Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To explore the relationship between the expression levels of serum cingulate protein(CGN)and polyligand glycan 1(SDC-1)and the disease condition and outcome of hypertensive basal ganglia hemorrhage(HBGH).Methods A total of 123 patients with HBGH admitted to the Second People's Hospi-tal of Lianyungang from February 2019 to February 2022 were selected as the study objects,and 120 healthy volunteers who underwent physical examination in the hospital during the same period were selected as the health group.Serum CGN and SDC-1 expression levels were detected in the two groups.According to the dis-ease outcome,the patients were divided into the improved group(92 cases)and the deteriorated group(31 ca-ses).Receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to analyze the predictive value of serum CGN and SDC-1 expression levels on the disease outcome of patients with HB-GH.Results Serum CGN and SDC-1 expression levels in the severe group were higher than those in the mod-erate group and the mild group,and serum CGN and SDC-1 levels in the moderate group were higher than those in the mild group,and the differences were statistically significant(P＜0.05).Serum CGN and SDC-1 expression levels in HBGH patients in three groups were higher than those in health group,and the differences were statistically significant(P＜0.05).Serum CGN and SDC-1 expression levels in the deteriorated group were higher than those in the improved group,and the differences were statistically significant(P＜0.05).The AUC of serum CGN and SDC-1 for predicting the disease outcome of HBGH patients was 0.742(95％CI:0.792-0.697)and 0.861(95％CI:0.906-0.910),respectively,and the AUC of the combination of the two was 0.917(95％CI:0.962-0.870).The amount of blood loss and ventricular rupture in the deteriorated group were higher than those in the improved group,and the Glasgow Coma Scale(GCS)score on admission was lower than that in the improved group,and the differences were statistically significant(P＜0.05).Multi-variate Logistic regression analysis showed that serum CGN≥51.63 pg/mL(OR=3.815),serum SDC-1≥450.67 μg/L(OR=4.230)and GCS score ≤8(OR=5.333)were the influencing factors for disease outcome of HBGH patients(P＜0.05).Conclusion The increased expression levels of serum CGN and SDC-1 are closely related to the disease aggravation and the deterioration of the disease outcome in patients with HBGH,and they have certain predictive value for the disease outcome in patients with HBGH.

Objective To explore the clinical application value of deep learning image reconstruction(DLIR)-based technique for radiation dose reduction with different noise index(NI)in CT-guided percutaneous transthoracic needle biopsy(PTNB).Methods Thirty-two patients undergoing PTNB were selected,and three sets of CT images with NI of 15,30,and 45 sequentially were obtained after adjusting the puncture needle using the scanning parameters of a small range(40 mm),tube voltage 100 kV,and automatic tube cur-rent modulation(ATCM).Group A was 50％weight of adaptive statistical iterative reconstruction-Veo(ASIR-V)scanned with NI 15,and group B and C were the DLIR-high reconstructed images with NI 30 and NI 45 respectively.The CT value and standard devia-tion(SD)value of paraspinal muscles,subcutaneous fat,and arterial vessels were measured at the puncture center point and its upper and lower 10 mm sclices,respectively,and the signal-to-noise ratio(SNR)and the contrast-to-noise ratio(CNR)were also calculated.Then the images were subjectively scored by two physicians,meanwhile the effective dose(ED)among the three groups was com-pared.Results According to the subjective evaluation,the image quality of group A,B,and C all met the clinical requirement for puncture.The SD and SNR of the images in group B were better than those in groups A and C.The SD and SNR of paraspinal mus-cles and sudcutaneous fat were significantly different between groups A and B,and between groups B and C(P＜0.05),however those of paraspinal muscles and subcutaneous fat between groups A and C were not significant.The differences in ED among the three groups were all statistically significant(P＜0.05).Compared with group A,the ED in groups B and C were reduced by 82.86％and 93.90％respectively,and the ED in group C was reduced by 64.44％compared with group B.Conclusion Increasing the NI combined with the DLIR technique can significantly reduce the radi-ation dose during CT-guided PTNB.

Objective To explore the effect of deep learning image reconstruction(DLIR)algorithm combined with"double low"[low voltage(kV)and low contrast agent dosage]technique on the image quality of coronary computed tomography angiography(CCTA)in overweight patients compared with adaptive statistical iterative reconstruction(ASIR-V)and filtered back projection(FBP).Methods Fifty-two patients with body mass index(BMI)between 25.1 kg/m2and 28 kg/m2 who underwent CCTA scanning were prospectively selected,all of whom scanned on a GE Revolution APEX-CT with a tube voltage of 80 kV,a smart mA(500-1 300 mA),a noise index of 30,and a contrast dosage of 0.5 mL/kg;four groups of images were reconstructed for each patient,FBP,50％ASIR-V,DLIR-M,and DLIR-H.The CT and SD values of the aorta(AO)root,the proximal segment of the right coronary artery(RCA),the left circumflex(LCX),the left anterior descending branch(LAD)and the pericardial fat were measured,and the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two doctors experienced in the diagnosis of cardiovascular disease were selected to subjectively score the reconstructed images using a double-blind method.The SD value,SNR value,CNR value and subjective scores of images in the four groups were compared.Results In the objective image quality evaluation,there were statistically significant differences in SD value,SNR value and CNR value of reconstructed images in the four groups(P＜0.05).As the four groups of reconstruction algorithms FBP,50％ASIR-V,DLIR-M,and DLIR-H were changed sequentially,the image SD value gradually decreased,the SNR value and CNR value gradually increased,and the DLIR-H group had the lowest SD value and the highest SNR and CNR values.In the subjective image quality evaluation,the subjective scores of the two doctors had good consistency(Kappa value=0.900),and the difference between them was statistically significant(P＜0.001).The subjective scores of DLIR-M and DLIR-H groups were higher.Conclusion DLIR algorithm combined with"double-low"technique can significantly improve the CCTA image quality of overweight patients,which is better than 50％ASIR-V and FBP.

Objective To explore the application value of three dimensional reconstruction technique in laparoscopic hepatectomy for hepatic carcinoma.Methods From September 2019 to March 2022,the clinical data of 62 patients with primary hepatic carcinoma were gathered.The enhanced CT scanning was performed before surgery.Patients with three dimensiona reconstruction technology were set as observation group(n=31).Patients who did not use three dimensiona reconstruction technology were set as the control group(n=31),and intraoperative conditions(time of operation,bleeding volume during operation)and postoperative conditions(occurrence rate of postoperative complications,postoperative length of stay)of the two groups were compared.Results 62 patients successfully completed laparoscopic hepatectomy without liver failure or death.For patients with tumors located in liver segmentⅡ and Ⅲ,there were no significant difference of operation time,intraoperative blood loss,postoperative hospital stay and postoperative complication total rate between control group and observation group(P＞0.05).For patients with tumors located in liver segment Ⅳ-Ⅵ,operation time[(211.36±11.22)minutes vs(231.69±19.73)minutes],intraoperative blood loss[(274.29±23.84)ml vs(306.54±21.05)ml],postoperative hospital stay[(7.93±1.33)days vs(9.62±1.80)days]in observation group were lower than those in control group(P＜0.05),and there was no significant difference of postoperative complication total rate between two groups(P＞0.05).For patients with tumors located in liver segmentⅠ,Ⅶ and Ⅷ,operation time[(165.88±10.60)minutes vs(187.30±17.29)minutes],intraoperative blood loss[(271.25±12.17)ml vs(308.00±28.21)ml],postoperative hospital stay[(7.63±0.74)days vs(9.30±1.06)days]in observation group were lower than those in control group(P＜0.05),and there was no significant difference of postoperative complication total rate between two groups(P＞0.05).Conclusion The three dimensiona reconstruction technique may have prominent guiding significance for complex laparoscopic hepatectomy for hepatic carcinoma.

Objective:To discuss the performance of visual score and heart-to-contralateral lung (H/CL) ratio of 99Tc m-pyrophosphate (PYP) SPECT/CT scintigraphy for diagnosing transthyretin-related cardiac amyloidosis (ATTR-CA) by using Meta-analysis. Methods:Relevant studies on 99Tc m-PYP SPECT/CT diagnosis of ATTR-CA published before August 20, 2023 from databases including Pubmed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and China Science and Technology Journal Database (VIP) were retrieved. Articles were screened and indices which reflect the diagnostic efficiency such as sensitivity and specificity were extracted. Forest plots were drawn, and subgroup analysis was performed to analyze the heterogeneity. Results:A total of 160 articles were retrieved, and 11 articles involving 1 802 patients were enrolled, of whom 605 were diagnosed with ATTR-CA. All 11 articles were enrolled when analyzing the diagnostic efficiency of visual score for diagnosing ATTR-CA. After integration, the sensitivity and specificity were 0.95(95% CI: 0.91-0.97) and 0.95(95% CI: 0.90-0.98), respectively. Ten articles (1 611 patients) were enrolled when analyzing the diagnostic efficiency of H/CL ratio for diagnosing ATTR-CA. After integration, the sensitivity and specificity were 0.93(95% CI: 0.82-0.98) and 0.99(95% CI: 0.90-1.00), respectively. Subgroup analysis indicated that lack of uniformity in diagnostic criteria was the primary source of heterogeneity. Conclusion:99Tc m-PYP SPECT/CT scintigraphy exhibits high diagnostic efficiency for ATTR-CA.

【Objective】 To establish a management information system (referred to as the system) for plasma collection stations in Zhejiang province, so as to explore the current situation of plasma donors and implement effective supervision in Zhejiang. 【Methods】 The system was developed and connected to four plasma collection stations that were officially operating in Zhejiang in terms of plasma station setting and approval, as well as the publicity, recruitment and management of plasma donors, information management of the whole process of plasma collection, management of deferral plasma donors, plasma quality management and administrative supervision etc. Relevant plasma donor information was uploaded to the system by each plasma station, and information before (January 2016 to December 2020) and after (January 8, 2021 to June 2021) the system was collected. Information included the number of plasma donors/donations, demographic information of eligible plasma donors in the past 5 years, the type of plasma donors, and the deferral donors after the system was activated. The online approval of Plasma Donation Certificate and the intelligent supervision of key points of plasma apheresis stations in Zhejiang were also conducted. The frequency and composition ratio were described, and chi-square test was used for statistical analysis. 【Results】 The system (V1.0) was established and was officially launched on January 8, 2021, realizing the interconnection of blood donation and plasma donation information as well as the unified management of 24 quality indicators. Since the system was applied (January 8, 2021-June 2021), the proportion of donors both donated blood and plasma over the province was 3.56 (832/23 389), and 352 deferred donors were masked by the system. And 30.11% (106/352) , who intended to donate plasma, were deferred due to insufficient interval after blood donation; 11.65% (41/352) due to permanent masking in blood donations; 23.86% (23.86%) , who intended to donate blood, were deferred due to insufficient interval after plasma donation ( 84/352); 34.38% (121/352) due to permanent masking in plasma donations. The median approval rate of four plasma stations applying for Plasma Donation Certificate before the system (January 1, 2016 to January 7, 2021) and after the system (January 8 to June 2021) were 93.38% (10 609/11 361) vs 99.50% (2 602/2 615). Before the system was put into launch, the ratio of male to female donors and the proportion of regular donors showed an overall upward trend, while the age decreased slightly. The median proportion of women in the past 5 years was 61.52 %, significantly higher than that in last 6 months after the launch(58.86%). 【Conclusion】 The application of the system can realize information interconnection between blood centers and plasma collection stations in Zhejiang as well as the real-time supervision of plasma collection process, which is helpful to overcome the shortcomings in plasma donor management.

OBJECTIVE: To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis. METHODS: Clinical data of the proband and members of his pedigree were collected. Whole exome sequencing was carried out to detect variants of the TSC1 and TSC2 genes. Candidate variants was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband and his mother, who also had mild features of tuberous sclerosis, were found to harbor a novel heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene, which was absent in the 4 healthy relatives. Bioinformatic analysis suggested the variant to be likely pathogenic. CONCLUSION The heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene probably underlay the disease in this pedigree. Above finding has expanded the spectrum of TSC2 gene variants. The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.
China ; Humans ; Mutation ; Pedigree ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

Objective:To investigate the number of necroptotic renal tubular epithelial cells in renal tissues of patients with chronic kidney disease (CKD) and the correlation with clinicopathologic parameters, and explore its role in the progression of the excessive loss of renal tubular cells and chronic kidney injury.Methods:Renal tissue samples from 60 patients (18-65 years old) with CKD proven by kidney biopsy in the First Affiliated Hospital of Hainan Medical University from June 2017 to June 2019 were collected. According to internationally accepted K/DOQI guidelines, the patients were divided into 1-4 stages of CKD, with 15 cases in each stage. The number of necroptotic renal tubular epithelial cells in patients with different stages of CKD was detected using receptor-interacting protein 3 (RIP3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) fluorescent staining, and the expression of RIP3 and MLKL, marker protein of necroptosis, was detected by immunohistochemistry. Pearson correlation analysis was used to analyze the correlation between the percentage of necroptotic renal tubular epithelial cells and clinicopathologic parameters. In addition, the expression of angiotensinogen Ⅱ receptor (AT2R) in renal tissue and its correlation with the percentage of necroptotic renal tubular epithelial cells were analyzed.Results:With the development of CKD, the structural destruction of renal tubules in patients with CKD was gradually aggravated, and the renal tubules in the corresponding areas were atrophied, accompanied by worsening interstitial fibrosis. The adjacent renal tubules were focally dilated and numerous protein tubules were seen in the tubules. Importantly, renal tubular injury score in second and third stage of CKD was significantly higher than that in control group (both P<0.01). TUNEL+RIP3 immunofluorescence staining results showed that the percentage of TUNEL/RIP3 double positive renal tubular epithelial cells (necroptotic renal tubular epithelial cells) in renal tubules of the second and third stage of CKD was higher (all P<0.01). Immunohistochemical results showed that RIP3, MLKL and AT2R proteins were mainly expressed in cytoplasm of renal tubular epithelial cells, and the expression of RIP3, MLKL and AT2R in renal tubular epithelial cells was higher in the second and third stage of CKD patients (all P<0.05). Pearson correlation analysis showed that the percentage of necroptotic renal tubular epithelial cells was positively correlated with blood urea nitrogen ( r=0.514, P=0.003), serum creatinine ( r=0.507, P=0.019), serum cystatin C ( r=0.571, P=0.026), serum uric acid ( r=0.592, P=0.008), renal tubules injury score ( r=0.901, P<0.001), renal interstitial fibrosis index ( r=0.700, P=0.001) and the expression of AT2R protein in renal tissue ( r=0.715, P=0.001). Conclusions:As CKD progresses, necroptosis of renal tubular epithelial cells in CKD patients occurs. The necroptotic cell death may be an important factor leading to renal tubular epithelial cell excessive death and the progression of chronic kidney injury. Furthermore, necroptosis of renal tubular epithelial cells may be related to the high expression of AT2R in kidney tissue.

Pre-transfusion compatibility testing is complicated in autoimmune hemolytic anemia (AIHA) patients due to the presence of autoantibodies. Delays in blood transfusion or even life-threatening would occur if blood type, isoantibodies/ autoantibodies of these patients could not be correctly identified to choose the appropriate blood components. Knowing the detection and treatment countermeasures against blood transfusion compatibility in AIHA patients is of great significance to ensure the timeliness and safety of blood transfusion. Based on the research progress at home and abroad, this article summarizes the serological characteristics, autoantibody types, blood group identification methods, antibody screening and antibody identification methods, and blood transfusion strategies about AIHA patients, in order to eliminate the interference of autoantibodies and provide transfusion guidance for the staff of Blood Transfusion Department.