Bispecific killer cell engagers (BiKEs) are a powerful tool to incite the killing power of natural killer (NK) cells. Here, we posited that the BiKE technology could be utilized to deplete activated immune cells expressing programmed death-1 (PD-1⁺ cells), and hence treat autoimmune diseases since these cells drive the disorders. We designed and generated PD-1 BiKE that targets an activating NK cell receptor, CD16, and PD-1. PD-1 BiKE showed specific binding to PD-1⁺ cells and engaged CD16 simultaneously. PD-1 BiKE enhanced NK cell-mediated apoptosis and depletion of PD-1⁺ Raji cells, but not PD-1^- Raji cells. Further, PD-1 BiKE induced apoptosis of primary PD-1⁺ T lymphocytes that are highly relevant to autoimmune disease progression. The BiKE depleted 42% of primary T cells that were stimulated in vitro. Importantly, those ablated primary T cells were activated cells. Meanwhile, naive T cells were spared by the BiKE treatment, supporting the crucial selectivity of PD-1 BiKE-directed cell depletion. Lastly, PD-1 BiKE is more effective than a conventional depleting antibody in the depletion of PD-1⁺ cells. The current work supports PD-1 BiKE is a selective, potent, and safe tool to deplete PD-1⁺ cells.

Background and Aims:Whether to close mesenteric fissures during laparoscopic radical resection of colorectal cancer remains controversial.Traditional suture closure is technically demanding and may injure mesenteric vessels.This study aimed to evaluate the safety and efficacy of using α-cyanoacrylate medical glue to close mesenteric fissures during laparoscopic colorectal cancer surgery.Methods:A retrospective analysis was conducted on patients who underwent laparoscopic radical resection of colorectal cancer in the Department of Colorectal Surgery,the Sixth Affiliated Hospital of Sun Yat-sen University,from January 2022 to December 2023.Seventy-eight patients who received intraoperative α-cyanoacrylate glue closure of mesenteric fissures were included as the observation group,and 74 patients without fissure closure were selected as the control group using the propensity score matching method.Perioperative parameters,postoperative recovery,and complications were compared between the two groups.Results:No significant differences were observed in baseline characteristics or main intraoperative variables between groups(all P>0.05).The observation group had significantly less ascitic drainage within 3 days after operation[(203.14±116.44)mL vs.(384.53±243.89)mL,P<0.01]and shorter postoperative gas passage,defecation,and drainage tube removal times(all P<0.01).The incidence of postoperative complications and intestinal obstruction was comparable between groups(all P>0.05).Multivariate analysis showed that intraoperative application of α-cyanoacrylate glue was an independent promoting factor for intestinal exhaust within 3 days after surgery(OR=5.739,P=0.000).Conclusion:The use of α-cyanoacrylate medical glue for closing mesenteric fissures during laparoscopic radical resection of colorectal cancer is safe and feasible.It effectively reduces postoperative ascitic drainage and accelerates bowel recovery,offering a simple and reliable alternative to traditional suture closure.

Background and Aims:Whether to close mesenteric fissures during laparoscopic radical resection of colorectal cancer remains controversial.Traditional suture closure is technically demanding and may injure mesenteric vessels.This study aimed to evaluate the safety and efficacy of using α-cyanoacrylate medical glue to close mesenteric fissures during laparoscopic colorectal cancer surgery.Methods:A retrospective analysis was conducted on patients who underwent laparoscopic radical resection of colorectal cancer in the Department of Colorectal Surgery,the Sixth Affiliated Hospital of Sun Yat-sen University,from January 2022 to December 2023.Seventy-eight patients who received intraoperative α-cyanoacrylate glue closure of mesenteric fissures were included as the observation group,and 74 patients without fissure closure were selected as the control group using the propensity score matching method.Perioperative parameters,postoperative recovery,and complications were compared between the two groups.Results:No significant differences were observed in baseline characteristics or main intraoperative variables between groups(all P>0.05).The observation group had significantly less ascitic drainage within 3 days after operation[(203.14±116.44)mL vs.(384.53±243.89)mL,P<0.01]and shorter postoperative gas passage,defecation,and drainage tube removal times(all P<0.01).The incidence of postoperative complications and intestinal obstruction was comparable between groups(all P>0.05).Multivariate analysis showed that intraoperative application of α-cyanoacrylate glue was an independent promoting factor for intestinal exhaust within 3 days after surgery(OR=5.739,P=0.000).Conclusion:The use of α-cyanoacrylate medical glue for closing mesenteric fissures during laparoscopic radical resection of colorectal cancer is safe and feasible.It effectively reduces postoperative ascitic drainage and accelerates bowel recovery,offering a simple and reliable alternative to traditional suture closure.

Objective:To explore the value of the aMAP risk score (age, male, albumin -bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods:This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors.Results:Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group ( P=0.001). Conclusions:The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..

Objective To explore the possible risk factors for autism spectrum disorders (ASD),and to pro-vide a basis for exploring the etiology of the disease.Methods This case -control study included 68 patients diag-nosed as ASD for a first lifetime(according to the fourth edition of the American Diagnostic and Statistical Manual of Mental Disordersfor ASD diagnosis)from May 201 4 to January 201 5,and 77 non -ASD controls (normal children, matched on gender)in Jiangxi Children′s Hospital were selected to undergo the risk factor survey for ASD.The survey content included 1 0 categories:general status,birth,feeding,the past history,mother′s pregnancy and her health condi-tion during pregnancy and environmental exposure,parents′occupational exposure,family history and relevant test re-sults.Logistic regression analysis was performed to analyze the results of the survey.Results The possible risk factors for ASD increased if mother had virus infection 2 years before pregnant (OR =7.97,95%CI:2.42 -26.31 ),had occu-pational exposure (OR =3.99,95%CI:1 .27 -1 2.52),volatile organic compounds exposure during pregnancy (OR =22.21 ,95%CI:2.28 -21 6.09),as well as living closely to transport passage ways during pregnancy (OR =0.59,95%CI:0.38 -0.93)or having a family heredity history (OR =58.50,95%CI:5.81 -589.57).Breastfeeding (OR =0.81 ,95%CI:0.66 -0.98)might be a protective factor in ASD.Conclusions In addition to genetic factors,the ute-rine environment from conception to birth and growth environment play an important role in the pathogenesis of ASD.

Objective To explore the significant risk factors in patients with Tile C pelvic frac-tures.Methods We conducted a retrospective review of all patients with Tile C pelvic fractures in Nanjing First Hospital from January 2010 to December 2014.The data gathered on each patient in-cluded:age,sex,mechanism of injury,visiting time after injury,shock index,Injury severity scale (ISS),Revised trauma score (RTS),Glasgowcoma scale (GCS),lowest PaO2/FiO2 ,6 h lactate clearance rate,concomitant injures and interventious of Tile C pelvic fractures.The data were tested using Student’t-test,χ2 test and logistic regression method.Results The study include 139 consecutive patients.The total mortality was 29.5%.Among them,36 (25.9%)patients died within 48 hours after admission.Multivariate regression analysis showed that shock index (OR=2.591,95%CI 1.041-4.216), ISS (OR = 47.96,95%,CI 15.89-147.23 ),RTS (OR = 6.917,95% CI 1.147-13.862 ),GCS (OR =4.172,95%CI 2.962-6.268),lowest PaO2/FiO2 (OR= 117.016,95% CI 51.011-176.032),6 h lactate clearance rate (OR=2.785,95%CI 1.191-4.892),concurrent head (OR=6.302,95%CI 2.270-13.175)or chest (OR=12.233,95%CI 5.193-33.985)injures were associated with high morality of Tile C pelvic frac-ture (P <0.01).The performing digital subtraction angiography with intravascular embolization can cut the mortality (OR=0.887,95%CI 0.875-0.899).Conclusion In our study,high trauma score,serious shock, coma,PaO2/FiO2 decreased and 6 h lactate clearance rate decreased,combined with the head and chest inju-ry are the important reasons of mortality in patients with Tile C pelvic fracture.It’s vital to control shock actively,use trauma scale and emphasize multidisciplinary cooperation to reduce mortality in patients with Tile C pelvic fractures.

Animals ; Copper ; toxicity ; Disulfiram ; toxicity ; Humans ; Leukemia, Myeloid, Acute ; Mice ; Mice, Inbred NOD ; Mice, SCID

Objective To observe the apeptosis in liver injury following limbs ischemia-reperfusion(IR) in rats and the protective effects of taurine.Methods The model of limbs ischemia-reperfusion injury was established.30 Wistar rats were randomized into 3 groups: control group,IR group and tanrine + reperfusion group (TR group) (n = 10 for each group).The levels of malondialdehyde (MDA) and xanthineoxidas (XOD), calcium and myeloper-oxidase (MPO) in the liver tissue were measured.DNA fragmentation was observed and analyzed by agarose gel e-lectrophoresis.Apoptosis was detected by TUNEL methods.The morphologic changes were observed with HE stai-ning.Results Compared with control group,the values of MDA, XOD, MPO, calcium in liver tissue were increased significantly in IR group (P<0.01), but the values of those in TR group were lower than in IR group (P<0.01).The percentage of apeptosis cell was higher in IR group than in control group(P<0.01).Compared with IR group, the percentage of apoptosis cell was lower in TR group (P<0.01).IR group presented DNA ladder pattern, while TR group showed no specific DNA ladder pattern in agarose gel electrophoresis.Conclusion Apoptosis participates in the liver injury after limb ischemia-reperfusion.Taurine can mitigate the liver injury and apoptosis after limb is-chemia-reperfusion injury in rats.

BACKGROUND: Rabbit serum samples are widely used in basic researches, and two-dimensional gelelectrophoresis (2-DE) is the most classic technique for protein separation. Therefore, it is of great significance to establish a stable technique system of 2-DE for rabbit serum.OBJECTIVE: To establish a 2-DE technique system for rabbit serum protein separation. DESIGN, TIME AND SETTING: A single sample observational experiment was performed at Tianjin Key Laboratory of Biomarkers for Occupational and Environmental Hazard of Chinese People's Armed Police Forces Medical College from June to July in 2008. MATERIALS: Six healthy rabbits were provided by the Animal Experimental Center of Tangshan Vocational Technical College METHODS: Health rabbit serum was dissolved in rehydration sample loading buffer before and after eliminating high abundance proteins to make proteins in it schizolysis adequately. After reductive alkylation, the samples were loaded into the rehydration tray to undergo passive rehydration for 14 hours. Isoelectric focusing (IEF) electrophoresis was followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). After sliver staining, the gel was analyzed by PDQuest7.4. MAIN OUTCOME MEASURES: ①Efficiency of eliminating high abundance proteins. ②Two-dimensional eleotrophoregrams (2-D electrophoregrams)RESULTS: Distinct 2-D eleotrophoregrems were obtained with high resolution and good reproducibility. The removal of high abundance proteins in serum failed to result in better 2-D electrophoregrams.CONCLUSION: We have successfully established a 2-DE technique for rabbit serum proteome, which can lay the foundation for the further study of serum proteomics of diseases.

BACKGROUND: Limb ischemia reperfusion (LIR) as a stressor leads to gastric mucosal injury, and then results in the occurrence of stress ulcer.OBJECTIVE: To observe the effects of LIR on gastric mucosal injury, investigate part of the mechanism, and the role of several transient limb ischemia in the occurrence of gastric mucosal injury.DESIGN: A randomized grouping design and controlled animal experiment.SETTING: Department of Pathophysiology of North China Coal Medical College.MATERIALS: The experiment was carried out in the pathophysiological laboratory of North China Coal Medical College from January to June 2002. Fifty-four healthy adult male Wistar rats were randomly divided into three groups with 18 rats in each group. Ischemia reperfusion (I/R) group: The rats were duplicated into models according to the Rosenthal method that under superficial anesthesia with ether, the roots of both hindlimbs were ligated by wrapping with rubber strap, blood flow was blocked for 4 hours and then recovered to perfusion for 4 hours, and finally killed by bleeding from abdominal aorta. Ischemic preconditioning group: Before model establishment, blood flow of both hindlimbs was blocked for 5 minutes, and then recovered to perfusion for 5 minutes, which was repeated for four times, and the following operations were the same as those in the I/R group. Control group: The operations were the same as those in the I/R group,but both hindlimbs were ligated at relaxation without blocking the blood flow.METHODS: Sections of gastric mucosa were prepared, and then observed under light microscope and electron microscope, and the index of gastric mucosal injury was determined according to the Guth standard. The colorimetric assay was performed with 721 spectrophotometer at 650 nm, and the amount of gastric combining mucus was calculated.Meanwhile, the blood flow of gastric mucosa, contents of phospholipid and hexosamine in gastric mucus, content of nitric oxide in plasma and gastric tissue and activity of nitric oxide synthase (NOS) in gastric mucosa were determined.MAIN OUTCOME MEASURES: Index of gastric mucosal injury, amount of gastric combining mucus, blood flow of gastric mucosa, contents of phospholipid and hexosamine in gastric mucus, contents of nitric oxide in plasma and gastric tissue and NOS activity in gastric mucosa.RESULTS: All the 54 rats were involved in the analysis of results. ① In the I/R group, gastric mucosal injury was serious, edema, hyperemia, erosion and disintegration of gland of mucosal glands were observed, infiltration of inflammatory cells (formation of ulcer) was observed in basal and inferior mucosa. In the ischemic preconditioning group, the gastric mucosa was complete, and the damaged severity was milder than that in the I/R group; Under electron microscope, the organell structures of gastric parietal and chief cells were incomplete and destroyed. The cell injuries in the ischemic preconditioning group were milder than those in the I/R group (index of injury: 18.00±10.71, 34.00±15.01, P＜ 0.01). ② The blood flow and combining mucosal amount of gastric mucosa, contents of phospholipid and hexosamine in gastric mucus in the ischemic preconditioning group and I/R group were all obviously lower than those in the control group [(2.12±0.56), (10.84±2.56), (25.52±2.97) mL/(kg·h); (2.01±0.91), (2.79±0.73), (3.99±0.87) mg;(7.68±1.95), (9.74±1.04), (11.98±1.98) mg/g; (3.83±1.18), (5.42±0.47), (5.76±1.21) mg/g, P ＜ 0.05, 0.01], those the above indexes were all higher in the ischemic preconditioning group than in the I/R group. ③ The contents of nitric oxide in plasma and gastric tissue and NOS activity in gastric mucosa in the ischemic preconditioning group and I/R group were significantly lower than those in the control group [(250.0±5.6), (270.0±11.3), (210.0±7.4) μmol/L; (9.34±0.67), (11.34±1.00), (7.50±0.67) μ kat/g, P ＜ 0.01], those were also signficantly higher in the ischemic preconditioning group than in the I/R group.CONCLUSION: As a stressor, LIR can lead to gastric mucosal injury, and cause stress ulcer.Ischemic preconditioning can alleviate the gastric mucosal injury following LIR