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Objective To establish the methods of galvanic vestibular stimulation-vestibular evoked myogenic potentials(GVS-VEMPs)in healthy children and to obtain the normal value of GVS-cVEMP and GVS-oVEMP in these children in China.Methods Twenty(3～14 years)healthy children and 24 healthy adults(18～30 years)were enrolled for conventional examinations of GVS-cVEMP and GVS-oVEMP.Using the galvanic stimulation in-tensity under 3 mA/1 ms for children and 5 mA/1 ms for adults.The characteristics of elicitation and parameter re-sults of GVS-cVEMP and GVS-oVEMP in children and adults,as well as the pain scores and the elicitation of differ-ent stimulus intensities in the two age groups were recorded.Results The elicitation of GVS-cVEMP and GVS-oVEMP were both 100.0％in children and adult groups.The p1 latency,n1 latency and p1-n1 interval latency of GVS-cVEMP were 10.46±1.84 ms,16.98±2.12 ms and 6.52±1.42 ms respectively in children group,the n1 la-tency and p1-n1 interval latency were significantly shorter than the adult group(P＜0.05).The n1 latency,p1 la-tency and p1-n1 interval latency of GVS-oVEMP were 8.87±1.40 ms,12.25±1.80 ms and 3.39±1.07 ms re-spectively in children group with no significant difference between the two groups.The thresholds of GVS-cVEMP and GVS-oVEMP in children group were significantly lower than adult group(P＜0.01),but no differences were found in adult group regarding on the amplitude and interaural amplitude asymmetry ratio.In addition,with the in-crease of the intensity of galvanic stimulation,the correlation between pain scores and the elicitation rates of GVS-cVEMP and GVS-oVEMP also increased.Conclusion Using appropriate stimulus intensity and recording methods,GVS-cVEMP and GVS-oVEMP could be successfully assessed and detected in healthy children over 3 years old and adolescents.The latency of GVS-cVEMP in children is slightly shorter than that in adults,therefore we recommend selecting the matched age group for assessment in the children group.

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Objective:To investigate the effect of tripartite motif-containing protein 59 (TRIM59) on glucose metabolism in macrophages and its role in regulating hypoxia-inducible factor-1α (HIF-1α)/IL-10 axis in macrophages under inflammatory conditions.Methods:The differentially expressed genes between macrophages with high expression of TRIM59 and control cells transfected with empty TRIM59 plasmid were analyzed by GO and KEGG. The expression of HIF-1α by RAW264.7 macrophages with high expression of TRIM59 was detected at different time points after lipopolysaccharide (LPS) stimulation by RT-qPCR and Western blot. Bone marrow was isolated from TRIM59-cKO and TRIM59 flox/flox mice and induced to differentiate into bone marrow-derived macrophages (BMDMs). These BMDMs were stimulated with LPS and the supernatants of cell culture were collected at 3, 6, 12 and 24 h after stimulation to detect IL-10 level by ELISA. In addition, mouse models of cecal ligation and puncture (CLP) were established, and bronchoalveolar lavage fluid (BALF) samples were collected at the same time points to detect IL-10 level by ELISA. Histopathological changes in lung tissues were observed after HE staining. Results:There was a significant change in glucose metabolism-related genes in macrophages with high expression of TRIM59, and the content of lactic acid increased significantly. Compared with the control group, the expression of HIF-1α at mRNA level in BMDMs from TRIM59-cKO mice decreased after LPS stimulation ( P<0.05); the level of IL-10 increased at 3 h and 24 h in the TRIM59-cKO group, but there was no significant difference in IL-10 level at 6 h or 12 h between the two groups. In the TRIM59-cKO mouse model of CLP, the levels of IL-10 in the BALF samples increased with time, but decreased at 24 h. The level of IL-10 was higher in the TRIM59-cKO mouse model group than that in the control group at each time point ( P<0.05 or P<0.01). Conclusions:TRIM59 can inhibit inflammation and lung injury by decreasing HIF-1α-mediated lactate secretion and IL-10 expression in macrophages. This study provides a new idea for developing novel anti-sepsis drugs based on TRIM59.

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@#Objective To investigate the clinical efficacy of multidisciplinary team (MDT) model combined with Da Vinci robot-assisted thoracic surgery in the treatment of early non-small cell lung cancer (NSCLC). Methods From July 2020 to December 2021, the patients with NSCLC who received Da Vinci robot-assisted thoracic surgery in the Department of Thoracic Surgery, General Hospital of Northern Theater Command were collected. According to whether MDT were performed before hospitalization, the patients were divided into an MDT group and a common group. The recovery and clinical efficacy were compared between the two groups. Results A total of 187 patients were enrolled, including 81 males and 106 females, aged 63 (56, 67) years. There were 85 patients in the MDT group, and 102 patients in the common group. Compared with the common group, the MDT group had lower incidence of postoperative complications (9.4% vs. 29.4%, P=0.017), shorter intraoperative operation time [55 (45, 61) min vs. 79 (65, 90) min, P<0.001], and less intraoperative blood loss [25 (20, 30) mL vs. 30 (20, 50) mL, P=0.029] in the same operation mode. In addition, the drainage volume on the second postoperative day [270 (200, 350) mL vs. 215 (190, 300) mL, P=0.004], the number of dissected lymph nodes groups [6 (5, 6) groups vs. 5 (3, 6) groups, P=0.004] and the number of dissected lymph nodes [16 (13, 21) vs. 13 (9, 20), P=0.005] in the MDT group were significantly better than those in the common group. The differences in the postoperative intubation time and postoperative hospital stay between the two groups were not statistically significant (P>0.05). Conclusion MDT combined with Da Vinci robot-assisted thoracic surgery can further reduce the risk of surgery, improve the clinical treatment effect, reduce the incidence of postoperative complications, and accelerate the rehabilitation of patients.

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@#Objective To investigate the safety and efficacy of totally no tube three-port thoracoscopic surgery (TNTT) for thymic tumor via lateral thoracic approach. Methods The clinical data of patients with thymoma admitted to the Department of Thoracic Surgery of the General Hospital of Northern Theater Command from November 2021 to May 2022 were retrospectively analyzed. The patients were divided into a TNTT group and a single utility port video-assisted thoracic surgery (SVATS) group according to different surgical methods. The clinical data were compared between the two groups. Results A total of 111 patients were collected. There were 44 patients in the TNTT group, including 20 males and 24 females, with an average age of 60.11±8.64 years, and 67 patients in the SVATS group, including 30 males and 37 females, with an average age of 62.40±7.92 years. There was no significant difference between the two groups in the baseline data (P>0.05). The postoperative hospital stay and intraoperative blood loss were shorter or less in the TNTT group (P<0.05), and the visual analogue scale score 48 hours after the operation was smaller in the SVATS group (P<0.05). Conclusion TNTT has a good surgical safety, and can shorten postoperative hospital stay, reduce intraoperative blood loss, and has significant advantages in enhanced recovery after surgery, but SVATS can reduce postoperative pain in patients.

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@#Objective To analyze the learning curve of Da Vinci robotic segmentectomy. Methods Cumulative sum analysis (CUSUM) was used to analyze the learning curve of Da Vinci robotic segmentectomy performed by the General Hospital of Northern Theater Command from February 2018 to December 2020. The learning curve was obtained by fitting, and R2 was used to judge the goodness of fitting. The clinical data of patients in different stages of learning curve were compared and analyzed. Results The first 50 patients who received Da Vinci robotic segmentectomy were included, including 24 males and 26 females, with an average age of 61.9±10.6 years. The operation time decreased gradually with the accumulation of operation patients. The goodness of fitting coefficient reached the maximum value when R2=0.907 (P<0.001), CUSUM (n) =0.009×n3−0.953×n2+24.968×n−7.033 (n was the number of patients). The fitting curve achieved vertex crossing when the number of patients reached 17. Based on this, 50 patients were divided into two stages: a learning and improving stage and a mastering stage. There were statistical differences in the operation time, intraoperative blood loss, postoperative drainage volume, number of lymph node dissection, postoperative catheter time, postoperative hospital stay, and postoperative complications between the two stages (P<0.05). Conclusion It shows that the technical competency for assuring feasible perioperative outcomes can be achieved when the cumulative number of surgical patients reaches 17.

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Objective @#To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer (FET) cycles in patients with polycystic ovary syndrome (PCOS) . @*Methods @#A retrospective analysis was conducted on patients ’data from 882 FET cycles . According to the pregnancy outcome , the patients were divided into non-implantation group (Group A) , abortion group ( Group B1) and live birth group ( Group B2) . Clinical data and laboratory parameters were compared among the three groups , and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET. Patients were also divided into four groups (C1-C4) based on the number of high-quality embryos obtained (0 - 3 , 4 - 6 , 7 - 10 , ≥11) , and their clinical data and laboratory parameters were compared .@*Results @#The clinical pregnancy rate , live birth rate , and miscarriage rate in the 882 treatment cycles were 71 . 09% (627/882) , 61 . 68% (544/882) , and 13 . 24% (83/627) ,respectively. Single-factor analysis showed significant differences in body mass index (BMI) , infertility type , human chorionic gonadotropin (hCG) day estradiol ( E2 ) level , number of retrieved oocytes , and number of high-quality embryos among Groups A , B1 , and B2 (P < 0. 05) . Further multiple Logistic regression analysis revealed that BMI(OR = 1 . 046 , 95% CI:1 . 001 - 1 . 093 , P = 0. 044) and a history of previous pregnancy(OR = 1 . 417 , 95% CI:1 . 030 - 1 . 950 , P = 0. 032) were independent risk factors for successful FET in PCOS patients , while an increased number of high-quality embryos was an independent protective factor for successful pregnancy. Based on the results of Group B2 , compared to Group A , OR = 0. 920 , 95% CI:0. 880 - 0. 962 , P = 0. 000;compared to Group B1 , OR = 0. 923 , 95% CI:0. 862 - 0. 988 , P = 0. 022 . Compared with the other three groups( C1-C3) , the total amount of gonadotropin (Gn) in the C4 group was the lowest and the number of oocytes obtained was the highest (P < 0. 05) . Multiple comparisons showed that Group C4 had lower BMI , follicle-stimulating hormone (FSH) , very low-density lipoprotein ( vLDL) levels , a higher luteinizing hormone and follicle-stimulating hormone ( LH/FSH) ratio compared to Group C1 (P < 0. 05) . Group C4 had lower fasting insulin (FINS) and homeostasis model assessment of insulin resistance ( HOMA-IR) levels compared to Group C3 , and higher high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A1) levels compared to Groups C2 and C3 (P < 0. 05) . @*Conclusion@#BMI , the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles . Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles .

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Objective To explore the clinical effects of hypoglycemic drugs on depression degree in patients with type 2 diabetes mellitus(T2DM).Methods A total of 160 newly diagnosed T2DM patients or T2DM patients who have not used hypoglycemic drugs in the past 3 months with mild to moderate depressive episodes and visited our outpatient department were enrolled in this study from January to December 2022.All the participants HbA1c were ranged from 7%to 9%.They were randomly divided into four groups:Metformin treatment group(Met,n=40),Met combined with sulfonylurea treatment group(Met+SUs,n=40),Met combined with DPP-4i treatment group(Met+DPP-4i,n=40),and Met combined with GLP-1 receptor agonist treatment group(Met+GLP-1RA,n=40).All the patients were scored with the Hamilton Depression Rating Scale(HAMD)and the Hamilton Anxiety Rating Scale(HAMA)in each group.Results The Met+DPP-4i and Met+GLP-1RA groups showed the most significant decrease in HAMD and HAMA scores after treatment(P<0.05),while the proportion of moderate depression and significant anxiety in HAMD decreased(P<0.05).Pearson correlation analysis showed that?HAMD,?HAMA were positively correlated with ?HbA1c in the Met+GLP-1RA group(P<0.05).Conclusion The combination of Met with DPP-4i and GLP-1RA has the most significant effect on improving the degree of depression in patients with T2DM and depression.

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Informed consent is an important ethical symbol in clinical research,and researchers have the responsibility to fully inform participants of the research information before conducting clinical research.However,it is difficult to obtain complete informed consent form participants or their guardians within a narrow treatment time period in clinical research conducted in emergency situations.Currently,in addition to traditional general informed consent,there are also reality-accepted informed consent,including exemption of informed consent,broad informed consent,and deferred informed consent.By introducing the origin and development process of deferred informed consent in clinical research,this paper sorted out the current application status of deferred informed consent,proposed the prerequisites for applying deferred informed consent in emergency situations,and explored the issues that need to be noted during the application process of deferred informed consent.It is hoped to provide an ethical defense and ethical procedure for the application of deferred informed consent in clinical research in emergency situations.

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BACKGROUND@#Radiotherapy is one of the most common treatments for lung cancer, and about 40%-50% of patients after radiotherapy will appear uncontrolled or recurrence in the case of local tumors. Radioresistance is the predominant cause of local therapeutic failure. Nevertheless, the lack of in vitro radioresistance models is an influential factor obstructing the study of its mechanism. Therefore, the establishment of radioresistant cell lines, H1975DR and H1299DR, was beneficial to explore the mechanism of radioresistance in lung adenocarcinoma.@*METHODS@#The radioresistant cell lines of H1975DR and H1299DR were obtained from H1975 and H1299 cells irradiated with equal doses of X-rays; Clonogenic assays were performed to compare the clone-forming ability of H1975 vs H1975DR cells, H1299 vs H1299DR cells, then fitting cell survival curve by linear quadratic model; The comet assay was employed to examine DNA damage repair and calculate the percentage of DNA tails; The optical microscopy, CCK-8, flow cytometry, Transwell invasion assays were used to compare biological characteristics such as cell morphology, cell proliferation, apoptosis level, cycle distribution, cell migration and invasion; Western blot was carried out to measure the protein expression of DNA damage repair factors, such as DNA-PKcs, 53BP1, RAD51, and p-ATM.@*RESULTS@#After five months of continuous irradiation and stable culture, radioresistant cell lines H1975DR and H1299DR were obtained. The cell proliferation activity, clone formation ability and DNA damage repair ability of the two radioresistant cell lines were significantly improved under X-ray irradiation. The proportion of the G2/M phase was markedly decreased and the proportion of the G0/G1 phase was increased. Cell migration and invasion ability were significantly enhanced. Relative expression levels of p-DNA-PKcs (Ser2056), 53BP1 in the nonhomologous end-joining (NHEJ) repair pathway and p-ATM (Ser1981), RAD51 in the homologous recombination (HR) repair pathway were higher than those in H1975 and H1299.@*CONCLUSIONS@#H1975 and H1299 cell lines can be able to differentiate into lung adenocarcinoma radioresistant cell lines H1975DR and H1299DR by equal dose fractional irradiation, which provided an in vitro cytological model for the study of radiotherapy resistance mechanism of lung cancer patients.

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Objective To construct a nomogram prediction model for the treatment effect of anlotinib with the participation of traditional Chinese medicine syndrome elements on the patients with extensive-stage small cell lung cancer (ES-SCLC) who previously received multiple lines of chemotherapy. Methods The clinical data of 127 patients with ES-SCLC who received at least two cycles of anlotinib treatment were retrospectively studied. Kaplan-Meier method was used to analyze the relationship between each factor and the overall survival time. Cox regression analysis was applied to screen the independent influencing factors of the prognosis of patients with ES-SCLC. R language was employed to build a nomogram prediction model, C-index was used to evaluate the model, and calibration curve was adopted to verify the accuracy of the model. Results Age, PS score, brain metastases, qi deficiency syndrome, yin deficiency syndrome, and blood stasis syndrome were related risk factors for ES-SCLC treated with anlotinib. PS score, brain metastasis, and blood stasis syndrome were independent prognostic factors. On the basis of these three independent influencing factors, a nomogram model was established to predict the prognosis of patients with ES-SCLC treated with anlotinib. The predicted risk was close to the actual risk, showing a high degree of coincidence. Conclusion The nomogram model established with PS score, blood stasis syndrome elements, and brain metastasis as independent factors can predict the prognosis of patients with ES-SCLC receiving second- and third-line treatment of anlotinib.

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OBJECTIVE@#To investigate the variations in the expression of voltage-gated sodium (Nav) channel subunits during development of rat cerebellar Purkinje neurons and their correlation with maturation of electrophysiological characteristics of the neurons.@*METHODS@#We observed the changes in the expression levels of NaV1.1, 1.2, 1.3 and 1.6 during the development of Purkinje neurons using immunohistochemistry in neonatal (5-7 days after birth), juvenile (12-14 days), adolescent (21-24 days), and adult (42-60 days) SD rats. Using whole-cell patch-clamp technique, we recorded the spontaneous electrical activity of the neurons in ex vivo brain slices of rats of different ages to analyze the changes of electrophysiological characteristics of these neurons during development.@*RESULTS@#The expression of NaV subunits in rat cerebellar Purkinje neurons showed significant variations during development. NaV1.1 subunit was highly expressed throughout the developmental stages and increased progressively with age (P < 0.05). NaV1.2 expression was not detected in the neurons in any of the developmental stages (P > 0.05). The expression level of NaV1.3 decreased with development and became undetectable after adolescence (P < 0.05). NaV1.6 expression was not detected during infancy, but increased with further development (P < 0.05). NaV1.1 and NaV1.3 were mainly expressed in the early stages of development. With the maturation of the rats, NaV1.3 expression disappeared and NaV1.6 expression increased in the neurons. NaV1.1 and NaV1.6 were mainly expressed after adolescence. The total NaV protein level increased gradually with development (P < 0.05) and tended to stabilize after adolescence. The spontaneous frequency and excitability of the Purkinje neurons increased gradually with development and reached the mature levels in adolescence. The developmental expression of NaV subunits was positively correlated with discharge frequency (r=0.9942, P < 0.05) and negatively correlated with the excitatory threshold of the neurons (r=0.9891, P < 0.05).@*CONCLUSION@#The changes in the expression levels of NaV subunits are correlated with the maturation of high frequency electrophysiological properties of the neurons, suggesting thatmature NaV subunit expressions is the basis of maturation of electrophysiological characteristics of the neurons.

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Objective:To explore the effect of pre-hospital health education based on "Internet +" on self-management efficacy, anxiety and depression of patients undergoing pulmonary tumor surgery, and provide reference for pre-hospital nursing care of this group.Methods:It was a randomized controlled trial. A total of 100 outpatients in Department of Pulmonary Oncology, Tumor Hospital of Tianjin Medical University to be hospitalized for surgery during November 2021 to March 2022, were divided into experimental group ( n=50) and control group ( n=50) by random number method according to the order of outpatient visits. Patients in control group received routine thoracic surgery nursing and health education after admission. Those in experimental group received "Internet +" pre-hospital health education during patients waiting for hospital beds for surgery, nursing care after admission was the same as that of the control group. The scores of Strategies Used by People to Promote Health (SUPPH) and Hospital Anxiety and Depression Score (HADS) were compared between the two groups 1 day before discharge. Results:At the time of outpatient visit, there was no statistically significant difference between the two groups in the comparison of all dimensions and total scores of SUPPH and the score of HADS ( P>0.05). Total SUPPH score, and self-decompression, self-decision and positive attitude score of experimental group were (110.62 ± 17.73) points, (38.74 ± 6.56) points, (11.98 ± 2.20) points, (59.90 ± 10.18) points, respectively, while in the control group, the scores were (92.86 ± 18.91) points, (32.46 ± 7.39) points, (9.76 ± 2.00) points and (50.64 ± 11.50) points, respectively, with statistically significant differences ( t values were -5.29--4.27, all P<0.01). Besides, the anxiety and depression scores of HADS in experimental group were (3.92 ± 2.25) points and (3.36 ± 2.38) points, respectively, while those in control group were (7.12 ± 3.49) points and (7.00 ± 3.53) points, respectively, and the differences were statistically significant ( t=5.45, 6.04, both P<0.01). Conclusions:The "Internet +" pre-hospital health education model can promote the self-management efficacy of patients undergoing pulmonary tumor surgery, and improve their psychological state during treatment. The study provided reference for promoting diversified extended nursing services in clinical practice.

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Objective:To explore the intervention effect of Shumu Peitu herb-partitioned moxibustion on clinical signs and symptoms and negative emotions of diarrhea-predominant irritable bowel syndrome (IBS-D) patients with liver-stagnation and spleen-deficiency pattern.Methods:A total of 72 patients with IBS-D of liver-stagnation and spleen-deficiency pattern treated in the Department of Gastroenterology of Nanjing Vniversity of Chinese Medicine from September 2021 to June 2022 were selected for randomized controlled trial. The patients were randomly divided into the observation group (2 cases dropped off, 34 cases in total) and control group (1 case dropped off, 35 cases in total) by random number table method. The patients in control group were treated with Tongxieyaofang (TXYF). The patients in observation group were treated with oral administration of TXYF and Shumu Peitu herb-partitioned moxibustion, and both groups were treated for 4 weeks. The clinical efficacy, Traditional Chinese Medicine (TCM) syndrome integral, IBS Quality of Life Questionnaire (IBS-QOL), IBS Symptom Severity Scale (IBS-SSS), Bristol Stool Form Scale and Hospital Anxiety and Depression Scale (HADS) were compared before and after treatment.Results:After treatment, the total effective rate of the observation group was 94.12%(32/34), which was higher than the 71.43%(25/35) in the control group, the difference was significant ( χ2 = 6.18, P<0.05). After treatment, the TCM syndrome integral in the observation group was (7.62 ± 4.08), which was lower than the (9.89 ± 4.71) in the control group, the difference was significant ( t = 2.14, P<0.05). After treatment of 3 days, the scores of quality of life in the five dimensions of dysthymia, behavior disorder, health worry, avoidance of eating and social function in the observation group were (82.44 ± 11.46), (80.25 ± 11.67), (76.23 ± 12.67), (59.80 ± 15.14) and (79.23 ± 11.59) points, which were different with the (73.57 ± 12.39), (72.35 ± 15.48), (69.76 ± 13.11), (50.00 ± 16.17) and (73.04 ± 13.11) points in the control group, the difference were significant ( t values were -3.09 - -2.08, all P<0.05). Three days after treatment, the score of IBS-SSS and Bristol fecal character in the observation group were (118.24 ± 40.64) and (5.09 ± 0.62) points, which were lower than the (146.86 ± 60.09) and (5.51 ± 0.66) points in the control group, the difference were significant ( t = 2.31 and 2.76, both P<0.05). After treatment, the score of HADS-A and HADS-D in the observation group were (6.26 ± 1.75) and (5.29 ± 1.47), which were different with the (7.26 ± 2.19) and (6.17 ± 2.11) in the control group, the difference were significant ( t = 2.08 and 2.00, both P<0.05). Conclusions:Shumu Peitu herb-partitioned moxibustion can effectively improve IBS-D patients with liver-stagnation and spleen-deficiency pattern, relieve clinical symptoms, reduce negative emotions, and improve quality of life.

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Epilepsy is a common chronic neurological disease, and its comorbidity has attracted more attention.The proportion of epileptic children with mental disorders is also increasing year by year.Among them, children with epilepsy have more depression and anxiety disorders.Repeated seizures can easily cause depression and anxiety, and depression and anxiety can also induce epilepsy, thus the two affect each other.The assessment, screening, diagnosis and intervention of comorbid depression and anxiety in children with epilepsy have become an important part of clinical practice.This review summarized the relationship between epilepsy and depression and anxiety disorders in children, and its research progress on pathogenesis, clinical diagnosis, evaluation and treatment.

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Obstructive sleep apnea hypopnea syndrome (OSAHS) is a sleep breathing disorder caused by obstruction of the upper airway during sleep from various causes. At present, the diagnosis and treatment of OSAHS are insufficient. OSAHS causes cognitive decline due to excessive oxidative stress and inflammatory response caused by sleep breathing disorder, and its alteration of the brain gray matter area may be related to cognitive dysfunction. This review investigates the correlation between cognitive dysfunction and brain gray matter areas changes in OSAHS, and elucidates the underlying mechanisms, which provide a theoretical basis for early clinical diagnosis and treatment.

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Objective:To investigate the role of protein phosphatase 4 catalytic subunit (PP4C) in regulating hepatitis B virus X protein (HBx) levels and its effects on the biological functions of HBx, thus to provide a potential therapeutic targets for hepatitis B virus (HBV)-related hepatocellular carcinoma.Methods:In vivo and in vitro interactions between HBx and PP4C were analyzed by co-immunoprecipitation (Co-IP) and GST pull-down assay. Recombinant plasmids of PP4C and HBx were co-transfected with Lipofectamine 3000 reagents into hepatoma cells to detect the protein levels of HBx by Western blot. The half-life of HBx in the transfected cells treated with cycloheximide (CHX) were detected. The phosphorylation assay was used to evaluate the effects of PP4C on HBx phosphorylation. CCK8 assay, wound healing assay and Matrigel invasion chamber assay were used to analyze the effects of PP4C on the biological functions of HBx. Results:PP4C interacted with HBx in vivo and in vitro. PP4C overexpression significantly increased the protein level and stability of HBx and the phosphorylation assay confirmed that PP4C overexpression decreased the serine phosphorylation of HBx in hepatoma cells. PP4C overexpression enhanced the migration and invasion of hepatoma cells, but had no significant effects on the proliferation. Conclusions:The interactions between HBx and PP4C promoted the stability of HBx and ultimately enhanced the migration and invasion of hepatoma cells, and the mechanisms might be related to the decrease of HBx serine phosphorylation by PP4C. This study provided a theoretical basis for further investigation of the pathogenic mechanisms of HBx, and targeting PP4C and HBx interaction might provide insights for developing novel treatment for HBV-related hepatocellular carcinoma.

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As the major means of outpatient payment for basic medical insurance (the insurance for short) relies on fee-for-service, it tends to encourage unreasonable growth of medical expenses. Based on the principal-agent theory, this paper analyzed the principal-agent relationship between the insurance handling agencies and the hospitals designated by the insurance, and constructed a benefit game model of outpatient payment methods and the supporting supervision game model. This practice aims to explore the optimal and balanced benefit of the insurance payment methods and supporting supervision mechanism, and provide decision support for promoting the reform of medical insurance outpatient payment in China. The analysis results of the benefit game model of payment methods showed that a system mixing the post-payment and pre-payment could optimize and maximize the total benefits and interests of all the stakeholders within the system. Specifically, the practice recommended was a mixed payment integrating ambulatory-payment-classification, fee-for-service and global-budget-payment. The analysis of the supporting regulatory game model found that the factors that must be considered to ensure the expected utility of the above mixed payment mode as follows: the gap between the unreasonable income obtained by the hospital by out-of-control charging and the reward obtained by under-control charging, the size of the penalty after the unreasonable income of the hospital was discovered, the size of the regulatory cost and the loss of benefits of the government and the insured group. It is suggested to adopt the mixed payment method mainly based on the ambulatory-payment-classification supported by fee-for-service and global-budget. At the same time, medical insurance agencies can improve their supervision mechanism from such aspects as perfecting penalties, reducing supervision costs, leveraging government administrative power and advocating public supervision.

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Objective To screen potential metabolites and significantly altered metabolic pathways of liver lesions by central carbon pathway metabolites. Methods 32 healthy volunteers (HC), 23 patients with biliary cysts (CYST), 19 patients with biliary stones (Stone), 45 patients with hepatocellular carcinoma (HCC), and 50 patients with hilarcholangiocarcinoma (HCCA) were recruited. Their serum samples were collected for UPLC-QQQ-MS analysis and further MPP statistical analysis. Pattern recognition was further used to discovery the differences in metabolome between groups, and to explore the significantly altered metabolic pathway and possible pathogenic mechanism of liver diseases. Results A total of 15, 7, 7, and 3 metabolites and a total of 8, 4, 4, and 1 metabolic pathway that were significantly different in serum between CYST, Stone, HCC, HCCA and healthy controls were identified and enriched through serum metabolomics analysis, respectively. Conclusion According to the above identified differential metabolites and enriched metabolic pathway results, it is shown that liver lesions mainly involved in the energy metabolism and amino acid metabolism & transport, in addition, inositol phosphate metabolism were significantly changed both in CYST, Stone, HCC and HCCA.

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Objective To observe the dynamic changes of cardiac lymphangiogenesis in Doxorubicin(DOX)-induced dilated cardiomyopathy(DCM)model mice,and to study the the protective mechanism of Kuoxin Decoction.Methods The DCM mouse model was established by intraperitoneal injection of DOX,and the dynamic observation was performed every week.On this basis,60 C57BL/6 mice were randomly divided into 6 groups(n=10):control group,Model group,L-KXD,M-KXD and H-KXD groups and Captopril group.After successful modeling,the KXD and the positive control drug Captopril were administered continuously for 28 days.Echocardiography was used to detect cardiac function in mice,HE staining and Masson staining were used to observe pathological and morphological changes of the heart,Whole-mount immunofluorescent staining was used to detect the expression of LYVE-1 and Podoplanin in epicardial lymphatic vessels,Western blot was used to detect the expression of VEGFR-3 protein,and qPCR was used to detect the expression of VEGFR-3 mRNA.Results DCM mice induced by DOX showed significant cardiac function decline from the third week(DOX:15 mg·kg-1,P<0.05),and significant ventricular remodeling at the fifth week(DOX:15 mg·kg-1,P<0.01);The lymphatic vessel area of the mouse heart decreased significantly from the fourth week(DOX:20 mg·kg-1,P<0.0001),and the expression of VEGFR-3 decreased significantly from the third week(DOX:15 mg·kg-1,P<0.01).Conclusion KXD can improve ventricular remodeling and cardiac function in DOX-induced DCM mice,promote cardiac lymphangiogenesis,and upregulate the expression of VEGFR-3 at protein and mRNA levels,with a better effect than captopril.DOX-induced cardiac lymphangiogenesis in DCM mice leads to severe myocardial fibrosis and weakened cardiac function,which gradually worsens with the accumulation of modeling time and dose.KXD can promote cardiac lymphangiogenesis and improve cardiac function in DOX-induced DCM mice.The mechanism may be related to the up-regulation of VEGFR-3 expression.