Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.

Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

BACKGROUND:Ursolic acid can promote the directed differentiation of bone marrow mesenchymal stem cells into osteoblasts.However,there are few reports on whether ursolic acid has osteogenic effect on human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of ursolic acid on proliferation and osteogenic differentiation of human periodontal ligament stem cells. METHODS:The human periodontal ligament stem cells were isolated and cultured.Passage 3 cells were selected and treated with ordinary medium containing different concentrations(0,1,2,4,6,8 μmol/L)of ursolic acid.After intervention for 1,3,5,7 days,the cell proliferation was detected by CCK-8 assay and the appropriate intervention concentration was screened.Passage 3 human periodontal ligament stem cells were treated with osteogenic induction solution containing 0,1,2,4 μmol/L ursolic acid,respectively.After 7 days of intervention,the mRNA expressions of alkaline phosphatase,Runx2,and osteocalcin were detected by qRT-PCR.After 14 days of intervention,the formation of mineralized nodules was observed by alizarin red staining.Passage 3 human periodontal ligament stem cells were taken and the control group was added with osteogenic induction solution;the ursolic acid group and the antagonist group were added with osteogenic induction solution containing ursolic acid(2 μmol/L)and the bone morphogenetic protein signaling pathway antagonist Noggin,respectively.The ursolic acid+antagonist group was added with osteogenic induction solution containing ursolic acid(2 μmol/L)and Noggin,the inhibitor of bone morphogenetic protein signaling pathway,and cultured for 7 days.qRT-PCR and western blot assay were used to detect the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2. RESULTS AND CONCLUSION:(1)1,2,4 μmol/L ursolic acid could promote the proliferation of human periodontal ligament stem cells.6,8 μmol/L ursolic acid could inhibit the proliferation of human periodontal ligament stem cells,and 1,2,4 μmol/L ursolic acid was selected to intervene in subsequent experiments.(2)Compared with 0 μmol/L,1,2,4 μmol/L ursolic acid could promote the expression of alkaline phosphatase,Runx2,and osteocalcin mRNA and the formation of mineralized nodules(P<0.05),and the effect of 2 μmol/L ursolic acid was the most significant.(3)Compared with the control group,the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2 in the ursolic acid group were increased(P<0.05),while mRNA and protein expressions of the above indexes were decreased in the antagonist group(P<0.05).Compared with the ursolic acid group,mRNA and protein expressions of above indexes were decreased in ursolic acid+antagonist group(P<0.05).(4)The results indicate that ursolic acid promotes osteogenic differentiation of human periodontal ligament stem cells through bone morphogenetic protein signaling pathway.

BACKGROUND:Exosomes derived from mesenchymal stem cells are prospective cell-free alternatives for treating osteoarthritis.Their therapeutic activity and clinical transformation potential can be further improved by adjusting cell culture condition. OBJECTIVE:To review the effect of cell culture conditions on exosome activity and to analyze its clinical transformation potential. METHODS:Articles concerning osteoarthritis/cartilage repair and mesenchymal stem cell-derived exosomes were retrieved on CNKI and PubMed using"exosomes,mesenchymal stem cells,osteoarthritis or cartilage repair"as Chinese search terms and"exosomes or extracellular vesicles,mesenchymal stem cells,osteoarthritis or cartilage repair"as English search terms.The search time was from 2010 to 2023.Finally,100 articles were included for summary and analysis. RESULTS AND CONCLUSION:(1)During cell culture,providing a physical environment favorable for chondrocyte growth or adding chondroprotective small molecules,chondrogenic factors,or inflammatory factors,can further improve the regulatory activity of exosomes secreted by mesenchymal stem cells in maintaining chondrocyte phenotype,promoting cartilage regeneration,and immunosuppression.Therefore,other physical or chemical factors with similar characteristics may also improve the effects of exosomes secreted by mesenchymal stem cells for treating osteoarthritis.(2)Some treatments during cell culture,such as hypoxia induction,pulsed electromagnetic field stimulation,bioreactor,and chondroprotective molecule(e.g.,human parathyroid hormone 1-34)stimulation are safe and scalable,which allows for the production of clinical-grade exosomes secreted by mesenchymal stem cells for osteoarthritis treatment.(3)Mesenchymal stem cell exosomes are expected to achieve modified treatment of osteoarthritis,and the feasibility of clinical transformation can be further improved by adjusting the cell culture regimen to enhance the therapeutic activity.

OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

Objective To explore the recognition capabilities of electronic nose combined with machine learning in identifying the breath odor map of benign and malignant pulmonary nodules and Traditional Chinese Medicine (TCM) syndrome elements. Methods The study design was a single-center observational study. General data and four diagnostic information were collected from 108 patients with pulmonary nodules admitted to the Department of Cardiothoracic Surgery of Hospital of Chengdu University of TCM from April 2023 to March 2024. The patients' TCM disease location and nature distribution characteristics were analyzed using the syndrome differentiation method. The Cyranose 320 electronic nose was used to collect the odor profiles of oral exhalation, and five machine learning algorithms including random forest (RF), K-nearest neighbor (KNN), logistic regression (LR), support vector machine (SVM), and eXtreme gradient boosting (XGBoost) were employed to identify the exhaled breath profiles of benign and malignant pulmonary nodules and different TCM syndromes. Results (1) The common disease locations in pulmonary nodules were ranked in descending order as liver, lung, and kidney; the common disease natures were ranked in descending order as Yin deficiency, phlegm, dampness, Qi stagnation, and blood deficiency. (2) The electronic nose combined with the RF algorithm had the best efficacy in identifying the exhaled breath profiles of benign and malignant pulmonary nodules, with an AUC of 0.91, accuracy of 86.36%, specificity of 75.00%, and sensitivity of 92.85%. (3) The electronic nose combined with RF, LR, or XGBoost algorithms could effectively identify the different TCM disease locations and natures of pulmonary nodules, with classification accuracy, specificity, and sensitivity generally exceeding 80.00%.Conclusion Electronic nose combined with machine learning not only has the potential capabilities to differentiate the benign and malignant pulmonary nodules, but also provides new technologies and methods for the objective diagnosis of TCM syndromes in pulmonary nodules.

Liver cirrhosis is the terminal stage of various chronic liver diseases， with the main clinical manifestation of portal hypertension， which can lead to spontaneous portosystemic shunt （SPSS）. SPSS is very common in clinical practice and is closely associated with the prognosis of patients. This article summarizes the recent studies in the clinical significance of cirrhotic portal hypertension with SPSS， the controversies in studies， and the current status and future prospects and challenges of treatment， in order to provide a reference for the standardized diagnosis and treatment of portal hypertension.

Artificial intelligence （AI） robots， as a dynamic force sweeping the world， have demonstrated remarkable influence in the field of medical education since their inception. They have continuously participated in medical education through online-assisted teaching of medical theory， interpretation of imaging materials， clinical skills practice， and other forms， bringing new opportunities and challenges for the development of medical education. Concurrent with transforming the field of education， AI technology has also given rise to a series of ethical issues due to the constraints of technological logic， such as algorithmic discrimination， technological dependence， data privacy breaches， emotional communication crises among teaching subjects， and blurred power boundaries. While drawing on Western ethical principles， it is crucial to maintain a sober awareness of local issues， pay attention to the realistic relationship between Confucian bioethics and medical education in China， emphasize the value-oriented function of benevolence principle in mitigating physical and mental risks， and guide students to become adults in “achieving success”； improve the institutional construction guided by the principle of the value of life， resist the risks of educational AI technology， and achieve technological goodness； build a harmonious human-machine relationship by adhering to the principle of human nature to prevent the development risks of educational AI.

ObjectiveTo explore the current situation of adverse medical behaviors in oncology patients and propose corresponding countermeasures to reduce the incidence of adverse medical behaviors in oncology patients， standardize their diagnosis and treatment order， and ensure the quality and safety of medical care. MethodsUsing the purposive sampling method， 16 oncology patients and caregivers from 3 communities in a city were selected for semi-structured and in-depth qualitative interviews from October to December 2023. Nvivo 12.0 software was used for data transcription and thematic analysis. ResultsThree themes were extracted. First， the adverse medical behaviors in oncology patients included overtreatment， non-standardized medication， and inaccurate recommendations of exorbitant examination items. Second， the influencing factors of adverse medical behaviors in oncology patients included limitations of the medical system and policy issues， difficulty in defending the rights of patients in a vulnerable position， as well as inadequacy of related ethical supervision and laws and regulations. Third， the countermeasures for adverse medical behaviours in cancer patients mainly encompassed improving the construction of medical systems and policies， optimizing the allocation of medical resources， enhancing the medical ethical literacy of medical personnel， standardizing the professional behaviour of medical personnel， strengthening medical ethical education for patients and enhancing their awareness of the protection of rights and interests， as well as strengthening ethical supervision and evaluation. ConclusionThe adverse medical behaviors in oncology patients are affected by tripartite factors， including medical staff， patients， and the system. The government， medical institutions， medical personnel， and patients should all adopt targeted countermeasures to deal with adverse medical behaviours， thus regulating diagnosis and treatment orders and ensuring the quality and safety of medical care.