OBJECTIVE:To introduce the application of control chart in quality trend analysis and abnormal location manage-ment of pharmaceutical production,thus encourage pharmaceutical manufacturing enterprises to more frequently use control chart as a statistical analysis tool in quality control process. METHODS:Taking a pharmaceutical manufacturing enterprise as examples,the way for selection of different kinds of control charts in different conditions(such as stability study,product quality review)was il-lustrated. Based on the given data of quality characteristic analysis and stability study of a certain product in this company,analysis process was demonstrated using control chart. RESULTS & CONCLUSIONS:When the sample capacity for analysis is not less than 25,meeting the minimum requirement for steady state estimation,Hugh Hart control chart (conventional control chart)alone can accurately locate the abnormal data;while under the adverse circumstance of small sample capacity,the modified control chart (such as the regression control chart)is still able to equally reflect the overall trend and out of trend(OOT)ones. As a statistical analysis tool,control chart introduced into quality management activities is an effective technic way for control.

OBJECTIVE:To explore the training method for the postgraduates majoring in medicine management,and provide reference for the teaching effect of medical management. METHODS:Based on the existing problems in the training mode of post-graduates majoring in medical management,the foundation,feasibility implementation process of the coalition of college and enter-prise were analyzed. RESULTS & CONCLUSIONS:The training mode of coalition of college and enterprise can really make teach-ers,students and enterprises to achieve a win-win situation;at the same time,through the feasibility analysis of the training mode, the performance evaluation method of multi-level evaluation system and fuzzy comprehensive evaluation are put forward to finally achieve the exploration of training management mode of undergraduates from the perspective of operational level. But in the owner-ship of intellectual property rights,technology security,personal safety of graduate and other aspects still exist some problems and need further improvement.

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 analyze the distribution and drug resistance characteristics of pathogenic bacteria isolated from blood cultures in the infected patients in our hospital during 2009-2013 to provide the newest evidence for the clinical anti-infection ther-apy.Methods The bacterial identification and drug susceptibility test were performed by applying the VITEK-32 System.The dis-tribution situation and the drug susceptibility test results of pathogens isolated from blood culture specimens in our hospital during this period were analyzed.Results 2 301 strains of positive bacteria were isolated from 14 006 cases of blood culture during these five consecutive years.The positive rate was 16.4%.Among them,1 303 strains were Gram positive bacteria(56.6%),954 strains of Gram negative bacilli(41.5%)and 44 strains of fungi(1.9%).Gram-positive bacteria were mainly Staphylococcus aureus,coagu-lase negative staphylococci(CNS),etc.Gram-negative bacteria were mainly E.coli,Klebsiella pneumoniae,etc.E.coli and Klebsiella pneumoniae were highly sensitive to carbapenem,amikacin,cefoxitin and antibacterial drugs containing enzyme inhibitor.The detec-tion rates of extended-spectrumβ-lactamase(ESBL)-producing Escherichia coli and Klebsiella pneumoniae were 55.8% and 18.4%respectively.Acinetobacter baumannii in blood culture had serious resistance to most of antibacterial drugs.Conclusion The kinds of pathogens isolated from blood culture are complex with different sensitivity to antibacterial drugs.Timely understanding the re-sults of blood culture has the important significance to adjust the treatment scheme in clinic and timely discover drug-resistant strains for serve clinic better.

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 To establish the type Ⅱ collagen specific T cell line of Wistar rat and observe its effect on transferring arthritis.Methods The Wistar rats were immunized with emulsified chicken type Ⅱ collagen (CCⅡ) in complete Freund′s adjuvant by intradermal injection to induce the rat model of collagen induced arthritis (CIA).The lymphocytes were obtained from mesenteric lymph nodes of CIA rats,and the type Ⅱ collagen reactive T cell line was selected and propagated by CCⅡ stimulating in vitro .The proliferation response and phenotype were analyzed by 3 H TdR incorporation and fluorescence activated cell sorter (FACS).The onset of arthritis and pathological characteristic in ankle joints of recipient rats were observed with naked eye and histochemical examination.Anti CCⅡ antibody in serum was assayed by enzyme linked immunosorbent assay (ELISA).Results A T cell line was successfully established.The results of FACS labeled with fluorescent antibodies showed that 98 2% of the line cells were T cells,of which 89 7% were CD4 + T cells.The results of adoptive transfer showed that the incidence of arthritis was 50% when the injected cell number was 5?10 7,meanwhile the level of anti CCⅡ antibody in serum was elevated more than that of the control.Conclusion A cell line has been successfully established.The result of arthritis transferring by T cell line shows that the T cell plays a great role in the pathogenesis of CIA and provides a research datum for rheumatoid arthritis therapy with T cell vaccine.

Objective To investigate the antibiotic resistance of clinical isolates from hospital for the guidance of rational use of antibiotics .Methods Automatic VITEK‐2 system was used to identify bacterial strains and analyze the antimicrobial resistance . WHONET 5 .6 was applied for data analysis according to the breakpoints of Clinical and Laboratory Standards Institute 2013 . Results A total of 3 880 nonduplicate strains were collected in 2013 ,35 .2% (1 366/3 880) of which were gram positive organisms ,64 .8% (2 514/3 880) were gram negative bacteria .The top 6 most frequently isolated microorganisms were E . coli (20 .2% ) , K . pneumoniae (12 .0% ) , P . aeruginosa (11 .1% ) , coagulase negative Staphylococcus (9 .8% ) , A . baumannii (9 .8% ) ,E .f aecalis (8 .1% ) .The bacteria were mainly isolated from respiratory tract (51 .0% ) ,urine (26 .2% ) , and blood (9 .4% ) .The prevalence of both meticillin‐resistant Staphylococcus was higher than 72 .0% .No staphylococcal strainwasfoundresistanttolinezolid,vancomycinortigecycline.Amongthe509Enterococcusisolates,E.faecalisandE. f aecium accounted for 61 .5% and 32 .8% ,respectively .No enterococcal strain was resistant to vancomycin or tigecycline . Enterococcal isolates also showed low resistance (<2 .0% ) to teicoplanin and linezolid .About 67 .4% of the E .coli strains and 32 .0% of the K lebsiella isolates produced extended spectrumbeta‐lactamases.Thestrainsof E.coli,Klebsiella spp.,Enterobacterspp.,and Proteusspp.wererelatively susceptible to beta‐lactam/beta‐lactamase inhibitor combinations such as cefoperazone‐sulbactam and piperacillin‐tazobactam , carbapenems such as meropenem ,imipenem and ertapenem ,and amikacin (< 15 .0% of the strains were resistant) . K . pneumoniae isolates were more resistant than other gram‐negative bacilli .P .aeruginosa was relatively susceptible to amikacin , tobramycin ,cefepime ,gentamicin ,piperacillin‐tazobactam ,but more than 20% of these strains were resistant to meropenem and imipenem .More than 35 .0% of the A . baumannii isolates were resistant to any of the antimicrobial agents tested . Conclusions Antimicrobial resistance is still a serious threat in clinical antimicrobial therapy .It is important to promote the rational use of antimicrobial agents so that resistance is minimized . It is necessary to conduct epidemiological survey and proactively implement effective interventions in the clinical setting with relatively heavy burden of antimicrobial resistance .

Objective Hypothyroidism(HypoPT) is one of the most common complications of thyroid reoperation,and hypocalcemia caused by HypoPT is a difficult problem in clinical practice.This study aims to investigate the risk factors for hypoealcemia after reoperation of thyroid cancer.Methods Data of 106 patients who underwent reoperation for thyroid cancer from 2013 to 2018 were retrospectively analyzed.According to the parathyroid area involved in the reoperation,the reoperation was graded:low-risk group,intermediate-risk group and high-risk group.Parathyroid hormone(PTH) and total calcium(Ca) levels were monitored at 12 to 24 hours after surgery.The follow-up period was at least 6 months.The PTH cut-off values of postoperative hypocalcemia were analyzed by ROC curve.The chi-square test and logistic regression analysis were used to analyze the risk factors of postoperative hypocalcemia.Results The incidence of transient HypoPT after reoperation was 35％,and the permanent HypoPT was 1.9％.The grade of reoperation was positively correlated with postoperative HypoPT.The ROC curve showed that the PTH cut-off values of postoperative hypocalcemia was 15 pg/ml and area under curve(AUC) was 0.636(95％ CI:0.530-0.742,P＜0.017).Univariate and multivariate analysis showed that reoperation grade and postoperative PTH＜15 pg/ml were independent risk factors for postoperative hypocalcemia.Conclusion The grade of reoperation and postoperative PTH value ＜15 pg/ml can predict postoperative hypocalcemia.

Objective To explore the feasibility and clinical outcome of lateral cervical incision via sternocleidomastoid intermuscular approach(SMIA)in the treatment of primary hyperparathyroidism.Methods The clinical data of 64 patients with primary hyperparathyroidism who underwent unilateral parathyroid surgery in the First Affiliated Hospital,School of Medicine of Zhejiang University from January 2019 to June 2022 were retrospectively analyzed.They were divided into lateral cervical incision via sternocleidomastoid intermuscular approach group(SMIA group)and linea alba cervicalis approach group(LACA group)based on the surgical incision and access route.The differences in clinical features,surgery-related outcomes and postoperative functions of the anterior cervical region were compared between the two groups.The EQ-5D-5L scale was used to assess the subjective feeling of postoperative neck discomfort,while the Hollander Wound Assessment Scale was used to assess the clinical outcome of incision healing.Results There were no statistical differences between the two groups of patients in terms of age,gender,intraoperative bleeding,parathyroid hormone or blood calcium levels before and after surgery(P＞0.05).The duration of surgery was significantly shorter in the SMIA group than in the LACA group[(39.77±5.69)min vs.(54.41±4.66)min].There was a statistical difference between the two groups in functional protection of the anterior cervical region at 1 month and 12 months after surgery(1 month,84.67±3.74 vs.79.47±5.38,P＜0.001;12 months,93.80±2.52 vs.89.94±2.39,P＜0.001),and the SMIA group was better than the LACA group.The Hollander Incision Assessment Scale scores of the SMIA group were better than those of the LACA group at 6 months and 12 months after surgery,and the difference was statistically significant(6 months,1.93±0.58 vs.2.41±0.66,P=0.003;12 months,1.03±0.67 vs.1.74±0.62,P＜0.001).Conclusion Parathyroidectomy via sternocleidomastoid intermuscular approach through lateral cervical incision is a simple,safe and effective surgical procedure,which makes it easier to search for parathyroid lesions and shortens the surgical time compared with the traditional incision,and has obvious advantages in the protection of anterior cervical region function.

OBJECTIVE: Taking polysuccinimide as the main chain, amine side chain and alkyl side chain were grafted to prepare the drug/gene co-delivery vector. The property of the polymers with various side links were investigated to select an optimal vector. METHODS: Poly-D, L-polysuccinimide was synthesized by polymerization reaction of D, L-aspartic acid as monomer. Therefore, N, N-dimethylenedipropyl-triamine and 3, 3'-diaminodipropylamine were grafted with dodecylamine/adecylamine/octadecylamine at different proportions by ring-opening reaction to obtain amphiphilic PEECs. The structure of the material was confirmed by ¹H NMR; the particle size and surface potential of the micelles were measured by dynamic light scattering; the critical micelle concentration (CMC) was determined by pyrene fluorescent probe; the RNA blocking ability was characterized by agarose gel electrophoresis; the release behavior of the PEECs was examined and the cytotoxicity, cellular uptake and gene silencing efficiency of the PEECs were studied at the cellular level. RESULTS A series of PEECs with different grafting rates was successfully synthesized. The particle sizes and surface potential of the PEEC derived micelles were between 250 nm and 350 nm and 27 mV and 45 mV, respectively, with a small CMC value. The RNA binding ratio of PEECs was at a mass ratio of about 0.8:1. MTT assay demonstrated that PEEC micelles had certain cytotoxicity. PEECs had excellent micelle formation, drug-loading and gene binding abilities, particularly, PEEC₁₆-2 showed high gene silencing efficiency at the cellular level. CONCLUSIONS PEECs are able to co-delivery drug and gene, and PEEC₁₆-2 micelles have the best ability of drug encapsulation and gene delivery.