[The effect of the AIM2 inflammasome in noise-induced cognitive dysfunction in rats].

Objective: To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats. Methods: In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1ß (IL-1ß) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining. Results: Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] (P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) (P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1ß and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) (P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant (P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups (P<0.05) . Conclusion: Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

[Arterial spin labeling in assessment of interstitial fibrosis in renal allografts].

Objective: To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation. Methods: This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC). Results: A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g)-1·min-1; ci1 group: (181.7±29.3) ml·(100 g)-1·min-1; ci2 group: (158.8±39.2) ml·(100 g)-1·min-1; ci3 group: (123.1±27.2) ml·(100 g)-1·min-1; F=14.02, P<0.001]. The renal cortical RBF was moderately negatively correlated with the ci score (r=-0.644, P<0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95%CI: 0.772-0.950) and 0.680 (95%CI: 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein (P=0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95%CI: 0.673-0.889) and 0.900 (95%CI: 0.795-0.963), respectively. Conclusion: ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.

Construction of molecular subgroups of ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition. PATIENTS AND METHODS: Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups. RESULTS: Patients with UC were classified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-α antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients. CONCLUSIONS: We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC.

[Genetic analysis of a family with hereditary hemorrhagic telangiectasia caused by endoglin gene mutation].

Objective: To explore the genetic characteristics of a family with hereditary hemorrhagic telangiectasia (HHT) caused by endoglin (ENG) gene mutations. Methods: A total of 17 individuals from a 3-generation HHT family attending the First Affiliated Hospital of Dali University were selected as the research subjects. Clinical data and familial disease status of the HHT family proband were collected. Whole exome sequencing technology was used to screen for suspected pathogenic genes in the proband, and Sanger sequencing was used for family validation. Results: The proband and her mother had recurrent epistaxis and skin mucosal telangiectasia, and enhanced CT scans of the chest of the proband and her mother, daughter, and cousin indicated the presence of varying degrees of pulmonary arteriovenous malformations. The results of the full exon sequencing results showed that the proband carried the ENG gene c.579_599del non-shift deletion mutation, and Sanger sequencing showed that the mother, daughter, and cousin carried the same mutation. Conclusion: ENG gene c.579_ 599del mutation may be the genetic basis of HHT in this family.

[Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF)].

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

[Application value of combined deep inhalation and breath-hold technique guided by four-dimensional CT in preoperative localization of solitary pulmonary nodules].

Objective: To explore the clinical value of four dimensional computed tomography (4 D CT) guided combined with deep inhalation and breath hold (DIBH) technique in the preoperative localization of solitary pulmonary nodules. Methods: The data of a total of 106 patients with solitary pulmonary nodules from March 2018 to May 2021 in the Ningbo First Hospital were collected retrospectively. Among them, there were 26 males and 80 females aged from 21 to 83 (47.4±14.2) years. According to different localization methods, 53 cases were divided into the control group, as the pulmonary nodules were located by CT guided injection of indocyanine green under calm breathing and 53 cases were divided into in the experimental group, as those patients were treated with indocyanine green injection under the guidance of 4 D CT combined with DIBH technology to locate pulmonary nodules. The three-dimensional distance deviation between pulmonary nodules and indocyanine green injection points was compared between the two groups to obtain the accuracy of pulmonary nodule localization. The preoperative positioning time of the two groups was compared by timing. Results: Among the 106 patients, there were 46 pure ground glass nodules, 32 sub solid nodules and 28 solid nodules, all of which were successfully localized before operation, with a success rate of 100%. The size of pulmonary nodules in the control group was (9.1±2.3) mm and the three-dimensional deviation[M(Q1, Q3)]between indocyanine green injection site and pulmonary nodules was X axis [7.0 (3.7, 12.6)] mm, Y axis [6.6 (2.9, 11.2)] mm, Z axis [3.0 (2.0, 6.0)]mm, respectively, and the preoperative positioning time was (11.4±3.8) min. The size of pulmonary nodules in the experimental group was (8.9±2.1) mm, and the deviations in 3 D direction were X axis [4.8 (3.0, 7.9)]mm, Y axis [3.8 (1.3, 7.5)]mm, Z axis [4.0 (2.0, 6.0)] mm, respectively. The preoperative positioning time was (9.3±3.0) min. There were statistically significant differences in preoperative positioning time and deviation of X and Y axis between the experimental group and the control group (P<0.05), but no statistically significant differences was found in deviation of Z axis (P>0.05). Conclusion: 4 D CT guided DIBH technology could improve the accuracy of preoperative localization of pulmonary nodules and save operation time, which is worthy of popularization.

[A study on the effect evaluation of virtual reality on workplace employees' emotional optimization].

Objective: To explore the effect of emotional optimization of workplace employees in immersive virtual natural environment. Methods: In July 2020, 15 subjects were selected to complete two groups of treadmill walking training experiments in virtual natural environment and daily environment respectively. At the same time, the subjects' skin electrical (EDA) , pulse frequency (Pf) , respiratory frequency (Rf) physiological data and Self-Assessment Manikin (SAM) data before and after walking were collected; the mean value of three dimensions of SAM and the emotion difference before and after the experiment were calculated. The differences of physiological indexes and subjective mood changes of subjects were tested by paired sample t-test. Results: Compared with the daily environment, the ΔEDA, ΔPf and ΔRf of the subjects in the virtual natural environment were all decreased , and the differences were statistically significant (P<0.05). There were statistically significant differences in pleasure and arousal between subjects before and after using the virtual natural environment (P <0.05). Compared with the daily environment, the Δpleasure degree of subjects using the virtual natural environment increased, and the Δarousal degree and Δdominance degree decreased, and the differences were statistically significant (P <0.05). Conclusion: Walking in virtual natural environment can help subjects improve their mood, relax and improve the regulation ability of autonomic nervous system.

LncRNA RPPH1 predicts poor prognosis and regulates cell proliferation and migration by repressing P21 expression in gastric cancer.

OBJECTIVE: The purpose of this study was to explore the expression and biological functions of long non-coding ribonucleic acid (lncRNA) ribonuclease P RNA component H1 (RPPH1) in gastric cancer (GC), and to analyze the correlations of lncRNA expression with the clinical features and prognosis of GC patients. PATIENTS AND METHODS: The relative expression of RPPH1 in tissue specimens from 60 GC patients was measured via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the correlations of RPPH1 expression with tumor-node-metastasis (TNM) stage, lymph node metastasis, etc. in GC patients were analyzed. Then, qRT-PCR was performed to detect the relative expression level of RPPH1 in GC cells. Moreover, colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) staining, wound-healing assay, and transwell assay were employed to investigate the influence of RPPH1 on GC cell functions. After interfering in the expression of RPPH1, the changes in p21 (CDKN1A, cyclin dependent kinase inhibitor 1A) expression were determined through qRT-PCR and Western blotting. RESULTS: It was shown in qRT-PCR assay results that the expression of RPPH1 was upregulated in 60 cases of GC tissues. Statistical analysis revealed that RPPH1 expression was positively correlated with the TNM stage, lymph node metastasis, and infiltration depth in GC patients. Besides, highly expressed lncRNA RPPH1 suggested poor prognosis of GC patients. Based on the results of qRT-PCR assay, the expression of RPPH1 in GC cells was upregulated. After interfering in RPPH1 expression, both colony formation assay and EdU staining indicated that the proliferative capacity of GC cells was repressed. Furthermore, it was manifested in the results of wound-healing and transwell assays that the migratory and invasive abilities of GC cells were weakened. Finally, the qRT-PCR and Western blotting assay results demonstrated that p21 expression was upregulated after interfering in the expression of RPPH1 in GC cells. CONCLUSIONS: The expression of lncRNA RPPH1 is upregulated in GC, suggesting that the prognosis of the patients is poor. Highly expressed RPPH1 promotes the proliferation and metastasis of GC cells by regulating p21 expression.

[Application of convolutional neural network to risk evaluation of positive circumferential resection margin of rectal cancer by magnetic resonance imaging].

Objective: To explore the feasibility of using faster regional convolutional neural network (Faster R-CNN) to evaluate the status of circumferential resection margin (CRM) of rectal cancer in the magnetic resonance imaging (MRI). Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-1800017410). Case inclusion criteria: (1) the positive area of CRM was located between the plane of the levator ani, anal canal and peritoneal reflection; (2) rectal malignancy was confirmed by electronic colonoscopy and histopathological examination; (3) positive CRM was confirmed by postoperative pathology or preoperative high-resolution MRI. Exclusion criteria: patients after neoadjuvant therapy, recurrent cancer after surgery, poor quality images, giant tumor with extensive necrosis and tissue degeneration, and rectal tissue construction changes in previous pelvic surgery. According to the above criteria, MRI plain scan images of 350 patients with rectal cancer and positive CRM in The Affiliated Hospital of Qingdao University from July 2016 to June 2019 were collected. The patients were classified by gender and tumor position, and randomly assigned to the training group (300 cases) and the validation group (50 cases) at a ratio of 6:1 by computer random number method. The CRM positive region was identified on the T2WI image using the LabelImg software. The identified training group images were used to iteratively train and optimize parameters of the Faster R-CNN model until the network converged to obtain the best deep learning model. The test set data were used to evaluate the recognition performance of the artificial intelligence platform. The selected indicators included accuracy, sensitivity, positive predictive value, receiver operating characteristic (ROC) curves, areas under the ROC curves (AUC), and the time taken to identify a single image. Results: The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CRM status determined by the trained Faster R-CNN artificial intelligence approach were 0.884, 0.857, 0.898, 0.807, and 0.926, respectively; the AUC was 0.934 (95% CI: 91.3% to 95.4%). The Faster R-CNN model's automatic recognition time for a single image was 0.2 s. Conclusion: The artificial intelligence model based on Faster R-CNN for the identification and segmentation of CRM-positive MRI images of rectal cancer is established, which can complete the risk assessment of CRM-positive areas caused by in-situ tumor invasion and has the application value of preliminary screening.

[Construction of key question list in the evidence-based guidelines for colorectal cancer screening in China].

Objective: To establish the key question list for the development of evidence- based guideline in China according to the content and limitation of current evidence-based guidelines around the world. Methods: First, we introduced the evidence-based guidelines in detail which met the criteria based on World Health Organization guideline development handbook and then formulated the draft list of key questions for the development of evidence-based guidelines. At last, the Delphi method was used to determine the list of key questions in developing evidence-based guidelines of colorectal cancer screening. Results: Totally, 34 questionnaires were collected, with experts from clinical and epidemiological fields. The average experts' authority coefficient was 0.81, indicating a high degree of authority. The concentration of opinions on all items in the questionnaire was relatively high, with the full score ratio greater than 75% and the coefficient of variation less than 0.3. The list of key questions on evidence-based guidelines for colorectal cancer screening has been divided into six parts: epidemiological problems, risk classification, screening age, screening tools, implementation and selection of steering group members, which covers the issues that need to be considered in the development of evidence-based colorectal cancer screening guidelines in China. Conclusion: The key question list for evidence-based guideline development in our study can be applied to the development of evidence-based guidelines for colorectal cancer screening in the future, as well as the development of evidence-based guidelines for other cancer screening in China.