Objective To investigate variation of lumbar spine stability in children with spastic cerebral palsy (SCP) after two types selective posterior rhizotomy (SPR) at lumbosacral and conical sites.Methods Forty-five cases of SCP have undergone with lumbosacral SPR and 38 with conical SPR. Posteroanterior, lateral, 40°-double-oblique, and dynamic (hyperextension and hyperflexion) position lumbar Xray films were taken for all of them before and three months to seven years ( 19 months in average) after operation to observe postoperative lumbar deformity, lumbosacral angle, lateral Cobb' s angle, arch-vertex distance, lordotic index, Posner's definition, and other stability indicators pre- and post-operation of the two groups. Results ① There was statistically significant difference in lumbosacral angle, lateral Cobb's angle, arch-vertex distance, lordotic index and Posner's definition at the 1 st to 2nd lumbar vertebrae (L1-L2 ), the 4th to 5th lumbar vertebrae ( L4 - L5 ), and the 5th lumbar to the 1st sacral vertebrae ( L5 - S1 ) among those with lumbosacral SPR before and after operation (P ＜0. 05). But, only Posner's definition at the 12th thoracic vertebra to the 2nd lumbar vertebra ( T12 - L2 ) varied significantly ( P ＜ 0. 05 ) among those with conical SPR ② Various lumbar deformity was observed in six cases ( 13% ) with lumbosacral SPR, three of them with instable neurological symptoms; while two cases (5%) did so after conical SPR,one with neurological symptoms, with statistical significance ( P ＜ 0. 05). Conclusions Little variation of lumbar spine stability is found among children with spastic cerebral palsy in mid-short term after SPR, while influence of conical SPR is much less on lumbar stability. Their long-term postoperative influence has to be followed-up further.

Objective To investigate the clinical value of tumor marker combined with cytokeratin 18 and 19 in the diagnosis of malignant tumors .Methods 264 patients with malignant tumor were selected as the observation group.During the same period,136 patients with benign tumor were selected as the control group .The tumor markers, cytokeratin 18 (CK18) and cytokeratin 19 (CK19) levels were compared between the two groups ,and the positive detection rate of tumor markers combined with CK 18 and CK19 were analyzed .Results The serum CK18 and CK19 levels of the observation group were (25.48 ±75.14) U/L,(18.67 ±64.85)U/L,respectively,which were signifi-cantly higher than those of the control group [(0.56 ±1.52)U/L,(0.76 ±0.43)U/L],the differences were statisti-cally significant (t=17.38,15.75,all P<0.05).The serum levels of CEA,CA125,CA50,CA19-9 and TSGF of the observation group were (21.24 ±30.16) μg/L,(69.85 ±112.75) mU/L,(47.32 ±121.81) mU/L,(41.87 ± 20.65) mU/L,(91.64 ±43.84) mU/L,respectively,which were significantly higher than those of the control group [(1.27 ±0.85) ng/mL,(15.82 ±3.87) mU/L,(12.85 ±31.65) mU/L,(6.89 ±4.85) mU/L,(38.35 ± 8.01) mU/L],the differences were statistically significant (t=15.73,16.89,14.86,17.79,16.73,all P<0.05).The positive detection rates of CK18 and CK19 for gastric cancer (66.67％) and lung cancer (77.14％) were signif-icantly higher than tumor markers ,and the differences were statistically significant (χ2 =5.67,6.78,all P<0.05). The positive detection rate of tumor markers combined with CK 18 and CK19 for malignant tumors ( 75.00％) was significantly higher than CK18 and CK19 joint detection (65.91％),tumor markers (46.97％),the differences were statistically significant (χ2 =6.78,7.12,all P<0.05).Conclusion Tumor markers combined with CK18 and CK19 detection is helpful to improve the detection rate of malignant tumors and provide effective basis for following treatment.

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Objective To study the auditory brainstem response (ABR) of normal adult CBA,C57BL,Kunming and 129 mice and analyze the ABR thresholds and latencies in order to obtain normal values and standardized testing process,thereby providing important reference for future auditory hearing research in mouse.Methods Six -week-old normal mice of CBA,C57BL,Kunming and 129(each strain containing 20 ears of 20 mice) were used in this study.ABR test with both the click and tone burst were carried on.The incidence of each wave and the thresholds and latencies of various strains of mice were recorded.Results For these four strains of mice,wave Ⅱ had the highest occurrence rate and was used to determine the thresholds.Four strains of mice all were sensitive to the sound at 8,12,16 kHz,most to 12 kHz.Under anesthesia condition,the latency of each ABR wave prolonged as testing time increase,especially the waves Ⅲ ～ V which reflected the functions of the part near the cerebral center.Conclusion Under anesthesia state,for these four strains of mice,wave Ⅱ has the highest occurrence rate and is used to determine the threshold.We determine the intensity level at which Wave Ⅱ just appeared as the ABR threshold.The stain of CBA mice is the best one to establish an animal model related to hearing function research because ABR of the other three strains are not stable as the CBA mice.Wave SP can reflect the hair cell functions indirectly.

OBJECTIVE： To study the long-term toxicity of Liqi sanjie extractum in rats after intragastric administration， and to provide reference for safety evaluation before clinical practice. METHODS： A total of 160 rats were randomly divided into control group （normal saline） and Liqi sanjie extractum low-dose， medium-dose and high-dose groups （7.828 0， 15.656 0， 31.312 0 g/kg， calculated by crude drug）， with 40 rats in each group. They were given relevant medicine intragastrically once a day from Monday to Saturday. The experimental period was 120 days， and the recovery period was 30 days after the end of the experiment. General information of rats was observed， and body weight and feed consumption of rats were measured once a week. At the 61st day of administration， the end of administration and the end of recovery period， 10， 20 and 10 rats were collected from each group to observe their hematology， blood biochemistry， organ coefficient and histopathology changes. RESULTS： From 61st day to 120th day of administration， the rats of Liqi sanjie extractum high-dose group had hair loss and erection， and recovered after withdrawal of medicine. During medication， the body weight of mice in Liqi sanjie extractum low-dose and medium-dose groups increased faster than control group， while the body weight of rats in Liqi sanjie extractum high-dose group increased slower than control group. Compared with control group， the feed consumption of Liqi sanjie extractum low-dose group increased， while those of Liqi sanjie extractum medium-dose and high-dose groups decreased； the rats were recovered after drug withdrawal. On the 61st day of administration and after the end of administration， some hematological indexes， blood biochemical indexes and organ coefficients of rats in administration group were significantly different from those of control group （P＜0.05 or P＜0.01）. The hematology， blood biochemistry and organ coefficients of rats were basically recovered after the end of the recovery period. The number of erythrocyte， hematocrit， standard deviation of erythrocyte width， albumin， globulin ratio and potassium K+ levels in Liqi sanjie extractum low-dose group were significantly lower than those in control group （P＜0.05 or P＜0.01）. The absolute value of intermediate cells in blood of rats in Liqi sanjie extractum medium-dose group was significantly higher than that of control group （P＜0.05）， and the mean hemoglobin concentration， K+ and uterine coefficient in blood were significantly lower than those of control group （P＜0.05）. The number of white blood cells， absolute value of lymphocyte， absolute value of intermediate cells， the percentage of intermediate cells， prothrombin time and spleen coefficient in Liqi sanjie extractum high-dose group were significantly higher than those in the control group （P＜0.05 or P＜0.01）. Mean hemoglobin concentration， granulocyte percentage， albumin， alkaline phosphatase and K+ were significantly lower than those in the control group （P＜0.05 or P＜0.01）. No abnormalities in systemic autopsy and histopathology were noticed in rats. CONCLUSIONS： Long-term intragastric administration of Liqi sanjie extractum can cause certain toxic reactions in rats， and low dose of Liqi sanjie extractum causes less and lighter toxic reactions which can be automatically recovered after drug withdrawal. It can provide reference for the determination of clinical safe dose.

OBJECTIVE： To investigate the improvement effects of Liqi sanjie granule on liver-qi stagnation model rats. METHODS： According to the weight， totally 80 rats were randomly divided into blank control group （normal saline）， model control group （normal saline）， Xiaoyao pill control group （positive control a， 750 mg/kg ，calculated by crude drug）， Xiaojin pill control group （positive control b， 200 mg/kg， calculated by pill weight）， Liqi sanjie pill control group （prototype control， 1 957 mg， calculated by crude drug） and Liqi sanjie granule low-dose， medium-dose and high-dose groups （978.5， 1 957， 3 914 mg/kg， calculated by crude drug）， with 10 rats in each group. Each group was given medicine 20 mL/kg intragastrically once a day， for consecutive 21 d. 1 h after per medication， liver-qi stagnation model was established in those groups by binding method except for blank control group. The syrup preference of rats was determined by designing syrup preference test. Rattail suspension test was adopted to determine the hanging immobility time and struggling times of mice. Open-field behavior test was used to determine total behavior score so as to judge the extent of liver-qi stagnation and effect of the drug in rats. RESULTS： Compared with blank control group， hanging immobility time of model control group was significantly prolonged， the syrup preference and the total behavior score of open field test were decreased significantly， with statistical significance （P＜0.05 or P＜0.01）. Compared with model control group， the struggling times of rats were increased significantly in Xiaojin pill control group， Liqi sanjie pill control group and Liqi sanjie granule medium-dose group （P＜0.05 or P＜0.01）； the hanging immobility time of Xiaoyao pill control group， Xiaojin pill control group， Liqi sanjie pill control group， Liqi sanjie granule low-dose and medium-dose groups were shortened significantly； syrup preference and total behavior score of open-field behavior test were increased significantly （P＜0.05 or P＜0.01）. Compared with Liqi sanjie pill control group， the struggling times of rats were decreased significantly and hanging immobility time were prolonged significantly only in Liqi sanjie granule high-dose group （P＜0.05 or P＜0.01）； there was no statistical significance in above indexes of rats in Liqi sanjie granule low-dose and medium-dose groups （P＞0.05）. CONCLUSIONS： Liqi sanjie granule can significantly improve liver-qi stagnation caused by binding method， and the effects of low-dose and medium-dose Liqi sanjie granule are similar to those of Liqi sanjie pill.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).