As a new type of model organism， zebrafish is gradually gaining prominence in the field of scientific research. The unique biological characteristics and advantages of zebrafish make them play an increasingly important role in the quality evaluation of traditional Chinese medicine. Compared with other common experimental animals， zebrafish have a fast reproductive and growth speed and high embryo transparency， making them an ideal model for evaluating the quality of traditional Chinese medicine. This provides a new perspective and method for research on traditional Chinese medicine. With the growing global interest in traditional Chinese medicine， it has become crucial to find scientific and accurate methods to evaluate the quality and effectiveness of traditional Chinese medicine. The introduction of the zebrafish model has brought new breakthroughs in the quality evaluation of traditional Chinese medicine. To further promote the application of zebrafish in evaluating the quality of traditional Chinese medicine， this article systematically searched and sorted out the previous studies related to the application of zebrafish for this purpose since 2023. The commonly used disease models and indicators of zebrafish in evaluating the effectiveness of traditional Chinese medicine， as well as the mechanism of zebrafish in exploring the active ingredients of traditional Chinese medicine， were primarily reviewed. The application of zebrafish in evaluating the safety of traditional Chinese medicine and the typical examples in ensuring the quality of traditional Chinese medicine were demonstrated. The limitations encountered by zebrafish models in evaluating the quality of traditional Chinese medicine were highlighted. The resolution of these problems will help further improve the accuracy and reliability of zebrafish in evaluating the quality of traditional Chinese medicine. The article discussed the evaluation of effectiveness， safety， and quality control of zebrafish applied in traditional Chinese medicine， so as to provide a reference for establishing standards for traditional Chinese medicine and promoting its modernization in the future.

ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Transverse sinus is an important pathway of intracranial venous reflux,which is also crucial for maintaining cerebral circulation and stabilizing intracranial pressure.Transverse sinus stenosis(TSS)is the most common variation of transverse sinus,which might lead to changes in sinus hemodynamics and pressure and closely related to idiopathic intracranial hypertension,pulsatile tinnitus and chronic headache.The progresses in imaging researches of transverse sinus stenosis were reviewed in this article.

ObjectivesTo investigate the effect of acupuncture intervention at different time during the acute phase of ischemic stroke on limb motor dysfunction 6 months after onset. MethodsThe enrolled ischemic stroke patients from four tertiary hospitals all received western basic treatment for ≥14 days； additionally， they were given the cleaning-mind and opening-orifices acupuncture method， with acupuncture at bilateral Neiguan （PC 6）， Shuigou （GV 26）， and Sanyinjiao （SP 6） of the affected side， once a day for at least 2 times. Three cohorts were formed by the timing of acupuncture intervention of the onset of the disease within 10 days， namely， the acupuncture group of 1-3 days after onset of the disease （195 cases）， the acupuncture group of 4-7 days after onset of the disease （171 cases）， and the acupuncture group of 8-10 days after onset of the disease （96 cases）. Propensity score matching was performed using R4.3.3 software， and there were 89 patients in each of the three groups after matching. Modified Rankin Scale （mRS） score， Fugl-Meyer Scale （FMA） score， EuroQoL 5-Dimension 5-Level （EQ-5D-5L） score and the proportion of good functional outcome were observed in the 3 groups of patients before treatment and 6 months after onset. A logistic regression model was constructed to analyse the effect of the timing of acupuncture intervention on the effectiveness of acupuncture treatment for limb motor dysfunction in ischaemic stroke. ResultsCompared with the pre-treatment of this group， mRS and EQ-5D-5L scores decreased and FMA increased in all three groups 6 months after onset （P＜0.01）， and all the indexes of the onset 1-3 days acupuncture group and the onset 4-7 days acupuncture group were better than those of the onset 8-10 days acupuncture group （P＜0.05）. The proportions of good functional outcome in the onset 1-3 days acupuncture group， the onset 4-7 days acupuncture group， and the onset 8-10 days acupuncture group were 76.40%， 80.90%， and 57.30%， respectively， and the proportions of good functional outcome in the onset 1-3 days acupuncture group and the onset 4-7 days acupuncture group were significantly higher than those in the onset 8-10 days acupuncture group （P＜0.05）. Multifactorial logistic analysis showed that compared with the group with 8-10 days of onset， the group with 1-3 days of onset （OR=2.796， 95%CI： 1.340~5.836， P = 0.006）， and the group with 4-7 days of onset （OR=3.482， 95%CI： 1.647~7.362， P = 0.001） increased the likelihood that patients would be nondisabled 6 months after onset. ConclusionThe intervention of cleaning-mind and opening-orifices acupuncture within 1-7 days of onset for patients with acute ischemic stroke can reduce the rate of disability 6 months after onset， improve limb motor function， and enhance the quality of life.

Objective: To analyze the prevalence and related factors of pediatric flexible flatfoot (PFF) among 7-8 year old children in Changzhou, so as to provide a feasible basis for the prevention and treatment of PFF. Methods: From December 2023 to February 2024, a total of 1 685 children aged 7-8 from 10 primary schools in Changzhou were selected by stratified cluster random sampling method, and screened for PFF by using a foot optical assessment recording device. Information including sex, body mass index (BMI), diet, exercise and shoe wearing habits were collected. The valgus angle of the hindfoot was measured on the body surface by using an orthopedic measuring ruler in the standing position. Pain levels were evaluated by using visual analogue score (VAS) for children with flatfoot syndrome. Multivariate Logistic analysis was used to analyze related factors of PFF. Results: The overall detection rate of PFF was 27.4%, and there was a significant difference in the detection rate of PFF between boys and girls, with 30.3% and 24.1% respectively ( χ 2=7.96, P < 0.01 ). Most cases of PFF were mild flatfoot (60.8%) and bilateral ( 60.4% ). Approximately 13.2% of children with PFF had flatfoot syndrome, with a mean VAS of (2.86±0.73). About 56.1% of children with PFF had a normal valgus angle of the hindfoot. Sex, high BMI and preference for shoe last with front upturned shoe shape were positively correlated with the detection of PFF ( OR= 1.74, 1.54, 1.13, P <0.05). After stratified by sex, regular exercise in boys and age in girls were negatively correlated with the detection of PFF ( OR=0.40, 0.64, P <0.05). Conclusions The detection rate of PFF in 7-8 year old children is high. Additionally, PFF combined with flatfoot syndrome or valgus hindfoot is relatively rare and is likely to be underestimated, which emphasizes the importance of early detection and intervention for PFF.

Objective:To investigate the hemodynamic characteristics of transverse sinus with sigmoid sinus wall dehiscence (SSWD) of pulsatile tinnitus (PT) based on 4D flow MRI.Methods:Retrospective analysis was performed on all patients admitted to Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2021 for dehiscent sigmoid plate pulsatile tinnitus. A total of 26 patients (sides) who met the criteria and underwent 4D flow MRI were included. A total of 26 subjects (46 sides), matched 1∶1 according to gender and age, were included in the normal healthy control group. Nonparametric rank sum test, Student′s t test, and ANOVA were performed by SPSS 19.0 software. Binary Logistic regression was applied to the data with statistical significance. Results:There were more patients with dominant drainage on the affected side in PT group than in control group (73.1% vs. 42.3%). The incidence of transverse with a focal intraluminal filling defect and tapered stenosis was higher than that in control group (21.7% vs. 69.2%; 17.4% vs. 42.3%). Average through-plane velocity and maximum through-plane velocity in PT group were higher than those in control group [(33.75±13.88) cm/s vs. (15.84±7.21) cm/s; (93.19±33.55) cm/s vs. (40.40±14.40) cm/s]. The middle part and proximal end of Flow avg (ml/s) in PT group were larger than those in control group [4.69 (2.87; 5.62) ml/s vs. 2.76 (1.67; 4.99) ml/s; 3.41 (2.16; 5.47) ml/s vs. 2.67 (1.68; 4.41) ml/s]. In control group, the velocity of transverse sinus changed relatively gently, while in PT group, the velocity of proximal sinus increased significantly. Binary Logistic regression showed that SSWD PT was independently correlated with proximal maximum flow velocity [ OR=1.086(1.029-1.146), P=0.003]. Conclusion:4D flow MRI showed that the dominant drainage and higher velocity at the proximal end of the transverse sinus might be an important hemodynamic characteristics of dehiscent sigmoid plate pulsatile tinnitus.

Objective:To investigate the clinical characteristics of cases with different congenital pulmonary airway malformations (CPAM) volume ratios (CVR) and the effect of maternal glucocorticoid treatment during pregnancy on CPAM.Methods:A retrospective study was conducted on 56 singleton pregnant women with fetal CPAM diagnosed prenatally in the Department of Obstetrics and Gynecology at Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, from September 2020 to May 2023. Among these, three cases received maternal glucocorticoid treatment during pregnancy and clinical conditions were reported in detail. Statistical analyses were performed using independent sample t-tests, non-parametric tests, Chi-square tests, or Fisher's exact test. Results:(1) General information: The average age of the 56 pregnant women with CPAM fetuses was (32.0±0.7) years. All fetuses had unilateral lesions, with 25 cases (44.6%) on the left side. Types Ⅰ, Ⅱ, and Ⅲ CPAM accounted for 5.4% (3/56), 50.0% (28/56), and 44.6% (25/56), respectively. Fetal hydrops occurred in two cases, and the maximum CVR during the fetal period for the other 54 non-hydropic fetuses was 0.79±0.66. (2) The CVR threshold for the risk of fetal hydrops was set as the mean maximum CVR of non-hydropic CPAM fetuses plus 2 standard deviations (0.79+2×0.66=2.1). The subjects were divided into two groups based on the maximum CVR during the fetal period: CVR≤2.0 group ( n=50) and CVR>2.0 group ( n=6). Comparison between the CVR>2.0 group and CVR≤2.0 group: The CVR>2.0 group had significantly higher rates of fetal hydrops [2/6 vs. 0.0% (0/50), Fisher's exact test], mediastinal shift [5/6 vs. 32.0% (16/50), χ 2=4.03], polyhydramnios [6/6 vs. 4.0% (2/50), Fisher's exact test], and postnatal surgery [4/5 vs. 22.2% (10/45), continuity correction χ 2=4.86] (all P<0.05). None of the fetuses with CVR≤2.0 had hydrops or received intrauterine intervention. The overall live birth rate was 89.3% (50/56). (3) Maternal glucocorticoid treatment during pregnancy: three of six fetuses with CVR>2.0 were treated with maternal glucocorticoid during pregnancy, and all were delivered alive at term after the intervention with resolution of edema and/or reduction in mass size. Two of them were treated with postnatal thoracoscopic surgery and were followed up to 5 and 14 months of age, respectively, with no abnormalities in feeding and development; the other was not treated surgically until 3 months of age, with no respiratory-related symptoms and no abnormalities in feeding and development. Conclusions:Prenatal ultrasound indicating CVR>2.0 is associated with increased rates of fetal hydrops, mediastinal shift, and polyhydramnios. Maternal glucocorticoid treatment during pregnancy may lead to favorable pregnancy outcomes for these CPAM fetuses.

Objective:To construct a composite evaluation index of fourth-level surgical, for references for horizontal comparison of fourth-level surgical between clinical departments of hospital and hospital performance appraisal.Methods:The data were extracted from the medical record information system and disease diagnosis related group information system of a tertiary public hospital, including the number of surgical patients, the number of fourth-level surgical patients, the case mix index (CMI), and the average length of hospital stay for 23 surgical departments from 2019 to 2023. Based on disease diagnosis related groups, the average length of hospital stay for patients undergoing fourth-level surgery was standardized to obtain the time cost index; Multiply the CMI and time cost index by the fourth-level surgical ratio to obtain the quality coefficient. This coefficient was used to weight the number of fourth-level surgeries to establish the contribution degree of fourth-level surgeries, which was used for the comprehensive evaluation of fourth-level surgery quality and quantity for each surgical department.Results:A total of 329 177 surgical patients were included in this study, including 139 704 patients with fourth-level surgery. From 2019 to 2023, the top 3 departments in terms of the proportion of fourth-level surgery were department J, B and A, and the proportion of fourth-level surgery in departments with high surgical difficulty, such as C and I, ranked 8th and 16th. The top 3 departments with the contribution degree of fourth-level surgery were department A, B and C, I rosed to the 9th, and J felled to the 11th.Conclusions:The fourth-level surgery contribution degree combined the four factors of surgical composition, difficulty, cost and quantity, which could objectively evaluate fourth-level surgeries in different departments.

Objective To investigate the clinical diagnostic value of routine electroencephalogram(EEG)combined with serum miR-146a and miR-129-5p levels in drug-resistant epilepsy.Methods Sixty patients with refractory epilepsy admitted to our hospital from June 2021 to June 2023 were included in the refractory epilepsy group,and 40 healthy volunteers were included in the control group.Human microvascular endothelial drug-resistant cells(HBMECs)continuously exposed to PHT2 were cultured in vitro and transfected with miR-NC(the miR-NC group),miR-146a mimics(the miR-146a mimics group)and miR-129-5p mimics(the miR-129-5p mimics group),respectively.Western blod assay was used to detect the expression of high-mobility group protein B1(HMGB1)in each group.Serum miR-146a and miR-129-5p levels were detected by fluorescent quantitative PCR(polymerase chain reaction),and serum HMGB1 protein expression was detected by Western blod assay.The sensitivity,specificity and accuracy of routine EEG,serum miR-146a and miR-129-5p levels and combined diagnosis of drug-resistant epilepsy were evaluated using the comprehensive consultation results of several expert physicians as the gold standard,and ROC curves were drawn.Results Compared with the control group,the expression of HMGB1 was significantly decreased in the drug-resistant group.Compared with the miR-NC group,HMGB1 expression was significantly decreased in the miR-129-5p mimics group and the miR-146a mimics group(P＜0.05).Compared with the healthy group,the serum HMGB1 protein expression was down-regulated and miR-146a and miR-129-5p expression levels were significantly up-regulated in the refractory epilepsy group.ROC curve analysis indicated that the area under the curve,sensitivity,specificity and accuracy of conventional EEG combined with serum miR-146a and miR-129-5p levels were higher in the diagnosis of refractory epilepsy than that of single diagnostic method.Conclusion The combination of routine EEG and serum miR-129-5p and miR-146a levels can provide help for the diagnosis of drug-resistant patients.