Objective:To explore clinical and genetic features of persistent asymptomatic microscopic hematuria in children.Methods:A retrospective case analysis of 135 individuals admitted to Xi ′an Children′s Hospital with persistent asymptomatic microscopic haematuria between January 2016 to December 2023 was conducted. The demographic characteristics, kidney pathology and gene results of 135 individuals were analyzed. One hundred and thirty-five individuals were divided into 2 groups (positive group and negative group) according to family history of glomerulogenic hematuria in first-degree relatives. The differences of hematuria remission, proteinuria and gene variation were compared between the 2 groups. Two independent sample t test, Wilcoxon rank sum test, Pearson Chi-square, Yates′ corrected Chi-squared test or Fisher exact test were used for comparison between groups. Results:All 135 children, with 48 males and 87 females, were 8.5 (6.5, 9.5) years old at first presentation. Kidney biopsy was performed in 73 cases (54.1%). Kidney pathology showed mild lesions in 41 cases (56.2%), thin basement membrane disease (TBMD) in 24 cases (32.9%), typical pathological features of Alport syndrome in 5 cases (6.8%), and other manifestations in 3 cases (4.1%). The positive group comprised 52 individuals, whereas the negative group consisted of 83 individuals. The positive group demonstrated a higher susceptibility in proteinuria and gene variation, while the negative group exhibited a greater rate of hematuria remission ( χ2=5.00, 5.27, 8.52, all P<0.05). Whole exome sequencing was performed in 80 individuals and 18 individuals (22.5%) had a pathogenic or likely pathogenic variant in COL4A3-5. COL4A5 was the most common gene afected, accounting for 11 cases. The 135 individuals were followed up for 4.2 (2.9, 5.1) years, of which 31 cases (22.9%) had complete hematuria remission at 2.1 (1.4, 2.7) years. Up to March 2024, there were also 7 individuals (5.2%) with varying degrees of proteinuria, and 3 individuals (2.2%) with proteinuria progressed to chronic kidney insufficiency. Conclusions:The most common kidney pathological types in children with persistent asymptomatic microscopic hematuria are minor lesions and TBMD. Children with microscopic hematuria whose first-degree relatives have a family history of hematuria are more likely to have proteinuria and gene variants. COL4A3-5 genetic screening could be considered a priority in these children.

Objective:To explore clinical and genetic features of persistent asymptomatic microscopic hematuria in children.Methods:A retrospective case analysis of 135 individuals admitted to Xi ′an Children′s Hospital with persistent asymptomatic microscopic haematuria between January 2016 to December 2023 was conducted. The demographic characteristics, kidney pathology and gene results of 135 individuals were analyzed. One hundred and thirty-five individuals were divided into 2 groups (positive group and negative group) according to family history of glomerulogenic hematuria in first-degree relatives. The differences of hematuria remission, proteinuria and gene variation were compared between the 2 groups. Two independent sample t test, Wilcoxon rank sum test, Pearson Chi-square, Yates′ corrected Chi-squared test or Fisher exact test were used for comparison between groups. Results:All 135 children, with 48 males and 87 females, were 8.5 (6.5, 9.5) years old at first presentation. Kidney biopsy was performed in 73 cases (54.1%). Kidney pathology showed mild lesions in 41 cases (56.2%), thin basement membrane disease (TBMD) in 24 cases (32.9%), typical pathological features of Alport syndrome in 5 cases (6.8%), and other manifestations in 3 cases (4.1%). The positive group comprised 52 individuals, whereas the negative group consisted of 83 individuals. The positive group demonstrated a higher susceptibility in proteinuria and gene variation, while the negative group exhibited a greater rate of hematuria remission ( χ2=5.00, 5.27, 8.52, all P<0.05). Whole exome sequencing was performed in 80 individuals and 18 individuals (22.5%) had a pathogenic or likely pathogenic variant in COL4A3-5. COL4A5 was the most common gene afected, accounting for 11 cases. The 135 individuals were followed up for 4.2 (2.9, 5.1) years, of which 31 cases (22.9%) had complete hematuria remission at 2.1 (1.4, 2.7) years. Up to March 2024, there were also 7 individuals (5.2%) with varying degrees of proteinuria, and 3 individuals (2.2%) with proteinuria progressed to chronic kidney insufficiency. Conclusions:The most common kidney pathological types in children with persistent asymptomatic microscopic hematuria are minor lesions and TBMD. Children with microscopic hematuria whose first-degree relatives have a family history of hematuria are more likely to have proteinuria and gene variants. COL4A3-5 genetic screening could be considered a priority in these children.

Objective:To evaluate the bioequivalence and safety of domestic and original pyrazinamide tablets under fasting condition.Methods:A single center, randomized, open-label, two period self-crossover trial was conducted in healthy adult volunteers. The test preparation (T) of pyrazinamide tablets was produced by Taicang Pharmaceutical Factory and the reference preparation (R) was produced by A&Z Pharmaceutical Inc. (Pyrazinamide ?). The healthy subjects were randomly divided into 2 groups and took the drugs for 2 times with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 8) and T-R group (subjects took T on day 1 and then R on day 8). Pharmacokinetic parameters were used as endpoints to assess the bioequivalence. Peripheral venous blood samples (3 ml) were collected from subjects within 1 hour before taking the drug and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, and 210 minutes and 4, 5, 6, 8, 12, 24, 36, and 48 hours after taking the drug. Plasma was frozen after centrifugation of the blood samples. The plasma pyrazinamide concentrations were determined by a tandem liquid chromatography-mass spectrometry method and the main pharmacokinetic parameters such as peak concentration ( Cmax) and the area under the concentration-time curve (AUC), including AUC from time zero (pre-dose) to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞), were calculated. The test and reference preparations were judged as bioequivalence when the 90% confidence intervals ( CI) of geometric mean ratios for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.80 to 1.25. Adverse events occurred in subjects during the trial were observed and recorded. Results:A total of 24 healthy volunteers were enrolled in the trial, including 16 males and 8 females aged 18-50 years, with 12 in the R-T and T-R groups, respectively. All subjects completed the trial. After taking medicine under fasting condition, the 90% CI of the geometric mean ratios of Cmax, AUC 0-t, and AUC 0-∞ for the test and reference preparations were 0.93-1.09, 0.98-1.03, and 0.98-1.03, respectively. During the trial, the incidence of adverse events was 25.0% (6/24) and 3 cases occurred after taking the test and reference preparations respectively, which were grade 1 in severity. Conclusion:The domestic and original pyrazinamide tablets were bioequivalence and with good safety when taken under fasting condition.

Objective:To evaluate the bioequivalence and safety of domestic and original pyrazinamide tablets under fasting condition.Methods:A single center, randomized, open-label, two period self-crossover trial was conducted in healthy adult volunteers. The test preparation (T) of pyrazinamide tablets was produced by Taicang Pharmaceutical Factory and the reference preparation (R) was produced by A&Z Pharmaceutical Inc. (Pyrazinamide ?). The healthy subjects were randomly divided into 2 groups and took the drugs for 2 times with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 8) and T-R group (subjects took T on day 1 and then R on day 8). Pharmacokinetic parameters were used as endpoints to assess the bioequivalence. Peripheral venous blood samples (3 ml) were collected from subjects within 1 hour before taking the drug and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, and 210 minutes and 4, 5, 6, 8, 12, 24, 36, and 48 hours after taking the drug. Plasma was frozen after centrifugation of the blood samples. The plasma pyrazinamide concentrations were determined by a tandem liquid chromatography-mass spectrometry method and the main pharmacokinetic parameters such as peak concentration ( Cmax) and the area under the concentration-time curve (AUC), including AUC from time zero (pre-dose) to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞), were calculated. The test and reference preparations were judged as bioequivalence when the 90% confidence intervals ( CI) of geometric mean ratios for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.80 to 1.25. Adverse events occurred in subjects during the trial were observed and recorded. Results:A total of 24 healthy volunteers were enrolled in the trial, including 16 males and 8 females aged 18-50 years, with 12 in the R-T and T-R groups, respectively. All subjects completed the trial. After taking medicine under fasting condition, the 90% CI of the geometric mean ratios of Cmax, AUC 0-t, and AUC 0-∞ for the test and reference preparations were 0.93-1.09, 0.98-1.03, and 0.98-1.03, respectively. During the trial, the incidence of adverse events was 25.0% (6/24) and 3 cases occurred after taking the test and reference preparations respectively, which were grade 1 in severity. Conclusion:The domestic and original pyrazinamide tablets were bioequivalence and with good safety when taken under fasting condition.

Lager yeast is the most popular yeast strain used for beer production in China. The flocculation of yeast plays an important role in cell separation at the end of fermentation. Therefore, appropriately enhancing the flocculation capability of the lager yeast without affecting its fermentation performance would be desirable for beer industry. Our previous study showed that the defect of gene RIM21 might contribute to the enhanced flocculation capability of a lager yeast G03. To further investigate the role of the RIM21 gene in flocculation of strain G03, this study constructed a RIM21-deleted mutant strain G03-RIM21Δ through homologous recombination. Deletion of RIM21 improved the flocculation capability of strain G03 during wort fermentation at 11 °C without changing its fermentation performance significantly. The expression of FLO5, Lg-FLO1 and some other genes involved in cell wall integrity pathway were up-regulated in strain G03-RIM21Δ. In addition, the disruption of RIM21 enhanced resistance of yeast cells to cell wall inhibitors. These results provide a basis for elucidating the flocculation mechanism of lager yeast under low-temperature fermentation conditions.
Beer ; Fermentation ; Flocculation ; Receptors, Cell Surface ; Saccharomyces/metabolism* ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism*

OBJECTIVE To observe the neurotoxicity of 1-bromopropane(BP) and investigate the protective effects of edaravone(Edv) against BP-induced deficits of spatial learning and memory ability in rats by its anti-inflammatory mechanism. METHODS Adult male Wistar rats were ig given BP 800 mg·kg-1 to develop the model, followed by Edv 1, 3 and 5 mg·kg-1 ip treatment respectively 4 h later for consecutive 12 d. From the 7th day (d 7), all rats were subjected to the five-day place navigation in Morris water maze (MWM) to measure the escape latency and the total swimming distance. On d 6 of MWM, spatial probe test was performed and the crossing times of rats were recorded to evaluate the spatial memory ability. At the end of the behavioral experiment, four rats in each group were randomly selected and the frozen section of the whole brain was sliced for thionin staining and immunohisto?chemistry. The other eight sacrifced rat brains from each group were harvested for the determination of the tumor necrosis factor-α (TNF-α) and nitric oxide (NO) by ELISA and nitrate reductase method, respectively. RESULTS The results of MWM test showed that compared with control rats the escape latencies of rats in BP group were increased by 60.8%, 81.9%,124.0% and 323.3%, respectively, during the d 2-d 5 of MWM, and the total swimming distance increased by 47.0%, 66.4%, 106.0% and 277.6%, respectirely. All the differences between BP group and control group were significant (P<0.05, P<0.01). In the spatial probe trial, the crossing times of rats in BP group were significantly decreased, compared with the control rats (P<0.01). Morphologically, thionin staining and immunohistochemistry revealed significant microglia activation and neuron loss in the rat forebrains, accompanied by a 147.6% and 18.7% increase in NO and TNF-α levels in rats treated with BP respectively compared with control values (P<0.05, P<0.01). After co-treatment at different dosages of Edv with BP, the escape latencies of rats in BP+Edv 5 mg·kg-1 group were decreased by 38.4%and 44.3%(P<0.01), and the total swimming distance decreased 34.5%and 43.3%(P<0.05, P<0.01), respectively, compared with the BP treated rats on the d 4 and d 5 of MWM test. The microglia activation and neuron damage in the brain of rats induced by BP treatment were significantly alleviated in BP+Edv groups. In addition, the contents of NO and TNF-α were decreased in BP+Edv 1, 3 and 5 mg · kg-1 groups, with a decrease of 53.8%, 55.4% and 59.8% in NO, and 12.2%, 15.8% and 22.2% in TNF-α(P<0.05, P<0.01), respectively. CONCLUSION Edv could effectively protect against central neurotoxicity induced by BP via anti-neuro?inflammation.

Objective .To prove aristolochic (AA) caused vascular endothelial cells (VEC) injury via intracellular calcium overloa-ding and investigate the mechanism of calcium dobesilate antagonism. Methods Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and randomly divided into three groups: Control group, AA group, intervention group. Microscope and transmission elec-tron microscopy were used to observe changes of cell morphology and ultrastructure. ELISA method were applied to determine thrombomedu-lin (TM) in cell culture supernatant, fluorescent indicator FLuo-3/AM and intracellular calcium concentration ([Ca2+]. Results TM val-ue and average [Ca2+] i of AA group were significantly higher than that of control group (P < 0.05). Compared with the AA group, when the concentration of calcium dobesilate was 25 μM or 50 μM, TM value and average [Caz +] significantly decreased in intervention group (P < 0.05). Compared with control group, endoplasmic reticulum was pool expansion shaped, and mitochondrial cristae was absent in AA group cells. Endoplasmic reticulum and mitochondria patterns in the intervention group cells showed some improvement, compared with AA group. Conclusion AA induced VEC calcium overloading, 'I'M secretion and injury of endothelial ceils, endoplasmic reticulum and mito-chondria destruction. Dabesilate calcium could protect endoplasmic reticulum and mitochondria and reduce AA induced VEC calcium over-loading, and these could protect VEC.