ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

Objective:To explore the application value of P1 response threshold of cortical auditory evoked potential（CAEP） in evaluating the rehabilitation effect of cochlear implant in young children. Methods:Thirty-three young children after cochlear implantation were divided into groups according to hearing age: Group A（hearing age 1-<2 years old） 10 people; Group B（hearing age 2-<3 years old） 13 people; Group C（hearing age 3-<4 years old） 10 people. The subjective assessment was carried out using the assessment tool for hearing-impaired children- "Criteria and Methods for assessing Auditory and language ability of hearing-impaired children" and objective electrophysiological examination was carried out using CAEP to evaluate the rehabilitation effect. SPSS 25.0 software was used for statistical analysis. Results:The results of subjective assessment of auditory ability and language ability in each group showed an increasing trend with the increase of auditory age. In this study, the P1 response threshold of CAEP in CI implanted children had a significant positive correlation with the 2 kHz hearing threshold after intervention, and the P1 response threshold of CAEP was negatively correlated with many items in subjective auditory ability and language ability assessment. Conclusion:The P1 response threshold of CAEP has a stable correlation with the results of speech audiometry, which can effectively and objectively evaluate the postoperative rehabilitation effect of young children with cochlear implantation.
Humans ; Child, Preschool ; Infant ; Male ; Female ; Evoked Potentials, Auditory ; Cochlear Implantation/rehabilitation* ; Cochlear Implants ; Auditory Threshold

Objective:To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes.Methods:A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children′s Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out.Results:CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%).Conclusion:The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.

Osteosarcoma is a common primary malignant bone tumor in adolescents and children,characterized by a high recurrence rate and metastasis,making its treatment extremely challenging.Traditional treatment modalities,including surgery,radiation therapy,and chemotherapy,can alleviate symptoms to some extent,but improving long-term survival rates remains a pressing issue.With the continuous development of immunotherapy,breakthroughs have been made in the research of tumor immune microenvironment and the application of immunotherapy in recent years,providing new perspectives and strategies for osteosarcoma treatment.Currently,immunotherapy strategies include tumor vaccines,targeted cytokines,immune checkpoint inhibition,adoptive cell therapy,combination therapy,etc.,significantly enhancing patient immune responses from the aspects of boosting immunity,overcoming immune tolerance,and preventing immune evasion,thereby effectively improving the patients'survival rates and prognosis.This review aims to systematically introduce the immune microenvironment of osteosarcoma and discuss the latest advances in immunotherapy in clinical translational research of osteosarcoma.By deeply understanding the immune characteristics of osteosarcoma and corresponding treatment methods,it is hopeful to provide more effective strategies for personalized treatment,contributing to the improvement of the patients' survival rates and prognosis.

Objective:To explore the efficacy and safety of treating advanced esophageal cancer by implanting the common stent and the radioactive 125I particle stent with endoscope. Methods:The clinical data of patients with advanced esophageal cancer admitted to Jingbian County People's Hospital of Shaanxi Province, the First Affiliated Hospital of Xi'an Medical University, Xijing Hospital of Digestive Diseases of Air Force Medical University and the First Hospital of Yulin of Shaanxi Province from December 2014 to December 2020 were retrospectively analyzed. Patients were divided into common stent group ( n=66) and radioactive particle stent group ( n=34) according to different stent types. The postoperative complications, Karnofsky performance status (KPS) score, dysphagia score, restenosis rate and quality of life were compared between the two groups. Results:The incidences of postoperative retrosternal pain in the common stent group and the radioactive particle stent group were 65.2% (43/66) and 47.1% (16/34) respectively. The incidences of pharyngeal pain and hoarseness were 12.1% (8/66) and 5.9% (2/34) . The incidences of abdominal pain were 9.1% (6/66) and 2.9% (1/34) . The incidences of errhysis were 3.0% (2/66) and 2.9% (1/34) . The incidences of vomiting and nausea were 7.6% (5/66) and 5.9% (2/34) respectively. There were no statistically significant differences between the two groups ( χ2=3.04, P=0.081; χ2=0.40, P=0.527; χ2=0.53, P=0.467; χ2<0.01, P>0.999; χ2<0.01, P>0.999) . In the two groups, KPS scores in the first, second, third and sixth month after operation were higher than those before operation (all P<0.05) . KPS scores of the radioactive particle stent group in the second, third and sixth month were significantly higher than those of the common stent group [ (89.73±7.84) points vs. (82.37±7.42) points, t=4.62, P<0.001; (93.63±8.13) points vs. (88.33±7.28) points, t=3.74, P<0.001; (92.78±6.26) points vs. (87.28±8.73) points, t=3.77, P<0.001]. The dysphagia scores of patients in the two groups in the first, second, third and sixth month were lower than those before operation (all P<0.05) . The dysphagia scores of the radioactive particle stent group in the third and sixth month after operation were significantly lower than those of the common stent group [ (0.68±0.12) points vs. (2.33±0.32) points, t=26.20, P<0.001; (0.82±0.22) points vs. (2.67±0.24) points, t=36.92, P<0.001]. In the third month after operation, the restenosis rate of the radioactive particle stent group was significantly lower than that of the common stent group [5.88% (2/34) vs. 42.4% (28/66) , χ2 =14.27, P<0.001]. The scores of QLQ-C30 and OES-18 scales in the first, second, third and sixth month after operation were lower than those before operation (all P<0.05) . The scores of QLQ-30 scale in the radioactive particle stent group in the second, third and sixth month were significantly lower than those in the common stent group [ (19.12±3.02) points vs. (21.22±2.87) points, t=3.39, P=0.001; (15.04±1.68) points vs. (20.43±2.23) points, t=12.39, P<0.001; (14.38±2.18) points vs. (19.77±3.67) points, t=9.20, P<0.001]. The scores of OES-18 scale in the radioactive particle stent group were also significantly lower than those in the common stent group [ (17.13±2.07) points vs. (20.64±2.11) points, t=7.95, P<0.001; (15.22±1.88) points vs. (19.24±1.76) points, t=10.62, P<0.001; (14.74±2.36) points vs. (18.53±3.27) points, t=6.01, P<0.001]. Conclusion:The radioactive particle stent can improve the quality of life of patients with advanced esophageal cancer with esophageal stenosis, so as to improve dysphagia and reduce the restenosis rate after operation. However, whether it is obviously superior to common stent in prolonging survival time and reducing complications needs to be further confirmed by a multicenter, prospective, large-sample randomized controlled study.

In modern medicine, bone and dental loss and defects are common and widespread morbidities, for which regenerative therapy has shown great promise. Mesenchymal stem cells, obtained from various sources and playing an essential role in organ development and postnatal repair, have exhibited enormous potential for regenerating bone and dental tissue. Currently, mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering. Nevertheless, the efficacy of MSC-based regeneration is not always fulfilled, especially in diseased microenvironments. Specifically, the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs, both as donors and recipients. Accordingly, approaches targeting a diseased microenvironment have been established, including improving the diseased niche to restore endogenous MSCs, enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies. Moreover, the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy. In this review, we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment, emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.

OBJECTIVE:To observe clinical efficacy and safety of alprostadil combined with salvia ligustrazine in the treat-ment of aged patrents with unstable angina pectoris. METHODS:A total of 150 patients with unstable angina pectoris department of our hospital during Oct. 2011-Mar. 2015 were randomly divided into alprostadil group,salvia ligustrazine group and combination group according to random number table,with 50 cases in each group. Three groups received routine treatment. Alprostadil group additionally received Alprostadil injection 100 μg added into 0.9％ Sodium chloride injection 250 mL,ivgtt,qd,on the basis of routine treatment. Salvia ligustrazine group additionally received Salvia ligustrazine injection 10 mL added into 0.9％ Sodium chlo-ride injection 250 mL,ivgtt,qd,on the basis of routine treatment. Combination group additionally received constant dose of Al-prostadil injection and Salvia ligustrazine injection. Hemorheological indexes (high shear whole blood viscosity,low shear whole blood viscosity,plasma viscosity,hematocrit,fibrinogen),cardiac function indexes(LVEF,SV,LVEFD,LVST),serum CRP, NO,ET,SOD and clinical efficacies were observed in 2 groups before and after treatment;the occurrence of ADR was compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in hemorheological indexes,cardiac function indexes or serum CRP,NO,ET,SOD level between 2 groups (P>0.05). After treatment,plasma viscosity,the whole blood high and low shear viscosity,hematocrit,fibrinogen,serum CRP and ET levels of 3 groups were decreased significantly,while LVEF,SV,serum levels of NO and SOD were increased significantly,combination group was significantly better than alprostadil group and salvia ligustrazine group,with statistical significance (P<0.05). There was no statistical significance in above indexes between alprostadil group and salvia ligustrazine group (P<0.05). Total response rate of combination group was 90.00％,which was significantly higher than 74.00％of alprostadil group and 72.00％of salvia ligustrazine group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Alprostadil combined with salvia ligustrazine can effectively reduce the blood viscosity of patients with unstable angina pectoris,improve cardi-ac function and endothelial function,reduce myocardial ischemia injury and show significant therapeutic efficacy and safety without increasing the incidence of ADR.

ObjectiveTo investigate the clinical effect and safety of albumin-bound paclitaxel (Nab-P) as the first-line treatment for advanced primary liver cancer. MethodsA retrospective analysis was performed for the clinical data of 23 patients with advanced primary liver cancer who were admitted to the Department of Medical Oncology in Chinese PLA General Hospital from May 2014 to December 2015. According to the treatment regimen, these patients were divided into observation group and control group. The 12 patients in the observation group were treated with Nab-P, among whom 5 were treated with Nab-P combined with tegafur, gimeracil and oteracil, 5 were treated with Nab-P combined with capecitabine, and 2 were treated with Nab-P alone; the 11 patients in the control group were treated with gemcitabine combined with oxaliplatin. One cycle of the treatment was 21 days for each treatment regimen; therapeutic effect was evaluated every 2 cycles, and adverse events were evaluated every cycle. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups, the Kaplan-Meier survival curves were used to analyze progression-free survival, and the log-rank test was used to compare survival rates between groups. ResultsAll the patients were eligible for evaluation of clinical outcome and adverse events. In the observation group, 2 patients achieved partial remission, 7 had a stable disease, and 3 had a progressive disease; in the control group, 2 achieved partial remission, 5 had a stable disease, and 4 had a progressive disease. There was no significant difference in disease control rate between the two groups (75% vs 64%, χ2=0.350, P＞0.05). There was also no significant difference in the median progression-free survival between the two groups ［5.1 (2.7-6.7) months vs 4.3 (2.5-5.4) months, χ2=0.647, P＞0.05］. As for adverse events, no patient experienced serious adverse events, and there were significant differences in the incidence rates of platelet toxicity and increased aspartate aminotransferase between the two groups (χ2=5.490 and 6.135, P=0.036 and 0.027). ConclusionIn the treatment of advanced primary liver cancer, the medication based on Nab-P shows a good clinical effect and tolerable toxic and side effects; however, due to the small sample size in this study, the clinical studies with a large sample size are needed.

Objective　To observe the methylation status of p16 tumor suppressor gene in human soft tissue leiomyosarcoma (LMS) and its relationship with p16 protein expression. Methods　Methylation-specific PCR (MSP) assay was used to analyze the methylation status of 5′CpG island promoter / exon I region of p16 tumor suppressor gene in 38 LMS, 10 leiomyomas and 5 normal smooth muscle tissues. p16 expression in these tissues were examined by immunohistochemical assay. Results　Hypermethylation of p16 was observed in 23.7% (9/38) of cases, of which 7 with negative pl6 staining and 2 with faint positive staining. In the cases without protein expression, hypermethylation rate of p16 was 50% (7/14). Conclusions　Epigenetic change due to 5′CpG methylation is the main cause of inactivation of p16(INK4) gene which may be involved in tumor pathogenesis.