Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

OBJECTIVE To reduce dispensing errors in pharmacy intravenous admixture service （PIVAS） of children’s hospitals. METHODS The risk of dispensing procedures in our PIVAS was identified by applying failure mode and effect analysis （FMEA） model. Potential failure modes that might lead to dispensing errors in each link were determined， and failure causes were analyzed. The severity， incidence and detection degree of potential failure modes were quantitatively scored， and their risk priority number （RPN） was calculated to screen failure modes that needed to be improved in priority； the corresponding improvement measures were developed by 6S management method from six aspects， namely， finishing （seiri）， rectifying （seiton）， sweeping （seiso）， sanitation （seiketsu）， literacy （shitsuke） and safety. The effect of intervention before and after rectification was evaluated. RESULTS Based on the RPN， 32 potential failure modes were selected， of which a total of 18 critical failure modes that needed to be improved in priority. After implementing corresponding measures according to 6S management method， the RPN of 18 critical failure modes decreased. The total RPN decreased from 497 to 142 with a decrease rate of 71.43%. The error rates of 15 critical failure modes were significantly lower than before implementation （P＜0.05）. CONCLUSIONS Applying FMEA model and 6S management method to the risk control of all aspects of PIVAS workflow can effectively reduce the risk of PIVAS dispensing errors and ensure the safety of children’s intravenous medication.

Diabetes cardiomyopathy(DCM)is a cardiovascular disease with structural damage and dysfunction of myocardium under the condition of glucose and lipid metabolism disorder in diabetes.The main pathological characteristics are ventricular hypertrophy,myocardial remodeling and cardiomyocyte death,which induce heart failure.DCM has become one of the main causes of death in patients with diabetes.As a pro-inflammatory programmed cell death pathway,pyroptosis mediated by inflammasomes is considered an important driver of chronic inflammation due to its exces-sive activation.Recently,it was found that the over activation of pyroptosis promoted the course of DCM and became the hub connecting the disorder of glucose and lipid metabolism in diabetes and myocardial injury.With the discovery of more and more roles of Traditional Chinese Medicine(TCM)in regulating pyroptosis,TCM affects the occurrence and develop-ment of DCM by regulating pyroptosis or protein expression,which has become a research hotspot of myocardial protection strategies in diabetes.This article reviews the mechanism of pyroptosis in DCM and the research progress of TCM mono-mers and compound prescriptions in regulating the process of pyroptosis in DCM,in order to provide new ideas and targets for clinical research and treatment of DCM.

OBJECTIVE To explore the pharmaceutical service model in multidisciplinary diagnosis and treatment （MDT） of rare diseases in children. METHODS Clinical pharmacists of West China Second University Hospital （hereinafter referred to as “our hospital”） participated in the process of MDT of children’s rare diseases. Clinical pharmacists took part in the entire diagnosis and treatment process of children and established the MDT pharmaceutical service model of children’s rare diseases by formulating drug treatment plans based on evidence-based practice， improving the accessibility of drugs， pharmaceutical monitoring and drug treatment management. RESULTS From January 2021 to April 2022， clinical pharmacists of our hospital had participated in a total of 39 cases of rare diseases MDT in children， including 21 hospitalized children with rare diseases and 18 outpatient com children with rare diseases， involving a total of 23 rare diseases. Clinical pharmacists completed 45 pharmaceutical zhanglingli@scu.edu.cn rounds and 26 pharmaceutical consultations for rare diseases inpatients， 25 outpatients’ MDT and 5 pharmaceutical outpatient service for outpatients with rare diseases， 38 medication educations for inpatients and outpatients with rare diseases and 25 follow-up services for out-of-hospital patients. There were 24 cases （61.54%） of off-label drug use， involving 13 rare diseases and 16 therapeutic drugs， among which off-label drug use registration of 11 drugs had been completed or was in progress. The temporary purchase evaluations of 3 drugs had been completed； 268 cases of medical insurance drug and high-value drug prescription had been reviewed. CONCLUSIONS Our hospital have primarily established a loop pharmaceutical service model of MDT for children with rare diseases， which covers inpatients and outpatients. The model improves the availability and standardization of clinical application of therapeutic drugs， and diagnosis and treatment level for children with rare diseases in our hospital.

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Humans ; Radiotherapy, Intensity-Modulated ; Immune Tolerance ; Nasopharyngeal Carcinoma ; ROC Curve ; Nasopharyngeal Neoplasms/radiotherapy*

Objective:To compare the pros and cons of harvesting ear cartilage through anterior and posterior auricular approaches during rhinoplasty.Methods:From January 2017 to December 2018, 63 patients with otochondral rhinoplasty in our hospital were enrolled in this study, 60 were female and 3 were male; the average age was 31.6 years (range, 18 to 43) . They were randomly divided into anterior auricular approach group with 32 cases (64 sides) and posterior auricular approach group with 31 cases (62 sides). Surgical duration, complications and postoperative scar of the two methods were analyzed.Results:The average time for harvesting the ear cartilage through posterior auricular approach and anterior auricular approach was (20.8±1.7) min and (12.6±1.1) min, respectively ( P<0.01). The overall complication rate was 15.6% for posterior auricular approach group and 4.8% for anterior auricular approach group. The wound healed well in both groups, and there was no significant difference in postoperative scar between the two groups during an average 13 months follow-up period. Conclusions:While both the anterior and the posterior auricular approaches present with similar inconspicuous scarring, the use of anterior auricular approach alone to harvest ear cartilage during rhinoplasty provides both the surgeons and the patients with easier access, shorter surgical duration, and fewer complications. Hence, we believe that the anterior auricular approach possesses greater advantages than the posterior auricular approach.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

OBJECTIVE：To investigate the status quo and influential factors for scientific research training of pharmacists （nurses）in PIVAS of China ，to provide direction and reference for the development of PIVAS. METHODS ：The survey method was used to conduct a questionnaire survey of PIVAS pharmacist （nurses）from 29 tertiary and secondary hospitals in 24 provinces， autonomous regions ， municipalities from eastern ， western and central China through the i nternet by using self-designed questionnaire. The survey period was from Mar. to Apr. 2019. The survey content included the basic information （gender，region， hospital level ，professional and technical title ，education background ，employment nature ）of the survey participants and the status quo of scientific research training （frequency and content of scientific research training ，degree of need for scientific research ， degree of interest in scientific research ，etc.）and status quo of scientific research output （publication and application of the project）. Main influential factors for scientific research training were analyzed. RESULTS ：A total of 504 questionnaires were sent out，and 501 valid questionnaires were collected ，with effective response rate of 99.40％ . Totally 63.1％（316/501）of the respondents had scientific training ，and the frequency of scientific training was mainly less than one time/month （26.1％，131/501） and 1-2 times/month（25.0％，125/501）；72.1％（361/501）of the respondents have medium or above scientific research needs ， 82.4％（413/501）of the respondents have medium or above interest in scientific research ，only 6.0％（30/501）of the respondents had mastered the major scientific research methods ， only 5.4％（27/501）of the respondents thought that their scientific research ability were strong. The pharmaceutical re search - direction was mainly related to clinical rational use of drugs ， song_123@126.com less to precision medicine ，new drug and new dosage form： development， therapeutic drug monitoring research ， 028-85503220。E-mail：linyunzhu99@163.com translational medicine ， etc. Only 16.6％ （83/501） of the respondents had published articles after working in PIVAS ，and 9.0％（45/501）had applied for projects. There were statistical significances in the scientific research training among the respondents with different regions ，professional and technical titles ， educational backgrounds and employment natures （P＜0.05）. CONCLUSIONS ：The scientific research training of PIVAS pharmacist（nurses）in China is inadequate and the research output is low. Main influential factors for scientific research training include region ，professional and technical title ，educational background and employment nature .

Objective:To summarize the scientific research management response strategies and practices of designated hospitals under the prevention and control of new coronary pneumonia, provide reference for the scientific and technological management of public health emergencies in domestic hospitals.Methods:Take the hospital scientific research management response under the prevention and control of the new coronavirus pneumonia epidemic in 2020 as an example, discuss and summarize the response strategies and mechanism establishment, work practice and existing problems of designated hospitals in the research management of prevention and control of public health emergencies represented by COVID-19 from the aspects of management system, resource integration, project operation, and scientific and technological service.Results:As a designated hospital of COVID-19 in Beijing, Youan hospital has actively carried out scientific and technological research on epidemic prevention and control while successfully completing patient treatment, established a scientific and efficient scientific and technological research management system, and integrated resources to form an efficient project operation mechanism, Providing a full range of scientific management services, providing policy and material guarantee for the rapid and high-quality completion of scientific and technological research on epidemic prevention and control.Conclusions:The scientific and technological research on public health emergencies has the characteristics of demand-driven, focused on key points, collaborative research, scientific decision-making, In order to carry out the research work smoothly, it is particularly important to form a benign interaction, straighten out the system, do a good job in long-term planning and layout, and establish a scientific and efficient research and management mechanism.

OBJECTIVE： To establish the management system for off-label drug use in a medical institutions， and to standardize the behaviors of off-label drug use and improve the rational drug use. METHODS： Based on evidence-based researches for off-label drug use， management system of off-label drug use was established in our hospital， and off-label drug use management was carried out. The effects of management system were evaluated with the number of records for off-label drug use and pass rate of approval as indexes. RESULTS： Since the year of 2011， the management system for off-label drug use had gradually established and improved in our hospital； the mode of registration and approval for off-label drug use was established by based on a multi-disciplinary team management and quality classification for clinical evidence. Up to 2016， a total of 252 records for off-label use were submitted， among which 159 （accounting for 59.77％） were for pediatrics and 93 （accounting for 34.96％） were for gynecology and obstetrics. Among the submitted records， 181 had passed the examination and approval， and the pass rate was 64.29％. Special prescription comments indicated that the numbers of off-label use medical orders in inpatient medical orders showed a downward trend， and the proportion of recorded medical orders of off-label use had increased from 17.33％ in 2013 to 84.00％ in 2016. CONCLUSIONS： The management system for off-label drug use in medical institutions can effectively improve the clinical understanding of off-label drug use， standardize the behavior of off-label drug use.