OBJECTIVE To clarify the features of nosocomial infections for patients with multiple myeloma(MM).METHODS One hundred and seventy eight cases of MM treated in our hospital from Oct 1982 to Dec 2006 were analyzed retrospectively.RESULTS Eighty five patients(47.8%) suffered from nosocomial infections.The nosocomial infection took place more frequently on respiratory tract.Elder,granulocytopenia,hypoproteinemia,severe anemia,and diabetes were the risk factors.Totally 91 pathogens were isolated.Gram-negative bacilli accounted for 45.1%,and were the major pathogens.Fungi accounted for 37.4% and Gram-positives accounted for 17.6%.The ESBLs producing strains accounted for 31.6% in Klebsiella pneumoniae and Escherichia coli.Vancomycin resistant strains were found.The top one of fungi presented organism was the Candida albicans.CONCLUSIONS Nosocomial infections for patients with multiple myeloma has a high incidence.There are many risk factors.The resistance of commonly encountered bacteria to antimicrobial agents is a serious problem.Immunity protection and the rational use of antimicrobial agents should be emphasized.

Objective:To investigate the effect of Xidi Liangxue recipe on the proliferation and apoptosis of HaCaT cells through the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) /microRNA (miR) -485-5p/signal transducer and activator of transcription 3 (STAT3) regulatory network. Methods:HaCaT cells were induced by interleukin-17 (IL-17), and the mRNA and protein expression of lncRNA NEAT1, miR-485-5p and STAT3 was detected in IL-17-induced HaCaT cells and normal human epidermal keratinocytes (NHEK) by quantitative PCR (qPCR) and Western blot analysis, respectively. The location of lncRNA NEAT1 and miR-485-5p in IL-17-induced HaCaT cells was observed by fluorescence in situ hybridization (FISH), and the targeted regulatory relationship among lncRNA NEAT1, miR-485-5p and STAT3 was verified by double-luciferase reporter gene assay. Chinese herbs were decocted according to the Xidi Liangxue recipe, SD rats were divided into two groups to be gavaged with the above decoctions (medicated group) or physiological saline (control group) for 5 days, and then serum samples were collected from the above two groups of rats separately. The IL-17-induced HaCaT cells were divided into 4 groups: control group treated with the control sera, lncRNA-NEAT1 overexpression group transfected with lncRNA-NEAT1 overexpression vectors and treated with the control sera, Xidi Liangxue recipe group treated with the medicated sera, and Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group transfected with lncRNA-NEAT1 overexpression vectors and treated with the medicated sera. qPCR, Western blot analysis, flow cytometry, and cell counting kit (CCK8) assay were performed to determine the mRNA and protein expression of lncRNA NEAT1, miR-485-5p and STAT3, and to evaluate cell proliferation and apoptosis. The two independent samples t-test was used for comparisons between two groups, one-way analysis of variance for comparisons among multiple groups, and least significant difference (LSD) t-test for multiple comparisons. Results:The IL-17-induced HaCaT cell group showed significantly increased relative expression levels of lncRNA NEAT1 and STAT3 mRNA (1.84 ± 0.21, 2.20 ± 0.24, respectively) and significantly increased protein expression of STAT3 and p-STAT3 (1.27 ± 0.13, 2.43 ± 0.16, respectively), but significantly decreased expression level of miR-485-5p (0.32 ± 0.04) compared with the NHEK group (lncRNA NEAT1 and STAT3 mRNA: 1.00 ± 0.11, 1.00 ± 0.11, respectively, both P < 0.05; STAT3 and p-STAT3 protein: 1.00 ± 0.11, 1.00 ± 0.10, t = 2.54, 3.02, respectively, both P < 0.05; miR-485-5p: 1.00 ± 0.12, t = 2.94, P = 0.015). FISH demonstrated that miR-485-5p and lncRNA NEAT1 were co-located in the cytoplasm of HaCaT cells. The double-luciferase reporter gene assay showed that the relative activity of luciferase was significantly lower in the miR-485-5p group than in the negative control group (both P < 0.05) after the transfection with wild-type lncRNA NEAT1 or STAT3 recombinant plasmids, while there were no significant differences between the miR-485-5p group and negative control group after the transfection with mutant lncRNA NEAT1 or STAT3 recombinant plasmids (both P > 0.05). Compared with the control group, the lncRNA-NEAT1 overexpression group showed significantly increased expression of lncRNA NEAT1 and STAT3 (including STAT3 mRNA, STAT3 protein, and p-STAT3 protein) in HaCaT cells (all P < 0.05), but significantly decreased miR-485-5p expression ( P < 0.05) ; the Xidi Liangxue recipe group showed significantly decreased expression of lncRNA NEAT1 and STAT3 (all P < 0.05), but significantly increased miR-485-5p expression compared with the control group ( P < 0.05) ; significantly decreased expression of lncRNA NEAT1 and STAT3, but significantly increased miR-485-5p expression was observed in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group compared with the lncRNA-NEAT1 overexpression group (all P < 0.05). After 24-, 48-, and 72-hour intervention, CCK8 assay showed that the proliferative activity of HaCaT cells was significantly higher in the lncRNA-NEAT1 overexpression group than in the control group (all P < 0.05), as well as in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group than in the Xidi Liangxue recipe group (all P < 0.05), and the cellular proliferative activity was significantly lower in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group and Xidi Liangxue recipe group than in the control group (all P < 0.05). The apoptosis rate was significantly lower in the lncRNA-NEAT1 overexpression group (5.84% ± 0.28%) than in the control group (14.75% ± 0.83%, LSD- t = 3.48, P = 0.002), but significantly higher in the Xidi Liangxue recipe group (35.72% ± 3.62%) than in the control group (LSD- t = 5.34, P = 0.001) ; the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group showed significantly increased apoptosis rate (27.64% ± 2.82%) compared with the lncRNA-NEAT1 overexpression group (LSD- t = 9.06, P < 0.001) . Conclusion:The Xidi Liangxue recipe could inhibit the proliferation of IL-17-induced HaCaT cells and promote their apoptosis, which may be related to the intervention in the lncRNA NEAT1/miR-485-5p/STAT3 regulatory network.

Objective:To investigate the clinical features, therapy and prognosis of human cytomegalovirus(HCMV)pneumonia in pediatric patients, and to analyze the diagnosis value of detecting HCMV DNA in bronchoalveolar lavage fluid(BALF)by real-time PCR.Methods:The clinical characteristics of 58 pediatric inpatients who were HCMV DNA positive in BALF were retrospectively reviewed.All the patients were from Shengjing Hospital of China Medical University from January 2015 to December 2019.Clinical, radiologic, laboratory and microbiologic data was collected for each patient.The study cohort was divided into HCMV productive infection and latent infection consisting of 22 and 36 patients respectively, based on the HCMV active infection in lung or not.Receiver operating characteristic(ROC)curve was used to assess utility of detecting HCMV DNA in BALF and establish a threshold for diagnosis.Results:(1)Compared with patients in latent infection group, the children in productive infection group had a lower age of onset( P<0.05), a higher proportion of male( P<0.05), and more prolonged hospitalization stay( P<0.05). Pulmonary rales, hypoxemia and higher AST, CK, LDH in serum were easier to detect in productive infection group( P<0.05). Higher HCMV DNA copies in BALF was also detected( P<0.01). Patients in productive infection group had significantly more exposure to additional oxygen treatment or mechanical ventilation and systemic hormone therapy( P<0.05), while with poorer outcomes( P<0.05). (2) ROC curve analysis showed that the AUC for HCMV DNA in BALF in diagnosis of HCMV pneumonia was 0.708 with a threshold of 8.83×10 3 copies/mL, a sensitivity of 77.27%, and a specificity of 58.33%. Conclusion:Those who are diagnosed HCMV pneumonia have a lower age of onset with higher male proportion.These children suffered severer clinical signs.The patients with HCMV DNA copies higher than 8.83×10 3 copies/mL in BALF would be more likely to be diagnosed as HCMV pneumonia.

Objective:To analyze the incidence and prognosis of epilepsy in frontotemporal lobe glioma.Methods:The clinical data of 208 patients with frontotemporal lobe gliomas in Sanbo Brain Hospital Capital Medical University from 2019 to 2021 were analyzed retrospectively. According to the 2016 World Health Organization (WHO) classification of tumors of the central nervous system, the incidence of epilepsy, Modified Rankin Scale (MRS) score, and Engel Outcome Scale of patients with different grades of tumors were calculated.Results:Among all the patients with frontotemporal lobe gliomas, there was more males than females, and it was more common in the 40 -59 age group. The incidence of epilepsy associated with WHO grade Ⅰand Ⅱ glioma was 100.0% (33/33) and 60.9% (14/23), respectively, while that of WHO grade Ⅳ glioma was 19.0%(19/100). The average follow-up time was (22 ± 9) months. During the follow-up period, the incidence of WHO grade Ⅰ, Ⅱ and Ⅲ glioma-related epilepsy decreased significantly. There was no significant difference in the incidence of glioma-related epilepsy between the total and subtotal resection groups ( P>0.05). There was no statistical correlation between the side of tumor occurrence and the occurrence of epilepsy ( P>0.05), also between the gene phenotype and the occurrence of epilepsy ( P>0.05). There was no significant difference in the Engel Outcome Scale among different grades of gliomas ( P>0.05). The prognosis of patients with Engel Outcome Scale Class 1 was significantly better than that of other grades. Conclusions:The incidence of glioma-related epilepsy is negatively correlated with tumor grade. Age and sex are risk factors for glioma-related epilepsy. The incidence of postoperative epilepsy in patients with low grade glioma is significantly lower than that in patients with high grade glioma, and the prognosis is better. However, there is no significant difference in the Engel Outcome Scale among different grades of gliomas.

OBJECTIVE： To provide reference for improving pediatric medication of National Essential Medicine List （NEML） and establishing Chinese essential medicine list for children. METHODS： NEML （2018 edition） were compared with WHO Essential Medicines List for Children （WHO EMLc） in respects of target population， special symbols， categories and varieties， dosage form and specification. The related suggestions were put forward. RESULTS & CONCLUSIONS： WHO EMLc is specifically used for children under 12 years old， and defines specific age and body mass. NEML is applicable to all age groups （including children）. WHO EMLc includes 4 types of special symbols， i.e. “□” （the drug with the best efficacy and safety in the same kind of drugs， which matches the selection principle of NEML）， “a” （limited age or body weight， not found in NEML）， “*” （special dosage， specially emphasized indications and age not recommended for use， listing substitute drugs， not found in NEML）， “[c]” （placed next to a drug or a specification indicating that they are only used by children； and placed next to a supplementary list indicating that they need expert diagnosis， monitoring facilities， medical care for children， similar to the “Δ” in NEML）. NEML in China includes chemical drugs and biological products， Chinese patent medicines and TCM decoction pieces. Among them， there are 26 categories and 417 types of chemical drugs and biological products. Compared with WHO EMLc， NEML has no blood products and special drugs for newborns. As far as antimicrobial agents are concerned， WHO EMLc has strict limits and classifications. However， due to the lack of guidelines for special antimicrobial agents for children in China， the application of NEML antimicrobial agents in pediatrics is still difficult to define and classify. The number of coincident varieties in the 2 lists was 149， and the coincidence rate was 35.2％. In terms of drug dosage， WHO EMLc’s dosage form are more abundant and flexible， such as scored tablet， compressible fragments， intramuscular injections， and oral solutions suitable for children which are not included in NEML. In terms of drug specifications， 2 lists basically consider about the special needs of children taking small dosage and to some extent take into account the complementarity of dosage forms and specifications. The author suggests that the relevant departments in China should draw lessons from the mature experience of WHO EMLc， add new labeling symbols in NEML， expand drug dosage forms， implement classified management of antimicrobial drugs， and timely launch Chinese Essential Medicines List for Children so as to lay a solid foundation for further improving the accessibility and safety of essential medicines for children in China.

OBJECTIVE：To provide reference for improving th e availability of clinical medication for children in China. METHODS：Based on the current laws and regulations of China ，referring to the relevant excellent experience and mode of foreign countries，the definition and regulatory attributes of intermediate products and final small-sized children ’s preparations were analyzed，and the feasible regulatory pathway of children ’s medicine preparedby intermediate products entering medical institutions were discussed. RESULTS & CONCLUSIONS ：According to the clinical dosage and characteristics of medication ，small-sized preparations for children in medical institutions could be divided into preparations for children ’s medical institutions and personalized preparations for children. From the analysis of foreign experience ，legal policies and technical conditions ，it was feasible for medical institutions to use intermediate products to formulate children ’s small-sized preparations ，but they also faced certain difficulties as the difficulty to supervise ，unclear quality standards ，vague subject and scope of use ，etc. In terms of supervision，it wa s suggested that intermediate products should be taken as the main quality management object when children ’s small-sized preparations prepared by intermediate products entered medical institutions. Meanwhile ，quality risk management should be paid attention to it. In the management of small-sized preparations for children in medical institutions ，it is necessary to formulate the preparation specifications of small-sized preparations for children in medical institutions ，prepare guidelines for the use of excipients and improve the quality inspection standards of preparations ；in the aspect of preparation supervision ，the small-sized preparations for children in medical institutions with large clinical demand are strictly controlled ，and those with high personalized degree in medical institutions are under loose supervision ；in terms of registration and approval ，technical evaluation should be carried out at the same time as the implementation of registration/filing management ；in terms of price setting ，appropriate profit margins should be formulated according to the innovation degree ，clinical demand ，children’s family affordability and public opinion feedback of price of children ’s small-sized preparations in medical institutions. Indiviclualized preparations are forma- lated ased on the price of preparations inmedical institutions ， with reference to the differential price comparice rules. Mean- while，pharmaceutical service fees are charged to compensate pharmacists’time and labor ；in terms of medical insurancepayment，the drugs are classified and managed according to whether they are included in the medical insurance list ，so as to ensure the same drug availability for children and adults .

OBJECTIVE： To explore the current situation of service ability and pharmaceutical service construction of primary healthcare institutions in Jiangsu province. METHODS： Questionnaire survey was conducted among primary healthcare institutions of 13 prefecture level cities in Jiangsu province， involving basic service information （such as serving mode， medical departments）， resource allocation （such as hardware， human resource） and pharmaceutical care construction （such as the leaders of the drug procurement， pharmaceutical departments allocation， mediation safety management）. The current situation of service ability and pharmaceutical service construction was evaluated in primary healthcare institutions of Jiangsu province. RESULTS： A total of 579 primary healthcare institutions in Jiangsu province were investigated and 579 questionnaires were collected （some items in the questionnaires were not answered）. Outpatient service （543/555，97.8％） was the main mode of service provided by primary healthcare institutions in Jiangsu province， followed by emergency call （321/555，57.8％） and hospitalization （292/555，52.6％）； the frequently established department in primary healthcare institutions was the medical department for all （452/568，79.6％）， preventive healthcare department（401/568，70.6％）， internal medicine department （365/568，64.3％）； 16.1％ （93/533）of the primary healthcare institutions had no beds； 36.4％ （211/579）of the institutions had no chief physician； 20.9％ （111/532）of the primary healthcare institutions medicine procurement were managed by pharmacists； 42.5％ （212/499）of the institutions had no pharmaceutical departments； physicians were responsible for patients' medication safety in 43.9％ （236/537） of the primary healthcare institutions and pharmacists were responsible for patients' medication safety in only 16.2％ （87/537）of the institutions. CONCLUSIONS： Primary healthcare institutions in Jiangsu province have made some achievements in service capability building. Human resources， equipment and facilities， pharmaceutical care construction and other aspects still need to be improved.

OBJECTIVE：To provide reference for improving the level of pediatric pharmacoeconomic research in China. METHODS： Using “Pediatric”“Pharmacoeconomics”“Cost-effectiveness”“Cost-utility”“Cost-benefit”“Minimum cost ” as keywords，pediatric pharmacoeconomic research literatures published during Jan. 2009 to Dec. 2018 were retrieved from CNKI ， Wanfang，VIP and CBMdisc. The Pediatric Quality Appraisal Questionnaire was used to evaluate the quality of the literatures. The problems of these literatures were analyzed to put forward the suggestions. RESULTS & CONCLUSIONS ：Totally 140 literatures were eventually included. The number of published literatures was increasing and the distrubtion of journals was scattered. The first auther was mainly from medical institutions. Included literatures mainly involved respiratory disease and drug treatment ，etc. Among them ，15 literatures indicated the research angle ；research time limit of 109 literatures was equal to or less than one year ；6 literatures carried out sensitivity analysis. Most of them adopted cost-effectiveness analysis and decision analysis model. The results of quality evaluation showed that the economic evaluation ，camparators，target population ，outcomes，analysis and conclusions domains had high scores （0.62 to 1.00 score），time horizon and discounting domains had middle scroes （0.49 and 0.53 score respectively），but perspective ，costs and resource use ，incremental analysis ，sensitivity analysis and conflict of intrest domains had low scores （0.10 to 0.31 score）. The main problems of pediatric pharmacoeconomic literatures in China focused on selection of research perspective ，measurement of costs and clinical outcomes ，and selection of analytical methods. The quality of pediatric pharmacoeconomic evaluations in China need to improve. It is suggested to supplement the content of pediatric pharmacoeconomics in China Guidelines for Pharmacoeconomic Evaluations . It is also suggested for pediatric pharmacoeconomic evaluations to clarify the perspective ，standardize the cost identification ，reasonably select health outcome indicators and correctly apply analysis method in order to improve the quality.

Based on the current laws and regulations framework of China， combined with practical cases， this paper systematically and comprehensively analyzes the supervision attributes， clinical trial supervision model and existing problems of tumor neoantigen vaccine， aiming to provide reference for the construction of the supervision system of clinical trial of tumor neoantigen vaccine in China. The results showed that， at present， the clinical trials of tumor neoantigen vaccine in China adopt a dual-track supervision model： clinical trials initiated by pharmaceutical enterprises and clinical trials initiated by researchers. This supervision model lags behind the development speed of the industry， mainly in the following aspects： challenges brought by dual- track supervision； the clinical trial data initiated by researchers are not effectively connected with new drug research applications； the guiding principles of clinical trial supervision need to be improved. Relevant medical institutions， regulatory authorities and cooperative enterprises can help the development of the regulatory system for clinical trials of tumor neoantigen vaccine in China from the above aspects.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.