Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Objective To investigate the expression level and clinical significance of microRNA(miR)-181c and microRNA(miR)-578 in the serum of patients with sepsis complicated by acute kidney injury(AKI).Methods Eighty patients with sepsis complicated by AKI(AKI group)and 80 patients with simple sepsis(non AKI group)who were hospitalized in Sinopharm Gezhouba Central Hospital from January 2022 to December 2022 were collected as research subjects.The serum levels of miR-181c and miR-578 in two groups were detected and compared.Logistic regression was applied to analyze the influencing factors of sepsis patients complicated by AKI.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum miR-181c and miR-578 levels for patients with sepsis complicated by AKI.Results The proportion of pulmonary infection,the level of arterial blood lactic acid,creatinine,urea nitrogen and APACHEⅡ score in AKI group were higher than those in non-AKI group,and the oxygenation index was lower,the differences were statistically significant(χ2=7.364,t=14.298,26.691,17.925,7.104,12.676,all P＜0.05).The serum miR-181c level in the AKI group(1.47±0.36)was higher than that in the non AKI group(1.03±0.28),the serum miR-578 level(0.76±0.19)was lower than that in the non AKI group(1.05±0.31),and the differences were statistically significant(t=8.629,7.134,all P=0.000).Logistic regression analysis showed that miR-181c[OR(95%CI):2.984(1.628～5.468)],pulmonary infection[OR(95%CI):1.946(1.250～3.031)],arterial blood lactic acid[OR(95%CI):1.457(1.073～1.978)],and APACHE Ⅱ score[OR(95%CI):2.283(1.393～3.741)]were risk factors for AKI in sepsis patients(all P＜0.05);miR-578[OR(95%CI):0.742(0.631～0.873)]and oxygenation index[OR(95%CI):0.342(0.130～0.904)]were protective factors(all P＜0.05).The combined prediction of serum miR-181c and miR-578 for AKI in sepsis patients had an AUC of 0.915,a sensitivity and a specificity of 83.65%,88.75%,respectively,which was superior to their individual predictions(Z=3.118,3.460,P=0.002,0.001).Conclusion The serum miR-181c expression is obviously up-regulated and miR-578 expression is obviously down-regulated in patients with sepsis complicated by AKI.The combination of the two has good reference value for predicting sepsis complicated by AKI.

Objective:To explore the genetic etiology for a premature ovarian insufficiency (POI) patient from a consanguineous Chinese family, and to provide basis for genetic counseling and fertility counseling.Methods:Whole-exome sequencing was performed using DNA extracted from the blood sample of POI patient. Suspected pathogenic mutation was analyzed by bioinformatics methods and verified by Sanger sequencing. The pathogenicity of the variation was assessed according to the ACMG genetic variation classification criteria and guidelines.Results:A homozygous variation, c. 32G>T (p.G11V), of PSMC3IP was identified in the patient. Bioinformatics analysis revealed that the variation was conserved in different animal species, and this variation was classified as possible pathogenic variation according to the ACMG genetic variation classification criteria and guidelines.Conclusions:The homozygous missense variation of PSMC3IP is the cause of the POI patient in this family. We are reporting for the first time the missense variation in PSMC3IP gene caused POI, which enriched the mutation spectrum of PSMC3IP and provided the basis for genetic counseling and fertility guidance of this family.

Objective:To investigate the efficacy of local application of methimazole cream in the patients with hyperthyroidism complicated with liver failure, and to provide reference for its clinical treatment.Methods:Two patients were admitted to hospital with jaundice as the main performance.Liver function and coagulation function supported the diagnosis of liver failure.The thyroid function indicators suggested hyperthyroidism.Combined with other related examination results, liver failure, hyperthyroidism and hepatitis B virus were diagnosed, and the local treatment of methimazole cream and other related treatments were given.Results:After treatment, the liver function of two patients returned to normal and the thyroid function was improved.After follow-up, one patient changed the external use of methimazole cream to oral treatment, and another patient was still treated in a local manner.Conclusion:There is a conflict in the treatment of hyperthyroidism complicated with liver failure.The local application of methimazole cream in the topic of reducing the risk of liver damage caused by drugs has good results in the treatment of hyperthyroidism.This method also provides the new ideas for its clinical treatment.

Objective To investigate the expressions of transforming growth factor β1 (TGF-β1) and brain natrium peptide (BNP) in patients with diastolic heart failure (DHF),and to explore the correlation between plasma levels of TGF-β1,BNP and TGF-β1/BNP with parameter of diastolic function,diastolic dysfunction and New York Heart Association (NYHA) classification of cardiac function.Methods Hospitalized patients with DHF from October 2016 to November 2017 in Beijing Chaoyang Hospital were selected as subjects.At the same time,the age-and gender-matched non-heart failure hospitalized patients were selected as the control.The diastolic function index (E/e') was measured using cardiac ultrasound spectral Doppler and tissue Doppler methods.The diastolic dysfunction classification was evaluated according to the American Society of Echocardiography guidelines.Cardiac function was evaluated with NYHA classification.The levels of plasma TGF-β1 and BNP were measured with method of enzyme linked immunosorbent assay (ELISA).The correlation between the indicators was analyzed and the receiver operating characteristic (ROC) curve was drawn.Results A total of 186 patients were enrolled,including 114 patients as DHF group [54 males and 60 females,mean age (70.75 ± 11.45) years old] and 72 cases as control group [41 males and 31 females,mean age (68.74 ± 10.86) years old].The levels of TGF-β1 [(77.68 ± 42.31) ng/L] and BNP [(1 153.84 ± 564.96) ng/L] in patients with DHF were significantly higher than those of the control group [(18.76 ± 13.70),(264.07 ± 179.43) ng/L,t =15.62,13.77,P ＜ 0.01].Pearson correlation analysis showed that level of plasma TGF-β1 had a significant liner correlation with index E/e' (r =0.582,P ＜ 0.01),level of plasma BNP had a low-degree liner correlation with index E/e' (r =0.261,P ＜ 0.01),and TGF-β1/BNP had no correlation with index E/e' (r =0.081,P ＞ 0.05).Spearman correlation analysis showed that the levels of TGF-β1 and BNP were significantly correlated with diastolic dysfunction grading (r =0.473,0.417,P ＜ 0.01),while TGF-β1/BNP had no correlation with diastolic dysfunction grading (r =0.062,P ＞ 0.05).Plasma TGF-β1 and BNP had low-degree correlation with NYHA classification of heart failure (r =0.309,0.326,P ＜ 0.01),TGF-β1/BNP had no correlation with NYHA classification of heart failure (r =0.011,P ＞ 0.05).Logistic analysis showed that both plasma TGF-β1 and BNP were independent predictors of DHF (OR =1.264,2.283,P ＜ 0.05 or ＜ 0.01).The area under ROC curve (AUC) of BNP for prediction of DHF was 0.937 ± 0.064,and TGF-β1 was 0.597 ± 0.042.AUC areas of BNP and TGF-β1 were significantly different (P ＜ 0.01).Conclusions The expressions of plasma TGF-β1 and BNP in patients with DHF are higher than those without DHF.The levels of plasma TGF-β1 and BNP are significantly correlated with index E/e',diastolic dysfunction grading and NYHA classification.Both elevated BNP and TGF-β1 levels are independent predictors of DHF.Both plasma BNP and TGF-β1 have auxiliary diagnostic value on DHF and the diagnostic value of plasma BNP is greater than plasma TGF-β1.

Objective To explore whether the lung ultrasound( LUS) score can be used to assess and predict the criticality of neonates with pulmonary disease at an early stage . Methods T he new borns born in the obstetrics department of Affiliated Hospital of Jining M edical University from April to October 2018 were transferred to the neonatal intensive care unit due to respiratory distress . T he children underwent LUS examination and scoring at 2 hours after birth . T he correlation analysis were performed between LUS score and neonatal critical illness score ( NCIS ) ,NCIS +single index ,respectively . And the ROC curve was used to analyze the value of LUS score in predicting neonatal criticality . Results ①T he LUS score of non‐critical neonates was significantly lower than that of critically ill newborns , the difference was statistically significant ( P ＝0 .005) ; LUS score was an independent risk factor for critical neonates ( OR＝1 .71 ,95%CI :1 .059－2 .765 , P ＝ 0 .028 ) . ② T he correlation coefficient between LUS score and NCIS was －0 .48 ( P ＝0 .002) . T he correlation coefficient between the LUS score and the NCIS + single index was －0 .44 ( P＝0 .005) . ③T he area under the ROC curve of LUS score predicting neonatal criticality was 0 .88 ( 95%CI :0 .725－0 .965 , P ＜0 .000 1) ,the optimal diagnostic threshold was 6 points with sensitivity of 80% and specificity of 100% . Conclusions The LUS score at a postnatal age of 2 hours after birth can early assess and predict the criticality of neonates with pulmonary disease . And the LUS score greater than 6 has the highest diagnostic value .

Objective: To explore whether the lung ultrasound(LUS) score can be used to assess and predict the criticality of neonates with pulmonary disease at an early stage. Methods: The newborns born in the obstetrics department of Affiliated Hospital of Jining Medical University from April to October 2018 were transferred to the neonatal intensive care unit due to respiratory distress. The children underwent LUS examination and scoring at 2 hours after birth. The correlation analysis were performed between LUS score and neonatal critical illness score (NCIS ), NCIS+ single index, respectively. And the ROC curve was used to analyze the value of LUS score in predicting neonatal criticality. Results: ①The LUS score of non-critical neonates was significantly lower than that of critically ill newborns, the difference was statistically significant (P=0.005); LUS score was an independent risk factor for critical neonates (OR=1.71, 95% CI: 1.059-2.765, P=0.028). ②The correlation coefficient between LUS score and NCIS was -0.48 (P=0.002). The correlation coefficient between the LUS score and the NCIS+ single index was -0.44 (P=0.005). ③The area under the ROC curve of LUS score predicting neonatal criticality was 0.88 (95% CI: 0.725-0.965, P<0.000 1), the optimal diagnostic threshold was 6 points with sensitivity of 80% and specificity of 100%. Conclusions The LUS score at a postnatal age of 2 hours after birth can early assess and predict the criticality of neonates with pulmonary disease. And the LUS score greater than 6 has the highest diagnostic value.

Advanced glycation end-products (AGEs) are stable and toxic by-products of non-enzymatic metabolic reaction of proteins,lipids and nucleotides.The elevated serum AGEs level in pregnant women is strongly associated with hyperglycemia,oxidative stress and insulin resistance and may be one of the cause for the onset and development of the gestational diabetes mellitus(GDM).This review mainly focuses on the pathogenesis of AGEs and GDM.

OBJECTIVETo determine the molecular etiology for a Chinese pedigree affected with epidermolysis bullosa simplex (EBS).

METHODSTarget region sequencing using a hereditary epidermolysis bullosa capture array combined with Sanger sequencing and bioinformatics analysis were used. Mutation taster, PolyPhen-2, Provean, and SIFT software and NCBI online were employed to assess the pathogenicity and conservation of detected mutations. One hundred healthy unrelated individuals were used as controls.

RESULTSTarget region sequencing showed that the proband has carried a unreported heterozygous c.1234A>G (p.Ile412Val) mutation of the KRT14 gene, which was confirmed by Sanger sequencing in other 8 affected individuals but not among healthy members of the pedigree. Bioinformatics analysis indicated that the mutation is highly pathogenic. Remarkably, 3 members of the family (2 affected and 1 unaffected) have carried a heterozygous c.1237G>A (p.Ala413Thr) mutation of the KRT14 gene, which was collected in Human Gene Mutation Database (HGMD). Bioinformatics analysis indicated that the mutation may not be pathogenic. Both mutations were not detected among the 100 healthy controls.

CONCLUSIONThe novel c.1234A>G(p.Ile412Val) mutation of the KRT14 gene is probably responsible for the disease, while c.1237G>A (p.Ala413Thr) mutation of KRT14 gene may be a polymorphism. Compared with Sanger sequencing, target region capture sequencing is more efficient and can significantly reduce the cost of genetic testing for EBS.

Adult ; Amino Acid Sequence ; Case-Control Studies ; Epidermolysis Bullosa Simplex ; genetics ; Female ; Humans ; Keratin-14 ; genetics ; Male ; Mutation ; genetics ; Pedigree ; Young Adult

OBJECTIVETo explore the molecular mechanism in the formation of unstable plaques.

METHODSThe cDNA microarray E-MTAB-2055 was downloaded from ArrayExpress database to screen the differentially expressed genes in 24 ruptured plaques against 24 stable plaques. Functional enrichment analysis was conducted to define the biological processes and pathways involved in disease progression. The protein-protein interaction network was constructed to identify the risk modules with close interactions. Five pairs of carotid specimens were used to validate 3 differentially expressed genes of the risk modules by real-time PCR.

RESULTSA total of 439 genes showed differential expression in our analysis, including 232 up-regulated and 207 down-regulated genes according to the data filter criteria. Immune-related biological processes and pathways were greatly enriched. The protein-protein interaction network and module analysis suggested that TYROBP, VCL and CXCR4 might play critical roles in the development of unstable plaques, and differential expressions of CXCR4 and TYROBP in carotid plaques were confirmed by real-time PCR.

CONCLUSIONOur study shows the differential gene expression profile, potential biological processes and signaling pathways involved in the process of plaque rupture. TYROBP may be a new candidate disease gene in the pathogenesis of unstable plaques.

Adaptor Proteins, Signal Transducing ; genetics ; Disease Progression ; Down-Regulation ; Gene Expression Profiling ; Humans ; Membrane Proteins ; genetics ; Oligonucleotide Array Sequence Analysis ; Plaque, Atherosclerotic ; genetics ; Protein Interaction Maps ; Real-Time Polymerase Chain Reaction ; Receptors, CXCR4 ; genetics ; Transcriptome ; Up-Regulation ; Vinculin ; genetics