Three-dimensional flat bands in pyrochlore metal CaNi2.

Electronic flat-band materials host quantum states characterized by a quenched kinetic energy. These flat bands are often conducive to enhanced electron correlation effects and emergent quantum phases of matter1. Long studied in theoretical models2-4, these systems have received renewed interest after their experimental realization in van der Waals heterostructures5,6 and quasi-two-dimensional (2D) crystalline materials7,8. An outstanding experimental question is if such flat bands can be realized in three-dimensional (3D) networks, potentially enabling new materials platforms9,10 and phenomena11-13. Here we investigate the C15 Laves phase metal CaNi2, which contains a nickel pyrochlore lattice predicted at a model network level to host a doubly-degenerate, topological flat band arising from 3D destructive interference of electronic hopping14,15. Using angle-resolved photoemission spectroscopy, we observe a band with vanishing dispersion across the full 3D Brillouin zone that we identify with the pyrochlore flat band as well as two additional flat bands that we show arise from multi-orbital interference of Ni d-electrons. Furthermore, we demonstrate chemical tuning of the flat-band manifold to the Fermi level that coincides with enhanced electronic correlations and the appearance of superconductivity. Extending the notion of intrinsic band flatness from 2D to 3D, this provides a potential pathway to correlated behaviour predicted for higher-dimensional flat-band systems ranging from tunable topological15 to fractionalized phases16.

Heterointerface effects in the electrointercalation of van der Waals heterostructures.

Molecular-scale manipulation of electronic and ionic charge accumulation in materials is the backbone of electrochemical energy storage1-4. Layered van der Waals (vdW) crystals are a diverse family of materials into which mobile ions can electrochemically intercalate into the interlamellar gaps of the host atomic lattice5,6. The structural diversity of such materials enables the interfacial properties of composites to be optimized to improve ion intercalation for energy storage and electronic devices7-12. However, the ability of heterolayers to modify intercalation reactions, and their role at the atomic level, are yet to be elucidated. Here we demonstrate the electrointercalation of lithium at the level of individual atomic interfaces of dissimilar vdW layers. Electrochemical devices based on vdW heterostructures 13 of stacked hexagonal boron nitride, graphene and molybdenum dichalcogenide (MoX2; X = S, Se) layers are constructed. We use transmission electron microscopy, in situ magnetoresistance and optical spectroscopy techniques, as well as low-temperature quantum magneto-oscillation measurements and ab initio calculations, to resolve the intermediate stages of lithium intercalation at heterointerfaces. The formation of vdW heterointerfaces between graphene and MoX2 results in a more than tenfold greater accumulation of charge in MoX2 when compared to MoX2/MoX2 homointerfaces, while enforcing a more negative intercalation potential than that of bulk MoX2 by at least 0.5 V. Beyond energy storage, our combined experimental and computational methodology for manipulating and characterizing the electrochemical behaviour of layered systems opens new pathways to control the charge density in two-dimensional electronic and optoelectronic devices.

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.

JPT2 in subclinical hypothyroidism-related miscarriage as a transcription co-factor: involvement of LEPR/STAT3 activation.

BACKGROUND AND PURPOSE: Subclinical hypothyroidism (SCH) has been identified to be associated with implantation failure, in which the dysfunction of trophoblast cells is involved. In this study, the transcriptomics of aborted placenta from SCH rats were analyzed. Jupiter microtubule-associated homolog 2 (JPT2) was downregulated in the aborted placenta. This study aims to investigate its role in SCH-associated miscarriage. METHODS: Spontaneous abortion was observed in SCH rats generated by thyroidectomy combined with levothyroxine administration. The transcriptomics analysis was performed using aborted placenta. Afterward, the effects of JPT2 on trophoblast cells were explored using gain-and loss-of-function experiments. RESULTS: Transcriptomics analysis showed 1286 downregulated genes and 2300 upregulated genes in the aborted placenta, and JPT2 was significantly downregulated in the aborted placenta from SCH rats. Afterward, gain-and loss-of-function experiments exhibited that overexpression of JPT2 promoted the proliferation, migration, invasion, spheroid formation of HTR-8/SVneo trophoblast cells and their attachment to endometrial stromal cells, while these biological behaviors were suppressed by JPT2 knockdown. Furthermore, JPT2 accelerated the transcription of leptin receptor (LEPR), and activated signal transducer and activator of transcription 3 (STAT3) signal in a transcription factor AP-2γ-dependent manner. In addition, silencing of LEPR abolished the role of JPT2. CONCLUSION: Our results revealed that JPT2, which was downregulated in the aborted placenta from SCH rats, promoted proliferation, migration, invasion, spheroid formation, and attachment of trophoblast cells via regulating LEPR/STAT3 axis as a transcription co-factor. It is indicated that low expression of JPT2 may contribute to the abortion in individuals with SCH.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

[Clinical value of focused ultrasound ablation surgery in the treatment of abdominal wall endometriosis].

Objective: To explore the effectiveness and safety of focused ultrasound ablation surgery (FUAS) for abdominal wall endometriosis. Methods: From November 2019 to October 2022, a total of 34 patients with abdominal wall endometriosis who underwent FUAS were collected, and their clinical features, imaging features, intraoperative treatment and side effects after treatment were analyzed retrospectively, and the improvement of symptoms and re-intervention were followed up. Results: (1) Characteristics of clinical data: the average age of 34 patients with abdominal wall endometriosis was (32.8±3.8) years old. The largest diameter of the lesion was 48 mm, and the median lesion diameter was 24 mm. Thirty cases (88%, 30/34) had moderate to severe periodic pain in abdominal incision before FUAS. All patients were diagnosed by preoperative magnetic resonance imaging, including 19 cases (56%, 19/34) of superficial type, 8 cases (24%, 8/34) of intermediate type and 7 cases (21%, 7/34) of deep type. (2) FUAS treatment parameters: ablation was completed with average operation time of (64±18) minutes, average sonication time was (385±108) s, (103±11) W of average power, (38 819±16 309) J of average total energy, the average treatment area volume of (3.11±1.42) cm3, and (377.79±106.34) s/h of average treatment intensity. (3) Efficiency: the pain of patients after FUAS was significantly relieved, and the pain scores of patients after 1 month, 3 months, 6 months and 1 year after FUAS were significantly decreased (Z=-4.66, -5.13, -5.11 and -4.91, all P<0.01). One year after FUAS, the near relief and effective pain relief rate was 74% (25/34), and the clinical effective rate was 85% (29/34). Five patients recurred after one year, including 3 patients who underwent abdominal wall endometriosis lesion resection and 2 patients who received drug treatment. One month after FUAS, the size of the lesion did not change significantly compared with that before FUAS (P>0.05), and the size of the lesion decreased significantly after FUAS at 3 months, 6 months and 1 year (Z=-2.15, -2.67 and -3.41, all P<0.05). It has no difference in pain relief among different types (P>0.05), but has significant difference in focus reduction among three types (P<0.01). (4) Safety: there were 34 cases (100%, 34/34) of skin burning sensation, 19 cases (56%, 19/34) of pain in the treatment area and 2 cases (6%, 2/34) of hematuria. All patients got better after corresponding treatments. Conclusion: FUAS is safe and effective for the treatment of abdominal wall endometriosis, which has clinical application value.

[Interpretation of T-cell and NK-cell lymphoid proliferations and lymphomas in the 5th edition of the WHO classification of haematolymphoid tumours].

The 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumours used the hierarchical system to classify T-cell and NK-cell lymphoid proliferations and lymphomas (T/NK-LPD/LYM) based on research advances and clinicopathological characteristics of the diseases. In this edition of classification, tumour-like lesions were included, some tumors were added/deleted, the names or terms of certain diseases were refined, and the diagnostic criteria or subtypes of some diseases were revised. This group of diseases was reintegrated from non-clonal hyperplasia to highly aggressive lymphoma, which would further reflect the nature of T/NK-LPD/LYM and benefit to clinical application.

[Expression changes of RNA m6A regulators in mouse cerebellum affected by hypobaric hypoxia stimulation].

Objective: To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment. Methods: Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella. Results: Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced (P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella (P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice (P<0.05). Conclusions: Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

[Value of constructing a non-invasive diagnostic model based on serum heme oxygenase-1 and glucose regulatory protein 78 for non-alcoholic fatty liver disease].

Objective: To analyze the clinical application value of serum heme oxygenase (HO)-1expression level in non-alcoholic fatty liver disease (NAFLD) and, based on that, establish a diagnostic model combined with glucose regulatory protein 78 (GRP78) so as to clarify its diagnostic effectiveness and application value. Methods: A total of 210 NAFLD patients diagnosed by abdominal B-ultrasound and liver elastography were included, and at the same time, 170 healthy controls were enrolled. The general clinical data, peripheral blood cell counts, and biochemical indicators of the research subjects were collected. The expression levels of HO-1 and GRP78 were detected using an enzyme-linked immunosorbent assay. Multivariate analysis was used to screen independent risk factors for NAFLD. Visual output was performed through nomogram diagrams, and the diagnostic model was constructed. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the diagnostic effectiveness of NAFLD. Measurement data were analyzed using a t-test or Mann-Whitney U rank sum test to detect data differences between groups. Enumeration data were analyzed using the Fisher's exact probability test or the Pearson χ(2) test. Results: Compared with the healthy control group, the white blood cell count, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase (GTT), fasting blood glucose (Glu), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum HO-1, and GRP78 levels were significantly increased in the NAFLD group patients (P < 0.05). Binary logistic analysis results showed that AST, TG, LDL-C, serum HO-1, and GRP78 were independent risk factors for NAFLD (P < 0.05). A nomogram clinical predictive model HGATL was established using HO-1 (H), GRP78 (G) combined with AST (A), TG (T), and LDL-C (L), with the formula P=-21.469+3.621×HO-1+0.116 ×GRP78+0.674×AST+6.250×TG+4.122 ×LDL-C. The results confirmed that the area under the ROC curve of the HGATL model was 0.965 8, with an optimal cutoff value of 81.69, a sensitivity of 87.06%, a specificity of 92.82%, a P < 0.05, and the diagnostic effectiveness significantly higher than that of a single indicator. The calibration curve and DCA both showed that the model had good diagnostic performance. Conclusion: The HGATL model can be used as a novel, non-invasive diagnosis model for NAFLD and has a positive application value in NAFLD diagnosis and therapeutic effect evaluation. Therefore, it should be explored and promoted in clinical applications.

Fragmentomic analysis of circulating tumor DNA-targeted cancer panels.

BACKGROUND: The isolation of cell-free DNA (cfDNA) from the bloodstream can be used to detect and analyze somatic alterations in circulating tumor DNA (ctDNA), and multiple cfDNA-targeted sequencing panels are now commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide treatment. More recently, cfDNA fragmentation patterns have emerged as a tool to infer epigenomic and transcriptomic information. However, most of these analyses used whole-genome sequencing, which is insufficient to identify FDA-approved biomarker indications in a cost-effective manner. PATIENTS AND METHODS: We used machine learning models of fragmentation patterns at the first coding exon in standard targeted cancer gene cfDNA sequencing panels to distinguish between cancer and non-cancer patients, as well as the specific tumor type and subtype. We assessed this approach in two independent cohorts: a published cohort from GRAIL (breast, lung, and prostate cancers, non-cancer, n = 198) and an institutional cohort from the University of Wisconsin (UW; breast, lung, prostate, bladder cancers, n = 320). Each cohort was split 70%/30% into training and validation sets. RESULTS: In the UW cohort, training cross-validated accuracy was 82.1%, and accuracy in the independent validation cohort was 86.6% despite a median ctDNA fraction of only 0.06. In the GRAIL cohort, to assess how this approach performs in very low ctDNA fractions, training and independent validation were split based on ctDNA fraction. Training cross-validated accuracy was 80.6%, and accuracy in the independent validation cohort was 76.3%. In the validation cohort where the ctDNA fractions were all <0.05 and as low as 0.0003, the cancer versus non-cancer area under the curve was 0.99. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that sequencing from targeted cfDNA panels can be utilized to analyze fragmentation patterns to classify cancer types, dramatically expanding the potential capabilities of existing clinically used panels at minimal additional cost.

Quantum Simulation of Topological Zero Modes on a 41-Qubit Superconducting Processor.

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

Detection of haemodynamic obstruction in hypertrophic cardiomyopathy using the sub-aortic complex: a cardiac MRI and Doppler study.

AIM: To investigate the "sub-aortic complex (SAC)", a new cardiac magnetic resonance imaging (CMRI)-derived parameter, for the evaluation of left ventricular (LV) outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy (HCM), compared with conventional CMRI parameters and Doppler echocardiography. MATERIALS AND METHODS: A total of 157 consecutive patients with HCM were recruited retrospectively. The patients were divided into two groups, 87 with LVOT obstruction and 70 without obstruction. The SAC was defined as a specific anatomical SAC affecting the LVOT, which were measured on the LV three-chamber steady-state free precession (SSFP) cine image at the end-systolic phase. The relations between the existence and severity of obstruction and SAC index (SACi) were evaluated using Pearson's correlation coefficient, receiver operating characteristic (ROC) curves, and logistic regression. RESULTS: The SACs were significantly different between the obstructive and non-obstructive groups. The ROC curves indicated that the SACi was able to discriminate obstructive and non-obstructive patients with the best predictive accuracy (AUC = 0.949, p<0.001). The SACi was an independent predictor of LVOT obstruction and there was a significant negative correlation between resting LVOT pressure gradient and SACi (r=0.72 p<0.001). In the subgroup of patients with or without severe basal septal hypertrophy, the SACi was still able to predict LVOT obstruction with excellent diagnostic accuracy (AUC = 0.944 and 0.948, p<0.001, respectively). CONCLUSION: The SAC is a reliable and straightforward CMRI marker for assessing LVOT obstruction. It is more effective than CMRI two-dimensional flow in diagnosing the severity of obstruction in patients with HCM.

"But not the music": psychopathic traits and difficulties recognising and resonating with the emotion in music.

Recognising and responding appropriately to emotions is critical to adaptive psychological functioning. Psychopathic traits (e.g. callous, manipulative, impulsive, antisocial) are related to differences in recognition and response when emotion is conveyed through facial expressions and language. Use of emotional music stimuli represents a promising approach to improve our understanding of the specific emotion processing difficulties underlying psychopathic traits because it decouples recognition of emotion from cues directly conveyed by other people (e.g. facial signals). In Experiment 1, participants listened to clips of emotional music and identified the emotional content (Sample 1, N = 196) or reported on their feelings elicited by the music (Sample 2, N = 197). Participants accurately recognised (t(195) = 32.78, p < .001, d = 4.69) and reported feelings consistent with (t(196) = 7.84, p < .001, d = 1.12) the emotion conveyed in the music. However, psychopathic traits were associated with reduced emotion recognition accuracy (F(1, 191) = 19.39, p < .001) and reduced likelihood of feeling the emotion (F(1, 193) = 35.45, p < .001), particularly for fearful music. In Experiment 2, we replicated findings for broad difficulties with emotion recognition (Sample 3, N = 179) and emotional resonance (Sample 4, N = 199) associated with psychopathic traits. Results offer new insight into emotion recognition and response difficulties that are associated with psychopathic traits.

Molecular cloning and expression analysis of Myxovirus resistance gene in Yangzhou goose (Anser cygnoides domesticus).

1. Myxovirus resistance (Mx) is a protein produced by the interferon-induced natural immune response with broad spectrum antiviral function. However, the role and expression characteristics of the Mx gene in immune defence against viral infection in goose have not yet been reported.2. This study found a 2576 bp genomic sequence and a 2112 bp mRNA sequence for Mx, encoding 703 amino acids. Multiple sequence alignments of the amino acid sequences showed that the Yangzhou goose Mx (goMx) had 86.99% similarity to the mallard duck (Anas platyrhynchos).3. Tissue-specific expression profiling revealed that the expression of goMx was highest in the lung and spleen. Both poly (I:C) and GPV were found to elevate the expression of goMx. The upregulated expression of goMx was associated with interferon pathway-related genes IRF7, JAK1, STAT1, and STAT2. Furthermore, overexpression of goMx significantly activated the transcription of poly (I:C) induced TNF-α, IL-1ß, IL-6, and IL-18.4. The findings of this study suggest that the goMx modulation of the antiviral response is mediated by the interferon pathway.

[Clinical and chest CT features of immune checkpoint inhibitor-related pneumonitis].

Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.

[Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageâ A lung cancer].

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.

[The performance of digital chest radiographs in the detection and diagnosis of pulmonary nodules and the consistency among readers].

Objective: To investigate the detection and diagnostic efficacy of chest radiographs for ≤30 mm pulmonary nodules and the factors affecting them, and to compare the level of consistency among readers. Methods: A total of 43 patients with asymptomatic pulmonary nodules who consulted in Cancer Hospital, Chinese Academy of Medical Sciences from 2012 to 2014 and had chest CT and X-ray chest radiographs during the same period were retrospectively selected, and one nodule ≤30 mm was visible on chest CT images in the whole group (total 43 nodules in the whole group). One senior radiologist with more than 20 years of experience in imaging diagnosis reviewed CT images and recording the size, morphology, location, and density of nodules was selected retrospectively. Six radiologists with different levels of experience (2 residents, 2 attending physicians and 2 associate chief physicians independently reviewed the chest images and recorded the time of review, nodule detection, and diagnostic opinion. The CT imaging characteristics of detected and undetected nodules on X images were compared, and the factors affecting the detection of nodules on X-ray images were analyzed. Detection sensitivity and diagnosis accuracy rate of 6 radiologists were calculated, and the level of consistency among them was compared to analyze the influence of radiologists' seniority and reading time on the diagnosis results. Results: The number of nodules detected by all 6 radiologists was 17, with a sensitivity of detection of 39.5%(17/43). The number of nodules detected by ≥5, ≥4, ≥3, ≥2, and ≥1 physicians was 20, 21, 23, 25, and 28 nodules, respectively, with detection sensitivities of 46.5%, 48.8%, 53.5%, 58.1%, and 65.1%, respectively. Reasons for false-negative result of detection on X-ray images included the size, location, density, and morphology of the nodule. The sensitivity of detecting ≤30 mm, ≤20 mm, ≤15 mm, and ≤10 mm nodules was 46.5%-58.1%, 45.9%-54.1%, 36.0%-44.0%, and 36.4% for the 6 radiologists, respectively; the diagnosis accuracy rate was 19.0%-85.0%, 16.7%-6.5%, 18.2%-80.0%, and 0%-75.0%, respectively. The consistency of nodule detection among 6 doctors was good (Kappa value: 0.629-0.907) and the consistency of diagnostic results among them was moderate or poor (Kappa value: 0.350-0.653). The higher the radiologist's seniority, the shorter the time required to read the images. The reading time and the seniority of the radiologists had no significant influence on the detection and diagnosis results (P>0.05). Conclusions: The ability of radiographs to detect lung nodules ≤30 mm is limited, and the ability to determine the nature of the nodules is not sufficient, and the increase in reading time and seniority of the radiologists will not improve the diagnostic accuracy. X-ray film exam alone is not suitable for lung cancer diagnosis.

[The impact of the number of previous miscarriages on embryo euploid rate and pregnancy outcomes in patients with unexplained recurrent pregnancy loss].

Objective: To investigate the impact of the number of previous miscarriages on embryo euploid rate and pregnancy outcomes after preimplantation genetic testing for aneuploidies (PGT-A) in patients with unexplained recurrent pregnancy loss (uRPL). Methods: A retrospective cohort study was conducted. 799 women with uRPL who underwent PGT-A for the first time between January 2015 and December 2021 at the Reproductive center of Shandong University were enrolled. These patients were divided into three groups according to the number of previous miscarriages (2, 3, and≥4). Stratified analysis was conducted according to female age (≤37 years and>37 years). The embryo euploidy rate, good-quality blastocyst formation rate, cumulative live birth rate, and cumulative clinical pregnancy loss rate of three groups were compared in younger and older patients, respectively. Meanwhile, the cumulative live birth rate, clinical pregnancy loss rate, and embryo euploidy rate were analyzed by multivariate logistic regression analysis. Results: Patients' age was (34.7±5.1) years old. In the three groups with 2, 3 and ≥4 previous miscarriages, there was no significant difference in the embryo euploidy rate between groups in the younger [48.9% (539/1 103), 50.6% (354/700) and 52.1% (152/292), P=0.567] and older [26.2% (103/393), 28.8% (55/191) and 20.5% (16/78), P=0.377] age population. Compared with 2 and 3 previous miscarriages, the cumulative live birth rate was significantly decreased [52.6% (153/291), 52.8% (93/176) and 34.3% (25/73), P=0.014] and the cumulative clinical pregnancy loss rate was significantly increased [15.8% (31/196), 15.3% (18/118) and 46.9% (23/49), P<0.001] in younger women with ≥4 miscarriages. After adjusting for maternal age, BMI, AMH, endometrial thickness on hCG trigger day and antral follicle count, the number of previous miscarriages ≥4 was a relevant factor for cumulative live birth rate (OR=0.461, 95%CI: 0.263-0.807, P=0.007) and the cumulative clinical pregnancy loss rate (OR=4.382, 95%CI: 2.165-8.873, P<0.001) in younger patients, but it was not significantly correlated with the cumulative live birth rate, cumulative clinical pregnancy loss rate and embryo euploidy rate in patients with advanced age. Conclusion: In uRPL patients,≥4 previous miscarriages decreased cumulative live birth rate and increased cumulative clinical pregnancy loss rate in women aged≤37 years old.

[Effects of remimazolam versus propofol on postoperative recovery quality in elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy].

Objective: To investigate the effects of remimazolam versus propofol on postoperative recovery quality in elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy. Methods: A total of 108 elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy under general anesthesia in the Affiliated Cancer Hospital of Zhengzhou University from May to October 2022 were prospectively included. The participants were divided into two groups by the random number table method: remimazolam group (R group, n=54) and propofol group (P group, n=54). There were 54 cases in the R group, with 35males and 19 females, and aged (65.4±3.1) years. Meanwhile, there were 54 cases in the P group, with 33males and 21 females, and aged (64.5±3.0) years. Anesthesia was induced as follows: remimazolam 0.2-0.3 mg/kg and remifentanil 0.5-1.0 µg/kg were intravenously injected in R group, while propofol 1-2 mg/kg and remifentanil 0.5-1.0 µg/kg were intravenously injected in P group. Subsequently, anesthesia was maintained as follows: remimazolam 0.4-1.0 mg·kg-1·h-1 and remifentanil 0.05-0.2 µg·kg-1·min-1 were intravenously infused in group R, while propofol 4-10 mg·kg-1·h-1 and remifentanil 0.05-0.2 µg·kg-1·min-1 were intravenously infused in group P. Bispectral index (BIS) was maintained at 45-60 during operation. The main outcome measures were the 15-item quality of recovery (QoR-15) scores 1 day before surgery, 1 day and 3 days after surgery. Secondary outcome measures included mean arterial pressure (MAP), heart rate and pulse oxygen saturation (SpO2) recorded 5 min before anesthesia induction (T0), 1 min after induction (T1), 1 min after endotracheal intubation (T2), immediately after skin incision (T3) and tracheal extubation (T4). The incidence of bradycardia and hypotension and the frequency of application of vasoactive drugs during anesthesia were recorded. Restlessness score (RS) and Ramsay sedation scale during the awakening period were recorded. Emergence time, tracheal extubation time, duration of postanesthesia care unit (PACU) stay and postoperative length of hospital stay were recorded. The incidence of postoperative pulmonary infection and other complications were also recorded. Results: The QoR-15 scale scores [M (Q1, Q3)] of R group 1 day and 3 days after surgery were 114.0 (109.0, 118.3) and 131.0 (127.8, 133.0), which were higher than those of P group [106.0 (101.0, 112.0) and 127.0 (125.0, 129.3)] (both P<0.001). The incidence of bradycardia, hypotension and the frequency of application of vasoactive drugs of R group during anesthesia were 5.6% (3/54), 35.2% (19/54) and 27.8% (15/54), which were lower than those in P group [33.3% (18/54), 63.0% (34/54) and 55.6% (30/54), respectively] (all P<0.05). RS score during the awakening period in R group was 0.9±0.5, which was lower than that of P group (1.1±0.6) (P=0.046). Emergence time, tracheal extubation time and postoperative length of hospital stay of R group were (15.4±4.9) min, (16.6±4.7) min and (11.6±1.4) d, which were shorter than those of P group [(26.2±6.4) min, (27.8±5.8) min and (12.6±1.3) d] (all P<0.05). There were no statistically significant differences in Ramsay scores during the awakening period, duration of PACU stay and the incidence of postoperative complications (all P>0.05). Conclusions: Both remimazolam and propofol can achieve satisfactory postoperative recovery quality in elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy. Remimazolam has more stable hemodynamics and lower incidence of adverse reactions.

[Genetic mutation profiles for children with congenital hypothyroidism in Fujian province].

Objective: To explore the mutation characteristics of pathogenic genes in children with congenital hypothyroidism (CH) in Fujian. Methods: The clinical data of 116 unrelated CH children diagnosed in Fujian Provincial Maternal and Child Health Hospital from January 2019 to September 2020 were retrospectively analyzed, including 50 females and 66 males, with an average age of (20±10) days at diagnosis. Targeted exome sequencing technology was used to detect the mutation frequency, type and distribution characteristics of 29 genes related to thyroxine synthesis or thyroid development. Results: Three hundred and fifty-one potential functional mutations were detected in 105 of 116 CH patients, with a detection rate of 90.5% (105/116). DUOX2 (66.4%, 77/116) was the most frequent mutated gene, followed by TG (23.3%, 27/116), DUOXA1 (23.3%, 27/116), and TPO (12.1%, 14/116), which were all involved in thyroid hormone synthesis. Among the 105 children with CH, 70 cases carried double allele mutation. Except for 3 cases of thyroid dysplasia related genes (2 cases of TSHR and 1 case of GLIS3), the rest were also related to thyroid hormone synthesis. The gene with the highest carrier rate was DUOX2 (68.8%, 59/70), followed by TG (8.6%, 6/70), TPO (4.3%, 3/70), DUOXA2 (1.4%, 1/70) and DUOXA1 (1.4%, 1/70). Conclusion: The main mutated genes in CH children in Fujian are the key genes involved in thyroid hormone synthesis, such as DUOX2, TG and TPO.