Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

SARS-CoV-2 has posed a significant threat to a subset of the patient population.The occurrence of hematological malignancies and tumor treatment can lead to immunosuppression in patients,which significantly increases the risk of serious complications,severe incidence and mortality after SARS-CoV-2 infection.The treatment of a patient with follicular lymphoma infected with SARS-CoV-2 was described in detail.The patient remained positive for RT-PCR tests during the hospitalization for nearly 90 days.After undergoing 5 rounds of antiviral treatment,along with glucocorticoid anti-inflammatory therapy,low-molecular-weight heparin for anticoagulation,antibiotics for infection control,and respiratory support through the use of a ventilator,the patient eventually obtained negative result of the RT-PCR test.Subsequently,the patient was successfully weaned from mechanical ventilation and discharged.By summarizing the treatment process of this case,we hoped to provide reference and experience for future clinical diagnosis and treatment.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective To understand the epidemiological and clinical characteristics of healthcare-associated infec-tion(HAI)in neonates with different gestational ages and birth weights,and provide guidance for personalized cli-nical diagnosis and treatment.Methods According to the inclusion and exclusion criteria,240 neonates with HAI in the neonatal intensive care unit(NICU)of a hospital in Handan City from January 2018 to December 2022 were selected as the study group,720 neonates without HAI were selected as the control group based on systematic sam-pling method with a ratio of 1∶3.The incidence of HAI,distribution characteristics of infection site,pathogenic features of HAI,as well as the effect of different delivery modes on HAI in neonates with different gestational ages and birth weights were analyzed.Results Neonates with gestational age＜28 weeks and birth weight＜1 000 g had the highest incidence of HAI,which were 19.48％and 20.41％,respectively.Among neonates with gestational age＜28 weeks,unidentified site infection were the most(37.50％),while in all gestational age groups within 28-36+6 weeks,bloodstream infection(BSI)and respiratory system infection were predominant.For neonates with gestational age ≥37 weeks,BSI and unidentified site infection occurred frequently.Among neonates in all weight groups,BSI was the most frequent,followed by respiratory system infection.Pathogens from different sites of in-fections in neonates with different gestational ages and birth weights varied.Among neonates with gestational age of 28-31+6 weeks and birth weight of 1 000-1 499 g,the constituent of birth modes showed statistically significant difference between neonates with and without HAI(both P＜0.05).Conclusion Epidemiological and clinical chara-cteristics of HAI in neonates with different gestational ages and birth weights are different.For the prevention and control of HAI,individualized diagnosis and treatment plans should be developed to achieve precise prevention and control,reduce the incidence of HAI,and improve the overall treatment level of neonates.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Interleukin-11(IL-11)is a multifunctional cytokine that plays a crucial role in various bio-logical processes,including the promotion of hematopoiesis,regulation of the immune system,and facili-tation of tissue repair.These functions highlight its significant importance in both medical research and clinical therapy.Consequently,the precise detection and assessment of IL-11's biological activity are es-sential.The currently employed cell proliferation inhibition assay is cumbersome,time-consuming,and susceptible to interference from Interleukin-6.Here we study the JAK-STAT signaling pathway,a key mechanism of IL-11 actions.We initially establish a stable monoclonal cell line that expresses a luciferase reporter gene responsive to IL-11.We subsequently optimized critical parameters,including the pre-dilu-tion concentration and gradient of IL-11,cell inoculum size,and IL-11 incubation duration.Comprehen-sive validation was undertaken to evaluate accuracy,precision,specificity,stability,and concordance with pharmacopeial methods,ultimately leading to the establishment of a novel reporter gene-based ap-proach for detecting the biological activity of IL-11.This innovative method significantly enhances the de-tection accuracy and sensitivity while reducing the testing time,thereby offering promising prospects for broad applications.

Objective:To analyze the prognostic nutritional index(PNI),controlling nutritional status(CONUT)and fibrinogen/albumin ratio(FAR)levels in elderly patients with multiple myeloma(MM)and their prognostic impact.Methods:The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed.The optimal cut-off values for PNI,CONUT score and FAR were obtained by receiver operating characteristic(ROC)curve,which were used for grouping patients.The correlation of above three indexes with clinical parameters such as sex,serum calcium(Ca),β2-microglobulin(β2-MG),serum creatinine(Cr)in elderly MM patients were analyzed.The survival rates of patients with different levels of each index were compared.Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed.Results:The optimal cut-off values for PNI,CONUT score and FAR were 39.775,3.5 and 0.175,respectively,according to which the patients were divided into high and low group.Statistical analysis showed that there were significant differences in albumin level among different groups(all P＜0.05).In addition,there was a significant difference in hemoglobin between high-PNI group and low-PNI group(P＜0.05),while in sex distribution between high-FAR and low-FAR group(P＜0.05).The survival rate of elderly MM patients with increased PNI,decreased CONUT score and FAR was higher(all P＜0.05).Univariate and multivariate analysis showed that β2-MG,Cr,PNI,CONUT score and FAR were independent prognostic factors for elderly MM patients.Conclusion:PNI,CONUT score and FAR are related to some clinical indicators of elderly MM patients,and have an impact on the prognosis.

Objective:To analyze the clinical characteristics and occurrence of thrombotic/bleeding events of patients with myeloproliferative neoplasm(MPN),and explore the main influencing factors,and create a risk prediction.Methods:The clinical data of 126 MPN patients with BCR-ABL fusion gene negative in the Department of Hematology of Gansu Provincial Hospital from January 2016 to September 2021 were collected,and their clinical characteristics,occurrence of thrombotic/bleeding events and main influencing factors were analyzed and summarized retrospectively.Then,a risk prediction model for thrombotic/bleeding events in MPN patients was constructed.Results:Among 126 MPN patients,50 patients(39.7％)had experienced thrombotic/bleeding events,including 44 patients(34.9％)with thrombotic events and 6 patients(4.8％)with bleeding events.Among thrombotic diseases,cerebral thrombosis was the most common(23/44,52.3％),followed by 9 cases of limb artery thrombosis mainly characterized by finger and toe tip artery ischemia,occlusion and gangrene(9/44,20.5％).Bleeding events included intracerebral hemorrhage and gastrointestinal hemorrhage.Univariate analysis showed that hypertension,hyperhomocysteinemia,white blood cell(WBC)≥10 × 109/L,hematocrit(HCT)≥49％,platelet(PLT)≥600 × 109/L and JAK2V617F gene mutation were risk factors for thrombotic/bleeding events in MPN patients,while CALR gene mutation was a protective factor.Multivariate analysis showed that hypertension and PLT ≥ 600 × 109/L were independent risk factors for thrombotic/bleeding events in MPN patients.The goodness of fit of the constructed risk prediction model was 0.872,and the area under the ROC curve was 0.838.The model was validated with clinical data,the sensitivity,specificity and accuracy was 78.85％,87.83％and 84.13％,respectively.Conclusion:The risk of thrombotic/bleeding events in MPN patients with high WBC count,hypertension and hyperhomocysteinemia is higher.Controlling hypertension and hyperhomocysteinemia and reducing WBC and PLT counts are helpful to prevent thrombotic/bleeding events and improve the life quality of patients.

Objective: To compare the effects of the China Children's Asthma Action Plan (CCAAP)-based remote joint management model with traditional management model on the control of childhood asthma. Methods: A retrospective cohort study was conducted to analyze the general data and asthma control assessment data of 219 children with asthma who attended the respiratory department of Guangzhou Women's and Children's Medical Center from April 2021 to October 2021 and were followed up for 1 year or more. According to the follow-up management model, the CCAAP-based remote joint management model was used in the observation group and the traditional management model was used in the control group, and the propensity score matching method was applied to match the data of children in the two management models for comparison. Paired-samples t-test, Wilcoxon signed-rank test, McNemar χ²-test or χ²-test or nonparametric tests were used to compare the general data and asthma control assessment data between the two matched groups of children. Results: Among 219 children with asthma, 145 were male and 74 were female, aged at consultation (7.2±2.4) years. There were 147 cases in the observation group and 72 cases in the control group, and 27 cases in each of the observation and control groups were successfully matched. The number of asthma exacerbation aura, acute exacerbations, and emergency room visits or hospitalizations for asthma exacerbations were lower in the observation group than in the control group after pairing (1 (0, 2) vs. 3 (1, 5) times, 0 (0,0) vs. 0 (0, 1) times, 0 (0,0) vs. 1 (0, 1) times, Z=-3.42, -2.58, -3.17, all P<0.05). The use of peak flowmeters was higher in children aged 5 years and older in the observation group than in the control group after pairing (100% (22/22) vs. 13% (3/23), χ²=54.00,P<0.001). The ratio of actual to predicted 1st second expiratory volume of force after follow-up in the observation group after pairing was higher than that before follow-up in the observation group and after follow-up in the control group ((95±11)% vs. (85±10)%, (95±11)% vs. (88±11)%, t=-3.40, 2.25, all P<0.05). The rate of complete asthma control after follow-up was higher in both the observation and control groups after pairing than before follow-up for 12 months in both groups (93% (25/27) vs. 41% (11/27), 52% (14/27) vs. 41% (11/27), H=56.19, 45.37, both P<0.001), and the rate of complete control of asthma in children in the observation group was higher than that in the control group at 3 and 12 months of follow-up management (56% (15/27) vs. 25% (5/20), 93% (25/27) vs. 52% (14/27), χ²=47.00, 54.00, both P<0.001). The number of offline follow-up visits, inhaled hormone medication adherence scores, and caregiver's asthma perception questionnaire scores were higher in the observation group than in the control group after pairing (6 (4, 8) vs. 4 (2,5), (4.8±0.3) vs. (4.0±0.6) score, (19.3±2.6) vs. (15.2±2.7) score, Z=6.58, t=6.57, 5.61, all P<0.05), and the children in the observation group had lower school absences, caregiver absences, asthma attack visit costs, and caregiver PTSD scores than the control group (0 (0,0) vs.3 (0, 15) d, 0 (0,0) vs. 3 (0, 10) d, 1 100 (0, 3 700) vs. 5 000 (1 000, 10 000) yuan, 1.3 (1.1, 1.9) vs. 2.0 (1.2, 2.7) score, Z=-2.89, -2.30, 2.74, 2.73, all P<0.05). Conclusion: The CCAAP-based joint management model of asthma control is superior to the traditional management model in the following aspects: it can effectively improve asthma control, self-monitoring, and lung function in children; it can improve treatment adherence and caregivers' asthma awareness; and it can reduce the duration of absenteeism from school, the cost of asthma exacerbation visits, and caregiver's negative psychology.
Humans ; Child ; Female ; Male ; Retrospective Studies ; Asthma/therapy* ; China ; Hospitalization ; Hospitals

It is of great significance to apply the nanocrystals self-stabilized Pickering emulsion (NSSPE) to traditional Chinese medicine (TCM) compounds, and to study the effect of NSSPE on the oral absorption of various components with different solubility and permeability. In the study, NSSPE of Tongmai prescription was prepared by the high pressure homogenization method with nanocrystals of main active components (puerarin, ferulic acid, salvianolic acid B and tanshinone IIA) of Tongmai prescription as solid particle stabilizers and a mixture of Ligusticum chuanxiong essential oil and Labrafil M 1944 CS as oil phase. The NSSPE had better physical stability than nanocrystals suspension and blank emulsion. The adsorption of nanocrystals on the surface of oil droplets was confirmed by scanning electron microscopy and fluorescence microscopy. The surface adsorption rates of puerarin, ferulic acid, salvianolic acid B and tanshinone ⅡA in NSSPE were 15.40% ± 3.19%, 15.39% ± 5.07%, 10.97% ± 3.70% and 31.51% ± 1.60%, respectively. When solid active components were prepared into nanocrystals suspension, the cellular uptake and transport across Caco-2 cells were increased significantly for puerarin and tanshinone IIA. The uptake rates of ferulic acid, ligustilide and tanshinone IIA in NSSPE were further increased compared with the physical mixture of nanocrystals suspension and oil, and the transports of ligustilide and tanshinone IIA were also significantly improved. The main absorption mechanisms of NSSPE were passive diffusion and caveolin-mediated endocytosis, which were determined mainly by the microstructure of NSSPE. In conclusion, NSSPE could be applied to complicated TCM. The "micro" and "nano" synergistic microstructure with drug nanocrystals adsorbed on the surface of micron-sized oil droplets could not only improve the physical stability of NSSPE, but also promote the absorption of various components in NSSPE, which made NSSPE a promising oral drug delivery system for TCM.