Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

Objective:To explore the construction of abdominal aortocaval fistula (ACF) model in adenine-induced renal failure rats, and to provide a suitable animal model for subsequent mechanism and intervention researches.Methods:Adult female Sprague-Dawley rats (250-300 g) were fed with 0.75% adenine diet (renal failure group, n=60) and the same diet without adenine (control group, n=10) for 4 weeks, and the rats were randomly grouped by block randomization method with a ratio of 6∶1. Thirty rats in the renal failure group were randomly selected by block randomization method at a ratio of 1∶1 to undergo laparotomies to establish ACF models (renal failure+ACF group). The serum creatinine, blood urea nitrogen detection and Masson staining were used to evaluate the establishment of renal failure model. Small animal ultrasound imaging system was applied to verify the successful construction of the ACF model. After 6 weeks of ACF observation, blood samples were collected from the heart of rats, and ACF-vascular tissues were collected for pathological study (HE staining). Results:At 4 weeks of feeding, compared with the control group, serum creatinine [(63.8±23.5) μmol/L vs. (33.0±3.8) μmol/L, Z=3.651, P<0.001] and blood urea nitrogen [(13.1±6.9) mmol/L vs. (5.3±0.6) mmol/L, Z=3.254, P=0.001] in the renal failure group were both higher. Masson staining showed renal tubulointerstitial inflammatory cell infiltration, renal tubular epithelial cell atrophy, interstitial fibrosis and vascular injury. Five rats sacrificed after ACF surgeries, and the survival rate was 83.3%. Doppler ultrasound showed turbulent blood flow of arterial to venous shunt at the anastomosis of open ACF (23/25) in the renal failure+ACF group. HE staining showed typical eccentric neointimal hyperplasia in the outflow tract of ACF vein in the renal failure+ACF group. Conclusions:The adenine-induced ACF rat model is successfully constructed, and ACF shows typical eccentric neointimal hyperplasia. The ACF construction would provide a reliable animal model to study the mechanism and intervention of neointimal hyperplasia for autologous arteriovenous fistula.

Objective To compare the clinical efficacy of three different therapies,including transjugular intrahepatic portosystemic shunt(TIPS)treatment,endoscopic treatment and medication treatment,combined with transhepatic arterial chemoembolization(TACE)in treating primary liver cancer complicated by portal hypertension and upper gastrointestinal bleeding.Methods A total of 105 patients with primary liver cancer associated with portal hypertension and upper gastrointestinal bleeding,who were admitted to the No.980 Hospital of PLA Joint Logistics Support Forces of China to receive treatment between January 2014 and June 2020,were enrolled in this study.According to the therapeutic scheme,the patients were divided into TIPS+TACE group(TIPS group,n=25),endoscopy+TACE group(endoscopy group,n=30),and medication+TACE group(medication group,n=50).The clinical efficacy,recurrence rate of bleeding,incidence of hepatic encephalopathy,and survival rate were compared between each other among the three groups.Results The differences in the postoperative 6-month,12-month and 24-month recurrence rates of bleeding between each other among the three groups were statistically significant(all P＜0.05).In TIPS group,the portal vein pressure decreased from preoperative(38.47±9.35)mmHg(1 mmHg=0.133 kPa)to postoperative(25.24±5.68)mmHg,the difference was statistically significant(P＜0.05).After treatment,the hemoglobin level in the three groups showed varying degrees of elevation,which in the TIPS group and endoscopy group were better than that in the medication group,the differences were statistically significant(P＜0.05).In all three groups,the differences in the recurrence rate of bleeding between postoperative 6-month value,12-month value and 24-month value were statistically significant(all P＜0.05).The postoperative 6-month,12-month and 24-month recurrence rates of bleeding in the TIPS group were lower than those in the endoscopy group and the medication group,and the differences were statistically significant(P＜0.05).The postoperative 12-month and 24-month recurrence rates of bleeding in the TIPS group were lower than those in the endoscopy group,and the differences were statistically significant(P＜0.05).The postoperative 12-month and 24-month recurrence rates of bleeding in the endoscopy group were lower than those in the medication group(P＜0.05),and the difference in the postoperative 6-month recurrence rate of bleeding between the two groups was not statistically significant(P＞0.05).The postoperative 6-month and 12-month incidences of hepatic encephalopathy in the TIPS group were higher than those in the endoscopy group and the medication group,the differences were statistically significant(P＜0.05),while the differences in the postoperative 6-month and 12-month incidences of hepatic encephalopathy between the endoscopy group and the medication group were not statistically significant(P＞0.05),and the differences in the postoperative 24-month incidence of hepatic encephalopathy between each other among the three groups were not statistically significant(P＞0.05).No statistically significant difference in the 6-month mortality existed between TIPS group and endoscopy group(P＞0.05),and the 6-month mortality of both TIPS group and endoscopy group was remarkably lower than that of the medication group(P＜0.05).The postoperative 12-month mortality and 24-month mortality in TIPS group were lower than those in the endoscopy group and the medication group,and the differences were statistically significant(P＜0.05),but the differences in the postoperative 12-month mortality and 24-month mortality between the endoscopy group and the medication group were not statistically significant(P＞0.05).Conclusion For primary liver cancer associated with portal hypertension and upper gastrointestinal bleeding,TIPS combined with TACE can effectively control tumor progression and prolong survival.(J Intervent Radiol,2024,32:33-37)

Objective:To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+ 0.Methods:A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. Results:The female partner was identified as a carrier of the rare SMN1[2+ 0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. Conclusion:PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+ 0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Objective:To comprehensively evaluate the clinical value of Elecsys serum abnormal prothrombin (PIVKA-Ⅱ) test reagent for auxiliary diagnosis of hepatocellular carcinoma (HCC) in the Chinese population.Methods:A multicenter case-control design was used in the study. Samples from patients with first-time confirmed, diagnosed, and untreated HCC, benign liver disease and interfering controls were collected continuously. Elecsys PIVKA-II and alpha-fetoprotein (AFP) were tested for analysis. Various clinical details of the subjects were collected and analyzed. The efficacy of PIVKA-II (21.29 ng/ml) and AFP (400 ng/ml) for HCC diagnosis was calculated at specific positive cut-off values. Statistical analysis was performed using the Kruskal-Wallis test or receiver operating characteristic curve.Results:A total of 448 subjects were eventually enrolled from five centers, including 185 HCC cases. PIVKA-II had a higher diagnostic sensitivity and accuracy than AFP (84.86% vs. 30.81% and 89.01% vs. 63.66%) when the benign liver disease group was used as the control group, while the specificity was slightly lower. A sensitive analysis showed that PIVKA-II had a sensitivity of >80% at this specific positive cut-off value in the subgroup of AFP-negative subjects, patients with different etiologies, and HCC patients with multiple Barcelona Clinic liver cancer stages (including early-stage HCC). At the same time, the PIVKA-II subject had a slightly higher area under the receiver operating characteristic curve than the AFP (0.920 0 vs. 0.880 9).Conclusion:The clinical efficacy of Elecsys PIVKA-Ⅱ is good and stable in the Chinese population. Additionally, it has the clinical potential to improve the current missed diagnosis status of AFP-negative HCC and HCC monitoring at an early stage, as well as the effectiveness of accuracy promotion for HCC auxiliary diagnosis in China.

Objective:To explore the association between thyroid function and chronic kidney disease (CKD) in adults.Methods:A cross-sectional study was conducted in adults who received health checkup in the First Affiliated Hospital of Shandong First Medical University from January to December in 2021. Clinical data were collected, including age, gender, height, weight, blood pressure, etc. And blood glucose, blood lipid, blood creatinine, blood uric acid, routine urine function, thyroid function (free triiodine, free thyroxine, thyroid stimulating hormone) were measured. Multivariate logistic regression model was used to investigate the correlation between thyroid function indicators and the onset of CKD; and receiver operator characteristic (ROC) curve was used to explore the ability of thyroid function indicators in evaluating CKD.Results:In the study, 46 342 adults with an average age of (47.6±14.3) years were enrolled, of which 56.2% were males. The prevalence of DeGFR (eGFR<60 ml·min -1·(1.73 m 2) -1), proteinuria and CKD was 1.15%, 0.53% and 1.58%, respectively. The TSH subgroup analysis showed that the prevalence of DeGFR, albuminuria and CKD in the hypothyroidism group was significantly increased to 1.07%, 2.36% and 3.20%, respectively (all P<0.05). After adjusting for confounding factors, multivariate logistic regression analysis showed that FT3 was negatively associated with CKD ( OR=0.63, 95% CI: 0.54-0.74), however FT4 ( OR=1.05, 95% CI: 1.03-1.07) and TSH ( OR=1.03, 95% CI: 1.01-1.04) were positively correlated with CKD. Similar results were obtained in the subgroup without hypertension and diabetes ( P<0.05). The ROC analysis indicated that FT3 had a better capability for evaluating CKD than FT4 and TSH, with an area under the curve of 0.63, a cut-off value of 4.18 pmol/L, and a sensitivity and specificity of 57.5% and 62.6%, respectively. Conclusions:Thyroid function status is closely associated with the onset of CKD in the adult population receiving health check-up. FT3 is a risk factor for the onset of CKD.

Objective:To study the clinicopathological features of Sjogren′s syndrome (SS) with liver injury and to improve the understanding of this disease.Methods:Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson′s trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted .Results:The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group ( P=0.006) and NALFD group ( P=0.011) were significantly higher than those in other groups ( P<0.05). Conclusions:The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Aim To investigate the effect of CDR132L(miR-132 antisense oligonucleotide)on vascular remode-ling and function in mice with hypertension and hyperlipidemia,and explore its possible mechanism.Methods A total of 30 8-week-old male C57BL/6 mice were randomly divided into three groups:control group,model group and CDR132L group,with 10 mice in each group.The control group received with a standard diet while the model group and CDR132L group received N-nitro-L-arginine methyl ester(L-NAME)and high-fat diet to induce hypertension and hyperlip-idemia.The CDR132L group was administered with intraperitoneal injection of CDR132L at a dose of 20 mg/kg once weekly for six consecutive weeks,whereas the control group and the model group were given intraperitoneal injection of an equivalent volume of normal saline.The tail-cuff method was utilized for blood pressure measurement,blood lipid and glucose levels were assayed by an automatic biochemical analyzer,the thoracic aorta structure was observed by HE staining,endothelium-dependent relaxation of the thoracic aorta was evaluated by the vascular ring test,the expression level of miR-132 in the thoracic aorta was measured by qPCR,the protein expression levels of Gab1 and endothelial nitric oxide synthase(eNOS)in the thoracic aorta were determined by Western blot.Results Compared with the control group,the model group demonstrated notable rises in systolic and diastolic blood pressure,serum triglyceride,total cholesterol lev-els,and body weight.Moreover,the intima of thoracic aorta and the thickness of vascular wall was uneven,the smooth muscle cells of the tunica media were arranged irregularly,with a large amount of fat deposition in the vascular wall,and the endothelium-dependent relaxation response of thoracic aorta was decreased(P＜0.05).The expression level of miR-132 in the thoracic aorta was significantly increased(P＜0.05),while the expression level of Gabl and eNOS protein was markedly decreased(P＜0.05).Compared with the model group,the CDR132L group showed no significant differences in systolic and diastolic blood pressure,serum triglyceride and total cholesterol levels,as well as body weight(P＞0.05).However,the CDR132L group exhibited a complete and smooth intima of the thoracic aorta with minimal intravascular lipid deposition,the thickness of the vascular wall was uniform,the smooth muscle cells of the tunica media were arranged order-ly,accompanied by enhanced endothelium-dependent relaxation response of the thoracic aorta(P＜0.05).The expression level of miR-132 in the thoracic aorta was significantly decreased(P＜0.05),while the expression levels of Gab1 and eNOS protein were significantly increased(P＜0.05).Conclusion CDR132L can improve vascular remodeling and endothelium-dependent relaxation in hypertensive and hyperlipidemia mice,which may be related to the decrease of miR-132 expression level and the up-regulation of Gab1 and eNOS protein expression levels in the thoracic aorta.