Objective To investigate whether the pituitary tumor transformation gene 1(PTTG 1)plays a role in colitis by regulating intestinal epithelial cells pyroptosis.Methods Ten PTTG 1 wild-type(WT)mice and Ten PTTG 1 knockout(KO)mice were randomly divided into 4 groups of 5 each,respectively PTTG1 WT control and experimental group,PTTG1 KO control and experimental group.The mice in the experimental group were given 3%dextran sodium sulfate(DSS)for 6 days to induce acute colitis,and the control group was given sterile double distilled water(ddH2O).The disease activity index of the respective group of mice was observed and recorded.Mouse colonic tissue were collected,and the expression levels of NLRP3,ASC,and GSDMD were determined by immuno-histochemistry and western blot.In HCoEpiC,PTTG1 expression was knocked down using shRNA,and the cells were subsequently treated with TNF-α to induce inflammation.Then,the expression of GSDMD was detected.Results The expression of PTTG1 was decreased in colonic mucosal tissue in mice with acute colitis(P<0.01).Compared with WT mice,the colitis was significantly aggravated in PTTG1 KO mice after 3%DSS treatment.The expression of pyroptosis-related proteins was significantly up-regulated in the colon mucosal tissues of PTTG1 KO experimental mice(P<0.05).After knocking down the expression of PTTG1 in HCoEpiC and TNF-α treatment,the expression levels of GSDMD were significantly up-regulated(P<0.05).Conclusion PTTG1 reduced pyroptosis in intestinal epithelial cells(IECs),while PTTG1 loss can enhance IEC pyroptosis,aggravating colonic inflammation.

Objective:To explore the protective mechanism of tea polyphenols (TP) on mouse oral cancer.Methods:A total of 50 mice were divided into control group, model group, TP group, Selisistat group, TP+ Selisistat group, with 10 mice in each group. The control group was gavaged with physiological saline, while the model group, TP group, Selisistat group, and TP+ Selisistat group were gavaged with 300 mg/L 4-NQO to establish a mouse oral cancer model. Physiological saline, 200 mg/kg TP, 0.01 mg/kg Selisistat, and 200 mg/kg TP+ 0.01 mg/kg Selisistat were gavaged respectively. The weight changes of each group of mice were compared; HE staining was used to observe the morphology of mouse oral tumor tissue; Enzyme linked immunosorbent assay was used to detect the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum; Immunoblotting and immunohistochemistry were used to detect the expression of silencing information regulatory factor (Sirt1) and nuclear factor E2 related factor 2 (Nrf2) proteins in mouse oral tissues.Results:Compared with the control group, the model group mice had a decrease in body weight [(23.19±1.36)g], a decrease in serum SOD level [(91.64±8.75)U/ml], an increase in MDA level [(5.18±0.46)nmol/ml], a decrease in Sirt1 (0.38±0.05) and Nrf2 (0.36±0.05) protein expression in oral tissue, and an increase in Nrf2 acetylation level (0.84±0.11) (all P<0.05). Compared with the model group, the TP group mice had an increase in body weight [(25.28±1.25)g], elevated serum SOD levels [(121.24±10.68)U/ml], decreased MDA levels [(3.89±0.42)nmol/ml], increased expression of Sirt1 (0.61±0.09) and Nrf2 (0.58±0.06) proteins in oral tissue, and decreased Nrf2 protein acetylation levels (0.39±0.05); The Selisistat group mice showed a decrease in body weight [(21.41±1.07)g], a decrease in serum SOD levels [(72.16±7.43)U/ml], an increase in MDA levels [(5.87±0.41)nmol/ml], a decrease in Sirt1 (0.23±0.04) and Nrf2 protein (0.24±0.03) expression in oral tissue, and an increase in Nrf2 acetylation levels (1.12±0.14) ( P<0.05). The body weight [(23.32±1.27)g], serum SOD levels [(92.58±8.13)U/ml], and oral Sirt1 (0.41±0.06) and Nrf2 (0.38±0.05) protein expression in the TP+ Selisistat group mice were higher than those in the Selisistat group, while MDA [(5.11±0.38)nmol/ml] and Nrf2 acetylation levels (0.82±0.09) were lower than those in the Selisistat group (all P<0.05). Conclusions:Tea polyphenols can alleviate oral tissue damage and alleviate oxidative stress in mice with oral cancer, and their mechanism may be related to the upregulation of the Sirt1/Nrf2 pathway.

Objective To explore the molecular mechanisms and cell-cell interactions in the injury process of pancreatic islet transplantation.Methods Single-cell transcriptome data from mouse islets treated with inflammatory factors were used,and data processing was performed using the Seurat package,with integrated data to remove batch effects.Cell subpopulations were annotated based on known markers.Cell-cell interactions in the inflammatory factor-treated group were analyzed using the CellChat package,and inferred based on the expression of cell surface receptors and ligands.Gene set enrichment analysis was used to clarify the biological processes enriched in β-cells after treatment with inflammatory factors.Finally,differentially expressed transcription factors were identified and verified using microarray datasets of donor islet ischemic injury and Western blotting.Results A total of 7 different cell subpopulations were found in mouse islets,with β-cells being the most abundant.Cell-cell interaction network analysis showed that the number and strength of interactions between ductal cells and other cells were the highest.Gene set enrichment analysis showed that after treatment with inflammatory factors,the immune response was positively enriched in β-cells,while peptide hormone metabolism,bile acid metabolism,and ion homeostasis were downregulated.The common differential transcription factors identified in the mouse single-cell transcriptome and the microarray dataset of donor islet ischemic injury were early growth response 1(EGR1),nuclear factor-κB inhibitor α(NFKBIA),and activating transcription factor 3(ATF3).Among them,NFKBIA and ATF3 were upregulated,while EGR1 was downregulated.The expression of EGR1 protein was downregulated after 24 h,48 h,and 72 h of cold ischemia.Conclusions EGR1 is a transcription factor closely related to islet cold ischemia,and future research should focus on the specific mechanisms of EGR1 and its downstream target genes,in order to provide more effective strategies for clinical treatment of islet transplantation.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4⁺ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.

Kidney Transplantation/adverse effects* ; Magnetics ; Anastomosis, Surgical ; Magnetic Phenomena

Objective:To investigate the clinical efficacy of anal dimple anorectoplasty on female infants with congenital anal atresia combined rectal vestibular fistula.Methods:Clinical data of 69 female infants with congenital anal atresia combined rectal vestibular fistula admitted to Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from July 2012 to July 2022 were retrospectively analyzed.They were divided into 2 groups according to the surgical methods: 34 cases of anal dimple anorectoplasty(group A) and 35 cases of anterior sagittal anorectoplasty(group B). The operation time, length of stay, short-term complications, long-term complications and bowel function (determined by the Rintala score at 6 months postoperatively) of the two groups were compared.The difference in the incidence of postoperative complications between groups was compared by Chi- square test, and the remaining differences between groups were compared by the paired t-test. Results:The operative time [(80.18±9.29) min vs.(103.85±8.26) min] and postoperative hospital stay[(6.10±1.52) d vs.(7.63±2.40) d] in group A were significantly shorter than those of group B ( t=11.40, 2.62; all P<0.05). The Rintala total score at 6 months postoperatively in group A was significantly higher than that of group B[(19.36±0.93) points vs.(18.76±0.44) points]( t=3.20, P<0.05). There were no significant differences in the incidences of short-term [(4/34, 11.8%) vs.(7/35, 20.0%)] and long-term complications [(2/34, 5.9%) vs.(4/35, 11.4%)]between group A and group B ( χ2=0.75, 0.75; all P>0.05). Conclusions:Anal dimple anorectoplasty for female infants with congenital anal atresia combined rectal vestibular fistula is safe and effective.

Objective:To investigate the application value of domestic robotic surgical system in radical resection of hilar cholangiocarcinoma (hCCA).Methods:The retrospective and descriptive study was constructed. The clinicopathological data of a 66-year-old male patient with hCCA who was admitted to the Second Hospital of Shandong University in November 2022 were collected. Radical resection of hCCA was performed using the Toumai? laparoscopic surgical robot system. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) follow-up. Count data were represented as absolute numbers and (or) percentages.Results:(1) Intraoperative conditions. The patient underwent radical resection of hCCA successfully using robotic surgical system, including tumor resection, lymph node dissection, and gastrointestinal reconstruc-tion. The operation time and volume of intraoperative blood loss were 400 minutes and 100 mL, respectively, and no intraoperative blood transfusion was required. (2) Postoperative conditions. The patient began ambulation on postoperative day 1 and began taking liquid food on postoperative day 4. Liver function examination and abdominal computed tomograph (CT) on postoperative day 5 showed a decrease in serum bilirubin, no biliary or intestinal leakage, and no edema or necrosis at the anastomotic site. The abdominal pre-anastomotic and post-anastomotic drainage tubes were removed on the 7th and 9th day after the surgery respectively, and the patient was discharged on the 10th day after surgery. Results of postoperative pathological examination showed moderately to poorly differentiated adenocarcinoma of the bile duct. Immunostaining was positive for CK7 and CK19. The Ki-67 proliferation index was 35%. The proximal and distal resection margin of bile duct were negative. The tumor diameter was 30 mm. Perineural invasion was positive. The surgical specimen margin was negative. Two lymph nodes were identified containing tumor cells positive for malignancy. No tumor cell metastasis was detected in the No.8, No.12 or gastric lesser curvature lymph nodes submitted for pathological examination. (3) Follow-up. The patient was followed up at postoperative 1-, 3-, 5-month after discharge. During follow-up period, results of liver function examination and abdominal CT showed liver function restore to normal levels, no complication such as biliary fistula, intestinal fistula, gastroparesis or tumor metastasis.Conclusion:The Domestic Toumai ? laparoscopic surgical robot system can be applied to radical resection of hCCA.

Objective:To determine the accuracy and clinical application of donor HLA quartile genotyping based upon transplanted kidney biopsy.Methods:The clinical and follow-up data are retrospectively reviewed for 38 recipients of kidney transplantation(KT)at First Affiliated Hospital of Xi'an Jiaotong University from 2019 to 2022.They are suspected of rejection.HLA quartile genotyping of donor kidney is performed through puncture and DNA analysis by LABType SSO method.Known HLA genotypes of recipients are compared for predicting HLA genotypes of donors.Donor-specific antibody(DSA)is detected by Labscreen Single kit.And SPSS18.0 statistical software is employed for processing baseline data, donor/recipient HLA typing data, recipient DSA antibody data and transplant nephropathy parameters.Results:Among them, 12(31.58%)belonged to HLA-A, B, C, DR and DQ.Four loci are detected in 14 cases(36.84%). Three sites are detected in 10 cases(26.32%). Two sites are detected in 2 cases(5.26%)and a negative correlation exists between detected sites and transplantation time( rs=-0.707, P=0.001). The detection rate of HLA loci is 78.94%(30 cases). B: 65.78%(25 cases); C: 84.21%(32 cases); DR: 57.89%(22 cases); DQ: 100% (38 cases); HLA sites detected in puncture tissue are 89.47% consistent with the results of donor whole blood test, among which HLA-C and HLA-DQ sites are 100% consistent and HLA-A and HLA-B sites 87.50% and 90% consistent and HLA-DR sites 66.7% consistent( P<0.01). Spearman's rank correlation analysis indicated that pathological diagnosis of interstitial inflammation( rs=-0.432, P=0.017), renal tubule atrophy( rs=-0.587, P=0.001)and interstitial fibrosis( rs=-0.560, P=0.001)are correlated negatively with HLA detected sites in transplanted kidney puncture tissue.DSA is detected in 42.1% of recipients and 68.75% of recipients belonged to HLA-DQ. Conclusions:HLA typing results of puncture tissue are consistent with those of whole blood test.Time after transplantation, infiltration of transplanted nephritis cells and degree of fibrosis may influence the detection of HLA loci.Donor HLA quartile genotyping using transplanted kidney biopsy has some diagnostic values for detecting the presence of DSA.

Objective:To investigate the diagnostic value of three-dimensional amide proton transfer-weighted imaging (APTWI) and its combination with diffusion weighted imaging (DWI) for differentiating breast benign from malignant lesions.Methods:This was a prospective study. From July to December 2020, 226 patients with breast lesions confirmed by surgery or puncture pathology in the First Affiliated Hospital of Zhengzhou University were collected. All patients underwent MR T 1-weighted imaging, T 2-weighted imaging, DWI, APTWI, and dynamic contrast-enhanced MRI, and the apparent diffusion coefficient (ADC) value and the magnetization transfer ratio asymmetry at an offset of 3.5 ppm [MTRasym(3.5 ppm)] were obtained from DWI and APTWI respectively. Mann-Whitney U test was used for the comparison of DWI and APTWI parameters between breast benign and malignant lesions. Receiver operating characteristic (ROC) curve was used to evaluate the differences of diagnostic efficacy between DWI, APTWI, and their combination. Results:There were 226 patients with 226 breast lesions, including 124 malignant and 102 benign lesions. The ADC values of patients with malignant breast lesions [1.03 (0.93, 1.13)×10 -3 mm 2/s] and MTRasym (3.5 ppm) [1.95% (1.10%, 2.88%)] were lower than those of benign breast lesions [1.38 (1.11, 1.55)×10 -3 mm 2/s, 3.30% (2.20%, 4.20%), respectively], and the differences were statistically significant ( Z=-8.19, -6.51, P<0.05). The area under the ROC curves (AUC) of DWI, APTWI, and its combination in the differential diagnosis of benign and malignant breast lesions were 0.817, 0.752, and 0.868, respectively. The AUC of the combination of DWI and APTWI was higher than that of DWI and APTWI ( Z=4.00, 2.93, P<0.05), and there was no significant difference in the AUC between DWI and APTWI diagnoses ( Z=1.58, P>0.05). Taking 1.25×10 -3 mm 2/s as the optimal cut-off value for ADC values, the sensitivity, specificity, and accuracy in differentiating benign from malignant breast lesions were 94.4% (117/124), 62.7% (64/102), and 80.1% (181/226), respectively; Taking 2.70% as the optimal cut-off value for MTRasym (3.5 ppm), the sensitivity, specificity, and accuracy in differentiating benign from malignant breast lesions were 73.4% (91/124), 64.7% (66/102), and 69.5% (157/226), respectively, and the sensitivity, specificity, and accuracy of DWI combined with APTWI in differentiating benign from malignant breast lesions were 82.3% (102/124), 79.4% (81/102), and 81.0% (183/226), respectively. Conclusion:APTWI can be used for the differential diagnosis of benign and malignant breast lesions, and the combination of APTWI and DWI can obtain the better diagnostic performance than the single method.