ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome， and to provide guidance for national medical decision-making， clinical drug promotion， and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs （Trial Version， 2021） using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software， this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions， including safety pre- and post-market launch， effectiveness in treating migraine， economy （cost-effectiveness）， and innovation， suitability， accessibility， and traditional Chinese medicine （TCM） characteristics in both its technology and clinical applications. ResultSafety： Duliang soft capsules were found to have good safety based on evidence from known adverse reactions （spontaneous reporting system （SRS） data， literature data， etc.）， pre-marketing toxicological research， and post-marketing drug monitoring. Effectiveness： A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy： Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation： Duliang soft capsules， with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components， hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction （CO₂ supercritical extraction technology） and formulation （soft capsule） processes. The product's innovation was rated as "Better". Suitability： A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility： Duliang soft capsules are moderately priced， making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics： The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio （Shi Zhai Bai Yi Xuan Fang） from the Song Dynasty， and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue （Jing Yue Quan Shu） as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch， and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness， suitability， and accessibility， and outstanding TCM characteristics. The product's safety， economy， and innovation received good ratings. In summary， Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics， the evidence was sufficient， and the result was confirmed， providing crucial references for clinical decision-making and pharmaceutical management.

Objective To construct myeloid-specific Spi1 gene knockout mice and analyze their genotypes,so as to provide animal model basis for the study of pathological mechanism of diseases and drug targets.Methods Ac-cording to the principle of CRISPR/Cas9 technology and Cre/LoxP system,sgRNA and Donor vectors were de-signed and constructed.The transcript of Exon 2(Exon 2)was used as the knockout region,and Loxp elements were placed on both sides of Exon 2.Cas9 protein,sgRNA and Donor vector were mixed and microinjected into the fertilized eggs of C57BL/6J mice,the fertilized eggs were transplanted into the uterus of C57BL/6J pregnant female mice,and F0 generation was obtained after 19～20 days.Positive F0 mice were mated with C57BL/6J mice to ob-tain stable F1 Spi1flox/+mice.Spi1flox/+mice of F1 generation were selfed to obtain Spi1flox/flox mice.Spi1flox/flox mated with Lyz2-Cre+mice to obtain Spi1flox/+/Lyz2-Cre+mice,and then mated with Spi1flox/flox,the Spi1flox/flox/Lyz2-Cre+mice were myeloid-specific Spi1 gene knockout(KO)mice.Spi1flox/flox/Lyz2-cre-mice were used as wild-type(WT)mice.DNA of WT and KO mice was extracted,and the genotypes were identified by agarose gel electro-phoresis after PCR amplification.Western blot was used to detect the expression of spleen focus forming virus provi-ral integration oncogene,Spi-1/purine rich box-1(PU.1)in immune cells of WT and KO mice.Results The results of PCR identification showed that the genotype of mice with only 220 bp amplified by flox primer was Spi1flox/flox homozygote,and the genotype of mice with 700 bp amplified by Lyz2-Cre primer was Lyz2-Cre+.Western blot showed that compared with WT group,the protein PU.1 was not expressed in bone marrow-derived macropha-ges(BMDMs)and peritoneal macrophages(PM)in KO group(P<0.01).There was no significant difference of statistics in the expression level of PU.1 in T cells between KO mice and WT mice.The results of PCR and West-ern blot showed that myeloid-specific Spi1 KO mice were successfully constructed.Conclusion The myeloid-spe-cific Spi1 gene KO mice are successfully constructed and identified,which provides animal model basis for further revealing the potential mechanism of PU.1 inimmune regulation.

Objective To breed and identify the T lymphocyte-conditional Spi1 knockout mice for the further in-vestgation of the specific role of Spi1-encoded protein PU.1.Methods The Lck-Cre mice were mated with Spi1flox/flox mice to obtain Lck-Cre×Spi1flox/flox mice(T lymphocyte-specific Spi1 knockout mice),and the genotype was determined by polymerase chain reaction(PCR)and agarose gel electrophoresis.Magnetic beads were used to sort out the splenic T lymphocytes,and the knockdown efficiency of PU.1 in T cells was detected by Western blot,quantitative real-time PCR(qPCR)and flow cytometry.Results The Lck-Cre×Spi1flox/flox mouse genotype was stably inherited.Compared with Spi1flox/flox mice,the expression level of PU.1 was significantly reduced in splenic T cells of Lck-Cre×Spi1flox/flox mice.Conclusion In this study,the T lymphocyte-specific Spi1 knockout mice was successfully constructed by applying Cre/LoxP system and CRISPR/Cas9 technology,which provided a reliable an-imal model for the subsequent experiments of the specific role of PU.1 in T cell-related diseases.

Objective To construct Csf1r-CreERT2 R26REYFP reporter gene mice and assess the efficacy of Csf1r-CreERT2-mediated enhancement of CSF1R in CD45+cells labeled with yellow fluorescein protein EYFP.Methods Csf1r-CreERT2 mice were crossbred with R26REYFP homozygous mice,and Csf1r-CreERT2R26REYFP mice were identified through PCR and Western Blot analyses.Flow cytometry was employed to evaluate CSF1R tag-efficiency in CD45+cells across different mouse tissues following tamoxifen induction.Results Csf1r-CreERT2 R26REYFP reporter gene mice were acquired.In addition,it was found that Csf1r-CreERT2-mediated EYFP could effectively mark CSF1R in various tissues of mice and CD45+cells in different locations.Compared to the R26REYF P group,the highest labeling efficiency was observed in the brain tissue(P＜0.001),the lowest in the thymus tissue(P＜0.05),and no sig-nificant difference was observed in the spleen tissue.Conclusion Adult Csf1r-CreERT2 mice and R26REYFP mice are effective ways to obtain Csf1r-CreERT2 R26REYFP induced conditional fluorescence mice.Csf1r-CreERT2 can mediate EYFP to effectively trace CSF1R in CD45+cells in different parts of mice.

Pain not only affects the physical and mental health of individuals, but also imposes a huge burden on society as a whole. Traditional pain management measures are diverse, but each has its limitations. Therefore, there is an urgent need for new tools. Digital therapies are booming, and virtual reality (VR) has been widely used, especially in the field of pain management. VR uses assistive tools, such as headsets, to build a three-dimensional virtual world with the participation of multiple senses, including vision, hearing, and smell, so that it can make user feel being there. This review aims to summarize the application and mechanism of VR in the field of pain management, with the hope of making VR a new choice for pain management.

Objective To observe the therapeutic effect and safety of inguinal intranodal lymphangiography in patients with abdominal and pelvic cavity traumatic lymphatic leakages.Methods Data of 12 patients with abdominal and pelvic cavity traumatic lymphatic leakages after ineffective conservative treatment and underwent inguinal intranodal lymphangiography were retrospectively analyzed.The clinical manifestations,therapeutic effects and complications were recorded.Results Totally 21 times of inguinal intranodal lymphangiography were performed in 12 patients,including 5 cases received 1 time,6 cases received 2 times and 1 case received 4 times,and the technical success rate of inguinal intranodal lymphangiography was 100%.After inguinal intranodal lymphangiography,7 cases(7/12,58.33%)were cured while 5 cases(5/12,41.67%)were not cured.The incidence of complications of inguinal intranodal lymphangiography was 14.29%(3/21),including chronic diarrhea after 2 times and puncture point pain in 1 case.No serious complication occurred.Conclusion Inguinal intranodal lymphangiography had certain therapeutic effect and high safety for abdominal and pelvic cavity traumatic lymphatic leakages.

Objective To analyze influencing factors of paclitaxel coated ballon(PCB)on long-term restenosis in patients with severe subpatellar artery lesions in type 2 diabetes mellitus(T2DM),and to construct a prediction model.Methods A total of 268 T2DM patients with severe infra-popliteal artery disease and received PCB treatment were selected.Patients were followed up for 1 year after treatment.Patients with target vessel restenosis were included in the observation group,and the other patients were included in the control group.Clinical data of two groups were analyzed.Multivariable Logistic regression analysis was used to analyze influencing factors of long-term restenosis in T2DM patients with severe infra-knee arterial disease,and a nomogram prediction model was constructed.Results A total of 260 patients(97.00%)completed the follow-up,and the incidence of restenosis was 13.85%(36/260).Both univariate and multivariate Logistic regression analysis showed that age,coexisting coronary heart disease,Trans-Atlantic Inter-Society Consensus(TASC)Ⅱ classification,Fontaine staging,glycosylated hemoglobin(HbA1c)and low density lipoprotein cholesterol(LDL-C)were independent influencing factors for the occurrence of long-term restenosis in T2DM patients with severe infra-popliteal artery disease(P<0.05).The risk factor with the highest score in the constructed nomogram prediction model was HbA1c,followed by age,LDL-C,TASCⅡ classification,Fontaine stage and coronary heart disease.According to the column chart,the total score was 210 points,and the probability of long-term restenosis was 90%.The discrimination of the nomogram model was 0.866,with a Brier score of 0.081 and a calibration slope of 0.733.When the risk threshold was 0.15 to 1.0,the net benefit rate of long-term restenosis in T2DM patients with severe infra-popliteal artery disease was greater than that of individual evaluation.The smaller the risk threshold,the greater the net benefit rate.The benefit was the best when the threshold reached 0.23.Conclusion The influencing factors for long-term restenosis in T2DM patients with severe subknee artery disease treated by PCB include age,combined coronary heart disease,TASCⅡ grade,Fontaine stage,HbA1c and LDL-C.The prediction model based on the above influencing factors has important value in predicting long-term restenosis in patients.

Congenital heart disease (CHD) is the most common birth defect, and in recent years, its neurodevelopmental disorder (NDD) has been gradually emphasized, among which neurodevelopmental disorder in complex congenital heart disease (CCHD) is more common, and the research on related risk factors is gradually deepening. The risk factors of CCHD neurodevelopmental disorder are complex and diversified, with synergistic and cumulative effects, which can be classified into preoperative, surgical-related and postoperative according to the time period, and involve various aspects such as genetics, hemodynamic disorders, extracorporeal circulation, nursing care, and family and social factors. In this paper, we try to review the risk factors of neurodevelopmental disorders in CCHD by combining the latest domestic and international studies.

Objective:To investigate the diagnostic value of vaginal color Doppler flow parameters in patients with epithelial ovarian cancer in different FIGO staging.Methods:178 patients with ovarian tumors who were treated by surgery in Dingzhou People’s Hospital from Jul. 2016 to Jul. 2022 were selected, and they were divided into ovarian cancer group (65 cases) and ovarian cyst group (113 cases) according to the results of postoperative pathological diagnosis. According to FIGO staging standards, ovarian cancer was divided into FIGO stage I (18 cases) , FIGO stage II (16 cases) , FIGO stage III (16 cases) and FIGO stage IV (15 cases) . The blood flow parameters of vaginal color Doppler ultrasound were measured, including arterial pulsatility index (PI) , end diastolic flow velocity (EDV) , resistance index (RI) , peak flow velocity (PSV) , serum vascular endothelial growth factor (VEGF) and human epididymal epithelial secretory protein 4 (HE4) . The levels of PI, EDV, RI, PSV, VEGF and HE4 were compared between the two groups and patients with different FIGO stages, and the value of ROC analysis of vaginal color Doppler flow parameters in predicting the occurrence of ovarian cancer was analyzed. The correlation between FIGO stage and vaginal color Doppler flow parameters and serum VEGF and HE4 levels was analyzed by person coefficient.Results:PI and RI levels in ovarian cancer group were (0.79 ± 0.15) , and (0.39 ± 0.12) , lower than those in ovarian cyst group (1.51 ± 0.17) , (0.72 ± 0.16) ; EDV, PSV, HE4, VEGF levels were (13.88 ± 4.18) cm/s, (25.61 ± 4.53) cm/s, (283.92 ± 28.97) pmol/L, and (372.55 ± 38.96) ng/mL, higher than those in ovarian cyst group ( P<0.05) . According to ROC analysis, the best cutoff values of transvaginal color Doppler blood flow parameters for predicting the occurrence of ovarian cancer were PI<1.235, EDV≥10.985 cm/s, RI<0.580, PSV≥22.975cm/s, all P<0.05. The levels of PI and RI in patients with different FIGO stages showed a decreasing trend with the increase of the severity of the disease, while the levels of EDV, HE4 and VEGF showed an increasing trend ( P<0.05) . There was no significant difference in PSV levels between patients with different FIGO stages ( P>0.05) . The correlation analysis showed that FIGO stage was positively correlated with the blood flow parameters EDV and the levels of serum HE4 and VEGF. FIGO stage was negatively correlated with PI and RI ( P<0.05) . Conclusions:There were significant differences in the levels of PI, RI and EDV in patients with ovarian cysts and ovarian cancer at different FIGO stages. The levels of PI, RI and EDV are closely related to the malignant degree of ovarian cancer.

Objective:To compare the efficacy and safety of drug-coated balloons (DCB) combined with bare metal stents (BMS) and BMS only for superficial femoral atherosclerosis obliterans.Methods:The clinical and follow-up data of 80 patients (82 limbs) who received combined treatment or BMS implantation at Cardiovascular Surgery Department of China Japan Friendship Hospital from Jan 2017 to Aug 2022 were retrospectively analyzed.Results:43 patients (43 limbs) were included in combined treatment group. 37 patients (39 limbs) were in BMS only. The average lesion length of combined group was longer than BMS group (19.54±7.04 cm vs. 16.25±6.43 cm, P=0.031). The primary patency rate of combined group at 36 months was not statistically different with BMS only group (56.9% vs. 38.5%, P=0.171). The subgroup analysis of superficial femoral artery TASC C/D (Trans-Atlantic Inter-Society Consensus) and CTO (chronic total occlusion) lesions indicated that efficacy of the combined group was superior to BMS only group. The patency rates of the combined group compared with the BMS group at 36 months were 57.6% vs. 23.8%, P=0.046, 60.2% vs. 31.4%, P=0.028, respectively. There was no significant difference in the FCD-TLR (free from clinical driven target lesion revascularization) between the two groups at 36 months (72.6% vs. 66.5%, P=0.706). There was no significant difference in major adverse events between the two groups ( P>0.05). Conclusion:Paclitaxel drug-coated balloon combined with bare metal stent is a safe and effective treatment for superficial femoral atherosclerosis obliterans, which is superior to bare metal stent, especially in TASC C/D and chronic total occlusive lesions.