Natural killer cells(NK)are important innate immune cells that do not require prior antigen exposure and can directly recognize and attack virus-infected cells and tumor cells.The activation and effector functions of NK cells are regulated by a balance of signals delivered through their surface activating receptors and inhibitory re-ceptors,which bind to ligands on target cells to achieve cytotoxicity via"induced self"and"missing self"recogni-tion models.The killing mechanisms of NK cells primarily include release of cytotoxic granules such as perforin and granzymes to induce target cell lysis,death receptor-mediated apoptosis,secretion of various cytokines,chemokines and growth factors to coordinate with other immune cells in killing tumor cells,thereby generating secondary im-mune responses and antibody-dependent cellular cytotoxicity(ADCC).

Objective:To investigate the expression of SAPCD2 in esophageal squamous cell carcinoma (ESCC) tissues and its effects on the biological function of ESCC cells in vitro, as well as the possible molecular mechanisms.Methods:By using the Gene Expression Profile Interaction Analysis (GEPIA) platform, the transcriptional level expressions of SAPCD2 in 182 ESCC samples and 286 normal esophageal tissue samples from the Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) database were analyzed. Immunohistochemical (IHC) staining was performed on clinical tissue chips of ESCC patients, and staining scores were evaluated. The expression differences of SAPCD2 protein between 61 cancer tissues and the paired adjacent tissues with the complete clinical data, as well as the distribution of patients with SAPCD2 high expression among patients stratifies by different clinicopathological features were compared. ESCC cell line KYSE-150 was transfected with plasmids carrying SAPCD2 sequence and short hairpin RNA sequence targeting SAPCD2, respectively, which was treated as the SAPCD2 overexpression group and SAPCD2 knockdown group; and the cells transfected with empty plasmids and plasmids carrying negative RNA sequence were treated as the overexpression control group and the knockdown control group. CCK-8 method (expressed with the absorbance value) and plate clone formation assay were used to detect the cell proliferation ability. Cell migration was detected by using cell scratch assay and Transwell cell migration assay were used to detect the cell migration ability. The reverse-real time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the mRNA levels of SAPCD2, matrix metalloproteinase-9 (MMP9), proliferating cell nuclear antigen (PCNA), and Vimentin in cells of all groups. Western blotting was used to detect the expression levels of SAPCD2 protein and proteins related to cell proliferation, invasion, metastasis, and AKT signaling pathway.Results:GEPIA platform analysis showed that the transcriptional expression level of SAPCD2 in ESCC tissues was higher than that in adjacent tissues, and the difference was statistically significant ( P < 0.01). IHC staining showed that the staining score of SAPCD2 protein in cancer tissues was higher than that in adjacent tissues [(8.2±2.8) points vs. (2.2±1.7) points], and the proportion of patients with positive SAPCD2 protein (staining score > 0 point) in cancer tissues was higher than that in adjacent tissues [95.1% (58/61) vs. 57.4% (35/61)], and the differences were statistically significant (all P < 0.001), while there were no statistically significant differences in the distribution of the high expression of SAPCD2 protein (staining score > 3 points) patients stratified by gender, age, tumor size, pathological grade, and T stage, N stage and M stage (all P > 0.05). CCK-8 assay showed that the absorbance value of KYSE-150 cells in the SAPCD2 overexpression group after 96 h of culture was higher than that in the overexpression control group, while the absorbance values of the SAPCD2 knockdown group after 72 h and 96 h of culture were lower than those in the knockdown control group, and the differences were statistically significant (all P < 0.05). The plate clone formation assay showed that the number of colonies of KYSE-150 cells cultured for 14 d in the SAPCD2 overexpression group was more than that in the overexpression control group [(800±30) vs. (458±47)], and that in the SAPCD2 knockdown group was less than that in the knockdown control group [(52±7) vs. (81±2)], and the differences were statistically significant (all P < 0.05). The cell scratch assay showed that after 24 h of culture, the scratch width of KYSE-150 cells in the SAPCD2 overexpression group was narrower than that in the overexpression control group [(51±9) μm vs. (89±7) μm], while that in the SAPCD2 knockdown group was wider than that in the knockdown control group [(120±22) μm vs. (37±10) μm], and the differences were statistically significant (all P < 0.01). Transwell cell migration assay showed that the migration number of KYSE-150 cells in the SAPCD2 overexpression group was more than that in the overexpression control group [(202±18) vs. (50±14)], and that in the SAPCD2 knockdown group was less than that in the knockdown control group [(227±27) vs. (483±16)], and the differences were all statistically significant (all P < 0.01). qPCR assay showed that the mRNA relative expression levels of MMP9, PCNA and Vimentin in KYSE-150 cells in the SAPCD2 overexpression group were all higher than those in the overexpression control group, while those in the SAPCD2 knockdown group were all lower than those in the knockdown control group, and the differences were statistically significant (all P < 0.05). Western blotting showed that the relative expression levels of PCNA and Vimentin proteins in KYSE-150 cells of the SAPCD2 overexpression group were higher than those of the overexpression control group, while the relative expression levels of epithelial cadherin (E-cad) and cleaved cysteine aspartate protease 3 (CASP3) proteins were lower than those of the overexpression control group; however, the expression levels in SAPCD2 knockdown group showed the opposite results, and the differences were statistically significant (all P < 0.05); the relative expression level of phosphorylated AKT (p-AKT) protein in the SAPCD2 overexpression group was higher than that in the overexpression control group, while that in the SAPCD2 knockdown group was lower than that in the knockdown control group, and the differences were statistically significant (all P < 0.01). Conclusions:SAPCD2 is highly expressed at both the transcriptional level and the protein level in ESCC tissues. SAPCD2 promotes the proliferation and migration of ESCC cells in vitro, which may be related to the AKT signaling pathway.

Objective:To investigate the expression of SAPCD2 in esophageal squamous cell carcinoma (ESCC) tissues and its effects on the biological function of ESCC cells in vitro, as well as the possible molecular mechanisms.Methods:By using the Gene Expression Profile Interaction Analysis (GEPIA) platform, the transcriptional level expressions of SAPCD2 in 182 ESCC samples and 286 normal esophageal tissue samples from the Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) database were analyzed. Immunohistochemical (IHC) staining was performed on clinical tissue chips of ESCC patients, and staining scores were evaluated. The expression differences of SAPCD2 protein between 61 cancer tissues and the paired adjacent tissues with the complete clinical data, as well as the distribution of patients with SAPCD2 high expression among patients stratifies by different clinicopathological features were compared. ESCC cell line KYSE-150 was transfected with plasmids carrying SAPCD2 sequence and short hairpin RNA sequence targeting SAPCD2, respectively, which was treated as the SAPCD2 overexpression group and SAPCD2 knockdown group; and the cells transfected with empty plasmids and plasmids carrying negative RNA sequence were treated as the overexpression control group and the knockdown control group. CCK-8 method (expressed with the absorbance value) and plate clone formation assay were used to detect the cell proliferation ability. Cell migration was detected by using cell scratch assay and Transwell cell migration assay were used to detect the cell migration ability. The reverse-real time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the mRNA levels of SAPCD2, matrix metalloproteinase-9 (MMP9), proliferating cell nuclear antigen (PCNA), and Vimentin in cells of all groups. Western blotting was used to detect the expression levels of SAPCD2 protein and proteins related to cell proliferation, invasion, metastasis, and AKT signaling pathway.Results:GEPIA platform analysis showed that the transcriptional expression level of SAPCD2 in ESCC tissues was higher than that in adjacent tissues, and the difference was statistically significant ( P < 0.01). IHC staining showed that the staining score of SAPCD2 protein in cancer tissues was higher than that in adjacent tissues [(8.2±2.8) points vs. (2.2±1.7) points], and the proportion of patients with positive SAPCD2 protein (staining score > 0 point) in cancer tissues was higher than that in adjacent tissues [95.1% (58/61) vs. 57.4% (35/61)], and the differences were statistically significant (all P < 0.001), while there were no statistically significant differences in the distribution of the high expression of SAPCD2 protein (staining score > 3 points) patients stratified by gender, age, tumor size, pathological grade, and T stage, N stage and M stage (all P > 0.05). CCK-8 assay showed that the absorbance value of KYSE-150 cells in the SAPCD2 overexpression group after 96 h of culture was higher than that in the overexpression control group, while the absorbance values of the SAPCD2 knockdown group after 72 h and 96 h of culture were lower than those in the knockdown control group, and the differences were statistically significant (all P < 0.05). The plate clone formation assay showed that the number of colonies of KYSE-150 cells cultured for 14 d in the SAPCD2 overexpression group was more than that in the overexpression control group [(800±30) vs. (458±47)], and that in the SAPCD2 knockdown group was less than that in the knockdown control group [(52±7) vs. (81±2)], and the differences were statistically significant (all P < 0.05). The cell scratch assay showed that after 24 h of culture, the scratch width of KYSE-150 cells in the SAPCD2 overexpression group was narrower than that in the overexpression control group [(51±9) μm vs. (89±7) μm], while that in the SAPCD2 knockdown group was wider than that in the knockdown control group [(120±22) μm vs. (37±10) μm], and the differences were statistically significant (all P < 0.01). Transwell cell migration assay showed that the migration number of KYSE-150 cells in the SAPCD2 overexpression group was more than that in the overexpression control group [(202±18) vs. (50±14)], and that in the SAPCD2 knockdown group was less than that in the knockdown control group [(227±27) vs. (483±16)], and the differences were all statistically significant (all P < 0.01). qPCR assay showed that the mRNA relative expression levels of MMP9, PCNA and Vimentin in KYSE-150 cells in the SAPCD2 overexpression group were all higher than those in the overexpression control group, while those in the SAPCD2 knockdown group were all lower than those in the knockdown control group, and the differences were statistically significant (all P < 0.05). Western blotting showed that the relative expression levels of PCNA and Vimentin proteins in KYSE-150 cells of the SAPCD2 overexpression group were higher than those of the overexpression control group, while the relative expression levels of epithelial cadherin (E-cad) and cleaved cysteine aspartate protease 3 (CASP3) proteins were lower than those of the overexpression control group; however, the expression levels in SAPCD2 knockdown group showed the opposite results, and the differences were statistically significant (all P < 0.05); the relative expression level of phosphorylated AKT (p-AKT) protein in the SAPCD2 overexpression group was higher than that in the overexpression control group, while that in the SAPCD2 knockdown group was lower than that in the knockdown control group, and the differences were statistically significant (all P < 0.01). Conclusions:SAPCD2 is highly expressed at both the transcriptional level and the protein level in ESCC tissues. SAPCD2 promotes the proliferation and migration of ESCC cells in vitro, which may be related to the AKT signaling pathway.

It is reported that iron metabolism and ferroptosis can influence the occurrence and development of myeloid tumors, which can serve as therapeutic targets. Dysregulation of iron metabolism is present in a variety of myeloid neoplasms. The prognosis of acute myeloid leukemia is related to differential expression of molecules related to iron metabolism. The prognosis of myelodysplastic syndrome patients with iron overload is poor. Myeloproliferative neoplasms are often characterized by the coexistence of iron deficiency and erythrocytosis, which can be treated by targeting hepcidin. Myeloid tumor cells are susceptible to oxidative damage caused by the accumulation of reactive oxygen species and are sensitive to ferroptosis. Ferroptosis has anti-tumor effect in acute myeloid leukemia and myelodysplastic syndrome. Targeting ferroptosis can reverse imatinib resistance in chronic myeloid leukemia. This article reviews the characteristics of iron metabolism in the development and progression of myeloid neoplasms, as well as the mechanism of ferroptosis, to provide a basis for the development of new therapeutic strategies.
Ferroptosis ; Humans ; Iron/metabolism* ; Myelodysplastic Syndromes/pathology* ; Reactive Oxygen Species/metabolism* ; Leukemia, Myeloid, Acute/pathology* ; Hepcidins/metabolism* ; Iron Overload/metabolism* ; Myeloproliferative Disorders/metabolism* ; Prognosis

Objective To investigate the imaging features and risk factors of white matter hyperin-tensities(WMH)in elderly patients without stroke symptoms in Dingxi area.Methods A total of 253 elderly WMH patients without stroke syndrome admitted to our department from January 2020 to June 2022 were recruited,and according to Fazekas classification,they were divided into a control group(92 cases)and a study group(161 cases).The general clinical data were compared between the two groups.Multivariate logistic regression analysis was used to analyze the risk fac-tors of WMH,and Spearman correlation analysis was employed to analyze the correlation between WMH severity and hypertension.Results Older age,larger proportions of male and internal carotid plaques,and higher Hcy and TG levels were observed in the study group than the control group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that age,TG,and Hcy were risk factors for WMH in elderly patients without stroke syndrome(OR=0.564,95％CI:0.338-0.942,P=0.029;OR=1.248,95％CI:1.153-1.351,P=0.000;OR=0.046,95％CI:0.016-0.132,P=0.000).The classification of hypertension had no correlation with the severity of WMH in elderly patients without stroke syndrome.Conclusion TG,Hcy and age are independ-ent risk factors for WMH in elderly patients without stroke symptoms.

Objective:To explore the dilemmas and demands encountered by enterostomal therapists in providing sexual education or guidance to young and middle-aged patients with enterostomy.Methods:From April to October 2022, purposive sampling was used to select 15 enterostomal therapists who received training at the International School of Stomatologists for semi-structured interviews. Colaizzi 7-step analysis method was used for data analysis.Results:Three themes were extracted, namely the "negative behavior" and "positive willingness" of enterostomal therapists, the multiple dilemmas in implementing sex education for young and middle-aged patients with enterostomy, and the demands for sexual education for young and middle-aged patients with enterostomy.Conclusions:Enterostomal therapists should actively pay attention to the sexual education for young and middle-aged patients with enterostomy, overcome multiple obstacles that affect the lack of sexual education for young and middle-aged patients with enterostomy, and persist in promoting sexual education for young and middle-aged patients with enterostomy in clinical practice, in order to improve the marital relationship and quality of marriage between patients and their spouses.

Objective:To establish a droplet digital polymerase chain reaction (ddPCR) detection method for monkeypox(mpox) virus.Methods:Specific primers and probe targeting the F3 L gene of mpox virus were used to develop a ddPCR detection method for the mpox virus′s nucleic acid. The ddPCR reaction conditions were optimized, and the specificity, sensitivity, and repeatability of ddPCR were assessed. Additional examination of clinical samples obtained from human pus swabs was performed and the ddPCR method′s ability to detect clinical samples was evaluated. Results:The result demonstrated that the mpox virus ddPCR detection method was established and the ddPCR reaction temperature and primer probe concentration has been optimized. The method had a minimal detection limit of 2 copies/μl and did not exhibit cross reaction with the remaining 8 viruses. Ten clinical samples of human skin pus swabs were tested for the mpox virus; five of the samples were tested positive by ddPCR, and four of the samples were tested positive by real time fluorescence quantitative PCR (qPCR).Conclusions:The established ddPCR for mpox virus is a fast, specific, and highly sensitive detection method, and can be used for the detection of mpox virus in clinical samples.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

Novel Coronavirus Pneumonia (NCP) is a class B infectious disease, which is prevented and controlled according to class A infectious diseases. Recently, children′s NCP cases have gradually increased, and children′s fever outpatient department has become the first strategic pass to stop the epidemic. Strengthening the management of the fever diagnosis process is very important for early detection of suspected children, early isolation, early treatment and prevention of cross-infection. This article proposes prevention and control strategies for fever diagnosis, optimizes processes, prevents cross-infection, health protection and disinfection of medical staff, based on the relevant diagnosis, treatment, prevention and control programs of the National Health and Health Commission and on the diagnosis and treatment experience of experts in various provinces and cities. The present guidance summarizes current strategies on pre-diagnosis; triage, diagnosis, treatment, and prevention of 2019-nCoV infection in common fever, suspected and confirmed children, which provide practical suggestions on strengthening the management processes of children′s fever in outpatient department during the novel coronavirus pneumonia epidemic period.