OBJECTIVES: To investigate the mechanism by which circ_EPHB4 regulates temozolomide (TMZ) sensitivity of glioma cells through the miR-424-5p/Wnt3 signal axis. METHODS: We detected the expression levels of circ_EPHB4, miR-424-5p and Wnt3 mRNA in glioma specimens from 25 patients with primary glioma and 25 patients experiencing relapse following temozolomide-based chemotherapy and in TMZ-sensitive and -resistant glioma A172 and SHG44 cells with circ_EPHB4 knockdown using qRT-PCR, and Wnt3 protein expression level was detected with Western blotting. Cell viability, colony-forming ability, and apoptosis of the cells with circ_EPHB4 knockdown were assessed, and the targeted regulation relationship between circ_EPHB4, miR-424-5p, and Wnt3 was verified by dual luciferase reporter assay and RNA immunoprecipitation (RIP) experiments. The effect of circ_EPHB4 knockdown on tumorigenesis of glioma cells was evaluated in subcutaneous tumor-bearing nude mouse models. RESULTS: The expression of circ_EPHB4 was significantly increased in glioma tissues and cells as compared with normal neural tissues and astrocytes (P=0.014). In TMZ-resistant glioma cells, circ_EPHB4 knockdown resulted in an obvious reduction of IC50 value of TMZ, inhibited cell colony formation, and promoted cell apoptosis, and these effects were reversed by miR-424-5p knockdown. The expressions of miR-424-5p and circ_EPHB4 were negatively correlated in glioma tissues (P=0.011). MiR-424-5p knockdown also attenuated the effect of circ_EPHB4 knockdown on expressions of PCNA, P-gp, MRP1 and bax. CONCLUSIONS Circ_EPHB4 regulates Wnt3 expression through "sponge adsorption" of miR-424-5p, thereby modulating TMZ-resistant glioblastoma cell clonogenesis, apoptosis, and TMZ sensitivity, suggesting the potential of circ_EPHB4 as a therapeutic target for reversing drug resistance of gliomas.
MicroRNAs/genetics* ; Humans ; Temozolomide ; Glioma/genetics* ; Animals ; Mice, Nude ; Cell Line, Tumor ; Wnt3 Protein/metabolism* ; Mice ; Apoptosis ; RNA, Circular ; Drug Resistance, Neoplasm ; Brain Neoplasms/pathology* ; Signal Transduction

OBJECTIVES: To investigate the oncogenic role of circular RNA circ_EPHB4 in glioma and its molecular mechanism. METHODS: Microarray analysis was performed to identify the differentially expressed circRNAs in glioma tissues. The effects of circ_EPHB4 on glioma cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and tumorigenicity in vivo were assessed using scratch wound healing assay, Transwell invasion assay and nude mouse models bearing subcutaneous tumors. RNA immunoprecipitation (RIP), RNA stability assays, and gene overexpression and silencing techniques were employed to validate the synergistic regulatory effect of circ_EPHB4 and the N6-methyladenosine (m⁶A) reader protein YTHDF3 on Wnt3 expression. RESULTS: Circ_EPHB4 was significantly overexpressed by 2.3 folds (|log2FC|=1.2, P<0.01) in glioma tissues compared to the adjacent tissues, and by 2.5 folds in glioma cell line U373 compared to normal cells (P<0.001). Overexpression of circ_EPHB4 significantly enhanced migration and invasion of glioma cells, and promoted the expressions of EMT markers N-cadherin and vimentin. In the tumor-bearing mouse models, the tumor volume in circ_EPHB4 overexpression group was significantly greater than that in the control group, and the lung metastatic foci increased by 4.2 folds. Overexpression of circ_EPHB4 promoted oncogenesis by upregulating Wnt3 expression, while YTHDF3 extended the half-life of Wnt3 mRNA in an m⁶A-dependent manner. Simultaneous knockdown of circ_EPHB4 and YTHDF3 resulted in an obvious reduction of Wnt3 mRNA expression by up to 47% compared to its level following knocking down either circ_EPHB4 or YTHDF3 alone. CONCLUSIONS Circ_EPHB4 and YTHDF3 promote glioma progression by jointly targeting the Wnt3 signaling pathway, which may provide a new therapeutic strategy for gliomas.
Glioma/genetics* ; Humans ; Animals ; Cell Line, Tumor ; RNA-Binding Proteins/genetics* ; RNA, Circular ; Epithelial-Mesenchymal Transition ; Mice, Nude ; Cell Movement ; Wnt3 Protein/genetics* ; Mice ; Disease Progression ; Adenosine/metabolism* ; Brain Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic

BackgroundPrevious studies have found that patients with generalized anxiety disorder （GAD） have impaired performance in executive function， and group cognitive behavioral therapy （CBT） has been shown to be effective in alleviating negative affect in patients with GAD， while its efficacy on executive function remains unclear. ObjectiveTo explore the efficacy of group CBT on anxiety symptom and executive function in GAD patients， so as to provide references for the rehabilitation program for GAD. MethodsA total of 80 consecutive patients with GAD who were hospitalized in Sleep and Psychosomatic Medical Center of Shiyan Taihe Hospital from March 2021 to August 2022 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for GAD were enrolled， and they were assigned into study group （n=40） and control group （n=40） using random number table methods. All patients were subjected to routine medication treatment and regular health education， based on this， study group received group CBT once a week （6 weeks， 60 to 90 minutes per session）. At the enrollment and after 6 weeks of treatment， patients were assessed using Hamilton Anxiety Scale （HAMA） and Frontal Assessment Battery （FAB）. ResultsANOVA with repeated measures on HAMA score revealed a significant time effect （F=1 870.320， P<0.01）， no significant group effect and no significant time×group interaction effect （F=1.254， 0.293， P>0.05）. Significant time effect， group effect and time×group interaction effect were reported on FAB scores （F=311.190， 4.399， 7.021， P<0.05 or 0.01）. Further analysis indicated that FAB scores of both groups after treatment were higher than those at baseline （t=200.569， 115.401， P<0.01）.And the FAB score of study group was higher than that of control group after treatment （t=-3.211， P<0.01）. ConclusionGroup CBT combined with medication treatment for GAD may alleviate the anxiety symptoms and improve executive function in GAD patients. ［Funded by Shiyan Science and Technology Bureau Pilot Scientific Research Project （number， 21Y21）］

Objective:To summarize and analyze the current application status of oral mucosal graft (OMG) technique in the repair of ureteral strictures in China, and clarify the feasibility, safety and effectiveness of this technique.Methods:The 175 patients who underwent repair of ureteral stricture using oral mucosal patches from June 2015 to February 2022 were etrospectively analyzed in 14 medical centers in China, including 49 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 32 cases in Affiliated Seventh Medical Center of PLA General Hospital, 3 cases in The Second Hospital of Anhui Medical University, 6 cases in The First Affiliated Hospital of Zhengzhou University, 56 cases in Peking University First Hospital, 3 cases in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 cases in Shanghai Sixth People' s Hospital, 4 cases in General Hospital of Estern Theater Command, 4 cases in Lanzhou University Second Hospital, 2 cases in Guizhou Province People 's Hospital, 2 cases in Peking University People' s Hospital, 5 cases in Jinzhou First People's Hospital, 5 cases in The First Affiliated Hospital of Wannan Medical College, 1 case in Shandong Provincial Hospital. In this study, 127 patients (72.6%) used lingual mucosal patches, 32(18.3%) labial mucosa, and 16(9.1%) buccal mucosa. The surgical approach for OMG ureteral reconstruction was mainly minimally invasive, with robot-assisted laparoscopy in 84 patients (48.0%), traditional laparoscopic surgery in 87 patients (49.7%), and open surgery in only 4 patients (2.3%). There were 133 males and 42 females with an average age of (35.0±17.2) years. The mean body mass index (BMI) and stenosis length were (23.1±4.1) kg/m 2 and (4.7±1.8) cm, respectively. The stricture was located in the left ureter in 116 patients, right ureter in 58 case and bilateral ureter in 1 case. The most common causes of ureteral stricture were endoscopic surgery in 88(50.3%)patients, congenital stricture in 55(31.4%)patients, failed ureteroplasty in 29(16.6%)patients, history of extracorporeal shock wave lithotripsy in 13(7.4%)patients, radiotherapy history in 3(1.7%)patients and other causes in 6(3.4%)patients. Strictures were mainly located in the upper ureter, accounting for 61.7% (108/175 cases), followed by 36.0% (63/175) at the ureteropelvic junction and 2.3%(4/175)in the middle ureter. According to the surgical methods, the patients were divided into robot-assisted laparoscopic surgery group ( n=84), traditional laparoscopic surgery group ( n=87)and open surgery group ( n=4). Subgroup analysis of patients in robot-assisted laparoscopic and traditional laparoscopic surgery groups was performed. There were no significant difference in preoperative data between the two groups except for age (32.0±18.3) years vs.(37.0±15.9)years, P=0.040], BMI[(22.5±4.3)kg/m 2 vs. (23.7±3.6)kg/m 2, P=0.028], and etiology of stenosis [endoscopic injury, 34(40.5%) vs. 53(60.9%), P=0.012]. Preoperative hydronephrosis and stricture length were assessed by CTU and ureterography. Ureterography 7-9 weeks after surgery showed patency of the reconstructed segment, or no recurrence of hydronephrosis was judged as success. Evaluate the operation method, operation time, success rate, length of OMG in repairing ureteral stricture between laparoscopic and robot-assisted groups. Results:The overall success rate of oral mucosal graft repair surgery reached 97.7%(171/175). The success rate of ureteral reconstruction in the two groups were 96.4%(81/84)and 98.9%(86/87), respectively ( P=0.351), and the difference was not statistically significant. There was no significant difference for operation time, intraoperative blood loss, and mean oral mucosal length between the robotic and laparoscopic groups[(244.7±85.8) min and (222.7±83.5)min ( P=0.116), (58.9±38.6) ml and (68.4±45.5) ml ( P=0.217), (5.0±2.0) cm and (4.6±1.5) cm ( P=0.350)], respectively.Postoperative complications were reported in 23 (13.1%) patients, such as fever, urinary leakage, lymphatic leakage, infection, but only 2 (1.4%) cases patients had complications of Clavien-Dindo score ≥ Ⅲ. The two patients developed urinary stricture after surgery with failed conservative treatment, and no urinary stricture occurred following endoscopic treatment.The short-term (three months after surgery)incidence of complications in the site where the oral mucosa was taken, such as difficulty in opening mouth, pain, and swelling, was 12.0% (21/175), and there was no significant difference for oral complications between patients harvesting different length of mucosal graft. Conclusions:Ureteroplasty with oral mucosal graft is a safe, feasible and reliable technique for ureteral reconstruction. At present, minimally invasive technology is the main surgical approach for ureteroplasty, and there is no significant difference in operation time and success rate between robotic surgery and laparoscopic surgery.

Objective:To explore the risk factors for depression in patients with cognitive impairment and construct a prediction model to preliminarily validate the predictive performance of the model, aiming to provide medical and nursing staff with a screening tool for high-risk groups.Methods:From January 2020 to December 2021, convenience sampling was used to select 1 130 patients with cognitive impairment admitted to the Affiliated Brain Hospital of Nanjing Medical University as the research subject. The research subjects were divided into a modeling group ( n=791) and a validation group ( n=339) at a ratio of 7∶3. The influencing factors of depression in patients with cognitive impairment were determined using binomial Logistic regression and a risk prediction model was established. The predictive performance of the prediction model was tested using the receiver operating characteristic (ROC) curve. Results:The incidence of depression in 1 130 patients with cognitive impairment was 51.3% (580/1 130). Binomial Logistic regression analysis showed that the influencing factors for depression in patients included age, Activities of Daily Living Scale score, Hamilton Anxiety Scale score, Pittsburgh Sleep Quality Index score, and Lewy Body Composite Risk score ( P<0.05). In the modeling group, the area under the ROC curve was 0.921, the Youden index was 0.716, the sensitivity was 0.834, the specificity was 0.882, and the prediction accuracy was 0.858. In the validation group, the area under the ROC curve was 0.896, the Youden index was 0.651, the sensitivity was 0.824, the specificity was 0.827, and the prediction accuracy was 0.825. Conclusions:The depression risk prediction model can effectively predict the risk of depression in patients with cognitive impairment, and can provide a screening tool for high-risk groups for medical and nursing staff.

Objective:To explore the application value of microsurgical tethered cord release in children with tethered cord syndrome under perioperative electro-neurophysiology monitoring.Methods:Ninety-six patients with tethered cord syndrome accepted tethered cord release in our hospital from January 2015 to December 2019 were chosen in our study; perioperative electro-neurophysiology monitoring was performed to evaluate whether there was neurological impairment. The surgical results, neuroelectrophysiological monitoring results, and follow-up results were retrospectively analyzed.Results:In these 96 patients, symptoms disappeared in 45 patients, improved in 34, not improved in 10, worsened in 3, and tethered again in 4 patients, with a total effective rate of 82.6%. No death was noted. Preoperative neuroelectrophysiological monitoring showed abnormal sensory and motor functions of lower limbs in 40 patients, and postoperative monitoring showed abnormal sensory and motor functions of lower limbs in 6 patients. Follow up was performed for an average of 13 months; symptoms improved in 79 patients, stabilized in 10 patients, and aggravated in 7 patients.Conclusion:In children with tethered cord syndrome, tethered cord release should be performed as soon as possible regardless of early neurological injury; perioperative electro-neurophysiology monitoring can protect spinal cord function, prevent nerve function injury, improve the surgical safety and improve the prognosis of these children.

Objective To understand the levels of posttraumatic growth in rescue nurses 6 years after the great Wenchuan earthquake, and analyze the reasons and influence factors. Methods The general information of the nurses and the post-traumatic growth inventory (PTGI) were used to carry out the cross- sectional study in 736 nurses who took part in the rescue works of the great Wenchuan earthquake. Results The average score of PTGI in rescue nurses was (45.39 ± 23.47) points.Rescue nurses had different posttraumatic growth who had different educational level (F=7.180, P=0.000), household income monthly per capita, the type of rescue work, financial loss, health status, residential satisfaction, satisfaction with social support, satisfaction with family members, satisfaction with leaders and colleagues, satisfaction with friends and relatives(F =3.000-17.484, P<0.050). There was also a statistically significant difference between the score of nurses who had received psychological support and who had received no psychological support (t=-3.657, P<0.05). Multiple linear regression analysis showed that satisfaction with friends and relatives, psychological support, household income monthly per capita and satisfaction with leaders and colleagues could affect the total score of PTGI. All the variables could explain 7.5% variance of posttraumatic growth. Conclusions Rescue nurses have relatively low posttraumatic growth. Satisfaction with friends and relatives, psychological support, household income monthly per capita and satisfaction with leaders and colleagues are related to the posttraumatic growth of rescue nurses.

Objective:To compare the personal characteristics between the patients with paradoxical insomnia and the patients with primary insomnia or the normal sleepers.Methods:A case-control study with the proportion at 1∶1∶1 was carried out.The patients with paradoxical insomnia were diagnosed in Sleep Medicine Center of West China Hospital of Sichuan University between March 2013 and December 2013.A case of paradoxical insomnia was matched with two controls:a primary insomnia patient and a normal sleeper.A total of 63 matched cases were collected.A face-to-face survey was conducted by using the following scales:General Data Scale and Eysenck Personality Questionnaire (EPQ).Results:The average scores of psychoticism,extraversion,and neuroticism for paradoxical insomnia cases were (52.1±10.2),(49.6±9.8),and (56.0±12.0),respectively.In general,31.7% of paradoxical insomnia patients had psychoticism or psychoticism tendency in their personality,which were more obvious than those in primary insomnia patients (7.9%) (x2=l 1.228,p<0.0125) and normal sleepers (0) (X2=23.774,P<0.0125).Moreover,19.0% of paradoxical insomnia patients had extroversion or extroversion tendency in their personality,which were more significant than those in primary insomnia patients (3.2%) (Z=-4.047,P<0.0125) but less obvious than those in normal sleepers (60.3%) (Z=-4.754,P<0.0125).Also,46.0% of paradoxical insomnia patients had neuroticism or neuroticism tendency in their personality,which were more significant than those in normal sleepers (0) (x2=37.670,P<0.0125) but similar to those in primary insomnia patients (52.4%) (x2=0.508,P>0.0125).Conclusion:The personal characteristics for paradoxical insomnia patients did not reached obviously abnormal level.However,their psychoticism tendency,extroversion tendency and neuroticism tendency needed to be paid attention.

Objective To explore the resilience status and its influencing factors of rescue nurses in Wenchuan earthquake, so as to provide evidence for future psychological intervention and psychological rehabilitation. Methods Totally 736 nurses who took part in the rescue works of the great Wenchuan earthquake were selected as the research objects. They were surveyed by a self-designed general information questionnaire and the Connor-Davidson resilience scale (CD-RISC) in order to understand the psychological resilience factors of rescue nurses in Wenchuan earthquake. Results Total score of CD-RISC of 736 rescue nurses was (59.03±20.67) points, scores of tolerance, strength and optimism were (29.64±11.58), (20.55±6.70), (8.83±3.50) points, respectively. Univariate analysis showed that rescue nurses had different posttraumatic growth who had different gender, cultural level, household income monthly per capita, financial loss in the disaster, rescue place, physical health status, satisfaction with houses, satisfaction with leaders and colleagues, friends and relatives. Multiple linear regression analysis showed that household income monthly per capita, satisfaction with leaders and colleagues, title and physical health status could affect the total score of CD-RISC (adjust R2=0.157, F=12.163, P<0.01). Conclusions After 6 years of earthquake, the resilience of rescue nurses in disaster areas is at moderate level and needs to be improved. Household income monthly per capita, satisfaction with leaders and colleagues, title and physical health status are independent factors affecting rescue nurses' resilience. It is suggested to pay attention to such high-risk groups, and give them positive and effective psychological intervention to improve the resilience level of disaster relief nurses.

OBJECTIVE: To evaluate the time and effect of shunt operation on cryptococcal meningitis.
 METHODS: A total 7 patients received shunt operation for the therapy of cryptococcal meningitis patients and the data was retrospectively analyzed.
 RESULTS: Intracranial hypertension-caused symptoms were resolved immediately. There was no complication, no infection dissemination and no recrudescence of cryptococcal meningitis. 
 CONCLUSION Shunt operation is effective for intracranial hypertension caused by cryptococcal meningitis. It does not affect the antifungal treatment.
Antifungal Agents ; therapeutic use ; Drainage ; Humans ; Intracranial Hypertension ; surgery ; Meningitis, Cryptococcal ; drug therapy ; surgery ; Recurrence ; Retrospective Studies