Objective To investigate the differential expression of P57kip2 and CDK5 in neural tube defects t(NTD) from the normal ,and provide the clue for the research of the molecular mechanism of the normal neurula formation .Methods A cDNA mi-croarray containing 1 100 known genes was used to compare differences in P57kip2 and CDK5 gene expression between the normal control group and the retinoic acid(RA)-induced NTD group on embryonic(E) day 9 .5 and 10 .5 .Two differentially expressed genes were randomly selected from the two groups for Northern blotting to verify the results of the cDNA microarray .Results Compared the differences of between P57kip2 and CDK5 in normal and E9 .5 d ,E10 .5 d ,E9 .5 d-NTD ,E10 .5 d-NTD ,P57kip2 and CDK5 expression was significantly up-regulated in the before and after the formation of the normal neurulation ,but them showed a downward trend in retinoic acid (RA)-induced NTD(including two phase E9 .5 d and E10 .5 d) .Conclusion P57kip2 and CDK5 in-volved in the physiological process of NTD ,and provide the useful clue for the research of the molecular mechanism of the normal neurula formation .

Objective:To understand main problems existing in the construction of advanced stroke centers in China and put forward solutions, for reference in promoting the standardization construction of advanced stroke centers and improving the efficiency of acute stroke treatment.Methods:The data were derived from relevant data of on-site export guidance in the construction of advanced stroke centers at 175 tertiary hospitals from 2020 to 2021, and the scores of on-site evaluation indicators for the establishment of stroke centers and their formal approval were compared and analyzed. Based on on-site investigation and expert consultation, the common problems existing in the construction of advanced stroke centers were summarized. All data were analyzed by descriptive analysis, the scores of on-site evaluation indicators were expressed by ± s, and paired t test was used for comparison between groups. Results:Compared with the total score(693.04±72.06) of on-site evaluation at the stage of project launch, the total score(747.94±78.10) of on-site evaluation for formal approval of stroke centers of 70 hospitals was higher, and the difference was significant( P<0.01). There were seven common problems in the construction of stroke centers in 175 hospitals, including insufficient attention paid by hospitals, lack of effective performance incentive policies, imperfect treatment procedures and medical norms, and so on. Conclusions:Experts on-site guidance plays an important role in the construction of stroke centers in China. At present, there were still problems to tackle in the construction of stroke centers in hospitals. In order to promote the standardized construction of stroke centers in China and improve the efficiency of stroke treatment, the authors suggest fuorther strengthening the importance attached by hospital leadership and the coordination and organization of functional departments, establishing stroke center models conforming to the actual situation of the hospital, seting up the post of brain and heart health manager, and improving the regional prevention and treatment level of acute stroke.

In order to explore a suitable pathway for the scientific and technological achievement transformation at prefecture-level public hospitals, in October 2020, a prefecture-level tertiary hospital carried out the " 3+ 3+ 3" mode for scientific and technological innovation and achievement transformation. A three-level management structure was established, consisting of the ministry of science and education, the working group on the transformation of scientific and technological achievements, and the leading group. Three management systems were improved and formulated, including the " measures for reimbursement and rewards of scientific and technological achievements ", the " measures for intellectual property management", and the " implementation plan for promoting the transfer and transformation of scientific and technological achievements". The management measures for the three stages of intellectual property protection, incubation of scientific and technological achievements, and transfer and transformation of achievements were improved. These measures provided organizational support, institutional support, and feasible paths for this practice. After nearly three years of practice, hospitals had reduced the number of low-quality patent applications, and the number and amount of scientific and technological achievements transformed increased from 1 achievement and 10 000 yuan in 2020 to 9 achievements and 320 000 yuan in 2022. This exploration could provide a reference for the transfer and transformation of professional scientific and technological achievements in prefecture-level public hospitals in China.

Objective:To investigate the clinical effect of modified atlantooccipital decompression combined with occipitocervical internal fixation on Chiari type I malformation combined with syringomyelia and atlantoaxial dislocation.Methods:Twenty-five patients with Chiari I malformation combined with syringomyelia and atlantoaxial dislocation accepted by modified atlantooccipital decompression combined with occipitocervical internal fixation in our hospital from January 2011 to March 2019. The clinical data of these patients were retrospectively analyzed. The changes of peak velocity of cerebrospinal fluid in the dorsal part of the spinal cord, electrophysiological results, atlantodental interval (ADI) values, sizes of syringomyelia, and Chicago Chiari outcome scale (CCOS) scores before and after operation were compared.Results:The peak velocity of cerebrospinal fluid in the dorsal spinal cord after surgery ([3.25±0.47] cm/s) was statistically higher in these patients than that before surgery ([2.13±0.19] cm/s, P<0.05). As compared with the preoperative results, ADI values, sizes of syringomyelia, and proportion of patients with abnormal electrophysiological monitoring at 6 months after surgery were significantly decreased, and CCOS scores at 6 months after surgery were significantly increased ( P<0.05). There were no new nerve function damage, infection, cerebrospinal fluid leakage, paralysis, respiratory failure or death. Conclusions:Modified atlantooccipital decompression combined with occipitocervical internal fixation plays effective role in atlantooccipital decompression and atlantoaxial anatomical reduction in patients with Chiari malformation type I combined with syringomyelia and atlantoaxial dislocation. The remission rate of syringomyelia is high, the symptoms and signs improve obviously, and the postoperative complications are less.

Cancer is a severe threat to human life and health.The over-activation of oncogenes is the main reason for poor treatment and prognosis of cancer patients.Most of these over-activated oncogenes are protein tyrosine kinase(PTK).Among many PTKs,non-receptor tyrosine kinase(NRTK)is an important signaling molecule that regulates cell proliferation and migration as the primary driver of intracellular signaling pathway transduction.Targeting NRTK has become the focus and difficulty in developing anti-tumor drugs.Traditional Chinese medicine(TCM),with its characteristics of multi-channel,multi-link,multi-target,and low toxicity,plays a significant advantage in treating adjuvant tumors.So far,it has been found various traditional TCM monomers can inhibit NRTK from playing an anti-tumor role.This review summarized the part of Src,Jak,Abl,Fak families,the prominent members of NRTK in tumor progression,as well as the TCM monomers acting on these members.We aimed to provide a theoretical basis for the anti-tumor therapy targeting NRTK and a reference for the search for TCM monomer inhibitors of NRTK.

OBJECTIVE To mine the safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity， and to provide reference for the selection of clinical rational treatment plan and the prevention and treatment of drug adverse reaction （ADR）. METHODS Reporting odds ratio method and proportion report ratio method were used to analyze adverse drug event （ADE） reports of FOLFOX scheme and FOLFIRI scheme in FDA adverse event reporting system during January 1， 2004-June 30， 2022. The potential safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity were mined. RESULTS The amounts of ADE reports related to FOLFOX scheme and FOLFIRI scheme were respectively 3 454 and 1 359； the proportions of male and female patients involved were 1.50∶1 and 1.67∶1 in these two schemes， respectively. The top five countries with the largest number of reports were the United States， Japan， France， Italy and the United Kingdom， respectively accounting for 58.48% and 53.79% of the total reported cases. More than 90% of patients took no more than 5 drugs in combination， the proportion of patients receiving FOLFOX scheme and FOLFIRI scheme combined with anti-angiogenic drugs or epidermal growth factor receptor inhibitors was 45.45% and 86.82%， respectively. Totally 443 ADE reports of FOLFOX scheme-induced hepatotoxicity were collected， and 22 ADR signals were generated， including hepatic sinusoidal obstruction syndrome， nodular regenerative hyperplasia， drug-induced liver injury， blood bilirubin increased， etc. Totally 128 ADE reports of FOLFIRI scheme- induced hepatotoxicity were reported， and 9 ADR signals were generated， including blood bilirubin increased， hepatotoxicity， steatohepatitis， hepatic steatosis， etc. CONCLUSIONS FOLFOX scheme and FOLFIRI scheme can cause different types of hepatotoxicity. Clinical drug monitoring should be strengthened to guarantee drug safety.

Objective To analyze the main active components and potential molecular mechanism of Sophora flavescens against breast cancer based on network pharmacology and molecular docking. Methods The chemical constituents were collected and screened by TCMSP, ETCM database and literature review. The targets of active ingredients were predicted by Swiss Target Prediction database. Breast cancer-related targets were collected by GeneCards, TTD, Drugbank and OMIM. The anti-breast cancer targets of Sophora flavescens were screened by Venny 2.1.0 software. Cytoscape software was used to construct the network diagram of Sophora flavescens-key active ingredients-targets. STRING database was used to analyze the common targets, and PPI network diagram was constructed. GO function enrichment analysis and KEGG pathway enrichment analysis of key target proteins were performed by DAVID database and Hiplot online platform. Schrodinger software was used to calculate the molecular docking between the active ingredients and targets. Molecular biological methods were used to verify the key targets. Results A total of 36 active components with clear structures were screened from Sophora flavescens. 70 anti-breast cancer targets of Sophora flavescens were screened out. 12 core targets including EGFR, AKT1, ESR1, SRC, CYP19A1, AR and ABCB1 participate in endocrine resistance, EGFR tyrosine kinase inhibitors and estrogen signaling pathways in breast cancer. Moreover, the docking score between the core component and the key target AR is the highest. In vitro experiments showed that the extract of Sophora flavescens can inhibit the proliferation of breast cancer cells, induce cell apoptosis and up-regulate AR protein expression. Conclusion It was revealed that Sophora flavescens plays an anti-breast cancer role by regulating complex biological processes through multiple components acting on multiple targets and signaling pathways. The upregulation of AR protein by Sophora flavescens may become a new therapeutic strategy for the treatment of breast cancer.

Paclitaxel is the first-line chemotherapy drug for a variety of cancers. However， the paclitaxel resistance greatly reduced the efficacy in the later treatment stage， which seriously increased the mortality and recurrence rate of cancer and limited the clinical application of paclitaxel. At present， Chinese medicine compound prescription， proprietary Chinese medicine， and Chinese medicine injection are widely used as the adjuvant chemotherapy drugs for the treatment of cancer in clinic. Chinese medicine has shown unique advantages in improving the efficacy of chemotherapy drugs and the prognosis of chemotherapy， and reducing the toxic and side effects. However， the specific mechanism and effective monomer composition of Chinese medicine for reversing the resistance of chemotherapy drugs are unclear， and the application of Chinese medicine in different types of cancer is also limited， which are worthy of further exploration. This review summarized the composition of Chinese medicine monomer with synergistic antitumor effect combined with paclitaxel in recent years. The specific mechanism and pharmacological activities of Chinese medicine monomer reversing paclitaxel resistance were classified. This review found that through acting on the membrane transport protein， Chinese medicine monomer promoted the accumulation of paclitaxel in tumor cells， inhibited the expressions of protein and metabolic enzyme related to multidrug resistance and the metabolism of paclitaxel， and regulated the levels of apoptosis genes and factors and apoptosis-related pathways to promote the inhibitory effect of paclitaxel on cell proliferation. Chinese medicine monomer also significantly improved paclitaxel chemotherapy sensitivity by regulating the expression levels of micro ribonucleic acid （microRNA） and long non-coding ribonucleic acid RNA （lncRNA）， inhibiting the characteristics of tumor stem cells and tumor metabolic reprogramming， improving tumor microenvironment， and triggering tumor cell death autophagy and oxidative stress response. This review provides a theoretical basis for clarifying the specific anti-tumor mechanism of Chinese medicine monomer combined with paclitaxel， which is of great significance for the development of new Chinese medicine and the clinical research of the drugs combined with paclitaxel， and has certain value for the application of Chinese medicine combined with other chemotherapy drugs.