Formulation and technology of oxymatrine-astragaloside IV coloaded liposomes based on quality by design / 药学学报

To optimize the formulation and technology of oxymatrine-astragaloside IV coloaded liposomes (Om-As-Lip) based on quality by design (QbD) principles, and further to verify the feasibility of its amplification process, Om-As-Lip was prepared by ethanol injection combined with pH gradient method. The critical material attributions of Om-As-Lip were evaluated by dual-risk analysis tools and Plackett-Burman design (PBD). The formulation of Om-As-Lip was further optimized with the Box-Behnken design (BBD). The design space was also established based on the contour plots of BBD. In order to further investigate the amplification process of Om-As-Lip, the critical process parameters of high-pressure homogenization (HPH) were optimized by single-factor test, and the quality of the final product was also evaluated. The results of risk analysis and PBD confirmed that the astragaloside concentration, cholesterol concentration, and phospholipid ratio (HSPC∶SPC) were the ctitical material attributes. The model established by BBD had a good predictability, and the optimized mass ratio of As to phospholipids was 1∶40, cholesterol to phospholipids was 1∶10, HSPC to SPC was 51∶9. The design space of Om-As-Lip was as follows: the ratio of cholesterol to phospholipids was 1∶12-1∶5 and HSPC to SPC was 1∶7-17∶3. The optimized high-pressure homogenization pressure was 600 bar, temperature was 4 ℃, and cycle times was 6 times for HPH-Om-As-Lip. The quality of Om-As-Lip prepared based on the QbD concept can meet the expected CQAs, and the formulation and technology established can provide a reliable experimental basis for its future development and applications.

Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy / 中国药房

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Study of miR-506 in M2 macrophage polarization and immune intervention in pancreatic cancer mice / 中华肝胆外科杂志

Objective:To analyze the effect of microRNA-506 (miR-506) on M2 macrophages polarization and immune intervention in pancreatic cancer mice.Methods:Macrophages from peripheral blood of healthy volunteers were cultured in vitro, polarized into M1 or M2 type macrophages, and transfected with miR-506 or control sequence (miR-ctrl), respectively. Polarized macrophages from M1+ miR-ctrl group, M1+ miR-506 group, M2+ miR-ctrl group and M2+ miR-506 group were collected. The relative expression of marker genes of M1 and M2 type macrophages of four groups were analyzed by qRT-PCR. The characteristic functions of M1 and M2 type macrophages of four groups were also detected, such as phagocytosis and nitric oxide (NO) synthesis (characteristic function of M1 type macrophages), arginase 1 activity and the secretion of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), interleukin-10 (IL-10) (characteristic function of M2 type macrophages). Sixty healthy male C57BL/6 mice without specific pathogen, weighing 20-25 g, were randomly divided into miR-ctrl programmed death-1 (PD-1) group, miR-506 PD-1 group, miR-ctrl iso group, and miR-506 iso group. They were injected with miR-506, miR-ctrl, PD-1 antibodies, and isotype control antibodies, with 15 in each group. The tumor volume, tumor weight, Ki-67 and interferon γ expression were analyzed three weeks later. Results:Compared with M2+ miR-ctrl group, the relative expression of M1 type macrophage marker genes increased, and the relative expression of M2 type macrophage marker genes decreased in M2+ miR-506 group, with significant difference (all P<0.05). Compared with M2+ miR-ctrl group, the phagocytic function and NO synthesis of macrophages in M2+ miR-506 group increased, the activity of arginase 1 and the secretion of VEGF, TGF-β and IL-10 decreased, with significant difference (all P<0.05). There was no significant differences in tumor weight, volume, Ki-67, and interferon γ expression between miR-ctrl iso and miR-ctrl PD-1 group (all P>0.05). The tumor weight, tumor volume and Ki-67 in miR-506 PD-1 group were lower than those in miR-ctrl PD-1 group [(0.32±0.13) g vs (0.85±0.24) g; (0.72±0.23) cm 3 vs (2.03±0.21) cm 3; (25.9±10.3)% vs (55.6±12.5)%], while interferon-γ expression was significantly higher than that in miR-ctrl PD-1 group [(122.4±15.3) ng/g vs (82.4±22.2) ng/g] (all P<0.05). Conclusion:miR-506 inhibits the polarization of M2 macrophages and increases the anti PD-1 immunotherapy sensitivity in pancreatic cancer.

Construction of human TCRP1 gene knockout chronic myeloid leukemia K562 cell line using CRISPR/Cas9 technology and its biological function detection / 中国医师杂志

Objective:To select human chronic myeloid leukemia (CML) cell line K562 as the experimental object, and use lentivirus mediated CRISPR/Cas9 gene editing technology to construct a stable CML cell line K562/TCRP1-KO that knocks out the tongue cancer resistance related protein 1 (TCRP1) gene; and through functional tests such as cell proliferation, apoptosis, and drug sensitivity, compare the phenotypic differences between K562/TCRP1-KO and control cells (K562/cas9-CTL), and preliminarily explore the possible mechanism of TCRP1 gene involvement in the pathogenesis of CML.Methods:The small guide RNA (sgRNA) targeting TCRP1 was designed at a specific location. After annealing, the oligonucleotide fragments were recombined with the linearized Cas9 expression vector, and the lentivirus packaging system was transfected into 293T cells. The purified virus was collected and infected with K562 cells. Positive polyclons were screened for puromycin pressure, and monoclonal K562/TCRP1-KO was further screened by limited dilution method. Stable cell lines were successfully knocked out by sanger sequencing and Western blot detection; Simultaneously, K562 cells transfected with lentiCRISPR vector were constructed as control cell lines (K562/cas9-CTL); Using cell counting method, cell counting kit 8 (CCK8) method, imatinib (IM) gradient dilution method, and flow cytometry cell proliferation, drug sensitivity, and apoptosis analysis were performed on K562/TCRP1-KO and K562/cas9-CTL, respectively.Results:The sgRNA-Cas9 recombinant plasmid vector for TCRP1 knockout was successfully constructed, and after transfection into 293T cells, TCRP1 knockout monoclonal cell lines were successfully screened using limited dilution method. Compared with K562/cas9-CTL cells, the proliferation ability of K562/TCRP1-KO cells was significantly reduced, IM drug sensitivity was significantly enhanced, and the process of cell apoptosis was significantly accelerated (all P<0.05). Conclusions:A CML cell line with TCRP1 knockout was successfully constructed using CRISPR/Cas9. TCRP1 may act as a cancer related gene to affect the proliferation, IM resistance, and apoptosis process of CML cells.

Related factors of acute exacerbation of chronic obstructive pulmonary disease and the value of inhaled glucocorticoid guided by eosinophil in peripheral blood / 中国医师杂志

Objective:To explore the risk factors of acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) and whether Eosinophil (EOS) in peripheral blood can guide the treatment of inhaled corticosteroids (ICS).Methods:This study was a single center, Prospective cohort study. The subjects of this study were from stable COPD patients who were treated in the Department of Respiratory Medicine of the Xiangya Second Hospital of Central South University from January 2020 to December 2021. Patient general information, past year AE status, exposure risk factors, modified version of the British Medical Research Council Respiratory Difficulty Questionnaire (mMRC) score, Chronic Obstructive Pulmonary Disease Assessment Questionnaire (CAT) score, ICS usage, lung function, blood routine, etc. were collected. We followed up the patient for one year. During the follow-up period, the clinical characteristics of patients with and without AE were compared to analyze the correlation between blood EOS and ICS use.Results:The median blood EOS of 617 stable COPD patients was 0.13×10 9/L, 289 patients (46.8%) with chronic obstructive pulmonary disease had a history of AE, and 207 patients (33.5%) experienced AE during 1-year follow-up. The results of univariate analysis showed that the future occurrence of AE in COPD was correlated with body mass index (BMI), AE history, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading, GOLD grouping, mMRC score, and CAT score (all P<0.05). The results of logistic multiple factor regression analysis showed that patients with BMI<24 kg/m 2, AE in the past year, severe AE in the past year, smoking history and other exposure factors, GOLD level 2 or above, GOLD C and D groups, and mMRC score≥ 2 had a higher risk of future AE (all P<0.05). There was no statistically significant difference in the incidence of AE between patients with COPD with different levels of EOS and those without ICS during a 1-year follow-up period (all P>0.05). Conclusions:The past 1-year AE history, BMI, exposure risk factors, degree of airflow restriction, and respiratory symptoms of patients with chronic obstructive pulmonary disease can predict future AE risk. There is no significant difference in future AE risk among patients with different levels of EOS, and EOS cannot guide ICS treatment to reduce AE risk.

Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors / 药物分析学报

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

Study on the mechanism of VEGF inducing tolerogenic dendritic cells in oral squamous cell carcinoma / 口腔医学

Objective@#To investigate the mechanism of vascular endothelial growth factor(VEGF) inducing tolerogenic dendritic cells(DCs) in oral squamous cell carcinoma (OSCC).@*Methods@#The DCs were divided into four groups: Control group (DC), VEGF group (VEGF added into DC), Co-culture group (DC co-cultured with SCC7) and Anti-VEGF group (anti-VEGF antibody added into DC co-cultured with SCC7). Flow cytometry (FCM) was used to detect DC surface markers. To detect the effect of DC on proliferation activity of T lymphocyte, the experiment included five groups: Nc group (T lymphocyte), Control group (T lymphocyte added into DC), VEGF group (T lymphocyte + DC + VEGF), Co-culture group (T lymphocyte + DC + supernatant of SCC7) and Anti-VEGF group (T lymphocyte + DC + supernatant of SCC7 + anti-VEGF antibody). Subsequently, the mixed lymphocyte reaction(MLR) was conducted. The expression levels of indole-2, 3-doxygenase(IDO)and programmed cell death 1 ligand 1(PD-L1)in DC were detected by western blot, real time PCR and FCM respectively. For the cytotoxic lymphocyte (CTL) assay, SCC7 cells and CTLs were mixed and CTL-mediated SCC7 cells cytotoxicity was tested. The experiment included four groups: Control group (T lymphocyte + DC), IDO inhibition group (T lymphocyte + DC + IDO inhibitor), Anti-PD-L1 antibody group (T lymphocyte + DC + anti-PD-L1 antibody) and Combination group (T lymphocyte + DC + IDO inhibitor + anti-PD-L1 antibody). The SCC7 tumor-bearing mice treated with IDO inhibitor and the anti-PD-L1 antibody were sacrificed and the tumor inhibition rate and the spleen index were determined. @*Results@#Compared with Control group, exogenous VEGF or SCC7 co-culture inhibited the relative number of DC expressing CD11C, CD80, CD86, CD40 and MHC Ⅱ. The positive DCs were increased in the Anti-VEGF group compared with VEGF or Co-culture group. In VEGF or Co-culture group, the number of T cells stimulated by SCC7-pulsed DCs was decreased compared with Control group. However, the ability of Anti-VEGF group to induce T cell proliferation was significantly increased compared with VEGF or Co-culture group. Significantly increased expression of IDO and PD-L1 were observed in VEGF and Co-culture group. However, this was partially reversed by addition of anti-VEGF antibody into the co-culture system. Compared with Control group, the expressions of CD11C and CD86 in DC in both the IDO inhibition group and Anti-PD-L1 antibody group were increased, and were significantly higher in the Combination group compared with the single drug groups. The similar results were exhibited in MLR and CTL assay. In vivo, the results revealed that the tumors obtained from the mice in three experimental groups were smaller than those in the control group. Furthermore, the tumor volume of the Combination group was the smallest. The spleen index of each group was calculated and the results showed the spleen index of the three experimental groups was significantly higher than that of Control group.@*Conclusion@#VEGF in OSCC micro-environment inhibits the maturation and function of DC that are transformed into tolerogenic DC by high expression of IDO and PD-L1.

Oral mucosal drug delivery system based on nano technology / 药学学报

Oral mucosal drug delivery has the advantages of rapid drug absorption, no first-pass effect and good patient compliance. However, factors such as low drug dissolution, saliva carrying the drug into the gastrointestinal tract and the existence of physiological barriers in the mucosa may affect the mucosal permeation and bioavailability of the drug. Nanotechnology applied to drug oral mucosa delivery can overcome the above disadvantages and obtain efficient absorption effect. This paper describes the physiological structure of oral mucosa and the factors affecting the absorption of drugs in oral mucosa, reviews the application of nanotechnology such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, polymer nanoparticles, polymer micelles and nanohybrid suspensions in oral mucosal drug delivery and the mechanism of promoting drug absorption, summarizes the main problems of current research, and gives an outlook on the application of nano oral mucosal drug delivery system. The main problems of current research are summarized, and the prospects for the application of nano oral mucosal drug delivery systems are discussed.

Investigation and analysis of radiation doses to CT examinees in 11 medical institutions in Shijiazhuang, China / 中国辐射卫生

Objective To investigate radiation doses to examinees undergoing computed tomography (CT) scanning of different body parts (the head, chest, and abdomen) in medical institutions of Shijiazhuang, China, and to provide a reference for optimizing radiation protection for examinees in medical institutions. Methods March 2021 to March 2022, eleven medical institutions of radiation monitoring in Shijiazhuang were surveyed for the basic information, scanning parameters, and dosimetric data of a total of 930 adults and children who received CT examinations. The dosimetric data of the subjects were analyzed and compared with the domestic and international diagnostic reference levels and the results of other cities in China. Results In the above hospitals, the CTDIvol(P50) of CT subjects in children's group were 17.42-50.45 mGy, 2.13-14.01 mGy and 3.58-28.20 mGy, respectively. DLP(P50) ranges from 228.87 to 966.97 mGy·cm, 33.20 to 296.03 mGy·cm, and 74.90 to 926.53 mGy·cm, respectively. In the adult group, the CTDIvol(P50) in the head, chest and abdomen of CT subjects were 37.28-54.05 mGy, 6.43-14.99 mGy and 8.28-18.75 mGy, respectively. DLP(P50) ranges from 372.81 to 630.56 mGy·cm, from 219.77 to 467.93 mGy·cm, and from 313.86 to 689.87 mGy·cm, respectively. The distribution of radiation doses in different-grade hospitals varied greatly. The abdomen dose of the children's hospital was higher than other hospitals. Especially the primary hospitals were significantly higher than the recommended diagnostic reference level (DRL). Conclusion In some secondary and primary hospitals, the setting of CT scanning parameters was simplified, not specific to the subjects’ age and body types. They should strictly comply with the principal of optimizing radiation protection to strengthen radiation dose optimization and supervision, reducing the radiation dose of examinees in future examinations .

Effect of three-dimensional motion platform training on balance and walking function of stroke patients / 中国康复理论与实践

ObjectiveTo explore the clinical efficacy of three-dimensional motion platform training on balance and walking function of stroke patients. MethodsFrom August, 2021 to August, 2022, 80 stroke patients from Second Affiliated Hospital of Guangzhou Medical University were selected and randomly divided into control group (n = 40) and experimental group (n = 40). The control group received routine rehabilitation training, and the experimental group received three-dimensional motion platform training on the basis of routine rehabilitation training. Before and four weeks after treatment, the Berg Balance Scale (BBS), Functional Ambulation Category (FAC) and 3D gait analysis (step speed, step frequency, percentage of standing phases on the affected side, percentage of double support phase) were used to assess the balance and walking function of patients. ResultsFour weeks after treatment, the scores of BBS, FAC, and step speed, step frequency, percentage of standing phases on the affected side and percentage of double support phase significantly improved in both groups (|t| > 4.423, |Z| > 5.292, P < 0.001), and they were better in the experimental group than in the control group (|t| > 3.748, |Z| = 2.646, P < 0.05). ConclusionThree-dimensional motion platform training could facilitate to improve the balance and walking function of stroke patients.

Efficacy and safety of olaparib in adjuvant therapy of BRCA1/2 mutated HER2-negative breast cancer：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of olaparib in adjuvant therapy of breast cancer susceptibility gene （BRCA） 1/2 mutated human epidermal growth factor receptor 2 （HER2）-negative breast cancer， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， ScienceDirect， the Cochrane Library and Embase databases， randomized controlled trials about adjuvant therapy of olaparib （trial group） versus adjuvant therapy of other drugs （control group） were collected. After literature screening and data extraction， meta-analysis， publication bias analysis and sensitivity analysis were performed by using RevMan5.4 software. RESULTS A total of 5 randomized controlled trials were included， with a total of 2 633 patients， including 1 495 cases in trial group and 1 174 cases in control group. Meta-analysis showed that in terms of efficacy， compared with control group， overall survival [HR＝1.02， 95%CI （1.01，1.03）， P＝0.000 8] and progression-free survival [HR＝1.78， 95%CI（1.46，2.17）， P＜0.000 01] were longer significantly in the trial group. In terms of safety， compared with the control group， the incidence of adverse drug reactions at any level in the trial group was higher [RR＝1.41， 95%CI （1.12， 1.78）， P＝0.004]， while there was no statistically significant difference in the incidence of adverse drug reactions above level 3 between the two groups [RR＝1.75， 95%CI （0.82， 3.74）， P＝0.15]. The results of publication bias indicated that the possibility of publication bias in this study was relatively low. The results of sensitivity analysis showed that the results obtained in this study were robust. CONCLUSIONS Compared with patients without adjuvant therapy of olaparib， adjuvant therapy of olaparib can prolong overall survival and progression-free survival of patients with BRCA1/2 mutated HER2-negative breast cancer，but the risk of adverse drug reactions is relatively high.

Outcomes and post-discharge follow-up of neonatal tracheotomy in NICU / 中国小儿急救医学

Objective:To study the outcomes and post-discharge follow-up of neonatal tracheotomy in neonatal intensive care unit(NICU).Methods:This study included patients who were admitted to NICU in Beijing Children′s Hospital from January, 2016 to August, 2021, and less than 28 days or 44 weeks(corrected age)on admission, and required tracheotomy.The patients were divided into tracheotomy group and the non-tracheotomy group (the parents signed to refuse the tracheotomy) according to whether perform tracheotomy.Demographic data, general hospitalization information, diagnosis, indications for tracheotomy, follow-up outcomes at 3/6/12 months of age after discharge of patients were collected and analyzed.Results:Totally 26 patients were included in this study, 14 cases in tracheotomy group and 12 cases in non-tracheotomy group.The average gestational age was(37.7±3.80)weeks and(38.99±1.83)weeks, and birth weight was(2 823.57±948.89)g and (3 320.83±378.76)g, respectively.There were no significant differences in sex, gestational age, birth weight, age on admission, weight on admission, age at diagnosis, ratio of endotracheal intubation for respiratory support on admission between two groups( P>0.05). The commonest indications of tracheotomy group were bilateral vocal cord paralysis(50.0%) and congenital anomaly/defect of throat/larynx(21.4%), and the commonest indications of non-tracheotomy group were bilateral vocal cord paralysis(50.0%) and vocal cord/subglottic mass(25.0%), and there was no significant difference between two groups( P>0.05). The rate of discharge-against-medical order of tracheotomy and non-tracheotomy group was 7.14% and 66.67%( P=0.003), respectively.The total follow-up rate of tracheotomy and non-tracheotomy group was 88.9% and 38.9%, while the follow-up rates at 3 months, 6 months, and 12 months were 100.0% vs. 50.0%, 83.3% vs. 41.7%, and 81.8% vs. 25.0%, respectively, whose differences were statistically significant(all P<0.05). In the 14 cases of tracheotomy group, 3 cases died, 4 cases successfully removed the tracheal cannula, 5 cases did not remove the tracheal cannula, and 2 cases were lost. Conclusion:Bilateral vocal cord paralysis is the commonest indication of neonatal tracheotomy.Parents′ compliance in the tracheotomy group is significantly higher than that in non-tracheotomy group.To give caring skill training for parents of neonates with tracheotomy before discharge is beneficial for improving the overall prognosis of children.

Effects of neonatal respiratory distress syndrome on thymus in 130 premature infants / 国际儿科学杂志

Objective:To investigate the effects of neonatal respiratory distress syndrome(NRDS)on thymus of premature infants.Methods:We collected baseline data from premature infants with gestational age of 28~32 weeks in neonatal intensive care unit of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 1, 2019 to December 31, 2019.The largest transverse diameter and the sagittal of thymus were measured by ultrasonography within 24 h of birth, then, the thymic index(TI)and thymic weight index(TWI)were calculated to assess the size of thymus.The preterm neonates were divided into NRDS group and non-NRDS group according to the diagnosic criteria of NRDS, and the two groups were then divided into antenatal corticosteroid administration(ACS)group and non-ACS group according to ACS exposure.We then compared the TI and TWI between these groups.Results:One hundred and sixty-three preterm neonates were enrolled in our study, including 98 NRDS preterm neonates and 65 non NRDS preterm neonates.After matching gestational age and birth weight of the preterm neonates from two groups, 65 preterm neonates with NRDS comprised the NRDS group, and 65 preterm neonates without NRDS served as controls.Preterm neonates in NRDS group had significantly smaller TI[(1.788 ± 0.803)cm 3 vs.(2.420±1.068)cm 3, t=3.818, P<0.01] and TWI[(1.278 ± 0.380)cm 3/kg vs.(1.695 ± 0.491)cm 3/kg, t=5.401, P<0.01] than those in non-NRDS group.Besides, preterm neonates in NRDS group had smaller lymphocytes count[(3.729 ± 1.263)×10 9/L vs.(4.437 ± 1.608)×10 9/L, t=2.789, P<0.01] than that in non-NRDS group.For NRDS preterm neonates, TI[(1.487 ± 0.515)cm 3 vs(2.185 ± 0.942)cm 3, t=3.542, P<0.01] ]and TWI[(1.134± 0.311)cm 3/kg vs(1.469± 0.385)cm 3/kg, t=3.882, P<0.01] in ACS group were significantly smaller than those in non-ACS group.For non-NRDS preterm neonates, TI and TWI in ACS group also were significantly smaller than those in non-ACS group( t=2.676、3.659, P<0.05). Conclusion:NRDS is associated with thymic involution of preterm neonates, and ACS exposure affected the size of thymic in premature infants.

Progress of breast milk oligosaccharides / 国际儿科学杂志

Human breast milk oligosaccharides are a kind of complex carbohydrates widely existing in human breast milk, which is the third major nutrient in human breast milk and is closely related to the growth and development of infants and some diseases.More than 200 different functional oligosaccharides have been identified for their role in regulating intestinal flora, regulating immunity and promoting brain development.This article reviews the structural composition, biological function, application and development trend of breast milk oligosaccharides, to provide reference for the application of oligosaccharides in functional food.

SHMT2 Promotes Invasion and Migration of Breast Cancer Cells Through Binding to and Up-regulating HAX1 / 肿瘤防治研究

Objective To explore the molecular mechanism of SHMT2 regulating the invasion and migration of breast cancer cells. Methods Bioinformatics analysis was used to verify the role of SHMT2 in breast cancer tissues. Transwell assay was used to detect the changes of invasion and migration abilities of breast cancer cells. Co-immunoprecipitation, knockdown plasmid transfection and Western blot were used to determine the regulatory relationship between different proteins. Results Bioinformatics analysis showed that the expression level of SHMT2 in invasive breast cancer tissues was significantly higher than that in adjacent normal tissues (P < 0.001). The 5-year disease-specific survival and overall survival in the SHMT2 high expression group were significantly lower than those in the SHMT2 low expression group (both P < 0.001). Transwell assay showed that SHMT2 knockdown significantly reduced the invasion ability (t=5.375, P=0.0058) and migration ability (t=6.274, P=0.0033) of MCF7 cells. Western blot showed that SHMT2 could combine to HAX1, and knockdown of SHMT2 reduced the protein level of HAX1. Transwell assay showed that the inhibitory effect of SHMT2 knockdown on the migration of MCF7 cells could be reversed by overexpression of HAX1 (t=6.274, P=0.0033; t=8.041, P=0.0013), while SHMT2 inhibitor (SHIN1, 10 nmol/L) significantly inhibited the migration of MCF7 cells induced by SHMT2 overexpression (t=10.16, P=0.0005; t=8.741, P=0.0009). Conclusion SHMT2 was closely related to the poor prognosis of breast cancer, and was a key factor in the invasion and migration of breast cancer cells. The mechanism was that SHMT2 increased the invasion and migration ability of breast cancer cells by binding to and up-regulating HAX1. It was verified that SHMT2 inhibitor could significantly reduce the migration ability of breast cancer cells. This study explored the therapeutic potential of SHMT2 inhibitor in metastatic breast cancer, and found potential intervention targets for its clinical treatment.

Experimental Study on the Inhibitory Effect of Eugenol on Inflammatory Activation of Hepatic Stellate Cells by MSCs / 中山大学学报(医学科学版)

ObjectiveThis study aimed to investigate the effects of eugenol on inhibiting the inflammatory activation of human umbilical cord mesenchymal stem cells （HUC-MSCs） and the pro-inflammatory phenotype of hepatic stellate cells （HSCs） in liver fibrosis， and to explore their underlying mechanisms. MethodsHUC-MSCs were cultured and identified in vitro， and the toxicity of eugenol to HUC-MSCs was evaluated by MTT method. The effect of eugenol on the migration ability of HUC-MSCs was investigated by in vitro scratch test. The expression of α-SMA， COL1A1， Smad2/3 and p-Smad2/3 of LX-2 cells activated by TGF-β1 treated with EU-MSCs-CM and MSCs-CM were detected by WB assay. EU-MSCs-CM and MSCs-CM treated THP-1 macrophages stimulated with Lipopolysaccharide （LPS） were analyzed for the expression of surface markers CD11b， CD86， and CD206 by flow cytometry. Additionally， the expression of pro-inflammatory genes TNF-α， IL-1β， and IL-6 in THP-1 macrophages was detected by qPCR. ResultsThe results of MTT method showed that the viability of the cells remained above 90% after 24 h and 48 h treatment at 0， 7.5， 15 μg/mL. In vitro scratches showed that eugenol treatment enhanced HUC-MSCs migration. WB results showed that compared with MSCs-CM treatment， EU-MSCs-CM treatment significantly inhibited the expression of α-SMA， COL1A1， Smad2/3， and p-Smad2/3 of activated HSCs. Flow cytometry showed that compared with MSCs-CM treatment， EU-MSCs-CM treatment had a more significant inhibitory effect on CD86， a M1-type polarization marker in THP-1 macrophages. The results of qPCR experiment showed that compared with MSCs-CM treatment， EU-MSCs-CM treatment more significantly inhibited the expressions of TNF-α， IL-1β and IL-6 of THP-1 macrophage proinflammatory genes. ConclusionsEugenol enhances the inhibitory effect of HUC-MSCs on inflammatory activation of HSCs， possibly by regulating TGF-β1/Smads signaling pathway. It also enhances the inhibitory effect of HUC-MSCs on the pro-inflammatory phenotype of macrophages. Proinflammatory macrophages can promote inflammatory activation of HSCs.

Biomechanical Analysis on NiTi Memory Alloy Stent for Lumbar Interbody Fusion / 医用生物力学

Objective To evaluate biomechanical properties of the nickel-titanium (NiTi) memory alloy stent and its in vitro biomechanical properties for lumbar interbody fusion. Methods The mechanical properties of the NiTi memory alloy stent were tested on mechanical testing machine. Moreover, lumbar interbody fusion was simulated on fresh lumbar specimens, and biomechanical properties of the NiTi memory alloy stent with matching bone graft for used for lumbar interbody fusion were analyzed and compared with the traditional box-shape cage. Results The maximum compressive strength of the NiTi memory alloy stent was ( 12 964 ± 962) N. The maximum deformation within the effective range of memory characteristics was (4. 68±0. 03) mm. The recovery rate of the NiTi memory alloy stent was up to 99. 86% . Compared with the intact lumbar model, the stability of the operative segment after the simulated lumbar interbody fusion using NiTi memory alloy stent alone was increased in the direction of anterior flexion, posterior extension, lateral flexion and rotation, which was equivalent to the box shape cage group (P>0. 05). After the combined use of autogenous bone granule and absorbable bone cement the ROM of the operative segment was further reduced (P0. 05). The pull-out strength of the NiTi memory alloy stent with matching bone graft group was significantly stronger than that of the box-shape cage group (P<0. 05). Conclusions The NiTi memory alloy stent in this study was designed with a matched bone granule-absorbable bone cement graft,which provided a new idea for the further optimization and development of lumbar interbody fusion. With excellent support and deformation properties, this NiTi memory alloy stent is biomechanical equivalent to the traditional box shape cage for lumbar interbody fusion, and can greatly improve the stability of surgical segment and the pull-out strength of implants after the combined use of autogenous bone granule and absorbable bone cement.

Mining and analysis for adverse drug event signals of liver failure in underage population based on the FAERS database / 中国药房

OBJECTIVE To conduct data mining on drugs causing liver failure in underage populations based on the FDA Adverse Event Reporting System （FAERS） database， so as to provide reference for clinical use of related drugs. METHODS The data on reported adverse drug event （ADE） of liver failure in this population （under 18 years old） from the first quarter of 2013 to the third quarter of 2022 were retrieved from the FAERS database for mining and analysis； they were divided into infants（≤1 year old）， young children（＞1-＜6 years old）， children（6-＜12 years old） and adolescents（12-＜18 years old） according to the age. The reporting odds ratio （ROR）， proportional reporting ratio and Bayesian confidence propagation neural network of the proportional imbalance method were used to screen ADE signals. RESULTS A total of 1 051 ADE reports of liver failure were collected from the underage population involving 60 drugs. The highest incidence was found in adolescents （410 cases， 39.01%）， followed by young children （297 cases， 28.26%）. The instructions of 14 drugs did not mention hepatobiliary system injury and liver failure risk， including 31 cases of levetiracetam （2.95%），18 cases of metronidazole （1.71%）， 16 cases of each of topiramate and methylprednisolone （1.52% each）， 12 cases of dexamethasone （1.14%）， 11 cases of tisagenlecleucel （1.05%）， 10 cases of each of ferrous sulfate， metformin and busulfan （0.95% each）， 9 cases of propofol （0.86%）， 8 cases of onasemnogene abeparvovec （0.76%）， 5 cases of each of diphenhydramine and omeprazole （0.48% each）， 4 cases of sebeliesterase α （0.38%）， totaling 165 cases， accounting for 15.70% of the total reported cases. Metformin was contrary to the known liver safety， and E-mail：libingchemical@163.com metronidazole and levetiracetam were new risk signals， which caused more serious clinical outcomes. CONCLUSIONS Fourteen new pharmacovigilance signals which cause liver failure in the underage population are found in this study； the liver function of patients should be closely monitored when using these drugs. Among those drugs， metformin neither undergoes liver metabolism nor has been reported in the relevant literature， and the liver-related ADE caused by metformin deserves further attention. The clinical outcomes caused by metronidazole and levetiracetam are relatively serious and need to be given sufficient attention.

Histopathological evaluation of cirrhosis reversal / 中华肝脏病杂志

A normal liver can develop cirrhosis through long-term and repeated stimulation from various etiologies. Histological manifestations like the collapse of hepatic lobular structure (including microvascular structure) and the formation of pseudolobules can lead to portal hypertension and even decompensated cirrhosis. More and more evidence suggests that effective etiological treatment can not only delay but also reverse the progression of cirrhosis. The mechanism of cirrhosis reversal mainly includes the degradation of extracellular matrix, hepatocyte regeneration, and hepatic lobular remodeling. The "gold standard" for the evaluation of cirrhosis reversal at present is still a liver biopsy. Therefore, the histopathological evaluation of cirrhosis reversal is very important for determining the disease's prognosis, efficacy, and mechanism of exploration.

The influencing factors of functional somatic discomfort in clinical nurses / 中华劳动卫生职业病杂志

Objective: To investigate the functional somatic discomfort status, and to analyze the effect of job stress, hostile attribution bias and ego depletion on functional somatic discomfort in clinical nurses. Methods: In May 2019, 10 cities in Henan Province and Fujian Province were randomly selected as sampling cities. Using the stratified cluster sampling method, nurses of clinical nursing posts in 22 third class hospitals and 23 second class hospitals were selected as the research objects. The general information, job stress, hostile attribution bias, ego depletion and functional somatic discomfort of clinical nurses were investigated by self-designed general information questionnaire, Perceived Stress Scale, Social Information Processing-attribution Bias Questionnaire, Self-regulatory Fatigue Scale, Patient Health Questionnaire-15. 1200 clinical nurses included, and a total of 1159 valid questionnaires were collected, the effective rate of questionnaire collection was 96.6%. The t test was used to compare the difference of the functional somatic discomfort scores of clinical nurses with different demographic characteristicst. The influence of job stress, hostile attribution bias and ego depletion on functional somatic discomfort of clinical nurses were analyzed with Bootstrap. Results: The functional somatic discomfort score of clinical nurses was (8.95±4.38), of which 859 (74.12%) had functional somatic discomfort symptom. The functional somatic discomfort score of clinical nurses aged 36-50 years old was higher than that of 19-35 years old, the functional somatic discomfort score of clinical nurses with service age ≥5 years was higher than that of <5 years, the functional somatic discomfort score of non-permanent clinical nurses was higher than that of permanent clinical nurses, the functional somatic discomfort score of clinical nurses in tertiary hospitals was higher than that of secondary hospitals, the functional somatic discomfort score of clinical nurses in surgical departments were higher than those in non-surgical departments, and the differences were statistically significant (P<0.05). Job stress affected functional somatic discomfort through the single mediating role of hostile attribution bias, the single mediating role of ego depletion, and the chain mediating role of hostile attribution bias and ego depletion (β=0.17, 95%CI: 0.10-0.20; β=0.16, 95%CI: 0.10-0.20; β=0.07, 95%CI: 0.03-0.10; P<0.05) . Conclusion: The functional somatic discomfort symptoms of clinical nurses are significant and varied among different age, working age, employment form, hospital grade and department groups. They are affected by work stress directly and through the separate mediating effect of hostile attribution bias and ego depletion, and the chain mediating effect of hostile attribution bias and ego depletion.