BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective:To retrospectively analyze the clinical phenotype and pathogenic variants in patients with Progressive myoclonus epilepsy (PME).Methods:Clinical data and results of genetic testing for 11 patients diagnosed with PME at the Department of Neurology, the First Affiliated Hospital of Zhejiang University School of Medicine from June 2017 to December 2022 were collected and analyzed.Results:All of the patients, including 4 males and 7 females, had predominant action myoclonus. Three patients had myoclonus as the initial manifestation, whilst eight were diagnosed through genetic testing, including three cases with NEU1 gene variants, two with EPM2A gene variants (1 was novel), one with MT- TK gene variant, one with ATN1 gene variant, and one with CSTB gene variant. No pathogenic variant was identified in the remaining three cases. Among the eight patients with a genetic diagnosis, three were diagnosed with sialidosis, two with Lafora disease, one with Dentatorubral-pallidoluysian atrophy (DRPLA), one with Unverricht-Lundborg disease (ULD), and one with Myoclonic epilepsy with ragging red fibers (MERRF). Conclusion:Compared with pediatric patients, adult patients with PME represent a distinct subtype with slower progression and milder cognitive impairment.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective:To establish fluid intake compliance motivation scale for hemodialysis patients and to test its reliability and validity.Methods:With protection motivation theory as the basic framework, the initial scale was established by means of literature analysis, patient interview and expert consultation. From April 2019 to July 2019, a total of 170 patients with hemodialysis in 10 blood purification center in Jiangsu Province were selected for preliminary investigation by convenient sampling method, and the tentative scale was formed through project analysis and exploratory factor analysis. A total of 550 hemodialysis patients were selected for formal testing to evaluate the reliability and validity of the scale.Results:The final scale consisted of 22 items. 7 common factors are extracted by exploratory factor analysis and the cumulative variance contribution rate was 75.949%. The Cronbach's α coefficient of the total scale was 0.928, Spearman-Brown coefficient was 0.841 and the retest reliability coefficient was 0.899. The content validity index of the scale was 0.987. The confirmatory factor analysis model fitted well.Conclusions:Fluid intake compliance motivation scale for hemodialysis patients has good reliability and validity, which can be used to assess fluid intake compliance motivation of patients.

Objective To investigate the efficacy and safety of whole brain radiotherapy combined with ectatinib hydrochloride in the treatment of non-small cell lung cancer (NSCLC) brain metastases. Methods A total of 44 patients with brain metastases from NSCLC from June 2013 to June 2017 were randomly divided into combination therapy group and radiotherapy group. The efficacy and safety between the two groups were compared. Results The median follow-up was 18.5 months. The mPFS of the combination therapy group and the radiotherapy group were 9.3 months and 6.6 months, respectively (log-rank P=0.006). The mPFS of the EGFR mutant and wild type in the combination group were12.2 months and 6.5 months (log-rank P=0.002). The mPFS of EGFR mutants and wild-type patients in the radiotherapy group were 6.4 months and 6.8 months, respectively (log-rank P=0.933). The mOS in the combination therapy group and the radiotherapy group were 14.2 months and 12.6 months, respectively (log-rank P=0.035). The mOS of the EGFR mutant and wild type in the combination group were 19.1 months and 12.7 months, respectively (log-rank P=0.006). The mOS of EGFR mutants and wild-type patients in the radiotherapy group were 12.6 months and 10.4 months, respectively (log-rank P=0.449).The ORR of the two groups was 78.3％ and 47.6％, respectively (log-rank P=0.035), and the DCR was 91.3％ and 85.7％, respectively (χ2=0.341, P=0.560).In terms of adverse reactions, the incidence of rash in the combined group was 56.5％, of which 3 cases were grade 3-4. The adverse reactions such as fatigue, nausea and vomiting, diarrhea, liver and kidney damage, and leukopenia were all grade 1-2, and there was no statistically significant difference between the two groups. Conclusion Ectinib hydrochloride combined with whole brain radiotherapy can improve the objective response rate of patients with non-small cell lung cancer with brain metastases, prolong the median local progression-free survival and median overall survival, and the patient's adverse reaction tolerance is good.

Objective To investigate the efficacy and safety of different course duration of rivaroxaban for deep venous thrombosis (DVT) in elderly patients with femoral neck fractures after artificial femoral head replacement.Methods A prospective case control study was conducted on 95 elderly cases of femoral neck fractures treated from February 2015 to July 2017.There were 18 males and 77 females,with average age of 80.8 years (range,70-98 years).There were 85 patients at stage Ⅲ and 10 at stage Ⅳ according to Garden classification.All patients received artificial femoral head replacement and were randomly divided into 3 groups (Group A:34 cases,rivaroxaban treatment for 2 weeks;Group B:31 cases,rivaroxaban treatment for 3 weeks;Group C:30 cases,rivaroxaban treatment for 5 weeks).At 2,3 and 5 weeks after operation,the patients were given 10 mg oral rivaroxaban once daily.General information,blood transfusion rate,hemoglobin volume,platelet count and DVT rate were recorded before and 6 weeks after operation.Results No significant difference among the groups in terms of division,age,body mass index,fracture classification,time interval from injury,intraoperative blood loss,quantity of drainage fluid after operation,and associated underlying diseases was observed (P ＞ 0.05).The blood transfusion rate of Groups A,B and C within 2 weeks after operation was 9％ (3/34),3％ (1/31) and 3％ (1/30) (P ＞ 0.05) respectively.The comparative difference in hemoglobin and platelet count had no statistical significance (P ＞ 0.05).The DTV rate after operation of Groups A,B and C was 21％ (7/34),13％ (4/31) and 0,respectively.There was no significant difference between Groups B and C (P ＞ 0.05),but the difference between Groups A and C was statistically significant (P ＜ 0.05).Conclusions For elderly patients with femoral neck fracture who underwent the artificial femoral head replacement,it is effective to prevent the occurrence of DVT by extending the course of rivaroxaban treatment to 5 weeks.In addition,it does not increase the risk of bleeding.

Objective To investigate the effect of p53-gene expression on renal function in rat with low birth weight ( LBW) .Methods Fifteen pregnant rats were randomly assigned into normal group, LBW group, and L-arginine ( L-Arg)-treated group.For normal group, pregnant rats were fed with 21% protein diet during pregnancy.For LBW and L-Arg treated groups, rats were fed with 10%protein diet.After de-livery, all rats were fed with 21%protein diet.For L-Arg-treated group, rats were given a supplementation with L-Arg (200 mg/kg) drinking water during 21 d lactation, other rats were given running water.At the age of 2m, the ultrastructural change in mesangial cell and podocyte was observed with electron microscope. At the age of 7 d, 21 d, 2 m, and 3 m old, the p53 mRNA expression in renal tissues was observed with re-verse transcription polymerase chain reaction ( RT-PCR) , blood and urine were collected to detect biochem-ical indicators of renal function and 24 h-urine protein.Results ⑴At the age of 3 m,the blood urea nitro-gen ( BUN) and urine cretinine ( UCr) in normal group were significantly lower than those in LBW group ( P <0.01).Compared to normal group, the Ucr of LBW group was significantly lower at the age of 2 m ( P<0.05).At the age of 3 m,the Ucr of L-Arg treated group and LBW group was significantly lower ( P <0.05), the level of 24 h-Urine protein was notably increased in LBW group and L-Arg treated group than that in normal group ( P <0.01, P <0.05) .⑵At the age of 3 m,the expression of p53 mRNA in LBW group was higher obviously than that in normal group.There is a significantly negative correlation between the expression of p53 mRNA and the level of Ucr in LBW group ( r =-0.91, P <0.05).⑶ There were mesangial cell proliferation with matrix increase, filtration membrane podocyte reduction, and partially dis-solved in LBW group, the mesangial cell proliferation of L-Arg treated group was decreased compared to that in LBW group.Conclusions The higher expression of p53 gene in LBW group might be one of reasons for the decreased renal function in LBW rats.

Objective To study the effect of renal p53 protein expression on kidney development in rats with intrauterine growth restriction ( IUGR) . Methods Pregnant rats were randomly assigned into normal group, IUGR group and L-Arg treated group. Normal group were fed with normal diet (21％protein). IUGR group and L-Arg treated group were fed with low-protein diet (10％ protein). During lactation, maternal rats in the three groups were all fed with normal diet. Maternal rats in L-Arg treated group were given additional special drinking water ( L-Arg:200 mg/kg) , while maternal rats in normal and IUGR group were given normal drinking water. Offspring weaned after 21 d and had free access to normal rodent diet and water. When the pups grew up to 2 m, the number of glomeruli was counted using acid digestion method, the proliferation and apoptosis of glomerular and tubular cells were studied using TUNEL and Ki-67 immunohistochemistry, and the ultrastructure of epithelial cells was determined by electron microscopy. At 7 d, 21 d, 2 m and 3 m, p53 protein expression in renal tissue was measured by Western blot, respectively. Results At 2 m, the number of glomerulus ( right kidney) in IUGR group was significantly lower than normal group [(23 647±541) vs. (27 689±492), P＜0. 01]; the index of renal cell apoptosis in IUGR group was higher than normal group [(21. 9 ± 2. 0) vs. (16. 7 ± 2. 5), P＜0. 05];however, IUGR group and normal group had no statistically significant difference (P＞0. 05). The proliferation of mesangial cells was found in IUGR and L-Arg treated group, but not in normal group. And the extent of proliferation in L-Arg treated group was lesser than IUGR group. A reduction of foot process and partial fusion of foot process could be observed in IUGR group and L-Arg treated group while the foot process morphology in normal group was normal. At 2 m and 3 m, p53 protein level in IUGR group and L-Arg treated group were higher than normal group [ 2 m: ( 0. 28 ± 0. 03 ) and ( 0. 21 ± 0. 01 ) vs. (0. 10±0. 02);3 m:(0. 39±0. 04) and (0. 26±0. 02) vs. (0. 17±0. 03);P＜0. 01], while IUGR group higher than L-Arg treated group ( P＜0. 05 ) . Conclusions The kidney of IUGR rats showed reduced glomerular number, increased renal cell apoptosis, enhanced p53 protein expression, increased proliferation of glomerular mesangial cells, decreased foot process, and partial fusion of foot process. And L-Arg could to some extent improve the organizational structure of the kidney in IUGR rats.

OBJECTIVETo study the clinical features, pathologic findings and prognosis of patients with dysplastic nodules of liver (DN) and early hepatocellular carcinomas (eHCC).

METHODSOne hundred and forty-five archival cases previously diagnosed as DN or eHCC or well-differentiated HCC during the period from 2000 to 2009 were retrieved and reevaluated with the new diagnostic criteria by two experienced pathologists, according to International Consensus Group for Hepatocellular Neoplasia (ICGHN) 2008. Immunohistochemical study (EnVision method) for CD34, HSP70, glutamine synthetase, glypican 3 and Ki-67 was carried out. The original diagnosis and diagnosis after review were compared and correlated with the survival data of the patients, with statistical analysis.

RESULTSWith the new criteria, 16 cases were diagnosed as low-grade DN, 50 cases as high-grade DN, 72 cases as DN with microinvasion, 7 cases as advanced HCC. Slide review showed no diagnostic discrepancy in 112 cases (77.2%). Amongst the 33 (22.8%) underdiagnosed cases, there were 7 cases of advanced HCC initially diagnosed as DN or DN with microinvasion and 26 cases of eHCC initially diagnosed as high-grade DN. Kaplan-Meier analysis showed that the diagnosis of high-grade DN or early HCC carried no statistically significant difference in overall survival (P = 0.778, 0.677) or disease-free survival (P = 0.949, 0.700) in all patients and in patients with no history of HCC. The co-existence of advanced HCC in patients with DN or eHCC significantly correlated with overall survival (P = 0.004) but not with disease-free survival (P = 0.079).

CONCLUSIONSThe new diagnostic criteria by ICGHN 2008 are useful in delineating high-grade DN and eHCC. The overall survival and disease-free survival of patients with eHCC or high-grade DN undergoing hepatectomy show no statistically significant difference. Patients with DN or eHCC have better prognosis than patients with advanced HCC, though there is still a high risk of tumor recurrence.

Antigens, CD34 ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; surgery ; Cell Transformation, Neoplastic ; Disease-Free Survival ; Female ; Follow-Up Studies ; HSP70 Heat-Shock Proteins ; metabolism ; Hepatectomy ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen ; metabolism ; Liver Cirrhosis ; metabolism ; pathology ; surgery ; Liver Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Survival Rate

Objective To study the clinical features , pathologic findings and prognosis of patients with dysplastic nodules of liver ( DN ) and early hepatocellular carcinomas ( eHCC ).Methods One hundred and forty-five archival cases previously diagnosed as DN or eHCC or well-differentiated HCC during the period from 2000 to 2009 were retrieved and reevaluated with the new diagnostic criteria by two experienced pathologists , according to International Consensus Group for Hepatocellular Neoplasia ( ICGHN) 2008.Immunohistochemical study (EnVision method) for CD34, HSP70, glutamine synthetase, glypican 3 and Ki-67 was carried out.The original diagnosis and diagnosis after review were compared and correlated with the survival data of the patients , with statistical analysis.Results With the new criteria , 16 cases were diagnosed as low-grade DN, 50 cases as high-grade DN, 72 cases as DN with microinvasion , 7 cases as advanced HCC.Slide review showed no diagnostic discrepancy in 112 cases ( 77.2%).Amongst the 33 (22.8%) underdiagnosed cases , there were 7 cases of advanced HCC initially diagnosed as DN or DN with microinvasion and 26 cases of eHCC initially diagnosed as high-grade DN.Kaplan-Meier analysis showed that the diagnosis of high-grade DN or early HCC carried no statistically significant difference in overall survival (P=0.778, 0.677) or disease-free survival (P=0.949, 0.700) in all patients and in patients with no history of HCC.The co-existence of advanced HCC in patients with DN or eHCC significantly correlated with overall survival (P=0.004) but not with disease-free survival (P=0.079).Conclusions The new diagnostic criteria by ICGHN 2008 are useful in delineating high-grade DN and eHCC.The overall survival and disease-free survival of patients with eHCC or high-grade DN undergoing hepatectomy show no statistically significant difference.Patients with DN or eHCC have better prognosis than patients with advanced HCC , though there is still a high risk of tumor recurrence .