OBJECTIVE To evaluate the effect of manipulation of Imipenem and cisplatin sodium （ICS） for injection on the consistency of its main drug imipenem （IPN） content， and the stability of different concentrations of ICS solution， to provide a reference for the safe and effective use of ICS in children. METHODS Three operators prepared ICS solutions according to the two commonly used dosage methods for children （10 mL or 20 mL 0.9% Sodium chloride injection to prepare the initial ICS solution and draw the required dose from the initial suspension）. The content of IPN was determined by ultra-high performance liquid chromatography-tandem mass spectrometry after parallel processing. The content consistency of solutions in each group was determined according to the coefficient of variation （CV）＜15% of the IPN content. ICS test solution X1 was prepared according to the instructions， and then test solutions X2 and X3 were prepared by diluting X1 with 0.9% Sodium chloride injection in the volume ratios of 1∶1 and 1∶2， which were stored at room temperature （[ 23.0±0.5） ℃]， in a thermostatic water bath at 30 ℃， and in a refrigerator at 2-8 ℃. The stability of the drug solution was determined by the ratio of the IPN mass concentration measured at the specified temperature and time to the initial （0 h） mass concentration （if the ratio was≥90%， it was considered that the drug solution was stable）. RESULTS CV of IPN content was ＜15% in each group of solutions prepared with two manipulation methods by each operator， indicating a small deviation in IPN content. The solutions at the three concentration levels were stable at room temperature for 6 h or refrigerated for 18 h. The test solutions X1 and X2 were also stable when placed at 30 ℃ for 6 h， but the IPN concentration in test solution X3 decreased by about 20% compared with that of 0 h. CONCLUSIONS The consistency of the content of IPN is good in the two commonly used methods for ICS manipulation in children. The stability of ICS solution is affected by concentration， temperature and time. Lower concentrations at higher temperatures resulted in decreased stability of IPN. Clinical attention should be paid to controlling the amount of solvent as well as temperature and time during preparation and use.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

Objective To explore the distribution and types of platelet antibodies in children with positive platelet anti-body in initial screening.Methods Blood samples of 80 pediatric patients who applied for platelet transfusion in our hospi-tal from September 2021 to May 2022 and tested positive for platelet antibodies were identified using the PAKPLUS kit for antibody identification,and the distribution of HLA and HPA antibodies were analyzed.Results Among the 80 reactive samples in initial screening,9 were negative,71 were positive.Among the 71 positive cases,1 was HLA-Ⅰantibody positive(1.41％,1/71),21 were HPA antibody positive(29.58％,21/71),and 49 were both HLA-Ⅰantibody and HPA antibody positive(69.01％,49/71).Among the70 HPA positive cases,23.95％(17/71)had a single HPA antibody,with18.31％(13/71)of anti GP Ⅱb/Ⅲa,2.82％(2/71)of anti GP Ⅰa/Ⅱa,2.82％(2/71)of anti GP Ⅳ and 0％(0/71)of anti GP Ⅰb/Ⅸ,while74.65％(53/71)presented multiple HPA antibodies.No statistically significant difference was found in antibody distribution among age,gender,transfusion history and disease types.Conclusion HLA-Ⅰ antibody combined with HPA antibody are the main types of platelet antibodies among children with positive platelet antibodies.Anti-GPⅡb/Ⅲa accounted for the largest proportion of HPA antibodies.Antibody distribution is not releted to age,gender,history of blood transfusion and disease types.

Objective:To construct the quality evaluation scale of specification of management for humanistic caring in outpatients and test its reliability and validity.Methods:Referring to the group standards in Specification of Management for Humanistic Caring in Outpatients released by the China Association for Life Care,as well as relevant guidelines and literature,a pool of items for the quality evaluation scale of specification of management for humanistic caring in outpatients was formed.After expert consultation and expert argumentation,a quality evaluation scale of specification of management for humanistic caring in outpatients was constructed.From January to February 2024,243 hospital managers from 5 hospitals in Zhengzhou were selected as survey subjects to conduct item analysis,and reliability and validity testing on the scale.Results:Two rounds of expert inquiry and two rounds of expert argumentation were conducted,with questionnaire response rates of 92.00%and 100.00%,respectively,and expert authority coefficients of 0.952.In the second round of the expert inquiry scale,the mean importance score of the first-level indicators was 4.80 to 5.00,the full score ratio was 88.00%to 100.00%,the coefficient of variation was 0.04 to 0.17,and Kendall's coefficient of concordance was 0.857(P＜0.001);the mean importance score of the second-level indicators was 4.60 to 5.00,the full score ratio was 80.00%to 100.00%,the coefficient of variation was 0.00 to 0.21,and Kendall's coefficient of concordance was 0.775(P＜0.001);the mean importance score of the third-level indicators was 4.60 to 5.00,the full score ratio was 76.00%to 100.00%,the coefficient of variation was 0.00 to 0.21,and Kendall's coefficient of concordance was 0.830(P＜0.001).Finally,a quality evaluation scale of specification of management for humanistic caring in outpatients was formed,including 5 first-level indicators,25 second-level indicators,and 58 third-level indicators.Exploratory factor analysis produced 5 common factors with a cumulative variance contribution rate of 74.628%.The Pearson correlation coefficients between the five-factor scores ranged from 0.648 to 0.798,and the correlation coefficients between the factor scores and the total score of the scale ranged from 0.784 to 0.938.The scale-level content validity index(S-CVI)of the scale was 0.945,the item-content validity index(I-CVI)was 0.725 to 1.000,the Cronbach's alpha coefficient of the total scale was 0.973,and the retest reliability coefficient was 0.934.Conclusion:The constructed quality evaluation scale of specification of management for humanistic caring in outpatients has good scientific validity and reliability,and can be used as an evaluation tool for specification of management for humanistic caring in outpatients.

Objective:To assess the feasibility of wavelet index (WLI) in monitoring the depth of sedation with propofol in pediatric patients.Methods:This was a prospective observational trial. One hundred and sixty-five pediatric patients, aged >1-12 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective surgery requiring general anesthesia with endotracheal intubation or laryngeal mask airway from July to December 2016 in our hospital, were divided into 11 age groups ( n=15 each): >1-2 yr group, >2-3 yr group, >3-4 yr group, >4-5 yr group, >5-6 yr group, >6-7 yr group, >7-8 yr group, >8-9 yr group, >9-10 yr group, >10-11 yr group, and >11-12 yr group. General anesthesia was induced by injection of propofol 3 mg/kg for more than 30 s. WLI and BIS values were recorded immediately before administration and at 30, 40, 50, 60, 90, 120, 180 and 240 s after the end of administration. If there were differences among age groups, age groups with no statistically significant differences were combined and re-grouped. Pearson linear correlation analysis and Bland-Altman consistency analysis were performed. Results:A total of 149 pediatric patients were actually included. There were no significant differences in BIS values between 4 groups aged > 1-5 yr and between 7 groups aged > 5-12 yr ( P>0.05). Regrouping was performed based on the aforementioned results, 4 groups of children aged > 1-5 yr were divided into > 1-5 yr group ( n=60), and 7 groups of children aged > 5-12 yr were divided into > 5-12 yr group ( n=89). WLI values and BIS values were significantly decreased at each time point after administration compared with immediately before administration in group aged > 1-5 yr and in group aged >5-12 yr ( P<0.05). The BIS values were the lowest at 60 s after the end of the administration, and the WLI values were the lowest at 120 and 180 s after the end of the administration in two groups ( P<0.05). There were no statistically significant differences between WLI values and BIS values at 90 s and 240 s after the end of the administration ( P>0.05), and there was statistically significant difference at the other time points in group aged > 1-5 yr ( P<0.05). There was no significant difference between WLI values and BIS values at 180 s and 240 s after the end of the administration ( P>0.05), but there were significant differences at the other time points in group aged > 5-12 yr ( P<0.05). The Pearson correlation coefficients between WLI values and BIS values were 0.61 and 0.56 in group aged > 1-5 yr and group aged > 5-12 yr, respectively ( P<0.001). Bland-Altman agreement analysis: In group aged > 1-5 yr and group aged > 5-12 yr, the 95% agreement limits were -0.484-0.621 and -0.551-1.015, respectively, and there were 4.6% (23/504) and 5.1% (40/777) of the points outside the 95% agreement limits, respectively, and both limits exceeded the clinically acceptable range. Conclusions:WLI is feasible for monitoring the depth of sedation with propofol in pediatric patients aged > 1-12 yr, but the accuracy is lower than BIS.

The α-amino acid ester acyltransferase (SAET) from Sphingobacterium siyangensis is one of the enzymes with the highest catalytic ability for the biosynthesis of l-alanyl-l-glutamine (Ala-Gln) with unprotected l-alanine methylester and l-glutamine. To improve the catalytic performance of SAET, a one-step method was used to rapidly prepare the immobilized cells (SAET@ZIF-8) in the aqueous system. The engineered Escherichia coli (E. coli) expressing SAET was encapsulated into the imidazole framework structure of metal organic zeolite (ZIF-8). Subsequently, the obtained SAET@ZIF-8 was characterized, and the catalytic activity, reusability and storage stability were also investigated. Results showed that the morphology of the prepared SAET@ZIF-8 nanoparticles was basically the same as that of the standard ZIF-8 materials reported in literature, and the introduction of cells did not significantly change the morphology of ZIF-8. After repeated use for 7 times, SAET@ZIF-8 could still retain 67% of the initial catalytic activity. Maintained at room temperature for 4 days, 50% of the original catalytic activity of SAET@ZIF-8 could be retained, indicating that SAET@ZIF-8 has good stability for reuse and storage. When used in the biosynthesis of Ala-Gln, the final concentration of Ala-Gln reached 62.83 mmol/L (13.65 g/L) after 30 min, the yield reached 0.455 g/(L·min), and the conversion rate relative to glutamine was 62.83%. All these results suggested that the preparation of SAET@ZIF-8 is an efficient strategy for the biosynthesis of Ala-Gln.
Escherichia coli/genetics* ; Glutamine ; Zeolites/chemistry* ; Amino Acids

ObjectiveTo investigate the relationship between lower limb muscle strength and walking speed in older adults, and to analyze the mediating role of flexibility and dynamic balance. MethodsFrom November to December, 2021, a total of 155 older adults at the Shanghai Senior Sports and Health Home were included. Their basic health information was collected, and the lower limb muscle strength, flexibility, dynamic balance and walking speed were tested. A mediated effects analysis was conducted. ResultsThere was a pairwise correlation among lower limb muscle strength, flexibility, dynamic balance and walking speed in older adults (r > 0.210, P < 0.01). In the mediated effects model, after controlling for age and gender, lower limb muscle strength did not directly predict walking speed in older adults (β = 0.029, P = 0.699), however, lower limb muscle strength could influence walking speed through the partial mediation of dynamic balance (effect = 0.0130, 95% CI 0.0073~0.0197) and the chain mediation of lower flexibility and dynamic balance (effect = 0.0019, 95% CI 0.0003~0.0043). ConclusionLower limb muscle strength can indirectly affect walking speed in older adults through the mediators of flexibility and dynamic balance, or the dynamic balance alone.

OBJECTIVES: This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS: Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS: Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p<0.05). Diabetes, hypertension, and kidney disease were also associated with higher glaucoma risk, while dyslipidemia was associated with lower risk (all p<0.05). After the model was adjusted for demographic, socioeconomic, and health-related variables, obesity was significantly associated with a 10.2% decrease in glaucoma risk according to the Cox proportional hazards model (hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.97) and an 11.8% risk reduction in the multivariate logistic regression analysis (odds ratio, 0.88; 95% CI, 0.80 to 0.97). A further subgroup analysis showed that obesity was associated with a reduced risk of glaucoma in people living in rural areas, in smokers, and in those with kidney disease (all p<0.05). Obesity also reduced glaucoma risk in people with diabetes, hypertension, or dyslipidemia more than in healthy controls (all p<0.05). CONCLUSIONS This cohort study suggests that obesity was associated with a reduced risk of glaucoma, especially in rural residents, smokers, and people with kidney disease. Obesity exerted a stronger protective effect in people with diabetes, hypertension, or dyslipidemia than in healthy people.

Objective:This study aimed to explore the application of interaction-dependent fucosyl-biotinylation (FucoID), a chemical biology-based proximity labeling technique, in capturing tumor antigen-specific T cells and its clinical value in chronic myelogenous leukemia (CML) .Methods:Flow cytometry and fluorescence microscopy were employed to evaluate the experimental parameters for FucoID in CML. Peripheral blood samples were obtained from 14 newly diagnosed CML patients in the chronic phase. These samples underwent flow cytometry-based sorting and were subsequently labeled with FucoID to facilitate the isolation of tumor cells and T cells, followed by the immunophenotypic identification of tumor antigen-specific T cells. Finally, the diagnostic and therapeutic potential of FucoID in CML was assessed.Results:Initially, the experimental parameters for FucoID in CML were established. The proportion of CD3 + T cells in patients was (8.96±6.47) %, exhibiting a marked decrease compared with that in healthy individuals at (38.89±22.62) %. The proportion of tumor-specific antigen-reactive T cells was (3.34±4.49) %, which demonstrated interpatient variability. In addition, the proportion of tumor-specific antigen-active T cells in CD4 + T cells was (3.95±1.72) %, which was generally lower than the proportion in CD8 + T cells at (5.68±2.18) %. Compared with those in tumor-specific antigen-nonreactive T cells, CCR7 -CD45RA - effector memory T cells and CCR7 -CD45RA + effector T cells were highly enriched in tumor-specific antigen-reactive T cells. Moreover, the intensity of tumor immune reactivity in patients exhibited a significant correlation with white blood cell count (WBC) and hemoglobin (HGB) levels in peripheral blood, while no such correlation was observed with other clinical baseline characteristics. Conclusion:The combination of FucoID and flow cytometry enables the rapid identification and isolation of tumor antigen-specific T cells in CML. The successful application of this method in CML and the implications of our findings suggest its potential clinical value in the field of hematologic malignancies.