Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

OBJECTIVE: To explore the inhibitory effects of Nardostachys Jatamansi DC. volatile oil (NJVO) on psychological factors substance P (SP)/cortisol (CORT)-induced hyperpigmentation. METHODS: The model of psychologically-induced hyperpigmentation of B16F10 cells was created using SP (10 nmol/L) + CORT (10 µmol/L) for 72 h. The levels of melanin content, tyrosinase (TYR) activity using NaOH lysis and L-dihydroxyphenylalanine (L-DOPA) oxidation methods were assessed, respectively. The effect of NJVO on SP/CORT-induced normal human skin tissue pigmentation was detected by Masson staining. Protein expressions of tyrosinase-related protein 1 (TRP-1), tyrosinase-relative protein 2 (DCT), and microphthalmia-associated transcription factor were determined using Western blot. The melanosome number, maturation, and melanosomal structure changes were detected through transmission electron microscopy and immunofluorescence experiments. In vivo, zebrafish pigment content was evaluated in SP/CORT-induced zebrafish hyperpigmentation model. RESULTS: NJVO significantly reduced the melanin content (P<0.01) and inhibited tyrosinase activity (P<0.01), the pigmentation of the normal skin tissue in the NJVO group was significantly lower than that in the SP/CORT group (P<0.05). And NJVO considerably downregulated expressions of melanogenesis-related proteins (TYR, TRP-1, DCT) in cells (P<0.01). In addition, the number of melanosomes was decreased and the dentrites formation of B16F10 cells was inhibited after NJVO treatment (P<0.01). In vivo, NJVO significantly reduced the pigment content in the zebrafish body (P<0.01). CONCLUSION NJVO effectively reversed SP/CORT-induced hyperpigmentation by suppressing the activity and expression of TYR and TRPs and inhibiting melanosome maturation in mouse B16F10 melanoma cells.
Animals ; Hyperpigmentation/psychology* ; Zebrafish ; Oils, Volatile/therapeutic use* ; Melanins/metabolism* ; Humans ; Monophenol Monooxygenase/metabolism* ; Mice ; Nardostachys/chemistry* ; Substance P ; Hydrocortisone ; Skin Pigmentation/drug effects* ; Cell Line, Tumor ; Melanosomes/ultrastructure* ; Microphthalmia-Associated Transcription Factor/metabolism* ; Melanoma, Experimental ; Oxidoreductases/metabolism* ; Intramolecular Oxidoreductases/metabolism*

AIM:This study aimed to investigate the effect of ischemic post-conditioning(I-post-C)on lung ischemia-reperfusion injury(LIRI)in rats and relationship between I-post-C and zinc homeostasis.METHODS:SPF SD rats(6～8 weeks old)were randomly divided into four groups,with eight rats in each group:control group,ischemia/reper-fusion(I/R)group,I-post-C group and I-post-C+zinc ion chelator TPEN group.Inductively coupled plasma mass spec-trometry(ICP-MS)was used to measure the concentration of zinc ions in lung tissues.HE staining,lung wet/dry weight ra-tio(W/D),total lung water content(TLW),and index of quantitative assessment(IQA)of lung injury were used to detect the degree of lung tissue injury in each group.Mitochondrial membrane potential was measured using extraction and JC-1 mitochondrial membrane potential detection kits.TUNEL assay was used to detect the level of apoptosis in lung tissues.Western blot was used to detect the protein expression levels of caspase-3,solute carrier family 39 member 8(SLC39A8/ZIP8),solute carrier family 30 member 9(SLC30A9/ZNT9),and PI3K/AKT/GSK-3β in lung tissues of each group.RT-qPCR was used to detect ZIP8 and ZNT9.RESULTS:Compared to the control group,the I/R group showed significantly aggravated lung tissue injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced cell apoptosis(P<0.05),re-duced mitochondrial membrane potential(P<0.01),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved caspase-3/pro-caspase-3 ratio(P<0.01),and reduced ZIP8 expression(P<0.05).Compared to the I/R group,the I-post-C group exhibited alleviated injury(P<0.05 or P<0.01),increased zinc ion levels(P<0.01),reduced apoptosis(P<0.01),restored mitochondrial membrane potential(P<0.01),elevated PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),decreased cleaved caspase-3/pro-caspase-3 ratio(P<0.05),and in-creased ZIP8 expression(P<0.05).Compared to the I-post-C group,the I-post-C+TPEN group demonstrated aggravated injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced apoptosis(P<0.01),reduced mitochondrial membrane potential(P<0.05),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved cas-pase-3/pro-caspase-3 ratio(P<0.05),and reduced ZIP8 expression(P<0.05).ZNT9 expression showed no significant differences among the groups(P>0.05).CONCLUSION:Ischemic postconditioning can improve LIRI by regulating zinc homeostasis,activating PI3K/AKT signaling pathway,inactivating glycogen synthase kinase 3β,inhibiting the de-cline of mitochondrial membrane potential,and antagonizing cell apoptosis in rats.

Objective:To investigate the differences in prosthesis implantation accuracy, biomechanical indicators, and 2-year postoperative clinical outcomes between robotic-assisted traditional posterior approach (RA-PLA) and robotic-assisted direct anterior approach (RA-DAA) in total hip arthroplasty (THA).Methods:This study is a prospective randomized controlled trial. Patients with unilateral femoral head ischemic necrosis or primary hip osteoarthritis who meet the inclusion and exclusion criteria and were admitted to the Department of Orthopedics,Xinqiao Hospital, Army Medical University from May to September 2022. Divided into RA-PLA group and RA-DAA group through central randomization. Use cumulative and fitting methods to analyze the learning curve of robotic surgery and eliminate cases before the inflection point of the learning curve. Compare the abduction angle and anteversion angle of acetabular cup implantation between two groups of patients, as well as the rate of falling into the safe zone, the difference in length between the two lower limbs, hip joint eccentricity, rotation center height, the complete accuracy of prosthesis planning (the number of cases in which acetabular cup prosthesis, femoral stem prosthesis specifications, and neck shaft angle were completely consistent with surgical planning during surgery/total cases×100%), patient reported outcome indicators (including Harris hip score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC), and 12 item Short Form Health Survey (SF-12) score) and clinical outcomes. Data comparison was conducted using independent sample t-test, Wilcoxon rank sum test, chi square test, Fisher′s exact probability method, or repeated measures analysis of variance. Results:A total of 98 patients were included in this study, with 48 in the RA-PLA group and 50 in the RA-DAA group. After excluding cases before the inflection point of the learning curve, 30 patients were included in each group. There was no statistically significant difference in baseline data between the two groups before surgery (all P>0.05). There was no significant difference in the values of the anterior tilt angle and abduction angle between the two groups of acetabular cups compared to preoperative planning (all P>0.05). The proportion of patients who fell into the Lewinnek and Callanan safe zones was 90.0% (27/30) and 96.7% (29/30), respectively ( χ2=0.268, P=0.605). There was no significant difference in postoperative lower limb length, hip joint eccentricity, and rotation center height deviation and grading between the two groups (all P>0.05). The complete accuracy of prosthesis planning in the RA-DAA group was higher than that in the RA-PLA group (86.7% (26/30) compared to 63.3% (19/30), χ2=4.356, P=0.037).All patients were followed up for more than 2 years. In terms of postoperative HHS, WOMAC, and SF-12 score, there was no statistically significant difference in the inter group effect comparison (all P>0.05), but there was a significant statistical significance in the time effect (all P<0.05). There was no significant difference in the incidence of perioperative complications and adverse events between the RA-DAA group and the RA-PLA group (20.0% (6/30) vs. 13.3% (4/30), χ2=0.480, P=0.488). Conclusions:RA-DAA and RA-PLA techniques can achieve similar clinical efficacy after two years of surgery, and both can achieve similar reconstruction accuracy in terms of acetabular cup implantation angle, lower limb length, hip joint eccentricity, and rotation center height. The accuracy of prosthesis planning in RA-DAA is higher.

Objective Aedes albopictus is the primary vector of the dengue virus.Screening and the analysis of immune-related genes in DENV2-infected Ae.albopictus provides a scientific basis for further research on blocking the extrinsic incubation period of the dengue virus.Methods Through the approach of literature mining,thirty-three potential immune-related genes were screened from species such as Aedes aegypti and Anopheles gambiae,which have a close genetic relationship with Ae.albopictus.The protein—protein interaction(PPI)analysis is employed to explore the interaction relationship of the proteins encoded by genes.The alterations in mRNA expression levels of the relevant genes in DENV2-infected Ae.albopictus midgut were detected using the qRT-PCR method.Results The PPI results indicates that TLR and Spz of Ae.albopictus;Rel1,Rel2,DefC,Spz,PIWI,Ago2,DOME and HOP of Ae.aegypti;and Rel1,Rel2,CACT,STAT and DOME of An.gambiae exhibit PPI relationships.After Ae.albopictus was infected with DENV2,10 genes showed significant difference in expression.Ago3(7.39,P<0.05),DOMEa(1.63,P<0.01),DOMEb(21.29,P<0.001),and TLRb(1.61,P<0.05)were significantly up-regulated.Rel1(0.62,P<0.001),CACTl(0.65,P<0.001),Rel2a(0.65,P<0.01),Rel2b(0.24,P<0.001),GATAa(0.64,P<0.01)and DefC(0.28,P<0.05)were significantly down-regulated.Conclusions The concordance of Ae.albopictus with Ae.aegypti was higher than that with An.gambiae.DOMEb,Ago3,Rel2b and DefC,can serve as the preferred target genes for subsequent studies on DENV2 immune blockade.

The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*