Hepatic ischemia-reperfusion injury (HIRI) has been considered as an inevitable process of liver transplantation. Hepatocyte ferroptosis is a key factor in HIRI development, yet precise mechanism and potential therapies are still unclear. Here, we demonstrated a strong correlation between hepatocyte ferroptosis and the downregulation of poly(rC)-binding protein (PCBP2), which compromised the stability of antiporter system Xc^- (consisted of SL3A2/SLC7A11). Besides, inhibiting PCBP2 contributed to facilitating cofactor p300 to enhance the transcriptional activity of HIF1α, leading to the expression and secretion of HMGB1. Then, released HMGB1 from ferroptotic hepatocytes worsened M1 macrophage recruitment and immune response during HIRI. Additionally, acteoside (ACT) was shown to assist PCBP2 in stabilizing the mRNA stability of Slc3a2 and Slc7a11, as well as enhance the binding affinity of PCBP2-system Xc^-. Beyond that, ACT also supported PCBP2 to limit HMGB1-induced M1 macrophage recruitment through imposing restrictions on p300 and HIF1α. Furthermore, specific knockdown of PCBP2 in hepatocytes directly interposed the therapeutic efficacy of ACT on HIRI mice. In conclusion, ACT alleviated hepatocyte ferroptosis and HIRI via promoting PCBP2 to maintain the stability of system Xc^- and limit HIF1α/p300-HMGB1 signaling. These findings highlight the therapeutic benefits of ACT in treating HIRI and offer insights into innovative therapeutic strategies.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective To evaluate the polishing finish of four different polishing tools.Methods Fifty specimens were selected from suitable zirconia and randomly divided into 5 groups with 10 specimens in each group.Group A was the negative control group;Group B was the EVE group;Group C was the SHOFU group;Group D was the Toboom group,and Group E was the NAIS group.All specimens were subjected to surface roughness measurements after each level of treatment.One specimen in each group was randomly selected after each level of treatment and put into the vacuum coater for surface gold spraying,and then put into the scanning electron microscope for surface morphology observation after vacuuming.Results Final Ra value:The negative group((1.677±0.066)μm)＞SHOFU group((0.357±0.037)μm)＞EVE group((0.248±0.051)μm)＞Toboom group((0.115±0.039)μm)and NAIS group((0.123±0.029)μm).Scanning electron microscope observation showed that the deepest and longest scratches were left on the surface of the specimen with the diamond needle,and the surface of the specimen was gradually smoothed by using the polishing kit to treat the surfacein turn.The surface of the specimens polished by NAIS group and Toboom group had the least and shallow scratches under the mirror.Conclu-sion Toboom and NAIS zirconia polishing tools provide the best polishing results.

Objective:To corelate thromboelastography (TEG)-related parameters and D-dimer and fibrinogen levels with the severity of preeclampsia and pregnancy outcomes in patients with preeclampsia.Methods:A case-control study was conducted involving 92 patients with preeclampsia who received treatment at Northwest Women's and Children's Hospital between March 2022 and September 2023 (patient group) and 92 healthy pregnant women who underwent routine check-ups during the same period (control group). All participants underwent TEG tests, and D-dimer and fibrinogen levels were measured. Intergroup comparisons were performed, and patients were categorized based on the severity of their condition. TEG parameters and D-dimer and fibrinogen levels were compared among patients with varying severities of preeclampsia. TEG-related parameters were correlated with D-dimer and fibrinogen levels. Adverse pregnancy outcomes in the patient group were statistically analyzed, and risk factors for these adverse outcomes in women with preeclampsia were identified.Results:In the patient group, the R and K values were (3.06 ± 0.36) minutes and (1.21 ± 0.14) minutes, respectively, both of which were significantly lower than those in the control group [(5.44 ± 0.61) minutes, (1.79 ± 0.21) minutes, t = 32.22, 22.04, both P < 0.001]. The α angle, CI value, MA value, and D-dimer and fibrinogen levels in the patient group were (71.31 ± 7.63)°, (3.89 ± 0.41), (65.71 ± 7.01) mm, (2.22 ± 0.24) mg/L, and (4.51 ± 0.49) g/L, respectively, all of which were significantly higher than those in the control group [(64.85 ± 6.79)°, (2.19 ± 0.23), (58.96 ± 6.09) mm, (1.92 ± 0.21) mg/L, (3.75 ± 0.40) g/L, t = -6.06, -34.68, -6.97, -9.02, -11.52, all P < 0.001]. In the patient group, severe cases had significantly lower R and K values compared with mild cases, while the α angle, CI value, MA value, and D-dimer and fibrinogen levels were significantly higher in severe cases than in mild cases ( t = 11.06, 7.16, -8.01, -12.05, -3.91, -13.74, -8.269, all P < 0.001). In patients with preeclampsia, the R and K values were negatively correlated with D-dimer levels, and the R value was negatively correlated with fibrinogen level ( r = -0.504, -0.612, -0.493, all P < 0.05). In addition, the MA and CI values were positively correlated with D-dimer level, and the α angle was positively correlated with fibrinogen level ( r = 0.436, 0.534, 0.492, all P < 0.05). Among the participants, 41 women experienced adverse pregnancy outcomes. In patients with adverse pregnancy outcomes, the R and K values were (2.48 ± 0.25) minutes and (1.12 ± 0.14) minutes, which were significantly lower than those in patients without adverse pregnancy outcomes [(2.75 ± 0.29) minutes, (1.28 ± 0.13) minutes, t = 4.71, 5.67; both P < 0.001]. The α angle, CI value, MA value, and D-dimer and fibrinogen levels in patients with adverse pregnancy outcomes were (76.62 ± 8.01)°, (4.42 ± 0.46), (69.77 ± 7.06) mm, (2.57 ± 0.27) mg/L, and (4.97 ± 0.51) g/L, all of which were significantly higher than those in patients without adverse pregnancy outcomes [(67.04 ± 7.01)°, (3.46 ± 0.37), (62.45 ± 6.82) mm, (1.94 ± 0.21) mg/L, (4.14 ± 0.43) g/L, t = -6.11, -5.03, -11.09, -12.25, -8.46, all P < 0.001]. Logistic regression analysis indicated that R and K values were protective factors for adverse pregnancy outcomes ( OR < 1, P < 0.05), while MA value, α angle, CI value, and D-dimer and fibrinogen levels were independent risk factors ( OR > 1, P < 0.05). Conclusion:TEG-related parameters differ significantly between patients with preeclampsia and healthy pregnant women. These parameters are correlated with the severity of preeclampsia, as well as with D-dimer and fibrinogen levels. TEG-related parameters are risk factors for adverse pregnancy outcomes in patients with preeclampsia.

In recent years,the use of bioprosthetic mitral valves has been increasing,leading to a growing number of patients experiencing bioprosthesis degeneration,significantly impacting their quality of life.The high risk of reoperation has deprived many patients with mitral bioprosthesis degeneration of the opportunity for a second surgery.With the rapid development of interventional procedures in our country,transcatheter mitral valve-in-valve replacement is gradually being accepted by a large number of patients with bioprosthesis degeneration.We report a case of transcatheter mitral valve-in-valve replacement via transseptal puncture.The surgical plan was carefully formulated based on preoperative CT evaluation,and the patient underwent the procedure smoothly with no significant adverse events postoperatively.Transcatheter mitral valve-in-valve replacement may be a better alternative for patients at high risk of mitral bioprosthesis degeneration.

Coronary artery bypass grafting (CABG) is one of the most effective revascularization treatments for coronary heart disease. Secondary prevention strategies, which rely on antiplatelet and lipid-lowering drugs, are crucial after CABG to ensure the durability of revascularization treatment effects and prevent adverse cardiovascular and cerebrovascular events in the medium to long term. Previous research conducted by Professor Zhao Qiang's team from Ruijin Hospital of Shanghai Jiao Tong University, known as the DACAB study, indicated that dual antiplatelet therapy (DAPT, specifically ticagrelor+aspirin) after CABG can enhance venous graft patency. However, it remains uncertain whether DAPT can further improve the medium to long-term clinical outcomes of CABG patients. Recently, the team reported the medium to long-term follow-up results of the DACAB study, termed the DACAB-FE study, finding that DAPT administered after CABG can reduce the incidence of major cardiovascular events over five years and improve patients' medium to long-term clinical outcomes. This article will interpret the methodological highlights and significant clinical implications of the DACAB-FE study.

Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0～35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.

【Objective】 To compare the risk of generalization in patients with ocular myasthenia gravis (OMG) receiving or not receiving immunosuppressive treatment. 【Methods】 The data of patients with OMG registered in Tangdu Hospital of Air Force Military Medical University from January 1, 2015 to May 1, 2019 were reviewed; the patients were divided into treatment group and control group according to whether they had received immunosuppressive treatment. The multivariate Cox proportional hazards regression model analysis was used to compare the risk of generalization between the two groups of patients within 2 years of onset. Sensitivity analysis was used to evaluate the duration of immunosuppressive treatment and the risk of generalization under different immunotherapy regimens. By using stratified analysis, the consistency of the main results across different levels of subgroup factors was evaluated. 【Results】 A total of 702 OMG patients were collected. Of them 367 patients (52.3%) were included in the treatment group, with an average onset age of (50.54±15.1) years, and 159 (43.3%) being female. Another 335 patients (47.7%) were included in the control group, with an average age of (49.1±14.6) years, and 159 ones (47.5%) were female. A total of 28 cases (7.7%) in the treatment group and 106 cases (31.6%) in the control group developed generalization during the observation period. After multivariate-adjusted Cox model analysis, patients who had received immunosuppressive treatment had a significantly lower risk of generalization compared with the control group (HR=0.24; 95% CI: 0.15-0.37; P<0.001). Sensitivity analysis found that the longer the duration of immunosuppression, the lower the risk of generalization (HR=0.88; 95% CI: 0.85-0.91; P<0.001). Stratified analysis showed that immunosuppressive therapy reduced the risk of generalization in different subgroups of patients. 【Conclusion】 Early immunosuppressive treatment can significantly reduce the risk of generalization in patients with OMG.

OBJECTIVE: Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome). METHODS: We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period. RESULTS: Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated. CONCLUSION Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
Rats ; Animals ; Arsenic/toxicity* ; Fluorides ; RNA, Ribosomal, 16S/genetics* ; Rats, Sprague-Dawley ; Metabolome ; Microbiota

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*