Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective To analyze the effects of deep learning image reconstruction(DLIR)and adaptive statistical iterative recon-struction V(ASIR-V)on the imaging quality of chest CT in patient with pulmonary nodules,and to evaluate the differences based on different image reconstruction techniques in the detection of efficiency of computer-aided diagnosis(CAD)for pulmonary nodules.Methods The image data of pulmonary nodules of eighty patients with chest CT screening were reconstructed with ASIR-V 80％,DLIR-low(DLIR-L),DLIR-medium(DLIR-M)and DLIR-high(DLIR-H)images,respectively.The objective image quality and sub-jective image quality of the four groups were compared and analyzed.Objective image quality includes CT value of region of interest(ROI),noise,signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR)and image average gradient.The diagnostic efficacy of CAD in detecting pulmonary nodules of reconstructed images among four groups were further evaluated.Results There were no signifi-cant difference in CT value of ROI of reconstructed images among the four groups(P＞0.05).The noise,SNR and CNR of DLIR-H images were similar to those of ASIR-V 80％(P＞0.05),but significantly better than those of DLIR-L and DLIR-M(P＜0.05).The average gradient of DLIR-L,DLIR-M and DLIR-H images were significantly higher than those of ASIR-V 80％(P＜0.05).The subjective image quality scores of DLIR-L,DLIR-M and DLIR-H images were significantly higher than those of ASIR-V 80％(P＜0.05),and the subjective image quality score of DLIR-H image was the highest.CAD showed the highest true positive rate in DLIR-H images for detecting pulmonary nodules(P＜0.05),and CAD showed the highest false positives per capita in ASIR-V 80％images for detecting pulmonary nodules(P＜0.05).Conclusion The noise,SNR and CNR of DLIR-H images are similar to those of ASIR-V 80％,with the significantly higher image clarity and subjective image quality scores.DLIR-H has advantages in CAD detection of pulmonary nodules,which is an ideal image reconstruction technology for chest CT pulmonary nodule screening.

Objective:To investigate the association between tumor necrosis factor-β (TNF-β) gene polymorphisms and genetic predisposition to gastric cancer, and to analyze the relationship between specific genotype of TNF-β and serum levels of TNF-β.Methods:Using case control study, we selected 153 patients with gastric cancer in Fudan University Shanghai Cancer Center between September 2021 and December 2022 as the gastric cancer group, and 150 healthy individuals were chosen as the healthy control group. In the previous study, 30 peripheral blood DNA samples of gastric cancer patients and healthy controls respectively were amplified by conventional PCR, which were sequenced to identify the genotype frequencies of TNF-β polymorphic loci (rs1041981, rs2229092, rs2229094 and rs78613290); consequently, Allele-Specific Quantitative PCR was used to further detect and analyze the genotype and genotype frequencies of TNF-β polymorphic loci; serum TNF-β levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA), and the relationship with specific genotypes of TNF-β was analyzed. Chi-square test and Fisher test were used to analyze the genotype distribution frequency of TNF-β polymorphic loci, and non-parametric statistics was used to analyze the differences in serum TNF-β expression levels.Results:The sequencing results showed that the genotype distribution of rs1041981 in gastric cancer group was CC 16.67% (5/30), CA 40.00% (12/30) and AA 43.33% (13/30). The genotype distribution in control group was CC 40.0% (12/30), CA 43.33% (13/30), AA 16.7% (5/30). The difference of genotype frequency between the two groups was statistically significant (χ 2=6.478, P=0.039). The genotypes of the polymorphic loci rs2229092 in both groups were AA, AG, and GG, with no statistically significant difference between the two groups (χ 2=1.888, P=0.612). The distribution frequencies of the genotypes of the polymorphic loci rs2229094 (TT and TC) and rs78613290 (GG and AG) showed no statistically significant differences between the two groups (both P>0.05). Further validation with an expanded clinical samples (153 cases in the gastric cancer group and 150 cases in the control group) found that the difference of rs1041981 genotype distribution between the gastric cancer group [CC 15.69%(24/153), CA 54.9%(84/153), AA 29.4%(45/153)] and the control group [CC 27.3%(41/150), CA 58.0%(87/150), AA 14.7%(22/150)] was significantly different (χ 2=12.366, P=0.002). Analysis of the influence of different allele frequencies on the risk of gastric cancer revealed that the odds ratio ( OR) of the A allele of rs1041981 for the risk of gastric cancer compared to the C allele was 1.701 (95% CI 1.235?2.355). Gene phenotype analysis combining the clinicopathological characteristics of gastric cancer patients found that the distribution frequency of the rs1041981 genotype was significantly different among groups of different genders, tumor invasion depths, and the lymph node metastasis, with statistically significant differences (All P>0.05). Additionally, gastric cancer patients with rs1041981 AA genotypes had higher serum TNF-β expression levels than those with CA and CC genotypes, (both P<0.05). Conclusions:The gene type frequency of the TNF-β gene polymorphic loci (rs1041981, C>A) exhibited significant differences between the gastric cancer group and the healthy control group. The presence of the A allele in rs1041981 site increased the susceptibility to gastric cancer, and patients with different gene types displayed vaning levels of serum TNF-β, among which AA genotype ranks the highest level.

OBJECTIVE: To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease (CGD). METHODS: Clinical manifestations of two brothers were analyzed. Whole exome sequencing was carried out for the sib pair. Suspected variants were verified by Sanger sequencing. RESULTS: Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene, which included a known pathogenic mutation of c.395T>C (p.I132T) and a previously unreported c.448-1(delAG) in the 5' end of exon 6 of the gene. CONCLUSION The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.
Asians/genetics* ; China ; Female ; Glycosylation ; Humans ; Male ; Mutation ; Pedigree ; Whole Exome Sequencing

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

OBJECTIVE: To propose a probabilistic neural network classification method optimized by simulated annealing algorithm (SA-PNN) to discriminate lung cancer and adjacent normal tissues based on permittivity. METHODS: The permittivity of lung tumors and the adjacent normal tissues was measured by an open-ended coaxial probe, and the statistical dependency (SD) algorithm was used for frequency screening.The permittivity associated with the selected frequency points was taken as the characteristic variable, and SA-PNN was used to discriminate lung cancer and the adjacent normal tissues. RESULTS: Three frequency points, namely 984 MHz, 2724 MHz and 2723 MHz, were selected by SD algorithm.SA-PNN was used to discriminate 200 samples with the permittivity at the 3 frequency points as the characteristic variable.After 10-fold cross-validation, the final discrimination accuracy was 92.50%, the sensitivity was 90.65%, and the specificity was 94.62%. CONCLUSIONS Compared with the traditional probabilistic neural network, BP neural network, RBF neural network and the classification discriminant analysis function (Classify) in MATLAB, the proposed SA-PNN has higher accuracy, sensitivity and specificity for discriminating lung cancer and the adjacent normal tissues based on permittivity.
Algorithms ; Humans ; Lung Neoplasms/diagnosis* ; Neural Networks, Computer ; Sensitivity and Specificity

Objective: To investigate the clinical characteristics of diabetic patients combined with acute myocardial infarction (AMI) and to compare the prognosis between diabetic and non- diabetic patients in 4-5 years after the onset of AMI. Methods: Followed the certain inclusive and exclusive criteria, a total of 420 patients with acute myocardial infarction were included and divided into diabetes group (group D) and non-diabetes group (group N) with numbers as 161 people and 259 respectively. Baseline data, clinical information, short-term outcome and long-term prognosis of the two groups were compared and analyzed. Results: Among the patients with diabetes, the average age was older (65.65±11.33 vs. 63.30±15.34), with fewer males (64.59% vs. 79.92%); and more likely to have other complications as hypertension (64.60% vs. 53.28%) or hyperlipidemia (42.24% vs. 26.25%). 59.29% of the patients in group D showed pathological changes in 3 major coronary arteries, which were significantly more than its counterpart (40.83%). The proportion of patients that had undergone the coronary artery bypass, grafting (11.11% vs. 5.31%) appeared also higher. There was no significant difference seen in the short-term outcomes between the two groups, but results from the long-term follow-up program showed that both the incidence of Major Adverse Cardiovascular Events (MACE) (50.67% vs. 27.72%) and the all-cause mortality (20.00% vs. 9.90%) in group D were higher than those appeared in group N (27.72%). Conclusions Patients suffered from the combination of both diabetes and acute myocardial infarction appeared older in age, more in females, with more complications and the coronary artery lesions were more severe and wider. During hospitalization, no significant difference was seen regarding the short-term outcomes between the two groups but the results from long-term follow-up process showing that the risk of MACE events was significantly higher in patients with type2 diabetes.

BACKGROUND:Precancerous lesions are a long-term development process in which many factors are involved. Bone marrow mesenchymal stem cel s can repair tissue injury. OBJECTIVE:To investigate the effect of bone marrow mesenchymal stem cel transplantation on gastric precancerous lesions in the rats. METHODS:Thirty-six Wistar rats were randomly divided into control group, model group and transplantation group. Animal models of gastric precancerous lesions were established in the model and transplantation groups. Rats in the transplantation group were given 1 mL of CM-dil-labeled bone marrow mesenchymal stem cel s (3×106 cel s) via the tail vein, once a week, total y three times. Rats in the model and control group were subjected to the tail vein injection of the same volume of normal saline. Then, rats were sacrificed 1 week after final injection, and pathohistological changes in rat gastric tissue sections were observed. The expression of vascular endothelial growth factor in the gastric mucosa and levels of serum cytokines were detected. RESULTS AND CONCLUSION:The severity of gastric mucosal injury in the transplantation group was lighter than that of the model group. The expression of vascular endothelial growth factor was significantly higher in the transplantation group compared with the model and control groups (P<0.05). The levels of serum interleukin-17 and interferon-γwere significantly higher in the model group than the transplantation group fol owed by the control group (both P<0.05). Therefore, bone marrow mesenchymal stem cel s can increase vascular permeability, reduce inflammation, block or ease the occurrence of precancerous lesions by up-regulating the expression of vascular endothelial growth factor in the gastric mucosa lesions and reducing the expression of interleukin-17 and interferon-γ.

BACKGROUND:Bone marrow mesenchymal stem cels have good proliferation and paracrine functions, which have irreplaceable advantages in the treatment of intestinal diseases. OBJECTIVE:To explore the effects of bone marrow mesenchymal stem cel transplantation on intestinal ischemia-reperfusion injury in rats. METHODS:Forty-eight Sprague-Dawley rats were enroled to make animal models of ischemic reperfusion injury of the intestine, and then model rats were randomized into experimental and control groups. After modeling, 1 mL bone marrow mesenchymal stem cels or the same volume of normal saline were injected into the intestinal mucosa of rats in the two groups, respectively. At hours 0, 2, 6, 24, 72, 120 after injection, serum diamine oxidase,tumor necrosis factor α, and D-lactic acid levels were detected by ELISA method. At 24 hours after injection, rat intestinal tissues were taken and observed pathologicaly under light microscopy, and their close connections were observed under transmission electron microscope. ZO-1 protein levels were detected by immunohistochemistry method. RESULTS AND CONCLUSION:Compared with the control group, the serum diamine oxidase, tumor necrosis factor α, and D-lactic acid levels were significantly lower in the experimental group at hours 6 and 24 after injection (P < 0.05). Intestinal necrosis, vilous edema, intestinal congestion and inflammatory cel infiltration in the experimental group were milder than those in the control group. In addition, the ZO-1 protein expression in the experimental group was higher than that in the control group. Experimental results show that bone marrow mesenchymal stem cel transplantation into the intestinal mucosa can improve the intestinal mucosal permeability in rats with intestinal ischemia-reperfusion injury.