Objective:To investigate the mechanism of miR-218-5p regulating the glycolytic process in human non-small cell lung cancer A549 cells by targeting phosphodiesterase 7A(PDE7A).Methods:A549 cells were routinely cultured,and miR-218-5p mimic,mimic-NC,PDE7A overexpression plasmid(PDE7A-oe)and PDE7A control plasmid(PDE7A-NC)were transfected into A549 cells using Lipo3000,and recorded as the miR-218-5p mimic group,the mimic-NC group,the PDE7A-oe group and the PDE7A-NC group.The transfection efficiency was verified by qPCR assay;the expressions of glycolysis key enzyme proteins were detected by WB assay;the 2-deoxyglucose and lactate contents in A549 cells of each transfection group were detected by glucose assay and lactate production assay;the target binding relationship between miR-218-5p and PDE7A was verified by dual-luciferase reporter gene assay,and the data from the TCGA database were used to analyze the expression level of PDE7A mRNA in lung cancer tissues.Results:miR-218-5p was successfully overexpressed in A549 cells(P<0.01).Overexpression of miR-218-5p significantly inhibited the expressions of PDE7A,HK2,PKM2 proteins(all P<0.01),glucose uptake and lactate production(both P<0.01)in A549 cells.Overexpression of PDE7A significantly promoted the expressions of PDE7A,HK2,and PKM2 proteins(all P<0.01),as well as glucose uptake and lactate production(both P<0.01)in A549 cells.miR-218-5p in A549 cells could directly bind to the 3′-UTR of PDE7A mRNA.Database data analysis showed that PDE7A mRNA was highly expressed in lung squamous cell carcinoma tissues(P<0.01).Conclusion:miR-218-5p targets PDE7A to regulate the expression levels of HK2 and PKM2 in A549 cells,which in turn inhibits the glycolytic process.miR-218-5p/PDE7A may be a potential target for clinical diagnosis and treatment of NSCLC.

Panax notoginseng saponins(PNSs)as the extracted bioactive components of Panax notoginseng,have a long history of application in prevention of thrombosis.PNSs down-regulate the expression of inflammatory factors,promoting endothelial cell growth,up-regulating the expression of anticoagulants and vasodilators,and regulating endothelial cell function;With multiple targets at which PNSs inhibit platelet adhesion,release,and aggregation;PNSs maintain the activity of the fibrinolytic system by regulating the dynamic balance of tissue type plasminogen activators and inhibitors;PNSs reduce blood viscosity,improve red blood cell indicators,and inhibit thrombosis through multiple pathways.

Objective To evaluate the efficacy and safety of pabolizumab plus low-dose apatinib combined chemotherapy in elderly patients with esophageal cancer.Methods A total of 188 elderly patients with esophageal cancer admitted to Shengli Oilfield Central Hospital from May 2020 to July 2022 were selected and divided into study group(n=94)and control group(n=94)by random number table method.The control group received pabolizumab combined with FP chemotherapy regimen,and the study group received low-dose Apatinib combined with Pabolizumab and FP chemotherapy regimen.Clinical efficacy,tumor markers,phosphatidylinositol 3 kinase(PI3K)/threonine protein kinase(Akt)signaling protein pathway,immune function,adverse reactions and survival were compared between the two groups.Results The objective remission rate of the study group was higher than control group(P＜0.05).After treatment,squamous cell carcinoma antigen(SCC),carcinoembryonic antigen(CEA),PI3K,Akt and CD8+were all decreased in the two groups(P＜0.05),and those in study group were lower(P＜0.05).After treatment,CD3+and CD4+were increased in both groups(P＜0.05),and higher in study group(P＜0.05).There was no difference in the total incidence of adverse reactions between the two groups(P＞0.05).The survival rate of the study group was higher than control group(P＜0.05).Conclusion Pabolizumab plus low-dose apatinib combined with chemotherapy is effective in the treatment of elderly esophageal cancer,which may inhibit tumor progression by reducing the activity of PI3K/Akt signaling protein pathway and improve the short-term survival rate.

Objective To evaluate the efficacy and safety of pabolizumab plus low-dose apatinib combined chemotherapy in elderly patients with esophageal cancer.Methods A total of 188 elderly patients with esophageal cancer admitted to Shengli Oilfield Central Hospital from May 2020 to July 2022 were selected and divided into study group(n=94)and control group(n=94)by random number table method.The control group received pabolizumab combined with FP chemotherapy regimen,and the study group received low-dose Apatinib combined with Pabolizumab and FP chemotherapy regimen.Clinical efficacy,tumor markers,phosphatidylinositol 3 kinase(PI3K)/threonine protein kinase(Akt)signaling protein pathway,immune function,adverse reactions and survival were compared between the two groups.Results The objective remission rate of the study group was higher than control group(P＜0.05).After treatment,squamous cell carcinoma antigen(SCC),carcinoembryonic antigen(CEA),PI3K,Akt and CD8+were all decreased in the two groups(P＜0.05),and those in study group were lower(P＜0.05).After treatment,CD3+and CD4+were increased in both groups(P＜0.05),and higher in study group(P＜0.05).There was no difference in the total incidence of adverse reactions between the two groups(P＞0.05).The survival rate of the study group was higher than control group(P＜0.05).Conclusion Pabolizumab plus low-dose apatinib combined with chemotherapy is effective in the treatment of elderly esophageal cancer,which may inhibit tumor progression by reducing the activity of PI3K/Akt signaling protein pathway and improve the short-term survival rate.

Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Objective:To investigate the current situation of motivations for hospice care volunteerism among undergraduate nursing students, and to analyze its influencing factors.Methods:Using the convenient sampling method, a total of 575 nursing students from Nursing Department of Xinjiang Medical University were selected as the research objects in August 2022. They were investigated using general information questionnaire, Chinese version of Inventory of Motivations for Hospice Palliative Care Volunteerism Scale, The Palliative Care Quiz for Nursing, the Organizational Climate Scale and Prosocial Tendencies Measure Scale.Results:The score of Motivations for Hospice Palliative Care Volunteerism Scale for 575 nursing students was (87.32±20.54) , score of Palliative Care Quiz for Nursing was (7.89±3.44) , score of Organizational Climate Scale was (49.35±10.33) and the score of Prosocial Tendencies Measure scale was (96.71±18.25) . Qualities and abilities that college student volunteers should possess, access to hospice care, pro-social tendencies, and knowledge of palliative care were influential factors in nursing students' motivation to volunteerism for hospice care ( P<0.05) , which could explain 19.9% of the total variation. Conclusions:The motivations for hospice care volunteerism of undergraduate nursing students is in a medium and above level. Nursing educators should strengthen education and training related to nursing students' participation in hospice care, so that nursing students will participate in voluntary service activities through their own professional advantages, strengthen the voluntary team of hospice care, and promote the development of voluntary hospice care services.

Objective:To explore the clinical value of preconception expanded carrier screening (PECS) in Chinese Han population of childbearing age.Methods:The gene detection results of infertile couples with PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from September 2019 to May 2022 were analyzed retrospectively. The carrier rate of pathogenic gene, the detection rate of high-risk couples and the clinical outcome of high-risk couples were counted and analyzed.Results:A total of 1 565 patients received PECS and they were all Chinese Han. A total of 504 patients received the 108 extended monogenic diseases testing, including 420 females and 84 males, the overall carrier rate of the target genes was 30.75% (129/420), and the detection rate of high-risk couples was 1.19% (1/84), the higher carrier rates of the tested genes were MMACHC [2.58% (13/504)], ATP7B [2.38% (12/504)], SLC22A5 [2.18% (11/504)], GALC [1.79% (9/504)], PAH [1.79% (9/504)] and MLC1 [1.19% (6/504)], the rest are less than 1%. There were 555 patients accepted FMR1 gene detection, and 5 patients with FMR1 gene mutation, accounting for 0.90%. Testing for direct relatives of patients with complete mutations, her mother is a pre mutation carrier with a CGG repeat count of 105. A total of 502 patients accepted SMN1 gene testing. Totally 14 femals and 2 males were found to be SMN1 gene carriers in this study, with a carrier rate of 3.19%. Conclusion:The carryier rate of single gene recessive disorder is high in the population. Screening before pregnancy can provide birth health guidance for patients, help them to choose preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis, to avoid the birth of silk children.

Objective:To explore the clinical value of preconception expanded carrier screening (PECS) in Chinese Han population of childbearing age.Methods:The gene detection results of infertile couples with PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from September 2019 to May 2022 were analyzed retrospectively. The carrier rate of pathogenic gene, the detection rate of high-risk couples and the clinical outcome of high-risk couples were counted and analyzed.Results:A total of 1 565 patients received PECS and they were all Chinese Han. A total of 504 patients received the 108 extended monogenic diseases testing, including 420 females and 84 males, the overall carrier rate of the target genes was 30.75% (129/420), and the detection rate of high-risk couples was 1.19% (1/84), the higher carrier rates of the tested genes were MMACHC [2.58% (13/504)], ATP7B [2.38% (12/504)], SLC22A5 [2.18% (11/504)], GALC [1.79% (9/504)], PAH [1.79% (9/504)] and MLC1 [1.19% (6/504)], the rest are less than 1%. There were 555 patients accepted FMR1 gene detection, and 5 patients with FMR1 gene mutation, accounting for 0.90%. Testing for direct relatives of patients with complete mutations, her mother is a pre mutation carrier with a CGG repeat count of 105. A total of 502 patients accepted SMN1 gene testing. Totally 14 femals and 2 males were found to be SMN1 gene carriers in this study, with a carrier rate of 3.19%. Conclusion:The carryier rate of single gene recessive disorder is high in the population. Screening before pregnancy can provide birth health guidance for patients, help them to choose preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis, to avoid the birth of silk children.

To understand the current situation, progress, main contents, and the relevant assessment tools of family care in palliative for pediatric oncology patients, this paper reviewed the relevant literature on family care in palliative for pediatric oncology patients and its assessment tools at home and abroad. Taking family care in palliative care as the starting point, this paper discussed the effect of effective family care on improving the treatment outcome, quality of life, prognosis of pediatric oncology patients and the psychological problems of their families, and to provide a basis for continuing to improve the hospital-family-community care model for pediatric oncology patients, bringing into play the active role of family in palliative care, and promoting the continued development of family care for pediatric oncology patients.

Objective:To study the performance of immune reconstitution in patients with chimeric antigen receptor (CAR)-T cell immunotherapy bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 61 patients with acute B lymphocytic leukemia (B-ALL) who received CAR-T cell bridging allo-HSCT in Beijing Lu Daopei Hospital from August 2018 to December 2021 were enrolled, and the clinical medical records of the above patients were retrospectively analyzed. The average age was 14 (7, 30) years old, including 39 males and 22 females. 32 patients were treated with CAR-T cell immunotherapy(CAR-T Group) and 29 didn't with CAR-T cell immunotherapy(non-CAR-T group). The follow-up period was 561 (235,784) days. Multicolor flow cytometry was used to detect the peripheral blood lymphocyte subsets, i.e. total lymphocytes, T lymphocytes, helper T cells, cytotoxic T cells, B lymphocytes, NK cells, and Treg cell counts before transplantation and 1, 2, 3, 6, 8, 10, and 12 months after transplantation, to evaluate the immune reconstitution performance post allo-HSCT.Results:Serum globulin before transplantation: The IgA level in the CAR-T group was 0.18 (0.06, 0.49) g/L, which was lower than that of 1.03 (0.63, 1.56) g/L in the non-CAR-T group ( U=103.5, P<0.001). The IgG level in the CAR-T group was 5.54 (4.04, 7.09) g/L, lower than that of 6.78 (5.27, 9.26) g/L in the non-CAR-T group, ( U=1 298.5, P=0.017), and the IgM level in the CAR-T group was 0.18 (0.05, 0.30) g/L, lower than that of 0.40 (0.26, 0.71) g/L in the non-CAR-T group ( U=166.0, P<0.001). In the CAR-T group before transplantation, the absolute count of total lymphocyte in peripheral blood was 833.00 (335.00, 1 727.50) /μl, lower than that of 1 052.00 (545.75, 1 812.50) /μl in the non-CAR-T group ( U=404.0, P<0.001). The absolute count of T lymphocyte in the CAR-T group before transplantation was 686.00 (233.00, 1 307.00)/μl, lower than that of 860.00 (391.00, 1 419.75) /μl in the non-CAR-T group ( U=406.0, P<0.001). The absolute count of helper T lymphocytes in the CAR-T group was 146.00 (40.50, 327.50) /μl, lower than that of 162.50 (66.00, 384.75) /μl in the non-CAR-T group ( U=494.0, P=0.002). The absolute count of cytotoxic T lymphocytes in the CAR-T group was 343.00 (56.50, 924.00) /μl, lower than that of 478.00 (143.50, 992.25) /μl in the non-CAR-T group ( U=483.5, P=0.001). The absolute count of B lymphocytes in CAR-T group was 22.00 (6.00, 186.00) /μl, lower than that of 33.00 (8.00, 220.00) /μl in the non-CAR-T group ( U=498.0, P=0.002). And when two groups of patients were monitored after transplantation, there was no statistical difference in absolute cell counts of each immune cell subpopulation( P>0.05). Comparing the clinical features of the two groups, the pre-transplant history of the CAR-T group was 981.00 (368.50, 1 514.75) d, longer than that of 323.00 (167.50, 450.50) d in the non-CAR-T group ( U=263.0, P=0.004). The dose of rabbit anti-human thymic immunoglobulin (ATG) in the pretreatment protocol of patients in the CAR-T group was 5.00 (5.00, 7.50) mg/Kg, lower than that of 7.00 (5.00, 7.50) mg/kg in the non-CAR-T group ( U=288.5, P=0.018). The infusion dose of CD34 +cells in the CAR-T group was 5.91 (4.23, 6.02) ×10 6/kg, higher than that of 4.51 (4.00, 5.93)×10 6/kg in the non-CAR-T group ( U=291.0, P=0.012). The duration of the application of cyclosporine after transplantation in the CAR-T group was 167.00 (119.25, 299.50) d, which was shorter than that of 197.00 (102.50, 450.50) d in the non-CAR-T group ( U=421.0, P=0.001). Conclusions:For patients in CAR-T group with low immune function before transplantation, it may be possible to make them comparable to non-CAR-T group in immune reconstitution state by reducing the dose of pretreatment ATG, increasing the counts of CD34 + cells infusion in the graft, and discontinuing cyclosporine as soon as possible after transplantation.