BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective:To explore the clinical phenotype and genetic basis of a child with Neutral lipid storage disease with myopathy (NLSDM).Methods:A child who was admitted to the First Affiliated Hospital of Zhengzhou University in February 2021 for a history of elevated creatine kinase (CK) for over 2 months was selected as the study subject. Clinical and laboratory examinations were carried out, and the child was subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing of her family members.Results:The patient, a 9-year-old female, had exhibited weakness in the lower limbs, elevated CK level, and refractory cardiomyotrophy. Genetic testing revealed that she has harbored c. 32C>G (p.S11W) and c. 516C>G (p.N172K) compound heterozygous variants of the PNPLA2 gene, which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The c. 32C>G (p.S11W) and c. 516C>G (p.N172K) compound heterozygous variants of the PNPLA2 gene probably underlay the myasthenia gravis and elevated creatine kinase in this child.

Protein arginine methylation is an important post-translational modification (PTM) mediated by protein arginine methyltransferase (PRMTs), which is closely related to the occurrence and development of many diseases. Methylation of arginine is closely related to inflammatory diseases and fracture healing. Decreased expression of PRMTs can lead to delayed or even non-healing of fractures. Both PRMT5 and PRMT6 play an important role in fracture healing and are closely related to the PI3K-AKT and NF-κB pathways. Exploration the relationship between protein arginine methylation and fracture healing can provide a new way to prevent delayed or even non-healing fracture.

Objective:To summarize the clinical features, treatments and prognoses of aggressive natural killer cell leukemia (ANKL) in children.Methods:Clinical data and follow-up results were retrospectively reviewed for one hospitalized case of ANKL in June 2019.Through a literature search, the relevant items were retrieved from the databases of China National Knowledge Infrastructure, WanFang and PubMed using the Chinese and English keywords of "aggressive natural killer cell leukemia" and "children" up to December 2021.Results:This 8-year-old girl was diagnosed with ANKL by flow cytometric immunophenotype and immunohistochemical stain.Fever was the initial manifestation accompanied by sallow complexion, fatigue, enlargement of liver, spleen and lymph node and hematopenia of three lines.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed after chemotherapy.As of April 2022, the child stayed in a disease-free survival state after follow-ups for over 2 years.The literature search finally yielded 7 eligible Chinese and 10 English reports with a total of 17 pediatric ANKLs.In this group, there were fever (n=15), rash (n=1), perineal mass (n=1) and diarrhea, vomiting and other digestive tract symptoms (n=1). Six cases were misdiagnosed during an early stage of disease.4 cases received chemotherapy alone, 3 cases received chemotherapy regimen for acute lymphoblastic leukemia, 1 child died and one death occurred after received chemotherapy regimen of "cisplatin + vincristine + doxorubicin + ifosfamide". Allo-HSCT was performed in 5 patients after remission with chemotherapy and one child died from multiple organ failure at 9 months after allo-HSCT.Nine cases gave up treatment.Conclusions:ANKL has a rapid disease progression, diverse clinical manifestations, easy misdiagnosis and poor prognosis.For suspected ANKL cases, clinicians perform multiple bone perforations at multiple sites and immunophenotype by flow cytometry as soon as possible to confirm the diagnosis.Currently allo-HSCT offers a long-term survival of ANKL patients.

Objective To systematically review the present status of oral Chinese patent medicines(CPMs)for treating functional dyspepsia(FD),explore the formation rules of CPMs,and reveal the potential problems by referring to the methods and procedures of Scoping review.Methods First,we screened all CPMs from the domestic-related drug catalogs which are generally accepted and own the force of law,then we sorted the CPMs based on the drug instructions while carrying out Chinese and English database document retrieval to review the clinical studies.Descriptive analysis of the basic feature and clinical research evidence of CPMs was performed combined with visual charts.Results This study included 42 CPMs for treating FD.Among the formulas of CPMs,Tangerine peel,Radices saussureae,Poria cocos,Glycyrrhiza,Atractylodes macrocephala,and Six Divine Qu appeared frequently.In addition,96 studies involving 21 CPMs were included,among which Zhizhu Kuanzhong Capsule,Liuwei Anxiao capsule,and Dalitong granules had more clinical literature.By analyzing the included 96 clinical studies,we found that the combination of Chinese and Western medicine was the main intervention,and the effective rate,clinical symptom score,and adverse reactions were the main outcomes that were concerned.In addition,8 studies had off-label use of diseases,involving the Wuling capsule to treat the FD whether the disease was accompanied by depression and anxiety symptoms or not,and Zhizhu Kuanzhong Capsule to treat the FD with anxiety and depression.Although the Wuling capsule and Zhizhu Kuanzhong capsule were off-label used in clinical practice,there was no beyond the scope of the guideline.Conclusion The qi-regulating drug,spleen-strengthening drug and digestant drugs are the usual Chinese medicines used for treating adult FD.In recent years,research on CPMs for treating adult FD has increased rapidly.But there is insufficient reflection of CPMs treatment characteristics,ambiguous differences from the primary and secondary outcomes,multiple composite outcomes,and not explicit information on FD or its symptoms in drug package insert,which needs to be improved in the future.

OBJECTIVE To establish a method for the determination of eriodictyol and luteolin in Xerochrysum braeteatum, and to evaluate their antioxidant activities in vitro. METHODS UPLC was used to investigate the coutent determination methodologically. Vitamin C and Trolox were used as the control, the IC50 values of eriodictyol and luteolin for scaving DPPH free radical were determined, and the antioxidant activity was compared. The kinetic characteristics of free radical scavenging reaction were preliminarily explained by the change of free radical scavenging rate within 4 h. RESULTS There was a good linear relationship (R=0.999 7) between the peak area and the concentration of eriodictyol in the range of 0.005 4-0.545 0 mg·mL-1 and luteolin in the range of 0.005 3-0.535 0 mg·mL-1. The precision, stability and recovery of the method were satisfactory. The scavenging ability of the 4 compounds from high to low was luteolin>eriodictyol>vitamin C>Trolox. Different from vitamin C and Trolox, the free radical scavenging process of eriodictyol and luteolin showed three stages:first fast and then slow. CONCLUSION The content determination method is simple and rapid, and can be used for the determination of eriodictyol and luteolin in Xerochrysum braeteatum. The resources of Xerochrysum braeteatum are worth further development because of their excellent antioxidant activities.

SARS-CoV-2 may have potential effects on the male reproductive system. Evidence has shown that SARS-CoV-2 is not likely to transmit through sexual intercouse. However, male infected with SARS-CoV-2 may experience sexual dysfunction, semen quality decline, testicular damage and abnormal sex hormones. The extent and duration of these damages are still unclear, and further multidimensional research is necessary.

Objective:To investigate the clinical value of the expression levels of biological protein markers regenerating islet-derived protein 3-alpha(REG3α), soluble tumor suppressor factor 2(sST2) and tumor necrosis factor receptor 1(TNFR1) in peripheral blood in the diagnosis and efficacy evaluation of intestinal acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Retrospective analysis of 50 children who underwent allo-HSCT, in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from January 2020 to February 2021 were enrolled, including 39 males and 11 females [median age: 8.5 (1-13) years]. The expression levels of above 3 biological proteins were detected before transplantation, 1 week, 2 weeks, 3 weeks, 5 weeks, 7 weeks, 9 weeks, 11 weeks and 13 weeks after transplantation, when intestinal aGVHD occured, and after treatment.Children with intestinal aGVHD were taken as the observation group, and children without intestinal aGVHD were taken as the control group.Whether differences in the expression levels of the 3 biological proteins in the peripheral blood of the 2 groups of children were statistically significant was analyzed.The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of the above three biological proteins for intestinal aGVHD, and independent sample t test was performed to compare the expression levels of the 3 biological proteins before and after treatment in children with intestinal aGVHD. Results:(1) The concentrations of REG3α, sST2, and TNFR1 in the peripheral blood of the observation group were (33 985.42±24 631.33) ng/L, (139 899.66±115 825.65) ng/L, (3 041.65±2 418.72) ng/L, respectively, which were higher than the control group of (7 457.39±4 547.49) ng/L, (32 059.57±23 452.85) ng/L, (1 944.51±1 170.35) ng/L, the difference was statistically significant ( t=6.04, 5.19, 2.17, all P<0.05). (2) The area under ROC curve (AUC) of REG3α combined with sST2 in the diagnosis of intestinal aGVHD was 0.952 (95% CI: 0.851-0.992, P<0.001), the maximum Youden index was 0.894, the corresponding sensitivity was 83%, and the specificity was 99%.Its diagnostic value was better than REG3α, sST2 and TNFR1 ( Z=1.763, 1.332, 3.001, all P<0.05). (3) The concentrations of REG3α, sST2, and TNFR1 before treatment in the peripheral blood of children having received effective treatment were (31 343.01±25 364.71) ng/L, (146 629.52±110 501.04) ng/L and (2 489.00±859.70) ng/L, respectively, which were (12 104.37±11 704.60) ng/L, (93 539.55±81 920.93) ng/L and (2 048.15±813.47) ng/L after treatment, lower than those before treatment.The expression levels of REG3α and sST2 were significantly reduced ( t=-3.23, -2.10, all P<0.05), while the difference of the expression level of TNFR1 before and after treatment was not statistically significant ( P>0.05). Conclusions:REG3α and sST2 can be used as important reference indicators for clinical auxiliary diagnosis of intestinal aGVHD, and have good auxiliary diagnostic value.REG3α and sST2 can be used as objective indicators to evaluate the efficacy of clinical treatment of intestinal aGVHD.

BACKGROUND: This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis. METHODS: First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system. RESULTS: A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011). CONCLUSION The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.
Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/genetics* ; Silicosis/genetics*

Objective:To investigate the clinical efficacy, safety and compliance of Voriconazole suspension formula on the prevention and treatment of invasive fungal infection (IFI) in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of 25 children treated Voriconazole suspension formula for the prevention and treatment of IFI during the period of allo-HSCT in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from August 1, 2020 to April 30, 2021 were retrospectively analyzed.The plasma trough concentration of Voriconazole was detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the genotype of CYP2C19 was detected by polymerase chain reaction-restriction fragment length polymorphism (RFLP). The effect of CYP2C19 genotype on Voriconazole trough concentration was analyzed by rank-sum test, and Fisher′ s accurate test was used to analyze the influence of severity of gastrointestinal mucositis on serum trough concentration of Voriconazole in children with allo-HSCT. Results:A total of 25 children, including 18 males and 7 females were recruited.The median age at allo-HSCT was 6 (2-13) years.After initial administration of conventional dose of Voriconazole suspension formula during transplantation, plasma trough concentration of Voriconazole was intermittently monitored.Only 13 cases (52.0%) reached the target plasma trough concentration, 11 cases(44.0%) reached the target plasma trough concentration after adjusting the dose according to the plasma concentration, and 1 cases(4.0%) failed to reach it after increasing the dose twice.Genotype detection of CYP2C19 was performed in 20 children, involving 4 cases of poor metabolizers (PM), 9 cases of intermediate metabolizers (IM), 6 cases of extensive metabolizers (EM), and 1 case of ultra extensive metabolizer (UEM). A significant difference in plasma trough concentration was detected among all groups ( F=24.012, P<0.01). During the transplantation, 12 cases developed mild to moderate gastrointestinal mucositis, and 7 cases had severe gastrointestinal mucositis.The stan-dard rate of plasma trough concentration in children with severe gastrointestinal mucositis (1/7 cases, 14.3%)was significantly lower than those with mild to moderate gastrointestinal mucositis (9/12 cases, 75.0%) ( P=0.02). Five children (71.4%) with severe gastrointestinal mucositis could reach the target trough concentration after increasing the drug dose, suggesting that severe gastrointestinal mucositis had a great influence on the plasma concentration of Vorico-nazole suspension.The incidence of IFI in 25 children with allo-HSCT was 0, and the compliance of children taking Voriconazole dry suspension was 100.0%.The incidence of adverse reactions was 24.0% and all adverse reactions were relieved after symptomatic treatment. Conclusions:The plasma concentration of Voriconazole varies greatly among children and in different states of the same patient.Therefore, it is necessary to monitor the trough concentration of the drug and adjust the drug dose.The use of Voriconazole suspension formula for the prevention and treatment of fungal infection during allo-HSCT in children is clinically safe and effective, with a good compliance in children.