A highly distorted ultraelastic chemically complex Elinvar alloy.

The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various industrial applications, from actuators and medical devices to high-precision instruments1,2. The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys3-including gum metals4,5 and strain glass alloys6,7-may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation3. Recently, chemically complex alloys, such as 'high-entropy' alloys8, have attracted tremendous research interest owing to their promising properties9-15. In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10-4) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported.

Salt-sensitive hypertension in GR mutant rats is associated with altered plasma polyunsaturated fatty acid levels and aortic vascular reactivity.

In humans, glucocorticoid resistance is attributed to mutations in the glucocorticoid receptor (GR). Most of these mutations result in decreased ligand binding, transactivation, and/or translocation, albeit with normal protein abundances. However, there is no clear genotype‒phenotype relationship between the severity or age at disease presentation and the degree of functional loss of the receptor. Previously, we documented that a GR+/- rat line developed clinical features of glucocorticoid resistance, namely, hypercortisolemia, adrenal hyperplasia, and salt-sensitive hypertension. In this study, we analyzed the GR+/em4 rat model heterozygously mutant for the deletion of exon 3, which encompasses the second zinc finger, including the domains of DNA binding, dimerization, and nuclear localization signals. On a standard diet, mutant rats exhibited a trend toward increased corticosterone levels and a normal systolic blood pressure and heart rate but presented with adrenal hyperplasia. They exhibited increased adrenal soluble epoxide hydroxylase (sEH), favoring an increase in less active polyunsaturated fatty acids. Indeed, a significant increase in nonactive omega-3 and omega-6 polyunsaturated fatty acids, such as 5(6)-DiHETrE or 9(10)-DiHOME, was observed with advanced age (10 versus 5 weeks old) and following a switch to a high-salt diet accompanied by salt-sensitive hypertension. In thoracic aortas, a reduced soluble epoxide hydrolase (sEH) protein abundance resulted in altered vascular reactivity upon a standard diet, which was blunted upon a high-salt diet. In conclusion, mutations in the GR affecting the ligand-binding domain as well as the dimerization domain resulted in deregulated GR signaling, favoring salt-sensitive hypertension in the absence of obvious mineralocorticoid excess.

Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside.

Decreased nicotinamide adenine dinucleotide (NAD+) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia-reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD+ precursor due to efficient NAD+ elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown. Furthermore, the influence of insulin, a known modulator of cardioprotective efficacy, on the protective effects of NR has not been investigated. Here, we used the isolated mouse heart allowing cardiac metabolic control to investigate: (1) whether NR can protect the isolated heart against IRI, (2) the metabolic pathways underlying NR-mediated protection, and (3) whether insulin abrogates NR protection. NR protection against cardiac IRI and effects on metabolic pathways employing metabolomics for determination of changes in metabolic intermediates, and 13C-glucose fluxomics for determination of metabolic pathway activities (glycolysis, pentose phosphate pathway (PPP) and mitochondrial/tricarboxylic acid cycle (TCA cycle) activities), were examined in isolated C57BL/6N mouse hearts perfused with either (a) glucose + fatty acids (FA) ("mild glycolysis group"), (b) lactate + pyruvate + FA ("no glycolysis group"), or (c) glucose + FA + insulin ("high glycolysis group"). NR increased cardiac NAD+ in all three metabolic groups. In glucose + FA perfused hearts, NR reduced IR injury, increased glycolytic intermediate phosphoenolpyruvate (PEP), TCA intermediate succinate and PPP intermediates ribose-5P (R5P) / sedoheptulose-7P (S7P), and was associated with activated glycolysis, without changes in TCA cycle or PPP activities. In the "no glycolysis" hearts, NR protection was lost, whereas NR still increased S7P. In the insulin hearts, glycolysis was largely accelerated, and NR protection abrogated. NR still increased PPP intermediates, with now high 13C-labeling of S7P, but NR was unable to increase metabolic pathway activities, including glycolysis. Protection by NR against IRI is only present in hearts with low glycolysis, and is associated with activation of glycolysis. When activation of glycolysis was prevented, through either examining "no glycolysis" hearts or "high glycolysis" hearts, NR protection was abolished. The data suggest that NR's acute cardioprotective effects are mediated through glycolysis activation and are lost in the presence of insulin because of already elevated glycolysis.

Research on the phase error of a Sagnac interferometer induced by modulation of a multifunctional integrated optical modulator.

High-precision IFOG requires an optical sensitivity of up to 10-8 rads-1 for interferometers; noise and error are two of the main reasons limiting its accuracy improvement. Any potential source of the signal error is worth being studied. This article introduces work on the modulation signal error caused by the mechanical vibration energy loss of MIOC crystals. This article theoretically derives and simulates the frequency spectrum of an energy loss from the perspective of electromechanical coupling and verifies it through experiments. This article also verifies the influence of MIOC mechanical loss on the output of a Sagnac interferometer through experiments. This study is an indispensable part of the bottleneck for improving the accuracy of ultrahigh-precision closed-loop IFOG and has potential engineering application value.

Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment.

The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.

Quantum chemistry and kinetics of hydrogen sulphide oxidation.

A fundamental understanding of the acid gas (H2S and CO2) chemistry is key to efficiently implement the desulphurisation process and even the production of clean fuels such as hydrogen or syngas. In this work, we developed a new kinetic model for the pyrolysis and oxidation of hydrogen sulphide by merging two previously reported models with the goal of covering a wider range of conditions and including the effect of carbon dioxide. The resulting model, which consists of 75 species and 514 reactions, was used to conduct rate of production and sensitivity analysis in plug flow reactor simulations, and the results were used to determine the most prominent reactions in which hydrogen sulphide, molecular hydrogen, and sulphur monoxide are involved. The resulting list of important reactions was screened and the kinetics of three of them, i.e., SO2 + S2 → S2O + SO, S2O + S2 → S3 + SO, and SO + SH → S2 + OH, was found to warrant further investigation. With the goal of improving the accurancy of our new kinetic model, we carried out a robust quantum chemistry and Rice-Ramsperger-Kassel-Marcus master equation study to obtain, for the first time, the forward and reverse rate constants for those three reactions at temperatures and pressures of interest for combustion and atmospheric chemistry. This work is the first step of a kinetic study that is aimed at improving the understanding of the chemistry of the pyrolysis and oxidation of H2S, highlighting the importance of sulphur-sulphur interactions and providing a fundamental basis for future kinetic models of H2S not only in the field of combustion, but also in atmospheric chemistry.

Interplay of metabolic dysfunction-associated fatty liver disease and papillary thyroid carcinoma: insights from a Chinese cohort.

PURPOSE: Thyroid cancer is one of a set of extrahepatic cancers that closely linked to metabolic dysfunction-associated fatty liver disease (MAFLD). However, the connection between MAFLD and the characteristics of papillary thyroid cancer (PTC) remains unexplored. METHODS: Between Jan 2020 and Oct 2022, surgical cases of PTC patients were examined at the first Affiliated Hospital of Wenzhou Medical University. Clinical data extracted from the electronic medical system underwent a rigorous comparison between two groups, classified based on MAFLD criteria, using logistic regression analysis. RESULTS: In this study of 4,410 PTC patients, 18.3% had MAFLD. MAFLD emerged as a distinct risk factor for lymph node metastasis (OR = 1.230, 95% CI 1.018-1.487) in this cohort, especially in females (OR = 1.321, 95% CI 1.026-1.702) and those with BMI ≥ 23 kg/m2 (OR = 1.232, 95% CI 1.004-1.511). The presence of MAFLD was found to significantly elevate the risk of BRAF V600E mutation in both subgroups characterized by FIB-4 score ≥ 1.3 (OR = 1.968, 95% CI 1.107-3.496) and BMI < 23 kg/m2 (OR = 2.584, 95% CI 1.012-6.601). Moreover, among the subset of individuals without non-alcoholic fatty liver disease (NAFLD), it was noted that MAFLD considerably increased the likelihood of tumor multifocality (OR = 1.697, 95% CI 1.111-2.592). Nevertheless, MAFLD did not exhibit any correlation with increased tumor size, extra-thyroidal extension (ETE), or later TNM stage in PTC. CONCLUSION: In this cross-sectional study, we discovered a significant association between MAFLD and increased occurrences of lymph node metastasis. Furthermore, MAFLD was linked to a higher chance of BRAF V600E mutation and the presence of multiple tumors in certain subgroups.

Development of a diagnostic model for pre-washout screening of primary aldosteronism.

PURPOSE: Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. METHODS: We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. RESULTS: PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. CONCLUSION: PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

Burden and trend of dietary risk-related colorectal cancer in China and its provinces: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: The objective of this experiment was to evaluate the spatial pattern and temporal trend of colorectal cancer (CRC) burden attributed to dietary risk factors in China from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. METHODS: Numbers and age-standardised rates of deaths, disability-adjusted life years (DALYs) and corresponding average annual percentage change (AAPC) were determined. The joinpoint regression analysis was used to assess the temporal trends of CRC deaths and DALYs from 1990 to 2019. RESULTS: In China, the number of diet-attributable CRC deaths and DALYs in 2019 were 90.41 (95% uncertainty interval: 65.69, 114.67) and 2234.06 (1609.96, 2831.24) per-1000 population, marking 2.05% and 1.68% annual increases since 1990, respectively. The region with the highest increase in age-standardised rates (ASRs) of diet-related CRC deaths and DALYs was in Taiwan with an AAPC of 2.00% (1.51, 2.48), whereas the highest decline in ASRs of CRC deaths and DALYs was observed in Hong Kong with an AAPC of -0.63% (-0.90, -0.35) (all P < 0.05). Nationally, men suffered higher CRC deaths and DALY burdens attributable to dietary risks than did women. Regarding the specific diet group, diets low in calcium, milk, and whole grains contributed to CRC deaths and DALYs the most. CONCLUSIONS: Diet is an important contributor to increasing CRC burden in China. Necessary measures should be taken to kerb the growing burden attributed to dietary factors, particularly in males and in regions with middle Socio-demographic Index or lower.

[A study of the correlation between gray matter atrophy in multiple sclerosis and impairment of cognitive function domains].

Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.

[Report of six cases with mast cell leukemia and a literature review].

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia (n=4), fatigue (n=3), fever (n=2), abdominal discomfort (n=2), osteolytic lesions (n=2), dizziness (n=1), skin flushing (n=1), and weight loss (n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) µg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

[The consistency between changes in Mandarin Tinnitus Questionnaire scores and tinnitus treatment outcomes].

Objective: To verify the consistency between changes in Mandarin Tinnitus Questionnaire (MTQ) scores and tinnitus treatment outcomes. Methods: Tinnitus patients attending the Department of Otorhinolaryngology-Head & Neck Surgery, West China Hospital of Sichuan University from September 2020 to September 2021were prospectively enrolled. The tinnitus severity was evaluated by the doctor's assessment, the patient's self-assessment, the MTQ, and the Visual Analogue Scale (VAS). Follow-up assessments were conducted 3 to 6 months later to evaluate the severity of tinnitus post-treatment, and information on the interventions received (pharmacologic/non-pharmacologic) and patients' self-reported clinical impressions of their treatment outcomes (tinnitus cured/improved/no change/exacerbated) was collected. Results: A total of 54 tinnitus patients aged (43.5±12.7) years were included, consisting of 16 males and 38 females. There were 38 cases in the medication group and 16 cases in the non-medication group. No statistically significant differences in baseline clinical data were observed (all P>0.05). The proportion of primary tinnitus in the medication group was higher than that in the non-medication group [97.4% (37/38) vs 75.0% (12/16), P=0.023]. The correlation coefficients of MTQ scores at the initial and follow-up visits with doctor's assessment, patient's self-assessment, and VAS scores were 0.679, 0.483, 0.606, 0.774, 0.779, and 0.756, respectively (all P<0.001). The ΔMTQ correlation coefficient with ΔVAS was 0.694 (P<0.001), with a mean difference of 3.704×10-7 and 95% limits of agreement ranging from -1.534 to 1.534 in Bland-Altman analysis. There were no statistically significant differences of ΔVAS and ΔMTQ between two groups (both P>0.05). Conclusions: MTQ correlates well with the doctor's assessment, the patient's self-assessment, and VAS. Changes in MTQ scores associate well with changes in VAS scores. Additionally, changes in MTQ scores are consistent with the effect of tinnitus treatment.

[Confirmatory factor analysis of the Chinese version of tinnitus handicap inventory].

Objective: To explore the validity of the Chinese version of tinnitus handicap inventory (THI-CM) using confirmatory factor analysis. Methods: A cross-sectional study was carried out. The patients who complained of tinnitus and visited the Department of Otolaryngology, Head and Neck Surgery at West China Hospital of Sichuan University from March 15 to June 28, 2023 were included. All participants underwent pure tone audiometry and acoustic impedance testing before filling out THI-CM, and the results were subjected to confirmatory factor analysis. Results: A cross-sectional study was carried out. A total of 300 patients aged (47±13) years participated in this study. There were 175 females (58.3%) and 125 males (41.7%). The confirmatory factor analysis showed that χ2/df was 1.597<3.00, root mean square error of approximation (RMSEA) was 0.039<0.05, and standardized root mean square residual (SRMR) was 0.091>0.08. The incremental fit index (IFI), Tucker-Lewis index (TLI), comparative fit index (CFI), and goodness of fit index (GFI) were 0.960, 0.954, 0.960, and 0.902, respectively. The overall model fitted well. Except for one item with a load of 0.493, the load values of the other items were between 0.553 and 0.771. The composite reliability (CR) values of the three dimensions of the scale were between 0.769 and 0.901 (all CR>0.7). The average variance extracted (AVE) values ranged from 0.403 to 0.505 (all AVE<0.7), indicating poor convergent validity of the scale. The square value of AVE in each dimension of the scale was smaller than the correlation coefficient between factors, indicating poor discriminant validity of the scale. Conclusions: The THI-CM has good structural validity, which can be used as an effective tool to evaluate the overall severity of tinnitus. However, its convergent validity and discriminant validity are poor.

[The effect of ubiquitin ligase Cullin3 on the proliferation, migration and invasion of triple-negative breast cancer cells and exploration of its mechanism].

Objective: To investigate the effects of ubiquitin ligase Cullin3 (CUL3) on the proliferation, migration and invasion ability of triple-negative breast cancer (TNBC) cells and its mechanism of action. Methods: Bioinformatics-based methods were used to obtain CUL3 gene and protein expression data in TNBC tissues, and to assess the expression of CUL3 in tumour tissues of TNBC patients (n=160) and in normal breast tissues (n=572), and its relationship with clinical prognosis. The effects of overexpression of CUL3 on the proliferation, migration and invasion ability of TNBC cells in vitro were detected by CCK8 cell proliferation assay, scratch assay and transwell assay; proteins that might interact with CUL3 were screened by immunoprecipitation combined with mass spectrometry analysis, and the substrate protein regulated by CUL3 was identified as Glutathione S-Transferase Pi 1 (GSTP1); the effects of overexpression of GSTP1 on the migration and invasion ability of TNBC cells were detected by scratch assay and Transwell assay, and it was explored whether overexpression of CUL3 could reverse the effects of GSTP1 on the migration and invasion ability of cells; and the effects of overexpression of GSTP1 on the migration and invasion ability of cells were detected by Western blot and IP (Immunoprecipitation) to detect the effect of CUL3 on the ubiquitination modification of GSTP1 protein, and to verify the molecular mechanism by which CUL3 regulates the expression of GSTP1 to affect TNBC migration and invasion. Results: CUL3 expression was significantly higher in TNBC (P<0.000 1), and high CUL3 expression was closely associated with poor prognosis of TNBC patients (OS, P=0.018; RFS, P=0.008); overexpression of CUL3 significantly increased the proliferation of TNBC cells (F=11.97, P=0.002 for the 231-cell group, F=51.92, P<0.001 for the 468-cell group), migration [74.7±4.0 and 128.0±6.1 perforating cells in the overexpression groups of 231 and 468 cell lines, compared with 21.0±2.7 and 70.0±6.6 in the blank control (NC) group, and the t-values of 231 and 468 cell groups were-19.24 and-11.23, with P-values<0.001] and invasive ability (48 h cell proliferation rates were 56.6%±4.4% and 51.6%±3.7% in the 231 and 468 cell line overexpression groups, compared with 40.5%±2.9% and 32.9%±4.8% in the NC group, respectively, t=-5.26, P=0.006 3 in the 231 cell group; t=-5.38 in the 468 cell group, P=0.005 8); GSTP1 expression was reduced in TNBC, and up-regulation of GSTP1 inhibited TNBC cell migration (the number of membrane-penetrating cells in the overexpression groups of 231 and 468 cell lines were 16.3±6.5 and 33.0±6.2, respectively, compared with 34.3±2.5 and 77.3±5.0 in the NC group, and t=5.44 in the 231 cell group, P=0.006; 468 cell group t=7.20, P=0.002) and invasion (48 h cell proliferation rates of 49.6%±1.7% and 36.2%±1.4% in the 231 and 468 cell line overexpression groups, compared to 59.4%±4.7% and 53.0%±1.7% in the NC group, t=3.42, P=0.027 in the 231 cell group; 468 cell group t=13.18, P<0.001), whereas up-regulation of CUL3 reversed the effects of GSTP1 on cell migration (37.0±1.0 and 67.0±5.3 membrane-penetrating cells in the overexpression groups of 231 and 468 cell lines, respectively, 231 cell group t=-3.97, P=0.017; 468 cell group t=-6.12, P=0.004), and invasion (48 h cell proliferation rates of 71.9%±3.6% and 59.4%±2.1% in the 231 and 468 cell line overexpression groups, respectively, with t-values of -9.61 and -16.01 in the 231 and 468 cell groups, respectively, P-values<0.001) inhibitory effects; and CUL3, by increasing GSTP1 ubiquitylation modification, promotes ubiquitin-proteasome system to degrade GSTP1 protein, thereby reducing the stability of GSTP1 protein. Conclusion: Overexpression of CUL3 promotes TNBC development by promoting GSTP1 ubiquitination degradation inducing cell migration and invasion.

[Correlation and predictive value analysis of iliac artery calcification score and restenosis of lower extremity arteries after drug-coated balloon combined with stent implantation in patients with lower extremity atherosclerotic occlusive disease].

Objective: To analyze the correlation between iliac artery calcification score and restenosis of lower extremity arteries in patients with lower extremity atherosclerotic occlusive disease (LEASO) who underwent drug-coated balloon (DCB) combined with stenting, and to assess the predictive value. Methods: A total of 105 patients with LEASO at Nanjing Drum Tower Hospital, Nanjing University Medicine School, from January 2018 to June 2023 were retrospectively included, and the patients were divided into 2 groups according to whether restenosis of the original lower limb arteries had occurred during follow-up after DCB combined stent implantation: the restenosis group (n=64) and the patency group (n=41). The clinical information of the study subjects was collected through the electronic case system, and all patients underwent CTA examination of both lower limb arteries before the operation, and the calcification scores of common iliac arteries and external iliac arteries of patients' bilateral and stenotic sides were calculated according to the results of the CTA examination. The follow-up time [M (Q1, Q3)] was 9.15 (5.67, 15.60) months in the patency group and 9.20 (6.85, 19.65) months in the restenosis group. Univariate and multivariate logistic regression models were used to analyze the factors associated with restenosis after DCB combined with stent implantation in LEASO patients. The predictive value of iliac artery calcification score for postoperative restenosis was assessed using the receiver operating characteristic (ROC) curves. Results: There were 44 males and 20 females in the restenosis group, aged (73±9) years; 31 males and 10 females in the patency group, aged (73±10) years. Compared with the patency group, the restenosis group had higher neutrophil counts, platelet counts, lymphocyte counts, neutrophil-to-lymphocyte ratios (NLR), platelet-to-lymphocyte ratios (PLR), C-reactive protein, fibrinogen, stent lengths, stent numbers, common iliac artery calcification scores (bilateral and stenotic side), and external iliac artery calcification scores (bilateral and stenotic side) (all P<0.05). Multifactorial logistic regression analysis showed that higher external iliac artery calcification score on the stenotic side (OR=1.480, 95%CI: 1.130-1.939, P=0.004) was an associated factor for restenosis of the lower extremity arteries after DCB combined with stenting.ROC curve analysis showed that the cut-off value of the external iliac artery calcification score on the stenotic side was 5.5 score, the area under the curve (AUC) for predicting restenosis of lower extremity arteries after DCB combined stent implantation in LEASO patients was 0.818 (95%CI: 0.731-0.904, P<0.001), with a sensitivity of 85.4% and a specificity of 68.8%. Conclusions: An elevated calcification score of the external iliac artery on the stenotic side is a correlate of restenosis of the lower extremity arteries after DCB combined stenting in patients with LEASO. With a cut-off value of 5.5 points, its sensitivity for predicting restenosis of the lower extremity arteries after DCB combined stenting is 85.4%, and its specificity is 68.8%.

[Evaluation of semicircular canal and otolith graviceptive pathway function in patients diagnosed with motion sickness disorder based on the diagnostic criteria of the Bárány society].

Objective: To investigate the altered function of the semicircular canal and otolith graviceptive pathway in patients diagnosed with motion sickness disorder (MSD) based on the diagnostic criteria of the Bárány society, and explore its relevance to the pathogenesis of MSD. Methods: This is a case-control study. Twenty patients with MSD and age-and sex-matched healthy controls without a history of MSD from the Department of Neurology of Aerospace Center Hospital between March and August 2022 were recruited. All subjects completed the motion sickness susceptibility questionnaire-short version (MSSQ-short) and the motion sickness assessment questionnaire (MSAQ). Canal function was evaluated using caloric stimulation test and video head impulse test (vHIT), and subjective visual vertical/horizontal (SVV/SVH) and vestibular evoked myogenic potential (VEMP) were employed to assess otolith graviceptive function. Differences in vestibular function and correlations between the two groups were analyzed. Results: Each group consisted of 20 cases (9 males and 11 females). The mean age of the MSD and control groups was (26.9±3.9) years and (27.0±3.4) years, respectively. The scores of MSSQ-short [27.0 (22.5, 38.8) vs 1.2 (0, 3.2), P<0.001] and MSAQ [70.1 (54.5, 78.1) vs 11.8 (11.1, 13.9), P<0.001] were significantly higher in the MSD group compared with those of the control group. Evaluation of canal function revealed a significantly higher incidence of caloric stimulation intolerance in MSD patients (60.0%, 12/20) compared with that of the control group (20.0%, 4/20) (P=0.010). Evaluation of otolith graviceptive pathway indicated no significant difference in SVV, SVH and cervical VEMP (cVEMP) abnormality rates between the two groups (all P>0.05). The ocular VEMP (oVEMP) abnormality rate was significantly higher in the MSD group (55.0%, 11/20) than that of the control group (10.0%, 2/20) (P=0.002), with a delayed P1-wave latency compared with the control group [(18.4±1.2) ms vs (17.6±0.8) ms, P=0.018]. Further correlation analysis revealed that P1-wave latency in oVEMP was positively correlated with MSSQ-short (r=0.486, P=0.002) and MSAQ (r=0.391, P=0.015) scores, and duration of caloric intolerance symptoms (r=0.377, P=0.004). Conclusion: The presence of hypersensitivity to caloric stimulation and delayed latency of otolith function in patients with MSD suggests a "separation" between semicircular canal and otolithic function, which may be related to sensory conflict.

[Comparison of clinical features of septic shock in children with hematological malignancies versus children without malignant tumors].

Objective: To investigate the clinical features of septic shock in children with hematological malignancies compared with those without malignant tumor in the pediatric intensive care unit (PICU). Methods: This retrospective study enrolled children with septic shock at the PICU of Capital Institute of Pediatrics' Children's Hospital from June 2015 to July 2022. According to the presence of hematological malignancies, patients were divided into the hematological malignancies group and without malignant tumor group. Clinical data were compared between the two groups, and logistic regression analysis was used to identify related factors for mortality. Results: A total of 164 children (97 males and 67 females) with a median age of 3.6 (interquartile range 0.8, 7.8) years were enrolled, including 75 (45.7%) patients with hematological malignancies and 89 (54.3%) patients without malignant tumors. Patients in the hematological malignancies group were older [6.0(3.6, 9.4) years vs 1.2 (0.4, 4.3) years, P<0.001] and more experienced hospital-acquired infections [48.0%(36/75) vs 21.3%(19/89),P=0.001], compared with patients without malignant tumors. Surgical emergencies were more frequent in patients without malignant tumors (32.6% vs 14.7%, P=0.013). Patients with hematological malignancies mainly had blood stream infections (58.7%), with Gram-negative bacilli (46.7%), meanwhile, patients without malignant tumors more experienced Gram-positive cocci infections (22.5%) of the respiratory system (40.4%) or digestive system (28.1%). There were significant differences regarding the infection sites (P<0.001) and pathogens (P=0.001). The types of antibacterial agents (P<0.001) and the frequency of noradrenaline (P=0.013) used in patients with hematological malignancies were significantly higher than those without malignant tumors. Patients with hematological malignancies had a higher incidence of multiple organ dysfunction (MODS) [100.0%(75/75) vs 80.9%(72/89), P<0.001] and higher 28-day mortality [34.8%(23/66) vs 19.0%(15/79),P=0.048]. Multivariate logistic regression analysis showed that Pediatric Critical Illness Score (PCIS) was an independent factor for death (odds ratio, OR=1.387, 95%CI: 1.161-1.657, P<0.001) in patients with hematological malignancies, and PCIS (OR=1.419, 95%CI: 1.140-1.767, P=0.002) and the 6-hour lactate clearance rate (OR=65.857, 95%CI: 2.953-1 468.638, P=0.008) were independent factors for death in patients without malignant tumors. Conclusions: Children with hematological malignancies were older, more frequently experienced bloodstream infections, and had a higher incidence of MODS and higher 28-day mortality. PCIS is related to poor prognosis of septic shock in children.

[Correlation analysis of carotid adipose tissue density and plaque stability in patients with carotid artery stenosis].

Objective: To investigate the correlation between perivascular fat density (PFD) and plaque stability in patients with carotid artery stenosis. Methods: Clinical data of 110 patients with carotid artery stenosis treated at Drum Tower Hospital, Nanjing University Medical School from January 2018 to December 2022 were retrospectively collected. Based on pathological results of carotid plaque specimens obtained from carotid endarterectomy (CEA), patients were categorized into stable plaque group (n=51) and vulnerable plaque group (n=59). All patients underwent preoperative carotid CT angiography (CTA) to measure PFD at the narrowest carotid artery. Preoperative levels of interleukin-6 (IL-6) and other hematological parameters were collected. Multivariable logistic regression analysis was used to identify factors associated with plaque stability in carotid artery stenosis patients. Area under the curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive value of PFD for plaque stability. Results: The stable plaque group consisted of 43 males and 8 females with a mean age of (67.6±9.0) years, while the vulnerable plaque group comprised 48 males and 11 females with a mean age of (69.3±9.0) years. The proportions of smokers were 31.4% (16/51) and 50.8% (30/59) in the stable and vulnerable plaque groups, respectively. The proportions of patients with diabetes were 33.3% (17/51) and 52.5% (31/59), respectively. IL-6 levels were 3.46(2.67, 5.34) and 4.51(3.62, 5.51) ng/L in the stable and vulnerable groups, respectively. Mean PFD values were (-69.04±5.35) and (-63.24±6.08) HU, respectively, with maximum PFD values of (-62.90±6.98) and (-56.93±5.90) HU, respectively. The differences were statistically significant (all P<0.05). Multivariable logistic regression analysis showed that increased mean PFD (OR=1.167, 95%CI: 1.029-1.324, P=0.016) and elevated IL-6 levels (OR=1.489, 95%CI: 1.151-1.926, P=0.002) were associated with vulnerability of carotid artery plaques. ROC curve analysis results showed that a cut-off value of -65.5 HU, the AUC for predicting plaque stability based on the mean PFD was 0.756 (95%CI: 0.667-0.844, P<0.001), with sensitivity of 64.4% and specificity of 74.5%. Conclusion: Increased mean PFD at the narrowest carotid artery is associated with vulnerability of plaques in patients with carotid artery stenosis.

[Risk factors analysis and prediction model establishment of contralateral central lymph node metastasis in intermediate-to-high risk unilateral papillary thyroid carcinoma].

Objective: To explore the risk factors of contralateral central lymph nodes (Cont-CLNs) metastasis in intermediate-to-high risk unilateral papillary thyroid carcinoma and establish a prediction model. Methods: The clinical data of 206 patients receiving thyroid cancer surgery at Nantong University Affiliated Hospital between January 2021 and June 2023 were retrospectively analyzed, including 50 males and 156 females, with an age of [M(Q1, Q3)] 49.0(33.8, 57.0) years old. The risk factors of Cont-CLNs metastasis were screened by univariate analysis and multivariate logistic regression analysis. A nomogram was constructed for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC. The area under the receiver operating characteristic (ROC) curve(AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the model's predictive ability, accuracy, and clinical applicability, respectively. R language was used to randomly select 70% of the patients to establish a validation group for internal validation of the model. Results: Patients were divided into a metastasis group (n=56) and a non-metastasis group (n=150) based on the occurrence of Cont-CLNs metastasis. The ages of the two groups were 39.0 (28.0, 56.8) years and 51.0 (38.8, 57.0) years, respectively. There were statistically significant differences in gender, maximum tumor diameter (>1 cm), ipsilateral central lymph nodes (Ipsi-CLNs) metastasis, number of Ipsi-CLNs metastases (≥4), and lateral lymph node metastasis and Cont-CLNs metastasis between the two groups (all P<0.05). The results of multivariate logistic regression analyses showed that males(OR=2.926, 95%CI: 1.063-8.051), maximum tumor diameter>1 cm(OR=4.471, 95%CI: 1.344-14.877), and number of Ipsi-CLNs metastases≥4 (OR=5.011, 95%CI: 1.815-13.834) were risk factors for Cont-CLNs metastasis (all P<0.05). The AUC of the ROC curve, sensitivity, and specificity for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC by the prediction model in the modeling group were 0.821 (95%CI: 0.744-0.898), 82.5%, and 63.4%, respectively. In the internal validation group, the AUC of the ROC curve, sensitivity, and specificity for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC by the prediction model were 0.810 (95%CI: 0.717-0.902), 63.3%, and 83.7%, respectively. The calibration curves of the modeling group and the validation group showed that the model had good calibration ability. The DCA curves of the modeling group and the validation group indicated that the prediction model had good clinical adaptability. Conclusions: The prediction model constructed in this study has good predictive performance for Cont-CLNs metastasis in intermediate-to-high uPTC. When patient with intermediate-to-high risk uPTC is male, with maximum tumor diameter>1 cm, and the number of Ipsi-CLNs metastases≥4 should be alert to Cont-CLNs metastasis, and bilateral central lymph node dissection may be considered.

[The clinicopathological features of adult thyroid tumors with DICER1 mutation].

A total of 37 cases of thyroid tumors with pathological features suggestive of DICER1 gene mutation were selected to detect the DICER1 gene and BRAF gene using Sanger sequencing. A total of 10 patients (27.0%) exhibited DICER1 gene mutation all of whom were female with an age of [M(Q1, Q3)] 38.0 (30.5, 47.5) years. All patients had wild-type BRAFV600E gene. The ultrasound examination showed high-low echogenic well-demarcated intra-thyroidal nodules with abundant peripheral and internal blood flow signals in the DICER1 mutated thyroid tumor. The tumor was confined within the thyroid gland, with a diameter of (3.68±1.31) cm. The pathological features are as follows: the majority of tumors are encapsulated, which mainly composed of large follicles rich in colloid and some are small and micro follicles. The nucleus is round and deeply stained or slightly light stained, small to medium-sized, with occasional nuclear grooves and a lack of nuclear pseudoinclusion bodies within the nucleus. Immunohistochemical staining shows that Ki67 proliferation index of approximately 2%-10%. All cases were followed up for 11 to 18 months, and there was no recurrences or distant metastase. This study confirmed that the DICER1 gene mutation is mutually exclusive with the BRAFV600E gene mutation. The thyroid tumor with DICER1 mutation are in big size and are more common in young females with a good prognosis. Cases with the wild-type DICER1 gene may exhibit similar morphological features, and molecular testing is recommended. If somatic DICER1 mutation is confirmed, patients should undergo germline mutation testing to rule out DICER1 syndrome in order to define whether genetic counseling is necessary.