Objective:To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease (PMD) caused by nuclear gene mutations.Methods:From May 2020 to March 2022, the clinical data, genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results:A total of 4 patients were enrolled, all with hyperlactatemia and metabolic acidosis. In case 1, the fetal cranial MRI showed agenesis of corpus callosum. In case 2, echocardiography after birth indicated hypertrophic cardiomyopathy. Whole exome sequencing found the following mutations: EARS2 nuclear gene c.1294C>T and c.971G>T variants, COA6 nuclear gene c.411_412insAAAG variant, ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants, FOXRED1 nuclear gene c.1054C>T and c.3dup variants. Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities. Cases 1 and 3 died during the neonatal period. Case 2 died at 2-year-and-2-month of age. Case 4 was followed up to 1 year of age with developmental delay.Conclusions:The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia, refractory metabolic acidosis and cardiomyopathy, which have a poor prognosis. Proactive genetic tests are helpful for early diagnosis.

Objective To observe the influence of dapagliflozin tablets on myocardial enzymes,mitral valve blood flow and major adverse cardiovascular events(MACE)in patients with acute myocardial infarction(AMI)complicated with type 2 diabetes mellitus(T2DM)after interventional therapy.Methods AMI patients with T2DM were divided into control group and treatment group by cohort method.The control group was given aspirin tablets 300 mg and ticagrelor 180 mg orally,qd,until the day of interventional treatment.After interventional therapy,aspirin tablets 100 mg,qd,oral ticagrelor tablets 90 mg each time,once in the morning and once in the evening.On the basis of the treatment in the control group,the patients in the treatment group were given dapagliflozin tablets 5-10 mg,qd,every morning after admission.After 3 months of continuous treatment,the clinical efficacy,blood glucose control effect[fasting plasma glucose(FPG),2 hour postprandial blood glucose(2 h PG)],myocardial enzymes indicators[creatine kinase(CK),creatine kinase isoenzyme-MB(CK-MB)],ventricular remodeling indicators[left ventricular ejection fraction(LVEF),left ventricular end systolic diameter(LVESD)],adverse drug reactions and MACE were compared between the two groups.Results There were 55 cases in the control group and 59 cases in the treatment group.After treatment,the total effective rates of the treatment group and the control group were 88.14％(52 cases/59 cases)and 72.73％(40 cases/55 cases),respectively,the difference was statistically significant(P＜0.05).After treatment,the FPG of the treatment group and the control group were(7.29±0.71)and(7.81±0.75)mmol·L-1,respectively;the 2 h PG were(8.66±1.33)and(9.59±1.38)mmol·L-1,respectively;the CK were(145.68±29.82)and(163.68±42.16)U·L-1,respectively;the CK-MB were(8.21±2.37)and(10.33±3.08)U·L-1,respectively;the LVEF were(57.63±8.74)％and(51.41±6.49)％,respectively;LVESD were(33.26±5.33)and(39.51±5.38)mm,respectively.The above indexes in the treatment group were significantly different from those in the control group(all P＜0.05).During the treatment,the adverse drug reactions in the treatment group mainly included nausea and vomiting,diarrhea,constipation.The adverse drug reactions in the control group mainly included hypoglycemia,diarrhea,headache.The total incidence of adverse drug reactions in the treatment group and the control group was 6.68％(4 cases/59 cases)and 9.09％(5 cases/55 cases),respectively,and the difference was not statistically significant(P＞0.05).After 3 months of follow-up,the total incidence of MACE in the treatment group and the control group was 5.08％and 18.18％,respectively,the difference was statistically significant(P＜0.05).Conclusion Dapagliflozin has a significant efficacy in the treatment of AMI patients with T2DM,and it can enhance the effect of blood glucose control,reduce the myocardial injury,inhibit the ventricular remodeling,and reduce the risk of MACE,with high safety.

Objective:To investigate the expression of replication factor C5 (RFC5) in cervical cancer, and its effect on the prognosis and immune regulation as well as its related mechanism.Methods:RFC5 mRNA expression data and the clinical data of 280 cervical cancer patients were downloaded from the Cancer Genome Atlas (TCGA) database in May 2023. The difference of RFC5 mRNA expression between cervical cancer tissues and paracancerous normal tissues was compared and the expression of RFC5 mRNA in patients with different clinicopathological characteristics was analyzed. According to the median expression level of RFC5 mRNA in cancer tissues, 280 patients were divided into the high expression group and the low expression group. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison. Gene Expression Profiling Interactive Analysis (GEPIA) 2 online tool was used to verify the relationship between RFC5 gene expression and the prognosis of cervical cancer. Univariate and multivariate Cox proportional risk models were used to analyze the factors influencing the overall survival (OS) of patients with cervival cancer in TCGA database. LinkedOmics database was used to screen the co-differentially expressed genes (DEG) related to RFC5 in cervical cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genesand Genomes (KEGG) pathway enrichment analysis of DEG related to RFC5 were performed based on the DAVID database. Based on the Tumor Immune Estimation Resource (TIMER) database, the relationship between RFC5 expression and tumor infiltrating immune cells in cervival cancer was analyzed by using Spearman method. The relationship between RFC5 expression and immunomodulatory factors in cervical cancer was analyzed based on tumor-immune system interactions database (TISIDB). The expression of RFC5 protein in cervical cancer tissues was analyzed based on Human Protein Atlas (HPA) database. The expression of RFC5 in pan-cancer and its correlation with OS were analyzed based on GEPIA2 online tool.Results:In TCGA database, the relative expression level of RFC5 mRNA in cervical cancer tissues (277 cases) was higher than that in paracancerous normal tissues (3 cases), and the difference was statistically significant ( P < 0.001), while there were no significant differences in the relative expression level of RFC5 mRNA in cancer tissues of patients with different age, pathological type and clinical staging (all P > 0.05). The OS of cervival cancer patients in high RFC5 expression group (139 cases) was better than that of patients in low RFC5 expression group (138 cases), and the difference was statistically significant ( P = 0.027). GEPIA tool verification indicated that expression of RFC5 in cervical cancer and its relationship with OS showed the same results. GO and KEGG enrichment analysis showed that RFC5-related genes were mainly involved in DNA replication, cell cycle, Fanconi anemia, mismatch repair, base excision repair, nucleotide excision repair and other signaling pathways. Multivariate Cox regression analysis showed that age ≥ 65 years, clinical staging Ⅳ and the low expression of RFC5 were independent risk factors of poor OS in patients with cervical cancer (all P < 0.05). TIMER database analysis showed that the expression of RFC5 was positively correlated with tumor purity ( rho = 0.198, P < 0.001), while weakly correlated or not correlated with the infiltration levels of B cells ( rho = 0.062, P = 0.306), CD8 + T cells ( rho = 0.168, P = 0.005), CD4 + T cells ( rho = -0.049, P = 0.418), macrophages ( rho = 0.034, P = 0.577), neutrophils ( rho = 0.169, P = 0.005) and bone marrow dendritic cells ( rho = 0.026, P = 0.667). Analysis of TISIDB data showed that RFC5 expression was mostly negatively correlated with immunosuppressive factors and immunostimulatory factors. HPA database showed that the expression level of RFC5 in cervical cancer tissues was higher than that in normal cervical tissues. GEPIA online tool database analysis showed that RFC5 expression was up-regulated in a variety of malignant tumors. The OS of thymoma patients with high RFC5 expression was better than that of those with low RFC5 expression, while the OS of acute myeloid leukemia patients with high RFC5 expression was worse than those with low RFC5 expression, and the differences in OS were statistically significant (both P < 0.05). Conclusions:RFC5 is highly expressed in cervical cancer and its expression is associated with prognosis of patients with cervival cancer. Overexpression of RFC5 may inhibit the expression of immunomodulatory factors, and it may regulate the development and progression of cervical cancer through DNA replication, cell cycle, mismatch repair, base excision repair and other related pathways.

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.
Humans ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Biological Assay ; Cell Cycle

Public exposure to radon has attracted increasing public concern. The newly issued "Standards for indoor air quality (GB/T 18883-2022)" has revised the radiological parameters of radon. This study analyzed and discussed the relevant technical contents about the derivation of radon limit, including the distribution level for indoor radon, exposure pathway, health effects, and the process for establishing the standard limits. Specific implementation and evaluation suggestions are also proposed.
Humans ; Radon/analysis* ; Air Pollution, Indoor ; China ; Housing

Public exposure to radon has attracted increasing public concern. The newly issued "Standards for indoor air quality (GB/T 18883-2022)" has revised the radiological parameters of radon. This study analyzed and discussed the relevant technical contents about the derivation of radon limit, including the distribution level for indoor radon, exposure pathway, health effects, and the process for establishing the standard limits. Specific implementation and evaluation suggestions are also proposed.
Humans ; Radon/analysis* ; Air Pollution, Indoor ; China ; Housing

Objective To study the effect of Kangdaxin on cardiac function in rats with cardio-renal syndrome, and to explore its protective mechanism based on ASK1-JNK/p 38 pathway. Methods Sixty SD rats were divided into sham group, heart failure group (HF group) , cardio-renal syndrome group (CRS group) , heart failure interventiongroup and cardio-renal syndrome intervention group. The sham group, heart failure group, cardio-renal syndrome group were given normal saline, the heart failure intervention group, and the cardio-renal syndrome intervention group were given 2. 7 m L·kg-1·d-1 Kangdaxin oral solution. Left ventricular shortening fraction and left ventricular ejection fraction were measured by cardiac ultrasound after modeling or treatment; heart weight/body weight (Hw/W) and left ventricular weight/body weight (LVw/W) were calculated after sacrifice of the rats. The gene and protein expression levels of ASK1, JNK and p38 in heart tissue of each group were detected by real-time quantitative polymerase chain reaction (q PCR) and immunob-lotting. The myocardial cells of each group were detected by flow cytometry.Results The left ventricular fraction, left ventricular ejection fraction, Hw/W and LVw/W in sham group were (31. 17 ± 2. 15) ％, (61. 08 ± 3. 45) ％, (3. 43 ± 0. 31) mg·g-1 and (2. 50 ± 0. 27) mg·g-1; the above indicators in heart failure group were (24. 42 ± 1. 98) ％, (42. 08 ± 4. 57) ％, (4. 10 ± 0. 21) mg · g-1, (2. 89 ± 0. 26) mg·g-1, the above indicators in cardio-renal syndrome group were (18. 50 ± 2. 84) ％, (38. 25 ± 3. 96) ％, (4. 84 ± 0. 32) mg·g-1, (3. 89 ± 0. 18) mg·g-1, compared with the sham operation group, all differences were statistically significant (all P < 0. 05) . The left ventricular shortening scores of heart failure intervention group and cardio-renal syndrome inte-rvention group were (27. 33 ± 3. 14) ％, (22. 67 ± 2. 66) ％, and the left ventricular ejection fraction were (50. 00 ± 3. 70) ％, (43. 83 ± 3. 78) ％, LVw/W were (2. 60 ± 0. 25) , (3. 63 ± 0. 22) mg·g-1.The differences between the heart failure group and the cardio-renal syndrome group were all statistically significant (all P < 0. 05) . The expressions of ASK1, JNK and p38 mRNA and protein in heart tissue of heart failure group and cardio-renal syndrome group were significantly lower than those in sham operation group (all P < 0. 05) .The apoptotic rate of cardiomyocytes in heart failure group and cardio-renal syndrome group were (24. 14 ± 5. 51) ％, (35. 60 ± 8. 75) ％, which was significantly higher than that in sham operation group (7. 87 ± 3. 13) ％ (all P < 0. 05) . The apoptotic rate of cardiomyocytes in heart failure intervention group and cardio-renal syndrome intervention group were (14. 12 ± 5. 98) ％, (26. 50 ± 7. 22) ％, compared with heart failure group and cardio-renal syndrome group, the differences were all statistically significant (all P < 0. 05) .Conclusion Kangdaxin oral solution has cardioprotective effect on cardio-renal syndrome rats which can inhibit the expressions of ASK1, JNK and p38 mRNA and protein in heart tissue, inhibit ASK1-JNK/p38 signaling pathway and decrease myocardial cell apoptosis.

OBJECTIVETo evaluate the significance of determining ascitic bacterial 16S rRNA by quantitative PCR combined with microarray (PCR-microarray) in the diagnosis of spontaneous bacterial peritonitis (SBP).

METHODSAscitic bacterial 16SrRNA was determined by real time fluorescent quantitative PCR-microarray in 76 cases of suspected SBP and 6 cases of non-infectious ascites with chronic liver diseases. The results were compared with ascitic bacterial culture simultaneously.

RESULTSOf 76 ascitic samples, 17 were detected bacteria positive by PCR-microarray, including 8 Grams positive(G+) and 9 Grams negative(G-), which was higher than that by bacterial culture which had only 6 ascitic samples detected positive (all G-); the positive rates were 22.4% vs 7.9%, respectively (P < 0.01). The bacterial strains detected by both methods in 6 cases had a consistency with each other. No bacteria were detected in another 6 cases of non-infectious ascites with chronic liver diseases.

CONCLUSIONSDetermination of ascitic bacteria 16S rRNA by PCR-microarray has a higher specificity and sensitivity in the diagnosis of SBP as compared with the bacteria culture. Application of this novel method can not only accelerate SBP diagnosis but also stratify the different pathogens.

Adult ; Aged ; Ascitic Fluid ; microbiology ; Bacterial Infections ; diagnosis ; microbiology ; Female ; Humans ; Liver Cirrhosis ; diagnosis ; microbiology ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Peritonitis ; diagnosis ; microbiology ; Polymerase Chain Reaction ; methods ; RNA, Bacterial ; isolation & purification ; RNA, Ribosomal, 16S ; isolation & purification