Progress of Ginsenoside Rb1 in neurological disorders.

Ginseng is frequently used in traditional Chinese medicine to treat neurological disorders. The primary active component of ginseng is ginsenoside, which has been classified into more than 110 types based on their chemical structures. Ginsenoside Rb1 (GsRb1)-a protopanaxadiol saponin and a typical ginseng component-exhibits anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-autophagy properties in the nervous system. Neurological disorders remain a leading cause of death and disability globally. GsRb1 effectively treats neurological disorders. To contribute novel insights to the understanding and treatment of neurological disorders, we present a comprehensive review of the pharmacokinetics, actions, mechanisms, and research development of GsRb1 in neurological disorders.

Immunological Features of Children with Gastrointestinal Bleeding Due to Henoch-Schönlein Purpura.

Background: This study aims to evaluate the immunological features of gastrointestinal (GI) bleeding in children with Henoch-Schönlein purpura (HSP). Study Design: This retrospective study was conducted on children with HSP. Demographic and clinical data were collected, including serum immunoglobulin (Ig) levels, complement C3 and C4 levels, and lymphocyte subtype percentage. Results: A total of 446 hospitalized children had HSP. Eighty-six children with HSP had GI bleeding, 114 had proteinuria, and 107 had hematuria. Lower arthralgia, prolonged glucocorticoid use, increased white blood cell counts, elevated neutrophils and neutrophil-to-lymphocyte ratio, reduced IgG and C3 levels, elevated CD19+ cell percentage, and reduced CD3+ cell and natural killer cell percentages were associated with GI bleeding risk in patients with HSP. Multivariate regression analysis revealed that arthralgia, glucocorticoid use, increased neutrophil percentage, reduced IgG and C3 levels, and increased CD19+ cell percentage were independent predictors of GI bleeding. Further analysis indicated that the combination of C3 and CD19+ cell percentages had a high predictive ability for GI bleeding in children with HSP. Conclusion: This study indicated that reduced C3 and increased CD19+ cell percentages contributed to the development of GI bleeding in children with HSP. Specific immunologic profiles may be strongly correlated with GI bleeding risk in children with HSP.

Tracking the evolution of esophageal squamous cell carcinoma under dynamic immune selection by multi-omics sequencing.

Intratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, it is discovered that genomic, epigenomic, and transcriptomic ITH are underpinned by ongoing chromosomal instability. Based on the RNA-seq data, we observe diverse levels of immune infiltrate across different tumor sites from the same tumor. We reveal genetic mechanisms of neoantigen evasion under distinct selection pressure from the diverse immune microenvironment. Overall, our work offers an avenue of dissecting the complex contribution of the multi-omics level to the ITH in ESCC and thereby enhances the development of clinical therapy.

An Experimental Study on Enhancing Microbial Desulfurization of Sulfide Ores Using Ultrasonic Treatment.

Ultrasonic technology is being increasingly explored in minerals processing. In this paper, ultrasonic treatment was introduced as a novel method for microbial desulfurization of sulfide ores. A Box-Behnken experiment was performed to find the best combination of factor levels for the following experiments; consequently, the combination of factor levels at the maximum 5-day average desulfurization rate at 20 g of ore was a particle size of 120-140 mesh, a shaker speed of 175 rpm, and a dosage of 111 mL of bacterial solution. Under these conditions, a microbial desulfurization experiment of sulfide ores by ultrasonic treatment was carried out, and the effect of the particle size, the ultrasonic action time, and the ultrasonic power were investigated. Results indicated that the ultrasonic effect was not significant for ore samples with larger particle sizes, and the appropriate increase in ultrasonic action time was beneficial to the improvement of desulfurization rate, but the effect showed a decreasing trend when it exceeded 50 min, and the best desulfurization effect was achieved when the power was 300 W. This study demonstrated that the effect of microbial desulfurization can be greatly enhanced by ultrasonic treatment.

Epigenetic regulation of intestinal peptide transporter PEPT1 as a potential strategy for colorectal cancer sensitization.

Human intestinal peptide transporter PEPT1 is commonly repressed in human colorectal cancer (CRC), yet its relationship with sensitivity to the common CRC treatment ubenimex has not previously been elucidated. In this study, we confirmed PEPT1 suppression in CRC using real-time quantitative polymerase chain reaction and western blotting and then investigated the underlying epigenetic pathways involved using bisulfite sequencing, chromatin immunoprecipitation, siRNA knockdown, and reporter gene assays. We found that PEPT1 transcriptional repression was due to both DNMT1-mediated DNA methylation of the proximal promoter region and HDAC1-mediated histone deacetylation, which blocked P300-mediated H3K18/27Ac at the PEPT1 distal promoter. Finally, the effects of the epigenetic activation of PEPT1 on the CRC response to ubenimex were evaluated using sequential combination therapy of decitabine and ubenimex both in vitro and in xenografts. In conclusion, epigenetic silencing of PEPT1 due to increased DNMT1 and HDAC1 expression plays a vital role in the poor response of CRC to ubenimex.

CYP2C9 inhibits the invasion and migration of esophageal squamous cell carcinoma via downregulation of HDAC.

Cytochrome P450 2C9 (CYP2C9) is involved in the metabolism of cancer drugs and exogenous carcinogens. In our study, CYP2C9 was downregulated in multiple cohorts of human esophageal squamous cell carcinoma (ESCC). Until now, its role and epigenetic regulation of CYP2C9 repression in ESCC remain poorly understood. CYP2C9 repression in collected ESCC patient tumor tissues was demonstrated by RT-qPCR and Western blot. The histone acetylation level was carried out by the treatment of histone deacetylase inhibitor TSA and RNA interference. Epigenetic analysis revealed that the increased expression of CYP2C9 in KYSE-150 and TE1 cells was characterized by inhibition of HDAC8 and HDAC1, respectively. TSA decreased the levels of HDAC occupancy around CYP2C9 promoter region greatly. Overexpression of CYP2C9 reduced the invasion and migration of ESCC cells.

[Relationship between vitamin D deficiency and necrotizing enterocolitis in preterm infants].

OBJECTIVE: To evaluate the relationship of vitamin D level with the development of necrotizing enterocolitis (NEC) in preterm infants. METHODS: A total of 429 preterm infants with a gestational age of <36 weeks, who were admitted to the department of neonatology within 2 hours after birth between January and December, 2016, were enrolled in the study. According to whether these infants developed NEC, the 429 subjects were divided into NEC group (n=22) and non-NEC group (n=407). Peripheral venous blood was collected from these preterm infants and their mothers at admission to measure the level of 25-hydroxyvitamin D (25-OHD). The two groups were compared in terms of the serum 25-OHD levels of preterm infants and their mothers. Pearson correlation analysis was used to investigate the correlation between the serum 25-OHD levels of preterm infants and their mothers. The distribution of vitamin D levels in preterm infants was compared between the two groups. The univariate logistic regression analysis was used to determine the risk factors for NEC in preterm infants. RESULTS: The serum 25-OHD levels of preterm infants and their mothers in the NEC group were significantly lower than in the non-NEC group (P<0.001). In both groups, the serum 25-OHD levels of mothers and preterm infants were positively correlated with each other (P<0.001). The distribution of vitamin D levels (normal vitamin D level, low vitamin D level, vitamin D deficiency, and severe vitamin D deficiency) was significantly different between the NEC and non-NEC groups (P<0.001). The univariate logistic regression analysis showed that gestational age, birth weight, 25-OHD levels of preterm infants and their mothers, the duration of mechanical ventilation, the duration of oxygen inhalation, and the length of hospital stay were associated with the development of NEC (P<0.05). CONCLUSIONS: The serum 25-OHD levels of preterm infants and their mothers may be related to the development of NEC in preterm infants, suggesting that vitamin D supplementation during pregnancy is important for preventing the development of NEC in preterm infants.

Differential expression and miRNA regulation of the GSTP1 gene in the regenerating liver of Chiloscyllium plagiosum.

Liver regeneration is a complicated process, and understanding the regulatory mechanism will be helpful in the treatment of diseases associated with liver. In this study, the one-third liver resection model was established in Chiloscyllium plagiosum, and the whole transcriptome of the C. plagiosum was generated using the Illumina-Solexa sequencing platform. Differentially expressed genes were analyzed using bioinformatics methods and verified using quantitative real-time PCR (qRT-PCR). Using miRanda and TargetScan, we screened the microRNA library for miRNAs that target the glutathione S-transferase P1(GSTP1) gene. Dual-luciferase reporter assays were used to confirm binding between the miRNA and GSTP1. Finally, we used western blotting analysis to determine expression of the GSTP1 protein. As a result, 65,356 unigenes were obtained in normal and damaged liver tissues, with mean length of 955 bp. A total of 359 differentially expressed genes were acquired; 217 of which were upregulated, and 142 were downregulated, including the GSTP1 gene, following liver resection. The presence of the GSTP1 protein in C. plagiosum was shown for the first time. Luciferase reporter assay revealed that GSTP1 messenger RNA was targeted by ipu-miR-143. The discovery and differential expression analysis of GSTP1 in C. plagiosum will be a valuable resource to explain the molecular mechanism of GSTP1 regulation of liver repair.

[Relationship between vitamin D deficiency and early-onset neonatal sepsis].

OBJECTIVE: To evaluate the effect of vitamin D level on early-onset sepsis (EOS) in neonates. METHODS: Seventy-eight full-term neonates with EOS were used as the research group (EOS group). sixty healthy full-term neonates without clinical and/or laboratory features related to infections were used as the control group. Blood samples of the neonates and their mothers in both groups were collected within 72 hours of delivery to determine 25-hydroxyvitamin D(25-OHD) levels. The rate of vitamin D deficiency in the neonates and the level of 25-OHD supplemented to their mothers during pregnancy were compared between the two groups. RESULTS: There was a significant positive correlation between the serum level of 25-OHD of the mothers and that of the neonates in both groups (EOS group: r=0.797, P<0.01; control group: r=0.929, P<0.01). The neonates and their mothers in the EOS group had significantly lower 25-OHD levels than those in the control group (P<0.01). The rate of vitamin D deficiency among the neonates in the EOS group was significantly higher than that of the control group (P<0.01). The level of vitamin D supplemented to the mothers during the last 3 months of pregnancy in the EOS group was significantly lower than that in the control group (P<0.01). CONCLUSIONS: Low serum level of 25-OHD is associated with the development of early-onset sepsis in full-term neonates.

Detection of piRNAs in whitespotted bamboo shark liver.

Piwi-interacting RNAs (piRNAs) are 26 to 31-nt small non-coding RNAs that have been reported mostly in germ-line cells and cancer cells. However, the presence of piRNAs in the whitespotted bamboo shark liver has not yet been reported. In a previous study of microRNAs in shark liver, some piRNAs were detected from small RNAs sequenced by Solexa technology. A total of 4857 piRNAs were predicted and found in shark liver. We further selected 17 piRNAs with high and significantly differential expression between normal and regenerative liver tissues for subsequent verification by Northern blotting. Ten piRNAs were further identified, and six of these were matched to known piRNAs in piRNABank. The actual expression of six known and four novel piRNAs was validated by qRT-PCR. In addition, a total of 401 target genes of the 10 piRNAs were predicted by miRanda. Through GO and pathway function analyses, only five piRNAs could be annotated with eighteen GO annotations. The results indicated that the identified piRNAs are involved in many important biological responses, including immune inflammation, cell-specific differentiation and development, and angiogenesis. This manuscript provides the first identification of piRNAs in the liver of whitespotted bamboo shark using Solexa technology as well as further elucidation of the regulatory role of piRNAs in whitespotted bamboo shark liver. These findings may provide a useful resource and may facilitate the development of therapeutic strategies against liver damage.

[Pathogen distribution and risk factors of nosocomial infections in neonates in the neonatal intensive care unit].

OBJECTIVE: To study the pathogen distribution and risk factors of nosocomial infections in neonates in the neonatal intensive care units (NICU). METHODS: The clinical data of 145 neonates with nosocomial infection in the NICU were retrospectively reviewed. RESULTS: Of the 145 neonates, 41 (28.3%) were infected with Klebsiella pneumoniae, 39 (26.9%) with Escherichia coli, 10 (6.9%) with Staphylococcus epidermidis, and 55 (37.9%) with other pathogens. Logistic regression analysis showed that a gestational age of ≤32 weeks (OR=5.57), birth weigh of <1500 g (OR=6.95), hospitalization time (OR=1.23), mechanical ventilation (OR=14.12) and parenteral nutrition (OR=3.01) were major risk factors for nosocomial infections caused by Klebsiella pneumoniae. The five factors were also main risk factors for nosocomial infection caused by Escherichia coli, with the OR of 3.42, 6.73, 9.96, 0.55 and 2.13 respectively. Klebsiella pneumoniae and Escherichia coli were highly resistant to ß-lactam antibiotics but were relatively sensitive to levofloxacin and meropenem. CONCLUSIONS: Klebsiella pneumoniae, Escherichia coli and Staphylococcus epidermidis are major pathogens of nosocomial infections in neonates in the NICU and they are resistant to ß-lactam antibiotics. Mechanical ventilation and hospitalization time are the most important risk factors for nosocomial infections caused by Klebsiella pneumoniae and Escherichia coli respectively.

The role of the 5-hydroxytryptamine pathway in reflux-induced esophageal mucosal injury in rats.

BACKGROUND: Dysfunction of the 5-hydroxytryptamine (5-HT) signaling pathway can lead to gastrointestinal motility and secretion abnormalities and to visceral hypersensitivity. The aim of this study is to investigate the role of 5-HT in reflux-induced esophageal mucosal injury. METHODS: Fifty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into a gastroesophageal reflux (GER) model group (30 rats) and a sham surgery control group (20 rats). Four weeks after surgery, the esophageal mucosa was collected for histological evaluation, 5-HT concentrations, and 5-HT selective reuptake transporter (SERT) mRNA and 5-HT4 receptor (5-HT4R) protein expressions. RESULTS: Twenty-seven rats in the GER model group survived, and three rats died. Histologically, in the GER model group, 20 rats had reflux esophagitis (RE group), and 7 rats had non-erosive reflux disease (NERD group). The 5-HT levels in the esophageal tissue from the RE group were significantly higher than those from the control and NERD groups. Both the RE and NERD groups showed significant increases in SERT mRNA expression of the esophageal mucosa than that of the controls, and the SERT mRNA level in the RE group was significantly higher than that in the NERD group. The 5-HT4R protein level of the esophageal mucosa in the RE group was significantly lower than that in the controls and the NERD group. CONCLUSIONS: We conclude that a 5-HT signaling pathway disorder could be a major factor in the pathogenesis of GER and RE.

[Value of protein array in the diagnosis of Helicobactor pylori infection in children].

OBJECTIVE: To study the value of multiple Helicobacter pylori (H.pylori) antibody detection by protein array in the diagnosis of H.pylori infection in children. METHODS: Biopsy specimens obtained by gastroscopy from 120 children with digestive system symptoms were detected by rapid urease test (RUT) and modified Giemsa staining. Positivity in both RUT and Giemsa staining was the "gold criterion" of H.pylori infection. Serum samples of these patients were obtained and the antibodies against cytotoxin associated gene A protein (CagA), vacuolating toxin A (VacA), urease, heat shock protein 60 (Hsp60) and RdxA (nitroreductase) were detected by protein array technique. RESULTS: H.pylori infection was identified according to the "gold criterion" in 60 children. Compared with the "gold criterion", the goodness of fit and the coefficient of contingency in the diagnosis of H.pylori infection of the following four groups antibody detection were all statistically significant (P<0.001): anti-Ure antibody alone, anti-Ure antibody combined with anti-CagA antibody, anti-Ure antibody combined with anti-VacA antibody and anti-Ure antibody combined with anti-CagA and anti-VacA antibody. The sensitivity, specificity and accuracy of the detection of anti-Ure antibody combined with anti-CagA antibody for the diagnosis of H.pylori infection were 81.7%, 91.7% and 86.7%, respectively. The antibody detection showed a high positive predictive value (90.7%) and a high negative predictive value (83.3%). CONCLUSIONS: The antibody detection by protein array, especially the detection of anti-Ure antibody combined with anti-CagA antibody, is valuable in the diagnosis of H.pylori infection.

[Effect of zinc deficiency on intestinal mucosal morphology and digestive enzyme activity in growing rat].

OBJECTIVE: In this study, a growing rat model of zinc deficiency was established to investigate the effect of zinc deficiency on intestinal mucosal morphology and digestive enzyme activity as well as to provide a scientific basis for zinc supplementation therapy in patients with diarrhea. METHOD: Three-week-old weaned Sprague-Dawley male rats (n = 30) were randomly divided into 3 groups with 10 in each: rats in the control group (ZA) were fed with a normal diet containing 30 µg/g zinc; rats in the zinc deficient group (ZD) were fed with a zinc-deficient diet containing 0.4 µg/g zinc (refer to AIN-76 formula); and rats in the paired fed group (PF) were fed with a normal diet, but the food intake was limited to intake of rats in ZD group in the previous day. All rats were provided with deionized water for drinking. Their body weight was measured and the food intake during the previous day was recorded early in the morning of the following day. Symptoms of zinc deficiency, such as anorexia, diarrhea, dermatitis, and growth retardation, were observed. Two weeks later, the rats were sacrificed and serum zinc concentration was measured. Jejunal mucosa was taken for biopsy and was stained with hematoxylin and eosin (HE). The height ratio of the jejunal mucosal villi and crypts was measured. In addition, the activity of lactase in the jejunal mucosal brush border, γ-glutamyl peptidase (GGT), and aminopeptidase N (APN) were measured. RESULT: The average weight of the rats in the ZA, ZD, and PF groups at the beginning of the experiment was (67.4 ± 5.3) g, (64.7 ± 4.8) g, and (66.5 ± 4.1) g, respectively, and the average daily food intake was (11.2 ± 1.0) g, (11.6 ± 1.6) g, and (11.2 ± 1.4) g, respectively. The intergroup differences were not significant. On the 7(th) day of experiment, no significant differences in average food intake were observed between the ZD group and the ZA and PF groups, but the average body weight in the ZD group was significantly lower than that in the ZA and PF groups (P < 0.01). At the end of the experiment (2 weeks), the average weight in the ZD group (112.0 ± 11.5) g was significantly lower than that in the ZA (164.0 ± 15.9) g and PF groups (137.5 ± 16.2) g. The average food intake in the ZD group (13.4 ± 5.1) g was significantly lower than that in the ZA group (18.2 ± 2.4) g (P < 0.01). Serum zinc level in the ZD group (733 ± 231) µg/L was significantly lower than that in the ZA (1553 ± 159) µg/L and PF groups (1457 ± 216) µg/L (P < 0.01). The height ratio of jejunal mucosa villus and crypt in the ZA, ZD, and PF groups was 2.98 ± 0.5, 2.77 ± 0.5, and 2.81 ± 0.7, respectively, and lactase activity was (26.1 ± 15.0) U/mg, (27.4 ± 12.8) U/mg, and (40.8 ± 18.5) U/mg, respectively, without significant intergroup differences. The GGT activity in the jejunal mucosa in the ZD group (12.7 ± 6.5) U/g was significantly lower than that in the ZA (19.1 ± 10.4) U/g and PF groups (18.5 ± 7.7) U/g, but the difference was not significant. The activity of APN in the jejunal mucosa in the ZD group (25.5 ± 7.5) U/g was significantly lower than that in the ZA (48.7 ± 16.8) U/g and PF groups (43.9 ± 14.5) U/g (P < 0.01). CONCLUSION: Zinc deficiency can cause loss of appetite, weight loss, and decreased activity of peptidase in the jejunal mucosal brush border. Zinc deficiency has little effect on the height ratio of the villus and crypt and lactase activity, thereby indicating that zinc deficiency may first affect protein digestion and absorption.