Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Purpose To investigate the clinicopathologic,immunophenotypic features,genetic alterations and prognosis of melanotic Xp11 neoplasms/melanotic TFE3-rearrangement neo-plasms.Methods Five cases were selected from the Depart-ment of Pathology,Union Hospital,Huazhong University of Sci-ence and Technology from November 2018 to July 2023.The clinicopathologic,immunohistochemical,FISH assays,next-generation sequencing(NGS)and follow-up details were collect-ed.Results There were 1 male and 4 females,with their ages ranging from 16 to 59 years(mean 28.2 years).The maximum diameters of the masses were 3-6 cm(average 4.7 cm).The tumors located in right kidneys(3 cases),tubal interstitium(1 case)and pelvis(1 case).Microscopically,most tumors shared similar morphology such as nested,acinar structures sep-arated by a delicate vascular network.Epithelioid tumor cells presented with clear to granular eosinophilic cytoplasm.Lym-phocytic infiltration was seen in the background;melanin depo-sition was noted in the cases;neoplastic necrosis was detected in 4 cases.Mitotic activity was low with 5 cases showing＜3/10 HPF.Intravascular tumor thrombus was detected in 2 cases,no lymphovascular and nerve invasions were detected in other 3 ca-ses.Immunohistochemically,all 5 cases expressed TFE3 dif-fusely,and expressed HMB45,Melan A to varying degrees,CK(AE1/AE3),CK7,EMA,PAX8,TFEB,S-100,SOX10,SMA,desmin were all non-reactive in the 5 cases.The Ki67-la-beling index was＜20％.TFE3 separation signal in 4 cases were detected by FISH,1 case was interpreted as negative due to atypical signal which was confirmed by next-generation se-quencing(NGS)assay as RBM10-TFE3.Clinical follow-up was available for five patients for 2-60 months,in which four pa-tients were alive with no evidence of disease after initial resec-tion,and one patient with thoracic spine metastasis was currently in stable condition.Conclusion Melanotic Xp1 1 neoplasms/melanotic TFE3-rearrangement neoplasms has unique morpholog-ic,immunophenotypic and genetic characteristics.It might be reclassified into a distinctive malignant mesenchymal tumor enti-ty.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.
Adult ; Asthenozoospermia/virology* ; COVID-19/physiopathology* ; China ; Gonadal Steroid Hormones/blood* ; Humans ; Male ; Progesterone/blood* ; Prolactin/blood* ; SARS-CoV-2 ; Semen/physiology* ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa/physiology* ; Time Factors

OBJECTIVE: To establish the in vivo traceable acute myeloid leukemia mice model with Luciferase-Expressing KG1a Cells. METHODS: KG1a cells with stable luciferase gene expression (called as KG1a-Luc cells) were constructed by lentivirus transfection, then sifted out by puromycin. Eighteen male NOD-SCID-IL2rg RESULTS: KG1a cells expressing luciferase stably were successfully obtained. The tumor luminescence wildly spread at day 17 captured by in vivo imaging. The KG1a-Luc tumor cells could be detected in the peripheral blood of the mice, with the average percentage of (16.27±6.66)%. The morphology and pathology result showed that KG1a-Luc cells infiltrate was detected in bone marrow, spleens and livers. The survival time of the KG1a-Luc mice was notably shorter as compared with those in the control group, the median survival time was 30.5 days (95%CI: 0.008-0.260). CONCLUSION The acute myeloid leukemia NOD-SCID-IL2rg
Animals ; Disease Models, Animal ; Interleukin Receptor Common gamma Subunit ; Leukemia, Myeloid, Acute ; Luciferases/genetics* ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID

Asymptomatic Infections ; Betacoronavirus ; Carrier State ; Coronavirus Infections ; transmission ; Female ; Humans ; Middle Aged ; Pandemics ; Pneumonia, Viral ; transmission

Objective To assess the clinical relevance of polymorphisms at position-251 in the promoter region of IL-8 gene and the incidence of sepsis in patients with severe trauma.Methods A total of 296 patients with severe trauma were included in the prospective cohort study.Incidence of sepsis was decided on the basis of the clinical manifestations and blood culture results.Muhiple organ dysfunction score (MODS) was performed using Marshall' s standard.IL-8/-251 gene polymorphisms were genotyped using restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP).IL-8 plasma level was determined using ELISA method.Results Genotype frequency at IL-8/-251 locus in trauma patients was in accord with Hardy-Weinberg equilibrium (P ＞ 0.05).Sepsis incidence in trauma patients with TT,TA,and AA genotypes at IL-8/-251 locus was 58.1％,49.6％,and 25.0％ respectively.Multiple regression analysis showed inverse correlation between sepsis incidence and quantity of A alleles [OR =0.637,95％ CI (0.421,0.963),P ＜ 0.05].Carriers of AA genotype presented lower MODS score than those of other two genotypes (P ＜ 0.05).IL-8 plasma level presented significant difference among carriers of the three genotypes (P ＜ 0.01) and A alleles were associated with the down-regulation of IL-8 (P ＜ 0.01).Conclusion IL-8/-251T/A polymorphisms are implicated in the development of posttraumatic sepsis and AA genotype is protective against posttraumatic sepsis.

OBJECTIVETo evaluate the value of pedicle parameter obtained by the reformation images on multi-slice spiral CT (MSCT) in the surgical treatment of lumbar spondylolisthesis.

METHODSFrom January 2009 to March 2010, 60 patients with lumbar spondylolisthesis failing in conservative treatment were enrolled into the study and divided into experimental and control group randomly (each group with 30 patients). There were 26 males and 34 females ranging in age from 18 to 59 years with an average of (42.60 +/- 9.36) years. The experimental group was examined with volumetric scanning on MSCT before operation. Reformation such as multiplanar reconstruction (MPR) and volume rendering (VR) were carried out at the work station. Transverse section angle (TSA), sagittal section angle (SSA), pedicle length (PL), pedicle width (PW) and pedicle height (PH) were measured on different images and pedicle screws were implanted according pedicle parameter. In control group, the pedicle screws were implanted according to conventional anatomic landmark. Preparative time of screw canal and accuracy of screw were compared between two groups.

RESULTSA hundred fifty-six screws were inserted in experiment group,143 screws were excellent, 11 good, and 2 poor. A hundred fifty screws were inserted in control group, 101 screws were excellent, 26 good, and 23 poor. There was significant difference in accuracy of screw between two groups (P < 0.001). The preparative time of screw canal in experiment group was (66.20 +/- 7.31) s, and was shorter than that of control group [(104.11 +/- 9.51) s, P < 0.001)].

CONCLUSIONAbundant information and parameter could be obtained with the MSCT reconstruction images. The images and parameters could make a perfect operative strategy before operation, adjust the direction of pedicle screws during operation, avoid and decrease operative complications effectively.

Adolescent ; Adult ; Bone Screws ; Female ; Humans ; Lumbar Vertebrae ; diagnostic imaging ; surgery ; Male ; Middle Aged ; Spondylolisthesis ; diagnostic imaging ; surgery ; Tomography, Spiral Computed ; methods

BACKGROUNDIt is unclear whether edge segments have different responses to paclitaxel eluting stent (PES) and sirolimus eluting stent (SES) implantation in patients with unstable angina. This study aimed to compare the different vascular edge responses in patients with unstable angina and single de novo coronary lesion treated with SES and PES.

METHODSTwo hundred and fifty-five patients with unstable angina and single de novo lesion were randomly assigned to PES and SES groups. Serial volumetric intravascular ultrasound (IVUS) images were taken immediately after stenting and at an eight-month follow-up. Five-mm edge segments proximal and distal to the stents were analyzed.

RESULTSBaseline characteristics were comparable between the two groups. At proximal-edge segment, the vessel area decreased and the plaque area increased significantly in the PES group as compared with the SES group. A significant net loss of lumen area was found in the PES group (from (11.10 +/- 3.12) mm(2) at baseline to (9.92 +/- 3.59) mm(2) at the follow-up, P < 0.001). At the distal-edge segment, the net loss of lumen area in the PES group (from (7.71 +/- 2.81) mm(2) at baseline to (6.66 +/- 2.29) mm(2) at the follow-up, P < 0.001) was attributed to a significant increase of plaque area. Proximal-edge stenosis was commonly seen in the PES group (20.0%) as compared with the SES group (5.0%, P = 0.001). This correlated with the higher incidence of target lesion revascularization in the PES group (P = 0.03). Subsegmentally, the smallest Delta lumen area was located at 2 mm proximally in both groups, at 0 mm distally in the PES group, and at 1 mm distally in the SES group.

CONCLUSIONSThe two groups demonstrated negative remodeling of edge segments. PES was less effective than SES in inhibiting the growth of plaque within the first 1-mm length proximal to the stent.

Aged ; Aged, 80 and over ; Angina, Unstable ; diagnostic imaging ; drug therapy ; therapy ; Coronary Angiography ; Drug-Eluting Stents ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Paclitaxel ; therapeutic use ; Sirolimus ; therapeutic use ; Treatment Outcome ; Ultrasonography