[Objective] To predict potential target genes for the treatment of glioblastoma (GBM) with stigmasterol and construct a relevant prognostic model, in order to reveal its antiglioma mechanism and the role of these target genes in the prognosis of GBM patients. [Methods] Differential expression genes in GBM and stigmasterol target genes were obtained via online databases. Venn diagram was used to select potential target genes for stigmasterol treatment of GBM, and enrichment analysis was performed using R language. Univariate COX regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were made to select stigmasterol target genes related to the prognosis of GBM patients and construct a relevant prognostic model. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting analyses were used to detect the effect of stigmasterol on the expressions of related target genes. [Results] In this study, a total of 31 potential target genes for the treatment of GBM with stigmasterol were identified. Enrichment analysis showed that these target genes were associated with the activation of the G protein coupled receptor (GPCR) signaling pathway and the regulation of lipid metabolism. Regression analysis identified two stigmasterol target genes, namely, fatty acid binding protein 5 (FABP5) and alpha 1B adrenergic receptor (ADRA1B), which are associated with the prognosis of GBM. A prognostic model constructed based on these two genes could accurately predict the prognosis of GBM patients. Finally, stigmasterol inhibited the expressions of these two genes in GBM cells (FABP5: t=9.909, P=0.001; ADRA1B: t=3.319, P=0.029). [Conclusion] Stigmasterol’s anti-tumor effect may be linked to its regulation of GPCR signaling pathways and lipid metabolism. By inhibiting the expressions of FABP5 and ADRA1B, stigmasterol could potentially enhance the prognosis for GBM patients. Additionally, a prognostic model based on the expression levels of FABP5 and ADRA1B can be valuable for predicting patient outcomes and monitoring therapeutic efficacy in GBM.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

【Objective】 To construct an adipose derived stem cell-based alphastatin peptide glioma targeting vector and detect its anti-angiogenesis effect in vitro. 【Methods】 The adipose derived stem cell-based alphastatin peptide glioma targeting vector (Al-ADSCs) was constructed by transfecting the alphastatin peptide lentivirus vector into adipose derived stem cells (ADSCs). The expressions of stem cell markers on the surface of targeted vector were detected by flow cytometry. The expression of alphastatin peptide in the targeted vector and in the cell culture supernatant of the targeted vector were detected by Western blotting and ELISA, respectively. Cell migration assay was used to detect the tendency of the targeted vector toward CD133+ glioma stem cells, and lumen formation assay was used to detect the effect of the targeted vector on endothelial cell angiogenesis in vitro. 【Results】 After transfection, the surface markers of stem cells expressed by targeted vector did not significantly change compared with ordinary adipose derived stem cells. Western blotting showed that the targeted vector could successfully express alphastatin peptide. ELISA showed that the alphastatin peptide was detected in the cell culture supernatant of targeted vector \mg/L]. Cell migration test showed no significant difference in the tendency of CD133+ glioma stem cells between the targeted vector and ordinary adipose derived stem cells \. Lumen formation experiment showed that the targeted vector could inhibit endothelial cell-mediated angiogenesis in vitro [Lumen count: Control group (13.33±0.76)/HPF, ADSCs group (19.40±1.71)/HPF, Al-ADSCs group (7.27±0.31)/HPF, P<0.01]. 【Conclusion】 In the process of constructing the adipose derived stem cell-based alphastatin peptide glioma targeting vector, the stem cell biological characteristics and tumor tendency of targeted vector have no significant changes. This targeted vector can stably express and secrete alphastatin peptide and inhibit endothelial cell-mediated angiogenesis in vitro.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with non-syndromic hearing loss (NSHL). METHODS: Commercialized gene chip was applied to detect common mutations associated with congenital deafness. Whole exome sequencing was carried out for patients for whom gene chip yielded a negative result. Candidate variants were verified by Sanger sequencing. RESULTS: Two patients from the pedigree were discovered to carry compound heterozygous variants of the TRIOBP gene, namely c.3299C>A and c.5185-2A>G. Their parents had normal hearing and were both heterozygous carriers of the above variants. Both variants had co-segregated with the disease phenotype in the pedigree and were unreported previously. CONCLUSION Pathogenic variants of the TRIOBP gene comprise an important factor for NSHL. The novel c.5185-2A>G and c.3299C>A variants discovered in this study have enriched the mutational spectrum of the TRIOBP gene and enabled molecular diagnosis and genetic counseling for the family.
Deafness/genetics* ; Hearing Loss, Sensorineural/genetics* ; Heterozygote ; Humans ; Microfilament Proteins/genetics* ; Mutation ; Pedigree ; Whole Exome Sequencing

【Objective】 To investigate the effects of silencing AEG-1 gene by shRNA on vasculogenic mimicry (VM) of a glioma xenograft model. 【Methods】 U87 glioma cells were infected with AEG-1 shRNA lentivirals. Real-time PCR and Western blotting were used to detect the mRNA and protein expressions of AEG-1 in U87 cells after infected by the AEG-1 shRNA lentivirals. A glioma xenograft model was generated and CD 34/PAS double-staining was performed to detect the VM channels in vivo. The immunohistochemical assay was performed to evaluate the expressions of MMP-2, MMP-9, VE-cadherin, and VEGF in glioma xenograft models. 【Results】 AEG-1 shRNA lentivirals could significantly inhibit the AEG-1 expression in glioma cells (P<0.01). Meanwhile, they also decreased the number of VM in the glioma xenograft model (P<0.01). Furthermore, the expressions of MMP-2, MMP-9, VE-cadherin, and VEGF in glioma significantly decreased in vivo (P<0.01). 【Conclusion】 These results suggest that silencing AEG-1 gene by shRNA can significantly inhibit VM of glioma in vivo, the mechanism of which may partly be through regulating MMP-2, MMP-9, VEGF, and VE-cadherin expressions.

【Objective】 To quantitatively analyze the surgical freedom of odontioectomy via endoscopic endonasal approach. 【Methods】 Seven adult head specimens were dissected by the endoscopic transnasal approach to the sellar region and craniocervical junction. The center of sellar floor (CenSF), opticocarotid recess (LOCR), foramen magnum, atlas, atlas-occipital joint and tip of odontoid process (TOP) were exposed. The surgical freedom of TOP was calculated by using the spatial coordinate positioning system of neuronavigation, and compared with that of LOCR and CenSF. 【Results】 CenSF and LOCR were common landmarks in the endonasal endoscopic approach. When the surgical freedom between TOP and CenSF and LOCR was compared, it indicated that ① The angle of attack on axial plane (AAAP):There was a significant difference among TOP, LOCR and CenSF (5.7 ° vs. 6.9 ° vs. 8.5 °, P=0.004). The comparison between the two groups showed that TOP was less than CenSF (P=0.003). ② The angle of attack on sagittal plane (AASP): There was a significant difference among TOP, LOCR and CenSF (6.3° vs. 7.0° vs. 9.5°, P=0.009). The TOP was less than CenSF (P=0.008). ③ There was no statistical significance between TOP and LOCR in surgical freedom (P=0.604, P=0.688). 【Conclusion】 Endoscopic transnasal approach can provide sufficient surgical freedom for odontoidectomy.

Objective To investigate the effects of stellate ganglion block(SGB)on attention and executive function in middle-aged and elderly patients after surgery.Methods Middle-aged and elderly patients aged 55-75 years who underwent hip replacement surgery under lumbar anesthesia were randomized into a control group and an SGB group.Patients in the SGB group received ultrasound-guided stellate ganglion block 30 min before surgery,and patients in the control group were given no additional treatment before surgery.All patients were tested with a modified version of the Trail Making Test-Part A (TMT-A)and a modified version of the Symbol Digit Modalities Test (SDMT)1 day before surgery and 7 days after surgery.The Z-score method was used to diagnose postoperative attention and/or executive function impairment.Results The modified versions of TMT-A and SDMT had good reliability and validity among Chinese middle-aged and elderly people aged 55-75 years.Age was the main influencing factor for the two tests,and their two parallel versions had good alternate-form reliability.There was no significant difference between the control group and the SGB group in scores of modified TMT-A and SDMT at 7 days after surgery(P＞0.1).However,the incidence of attention and/or executive function impairment was lower in the SGB group than in the control group(19.3％ vs.36.6％,P＜0.05).Conclusions The modified TMT-A and SDMT have good reliability and validity among Chinese middle-aged and elderly people aged 55-75 years.Preoperative SGB may protect attention and executive function in middle-aged and elderly patients.

Objective To investigate the characteristics of auditory event-related potentials(AERP) mismatch negativity and P300 in presbycusis patients.Methods Auditory event-related potentials were recorded from 20 presbycusis patients, 20 normal hearing elderly subjects and 20 normal young volunteers(the control group) in the Oddball stimulus paradigm.Mismatch negativity(MMN) was tested under the status of reading.P300 was tested under the status of concentrating.The latencies and amplitudes of 3 groups were compared.Results The latency of MMN in the presbycusis patient group(187.38±29.63ms) was significantly longer than those of the normal hearing older group(160.10±23.21±ms)and the control group(148.22±19.30 ms)(P<0.01).There were statistically significant differences between the normal hearing older group and control group(P<0.05).The amplitude differences were not statistically significant among the 3 groups(P>0.05).The latency of P300 in the presbycusis patient group (369.83±27.09 ms) was significantly longer than those of the normal hearing older group(332.89±25.60 ms)and the control group(318.51±22.32ms)(P<0.01).The amplitude differences were not statistically significant among the 3 groups(P>0.05).Conclusion The presbycusis patients show some central auditory processing dysfunction and cognitive impairment.MMN and P300 might be used as objective methods for evaluating central auditory processing and cognitive function in presbycusis patients.