OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

Global childhood and adolescent obesity has become a pressing public health challenge, imposing significant burdens on human health. Obesity is an independent risk factor for insulin resistance, which in turn serves as a critical initiating event for multiple chronic metabolic diseases. The Developmental Origins of Health and Disease (DOHaD) theory highlights the existence of a plastic ^”window period^” during early life, spanning pregnancy and lactation. Maternal nutritional status during this window period profoundly influences offspring metabolic health, with intergenerational transmission of gut microbiota acting as a key mediating pathway. This review summarizes current evidence on how maternal nutrition during the ^”window period^” shapes maternal and offspring gut microbial ecosystems and explores the relationship between these alterations and metabolic risks of obesity and other metabolic disorders in offspring. Based on emerging research, it has been found that maternal nutritional intake during this critical window period modulates early colonization of offspring gut microbiota through multiple pathways, thereby programming long-term metabolic trajectories. These findings suggest that targeting gut microbiota as a preventive strategy during the ^“window period^” may offer novel approaches for combating metabolic disorders, while also providing mechanistic insights into potential microbiota-modulating interventions. This perspective could inform future research directions and clinical applications in metabolic disease prevention.

Objective:To screen the main active components of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression; To predict the key targets and signaling pathways; To establish a multi-level network structure and comprehensively reveal the synergistic mechanism of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression.Methods:Main components of Danggui Buxue Decoction were searched in TCMSP detabase, combined with literature reports to supplement and improve information. The protein targets of compounds were standardized in the UniProt protein database. Myelosuppression targets were obtained by querying TTD database, GeneCards database, DrugBank detabase and OMIM database. The effective components and common targets of Danggui Buxue Decoction were screened, and the protein-protein interaction (PPI) network of intersection targets was analyzed by String platform to construct the PPI network of effective components and disease targets. Gene ontology (GO) analysis and enrichment pathway analysis of Kyoto gene and genome encyclopedia (KEGG) of key target proteins were conducted through Metascape data platform. Both the results of GO and KEGG analysis were presented. AutoDock software was used for molecular docking to explore the interaction between core targets and active components, and the results were imported into PyMOL software for visual analysis.Results:Danggui Buxue Decoction has a total of 22 active components of Chinese materia medica for improving chemotherapy-induced myelosuppression, 294 potential targets, 3 301 disease targets, and 210 common targets of Chinese materia medica and diseases. Core targets were obtained through network topology analysis and molecular docking. The first five were ESR1, MAPK1, RELA, AKT1, PIK3R1; GO enrichment results obtained 2 430 biological processes, 125 cellular components and 217 molecular functions, including responses to inorganic substances, membrane rafts, micro-organisms membrane region, transcription factor binding, etc.; KEGG enriched 385 pathways, of which cancer pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, etc. were the main signaling pathways; molecular docking results showed that β-sitosterol has the best binding performance with HSP90AA1, formononetin and RELA in astragalus when it was in Angelicae Sinensis Radix.Conclusion:Danggui Buxue Decoction regulates ESR1, MAPK1, RELA, AKT1 and other core targets through various active components such as quercetin, formononetin, and β-sitosterol. PI3K-AKT and other related signaling pathways can improve chemotherapy-induced myelosuppression and provide a basis for its clinical application.

Objective: To explore the impact of maternal anxiety during pregnancy on social emotional development of toddlers aged 1-3 year old, so as to provide references for scientific early parenting and early intervention for toddlers with social emotional difficulties. Methods: From September 2022 to March 2023, a total of 815 toddlers aged 1-3 who underwent physical examinations and their mothers at Nantong Maternal and Child Health Hospital were enrolled. The Chinese Infant Toddler Social and Emotional Assessment (CITSEA) was used to evaluate the social emotional ability among toddlers. Maternal anxiety evaluated using the Self rating Anxiety Scale (SAS) during prenatal visit was collected. Results: The average scores on the externalizing, internalizing, dysregulation and competence domains of the CITSEA were (49.40±9.48,47.42±9.60,48.67± 10.15 , 50.07± 10.20), respectively. Among boys, the score of externalizing domain (50.89±9.45) was higher than that of girls (48.76± 9.50 ), while the score of competence domain (49.22±10.30) was lower than that of girls (51.17±9.84), and the differences were statistically significant( t =2.10, -3.03, P <0.05). The detection rates of abnormalities in the externalizing, internalizing, dysregulation, and competence domains were 7.36%, 7.12%, 7.61%, and 7.24%, respectively. Among them, boys (8.43%,6.32%, 7.96 %,7.49%) and girls (6.19%, 7.99 %,7.22%,6.96%) showed no statistical differences ( χ 2=1.50, 0.85, 0.16, 0.09, P >0.05). There were significant differences in externalizing domain scores（47.77±9.52，49.56±8.95，52.51±9.77） and competence domain scores（51.70±10.38，49.65±10.05，46.68±10.03） among toddlers of different maternal anxiety（normal, mild, moderate to severe） （ F =7.05,7.10, P <0.01）. There were significant differences in the abnormal detection rate of externalizing domain （4.81%，7.54%，11.17%） and competence domain（4.81%，6.96%，11.73%）（ χ 2=6.60，7.98， P ＜0.05）. Conclusion Maternal anxiety during pregnancy has a negative impact on the social emotional development among toddlers. In order to improve social emotional development of toddlers, multidimensional social support and education during pregnancy should be carried out.

Colorectal cancer is one of the common malignant tumors with high morbidity， and changes in lifestyle， dietary structure and environment in China in recent decades have been associated with an increase in the incidence of colorectal cancer. A large number of studies have shown that traditional Chinese medicine（TCM） can be used as a complementary and alternative treatment for colorectal cancer after conventional western medicine treatment. TCM physicians have accumulated a lot of clinical experience in the treatment of patients with stage Ⅰ-Ⅲ colorectal cancer， and have proved that TCM has unique efficacy， but there is still a lack of relevant clinical practice guidelines to standardize and guide the diagnosis and treatment of TCM. Based on this， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， under the framework of relevant laws， regulations and technical guidance documents， combined with the evidence of relevant domestic and foreign clinical research in recent years for evidence grading and opinion recommendation， and then the Guidelines for TCM Intervention After Conventional Western Medicine Treatment for Stage Ⅰ-Ⅲ Colorectal Cancer were developed by expert consensus. This guideline introduces the etiology， pathogenesis， syndrome differentiation and treatment of TCM intervention for colorectal cancer， which can provide guiding opinions for TCM clinicians and clinicians of integrated traditional Chinese and western medicine engaged in the prevention and treatment of colorectal cancer.

Polymorphism refers to the simultaneous and frequent existence of two or more discontinuous variants or genotypes or alleles in a biological population, also known as genetic polymorphisms or genes Polymorphism. This gene polymorphism may have a certain degree of influence on the pharmacokinetics and pharmacodynamics of the drug. The study of genomics plays an important role in realizing personalized, patient-oriented precision medicine treatment. Population model analysis is to use a modeling method to quantitatively describe the correlation and variability between pharmacokinetic and pharmacodynamic parameters and individual characteristics and to quantify the impact of covariates. At present, this method has been widely used. This paper systematically introduces the application examples of using the population model approach to assess the effects of genetic polymorphisms on the drug PK/PD.

Objective:To investigate the potential key targets of Liujun Anwei Prescription and its effects on NF-κB/iNOS-NO in small intestine of mice with chemotherapy- associated diarrhea; To reveal the anti-inflammatory components and molecular mechanism.Methods:UPLC-Q/TOF MS combined with UNIFI software was used to analyze the chemical components of Liujun Anwei Prescription. PubChem database was searched to obtain the active components of Liujun Anwei Prescription, and the Swiss Target Prediction was used to predict the targets. The database of DisGeNET, OMIM and GeneCards were searched to obtain the targets of chemotherapy-related diarrhea. The potential targets of Liujun Anwei Prescription in the treatment of chemotherapy-related diarrhea diseases were obtained by crossing the targets of active components of Liujun Anwei Prescription and those related to diarrhea diseases. The PPI network and component-target-pathway network were constructed by Cytoscape 3.7.1 software, and the intersecting targets were analyzed by GO and KEGG based on David Database. The potential active components and potential targets predicted in the network were verified by using Autodock software. 60 C57BL/6J male mice were divided into normal control group, model group, positive control group and Liujun Anwei Prescription high-, medium- and low-dosage groups according to random number table method, with 10 mice in each group. In addition to the normal control group, the other groups of mice were intraperitoneally injected with 5-fluorouracil injection 50 mg/kg preparation to construct CID mouse model. After 14 days, the expressions of NF-κB and iNOS in jejunum were detected by Western blot.Results:A total of 197 compounds were identified, and 156 key compounds of Liujun Anwei Prescription were screened, involving 82 potential targets, mainly through NOS2 and other key targets, playing a role through cancer pathway, PI3K-Akt, NF-κB signal pathway. The experimental results showed that Liujun Anwei Prescription could significantly down-regulate the protein expressions of NF-κB and iNOS.Conclusion:This study reveals the pharmacodynamic material basis of Liujun Anwei Prescription, which can be achieved by decreaseing the levels of NF-κB and iNOS to affect the inflammatory response of intestinal tissue, improve intestinal mucosal barrier function, and thus improve chemotherapy related diarrhea.

Objective:To investigate the effect of liver cirrhosis complicated with thrombocytopenia on perioperative period.Methods:The retrospective and descriptive study was conducted. The clinical data of 75 cirrhosis patients complicated with thrombocytopenia who were admitted to the Fuyang City Second People's Hospital from July 2020 to February 2022 were collec-ted. There were 56 males and 19 females, aged (58±11)years. Observation indicators: (1) preoperative conditions; (2) intraoperative and postoperative conditions. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the one way ANOVA. Pairwise comparison was conducted using the LSD- t test. Count data were descri-bed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Results:(1) Preoperative conditions. Of 75 cirrhosis patients complicated with thrombocytopenia, there were significant differences in the preoperative Child-Pugh grading and platelet count between patients with mild, moderate, and severe thrombocytopenia ( P<0.05). Results of further analysis showed that compared with patients with mild thrombocytopenia, patients with moderate and severe thrombocytopenia had significantly lower preoperative platelet count ( P<0.05). Compared with patients with moderate thrombocytopenia, patients with severe thrombocytopenia had significantly lower preoperative platelet count ( P<0.05). (2) Intraoperative and postoperative conditions. Of 75 cirrhosis patients complicated with thrombocytopenia, there were significant differences in the surgical anesthesia methods, operation time, postoperative bleeding, duration of hospital stay between patients with mild, moderate, and severe thrombocytopenia ( P<0.05). Results of further analysis showed that compared with patients with mild or moderate thrombocytopenia, patients with severe thrombocytopenia had a higher proportion of general anesthesia during surgery ( P<0.05) and compared with patients with mild thrombocytopenia, patients with severe thrombocytopenia significantly increased operation time and duration of hospital stay ( P<0.05). Of the 6 patients with severe thrombocytopenia, 3 of 5 cases with intraoperative platelet transfusion and 1 case without intraoperative platelet transfusion experienced postoperative bleeding, respectively, showing no significant difference between them ( P>0.05). Four patients with postoperative bleeding were successfully stopped bleeding after treatment and there was no death in the 75 patients. Conclusions:Patients with severe thrombocytopenia have longer operation time and duration of hospital stay, and higher proportion of general anesthesia than those with mild or moderate thrombocytopenia. Perioperative platelet transfusion cannot reduce the risk of postoperative bleeding.

Objective:To observe the expression of adenosine kinase (ADK) in the hippocampus of patients with refractory epilepsy, and to explore the role of ADK in the pathogenesis of refractory epilepsy.Methods:Thirteen patients with intractable epilepsy who underwent surgical resection of hippocampal tissue at the First Affiliated Hospital of Harbin Medical University were collected as the epilepsy group; At the same time, 4 cases of relatively normal temporal lobe brain tissue from patients with traumatic brain injury undergoing debridement surgery (without previous history of epileptic seizures) were collected, and these 4 patients served as the control group. The expression of ADK in two groups of specimens was detected at the tissue, gene, and protein levels using methods such as dual fluorescence immunohistochemistry, real-time quantitative polymerase chain reaction (RT Real time PCR), and Western blotting.Results:In the human brain, ADK was mainly expressed in the nucleus of astrocytes. Through histological observation, ADK was weakly expressed in normal brain tissue, while there is significant proliferation of glial cells and excessive expression of ADK in the brain tissue of patients with refractory epilepsy. The percentage of ADK positive glial cells in the epilepsy group was (53.90±17.59)%, and the control group was (23.82±4.18)%, with a statistically significant difference ( P<0.01). At the genetic level, using RT Real time PCR, it was found that the expression level of ADK mRNA in the epilepsy group was higher than that in the control group, with a 2 -△△Cp of 13.36, which was 13.36 times higher than that in the control group. At the protein level, the expression of ADK protein in the epilepsy group was found to be higher than that in the control group using protein immunoblotting ( P<0.01). Conclusions:ADK is weakly expressed in the nucleus of astrocytes in normal human brain tissue. In the brain tissue of patients with refractory epilepsy, astrocytes significantly proliferate and there is excessive expression of ADK. ADK may play an important role in the occurrence and development of refractory epilepsy in humans.

Objective:To investigate effect of miR-20b on the motor dysfunction after traumatic brain injury (TBI) in mice and the underlying mechanism.Methods:Sixty C57BL/6J mice were divided into sham group, TBI group and TBI+miR-20b Agomir (Agomir-20b) group according to the random number table, with 20 mice per group. A model of severe TBI was induced by controlled cortical impact. After injury, the mice in TBI group were subjected to tail-vein injection of 200 μl Agomir-negative control at dosage of 50 μmol/L and the mice in TBI+Agomir-20b group were subjected to tail-vein injection of 200 μl Agomir-20b at dosage of 50 μmol/L. At days 3 and 7 postinjury, the rate of neuronal apoptosis in the pericontusional region was detected by TUNEL assay, expression levels of apoptosis-related proteins in the pericontusional region were detected by Western blot analysis, including cleaved caspase-3, cleaved poly adenosine diphosphate-ribose polymerases (PARP), B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), motor function was evaluated by beam walking test, and expression levels of cytokine mRNAs in the pericontusional region were detected by real-time quantitative PCR (RT-qPCR), including interleukin (IL)-1β, IL-6, IL-10, inducible nitric oxide synthase (iNOS), arginase (Arg) and macrophage mannose receptor 1 (CD206).Results:In TUNEL assay, the rate of neuronal apoptosis in sham group was significantly lower than that in TBI group and TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01), and there was a significantly lower rate of neuronal apoptosis in TBI+Agomir-20b group as compared with TBI group (all P<0.01). In Western blot analysis, significantly increased levels of cleaved caspase-3, cleaved PARP and Bax proteins and lowered level of Bcl-2 protein were observed in TBI group at days 3 and 7 postinjury as compared with sham group (all P<0.01); similar levels of cleaved caspase-3, cleaved PARP and Bax proteins were found in TBI+Agomir-20b group at days 3 and 7 postinjury as compared with sham group (all P>0.05), and level of Bcl-2 protein in TBI+Agomir-20b group also showed no obvious variation at day 7 postinjury as compared with sham group ( P>0.05) in regardless of a significant reduction at day 3 postinjury ( P<0.01). Significantly increased levels of cleaved caspase-3, cleaved PARP and Bax proteins as well as a significantly reduced level of Bcl-2 protein were found in TBI group at days 3 and 7 postinjury as compared with TBI+Agomir-20b group (all P<0.05 or 0.01). In beam walking test, the latency and foot slip rate in TBI group were significantly higher than those in sham group and TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01). In RT-qPCR analysis, levels of IL-1β, IL-6 and iNOS mRNA in TBI group were significantly higher than those in TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01), but the two groups were similar in levels of IL-10, Arg and CD206 mRNA (all P>0.05). In comparison with sham group, levels of IL-1β, IL-6, iNOS and IL-10 mRNA in TBI+Agomir-20b group had no obvious change at days 3 and 7 postinjury (all P>0.05); level of Arg mRNA in TBI+Agomir-20b group was significantly increased at days 3 and 7 postinjury (all P<0.01); level of CD206 mRNA in TBI+Agomir-20b group did not change significantly at day 3 postinjury ( P>0.05), but was significantly increased at day 7 postinjury ( P<0.01). Conclusions:miR-20b can obviously inhibit neuronal apoptosis to improve motor function after TBI in mice, for which the underlying mechanism is related to Agomir-20b inhibiting the transformation of microglia to pro-inflammatory M1 type after TBI.