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 current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

Male ; Humans ; Liquid Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Varicocele/diagnosis* ; Biomarkers

AIM: To observe the effect of RBC preservation solution with sodium pyruvate on the morphology, structure and function of RBC stored in vitro in type 2 diabetes rats. METHODS: Thirty SPF male SD rats, were randomly divided into 3 groups (n=10): non-T2DM conventional RBC preservation solution (group A), T2DM conventional RBC preservation solution (group B) and T2DM sodium pyruvate RBC preservation solution (group C). The leukoreduced RBC from the tail vein and stored for 0 d (T0), 7 d (T1), 14 d (T2), 21 d (T3) and 28 d (T4) to detect the morphology, structure and the contents of 2, 3-DPG, reactive oxygen species (ROS), malondialdehyde (MDA) and lactic acid (LA) of RBC in group A, B and C. The RBC stored for 14 days in vitro were labeled with PKH26, and its survival rate were tested in vivo at 1, 4, 10 and 16 hours after intravenous infusion. RESULTS: At T0, the RBC morphology of group A was intact, which was better than that of group B and group C. With the extension of storage time, the morphology of RBC in each group gradually transformed into a spindle-spherical shape. Compared with group A, the incidence of acanthocytes in group B and group C was higher, and the incidence of acanthocytes in group C was lower than that in group B. Compared with group A, the content of 2, 3-DPG in group B and group C decreased, while ROS and MDA increased at different time points (P<0.05). The content of 2,3-DPG in group C was higher than that in group B (P<0.05), and the contents of ROS and MDA were lower than those in group B (P<0.05). LA content in group B was higher than that in group A and group C (P<0.05). At T2-T4, the LA content in group C was lower than that in group A (P<0.05). The survival rate of RBC in group A was higher than that in group B and C, and the survival rate of RBC in group B was lower than that in group C (P<0.05). CONCLUSION: Sodium pyruvate added RBC preservation solution has a certain protective effect on RBC stored in vitro in type 2 diabetic rats, and its mechanism may be related to its antioxidant effect.

Objective:To evaluate the effect of novel erythrocyte preservation solution on the quality of erythrocytes in stored blood of type 2 diabetes mellitus (T2DM) rats.Methods:Forty SPF male Sprague-Dawley rats, aged 8 weeks, weighing 180-220 g, were used in this study. Ten rats randomly selected served as conventional erythrocyte preservation solution group (group A). T2DM model was prepared in the remaining 30 rats. Twenty T2DM rats were divided into 2 groups ( n=10 each) using a random number table method: T2DM conventional erythrocyte preservation solution control group (group C) and T2DM novel erythrocyte preservation solution observation group (group Y). Erythrocyte preservation solution was prepared to simulate the preoperative autologous blood donation process, and blood was collected from the tail vein to isolate the red blood cells, and then the corresponding preservation solution was added. Immediately after blood collection (T 0) and at 7, 14 and 21 days of preservation (T 1-3), the morphological structure of erythrocytes was observed with a light microscope, and the concentrations of 2, 3-diphosphoglycerate (2, 3-DPG) and reactive oxygen species (ROS) were also determined by enzyme-linked immunosorbent assay at T 0-T 3 and 28 days of preservation (T 4). PKH26 was used to label the erythrocytes stored in vitro for 28 days, and then the erythrocytes were transfused back into rats. The survival rate of erythrocytes was detected by flow cytometry at 1, 7, 13 and 18 h after retransfusion. Results:The erythrocyte damage was aggravated at different time points of preservation in group C when compared with group A. Compared with group C, the damage to erythrocytes was significantly alleviated at different time points of preservation in group Y. Compared with group A, the concentration of 2, 3-DPG in erythrocytes was significantly decreased at T 0 and T 2-T 4, the concentration of ROS was increased at T 0-T 4, and the survival rate of erythrocytes was decreased at 1, 7 and 18 h after retransfusion in group C ( P<0.05). Compared with group C, the concentration of 2, 3-DPG in erythrocytes was significantly increased at T 0-T 4, the content of ROS was decreased at T 1, T 3 and T 4, and the survival rate of erythrocytes was increased at 1, 7 and 18 h after retransfusion in group Y ( P<0.05). Conclusions:The novel erythrocyte preservation solution can improve the quality of stored erythrocytes and increase the survival rate of erythrocytes in vivo after retransfusion in T2DM rats.

OBJECTIVE: To explore the genetic basis for a patient with Alport syndrome (AS) and confirm the existence of a splicing variant. METHODS: An AS patient diagnosed at the Affiliated Hospital of Inner Mongolia Medical University on January 8, 2021 for significant proteinuria and occult hematuria was selected as the study subject. Clinical data was collected. Peripheral blood samples were collected for the extraction of genomic DNA. Whole exome sequencing and Sanger sequencing were carried out to identify potential genetic variants. An in vitro experiment was also conducted to verify the abnormal mRNA splicing. Bioinformatic software was used to analyze the conservation of amino acids of the variant sites and simulate the 3D structure of the variant collagen IV protein. Immunofluorescence and immunohistochemistry were carried out on renal tissues from the patient to confirm the presence of AS kidney injury. RESULTS: The patient, a 21-year-old male, had a 24-hour urine protein of 3.53 g/24 h, which fulfilled the diagnostic criteria for proteinuria. His blood uric acid has also increased to 491 μmol/L. DNA sequencing revealed that he has harbored a c.835-9T>A splice variant of the COL4A5 gene, which was not found in either of his parents. In vitro experiment confirmed that the variant has removed 57 bp from the exon 15 of the mRNA of the COL4A5 gene. The deletion may cause loss of amino acid residues from positions 279 to 297, which in turn may affect the stability of the secondary structure of the α5 chain encoded by the COL4A5 gene. The amino acids are conserved across various species. The result of homology modeling indicated that the trimerization of Col-IV with the mutated α5 chain could be achieved, however, the 3D structure was severely distorted. The AS kidney damage was confirmed through immunofluorescence assays. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.835-9T>A variant was classified as likely pathogenic (PVS1_Moderate+PS3_Moderate+PM2_Supporting+PS2+PP3+PP4). CONCLUSION The c.835-9T>A variant of the COL4A5 gene probably underlay the AS in this patient. In vitro experiment has confirmed the abnormal splicing caused by the variant. Histopathological examination of the kidney tissue has provided in vivo evidence for its pathogenicity. Above finding has expanded the mutational spectrum of the COL4A5 gene.
Humans ; Male ; Young Adult ; Amino Acids ; China ; Collagen Type IV/genetics* ; Exons ; Nephritis, Hereditary/genetics* ; RNA Splicing

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

Objective:To explore the changing characteristics of early warning information ability in children with transient tic disorder(TTD).Methods:A total of 32 children with TTD(TTD group) diagnosed and treated at Changzhou Children's Hospital from 2018 to 2022 and 36 healthy control children(HC group) recruited from ordinary primary schools in Changzhou city were tested with CPT-Go/Nogo task and their behavioral data and cue/uncue-N2, P3b and CNV components of event related potential(ERP) were analyzed and compared by SPSS 25.0 software.Results:(1)Comparison of behavioral data: there was no statistical difference in the correct number(37(34, 39) vs 38(37, 40)), false number(1(0, 2) vs 1(0, 2))and correct reaction time((511.27±99.27)ms vs(504.88±92.23)ms)between TTD and HC group(all P>0.05). (2) Comparison of ERP components: in the HC group, the amplitudes of cue-CNV were higher than those in uncue-CNV in lead Cz((-4.61±4.67)μV vs(-1.07±3.20)μV)and Pz((-4.17±3.74)μV vs(-1.79±3.49)μV) and the differences were statistically significant(both P<0.01). The amplitude of cue-P3b in lead Pz were higher than that in uncue-P3b((9.13±4.99)μV vs(6.12±6.24)μV) and the difference was statistically significant( P<0.01). Compare with HC group((-4.12±4.25)μV, (-4.61±4.67)μV, (9.13±4.99)μV), the amplitudes of uncue-N2, cue-CNV and cue-P3b in TTD group((-1.29±4.48)μV, (-2.03±3.19)μV, (6.59±3.41)μV) were respectively lower, and the differences were statistically significant(all P<0.05). Conclusion:Children with TTD may have dysfunction in conflict monitoring, attention allocation, and maintaining alertness when processing early warning information, but there may be corresponding compensation mechanisms for brain function.

Objective To evaluate the safety of immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flaps in the patients after neoadjuvant treatment. Methods From January 2019 to February 2021, the data of patients with breast cancer undergoing total mastectomy and immediate breast reconstruction using DIEP flap in Comprehensive Breast Health Center, Department of General Surgery, Ruijin Hospital were collected. Comparison of clinicopathological features was done between neoadjuvant treatment group and control group. Univariate analysis was used to compare the rate of surgical complications between two groups. Results A total of 110 patients were enrolled with 23 cases (20.9%) in neoadjuvant treatment group and 87 cases (79.1%) in control group. None of carcinoma in situ (0 vs. 19.5%, P=0.003) and higher pTNM stage (P<0.001) was present in neoadjuvant treatment group compared with those in control group. However, there were no significant differences in the number of flap perforator of DIEP (P=0.472), the proportion of bipedicled flaps (P=0.489), operative time (P=0.651) and hospital length of stay (P=0.275) between two groups. No significant difference was found in the incidence of postoperative complications between two groups. Breast seroma was the most common recipient complication (13.0%, 3 cases) without donor complication in neoadjuvant treatment group. The most common complication was fat necrosis (12.6%, 11 cases) in recipient site and abdominal seroma (3.4%, 3 cases) in donor site of control group. Reoperation was done in one case (4.3%) of neoadjuvant treatment group and 4 cases (4.6%) of control group. DIEP flap necrosis with total flap loss occurred in 2 cases (2.3%) in control group, but none in neoadjuvant treatment group. Conclusions The imme-diate breast reconstruction with epigastric free flap for breast cancer patients after neoadjuvant treatment would be a safe surgical scheme.

Objective: To determine the association between physical health fitness with Chinese reading ability of schoolaged children, so as to provide evidence for improving children s reading ability. Methods: A questionnaire survey was conducted among 1 923 school aged children in grades 2-6 in a primary school in Wuhan, Hubei Province, China. The questionnaire included basic demographic information and Dyslexia Checklist for Chinese Children and the Pupil Rating Scale Revised Screening. At the same time, participants underwent physical fitness tests which included an assessment of height, weight, and lung capacity, as well as a 50 meter run, sit forward bend, one minute skipping rope task, sit ups, and a 50 × 8 round trip. Results: A total of 59 children were identified with dyslexia. Normal children achieved higher scores than children with dyslexia in the total physical health score, as well as the one minute skipping rope score, one minute sit up score, and sitting forward score ( P <0.05). Multiple linear regression analyses showed that the reading ability of girls was higher than that of boys ( β =-3.04, P <0.01), and the children who regularly participated in more intense physical activity and who had higher fitness scores had a higher reading ability ( β =-1.68, -0.08, P <0.01). Children s reading ability increased significantly with parental educational level( P <0.05). Conclusion Gender, parents education level, physical exercise intensity, and children s physical fitness were identified as influencing factors of school age children s reading ability. A positive correlation was found between children s physical health level and reading ability.