OBJECTIVE:To evaluate the feasibility and effectiveness of Hazard analysis and critical control point (HACCP) system in the process of production of Loratadine tablets. METHODS:Taking wet granulation and tableting technology of Lorata-dine tablets as an example,and through the introduction of the concept of HACCP,the basic theory and method of HACCP were applied for hazard analysis on each production link to find critical control points and set critical limits for production quality man-agement. RESULTS:By HACCP analysis,three links namely drying,granules fitting and mixing,internal and external packaging were finally determined as the critical control points in the process of production of Loratadine tablets,thereby critical control lim-its were set for monitoring. After effective control over the risks in the process was ensured,HACCP work plan was made and veri-fied,and the results showed that HACCP system could effectively control and reduce the risks in the process of production and en-sure quality safety. CONCLUSIONS:Application of HACCP system to wet granulation and tableting technology of Loratadine tab-lets can fully embody its feasibility and effectiveness.

OBJECTIVE:To study the classification of deviation in drug production. METHODS:From the perspective of dom-inant and hidden deviation,combining with the theory of risk management,risk of deviation was evaluated with different risk man-agement tools to define the severity of the deviation,and it was handled by different methods. RESULTS & CONCLUSIONS:Ac-cording to the identifiability of deviation in actual management,the deviation was divided into dominance and hidden deviation. The dominant deviation can be divided into deep and shallow level. Whether the causes of deviation could be cleared and the conse-quences could be estimates were judged after the shallow level classification,and the deviation was further divided into simple and complex deviation. As for deviation complex,it could be evaluated with the tools of risk management to define the deviation severi-ty. As for hidden deviation,it needed beforehand preventing with the tools of risk management directly to define deviation levels and provide reference for preventive measures. In the process of deviation management,key point is to relay on the scientific meth-od to identify and classify deviation,and divide the influence levels. Combining the theory of risk management to select and use risk tools is the effective way to solve the problem.

Objective Thymidine phosphorylase (TP) cDNA was transfected into colorectal cancer cell lines LOVO with the lentiviral vector,the anticancer effeciency of 5'-deoxy-5-fluorouridine (5'-DFUR)and 5-fluorouracil (5-FU) on LOVO cells were evaluated.Methods TP cDNA were transfected into LOVO cell line with the lentiviral vector pLenti6.3_MCS_IRES2-EGFP,and the transfection efficiency was analyzed by flow cytometer and immunohistochemistry.Cells were divided into six groups:LOVO,LOVO-TP,LOVO-control,LOVO + INF-α2a,LOVO-TP + INF-α2a,LOVO-control + INF-α2a.TP protein expression and the relative quantitative analysis for TP mRNA in transfections cells were detected by Western blot and RT-PCR respectively.Volumes of converted 5-FU from either in the medium containing different concentration of 5'-DFUR,in which all cells were cultured,or in cells lysate,were detected by high performance liquid chromatography (HPLC).Results The transfection efficiency of TP cDNA in LOVO cells was 95％.The Mean gray value of TP protein expression in LOVO-TP and LOVO-TP + INF-α2a were 198.15 folds and 243.22 folds higher than LOVO cell,respectively (P ＜ 0.01).The RQ values of TP mRNA expression in LOVO-TP and LOVO-TP + INF-α2a were also 18.56 folds and 59.61 folds higher than wild LOVO cell,respectively (P ＜ 0.01).The IC50 values of 5'-DFUR on LOVO-TP and LOVO-TP + INF-α2a were 1 660 μ mol/L and 813 μ mol/L,respectively,significantly lower than 4 462.59 μ mol/L in wild LOVO (P ＜ O.01).The 5-FU volumes detected from media contained series concentration of 5'-DFUR for culturing LOVO-TP and LOVO-TP + INF-α2a were 2.0-5.3 folds,and 2.9-10.4 folds more than wild LOVO,respectively (P ＜ 0.01).Conclusions Transfected TP cDNA into colorectal cancer cell line LOVO with lentiviral vector increases the expression of TP mRNA and TP protein and the amount of 5-FU converted from 5'-DFUR,enhancing its anticancer effect.

Parathyroid carcinoma is a rare sporadic disease.Clinical manifestations include hypercalcemia,increased urinary calcium and urinary calculus,osteoporosis,and pathologic fracture.While this patient complained of pollakiuria,urgency,and painful urination,thus might lead to misdiagnosis or missing of diagnosis of parathyroid carcinoma.This article is herewith presented to call attention to discovery,diagnosis,and treatment of parathyroid carcinoma.

Objective To investigate the correlation between the mutation of pncA gene and the susceptibility to pyrazinamide ( PZA) in Mycobacterium tuberculosis complex ( MTBC) strains and to analyze the mutation of panD and rpsA genes in wild type isolates without pncA gene mutation.Methods The sus-ceptibilities of 108 MTBC strains to first-line drugs including PZA were detected by using the MGIT 960 TB system.PCR was performed to amplify the 16S rDNA and pncA, panD and rpsA genes.The PCR products were analyzed by DNA sequencing analysis .Results Among the 78 multidrug-resistant MTBC strains , 47 isolates (60%) were resistant to PZA.Four out of 30 (13%) strains that were sensitive to ethambutol , iso-niazid, rifampicin and streptomycin (EIRS) were resistant to PZA.The drug-resistant MTBC strains showed higher resistance rate to PZA than that of the EIRS sensitive strains .There were 49 ( 96%) PZA-resistant isolates and 4 (7%) PZA-sensitive isolates occurred pncA gene mutation.Most of the pncA gene mutations in the genomes of PZA-resistant strains were base substitution mutation , especially the His57Asp substitu-tion.The pncA gene mutations centralized in the regions of 160-169, 203-289, 309-396 and 413-467.Seven novel mutation sites of pncA gene were observed including T175C, C188A, G insertion at 68, AGC insertion at 235, C insertion at 339, CC insertion at 392 and GT deletion at 395.The mutation sites founded in the genomes of PZA-sensitive strains were different from those of the PZA-resistant strains .No mutation of the pncA gene and the upstream regulatory sequence was found in two PZA-resistant strains , NJ44 and NJ108 . The sequence analysis of panD and rpsA gene showed that the NJ 108 strain had panD gene mutation at G419A, but no mutation was detected in the NJ 44 strain.Conclusion The multidrug-resistant MTBC strains showed higher resistance rate to PZA .The pncA gene mutation was common in PZA-resistant MTB strains and the panD gene mutation was also worthy of attention .

Objective:To explore the serodiagnostic value of Rv0222/ESAT-6 fusion protein in tuberculosis.Methods:By using purified recombinant Rv0222/ESAT-6 fusion protein as antigen and enzyme-labeled antibody as secondary antibody,the serum of patients with tuberculosis and patients with human immunodeficiency virus(HIV)accompanied by tuberculosis,non-tubercu-losis patients and healthy people were detected with enzyme-linked immunosorbent assay(ELISA).The diagnostic value of the fusion protein in tuberculosis was evaluated.Results:By setting T lymphocyte spot test of infection with Mycobacterium tuber-culosis (T-SPOT)as the gold standard,the sensitivity and specificity of ELISA,of which Rv0222/ESAT-6 fusion protein was used as the antigen,in the diagnosis of tuberculosis were 86% and 100%,respectively.There was no statistically significant difference in the positive rate of tuberculosis between T-SPOT and ELISA.Conclusions:The ELISA with Rv0222/ESAT-6 fu-sion protein as antigen,has certain application value in the serodiagnosis of tuberculosis.

Objective To investigate the distribution and susceptibility patterns of common uropathogens causing community-acquired urinary tract infection (UTI) in Beijing.MethodsA total of 300non-duplicate isolates were randomly collected from 3 hospitals in Beijing between Jan,1 2010 and Mar,312011.Minimal inhibitory concentrations (MICs) were determined by the broth microdilution methods,which were performed and interpreted according to the guidelines established by the Clinical and Laboratory Standards Institute (CLSI).A panel of 8 antimicrobial agents were tested:amikacin,cefaclor,cefepime,cefoperazone/sulbactam,ciprofloxacin,levofloxacin,gentamicin and nitrofurantoin. Fosfomycin trometamol MICs were determined by the agar-dilution method in cation-adjusted MH agar supplemented with glucose 6-phosphate at a concentration of 25 mg/L as detailed in the guidelines issued by 2010 CLSI. All the Escherichia coli,Klebsiella pneumoniae and Proteus mirabilis strains were screened and confirmed by double-disk synergy test for extended-spectrum β-lactamase (ESBLs).Results Among the organisms cultured,E.coli wasthepredominantpathogen(65.0％ ), followedby Enterococcus(11.7％ ),Staphylococcus( 6.3％ ), Klebsiella pneumoniae( 5. 3％ ), Proteus mirabilis( 4. 7％ ), and Pseudomonas aeruginosa (3.0％).Lower susceptibility rates to ciprofloxacin and levofloxacin (31.4％ -47.4％ ) were observed among all the stains.Amikacin,cefoperazone/sulbactam,nitrofurantoin and fosfomycin trometamol were the most active drugs (92.1％,92.1％,88.4％ and 87.9％ susceptible strains,respectively) among the Gram-negative strains.Isolates of Staphylococcus were highly sensitive to amikacin ( 100.0％ ),cefoperazone/sulbactam (94.7％),nitrofurantoin ( 100.0％ ).Higher susceptibility rates to nitrofurantoin (91.4％) and fosfomycin trometamol (90.0％) were observed in Enterococcus.ESBLs-producing strains accounted for 52.3％ (102/195) in E.coli,43.8％ (7/16) in K.pneumoniae and 14.3％(2/14) in P.mirabilis,respectively.ConclusionsResistance is most common to ciprofloxacin and levofloxacin of all the stains.Currently,the most appropriate agents for the empirical management of uncomplicated UTI seems to be amikacin,cefoperazone/sulbactam,nitrofurantoin and fosfomycin trometamol.

Objective: To describe the spatial and temporal characteristics of human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS) in permanent residents and migrants in Shanghai during 2005 to 2015 and provide suggestions for the HIV/AIDS prevention. Methods: The data of HIV/AIDS was collected from the National HIV/AIDS Comprehensive Information Management System based on report date. The population data was collected from the statistical yearbook of Shanghai. Spatial analysis was conducted using the hotspots model in ArcGIS. SaTScan software was employed to determine the distribution of HIV clusters in space, time or both. Results: During 2005 to 2015, a total of 13 498 cases of HIV/AIDS were reported in Shanghai. The prevalence of HIV increased from 0.025/10⁵ (450 cases) to 0.093/10⁵ (2 236 cases). The prevalence of AIDS increased from 0.002/10⁵ (32 cases) to 0.028/10⁵ (683 cases). Hotspot analysis showed that the hot spot of incidence of migrants had moved from Hongkou (2005) (Z=2.96, P=0.003) to Changning (2006-2015) (all Z>1.96, P<0.05); whereas the hot spot of incidence of permanent residents had moving from Jinshan (2005-2007) (all Z>2.58, P<0.01) to downtown area (2006-2015) (all Z>1.96, P<0.05). The spatial high clusters of HIV and AIDS were same, including Huangpu, Xuhui, Changning, Jingan, Putuo, Hongkou and Yangpu; The temporal high clusters of HIV cases among permanent residents were 2011 to 2015, and the spatial clusters were Huangpu, Xuhui, Changning, Jingan. The temporal high clusters of HIV cases among migrants were 2014 to 2015, and the spatial clusters was Xuhui, Changning, Jingan. Conclusion The total HIV/AIDS incidence in Shanghai was clustered in downtown area. The cluster of the incidence of the permanent residents had moving towards that of migrants, indicating the cluster area deserves a close surveillance.

Objective:To analyze the epidemiological characteristics of imported COVID-19 cases in early phase in Shanghai, introduce measures and provide reference for prevention and control of imported COVID-19 cases.Methods:Data of imported COVID-19 cases in Shanghai reported as of 30 March, 2020 were obtained from National Notifiable Disease Report System of China CDC and field epidemiological investigation reports by CDCs in Shanghai. The information about measures of prevention and control was collected from official websites and platforms of the governments. Data cleaning and statistical analysis were performed with softwares of EpiData 3.1, Excel 2019 and SAS 9.4.Results:A total of 171 imported COVID-19 cases had been reported as of 30 March, 2020 in Shanghai, including 170 confirmed cases and 1 asymptomatic infection case. Among them, cases of Chinese nationality accounted for 71.3% (122/171) and cases of foreign nationality accounted for 28.7% (49/171). The median age of the cases was 23 years ( P 25, P 75: 18, 35 years), and the male to female ratio of the cases was 1.3∶1. Students accounted for 56.6% (97/171). About 45.6% (78/171) of the cases fell ill before arriving in Shanghai. The cases with mild or common clinical manifestation accounted for 96.5% (165/171) and no significant difference in clinical type was observed between overseas Chinese cases and foreign cases. The epidemic curve by diagnosis date reached peak on March 24, and the number of the cases gradually declined due to the closed-loop management process of joint port prevention and control mechanism. The 171 imported COVID-19 cases were mainly from 24 countries and regions, including the United Kingdom (64 cases, 37.3%), the United States (32 cases, 18.6%), France (19 cases, 11.0%) and Italy (16 cases, 9.4%). About 40.4% of the cases (69/171) planned to continue travelling to 21 other provinces and municipalities in China. Customs quarantine and community observation/detection points identified 43.9% (75/171) cases and 31.0% (53/171) cases, respectively. Conclusions:The imported COVID-19 cases in early phase in Shanghai were mainly young population and students accounted for high proportion. The imported risk of COVID-19 was consistent with the severity of the epidemic in foreign countries. The closed-loop management model of the joint port prevention and control mechanism plays an important role in the identification and management of the imported COVID-19 cases.

Objective To describe and analyze the epidemiologic and spatio-temporal characteristics of hepatitis E in China from 2004 to 2014.Methods Data on the incidence of hepatitis E in 31 provinces (municipality and autonomous region) from 2004 to 2014,were collected.Empirical Mode Decomposition (EMD) was applied to decompose the time-series data to accurately describe the trend of hepatitis E incidence.Mathematic model was used to estimate the annual change of incidence in each age group and the whole province.Software ArcGIS 10.1 and SaTScan 9.01 were used to analyze the spatio-temporal clusters.Results During 2004-2014,a total of 245 414 hepatitis E cases were reported in China.The overall incidence showed a slight increase (OR=1.05,95％CI:1.03-1.10).Incidence rates on hepatitis E were discovered different across the provinces,with significant increase appearing in the southern,central and northwestern areas.The highest increase was seen in the elderly,especially in the 65-69 and 70-74 year-olds.Results from the Local spatial autocorrelation analysis showed that the “high-high cluster” was moving from the north to the south and the “low-low cluster” disappeared as time went by.Data from Spatio-temporal scanning showed that there were five spatio-temporal clustering areas across the country.Conclusion The overall incidence of hepatitis E was on the rise from 2004 to 2014,in China,but with differences seen across the areas and age groups.