Objective To investigate the distribution of pathogens and changes in serum humanβ-defendin-3(HBD3)and FMS like tyrosine kinase 3 ligand(Flt3L)levels in patients with pulmonary infection after esophageal cancer radical surgery.Methods Prospectively,patients who underwent radical resection of esophageal cancer and developed pulmonary infection from January 2022 to January 2024 were selected as the infection group(75 cases),and patients who underwent radical resection of esophageal cancer and did not develop pulmonary infection were selected as the non-infection group(93 cases).Patients in the infection group were divided into the mild group(25 cases),the moderate group(39 cases),and the severe group(11 cases)based on the CURB-65 score.The distribution of pathogenic bacteria in patients of the infection group was analyzed by the fully automatic microbial identification instrument.The expression levels of HBD3 and Flt3L in serum were detected by enzyme-linked immunosorbent assay(ELISA).Multivariate Logistic regression was applied to analyze the risk factors for postoperative pulmonary infection in esophageal cancer patients.ROC curve was applied to analyze the diagnostic value of HBD3 and Flt3L levels for postoperative pulmonary infection in esophageal cancer patients.Results Among 75 infected patients,90 strains of pathogens were detected,including 49 strains(54.44％)of Gram negative bacteria,29 strains(32.22％)of Gram positive bacteria,and 12 strains(13.33％)of fungi.The serum HBD3 and Flt3L levels in the infection group were greatly higher than those in the non infection group(P＜0.05).The serum HBD3 and Flt3L levels in the severe group were higher than those in the moderate group and mild group(P＜0.05),while the serum HBD3 and Flt3L levels in the moderate group were higher than those in the mild group(P＜0.05).Multivariate Logistic regression analysis showed that HBD3,Flt3 L,tumor location in the upper/middle segment,intraoperative bleeding ≥ 500 ml,diabetes,and smoking history were all factors influencing the pulmonary infection after radical resection of esophageal cancer(P＜0.05).According to the ROC curve,the AUC value for diagnosing postoperative pulmonary infection in esophageal cancer patients with serum HBD3 level alone was 0.789.The AUC value for diagnosing postoperative pulmonary infection in esophageal cancer patients with serum Flt3L level alone was 0.863,the AUC value of the combined diagnosis of the two was 0.934,which was greatly higher than that of the individual diagnosis(Zcombination vs HBD3=3.723,Zcombination vs Flt3L=2.098,P＜0.05).Conclusion The serum HBD3 and Flt3L levels in patients with pulmonary infection after esophageal cancer radical surgery are highly expressed,and the serum HBD3 and Flt3L levels are correlated with the severity of pulmonary infection.The two are risk factors for postoperative pulmonary infection in esophageal cancer patients after radical surgery,and their combination can effectively diagnose postoperative pulmonary infection in esophageal cancer patients.

Objective:To screen high risk children for lysosomal storage diseases (LSD) in southern China and analyze the spectrum characteristics of LSD in this region.Methods:A cross-sectional study was conducted. A total of 7 435 children at high risk of LSD were screened at Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2009 to December 2024. The activities of 22 lysosomal enzymes from peripheral blood leukocytes or plasma were measured by fluorescence or colorimetric assays with synthetic substrates to screen for 24 LSD subtypes.Results:Among the 7 435 high risk children, 759 children were diagnosed with LSD (10.2%). The diagnosed cases included 506 males and 253 females, with an age at diagnosis of 3.0 (2.5, 5.5) years. The common disease types were mucopolysaccharidosis (MPS) (390 cases (51.4%)), sphingolipidoses (269 cases (35.4%)), glycogen storage disease (62 cases (8.2%)), and mucolipidosis types Ⅱ and Ⅲ (29 cases (3.8%)). Among the positive cases, 21 disease subtypes were identified. The 5 frequent subtypes, in descending order, were MPS type Ⅱ (197 cases (26.0%)), Gaucher disease (111 cases (14.6%)), MPS type ⅣA (87 cases (11.5%)), glycogen storage disease type Ⅱ (62 cases (8.2%)), and metachromatic leukodystrophy (MLD) (49 cases (6.5%)). The rarest subtypes were mannosidosis, multiple sulfatase deficiency and Wolman disease, each with 1 case (0.1%).Conclusions:Enzyme activity screening is essential for diagnosing high risk children with LSD. In Southern China, the most common LSD subtypes are MPS Ⅱ, Gaucher disease, MPS ⅣA, glycogen storage disease type Ⅱ, and MLD, while mannosidosis, multiple sulfatase deficiency and Wolman disease are the rarest.

Objective To investigate the distribution of pathogens and changes in serum humanβ-defendin-3(HBD3)and FMS like tyrosine kinase 3 ligand(Flt3L)levels in patients with pulmonary infection after esophageal cancer radical surgery.Methods Prospectively,patients who underwent radical resection of esophageal cancer and developed pulmonary infection from January 2022 to January 2024 were selected as the infection group(75 cases),and patients who underwent radical resection of esophageal cancer and did not develop pulmonary infection were selected as the non-infection group(93 cases).Patients in the infection group were divided into the mild group(25 cases),the moderate group(39 cases),and the severe group(11 cases)based on the CURB-65 score.The distribution of pathogenic bacteria in patients of the infection group was analyzed by the fully automatic microbial identification instrument.The expression levels of HBD3 and Flt3L in serum were detected by enzyme-linked immunosorbent assay(ELISA).Multivariate Logistic regression was applied to analyze the risk factors for postoperative pulmonary infection in esophageal cancer patients.ROC curve was applied to analyze the diagnostic value of HBD3 and Flt3L levels for postoperative pulmonary infection in esophageal cancer patients.Results Among 75 infected patients,90 strains of pathogens were detected,including 49 strains(54.44％)of Gram negative bacteria,29 strains(32.22％)of Gram positive bacteria,and 12 strains(13.33％)of fungi.The serum HBD3 and Flt3L levels in the infection group were greatly higher than those in the non infection group(P＜0.05).The serum HBD3 and Flt3L levels in the severe group were higher than those in the moderate group and mild group(P＜0.05),while the serum HBD3 and Flt3L levels in the moderate group were higher than those in the mild group(P＜0.05).Multivariate Logistic regression analysis showed that HBD3,Flt3 L,tumor location in the upper/middle segment,intraoperative bleeding ≥ 500 ml,diabetes,and smoking history were all factors influencing the pulmonary infection after radical resection of esophageal cancer(P＜0.05).According to the ROC curve,the AUC value for diagnosing postoperative pulmonary infection in esophageal cancer patients with serum HBD3 level alone was 0.789.The AUC value for diagnosing postoperative pulmonary infection in esophageal cancer patients with serum Flt3L level alone was 0.863,the AUC value of the combined diagnosis of the two was 0.934,which was greatly higher than that of the individual diagnosis(Zcombination vs HBD3=3.723,Zcombination vs Flt3L=2.098,P＜0.05).Conclusion The serum HBD3 and Flt3L levels in patients with pulmonary infection after esophageal cancer radical surgery are highly expressed,and the serum HBD3 and Flt3L levels are correlated with the severity of pulmonary infection.The two are risk factors for postoperative pulmonary infection in esophageal cancer patients after radical surgery,and their combination can effectively diagnose postoperative pulmonary infection in esophageal cancer patients.

Objective:To screen high risk children for lysosomal storage diseases (LSD) in southern China and analyze the spectrum characteristics of LSD in this region.Methods:A cross-sectional study was conducted. A total of 7 435 children at high risk of LSD were screened at Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2009 to December 2024. The activities of 22 lysosomal enzymes from peripheral blood leukocytes or plasma were measured by fluorescence or colorimetric assays with synthetic substrates to screen for 24 LSD subtypes.Results:Among the 7 435 high risk children, 759 children were diagnosed with LSD (10.2%). The diagnosed cases included 506 males and 253 females, with an age at diagnosis of 3.0 (2.5, 5.5) years. The common disease types were mucopolysaccharidosis (MPS) (390 cases (51.4%)), sphingolipidoses (269 cases (35.4%)), glycogen storage disease (62 cases (8.2%)), and mucolipidosis types Ⅱ and Ⅲ (29 cases (3.8%)). Among the positive cases, 21 disease subtypes were identified. The 5 frequent subtypes, in descending order, were MPS type Ⅱ (197 cases (26.0%)), Gaucher disease (111 cases (14.6%)), MPS type ⅣA (87 cases (11.5%)), glycogen storage disease type Ⅱ (62 cases (8.2%)), and metachromatic leukodystrophy (MLD) (49 cases (6.5%)). The rarest subtypes were mannosidosis, multiple sulfatase deficiency and Wolman disease, each with 1 case (0.1%).Conclusions:Enzyme activity screening is essential for diagnosing high risk children with LSD. In Southern China, the most common LSD subtypes are MPS Ⅱ, Gaucher disease, MPS ⅣA, glycogen storage disease type Ⅱ, and MLD, while mannosidosis, multiple sulfatase deficiency and Wolman disease are the rarest.

Objective:To investigate the effect of Edaravone and dexborneol(Eda.B)on oxidative stress pathway in peripheral blood of elderly patients with acute ischemic stroke.Methods:A total of 87 elderly patients with acute ischemic stroke in the Department of Neurology, Qinghai University Affiliated Hospital from July 2021 to January 2022 were selected as the study subjects.According to the random number table, they were divided into control group(44 cases)and edaravone dexborneol group(43 cases). Each group was divided into <12 h group, 12-24 h group and 24-48 h group according to the time of onset.Peripheral blood was collected in each group at admission and discharge, respectively.The serum levels of reactive oxygen species(ROS), Kelch-like epichlorohydrin-associated protein 1(Keap1), nuclear factor-E2-associated factor 2(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6), as well as superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were detected.Results:Elderly patients with acute ischemic stroke receving Eda.B treatment after admission could reduce the serum concentration of ROS, TNF-α and IL-6, as well as MDA content, and increase the concentration of Keap1, Nrf2, HO-1 and NQO1 and SOD activity.Except for ROS concentration in <12 h group and SOD activity in <12 h and 12 h-24 h groups, the differences between the other groups were statistically significant( P<0.05 for all). Compared with the control group, the serum concentration of TNF-α and IL-6 of patients in the Eda.B group at discharge decreased, while the concentration of Nrf2(24-48 h group)and HO-1(24-48 h group), and SOD activity increased, the differences were statistically significant( P<0.05 for all). In the control group at discharge, the concentrations of ROS(24-48 h group), TNF-α(<12 h group, 24-48 h group)and IL-6, as well as MDA content decreased, while the concentrations of Keap1, Nrf2(<12 h group, 12-24 h group)and HO-1(<12 h group, 12-24 h group)increased, the differences were also statistically significant( P<0.05 for all). Compared with admission, the concentration of Keap1(24-48 h group)and HO-1(24-48 h group), the activity of SOD(<12 h group, 12-24 h group)increased and the content of MDA(12-24 h group)in the Eda.B group decreased at discharge( P<0.05 for all). Conclusions:Eda.B can reduce oxidative stress and inflammatory response in peripheral blood of elderly patients with acute ischemic stroke by acting on the Keap1/Nrf2 pathway.

Objective:To evaluate the activity of iduronate-2-sulfatase (IDS) in fetal villi and peripheral blood plasma of pregnant women at high risk of mucopolysaccharidosis type Ⅱ (MPS Ⅱ), and to discuss the application of gene analysis in prenatal diagnosis of MPS Ⅱ.Methods:The enzymatic testing and gene analysis results of 23 pregnant women at high risk of MPS Ⅱ, who underwent prenatal diagnosis in Guangzhou Women and Children′s Medical Center from February 2013 to December 2020, were analyzed retrospectively.The IDS activity in fetal villi (30 cases) and plasma (28 cases) was detected by artificial substrate fluorescence.The IDS activity in fetal villi (28 cases) and plasma (34 cases) of normal pregnant women was taken as control.Meanwhile, the fetal villi of both pregnant women at high risk of MPS Ⅱ and normal pregnant women were also analyzed by gene testing and for fetal sex identification.Data were compared between groups by the independent samples t test. Results:The normal reference values of the IDS activity in fetal villi and plasma of normal pregnant women were(71.2±23.4) nmol/(mg·4 h) and (611.1±114.5) nmol/(mL·4 h), respectively.Among the 30 cases of high-risk fetal villi, the IDS activity in fetal villi of 8 affected male fetuses was (1.7±0.3) nmol/(mg·4 h), which was significantly lower than that of 11 unaffected male fetuses (83.2±6.3) nmol/(mg·4 h) and that of 9 non-carrier female fetuses (80.0±7.5) nmol/(mg·4 h) ( t=10.8, 8.8; all P<0.01). Meanwhile, the IDS activity was measured in the maternal peripheral plasma of 28 pregnant women at high risk of MPS Ⅱ.Among them, the IDS activity in 8 affected male fetuses was(225.4±20.5) nmol/(mL·4 h), which was significantly lower than that in non-affected male fetuses[(451.0±15.1) nmol/(mL·4 h)] and that in non-carrier female fetuses[(467.7±45.3)nmol/(mL·4 h)]. Eight known pathogenic mutations were found in 30 cases at high risk of MPS Ⅱ of fetal villi, and the mutation types were c. 1048A>C, c.212G>A, c.514C>T, c.257C>T, c.425C>T, and c. 998C>T.Of the 8 cases, 6 affected male fetuses had significantly reduced IDS activities, and the other 2 female carriers had normal IDS enzyme activities. Conclusions:The IDS activity in fetal villi and peripheral plasma of pregnant woman is consistent with the gene analysis results.The IDS activity has an important reference value for the prenatal diagnosis of MPS Ⅱ in the first trimester.When no genetic mutations are found in the probands or the pathogenicity of the new mutation remains unclear, the IDS activity in fetal villi can be detected separately for the prenatal diagnosis of MPS Ⅱ.

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. Methods: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. Results: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. Conclusion The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.

Objective: To investigate the prognostic value of radiomics analysis in predicting axillary lymph nodes (ALN) metastasis of breast cancer based on dynamic contrast-enhanced MR imaging (DCE-MRI). Methods: One hundred and ninety-six patients with suspected breast cancer were prospectively collected for dynamic breast DCE-MRI. Enhanced MR imaging data of 72 axillary lymph nodes were evaluated separately by a chief radiologist and a resident, and the consistency analysis was performed. Lymph nodes were dichotomized according to the pathology results derived from operation or biopsy under real-time virtual sonography based on MRI data. Clinical and imaging data were also divided into corresponding groups. (Imaging) Data from both groups were respectively classified as training set and testing set by stratified sampling in proportion with 3∶1. AK software was applied to extract 6 major categories of 385 features (including histogram, morphology, texture parameters, gray level co-occurrence matrix, run-length matrix and grey level zone size matrix from imaging), and a set of statistically significant features were subsequently obtained by dimension reduction. The prediction model was established through binary classification logistic regression and employed to externally test the validation set by the method of confusion matrix. Meanwhile, ROC analysis was applied to assess the diagnostic performance of the model. Results: Of the 72 axillary lymph nodes, 35 were metastatic negative and 37 were positive. The consistency of enhanced MRI radiomics features was good, between 0.841 and 0.980. Uniformity, ClusterProminence_AllDirection_offset1_SD, Correlation_AllDirection_offset1, LongRunEmphasis_angle90_offset7 and SurfaceVolumeRatio were statistically significant differences (P<0.01), the area under the ROC between 0.747 and 0.931. In the training and testing group, the areas under the ROC, sensitivity, specificity and accuracy of the model were 0.953, 0.893, 0.926, 92.6% (50/54) and 0.944, 0.900, 1.000, 88.9% (16/18) respectively. Conclusion The prediction model based on radiomic features may provide a non-invasive and effective approach to the assessment of the risk of ALN metastasis of breast cancer.

Objective To sum up and analyze the clinical and pathological characteristics in patients with both IgA nephropathy (IgAN) and diabetes mellitus. Methods A total of 500 patients were recruited, including 25 patients with both IgAN and diabetes mellitus, and 475 patients with IgAN only, who were diagnosed by renal-biopsy during Jan 2015 to Jan 2017 at the First Affiliated Hospital of Zhengzhou University. The clinical and pathological data were collected and analyzed using SPSS 22.0. Propensity Score Matching was used to match and select the patients in the both groups, and thereafter the depth of the basement membrane from the matched patients were compared using electron microscopy. The data of the patients whose follow - up time was ≥3 months were retrospectively collected, and Kaplan-Meier analysis was used to compare the difference of the prognosis. Results Compared to the patients with IgAN only, patients with both IgAN and diabetes mellitus were older [(46.36±13.49) years vs (34.00±13.80) years, P<0.001], had higher level of serum triglyceride [2.06(1.52, 3.11) mmol/L vs 1.51(1.01, 2.25) mmol/L, P=0.012] and thicker basement membrane [(384.33 ± 61.20) nm vs (346.72 ± 52.65) nm, P=0.044]. The patients with both IgAN and diabetes mellitus were more prone to reach the composite endpoint [4/7(57.14％) vs 25/265(9.33％), P<0.001] and had worse prognosis (Log-Rank test, P=0.004). Conclusions IgAN patients with diabetes mellitus have different clinical, pathological characteristics and prognosis from patients with IgAN alone. These patients need to be closely monitored and actively treated.

Objective To observe the influence of Kuailvning capsule(KLN)and its drug serum on the concentration of Ca2 + in rat ventricular muscle cells.Methods SD rats were randomly divided into five groups:the control group,serum control group,KLN high -dose group,KLN medium -dose group and KLN low -dose group,six mice in each group.The rat ventricular myocytes were separated by enzymatic hydrolysis.The influence of KLN and its drug serum on the concentration of Ca2 + in rat ventricular muscle cells were observed by Fluo -3 /AMprobe.Results The mean fluorescence intensity of cytosolic Ca2 + in the KLN high -dose group,KLN medium -dose group and KLN low -dose group after 50s,100s,150s,200s,250s were [(18.75 ±1.55),(16.69 ±0.93),(17.76 ±1.26)], [(25.47 ±1.118),(17.86 ±1.49),(17.81 ±1.13)],[(29.05 ±1.31),(20.14 ±1.73),(18.26 ±1.37)], [(35.21 ±1.33),(23.19 ±0.97),(18.18 ±1.46)],[(41.08 ±1.21),(26.34 ±1.69),(17.91 ±1.01)], which were higher than those in the control group(F =5.556,7.007,8.816,10.208,12.232,all P <0.01 ).The mean fluorescence intensity of cytosolic Ca2 + in the KLN high -dose group after 50s,100s,150s,200s,250s were (17.85 ±1.69),(18.95 ±1.73),(21.85 ±1.39),(23.01 ±1.48),(24.07 ±1.42),which were higher than those in the serum control group(t =3.642,4.406,6.074,7.402,8.625,all P <0.01 ).The mean fluorescence intensity of cytosolic Ca2 + in the KLN medium -dose group after 100s,150s,200s,250s were (18.01 ±1.42), (18.76 ±1.22),(19.73 ±1.37),(21.04 ±1.16),which were higher than those in the serum control group(t =3.902,4.033,4.126,4.326,all P <0.01).There were no statistically significant difference between the KLN low -dose group and the serum control group(P >0.05).Conclusion KLN drug serum can promote myocardial cell spon-taneous extracellular calcium influx,the mechanism of KLN antiarrhythmic effect may be related to the Ca2 + channel.