OBJECTIVES: Keratoconus (KC) is a progressive corneal ectasia disorder, arising from a myriad of causes including genetic predispositions, environmental factors, biomechanical influences, and inflammatory reactions. This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population. METHODS: Twenty-five patients with primary KC as well as 50 unrelated population-matched healthy controls, were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population. Sanger sequencing and whole-exome sequencing (WES) were used to analyze mutations in the zinc finger protein 469 (ZNF469) gene. Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis. RESULTS: Five novel heterozygous missense variants were identified in KC patients. Among them, 2 compound heterozygous variants, c.8986G>C (p. E2996Q) with c.11765A>C (p. D3922A), and c.4423C>G (p. L1475V) with c.10633G>A (p. G3545R), were determined to be possible pathogenic factors for KC. CONCLUSIONS Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population. These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
Adolescent ; Adult ; Female ; Humans ; Male ; Case-Control Studies ; China/ethnology* ; Exome Sequencing ; Genetic Predisposition to Disease ; Keratoconus/genetics* ; Mutation ; Mutation, Missense ; Transcription Factors/genetics* ; East Asian People/genetics*

Objective:To investigate the value of fibrinogen to albumin ratio (FAR), creatinine to albumin ratio (CAR) and platelet to lymphocyte ratio (PLR) in predicting the poor prognosis of hyperlipidemic acute pancreatitis (HLAP).Methods:Clinical data of HLAP patients admitted to the hospital from January 2021 to January and December 2023 were retrospectively collected. According to the prognosis, the patients were divided into two groups: good prognosis group and poor prognosis group.The independent risk factors of HLAP in different prognostic groups were obtained by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic value of FAR, CAR and PLR alone and in combination.Results:A total of 118 patients with HLAP were included, including 69 patients with good prognosis and 49 patients with poor prognosis.The difference of heart rate, lymphocyte, triglyceride, albumin, creatinine, urea nitrogen, blood calcium, blood glucose, C-reactive protein, procalcitonin, fibrinogen, FAR, CAR, PLR, Bedside indicator of acute pancreatitis Severity score, Acute Physiology and Chronic Health status score, hospitalization time assessment between the two groups was statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that FAR (odds ratio ( OR) = 25.949, 95% confidence interval (95% CI):3.190 ~ 211.080, P = 0.002), CAR ( OR = 1.453, 95% CI:1.095 ~ 1.928, P = 0.010) and PLR ( OR = 1.005, 95% CI: 1.001 ~ 1.009, P = 0.020) were independent risk factors for poor prognosis in HLAP patients. ROC curve analysis showed that the area under the ROC curve (AUC) of FAR, CAR and PLR to predict poor prognosis of HLAP patients were 0.823, 0.781 and 0.652, respectively.The AUC of FAR combined with CAR, FAR combined with PLR and CAR combined with PLR were 0.840, 0.845 and 0.849, respectively.The combined ability of FAR, CAR and PLR to predict poor prognosis in HLAP patients was (AUC=0.875,95% CI:0.814 ~ 0.937). When the cut-off value was 0.387, the sensitivity was 83.7%, and the specificity was 79.7%. Conclusions:The prognostic value of FAR, CAR and PLR in HLAP patients is better than that of single or pairwise combination.

Objective To investigate the correlations of serum levels of NOD-like receptor family CARD domain containing 3 (NLRC3) and extracellular matrix protein 1 (ECM1) with the development of acute respiratory distress syndrome (ARDS) in patients with sepsis. Methods A total of 133 patients with sepsis were enrolled in sepsis group, and 80 healthy individuals during the same period were included in control group. The sepsis group was further divided into ARDS group (52 cases) and non-ARDS group (81 cases) based on the presence or absence of ARDS. Serum levels of NLRC3 and ECM1 expression were measured using enzyme-linked immunosorbent assays (ELISA). Multivariate Logistic regression analysis was used to identify factors associated with the development of ARDS in sepsis patients. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of serum NLRC3 and ECM1 levels for ARDS in sepsis patients. Results Compared with the control group, the sepsis group had significantly lower serum NLRC3 level and higher ECM1 level (P < 0.05). The incidence of ARDS in the 133 sepsis patients was 39.10% (52/133). Compared with the non-ARDS group, the ARDS group had significantly lower serum NLRC3 level and higher ECM1 level (P < 0.05). Independent risk factors for the development of ARDS in sepsis patients were increased Sequential Organ Failure Assessment (SOFA) score, elevated blood lactate level and increased ECM1 level, while increased NLRC3 level was an independent protective factor (P < 0.05). The area under the curve for the combined prediction of serum NLRC3 and ECM1 expression in sepsis patients with ARDS was 0.887, which was greater than 0.811 and 0.792 predicted by serum NLRC3 and ECM1 expression alone (P < 0.05). Conclusion Decreased serum NLRC3 level and increased ECM1 level are closely associated with the development of ARDS in sepsis patients. The combined assessment of serum NLRC3 and ECM1 level has a high predictive value for ARDS in sepsis patients.

OBJECTIVE: To investigate the protective effects of total saponins from Panax japonicus (TSPJ) against high-fat dietinduced testicular Sertoli cell junction damage in mice. METHODS: Forty male C57BL/6J mice were randomized into normal diet group, high-fat diet group, and low-dose (25 mg/kg) and high-dose (75 mg/kg) TSPJ treatment groups (n=10). The mice in the normal diet group were fed a normal diet, while the mice in the other groups were fed a high-fat diet. After TSPJ treatment via intragastric administration for 5 months, the testes and epididymis of the mice were collected for measurement of weight, testicular and epididymal indices and sperm parameters. HE staining was used for histological evaluation of the testicular tissues and measurement of seminiferous tubule diameter and seminiferous epithelium height. The expression levels of ZO-1, occludin, claudin11, N-cadherin, E-cadherin and β-catenin in Sertoli cells were detected with Western blot, and the localization and expression levels of ZO-1 and β-catenin in the testicular tissues were detected with immunofluorescence assay. The protein expressions of LC3B, p-AKT and p-mTOR in testicular Sertoli cells were detected using double immunofluorescence assay. RESULTS: Treatment with TSPJ significantly improved high-fat diet-induced testicular dysfunction by reducing body weight (P < 0.001), increasing testicular and epididymal indices (P < 0.05), and improving sperm concentration and sperm viability (P < 0.05). TSPJ ameliorated testicular pathologies and increased seminiferous epithelium height of the mice with high-fat diet feeding (P < 0.05) without affecting the seminiferous tubule diameter. TSPJ significantly increased the expression levels of ZO-1, occludin, N-cadherin, E-cadherin and β-catenin (P < 0.05) but did not affect claudin11 expression in the testicular tissues. Immunofluorescence assay showed that TSPJ significantly increased ZO-1 and β-catenin expression in the testicular tissues (P < 0.001), downregulated LC3B expression and upregulated p-AKT and p-mTOR expressions in testicular Sertoli cells. CONCLUSION TSPJ alleviates high-fat diet-induced damages of testicular Sertoli cell junctions and spermatogenesis possibly by activating the AKT/mTOR signaling pathway and inhibiting autophagy of testicular Sertoli cells.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Testis ; Sertoli Cells ; beta Catenin ; Diet, High-Fat ; Occludin ; Proto-Oncogene Proteins c-akt ; Seeds ; Cadherins ; Intercellular Junctions

Objective:To analyze the prognostic risk factors of patients with traumatic pancreatitis (TP) and establish an early combined prediction of multiple indicators model for TP.Methods:Patients admitted to the ICU of the First Affiliated Hospital of Zhengzhou University from June 2017 to June 2022 were collected retrospectively. Based on their prognosis, the patients were divided into two groups: the good prognosis group and the poor prognosis group. The general data such as sex, age, underlying diseases, Glasgow Coma Scale (GCS), acute physiology and chronic health evaluationⅡ (APACHEⅡ), injury severity score (ISS), bedside index for severity in acute pancreatitis (BISAP), and clinical test indices such as blood routine, blood coagulation, blood gas analysis, and liver and kidney function at admission were compared between the two groups. Univariate analysis and multivariate logistic regression analysis were used to screen the early independent predictors of poor prognosis of TP, and the prediction model of TP was established by combining all of the independent indicators. The receiver operating characteristic (ROC) curve of each independent predictor and prediction model was drawn, and the area under the curve (AUC), sensitivity, specificity, and optimal cut-off value were calculated to examine the diagnostic impact of each independent predictor and the combined prediction model.Results:There were statistically significant differences in the complication rate of mental disorders, GCS, APACHE II, combined craniocerebral injury, combined chest injury, activated partial thromboplastin time, fibrin(pro)degradation products, lactate, aspartate aminotransferase, glomerular filtration rate, amylase, lipase, NT-proBNP, myoglobin, procalcitonin, ISS, and BISAP between the good and poor prognosis groups (all P<0.05). Multivariate logistic regression analysis showed that lactate ( OR=1.636, 95% CI: 1.046-2.559), lipase ( OR=1.005, 95% CI: 1.001-1.008), and ISS ( OR=1.161, 95% CI: 1.064-1.266) were independent risk factors influencing the prognosis of patients with TP. Based on the risk factors listed above, a prediction model was created: Logit P=-9.260+0.492×lactate+0.005×lipase+0.149×ISS, and the ROC curve was plotted. The AUC curve of the prediction model was 0.96 (95% CI: 0.91-1.00). Conclusions:Lactate, lipase, and ISS are early independent risk factors associated with the prognosis of TP. Their combined multi-indicator prediction model has an excellent clinical prediction effect, which can provide a clinical reference for early prediction and treatment of TP.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the childhood Epstein-Barr virus(EBV)-positive lymphoproliferative diseases(EBV + LPD). Methods:The clinical features, treatment course, and prognosis of 9 children with EBV + LPD who underwent allo-HSCT in Children′s Hospital Affiliated to Zhengzhou University from July 2019 to July 2022 were analyzed retrospectively. Results:All the 9 children underwent histopathological examination, including 6 patients with EBV-positive T-cell lymphoproliferative disease (EBV + T-LPD), 1 with pulmonary lymphomatoid granuloma, and 2 with systemic EBV-positive T-cell lymphoma.There were 6 males and 3 females, with the median age of 5.8 (1.5-13.0) years.At the initial diagnosis, plasma and peripheral EBV-DNA copy at the initial diagnosis was (5.67-865.00)×10 2/mL, and (5.13-1 250.00)×10 2/mL, respectively.The EBV-DNA load of cerebrospinal fluid increased to (5.18-291.00)×10 2/mL in 3 cases.The whole exon sequencing data showed no abnormality in 3 cases, pulmonary lymphomatoid granuloma with the IL2RG mutation in 1 case and EBV + T-LPD with a hemizygous mutation in the SH2D1A gene as the pathogenic mutation in 1 case.Pathogenic mutations were not detected in the remaining 4 cases.The course of disease before transplantation was 5.4(3.0-10.0) months.Disease status before transplantation was as follows: all 3 cases of lymphomas had partial regression; 2 cases of EBV + T-LPD had active disease; and 4 cases had no active disease.Among the donors, there were 5 cases of half-matched relatives, 2 cases of full-matched siblings and 2 cases of unrelated full-matched donors.The median number of mononuclear cells in peripheral blood and/or bone marrow hematopoietic stem cell was 6.60(3.64-12.18)×10 8/kg, while the median implantation time of neutrophils was 18(9-23) days.One month after the transfusion of hematopoietic stem cells, plasma EBV-DNA copy was negative in all cases, and peripheral EBV-DNA copy was negative in 7 cases.The copy number in the other 2 cases was 10 2/mL.At the 3-month evaluation, plasma and peripheral EBV-DNA copy were negative in all cases.In addition, 3 cases of lymphomas achieved radiographic complete remission, and 6 cases of EBV + T-LPD were inactive.All transplant-related complications were effectively controlled after medication.Following the median follow-up of 24 (11-42) months, all patients had disease-free survival.Serious impact on the quality of life due to graft versus host disease was not reported. Conclusions:allo-HSCT is an effective treatment of childhood EBV + LPD, which is able to control transplant-related complications.Children with EBV + LPD can achieve long-term disease-free survival through transplantation.

Acute Disease ; Allografts ; Humans ; Kidney ; Kidney Transplantation ; Nephritis ; Pyelonephritis ; Transplantation, Homologous

Objective:To explore the expression of fructose bisphosphate aldolase A (ALDOA) in the bone marrow of patients with acute myeloid leukemia (AML) and the correlation with clinical features and prognosis.Methods:The bone marrow samples of 90 newly diagnosed AML (non-acute promyelocytic leukemia) patients and 18 allogeneic hematopoietic stem cell transplantation donors who were treated from January 2013 to December 2015 in the First Affiliated Hospital of Zhengzhou University and the Children's Hospital Affiliated to Zhengzhou University were collected. The relative expression level of ALDOA mRNA in bone marrow samples was detected by using real-time quantitative polymerase chain reaction (qRT-PCR). Clinical data of these patients were retrospectively analyzed, and the patients were divided into continuous complete remission (CR) group and refractory recurrent (RR) group according to the clinical response and follow-up results. The differences of the relative expression level of ALDOA mRNA between AML group and the normal control group, CR group and RR group were analyzed. Univariate and multivariate Cox regression risk model were used for analysis of factors influencing prognosis of AML patients.Results:The relative expression level of ALDOA mRNA in AML group was higher than that in normal control group [(5.71±0.44) vs. (1.10±0.08), t = 4.74, P<0.001]. The relative expression level of ALDOA mRNA in the RR group was higher than that in the CR group [(6.69±0.67) vs. (4.30±0.36) , t = 2.79, P < 0.001]. In addition, there were statistically significant differences in the proportion of patients with ALDOA mRNA high expression and those with ALDOA mRNA low expression stratified by the number of white blood cell, the proportion of bone marrow blasts and whether complete remission could be achieved or not after 1 course of induction therapy (all P < 0.05). Overall survival in patients with ALDOA high expression was worse than that in patients with ALDOA low expression ( χ2 = 5.59, P = 0.018). Multivariate analysis showed that white blood cell count, prognosis stratification, whether complete remission could be achieved or not after 1 course of induction therapy and ALDOA expression were the independent prognostic factors for the death of AML patients (all P < 0.05). Conclusions:ALDOA may play an important role in the development and progression of AML, and the expression level of ALDOA in the bone marrow can be used as an index for the prognosis assessment of AML patients and may be a potential therapeutic target for AML.

Objective:To analyze the clinical data of pregnant women complicated with cardiovascular disease in our center in the past 10 years, and to explore the trend of incidence, clinical diagnosis, and treatment of the disease.Methods:Clinical data of pregnant women with cardiovascular disease who delivered in Beijing Anzhen Hospital, Capital Medical University from 2010 to 2019 were collected and analyzed retrospectively. According to the time of the establishment of multidisciplinary team (MDT) in the center, the pregnant women were divided into the first 5-year group (2010-2014) and the second 5-year group (2015-2019). The general data, the composition of pregnancy complicated with cardiovascular disease and the changes of maternal and infant outcomes of the two groups were analyzed.Results:(1) During 2010-2019, there were 2 267 cases of pregnancy complicated with cardiovascular disease (836 cases in the first 5-year group and 1 431 cases in the second 5-year group), with a total incidence of 10.2% (2 267/22 334). Among all kinds of cardiovascular diseases, arrhythmia (41.0%, 930/2 267) and congenital heart disease (38.2%, 865/2 267) were more common. (2) There were 212 cases (25.4%, 212/836) and 426 cases (29.8%, 426/1 431) classified as Ⅲ or Ⅳ by modified WHO cardiovascular risk classification in the first 5-year group and the second 5-year group, respectively, and the difference was statistically significant ( χ2 =5.076, P=0.024). Among all kinds of cardiovascular diseases, there were 111 cases (13.3%, 111/836) and 159 cases (11.1%, 159/1 431) with valvular disease in the first 5-year group and the second 5-year group, respectively. The change of the component ratio was -16.5% (the difference was significant when the absolute value of change>10%), showing a significant decreasing trend. Aortic disease was found in 16 cases (1.9%, 16/836) and 56 cases (3.9%, 56/1 431), respectively, with a significant upward trend of 105.3%. (3) The mortality rate of pregnant women with cardiovascular disease was 1.0% (22/2 267), and 1.2% (10/836) and 0.8% (12/1 431) in the first 5-year grouop and the second 5-year group, respectively. There was no significant difference between the two groups ( χ2=0.702, P=0.402). ICU occupancy rates in the first 5-year group and the second 5-year group were 25.6% (214/836) and 20.7% (296/1 431), respectively, and the difference between the two groups was statistically significant ( χ2=7.306, P=0.007). There were no significant differences in cesarean section rate, mortality rate and incidence of adverse events between the two groups of pregnant women, and there were no significant differences in birth weight, preterm birth rate, mortality rate and asphyxia rate between the two groups of newborns (all P>0.05). Conclusions:Pregnancy complicated with cardiovascular disease is a common cause of adverse obstetric outcomes. There are various types of specific cardiovascular diseases, and the prognosis varies greatly. In recent years, the disease composition ratio has changed, and the severity and complexity of diseases have increased. Hierarchical management, MDT and individual management could improve the treatment level and reduce adverse outcomes.

Objective:To investigate the effects of gestational diabetes mellitus (GDM) on neonatal metabolites.Methods:This retrospective cohort study recruited 580 singleton newborns who were born to women with GDM from January 2018 to December 2018 in Foshan Maternal and Child Health Care Hospital as the GDM group. Another 580 counterparts born to non-GDM singleton mothers with matching age were selected as the non-GDM group with an allocation ratio of 1 to 1. Neonatal genetic metabolic disease screening was performed within 3-7 days after birth. Two independent sample t-test, and multiple linear regression model were used for statistical analysis. Results:There were significant differences in seven amino acids and 10 fatty acids levels between the GDM and non-GDM group. The serum levels of six amino acids and eight fatty acids were increased in the GDM group, while the levels of piperamide [(140.79±32.60) vs (150.26±35.46) μmol/L, t=－4.733, P<0.001], palmitoyl carnitine [(2.59±0.81) vs (2.73±0.82) μmol/L, t=－2.940, P=0.003], and carbamate [(0.066±0.022) vs (0.069±0.022) μmol/L, t=－1.937, P=0.042] were decreased compared with the non-GDM group. After adjusting for maternal gravidity, parity, neonatal birth weight, and gender, multivariate linear regression analysis showed that GDM was positively correlated with three amino acids levels, which were cysteine ( ?=0.012), homocysteine ( ?=0.263) and leucine ( ?=4.225); and was negatively correlated with glycine ( ?=－6.271) and piperamide level ( ?=－9.885). With regard to the fatty acids, GDM was positively correlated with the neonatal propionyl carnitine ( ?=0.214), butyryl carnitine ( ?=0.014), 3-hydroxybutyryl carnitine ( ?=0.006), isovaleryl carnitine ( ?=0.009), 3-hydroxyisovaleryl carnitine ( ?=0.024), hexadecanoyl carnitine ( ?=0.001), decadienoyl carnitine ( ?=0.045), octadecadienyl carnitine level ( ?=0.128), but was negatively correlated with palmitoyl carnitine ( ?=－0.119), and carbamate ( ?=－0.002) (all P<0.05). Conclusions:Correlations between maternal GDM and the levels of amino acids and fatty acids in neonates was noted in this study, suggesting that maternal GDM may affect the metabolism of amino acids and fatty acids in offspring at early stage of life.