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 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.

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.

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

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.

Objective To observe the expression of interferon induced protein (IP)-10 and the role of nuclear factor-kappaB (NF-κB) signaling pathway in rat peritoneal mesothelial cells (RPMCs) under the action of lipopolysaccharide (LPS).Methods RPMCs were harvested from Sprague-Dawley rat peritoneal cavity and cultured under defined in vitro conditions.The cells were exposed respectively to different concentrations of LPS (0,10,100,1 000,10 000 ng/ml) for 3 h or treated with LPS (100 ng/ml)for different time points (0,1,3,6,12,24,48 h).For observing the effect of LPS on the expression of p-p65 and p65,the RPMCs were treated with LPS (100 ng/ml) for different time points (0,15,30,60,120 min).For observing the effect of BAY11-7085 on the expression of IP-10 mRNA,the RPMCs were treated by LPS or pretreated with BAY11-7085 (5 μ mol/L) for2 h,then treated with LPS for another 3 h,respectively.Expression of IP-10 mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR).Expression of NF-κB and p-NF-κB protein was detected by Western blot.The secretion of IP-10 was determined by enzyme-linked immunosorbent assay (ELISA).Results Compared with the control group,stimulation of RPMCs with 10 ng/ml LPS resulted in a significant increase in the expression of IP-10 mRNA (P ＜0.05).1 000 ng/ml LPS has the strongest effect on IP-10 expression compared with that of 10 ng/ml and 100 ng/ml LPS.Treatment with 100 ng/ml LPS resuhed in time-dependent increase in the gene level of IP-10,with the peak at 3 h.However,after that time point,the gene level of them was gradually attenuated.Following treatment with LPS (100 ng/ml),the level of p-NF-κB began to increase at 15 min,gradually reached the peak at 1 hour,and then decreased.But the level of which at 2 h is still significant higher than that of medium control.5 μmol/L BAY11-7085 significantly decreased the up-regulation of IP-10 induced by LPS.Conclusions LPS enhanced the expression of IP-10 on RPMCs in a concentration-dependent and a time-dependent manner.LPS induced expression of IP-10 depended on the NF-κB signal transduction pathway.

Objective To study the therapeutic effect of bitter gourd saponins on salt-sensitive kidney injury induced by high salt diet and its possible mechanism.Methods 50 Sprague Dawley (SD) rats were randomly divided into normal group,model group and low-dose,middle-dose and high-dose treatment group after 10 days of adaptive feeding.Each group had 10 rats.Except the normal group,the other four groups were given high salt diet (4.0％ high salt diet) to induce salt-sensitive kidney damage in rats.The normal group and the model group were given 1.0 m/(kg · d) normal saline,and the three dosage groups of total saponins of balsam pear were given 10 mg/(kg · d),20 mg/(kg · d) and 40 mg/(kg · d) respectively.After 8 weeks of treatment,rats were sacrificed and collect the 24-hour proteinuria,creatinine.Serum creatinine,serum aldosterone,serum sodium and serum potassium were measured,and renal histopathology and the expression of podocin and nephrin were detected.Results Pathological examination of model group showed obvious glomerular sclerosis and renal interstitial fibrosis,and glomerular sclerosis in the treatment group was obviously improved by bitter gourd saponins;The systolic pressure in the model group was 170 mmHg,significantly higher than that of the normal and treatment groups,the systolic blood pressure of the treatment groups were obvious decreased when treated by bitter gourd saponins (P ＜ 0.05);Compared with normal group,serum creatinine and 24 h proteinuria / urine creatinine in model group were significantly increased (P ＜ 0.05),while creatinine clearance rate and aldosterone were significantly decreased (P ＜ 0.05),and the above indexes in bitter gourd saponins treatment group were significantly improved;Compared with the model group,the protein and mRNA expression of podocin and nephrin were significantly decreased (P ＜ 0.05),while the two indexes can be revered by bitter gourd saponins in treatment group (P ＜ 0.05).Conclusions The bitter gourd saponins can significantly improve the symptoms of salt-induced hypertensive nephropathy in rats,which may be related with the expression of podocin and nephrin in renal tissue,thereby inhibiting glomerulosclerosis and improving renal interstitial fibrosis.