Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Objective:To compare the clinical efficacy of ultrasound-guided spinal nerve block (SNB) and paraverteral nerve block (PVB) in treating postherpetic neuralgia.Methods:A total of 52 patients with postherpetic neuralgia who visited the Pain Clinic of the Xiangya Hospital, Central South University from February 2020 to December 2022 were selected and randomly divided into an ultrasound-guided SNB group and a PVB group using a random number table method, with 26 patients in each group. Patients in the SNB group received ultrasound-guided spinal nerve block therapy; The PVB group received ultrasound-guided paraverteral nerve block treatment. Visual Analog Scale (VAS) scores, 36-Item Short Form Survey (SF-36) scores, and total effective rate were observed in two groups of patients before treatment, 2 weeks after treatment, 1 month after treatment, 3 months after treatment, and 6 months after treatment. Complications during treatment were also observed.Results:The total effective rates of SNB group patients at 1, 3, and 6 months after treatment were significantly higher than those of PVB group (all P<0.05). After treatment, the VAS scores of both groups of patients at each time point were significantly reduced compared to before treatment (all P<0.05); The VAS scores of patients in the SNB group were lower than those in the PVB group at 1, 3, and 6 months after treatment, but the difference was not statistically significant (all P>0.05). There was no statistically significant difference in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores between SNB and PVB groups before nerve block treatment (all P>0.05). The MCS and PCS scores of the two groups of patients were significantly higher than before treatment at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05). The MCS scores of the SNB group were significantly higher than those of the PVB group at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05), but there was no statistically significant difference in PCS scores between the two groups (all P>0.05). Both groups of patients did not experience any serious complications related to the treatment in this study during the follow-up period. Conclusions:Both ultrasound-guided spinal nerve block and paraverteral nerve block can safely and effectively treat postherpetic neuralgia. The clinical effect of ultrasound-guided spinal nerve block in treating postherpetic neuralgia is better than that of paraverteral nerve block.

Objective:To investigate the effect of prospective intervention on emergence agitation and postoperative recovery in patients with chronic sinusitis during preoperative visits.Methods:A total of 80 patients with chronic sinusitis who underwent general anesthesia in Dayi County People′s Hospital of Chengdu City from December 2019 to October 2020 were selected and randomly divided into group D and group G, with 40 patients in each group. Group D received preoperative visit with conventional methods and group G received preoperative visit with prospective intervention methods. The hemodynamic changes of patients in the two groups at 30 min before the operation (T 1) and 1 (T 2), 5 (T 3), 10 (T 4) and 30 min (T 5) after tracheal tube extraction were recorded. The anxiety and depression scores of patients before the intervention and 1 d after the operation were compared between the two groups. The incidence of emergence agitation after the operation and complications during anesthesia awakening period were observed in the two groups, sino-nasal outcome test-20 (SNOT-20) was used to assess the postoperative recovery. Results:The incidence of emergence agitation in group G was lower than that in group D: 7.5%(3/40) vs. 25.0%(10/40), the difference was statistically significant ( χ2 = 4.50, P<0.05). There was no significant difference in systolic blood pressure, diastolic blood pressure and heart rate between the two groups at T 1 and T 5 ( P>0.05), but the level of above indicators in group G at T 2, T 3 and T 4 were significantly higher than those in group D ( P<0.05). The scores of State-Trait Anxiety Inventory(S-AI) and Self-Rating Depression Scale (SDS) in group G at the first day after the operation were significantly lower than those in group D: (35.45 ± 5.32) scores vs. (39.35 ± 4.91) scores, (35.42 ± 7.82) scores vs. (38.76 ± 5.21) scores, the differences were statistically significant ( P<0.05). The incidence of complications during anesthesia awakening period in group G was slightly lower than that in group D ( P>0.05). After the operation, the scores of sinusitis symptoms and nasal symptoms in the two groups were significantly decreased compared with those before the operation, and the scores of group G were significantly lower than those in group D ( P<0.05). Conclusions:Prospective intervention before anesthesia in patients with chronic sinusitis surgery can reduce stress response, improve bad mood, reduce the incidence of emergence agitation, and promote the postoperative recovery.

Objective:To evaluate the pathological features of a heart failure with preserved ejection fraction(HFpEF) model, which is established by spontaneously hypertensive rats (SHR) through high-fat diet and diabetic factors.Methods:Twenty specific pathogen-free grade(SPF grade) and 14-week-old SHR rats were randomly divided into SHR group (normal diet) and HFpEF group [high-fat diet combined with intraperitoneal injection of streptozotocin (STZ, 25 mg/kg) were used to create a diabetic complex model] with 10 rats in each group. Ten SPF and 14-week-old WKY rats with the same genetic background were set as blank control group (WKY group). All rats were fed for 8 weeks. Echocardiography was performed to measure cardiac parameters: peak velocity of early diastolic mitral inflow(E), peak velocity of late diastolic mitral inflow(A), and the early diastolic mitral annulus e′ in the same cardiac cycle, left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), left atrial diameter, right atrial diameter and interventricular septal thickness(IVST). Serological testing included glucose (GLU) and glycosylated serum protein (GSP); Enzyme-linked immunoassay (ELISA) testing included insulin (INS), glucagon (PG), C-peptide (CP), leptin (LEP), atrial natriuretic peptide (ANP) and B-type brain natriuretic peptide (BNP). The rat heart tissue was stained with HE, and the morphological changes of atrial/ventricular tissue were observed under an optical microscope.Results:The pathological characteristics of HFpEF was established in SHR rats fed with high fat and diabetes. Echocardiography showed that compared with the WKY group, the values of E, E/A and E/e′ in the HFpEF group were significantly increased (all P<0.01), and e′and LAEF were significantly reduced (all P<0.01). In the HFpEF group, the anteroposterior and tranverse dimensions of the left atrium and the long-axis dimension of the right atrium increased to varying degrees (all P<0.05), and the IVST was also significantly increased ( P<0.01). At the same time, atrial wall was thickened obviously, myocardial cells were disordered, and myocardial fibers were broken. Compared with the WKY group, the levels of serum markers ANP and BNP in HFpEF group were significantly increased (all P<0.01), and the levels of serum insulin-related indicators INS, PG, CP, LEP, GSP, and GLU increased to varying degrees (all P<0.01). Conclusions:The composite model established by SHR rats through high-fat diet and diabetic factors can simulate the Doppler echocardiographic changes and pathological features of HFpEF, as well as abnormal changes in serum related markers and insulin indicators.

Objective:To explore the biological effects of the targeted nanocomposite on breast cancer 4T1 cells with hepatitis B virus-like particles (HBc-RGD-VLPs) as a carrier for the delivery of anti-cancer drugs, and to provide a new theoretical basis for reducing the toxicity of doxorubicin (DOX) anti-tumor drugs and changing the path of administration.Methods:The hepatitis B pseudoviral particles prepared in the early stage of this laboratory enveloped DOX to form a target nanocomposite HBc-RGD-VLPs/DOX. The homogeneity and morphology of particles were detected by transmission electron microscopy and granular size analyzer, and applied to 4T1 cells for in vitro bioactivity exploration.Results:The structure of the target nanocomposite HBc-RGD-VLPs/DOX was detected by means of a transmission electron microscope, in a homogenous form, and the particle size distribution was 30-35 nm. In vitro cell experiments showed that the safety of target vector HBc-RGD-VLPs was better, the cell survival rate was more than 80%, and the HBc-RGD-VLPs/DOX after encapsulation had a significant inhibitory effect on the growth of 4T1 cells, and the effective inhibitory concentration (IC50) for half of 4T1 tumor cells was 1.445 g/ml. Fluorescence microscopy showed that HBc-RGD-VLP/DOX can be specifically targeted to tumor cells relative to the isolated DOX.Conclusions:The safety of target vector HBc-RGD-VLPs is better, HBc-RGD-VLPs/DOX showed good proliferation inhibitory effect and certain tumor-targeting effect on tumor cells.

Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions. Newly-generated neurons in the subventricular zone migrate to the olfactory bulb (OB) and determine olfactory discrimination, but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear. Our previous study indicated the potential of APPL2 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system. In the present study, we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells (NSCs) and an in vivo animal model-APPL2 transgenic (Tg) mice. In the in vitro study, we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis. In the in vivo study, APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system, including the corpus callosum, OB, and rostral migratory stream. Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice. Furthermore, we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors. In conclusion, APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.

Objective:To test the usefulness of PET-range verification (RV) method for proton radiation accuracy verification in poly (methyl methacrylate) (PMMA) phantom using off-line PET/CT scanning.Methods:Proton irradiation dose of 2 Gy and 4 Gy were delivered in PMMA phantom. Given the difference of clinical target volume (CTV), 7 subgroups with different depth (5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0 cm) were set for each dose (14 radiation plans or radiation fields). PET/CT scan was performed 10 min after irradiation of 48-221 MeV proton beam. A co-registration between CT from treatment planning system and PET/CT was performed, as well as the smoothing and normalization of PET/CT data. The region of interest (ROI) and profile lines were drawn with the Raystation PET-RV software. The predictive induced radioactivity and the measured induced radioactivity profile lines were analyzed to evaluate the Δ R50, namely, the error at the position corresponding to 50% of the maximum predictive induced radioactivity at the end of both curves. Results:The size of each ROI was 5.0 cm×5.0 cm×2.5 cm. Profile lines were evenly distributed with the interval of 3 mm, and totally 289 pairs of profile lines were drew. The 2 Gy- and 4 Gy-dose groups yielded similar mean depth errors (Δ R50 between 1 mm and -1 mm with a standard deviation <1 mm). Conclusions:The off-line PET/CT scanning of PMMA phantom reveals a good agreement between predicted and measured PET data, with error of ±1 mm. The PET-RV method can be extended to clinical cases′ verification in human body treatment with further investigation.

Objective: To compare the biomechanical performance between the single- versus double-threaded cannulated screws in the treatment of femoral neck fractures of Pauwels type Ⅲ. Methods: Models of femoral neck fracture of Pauwels type Ⅲ (70°) were made of the Sawbone synthetic composite femurs. All specimens were divided into 2 groups (n=12). Group A was fixated with single-threaded cannulated screws and group B with double-threaded cannulated screws, both in an inverted triangle configuration. The screws ranged from 90 to 95 mm in length and from 7.3 to 7.5 mm in diameter. All the specimens were subjected to axial stiffness and failure load tests with 7° valgus (simulating normal two-legged weight-bearing stance) and 25° valgus (simulating normal one-legged weight-bearing stance) and torsion test as well. The 2 groups were compared in the torques at axial stiffness angles of 1°, 2°, 3°, 5° and 7°. Results: Group B had significantly greater axial stiffness at 7° valgus and 25° valgus (89±26 N/mm and 128±37 N/mm) and failure load (1,154±368 N) than group A did (36±12 N/mm and 47±16 N/mm; 688±94 N) (P< 0.05). The torques increased with the increase in rotation angle in both groups. However, the torques in group B (3.26±0.96, 4.16±1.23, 4.64±1.13, 5.59±1.26 and 6.53±1.47 N·m) were all significantly larger than in group A (1.44±0.19, 2.03±0.41, 2.33±0.62, 2.74±0.87 and 3.05±1.07 N·m) (P<0.05). Conclusion Double-threaded cannulated screws may provide better biomechanical stability than single-threaded ones, due to their substantial improvement in anti-compression and anti-rotation performance.

Objective To evaluate the clinical efficacy of super-selective prostatic arterial embolization(PAE) for the treatment of benign prostatic hyperplasia(BPH).Methods From February 2012to March 2015,a total of 17 patients with BPH who failed in medical treatment,or unwilling to accept surgery were selected for PAE as the study group.The mean age was 73 years (range 61-84 years) and the mean prostatic volume was 64.6 ml (ranging 50-85 ml).The study group underwent super selective arterial embolization.The internal iliac artery angiography was performed and the main blood vessel of prostate was showed.The femoral artery was punctured under local anesthesia and X-ray monitoring,a F4-5 Cobra catheter was inserted,and then the Embosphere microspheres were implanted.A total of 40 patients who underwent transurethral resection of the prostate(TURP) were selected as the control group.The mean age was 70 years (ranging 59-87 years).The mean prostatic volume was 68.7 ml(ranging 55-90 ml).All cases were followed up for 1 year.The changes of prostatic volume (PV),international prostate symptom score(IPSS),quality of life (QOL),pre-and post-treatment peak urinary flow (Qmax) were evaluated.Results For the 17 patients who underwent PAE,the PV decreased from (64.6 ± 10.2) ml to(42.0 ± 7.5) ml,the IPSS decreased from 23.9 ±4.9 to 13.1 ±3.5,QOL decreased from 4.1 ±0.7 to 2.1 ±0.7,and Q increased from (9.5 ± 3.7) ml/s to(21.8 ± 4.2) ml/s,which were statistically significant (P ＜ 0.05) compared with the pre-treatment parameters.The post-operative parameters of the control group were also significantly improved compared with the preoperative parameters (P ＜ 0.05).Conclusions PAE is safe and effective in treating BPH,especially for those failing in medical treatment,or unwilling to accept surgery.

Objective To investigate the clinical value of intraoperative ultrasound guided precise positioning and enucleation of the functional islet cell tumor.Methods The clinical data of 20 patients with functional islet cell tumor who were admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2005 to December 2011 were retrospectively analyzed.The method of precise positioning,surgical approach and prognosis of the patients were reviewed.Results The accurate rates of computed tomography (CT),magnetic resonance imaging (MRI) and transabdominal B ultrasound in detecting the position of the functional islet cell tumors were 12/18,2/6 and 7/13,respectively,and the diameters of the tumors were (1.7 ±0.8)cm,(1.3 ±0.2)cm and (1.9 ±0.9)cm,respectively.The accurate rates of arterial stimulation venous sampling and pancreatic perfusion CT imaging were 100％,and the diameters of the tumor detected were (0.7 ± 0.3) cm and (0.9 ± 0.4) cm.The accurate rate of intraoperative B ultrasound examination was 14/14,and the diameter of the tumor was (1.5 ± 0.6)cm.Routine surgery was carried out on 6 patients,and 2 patients were complicated with grade C pancreatic fistula,and 1 was complicated with grade A pancreatic fistula.Fourteen patients received precise enucleation of islet cell tumor,and 4 patients were complicated with grade A pancreatic fistula.Twenty patients were followed up.The general condition of the patients was good till April 2012,and no death,tumor recurrence and metastasis were detected.Conclusions Combination of pre-and intraoperative imaging positioning could precisely locate functional islet cell tumor.If the distance between the tumor and main pancreatic duct is above 3 mm,precise enucleation of the islet cell tumor should be considered.