Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

AIM:To investigate the effect of protein kinase C(PKC)-mammalian target of rapamycin(mTOR)pathway on the apoptosis of gastric smooth muscle cells in diabetic rats,and to explore the related mechanism.METHODS:Male and female 4-week-old specific pathogen-free Sprague-Dawley rats were randomly allocated to control,diabetes,diabetes+0.1 μmol/L phorbol 12,13-myristate acetate(PMA),diabetes+0.2 μmol/L PMA,diabetes+0.5 μmol/L PMA,diabetes+2 μmol/L bisindolylmaleimide I(GF109203X),diabetes+5 μmol/L GF109203X,and diabetes+10 μmol/L GF109203X groups(n=9).Primary rat gastric smooth muscle cells cultured in a high-glucose environment in vitro were treated with 0.1 μmol/L PMA,0.2 μmol/L PMA,0.5 μmol/L PMA,2 μmol/L GF109203X,5 μmol/L GF109203X,10 μmol/L GF109203X,or vehicle.The isolated muscle technique was used to evaluate the spontaneous contraction of gastric antral smooth muscle.The pathologic changes and apoptosis of rat gastric smooth muscle were identi-fied using HE staining and flow cytometry,respectively.The expression levels of stem cell factor(SCF),c-Kit,mTOR,phosphorylated(p)-mTOR,p70 ribosomal protein S6 kinase(p70S6K),p-p70S6K,eIF4E-binding protein 1(4E-BP1),p-4E-BP1,caspase-3,B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)in gastric smooth muscle were measured by Western blot.RESULTS:The contractility of the gastric antral smooth muscle was lower(P<0.05),gastric smooth muscle atrophy and the apoptosis rate was higher(P<0.01),and the expression of SCF,c-Kit,and p-mTOR was lower(P<0.05 or P<0.01)in the diabetes group than in the control group.There was no significant difference in the spon-taneous contraction of the gastric antral smooth muscle between the diabetes and diabetes+0.1 μmol/L PMA groups,but it was significantly greater in the diabetes+0.2 μmol/L PMA and diabetes+0.5 μmol/L PMA groups(P<0.05 or P<0.01).The phosphorylation levels of mTOR,p70S6K(T421/S424),and p70S6K(T389)were also higher in the diabetes+0.2 μmol/L PMA and diabetes+0.5 μmol/L PMA groups than in diabetes group(P<0.01).Furthermore,the phosphorylation of 4E-BP1 was higher(P<0.05)in the diabetes+0.5 μmol/L PMA group than in the diabetes group(P<0.01).There was no significant difference in the spontaneous contraction of the gastric antral smooth muscle between the diabetes and diabe-tes+2 μmol/L GF109203X groups,but it was significantly lower in the diabetes+5 μmol/L GF109203X and diabetes+10 μmol/L GF109203X groups(P<0.05 or P<0.01).The phosphorylation levels of mTOR and p70S6K(T389)were lower in the diabetes+5 μmol/L GF109203X and diabetes+10 μmol/L GF109203X groups(P<0.05),the phosphorylation of p70S6K(T421/S424)was lower in the diabetes+10 μmol/L GF109203X group(P<0.05),and the phosphorylation of 4E-BP1 was lower in the diabetes+GF109203X(2,5 and 10 μmol/L)groups(P<0.05)than in the diabetes group.Com-pared with the CK group,the apoptosis rate was high in the GF109203X-treated(2,5 and 10 μmol/L)groups(P<0.01),the expression of Bax and caspase-3 was low(P<0.05),and the expression of Bcl-2 was high in the PMA-treated(0.1,0.2 and 0.5 μmol/L)groups(P<0.05).CONCLUSION:The downregulation of the PKC-mTOR pathway in the gastric smooth muscle of diabetic rats leads to apoptosis of gastric smooth muscle cells through Bax/Bcl-2 and caspase-3 and the downregulation of SCF and c-Kit,which may play an important role in the gastric dysmotility that characterizes diabetes.

ObjectiveTo understand the current situation and hot spots of research on the treatment of constipation by traditional Chinese medicine （TCM） in China and foreign countries， and provide references and directions for future research. MethodIn this study， the data analysis software CiteSpace 5.8.R3C was used to conduct bibliometrics analysis of the relevant papers on the treatment of constipation by TCM from January 1， 2000 to December 31， 2021 in China National Knowledge Infrastructure （CNKI） and Web of Science core database. The visual display was carried out. ResultAfter retrieval， 2 133 papers were included in CNKI database and 224 papers were included in Web of Science core database. The statistical analysis showed that the overall annual publication volume in China and foreign countries was on the rise， but the publication volume in China had been declining for the past two consecutive years. The author co-occurrence analysis showed that the authors with the largest number of publications in China and foreign countries were LIU Chunqiang and CHUNGWAH CHENG， respectively. The institution co-occurrence analysis showed that the institutions with the largest number of publications in China and foreign countries were the Anorectal Department of Longhua Hospital Affiliated to Shanghai University of TCM and Beijing University of Chinese Medicine， respectively. The keyword analysis showed that research in this field in China and foreign countries mainly focused on TCM therapy， clinical research， etiology and pathogenesis， etc. ConclusionThe research on the treatment of constipation by TCM is mainly concentrated in China， but there is no closely-related scientific research team. The research in this field in China and foreign countries is still developing. With the continuous deepening of research， all research institutions should pay attention to interdisciplinary intersection， highlight technological innovation， and strive to achieve greater breakthroughs in this field.

Objective:To explore the effect of nursing based on enhanced recovery after surgery (ERAS) in the perioperative period of children with hydronephrosis who underwent robot-assisted laparoscopic pyeloplasty.Methods:From March 2020 to March 2021, convenience sampling was used to select 60 children with hydronephrosis who underwent robot-assisted laparoscopic pyeloplasty in the First Affiliated Hospital of Zhengzhou University as the research object. According to the random number table method, the children were divided into the control group and the observation group, 30 cases in each group. The control group was given routine perioperative nursing. On this basis, the observation group conducted nursing based on ERAS. The postoperative recovery and postoperative complications of the two groups were compared.Results:The time of first eating after surgery, the time of extubation of wound drainage tube after surgery, and the average hospital stay of the observation group were shorter than those of the control group, and the differences were statistically significant ( P<0.01) . The total incidence of postoperative complications in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The nursing based on ERAS can effectively reduce the incidence of postoperative complications in children with hydronephrosis after robot-assisted laparoscopic pyeloplasty, and promote the postoperative recovery of children, which is worthy of clinical promotion.

With accumulating dysregulated circular RNAs(circRNAs)in pathological processes,the regulatory functions of circRNAs,especially circRNAs as microRNA(miRNA)sponges and their interactions with RNA-binding proteins(RBPs),have been widely validated.However,the collected information on experimentally validated circRNA-disease associations is only preliminary.Therefore,an updated CircR2Disease database providing a comprehensive resource and web tool to clarify the relationships between circRNAs and diseases in diverse species is necessary.Here,we present an updated CircR2Disease v2.0 with the increased number of circRNA-disease associations and novel characteristics.CircR2Disease v2.0 provides more than 5-fold experimentally validated circRNA-disease associations compared to its previous version.This version includes 4201 entries between 3077 circRNAs and 312 disease subtypes.Secondly,the information of circRNA-miRNA,circRNA-miRNA-target,and circRNA-RBP interactions has been manually collected for various diseases.Thirdly,the gene symbols of circRNAs and disease name IDs can be linked with various nomenclature databases.Detailed descriptions such as samples and journals have also been integrated into the updated version.Thus,CircR2Disease v2.0 can serve as a platform for users to systematically investigate the roles of dysregulated circRNAs in various diseases and further explore the posttranscriptional regulatory function in diseases.Finally,we propose a computational method named circDis based on the graph convolutional network(GCN)and gradient boosting decision tree(GBDT)to illustrate the applications of the CircR2Disease v2.0 database.

Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/virology* ; COVID-19 Vaccines/immunology* ; Humans ; SARS-CoV-2/pathogenicity* ; Spike Glycoprotein, Coronavirus/immunology* ; Vaccines, Inactivated/immunology*

ObjectiveTo investigate the protective effect of Lycium barbarum polysaccharide (LBP) combined with aerobic exercise (AE) on the liver of rats with nonalcoholic steatohepatitis (NASH) induced by high-fat diet based on the p38 mitogen-activated protein kinase (p38 MAPK)-nuclear factor-κB (NF-κB) pathway. MethodsAfter 1 week of adaptive feeding, 45 Sprague-Dawley rats, aged 8 weeks, were randomly divided into control group (10 rats fed with normal diet) and high-fat group (35 rats fed with high-fat diet). At the end of week 28, the high-fat group was randomly divided into model group, LBP group, AE group, and LBP+AE group, with 8 rats in each group, and intervention was performed for 10 weeks. At the end of the experiment, fasting blood glucose was measure for all rats, and serum samples, liver tissue, and visceral fat were collected. Biochemical kits were used to measure the serum levels of triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST); ELISA kits were used to measure the serum levels of fasting insulin (FINS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1); quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of Toll-like receptor 4 (TLR4), p38 MAPK, and NF-κB in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group, the model group had significant increases in TG, TC, AST, ALT, FINS, and homeostasis model assessment of insulin resistance (HOMA-IR) (all P ＜0.05), a tendency of increases in the serum levels of the inflammatory factors MCP-1, TNF-α, and IL-6 (all P ＜0.05), and significant increases in the mRNA and protein expression levels of TLR4, p38 MAPK, and NF-κB in liver tissue (all P ＜0.05). Compared with the model group, each intervention group had significant reductions in TG, TC, AST, ALT, FINS, and HOMA-IR (all P ＜0.05), a tendency of reductions in the serum levels of the inflammatory factors MCP-1, TNF-α, and IL-6 (all P ＜0.05), and significant reductions in the mRNA and protein expression levels of TLR4, p38 MAPK, and NF-κB (all P ＜0.05). Compared with LBP group, the LBP+AE group had significant reductions in TG, ALT, FINS, HOMA-IR, MCP-1, the mRNA expression level of TLR4, protein expression levels of p38 MAPK and NF-κB(all P＜0.05). Compared with Ae group, the LBP+AE group had significant reductions in FINS, HOMA-IR, IL-6, MCP-1, the mRNA expression level of TLR4 (all P＜0.05). ConclusionLBP combined with AE may improve inflammation in NASH rats by regulating the p38 MAPK/NF-κB pathway.

Objective To investigate the effect of microRNA-1183 on proliferation and metastasis on gastric cancer cells and to explore the role of microRNA-1183 and CBL-B signaling pathways in this process. Methods MGC803 cells were transfected with a microRNA-1183 mimic. Real-time PCR detected the expression of microRNA-1183 in gastric cancer cell line MGC803. MTT detected the proliferative effect of microRNA-1183 on MGC803 gastric cancer cells. A Transwell assay detected the effect of microRNA-1183 on the metastasis of MGC803 gastric cancer cells. A dual luciferase reporter assay detected the binding ability between microRNA-1183 and CBL-B. The expression of the protein was tested by Western blotting. Results MTT assay results showed that microRNA-1183 promoted the proliferation of MGC803 cells. Transwell assay results revealed that microRNA-1183 promoted the metastasis of MGC803 cells. The results of BLAST contrast analysis show that CBL-B is one of the target genes of microRNA-1183. Western blotting analysis showed that the mimic microRNA-1183 inhibited the expression of CBL-B. A dual luciferase reporter assay showed that CBL-B was the target gene of microRNA-1183. A CBL-B knockdown promoted the proliferation and metastasis of MGC803 cells. microRNA-1183 promoted the proliferation and metastasis of MGC803 cells by inhibiting the expression of CBL-B. Conclusion microRNA-1183 can inhibit the proliferation and metastasis of gastric cancer cell lines by inhibiting the expression of CBL-B.

Objective To investigate the effect of Exosomes derived from lung cancer cells on the migration of secretory cells and homologous tumor cells and to explore the role of PI3K/Akt and SRC signaling pathways in this process.Methods Exosomes were isolated from the supematant post density gradient centrifugation of A549,lung cancer cells.Morphology of the Exosomes was studied using transmission electron microscopy.Protein expression was analyzed using Western blotting.Cell migration was analyzed by a transwell assay.Results The double-membrane-bound Exosomes appeared as discal-shaped structures,30-100 nm in diameter.Western blotting showed that CD9 was abundant in the Exosomes.The Exosomes promoted the migration of A549 cells and their homologous tumor cells,HCC827 in a dose-dependent manner,accompanied by the activation of Akt and SRC.Conclusion The Exosomes derived from A549 (lung cancer) cells promote the migration of the secreting cells and the homologous tumor cells.The mechanism may be correlated with the activation of Akt and SRC.

Objective To explore the effect of Exosomes isolated from the A549 lung cancer cells on the proliferation of these cells and their ho?mologous tumor cells,HCC827,and the role of the PI3K/Akt and SRC signaling pathways in this process. Methods Exosomes were isolated from the supernatant after density gradient centrifugation of A549 cells. The Exosomes morphology was observed by transmission electron microscopy. The expression of the Exosome?specific proteins was analyzed using Western blotting. Cell proliferation was investigated using the MTT assay. Re?sults The A549?derived Exosomes were 30?100 nm in diameter and had a bilayer membrane.Western blotting showed that CD9 was detected in these Exosomes. The isolated Exosomes promoted the proliferation of the A549 and the HCC827 cells in a dose?and time?dependent manner,ac?companied by the activation of Akt and SRC. Conclusion Exosomes isolated from A549 cells promote the proliferation of the secreting cells and the homologous tumor cells in a dose?and time?dependent manner. The mechanism may be related to the activation of Akt and SRC.