Pre-encoded responsiveness to type I interferon in the peripheral immune system defines outcome of PD1 blockade therapy.

Type I interferons (IFN-Is) are central regulators of anti-tumor immunity and responses to immunotherapy, but they also drive the feedback inhibition underlying therapeutic resistance. In the present study, we developed a mass cytometry approach to quantify IFN-I-stimulated protein expression across immune cells and used multi-omics to uncover pre-therapy cellular states encoding responsiveness to inflammation. Analyzing peripheral blood cells from multiple cancer types revealed that differential responsiveness to IFN-Is before anti-programmed cell death protein 1 (PD1) treatment was highly predictive of long-term survival after therapy. Unexpectedly, IFN-I hyporesponsiveness efficiently predicted long-term survival, whereas high responsiveness to IFN-I was strongly associated with treatment failure and diminished survival time. Peripheral IFN-I responsive states were not associated with tumor inflammation, identifying a disconnect between systemic immune potential and 'cold' or 'hot' tumor states. Mechanistically, IFN-I responsiveness was epigenetically imprinted before therapy, poising cells for differential inflammatory responses and dysfunctional T cell effector programs. Thus, we identify physiological cell states with clinical importance that can predict success and long-term survival of PD1-blocking immunotherapy.

A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Very-high-frequency oscillations in the main peak of a magnetar giant flare.

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.

All is not lost: learning from 9p21 loss in cancer.

The cancer research community continues to search for additional biomarkers of response and resistance to immune checkpoint treatment (ICT). The ultimate goal is to direct the use of ICT in patients whose tumors are most likely to benefit to achieve a refinement that is equivalent to that of a genotype-matched targeted treatment. Dissecting the mechanisms of ICT resistance can help us characterize ICT nonresponders more efficiently. In this opinion, we argue that there may be additional knowledge gained about immune evasion in cancer by analyzing the loss of the human 9p21.3 locus; as an example, we highlight findings of 9p21.3 loss from the investigator-initiated, pan-cancer INSPIRE study, in which patients were treated with pembrolizumab (anti-PD-1 antibody) ICT.

Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis.

AIM: To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). MATERIALS AND METHODS: One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40% ≤ LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. RESULTS: Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. CONCLUSION: LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

One-pot heat-up synthesis of short-wavelength infrared, colloidal InAs quantum dots.

III-V colloidal quantum dots (QDs) promise Pb and Hg-free QD compositions with which to build short-wavelength infrared (SWIR) optoelectronic devices. However, their synthesis is limited by the availability of group-V precursors with controllable reactivities to prepare monodisperse, SWIR-absorbing III-V QDs. Here, we report a one-pot heat-up method to synthesize ∼8 nm edge length (∼6.5 nm in height) tetrahedral, SWIR-absorbing InAs QDs by increasing the [In3+]:[As3+] ratio introduced using commercially available InCl3 and AsCl3 precursors and by decreasing the concentration and optimizing the volume of the reducing reagent superhydride to control the concentration of In(0) and As(0) intermediates through QD nucleation and growth. InAs QDs are treated with NOBF4, and their deposited films are exchanged with Na2S to yield n-type InAs QD films. We realize the only colloidal InAs QD photoconductors with responsivity at the technologically important wavelength of 1.55 µm.

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma.

BACKGROUND AND OBJECTIVES: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. METHODS: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. RESULTS: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. CONCLUSIONS: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Sodium fluoride-induced autophagy of ameloblast-like cells via the p-ULk1/ATG13/LC3B pathway in vitro.

OBJECTIVE: To investigate the effects of sodium fluoride on the ameloblast and reveal the mechanism of dental fluorosis. MATERIALS AND METHODS: Mouse ameloblast-like cell line (ALC) cells were treated with various concentrations of NaF, and subjected to Incucyte, fluorescence immunoassay, transmission electron microscopy, reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot for autophagy examination, alkaline phosphatase and alizarin red staining for mineralization after osteogenic induction. RESULTS: NaF exerts a dose-dependent inhibitory effect on ALC cell growth. TEM and fluorescence immunoassay showed that 1.5 mM or higher concentrations of NaF could induce a fusion of lysosome and mitochondria, finally increasing the number of autophagosome. RT-qPCR and western blot showed that the upregulation of autophagy related gene 13 (ATG13), downregulation of phosphorylated Unc-51-like kinase 1 (p-ULK1) were found in NaF-induced autophagy of ALC cells. The knockdown of ATG13 could rescue it as well as the expression of p-ULK1 and LC3B. Besides, alizarin red staining showed that fluoride under these concentrations could promote the mineralization of ALC. CONCLUSIONS: The data show that fluoride in higher concentration can induce autophagy via the p-ULk1/ATG13/LC3B pathway of ALCs than lower ones promote mineralization in vitro, which provides insight into the function of NaF in the autophagy and mineralization of ameloblast.

The emergence of all-or-none retrieval of chunks in verbal serial recall.

People often subdivide a list into smaller pieces, called chunks. Some theories of serial recall assume memories are stored hierarchically, with all-or-none retrieval of chunks, but most mathematical models avoid hierarchical assumptions. Johnson (Journal of Verbal Learning and Verbal Behavior, 8(6), 725-731, 1969) found steep drops in errors following correct recalls (transitional-error probabilities) within putative chunks during multi-trial letter-list learning, and viewed this as evidence for all-or-none retrieval. Here we test whether all-or-none retrieval occurs in lists studied only once. In serial recall of six-word lists (Experiment 1), transitional-error probabilities were inconsistent with all-or-none retrieval, both when participants were instructed to subdivide and when temporal grouping induced subdivision. Curiously, the same analysis of previous temporally grouped nine-letter lists produced compelling evidence for all-or-none retrieval, which may result from recoding rather than the formation of chunks. In Experiment 2, participants were pre-trained on three-word chunks. For nine-word lists constructed from those trained chunks, transitional-error probabilities exhibited more pronounced evidence of all-or-none retrieval. Nearly all effects reversed with post-cued backward recall, suggesting mechanisms that play out over the course of recall rather than encoding of the list. In sum, subdivided lists do not result in hierarchical memories after a single study trial, although they may emerge in lists formed from chunks that are previously learned as such. This suggests a continuous transition from non-hierarchical subdivision of lists to all-or-none retrieval over the course of chunk formation.

Effects of 3-nitrooxypropanol (3-NOP, Bovaer®10) and whole cottonseed on milk production and enteric methane emissions from dairy cows under Swiss management conditions.

The objective of this study was to determine the potential effect and interaction of 3- nitrooxypropanol (3-NOP; Bovaer®) and whole cottonseed (WCS) on lactational performance, and enteric methane (CH4) emission of dairy cows. A total of 16 multiparous cows, including 8 Holstein Friesian (HF) and 8 Brown Swiss (BS) [224 ± 36 d in milk, 26 ± 3.7 kg milk yield], were used in a split-plot design, where the main plot was the breed of cows. Within each subplot, cows were randomly assigned to a treatment sequence in a replicated 4 × 4 Latin Square design with 2 × 2 factorial arrangements of treatments with 4, 24-d periods. The experimental treatments were: 1) Control (basal TMR), 2) 3-NOP (60 mg/kg TMR DM), 3) WCS (5% TMR DM), and 4) 3-NOP + WCS. The treatment diets were balanced for ether extract, crude protein, and NDF contents (4%, 16%, and 43% of TMR DM, respectively). The basal diets were fed twice daily at 0800 and 1800 h. Dry matter intake (DMI) and milk yield were measured daily, and enteric gas emissions were measured (using the GreenFeed system) during the last 3 d of each 24-d experimental period when animals were housed in tie stalls. There was no difference in DMI on treatment level, whereas the WCS treatment increased ECM yield and milk fat yield. There was no interaction of 3-NOP and WCS for any of the enteric gas emission parameters, but 3-NOP decreased CH4 production (g/d), CH4 yield (g/kg DMI), and CH4 intensity (g/kg ECM) by 13, 14 and 13%, respectively. Further, an unexpected interaction of breed by 3-NOP was observed for different enteric CH4 emission metrics: HF cows had a greater CH4 mitigation effect compared with BS cows for CH4 production (g/d; 18 vs. 8%), CH4 intensity (g/kg MY; 19% vs. 3%) and CH4 intensity (g/kg ECM; 19 vs. 4%). Hydrogen production was increased by 2.85 folds in HF and 1.53 folds in BS cows receiving 3-NOP. Further, there was a 3-NOP ' Time interaction for both breeds. In BS cows, 3-NOP tended to reduce CH4 production by 18% at around 4 h after morning feeding but no effect was observed at other time points. In HF cows, the greatest mitigation effect of 3-NOP (29.6%) was observed immediately after morning feeding and it persisted at around 23% to 26% for 10 h until the second feed provision, and 3 h thereafter, in the evening. In conclusion, supplementing 3-NOP at 60 mg/kg DM to a high fiber diet resulted in 18 to 19% reduction in enteric CH4 emission in Swiss Holstein Friesian cows. The lower response to 3-NOP by BS cows was unexpected and has not been observed in other studies. These results should be interpreted with caution due to low number of cows per breed. Lastly, supplementing WCS at 5% of DM improved ECM and milk fat yield but did not enhance CH4 inhibition effect of 3-NOP of dairy cows.

Burden of lung cancer attributed to particulate matter pollution in China: an epidemiological study from 1990 to 2019.

OBJECTIVES: The aim of this study was to examine the disease burden of lung cancer attributable to particulate matter (PM2.5) pollution in China from 1990 to 2019. STUDY DESIGN: Data from the Global Burden of Disease Study 2019 were used to estimate the disease burden of tracheal, bronchus and lung cancer attributed to PM2.5 over time in China. METHODS: Joinpoint regression models were applied to disability-adjusted life years (DALYs) to assess the time trends and estimate the impact of PM2.5 on the overall disease burden of lung cancer. Furthermore, age-period-cohort models were conducted to assess the relationships between lung cancer DALYs attributed to PM2.5 exposure and age, calendar period and birth cohort trends in China from 1990 to 2019. RESULTS: Lung cancer DALYs attributable to household air pollution from solid fuels decreased with an average annual percent change (AAPC) of 2.9 % per 100,000 population, while those attributable to ambient particular matter pollution (APE) increased (AAPC: -4.7 % per 100,000 population) over the past 30 years. The burden of lung cancer in terms of DALYs in males was higher than in females, and it demonstrated an age-dependent increase. The period and cohort effects also had significant impacts on the DALYs rates of lung cancer attributable to APE, indicating an overall increase in lung cancer DALYs for all age groups in each year. CONCLUSIONS: This study highlights the need for effective strategies to reduce PM2.5 exposure in China, particularly from outdoor sources. Gender differences and age, period and cohort effects observed in the study provide valuable insights into long-term trends of lung cancer burden attributed to PM2.5.

Immediate Weightbearing after Modified Lapidus Arthrodesis Using a Medial Plate: A Retrospective Descriptive Cohort Study.

The modified Lapidus procedure has emerged as a versatile solution for various pedal pathologies, particularly hallux abducto valgus. There have been numerous modifications over time regarding fixation techniques, joint preparation methods, graft utilization, and weightbearing protocols. However, concerns persist regarding prolonged non-weightbearing postoperatively, prompting the need for alternative approaches. This retrospective descriptive cohort analysis assessed the outcomes of 40 feet from 34 patients who underwent the modified Lapidus procedure with a medial plating system, aimed to evaluate immediate weightbearing outcomes on union rate, fixation-related complications, and functional outcomes. Among the 40 feet, findings showed a 95% (38/40) union rate within 6 months, with 2.5% (1/40) experiencing delayed union and 2.5% (1/40) facing fixation-related complications. There is a single case of malunion in the cohort. Additionally, statistically significant improvements were observed across all domains of the Manchester-Oxford Foot Questionnaire at p < .001. These findings suggest immediate weightbearing as a potential alternative to traditional non-weightbearing protocols. However, the study's retrospective nature and lack of a comparative group warrant cautious interpretation. Further research is essential to validate these findings and refine postoperative care protocols. By challenging conventional practices, this study underscores the complexity of optimizing patient outcomes in modified Lapidus procedure management. Tailored approaches and prospective investigations are imperative for establishing definitive guidelines and enhancing surgical techniques in this domain.

[Clinical characteristics and prognosis of primary aldosteronism associated with subclinical Cushing syndrome].

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.

[Study of appropriate cut-off for diagnosis of primary aldosteronism by seated saline suppression test based on liquid chromatography with tandem mass spectrometry].

Objective: To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS). Methods: In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value. Results: The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% (n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% (n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95%CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95%CI 78.88%-87.56%) and specificity was 60.50% (95%CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion: PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.

[Value of transnasal high-flow oxygen therapy and noninvasive ventilation in the management of acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) is one of the most common syndromes in the intensive care unit, with a high mortality and morbidity. Refractory hypoxia is the typical feature of ARDS, and improving hypoxia is the key to the treatment of ARDS. Due to the rapid progression of ARDS, invasive ventilation is usually used to improve hypoxia. But in recent years, with the extending of the understanding of ARDS and the development of non-invasive oxygen therapy, high flow nasal oxygen (HFNO) and non-invasive ventilation (NIV) are gradually used in ARDS. Therefore, we reviewed the role of HFNO and NIV in ARDS in this paper.

[Effects of Dapagliflozin on contrast-induced acute kidney injury in patients with type 2 diabetes mellitus underwent percutaneous coronary intervention].

Objective: To investigate the effect of Dapagliflozin, sodium-glucose cotransporter 2 inhibitor (SGLT2i), on contrast-induced acute kidney injury (CIAKI) in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention(PCI). Methods: A cohort study. The clinical data of 366 patients with coronary heart disease combined with T2DM who underwent PCI in the Department of Cardiology, Tianjin University Chest Hospital, from June 2021 to June 2022 were retrospectively analyzed, including 218 males and 148 females, aged (64.6±11.0) years old. According to whether the patients had used Dapagliflozin or not, the selected patients were divided into SGLT2i group(n=124) and control group(n=242). The changes in cardiac indicators, renal function, and inflammatory response indicators before and 72 hours after PCI treatment were analyzed and compared between the two groups. The incidence rate of CIAKI in the two groups was analyzed, and the influencing factors of CIAKI were analyzed by multivariate logistic regression. The major adverse cardiac events (MACE) were recorded during the follow-up period of the two groups, and Kaplan-Meier survival analysis and log-rank test were used to compare the differences in MACE occurrence between the two group. Results: The left ventricular ejection fraction (LVEF) of the SGLT2i group was lower than that of the control group, and the proportion of patients with LVEF<45% and CIAKI risk score were higher than those of the control group, with statistical significance (all P<0.05). 72 h after PCI treatment, ß-2 Microglobulin(ß-2MG), cystatin-C(Cys-C), and neutrophil gelatinase-associated lipocalin (NGAL) in both groups were all increased compared to those before PCI treatment, with statistical significance (all P<0.05).ß-2MG, Cys-C, and NGAL in SGLT2i group were all lower than those in the control group, with statistical significance(all P<0.05).The levels of interleukin-6(IL-6), hypersensitive C-reactive protein (hs-CRP), and malondialdehyde in both groups of patients increased compared to preoperative levels, while the levels of superoxide dismutase (SOD) decreased compared to preoperative levels, with statistical significance (all P<0.05). The levels of IL-6, hs-CRP, and malondialdehyde in the SGLT2i group were lower than those in the control group, while SOD was higher than that in the control group, with statistical significance (all P<0.05). Among all patients included, 34 cases experienced CIAKI (9.8%), and the incidence of CIAKI in the SGLT2i group was lower than that in the control group [4.8% (6/124) vs 11.6% (28/242),P=0.037]. Multivariate logistic regression analysis showed that the use of dapagliflozin was a protective factor for CIAKI in T2DM patients receiving PCI treatment (OR=0.321, 95%CI: 0.127-0.816, P=0.017). After a follow-up of 14.0 (12.0, 16.2) months, the incidence of MACE in SGLT2i group was lower than that in the control group (7.3% vs 12.8%, P=0.048). Conclusions: Dapagliflozin may reduce the risk of CIAKI and MACE in T2DM patients after PCI treatment. Its mechanism may be related to the anti-inflammatory and antioxidant effects of SGLT2i.

[The detecting value of virtual non-calcium technique of dual-energy CT for bone marrow edema around nontraumatic osteonecrosis of the femoral head].

Objective: To evaluate the value of virtual non-calcium (VNCa) technique of dual-energy CT (DECT) for detecting bone marrow edema (BME) around nontraumatic osteonecrosis of the femoral head (ONFH) using MRI as reference standard. Methods: Nontraumatic ONFH patients were prospectively studied in the Fourth Medical Center of Chinese PLA General Hospital from October 2022 to May 2023, and their MRI and DECT images were analyzed. The diagnostic efficiency of the subjective assessment of BME around ONFH by two radiologists in VNCa color-coded images were calculated using the MRI results as the reference standard. The BME ranges were compared between VNCa images and MRI. Traditional CT values and VNCa CT values were compared between normal bone marrow and BME. The receiver operator characteristic (ROC) curve was established based on the statistically different CT values, and the area under the curve (AUC) was calculated to find the threshold to distinguish normal bone marrow from BME and evaluate the diagnostic efficacy. Results: Thirty patients with ONFH were included, including 24 males and 6 females, aged (39±12) years. There were 18 bilateral hips and 12 unilateral hips, with a total of 48 hips, 34 hips of which showed BME on MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of subjective detection of BME on VNCa color coded maps by two physicians were 97.1% (33/34) and 97.1% (33/34), 92.9% (13/14) and 71.4% (10/14), 97.1% (33/34) and 89.2% (33/37), 92.9% (13/14) and 90.9% (10/11), 95.8% (46/48) and 89.6% (43/48), respectively, with no statistical difference (all P>0.05).There was no statistical difference between VNCa color-coded images and MRI in the BME range (P=1.160). The traditional CT values measured by the two radiologists were in good agreement with VNCa CT values, with intraclass correlation coefficient (ICC) of 0.948 (95%CI: 0.908-0.971) and 0.982 (95%CI: 0.969-0.990), respectively. The traditional CT value of normal bone marrow was (400.7±82.8) HU, and that of BME was (443.7±65.7) HU, with no statistical difference (P=0.062). The VNCa CT value of normal bone marrow was (-103.1±27.8) HU, and that of BME was (-32.9±25.7) HU, with statistical difference (P<0.001). The AUC of distinguishing normal bone marrow from BME based on VNCa CT value was 0.958 (95%CI: 0.857-0.995). The best cut-off value was -74.5 HU, and when the VNCa CT value was higher than -74.5 HU, the sensitivity, specificity, PPV, NPV and accuracy of diagnosing BME were 97.1%, 92.9%, 97.1%, 92.9% and 95.8 %, respectively. Conclusion: The VNCa technique of DECT has high efficiency in detecting BME around ONFH, and can accurately demonstrate the range of BME.

[Analysis of MTHFR gene variants in fifteen children with hyperhomocysteinemia].

The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia admitted to Hangzhou Children's Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2015 to September 2021 were analysed retrospectively. A total of 15 pediatric patients were included, including 10 males and 5 females, with onset ages ranging from 6 days to 18 years old and confirmed ages ranging from 40 days to 18 years old. One confirmed case was detected through neonatal screening, and the remaining 14 cases were all diagnosed through genetic diagnosis after onset. The main clinical manifestations were feeding difficulties, hypotonia, epilepsy, developmental delay. All patients had elevated levels of blood homocysteine, with blood homocysteine levels before and after treatment being (151.46±57.44) µmol/L and (69.96±32.88) µmol/L, significantly decreased after treatment compared with before treatment, with a statistically significant difference (P<0.001). The blood methionine level before the treatment was 9.40 (6.20, 11.96) µmol/L, normal or slightly decreased compared to the reference range. The methionine level returned to normal after treatment. A total of 19 MTHFR gene variants were detected, with 6 being unreported variants and 13 being known variants. c.1316C>T (p.L439P) was the most common variant(16.6%,5/30). All the patients had varied neurological damages, with 7 patients improved after metabolic therapy by carnitine and folinic acid, 8 patients experiencing developmental delay, and 1 patient experiencing frequent epilepsy. The clinical manifestations of MTHFR gene variation-related hyperhomocysteinemia are complex and variable. Early-onset and homozygous variants often have a poor prognosis. Blood homocysteine, blood amino acid analysis, serum total homocysteine assay and gene testing are helpful for early diagnosis.

[Rudimentary horn pregnancy: clinical analysis of 12 cases and literature review].

Objective: To investigate the clinical characteristics, treatments and fertility recovery of rudimentary horn pregnancy (RHP). Methods: The clinical data of 12 cases with RHP diagnosed and treated in Peking University Third Hospital from January 1, 2010 to December 31, 2022 were retrospectively analyzed. Clinical informations, diagnosis and treatments of RHP and the pregnancy status after surgery were analyzed. Results: The median age of 12 RHP patients was 29 years (range: 24-37 years). Eight cases of pregnancy in residual horn of uterus occurred in type Ⅰ residual horn of uterus, 4 cases occurred in type Ⅱ residual horn of uterus; among which 5 cases were misdiagnosed by ultrasound before surgery. All patients underwent excision of residual horn of uterus and affected salpingectomy. After surgery, 9 patients expected future pregnancy, and 3 cases of natural pregnancy, 2 cases of successful pregnancy through assisted reproductive technology. Four pregnancies resulted in live birth with cesarean section, and 1 case resulted in spontaneous abortion during the first trimester of pregnancy. No uterine rupture or ectopic pregnancy occurred in subsequent pregnancies. Conclusions: Ultrasonography could aid early diagnosis of RHP while misdiagnosis occurred in certain cases. Thus, a comprehensive judgment and decision ought to be made based on medical history, physical examination and assisted examination. Surgical exploration is necessary for diagnosis and treatment of RHP. For infertile patients, assisted reproductive technology should be applied when necessary. Caution to prevent the occurrence of pregnancy complications such as uterine rupture, and application of cesarean section to terminate pregnancy are recommended.

[Advances in the construction of risk prediction models for chronic kidney failure].

Chronic kidney disease (CKD) is a major public health problem worldwide. When CKD patients progress to the stage of kidney failure, kidney replacement therapy (KRT) or conservative treatment (palliative or non-dialysis treatment) will be needed. The risk prediction models of chronic kidney failure have been developed in recent years. These models, focusing on demographic indicators, clinical indicators, and laboratory data, are used to predict the likelihood of progression to kidney failure and requiring KRT. This article will retrieve prediction models for chronic kidney failure as an outcome, demonstrate the current research progress, and hope that it may be helpful for the strategies of preventing chronic kidney failure.