OBJECTIVE To establish drug utilization evaluation （DUE） criteria for pyrotinib to promote its appropriate application in clinical practice. METHODS Based on the label of Pyrotinib maleate tablets， with relevant guiding principles and diagnostic and treatment guidelines as the evaluation basis， DUE criteria for pyrotinib were determined through the Delphi method. Attribute hierarchical model （AHM） and entropy weight method （EWM） were used to combine and assign weights to each indicator within the DUE criteria. Additionally， the weighted technique for order preference by similarity to an ideal solution （TOPSIS） method was applied to perform rationality evaluation of medication in archived medical records from Hainan Provincial Tumor Hospital and Hainan Western Central Hospital regarding the use of pyrotinib from November 2019 to November 2023. RESULTS The established DUE criteria for pyrotinib included 4 primary indicators （prescription authority， indications for use， medication process， and medication outcomes） and 11 secondary indicators. The secondary indicators with higher weights were the route of administration and dosage （0.257） and indications in the label （0.241）. Among the 88 archived cases included， there were 28 cases of inappropriate medication （31.82%）， 43 cases of generally appropriate medication （48.86%）， and 17 cases of appropriate medication （19.32%）. The main issues related to inappropriate medication involved off-label use （42.05%） and inappropriate routes of administration and dosage （43.18%）. CONCLUSIONS DUE criteria for pyrotinib established using the AHM-EWM-weighted TOPSIS method is highly operational and results in quantifiable evaluation outcomes. The overall rationality of the use of pyrotinib in the above hospitals remains to be improved， and there are some issues， like the off-label use，and inappropriate routes of administration and dosage being liaoyylyy@163.com unreasonable.

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Objective To establish the theories and methods for the compatibility of Chinese patent medicines in pre-scription review.Methods Based on the prescription combination theory and the classics literatures of traditional Chinese med-icine,the methods of prescription suitability review for the compatibility of Chinese patent medicines were discussed.Results Based on the examples of the compatibility of Chinese patent medicines,five basic principles of combined Chinese patent medi-cines and the key points for reviewing the combined Chinese patent medicines dosage form were discussed in detail.Conclusion The methods for the compatibility of Chinese patent medicines prescription review have been established,which can provide a theoretical reference for the review of combined Chinese patent medicines prescriptions.

Objective:To measure the retinal structural and functional parameters of adult Macaca fascicularis, and explore the similarity of the retinal structural and functional parameters between non-human primates and normal human retinas.Methods:Six eyes of 3 5-year-old adult Macaca fascicularis were examined by in vivo detection including color fundus photography, retinal optical coherence tomography (OCT) and electroretinogram (ERG) to determine the thickness of the inner/outer retina at the fovea and 1 000/2 000 μm away from the nasal, temporal, superior and inferior regions of the fovea, the thickness of the retinal nerve fiber layer (RNFL), the area of optic disc, the area of optic cup, the area ratio of cup to disc and the biological parameters of flash ERG.Differences in the above parameters between left and right eyes were analyzed.The similarity of parameters between Macaca fascicularis and human was compared with reference to published literature.The use and care of animals complied with the Regulation on the Management of Experimental Animals.The study protocol was approved by the Institutional Animal Care and Use Committee of Hubei Topgene Biotechnology (NO.IACUC-2019-012). Results:The foveal thickness, optic disc area, cup-disc area ratio, and average RNFL thickness in normal adult Macaca fascicularis were (252.31±4.79)μm, (1.89±0.05)mm 2, 0.14±0.01, and (103.53±0.58)μm, respectively.The b-wave amplitude of dark-adapted 0.01 ERG was (66.75±7.29)μV.The a- and b-wave amplitudes of dark-adapted 3.0 ERG response were (57.15±15.01) and (122.10±25.51)μV, respectively.The a- and b-wave amplitudes, the amplitude of oscillation potentials, and the latency of dark-adapted 10.0 ERG response were (72.98±20.14)μV, (131.67±13.78)μV, (49.98±10.08)μV, and (30.02±5.76)ms, respectively.The a- and b-wave amplitudes of light-adapted 3.0 ERG were (9.16±2.75) and (40.43±5.57)μV, respectively.The latency and the amplitude of the light-adapted 30 Hz flicker was (26.61±1.19)ms and (24.72±5.10)μV, respectively.There was no significant difference in the parameters between left and right eyes (all at P>0.05). The retinal thickness in central fovea, mean RNFL thickness, waveform and amplitude of ERG of Macaca fascicularis were similar to normal human. Conclusions:The structure and function of the retina of adult Macaca fascicularis are similar to those of normal humans.As a laboratory animal for preclinical drug research, in vivo studies of Macaca fascicularis can refer to normal human retinal parameters.

In order to understand the characteristics of avian leukosis virus(ALV)infection and the polymorphisms of receptor genes Tva,Tvb and NHE1 sequences in different Qingyuan Ma chick-en breeding farms,the isolation and identification of exogenous ALV virus,receptor gene amplifi-cation and sequencing analysis were carried out in five Qingyuan Ma chicken breeding farms.The results of virus isolation and subtype identification showed that the positive rate of exogenous ALV virus isolation in farms A,B and C was less than 5％,among which there was ALV-J infection alone in farm A,mixed infection with ALV-J and ALV-K in farm B,ALV-K infection a-lone in farm C,and no exogenous ALV infection was detected in farm D and E.Polymorphism anal-ysis of recipient genes showed that there were different frequencies of Tvar3,Tvar4 and Tvbr3 re-sistance alleles in A-E farms,and the distribution frequency of Tvar3 was 0.2-0.6,the distribution frequency of Tvar4 was 0.3-0.7,and the distribution frequency of Tvbr3 was 0.1-0.7.In addition,there were Tvar5 resistance alleles in both B and D farms,with a distribution frequency of 0.2.A to-tal of 18 SNP mutations occurred in the NHE1 receptor gene sequence,and further analysis showed that positions 1 279,1 361,1 369,1 406,1 442,and 1 912 were non-synonymous mutations,which could cause changes in amino acids.The study suggested that there were differences in the exogenous ALV and its subtypes among the five Qingyuan Ma chicken breeders,and each farm should have a more targeted and unique purification strategy.The distribution of Tva and Tvb re-sistance alleles at different frequencies,along with the occurrence of 6 non-synonymous mutations in the NHE1 gene,indicate that Qingyuan Ma chicken have the potential of genetic resistance breeding.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE: To explore the diagnosis, treatment and genetic analysis of an infant with Schaaf-Yang syndrome (SYS). METHODS: An infant suspected for SYS at the Hunan Provincial Children's Hospital on June 10, 2022 was subjected to trio-whole exome sequencing, and Sanger sequencing was used to verify the candidate variant. Structure of the wild-type and mutant proteins was constructed to analyze the potential hazard. RESULTS: The infant was found to harbor a heterozygous frameshifting variant of c.1908delG (p.R637Gfs*65) of the MAGEL2 gene, which was found in neither of his parents. The variant has not been recorded by the public databases, and no relevant literature was retrieved. As the result of the variant, the MAGEL2 protein only retained part of its proline domain, which may lead to destruction and/or down-regulation of its function. CONCLUSION The c.1908delG (p.R637Gfs*65) variant of the MAGEL2 gene probably underlay the pathogenesis in this child. Combined with his clinical characteristics, the child was diagnosed with SYS. Above finding has also enriched the mutational spectrum of the MAGEL2 gene.
Humans ; Infant ; Down-Regulation ; Heterozygote ; Mutation ; Parents ; Proteins

Objective:To investigate the clinical features, treatments and prognoses of children with antibody-mediated central nervous system (CNS) autoimmune diseases.Methods:Two hundred and seven children with antibody-mediated CNS autoimmune diseases confirmed by anti-neuronal antibody detection in blood and/or cerebrospinal fluid in Department of Neurology, Children's Hospital of Hunan Province from June 2014 to May 2022 were enrolled. Their clinical features, laboratory and imaging data, treatment regimens and prognoses were retrospectively analyzed.Results:Of the 207 children, 117 were positive for anti- N-methyl- D-aspartate receptor (NMDAR) antibodies, 63 for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies, 32 for anti-glial fibrillary acidic protein (GFAP) antibodies, 6 for anti-contactin-associated protein-like 2 (CNTNAP2) antibodies, 3 for anti-aquaporin 4 (AQP4) antibodies, 2 for anti-gamma-aminobutyric acid type B receptor (GABABR) antibodies, and 1 for anti-anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies. Acute disseminated encephalomyelitis (ADEM) was the most common clinical phenotype among the children, followed by optic neuritis (ON). Behavioral abnormalities, seizures, and involuntary movements were the most common clinical presentations of anti-NMDAR encephalitis for these children, while fever, headache, and disturbance of consciousness or vision were the most common symptoms for children with MOG antibody disease or autoimmune GFAP astrocytopathy. The coexistence of multiple anti-neural antibodies was detected in 17 patients, among which 10 had coexistent anti-NMDAR and anti-MOG antibodies (including 1 with anti-GFAP antibody), 3 had coexistent anti-NMDAR and anti-GFAP antibodies, 3 had coexistent anti-MOG and anti-GFAP antibodies, 2 had coexistent anti-NMDAR and anti-CASPR2 antibodies, and 1 had coexistent anti-GABABR and anti-CASPR2 antibodies. In our cohort, of the 202 children examined for cerebrospinal fluid, 154 had cerebrospinal fluid leukocytosis and 27 had elevated protein. Of the 203 children had electroencephalography, 179 was abnormal; abnormal EEG was mainly manifested as focal or global slow waves, and epileptic discharge in some children; 205 patients received immunotherapy. All survivors were followed up for at least 6 months; 164 recovered completely, 40 had varied sequelae, and 3 died; 28 had one or more relapses. Conclusion:Antibody-mediated CNS autoimmune diseases occur in children at all ages; most such pediatric patients have good response to immunotherapy, enjoying low mortality rate; however, some survivors have relapsing risk.

Abstract This paper focuses on the regulatory strategy of drug-led drug device combination products, comparing and analyzing the definition, scope and management mode of drug device combination products in the United States, the European Union, Japan, Canada and China; summarizing and analyzing the types of combination products in the Product-specific Guidances for Generic Drug Development(PSGs) of the US FDA's scientific and technical reports in the past five years, the results show that the top three PSGs newly added to the FDA were transdermal system, nasal sprays, and single-dose prefilled syringes/pens(including auto-injectors). As of March 1, 2023, the National Medical Products Administration(NMPA) had cumulatively announced the results of 339 combination products applied for attribute definition by enterprises, of which 88 were "drug-led drug device combination products", accounting for 26%; and 78 were "device-led drug device combination products", accounting for 23%; the results of "not belonging to drug device combination products" accounted for more than half (51.0%), which indicated that there was a big difference between the industry and the regulatory understanding of the definition of drug-device combination products, and that the existing guideline and documents were unable to provide clear and predictable positioning of the combination products under research and development for the time being. This paper also puts forward suggestions for solving the problems in the development of drug-device combination products in China, in order to improve the consistency, predictability and transparency of the classification and definition of drug-device combination products in China, and to provide references for the development and scientific supervision of this kind of products.

Objective:To evaluate the data quality of Shenzhen Type 1 Diabetes Alliance (SZT1D), and to provide a basis for evaluation and improvement for the continuous improvement of data quality.Methods:From December 2018 to July 2021, 697 first-visit type 1 diabetes (T1DM) patients (including 501 in Shenzhen and 196 out-of-Shenzhen) and 120 re-visited T1DM patients (including 113 in Shenzhen and 7 out-of-Shenzhen) who were registered by SZT1D in collaborative research platform network of China Type 1 Diabetes Alliance (hereinafter referred to as China T1D). The data quality was evaluated from three dimensions: data completion, accuracy and revisit. The data completion degree was evaluated by the overall data completion degree and the key indicator completion degree; the data accuracy was evaluated by the probability of abnormal blood glucose value; the patient′s return visit was evaluated by the return visit rate.Results:The main characteristics of T1DM in SZT1D were young and middle-aged adults [age: (34.4±17.1)years] with thin body [BMI: (19.80±3.52)kg/m 2)], half of male and female patients [proportion of male: 52.4%(365/697)]; the main types of diagnosis were classical T1DM [65.22%(150/230)] and latent autoimmune diabetes in adults(LADA) [26.08%(60/230)], and the fasting blood glucose (FPG) [(10.93±6.98)mmol/L] and glycosylated hemoglobin (HbA 1c) [(10.63±3.01)%] were high. The average completion rate of the overall data of the first diagnosed patients in SZT1D was only 60% [(62.9±31.5)%]: the number of patients with overall data completion ≥80% in SZT1D was only 50.2%(350/697); the number of patients with overall data completion ≥80% in Shenzhen was less than that outside Shenzhen [44.3%(222/501) vs 65.3%(128/196), P<0.001]. The key indicators with better completion rate of first-visit were disease course [76.2%(531/697)], age of onset [75.8%(528/697)], family history of diabetes [74.9%(522/697)], etc., but none of them had a completion rate of more than 80%, and the diabetes self-management behavior assessment questionnaire and scale score were completely missing; the frequency of daily blood glucose monitoring [46.1%(231/501) vs 64.3%(126/196), P<0.001], current insulin regimen [44.3%(222/501) vs 63.3%(124/196), P<0.001], number of diabetic ketoacidosis (DKA) since the onset of the disease [45.7%(229/501) vs 64.8%(127/196), P<0.001] and the number of symptomatic hypoglycemia in the past 1 month [39.3%(197/501) vs 63.8%(125/196), P<0.001] were higher in Shenzhen than those reported outside Shenzhen. In addition, the probability of abnormal FPG and postprandial glucose (PPG) [5.2%(24/466); 3.8%(19/236)] were low. The revisit rate was not high [17.2%(120/697)], and the revisit rate in Shenzhen was higher than that outside Shenzhen [22.6%(113/501) vs 3.6%(7/196), P<0.001]. The first revisit rate was 16.2%(113/697) and the second revisit rate was seriously insufficient [1.0%(7/697)]. Conclusions:The data quality of T1DM patients recorded by SZT1D needs to be further improved. Improving the information interconnection between China-T1D and SZT1D, employing quality control personnel and building a systematic data quality evaluation analysis and feedback mechanism are methods to promote the comprehensive, accurate and efficient input of T1DM data and continuously improve the evaluation methods to improve the overall data quality.