Spatially clustered type I interferon responses at injury borderzones.

Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone1,2. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA. Cardiomyocyte-selective deletion of Irf3 abrogated IFNIC colonies, whereas mice lacking Irf3 in fibroblasts, macrophages, neutrophils or endothelial cells, Ccr2-deficient mice or plasmacytoid-dendritic-cell-depleted mice did not. Interferons blunted the protective matricellular programs and contractile function of borderzone fibroblasts, and increased vulnerability to pathological remodelling. In mice that died after myocardial infarction, IFNIC colonies were immediately adjacent to sites of ventricular rupture, while mice lacking IFNICs were protected from rupture and exhibited improved survival3. Together, these results reveal a pathological borderzone niche characterized by a cardiomyocyte-initiated innate immune response. We suggest that selective inhibition of IRF3 activation in non-immune cells could limit ischaemic cardiomyopathy while avoiding broad immunosuppression.

Coherent control of an optical tweezer phonon laser.

The creation and manipulation of coherence continues to capture the attention of scientists and engineers. The optical laser is a canonical example of a system that, in principle, exhibits complete coherence. Recent research has focused on the creation of coherent, laser-like states in other physical systems. The phonon laser is one example where it is possible to amplify self-sustained mechanical oscillations. A single mode phonon laser in a levitated optical tweezer has been demonstrated through appropriate balance of active feedback gain and damping. In this work, coherent control of the dynamics of an optical tweezer phonon laser is used to share coherence between its different modes of oscillation, creating a multimode phonon laser. The coupling of the modes is achieved by periodically rotating the asymmetric optical potential in the transverse focal plane of the trapping beam via trap laser polarization rotation. The presented theory and experiment demonstrate that coherence can be transferred across different modes of an optical tweezer phonon laser, and are a step toward using these systems for precision measurement and quantum information processing.

Experimental Verification of Demon-Involved Fluctuation Theorems.

The limit of energy saving in the control of small systems has recently attracted much interest due to the concept refinement of the Maxwell demon. Inspired by a newly proposed set of fluctuation theorems, we report the first experimental verification of these equalities and inequalities in an ultracold ^{40}Ca^{+} ion system, confirming the intrinsic nonequilibrium in the system due to involvement of the demon. Based on elaborately designed demon-involved control protocols, such as the Szilard engine protocol, we provide experimentally quantitative evidence of the dissipative information and observe tighter bounds of both the extracted work and the demon's efficacy than the limits predicted by the Sagawa-Ueda theorem. Our results substantiate a close connection between the physical nature of information and nonequilibrium processes at the microscale, which help to further understand the thermodynamic characteristics of information and the optimal design of nanoscale and smaller systems.

Laser Excitation of the Th-229 Nucleus.

The 8.4 eV nuclear isomer state in Th-229 is resonantly excited in Th-doped CaF_{2} crystals using a tabletop tunable laser system. A resonance fluorescence signal is observed in two crystals with different Th-229 dopant concentrations, while it is absent in a control experiment using Th-232. The nuclear resonance for the Th^{4+} ions in Th:CaF_{2} is measured at the wavelength 148.3821(5) nm, frequency 2020.409(7) THz, and the fluorescence lifetime in the crystal is 630(15) s, corresponding to an isomer half-life of 1740(50) s for a nucleus isolated in vacuum. These results pave the way toward Th-229 nuclear laser spectroscopy and realizing optical nuclear clocks.

Dual-energy CT-based radiomics for predicting pathological grading of invasive lung adenocarcinoma.

AIMS: The purpose of the study was to build a radiomics model using Dual-energy CT (DECT) to predict pathological grading of invasive lung adenocarcinoma. MATERIALS AND METHODS: The retrospective study enrolled 107 patients (80 low-grade and 27 high-grade) with invasive lung adenocarcinoma before surgery. Clinical features, radiographic characteristics, and quantitative parameters were measured. Virtual monoenergetic images at 50kev and 150kev were reconstructed for extracting DECT radiomics features. To select features for constructing models, Pearson's correlation analysis, intraclass correlation coefficients, and least absolute shrinkage and selection operator penalized logistic regression were performed. Four models, including the DECT radiomics model, the clinical-DECT model, the conventional CT radiomics model, and the mixed model, were established. Area under the curve (AUC) and decision curve analysis were used to measure the performance and the clinical value of the models. RESULTS: The radiomics model based on DECT exhibited outstanding performance in predicting tumor differentiation, with an AUC of 0.997 and 0.743 in the training and testing sets, respectively. Incorporating tumor density, lobulation, and effective atomic number at AP, the clinical-DECT model showed a comparable performance with an AUC of 0.836 in both the training and testing sets. In comparison to the conventional CT radiomics model (AUC of 0.998 in the training and 0.529 in the testing set) and the mixed model (AUC of 0.988 in the training and 0.707 in the testing set), the DECT radiomics model demonstrated a greater AUC value and provided patients with a more significant net benefit in the testing set. CONCLUSIONS: In contrast to the conventional CT radiomics model, the DECT radiomics model produced greater predictive performance in pathological grading of invasive lung adenocarcinoma.

Optimizing the indication of initial radioiodine oncolytic treatment for metastatic differentiated thyroid cancer by diagnostic 131I scan.

AIM: As a classic theranostic radiopharmaceutical, radioiodine (131I) has been utilized in the management of differentiated thyroid cancer (DTC) for more than 8 decades, and the refinement of its clinical practice has been raised recently. This study was conducted to evaluate the efficiency of a diagnostic (Dx) 131I scan in optimizing the indication of initial radioiodine oncolytic treatment (ROT) for metastatic DTC by predicting therapeutic outcomes. RESULTS: A total of 100 patients (Dx positive, n=29; Dx negative, n=71) were eligible for patient-based analysis. The matching rate was 83.0% between the Dx and the post-therapeutic scans (kappa = 0.648, P<0.001). The biochemical remission rate and structural shrinkage rate induced by the initial ROT in the Dx-positive group were, respectively, greater than those in the Dx-negative group (83.3% vs. 17.4%, P<0.001; 37.9% vs. 4.2%, P<0.001). Notably, the predictive values of positive Dx scans for ROT responsiveness and negative Dx scans for ROT nonresponsiveness reached up to 89.7% and 84.5%, respectively. CONCLUSION: This Dx scan approach seems viable in characterizing the 131I-avidity of metastatic DTC and plays a pivotal role in optimizing the indication of initial ROT for metastatic DTC.

Improving image quality of triple-low-protocol renal artery CT angiography with deep-learning image reconstruction: a comparative study with standard-dose single-energy and dual-energy CT with adaptive statistical iterative reconstruction.

AIM: To investigate the improvement in image quality of triple-low-protocol (low radiation, low contrast medium dose, low injection speed) renal artery computed tomography (CT) angiography (RACTA) using deep-learning image reconstruction (DLIR), in comparison with standard-dose single- and dual-energy CT (DECT) using adaptive statistical iterative reconstruction-Veo (ASIR-V) algorithm. MATERIALS AND METHODS: Ninety patients for RACTA were divided into different groups: standard-dose single-energy CT (S group) using ASIR-V at 60% strength (60%ASIR-V), DECT (DE group) with 60%ASIR-V including virtual monochromatic images at 40 keV (DE40 group) and 70 keV (DE70 group), and the triple-low protocol single-energy CT (L group) with DLIR at high level (DLIR-H). The effective dose (ED), contrast medium dose, injection speed, standard deviation (SD), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of abdominal aorta (AA), and left/right renal artery (LRA, RRA), and subjective scores were compared among the different groups. RESULTS: The L group significantly reduced ED by 37.6% and 31.2%, contrast medium dose by 33.9% and 30.5%, and injection speed by 30% and 30%, respectively, compared to the S and DE groups. The L group had the lowest SD values for all arteries compared to the other groups (p<0.001). The SNR of RRA and LRA in the L group, and the CNR of all arteries in the DE40 group had highest value compared to others (p<0.05). The L group had the best comprehensive score with good consistency (p<0.05). CONCLUSIONS: The triple-low protocol RACTA with DLIR-H significantly reduces the ED, contrast medium doses, and injection speed, while providing good comprehensive image quality.

Three-dimensional analysis of mandibular morphology asymmetry and temporomandibular joint position in patients with unilateral Brodie bite.

OBJECTIVE: Previous studies have shown unilateral posterior crossbite is associated with mandibular asymmetry in morphology and position. However, it remains unclear whether unilateral Brodie bite plays a similar role in mandibular development. Therefore, this study aims to investigate the morphological and positional symmetry of mandibles in patients with unilateral Brodie bite by three-dimensional anaylsis. METHODS: Fourteen patients with unilateral Brodie bite (mean age 18.43 ± 4.24 years) and fourteen sex- and age-matched patients with normal occlusion (mean age 18.07 ± 5.48 years) underwent cone-beam computed tomography (CBCT) scans. 3D surface mesh models of their mandibles were established using Mimics Research 19.0. The surface matching percentage was compared between the original and mirrored mandible by Geomagic Control X software. Furthermore, the dimension and position of the temporomandibular joint (TMJ) were determined for both groups using InVivoDental 5.0. RESULTS: For surface-to-surface deviation analysis, the percentage of mismatch in patients with unilateral Brodie bite was significantly higher than the control group at ±0.50 mm, ±0.75 mm, and ±1.00 mm tolerance (P < .001). In patients with unilateral Brodie syndrome, the condyles on the scissors-bite side showed a significantly more anterior position (P = .03), greater medial inclination (P < .01), and larger posterior TMJ space (P = .01) than the non-scissors-bite side. CONCLUSION: Patients with unilateral Brodie bite exhibit a more asymmetrical mandibular morphology, with a greater anterior condylar position and posterior joint space on the scissors-bite side, indicating that early diagnosis and treatment may be necessary for patients with unilateral Brodie bite.

[Effects of normal mitochondrial transplantation on proliferation, apoptosis and stemness of triple-negative breast cancer cells].

Objectives: To observe the mitochondrial morphology of normal and triple-negative breast cancer cells, extract mitochondria from normal cells, and investigate the effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of triple-negative breast cancer cells. Methods: The morphology of mitochondria was observed by transmission electron microscope. Mitochondria were extracted by mitochondrial extraction kit, mitochondrial protein was identified by western blot, and mitochondrial activity was detected by mitochondrial membrane potential detection kit. MitoTracker Green or MitoTracker Deep Red fluorescent probes were used to label the mitochondria of living cells, and the degree of mitochondria entering LTT cells was observed by confocal laser microscopy at 12, 24, and 96 hours. The effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of breast cancer cells were examined by CCK8, colony formation assay, flow cytometry, and sphere formation assay after 24 hours of mitochondrial transplantation. Results: The mitochondria of normal cells were rod-shaped or elongated, while the mitochondria of triple-negative breast cancer cells were swollen and vacuolated. Western blot results showed that cytochrome c oxidase subunit I (MT-CO1) protein encoded by mitochondria was present in the isolated mitochondria. The content of heat shock protein 60 (HSP60) was higher in mitochondria than that in cytoplasm. The result of the multi-mode microplate reader showed that the content of mitochondrial J-aggregates/monomer was 1.67±0.06, which was significantly higher than 0.35±0.04 of the control group (P＜0.001). Exogenous mitochondria were observed in LTT cells at 12, 24, and 96 hours after mitochondrial transplantation. The results of the CCK8 experiment showed that OD450 of LTT cells was 0.27±0.13 after 48 hours transplantation, which was lower than 0.62±0.36 of the control group (P=0.023). The OD450 of MDA-MB-468 cells was 0.30±0.03, which was lower than 0.65±0.10 of the control group (P=0.004). After 120 hours of mitochondrial transplantation, OD450 in both groups was still significantly lower than that in the control group (P＜0.01). The number of clones formed by mitochondrial transplantation of LTT cells was 21.33±7.31, which was lower than 35.22±13.59 of the control group (P=0.016). Flow cytometry showed that the early apoptosis rate of LTT cells was (30.07±2.15)% after 24 hours of mitochondrial transplantation, which was higher than 2.07±1.58 of the control group (P＜0.001). The proportion of early apoptosis in MDA-MB-468 cells was 24.47%±5.22%, which was higher than (7.83±2.06)% in the control group (P=0.007). In addition, the number of mitochondria transplanted LTT cells into the cell sphere was 46.25±5.40, which was significantly lower than 62.58±6.43 of the control group (P＜0.001). Conclusion: Normal mitochondria can enter triple-negative breast cancer cells by co-culture, inhibit the proliferation and stemness of triple-negative breast cancer cells, and promote the apoptosis of triple-negative breast cancer cells.

[Establishment of acute graft-versus-host disease model after non-myeloablative haploidentical peripheral blood stem cell transplantation in aged mice].

Objective: To establish an acute graft-versus-host disease (aGVHD) model in aged mice after non-myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PSCT). Methods: C57BL/6 (H-2b) male mice aged 6-8 weeks were used as donor mice, and CB6F1 (H-2b×d) female mice aged 14-16 months were used as recipient mice. The donor mice were injected subcutaneously with rehuman granulocyte-colony stimulating factor (rhG-CSF) 5 days before transplantation for hematopoietic stem cell mobilization.The recipient mice were divided into control group (CG), spleen cell low-dose group (SL), spleen cell medium-dose group (SM) and spleen cell high-dose group (SH) according to random number table method, with 16 rats in each group, all of which received total linear accelerator X-ray irradiation (TBI) with a total dose of 6 Gy. Peripheral blood mononuclear cells (PBMC) and spleen cells of different doses (0.5×107/each, 1.0×107/each and 2.0×107/each in SL group, SM group and SH group, respectively) were transfused through the tail vein within 4 hours after TBI, and only the same amount of normal saline was transfused in CG group. After transplantation, the survival and weight changes of mice in each group were observed for 30 days, and the changes of blood routine were monitored regularly. Mice peripheral blood was collected 21 days after transplantation to detect the chimerism rate of the donor. Hematoxylin-eosin staining was performed on the skin, liver and colon of mice 21 days after transplantation to analyze the histopathological changes of aGVHD target organs. Results: All the mice in each group were successfully transplanted. After TBI, the weight and activity of mice in all groups decreased, and the phenomenon of bone marrow suppression appeared. During the observation period, all mice in CG group and SL group survived, 3 mice in SM group died with survival time of (26.0±5.8) days, and 6 mice in SH group died with survival time of (20.9±7.3) days. The body weight of mice in SH group was lower than that in CG group, SL group and SM group 21days after transplantation [(25.0±0.7), (25.5±0.4), (25.0±1.4) vs (20.8±0.8) g, all P<0.05]. Compared with CG group, SL group and SM group, the levels of leukocyte, erythrocyte, hemoglobin and platelet in SH group decreased 21 days after transplantation (all P<0.05). There was no significant difference in donor chimerism rate among SL group, SM group and SH group [(95.8%±0.8%), (95.5%±1.4%) and (95.1%±1.3%), respectively, all P>0.05]. Compared with CG group, SL group and SM group, the tissue structure of aGVHD target organs in SH group was severely damaged, with a large number of inflammatory cells infiltratedand higher histopathological scores than SL group and SM group (all P<0.05). Conclusion: For aging CB6F1 mice, after 6 Gy TBI pretreatment with linear accelerator X-ray, PBMC (1×107/each) and spleen cells (2.0×107/each) were injected to successfully induce aGVHD model after non-myelablative haplo-PSCT.

[HVPG minimally invasive era: exploration based on forearm venous approach].

Objective: The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach. Methods: Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis. Results: A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score (r = 0.47, P = 0.002), albumin-bilirubin score (r = 0.37, P = 0.001), Lok index (r = 0.36, P = 0.02), liver stiffness (r = 0.58, P = 0.01), and spleen stiffness (r = 0.77, P = 0.01), while negatively correlated with albumin (r = -0.42, P = 0.006). Conclusion: The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

[Advances in warfarin's anticoagulation therapy in Chinese population after mechanical valve replacement].

Warfarin is an irreplaceable oral anticoagulant for patients with mechanical heart valves, the stable pharmacogenetic-based warfarin dose prediction algorithms have improved the effectiveness and safety of warfarin anticoagulation therapy. Genetic factors are the main factors affecting the stable dose of warfarin. Single nucleotide polymorphisms such as VKORC1 and CYP2C9 affect the anticoagulation effect of warfarin through pharmacodynamic or pharmacokinetic pathways. Age, body surface area, combined use of drugs, and other nongenetic factors also affect the stable dose of warfarin. Previously published algorithms for warfarin dose prediction included mainly the white race, and most algorithms were constructed using traditional multiple linear regression. However, domestic studies have used machine learning methods to construct warfarin dose prediction algorithms based on the Chinese Han post-mechanical valve replacement population and have achieved better prediction efficiency. This article reviews the advances of warfarin anticoagulation influencing factors and the clinical application of stable dose prediction algorithms.

[Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer].

Objective: To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC). Methods: This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9(M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)µg/L(range: 1.4 to 13.4 µg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient's death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results: After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the "standardised pathology protocol" and the "1 mm" principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion: Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

[Clinical observation of the intraocular distribution characteristics of indocyanine green after epiretinal membrane peeling using a fluorescence detection system developed in Python].

Objective: To utilize a Python-based fluorescence area detection system to observe and quantitatively analyze the intraocular distribution characteristics and metabolic patterns of Indocyanine Green (ICG) following epiretinal membrane peeling. Methods: A prospective case series study was conducted on patients with idiopathic epiretinal membrane undergoing vitrectomy at West China Hospital of Sichuan University from March 2019 to March 2021. ICG staining was applied during surgery for peeling the epiretinal membrane and internal limiting membrane. Patients were followed up at 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively, with assessments including best-corrected visual acuity, intraocular pressure, fundus photography, near-infrared fundus fluorescence imaging (NIR-FF), and optical coherence tomography (OCT). A Python-based ICG intraocular metabolism detection system was developed to measure the residual area of ICG fluorescence on NIR-FF, predict the ICG metabolic pattern equation, and correlate it with postoperative visual acuity and peripapillary retinal nerve fiber layer thickness. Results: A total of 64 patients (64 eyes) were included, with an average age of 64.6±8.4 years, including 25 males (39.1%) and 39 females (60.9%). Preoperative NIR-FF images showed no ICG strong fluorescence. At 1 week postoperatively, diffuse ICG strong fluorescence appeared in the posterior pole, and the internal limiting membrane removal area exhibited a ring-like weak fluorescence. Over time, ICG strong fluorescence was observed along the vascular arch and nerve fiber trajectory, gradually diminishing toward the optic disc, with residual ICG fluorescence still visible at the optic disc at 1 year. The Python-based ICG fluorescence area detection system effectively measured intraocular residual ICG area. A predictive equation for the 12-month residual ICG area was constructed through linear regression analysis (Residual ICG area=0.22 × Residual ICG area at 6 months, R2=16%, P=0.002). Except for a negative correlation between the ICG residual area at 1 month and postoperative visual acuity (P=0.017, r=-0.195), no correlation was found between intraocular ICG fluorescence residual area and postoperative visual acuity or peripapillary retinal nerve fiber layer thickness at other follow-up times (all P>0.05). Conclusions: In patients with idiopathic epiretinal membrane undergoing ICG staining for internal limiting membrane peeling, ICG exhibits characteristic metabolic processes in the eye, with strong fluorescence along the vascular arch and nerve fiber trajectory, gradually converging toward the optic disc over time. The Python-based ICG fluorescence area detection system provides a clear display of the intraocular distribution characteristics of ICG after epiretinal membrane peeling and serves as a tool for predicting the metabolic patterns of ICG in the eye.

[Myocardial scar area predicts major adverse cardiovascular events after coronary artery bypass grafting in patients with ischemic cardiomyopathy].

Objective: To investigate the value of myocardium scar area in predicting adverse cardiovascular events (MACEs) after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM). Methods: The first part of this study was a retrospective study. Patients diagnosed with ICM and undergoing CABG surgery at Beijing Anzhen Hospital, Capital Medical University from January 2017 to December 2022 were enrolled as the discovery cohort. All patients underwent cardiac magnetic resonance-late gadolinium enhancement (CMR-LGE) before surgery. According to the occurrence of postoperative MACEs, the patients were divided into MACEs group and MACEs-free group. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. The primary endpoint was postoperative MACEs. Univariate and multifactor regression analyses were used to analyze the risk factors for MACEs. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive efficacy and optimal cut-off value of myocardial scar area for endpoint events. The second part of this study was a prospective study. Patients with ICM who received CABG at Beijing Anzhen Hospital, Capital Medical University from January 2023 to June 2023 were enrolled as a validation cohort, and were divided into MACEs group and MACEs-free group according to whether MACEs occurred after surgery. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. Verify the reliability of the cut-off value obtained by ROC curve in the validation cohort. Results: A total of 120 patients with ICM (30 patients in MACEs group and 90 patients in MACEs-free group), aged (61.6±8.7) years, including 93 males, were included in the discovery cohort. A total of 22 ICM patients (5 patients in MACEs group and 17 patients in MACEs-free group), aged (59.5±8.2) years, including 18 males, were included in the validation cohort. Multivariate Cox regression showed that myocardial scar area (HR=1.258, 95%CI 1.096-1.444, P=0.001) was an independent risk factor for the primary endpoint event. The area under ROC curve of myocardial scar area for predicting postoperative MACEs was 0.90 (95%CI 0.83-0.95), and myocardial scar area≥36.0% was the optimal cut-off value for predicting postoperative MACEs, and its sensitivity, specificity and accuracy were 96.7%, 72.2% and 78.3%, respectively. In the validation cohort, the sensitivity, specificity and accuracy of myocardial scar area in predicting postoperative MACEs in patients with ICM after CABG were 80.0%, 82.4% and 81.8%, respectively. Conclusion: Myocardial scar area is an independent risk factor for MACEs after CABG in patients with ICM, and myocardial scar area≥36.0% is the optimal cut-off value for predicting MACEs after CABG. Myocardial scar area can help to identify patients at high risk of surgery and provide a basis for risk stratification of patients.

New Limits on Exotic Spin-Dependent Interactions at Astronomical Distances.

Exotic spin-dependent interactions involving new light particles address key questions in modern physics. Interactions between polarized neutrons (n) and unpolarized nucleons (N) occur in three forms: g_{S}^{N}g_{P}^{n}σ·r, g_{V}^{N}g_{A}^{n}σ·v, and g_{A}^{N}g_{A}^{n}σ·v×r, where σ is the spin and g's are the corresponding coupling constants for scalar, pseudoscalar, vector, and axial-vector vertexes. If such interactions exist, the Sun and Moon could induce sidereal variations of effective fields in laboratories. By analyzing existing data from laboratory measurements on Lorentz and CPT violation, we derive new experimental upper limits on these exotic spin-dependent interactions at astronomical ranges. Our limits on g_{S}^{N}g_{P}^{n} surpass the previous combined astrophysical-laboratory limits, setting the most stringent experimental constraints to date. We also report new constraints on vector-axial-vector and axial-axial-vector interactions at astronomical scales, with vector-axial-vector limits improved by ∼12 orders of magnitude. We extend our analysis to Hari Dass interactions and obtain new constraints.

Rheumatoid arthritis and the risk of major cardiometabolic diseases: a Mendelian randomization study.

OBJECTIVE: Rheumatoid arthritis (RA) is suggested to be implicated in the development of cardiometabolic diseases. We conducted a Mendelian randomization (MR) study to assess potential causality for associations of RA with the risk of cardiometabolic diseases, including type 2 diabetes (T2D), coronary artery disease (CAD), and ischaemic stroke. METHOD: Seventy independent single-nucleotide polymorphisms (SNPs) associated with RA were identified as instrumental variables from a genome-wide association study (GWAS) of 58 284 European subjects. Summary-level data for the associations of the 70 genetic variants with T2D, CAD, and ischaemic stroke were taken from three GWASs with a total of 1 529 131 participants. Inverse-variance weighted (IVW) MR was used in the main analyses. RESULTS: The main IVW MR analysis showed that genetically determined RA was associated with higher risks of T2D [odds ratio (OR): 1.04, 95% confidence interval (CI) 1.02-1.05; p < 0.001] and CAD (OR: 1.02, 95% CI 1.00-1.03; p = 0.012), but not ischaemic stroke (OR: 1.00, 95% CI 0.99-1.02; p = 0.961). Sensitivity analyses with multiple MR methods confirmed these associations. MR-Egger regression showed no evidence of pleiotropy in the association between genetically determined RA and the risk of T2D, CAD, and ischaemic stroke. Leave-one-out sensitivity analysis showed that the association between genetically determined RA and the risk of T2D, CAD, and ischaemic stroke was not driven by any individual SNP. CONCLUSION: Genetically determined RA was associated with increased risks of T2D and CAD, suggesting that RA plays a crucial role in the pathogenesis of T2D and CAD.

Androgens in endometrial carcinoma: the killer or helper?

PURPOSE: The aim of this review is to discuss the role of androgens in the progression of endometrial carcinoma (EC) with particular focus on the different kinds of androgenic hormones, androgen receptor (AR) and intracrine androgen metabolism. METHODS: A comprehensive literature search within PubMed was performed. Selected publications related to androgens and EC were reviewed. RESULTS: There are different kinds of androgenic hormones, and different kinds of androgens may have different effects. Elevated androgens (especially testosterone) have been associated with an increased EC risk in postmenopausal women. 5α-reductases (5α-Reds) and 17ß-hydroxysteroid dehydrogenase type 2 (17ßHSD2) pathway may inhibit the progression of EC mediated by dihydrotestosterone (DHT), but aromatases stimulate further progression of EC. The most of studies accessing the prognostic value of AR have found that AR expression may be a favorable prognostic indicator. CONCLUSION: Androgens may have both oncogenic and tumor suppressive roles. Androgen-specific biases in metabolism and the expression of AR may contribute to the different prognosis of patients with EC.

Vitamin D levels in the assessment of Crohn's disease activity and their relation to nutritional status and inflammation.

BACKGROUND: Crohn's disease (CD) is frequently associated with malnutrition, inflammation and a deficiency of vitamin D (VD) with the relationships between these symptoms being poorly defined. VD is a modulator of the immune system and is associated with the onset of CD and disease activity. The level of serum VD may have potential in the assessment of CD activity. This study aimed to evaluate the relationships between VD, nutritional status and inflammation, and to identify more accurate VD thresholds. METHODS: The study included 76 outpatients with CD diagnosed between October 2018 and October 2020 and 76 healthy volunteers. Levels of serum 25(OH)D and nutritional indicators, as well as biochemical and disease activity assessments, were conducted. RESULTS: Patients with CD and healthy participants were found to differ significantly in their 25(OH)D levels as well in levels of nutritional and inflammatory indicators. The optimal VD cut-off value was found to be 46.81 nmol/L for CD development and 35.32 nmol/L for disease activity. Levels of 25(OH)D were correlated with both nutritional status and inflammation. CONCLUSIONS: The VD level is likely to be a useful additional tool in the evaluation of CD patients and predicting the disease activity and clinical response. The VD level may relate both to the nutritional status and levels of inflammation in CD patients, and disease progression.

miR-199-3p suppresses cellular migration and viability and promotes progesterone production in goose ovarian follicles before selection through regulating ITGB8 and other ECM-related genes.

1. The extracellular matrix (ECM) constitutes the basal lamina and the area between follicular cells. Remodelling the ECM is believed to be a key event in follicular development, especially during selection, and plays an important role in cell migration, survival, and steroidogenesis. miR-199-3p is differentially expressed in the goose granulosa layer during follicular selection and is reported to play a primary role in inhibiting cell migration and invasion. Nevertheless, the effect of miR-199-3p on ovarian follicles and its role in follicular cellular migration is not understood.2. In this study, qRT-PCR assays revealed that miR-199-3p was differentially expressed in the granulosa layer from goose ovarian follicles before and after follicular selection. Additionally, miR-199-3p overexpression in cultured granulosa cells (GCs) from goose pre-hierarchical follicles significantly suppressed cell viability and migration. It elevated the concentration of progesterone and the expression of key progesterone production genes. Furthermore, miR-199-3p overexpression in the GCs of goose pre-hierarchical follicles inhibited the expression of ECM-related genes (ITGB8, MMP9 and MMP15) yet promoted the expression of another two ECM-related genes (COL4A1 and LAMA1). Finally, dual-fluorescence reporter experiments on 293T cells established the direct targeting of ECM gene ITGB8 by miR-199-3p.3. In conclusion, miR-199-3p may participate in granulosa cell migration, viability, and steroidogenesis in goose ovarian follicles before selection by modulating ITGB8 and other ECM-related genes.