 2 groups. Results: The inhibitory rate of platelet ADP receptor in CAD+CKD- group (64.9 ± 27.2) % was higher than that in CAD+CKD+ group (56.6 ± 27.4) %,P=0.039. Based on clinical standard of platelet’s ADP and AA inhibitory rates, in CAD+CKD- group, there were 24/257 (9.4%) of patients only insensitive to clopidogrel, in comparison with 25 (9.7%) of patients only insensitive to aspirin,P=0.99. While in CAD+CKD+ group, there were 21/166 (12.7%) of patients only insensitive to clopidogrel, in comparison with 11 (6.6%) of patients only insensitive to aspirin,P= 0.045. Conclusion: Clopidogrel has decreased effect on anti-platelet therapy in CAD patients combining with CKD, such patients have reduced sensitivity to relevant medication.

BACKGROUND: Vitamin D receptor (VDR) gene shows restriction fragment length polymorphism with incision enzyme Bsm Ⅰ ,Apa Ⅰ ,Taq Ⅰ ,which is related to bone mineral density (BMD).However, it is unclear that the relationship between VDR gene (Bsm Ⅰ ) polymorphisms and BMD,osteoporosis.OBJECTIVE: To analyze the distribution regularity of vitamin D receptor gene polymorphism related to BMD in postmenopausal women of Han,Uygur, Kazak and Mongoloid nationality in China. DESIGN: controlled observation.SETTING: Institute of Gerontology,General Hospital of Chinese PLA.PARTICIPANTS: Totally 179 women of Han,who were taking physical examination in General Hospital of Chinese PLA from January 2002 to December 2003, at the average age of (59±3) years,were selected. A total number of 122 women of Uygur with average age of 56.49 years; 63 women of Kazak with average age of (55±3) years; and 112 women of Mongoloid with average age of (57±3) years,who were all taking physical examination in department of geriatrics, Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA from January 2001 to December 2003.All of them were informed consent.METHODS: VDR genotypes(Bsm Ⅰ ) were defined with polymerase chain reaction-restriction fragment length polymorphism,so as to analyze distribution of Vitamin-D receptor gene (Bsm Ⅰ )polymorphisms of postmenopausal women in Han,Uygur, Kazak,Mongoloid nationality,and compared with the data of USA,Australia,France,Japan,Korea. Enumeration data were compared with Chi-square test.MAIN OUTCOME MEASURES: VDR (Bsm Ⅰ ) polymorphisms in healthy postmenopausal women from Han, Uygur, Kazak, Mongoloid populations in China, which were compared with the data of USA, Australia,France, Japan, Korea.RESULTS: For women of Han, Uygur, Kazak and Mongoloid nationality,the BB genotypes accounted for 0, 4.1%, 6.35% and 4.46%, the bb genotypes accounted for 90.5%, 69.67%, 38.1% and 50% respectively. There was a significant difference between women of Han, Uygur, Kazak, and Mongoloid nationality(P ＜ 0.01). There was insignificant difference in comparation of distribtuion of VDR genotype between Kazak nationality and the west races, but it was significantly different to that in Japan,Korea races.CONCLUSION:VDR genotype polymorphisms is characterized by obvious racial diversify in postmenopausal women of Han,Uygur, Kazak,Mongoloid populations in China;Distribution of VDR gene frequency of Kazak population is similar with the west race ,but is different to Japanese and Korea's race.

The parameters of illumination conditions include duration,illumination intensity,color temperature and so on.Different combinations of these conditions have different effects on human beings at the visual and psychological level and are related to occurrence or prevention of psychological diseases.Extension of illumination time and phase change of circadian rhythm increase the risk of bipolar disorder;changes in daytime,night or all-day illumination intensity have psychological effects,especially exposure to light at night increases risk of depression;inaddition,changes in color temperature of light also have psychological effects.This paper reviewed the effects of different illumination conditions on visual psychology.

Objective:To analyze the supply efficiency and influencing factors of medical and health services in 31 provinces in China from 2011 to 2020, providing reference for rational allocation of medical and health resources and improving service efficiency.Methods:The data related to the input-output indicators of China′s medical and health services from 2011 to 2020 were collected from China Health Statistical Yearbook, China Statistical Yearbook and China Social Statistical Yearbook. Data envelopment analysis was used to calculate the static efficiency of China′s medical and health service supply, the Malmquist index method was used to analyze the dynamic efficiency of China′s medical and health service supply, and the Tobit model was used to analyze the factors affecting the efficiency. Results:In 2020, the comprehensive efficiency of medical and health service supply in 15 provinces (Tianjin, Shanghai, Zhejiang, etc.) was 1.000, and the scale benefit remained unchanged. The comprehensive efficiency in 16 provinces (Heilongjiang, Jilin, Inner Mongolia, etc.) was less than 1.000. Among them, 15 provinces showed a decreasing scale benefit, while 1 province showed an increasing scale benefit.From 2011 to 2020, the total factor production efficiency index of China′s healthcare service supply increased from 0.988 to 1.036. The factors affecting the efficiency included number of people with a college degree or above per 10 000 people, the utilization rate of hospital bed rate, population density, asset liability ratio, and average length of stay ( P<0.05). Conclusions:In recent years, the efficiency of healthcare service supply in China showed a growth trend featuring regional differences and multiple influencing factors. It is suggested to further narrow the regional differences of the efficiency, reasonable control the scale of medical institutions, optimize medical service technology and management levels, shorten the average transfer day and improve bed utilization to improve the overall efficiency of medical and health service supply.

Abstract This paper focuses on the regulatory strategy of drug-led drug device combination products, comparing and analyzing the definition, scope and management mode of drug device combination products in the United States, the European Union, Japan, Canada and China; summarizing and analyzing the types of combination products in the Product-specific Guidances for Generic Drug Development(PSGs) of the US FDA's scientific and technical reports in the past five years, the results show that the top three PSGs newly added to the FDA were transdermal system, nasal sprays, and single-dose prefilled syringes/pens(including auto-injectors). As of March 1, 2023, the National Medical Products Administration(NMPA) had cumulatively announced the results of 339 combination products applied for attribute definition by enterprises, of which 88 were "drug-led drug device combination products", accounting for 26%; and 78 were "device-led drug device combination products", accounting for 23%; the results of "not belonging to drug device combination products" accounted for more than half (51.0%), which indicated that there was a big difference between the industry and the regulatory understanding of the definition of drug-device combination products, and that the existing guideline and documents were unable to provide clear and predictable positioning of the combination products under research and development for the time being. This paper also puts forward suggestions for solving the problems in the development of drug-device combination products in China, in order to improve the consistency, predictability and transparency of the classification and definition of drug-device combination products in China, and to provide references for the development and scientific supervision of this kind of products.

Abstract OBJECTIVE To introduce the scientific progress in the regulation of nasal preparations by the US Food and Drug Administration(FDA), and provide reference and inspiration for the development, manufacture, quality control and supervision of nasal preparations in China. METHODS Regulations and literature relevant to the nasal preparations were translated and collated, and research projects and latest developments of FDA regulatory science were introduced. The difficulties encountered in the development of nasal preparations and the future development direction were analyzed. RESULTS The main directions of FDA nasal regulatory science were to evaluate potential bioequivalence(BE) methods as an alternative to comparative clinical endpoint BE studies, to employ digital technology to establish computer models, to study the factors influencing nasal absorption, pharmacokinetics and pharmacodynamics characteristics, as well as pediatric drug use studies, nasal-brain delivery, and to develop new tools, new methods, and new standards. It provided a scientific basis for optimizing regulatory strategy and improving regulatory efficiency. CONCLUSION This article summarizes the latest research on the regulatory science of nasal preparation, provides a reference for the management personnel of regulatory agencies, and provides new ideas and new methods for improving the quality and efficiency of China's drug regulation and realizing international standards.