Measured proton electromagnetic structure deviates from theoretical predictions.

The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities1 that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities2 map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades2. Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.

Giant thermal Hall conductivity in the pseudogap phase of cuprate superconductors.

The nature of the pseudogap phase of the copper oxides ('cuprates') remains a puzzle. Although there are indications that this phase breaks various symmetries, there is no consensus on its fundamental nature1. Fermi-surface, transport and thermodynamic signatures of the pseudogap phase are reminiscent of a transition into a phase with antiferromagnetic order, but evidence for an associated long-range magnetic order is still lacking2. Here we report measurements of the thermal Hall conductivity (in the x-y plane, κxy) in the normal state of four different cuprates-La1.6-xNd0.4SrxCuO4, La1.8-xEu0.2SrxCuO4, La2-xSrxCuO4 and Bi2Sr2-xLaxCuO6+δ. We show that a large negative κxy signal is a property of the pseudogap phase, appearing at its critical hole doping, p*. It is also a property of the Mott insulator at p ≈ 0, where κxy has the largest reported magnitude of any insulator so far3. Because this negative κxy signal grows as the system becomes increasingly insulating electrically, it cannot be attributed to conventional mobile charge carriers. Nor is it due to magnons, because it exists in the absence of magnetic order. Our observation is reminiscent of the thermal Hall conductivity of insulators with spin-liquid states4-6, pointing to neutral excitations with spin chirality7 in the pseudogap phase of cuprates.

Thermodynamic signatures of quantum criticality in cuprate superconductors.

The three central phenomena of cuprate (copper oxide) superconductors are linked by a common doping level p*-at which the enigmatic pseudogap phase ends and the resistivity exhibits an anomalous linear dependence on temperature, and around which the superconducting phase forms a dome-shaped area in the phase diagram1. However, the fundamental nature of p* remains unclear, in particular regarding whether it marks a true quantum phase transition. Here we measure the specific heat C of the cuprates Eu-LSCO and Nd-LSCO at low temperature in magnetic fields large enough to suppress superconductivity, over a wide doping range2 that includes p*. As a function of doping, we find that Cel/T is strongly peaked at p* (where Cel is the electronic contribution to C) and exhibits a log(1/T) dependence as temperature T tends to zero. These are the classic thermodynamic signatures of a quantum critical point3-5, as observed in heavy-fermion6 and iron-based7 superconductors at the point where their antiferromagnetic phase comes to an end. We conclude that the pseudogap phase of cuprates ends at a quantum critical point, the associated fluctuations of which are probably involved in d-wave pairing and the anomalous scattering of charge carriers.

Exotic Magnetism in Perovskite KOsO_{3}.

A new perovskite KOsO_{3} has been stabilized under high-pressure and high-temperature conditions. It is cubic at 500 K (Pm-3m) and undergoes subsequent phase transitions to tetragonal at 320 K (P4/mmm) and rhombohedral (R-3m) at 230 K as shown from refining synchrotron x-ray powder diffraction (SXRD) data. The larger orbital overlap integral and the extended wave function of 5d electrons in the perovskite KOsO_{3} allow to explore physics from the regime where Mott and Hund's rule couplings dominate to the state where the multiple interactions are on equal footing. We demonstrate an exotic magnetic ordering phase found by neutron powder diffraction along with physical properties via a suite of measurements including magnetic and transport properties, differential scanning calorimetry, and specific heat, which provide comprehensive information for a system at the crossover from localized to itinerant electronic behavior.

Revisiting the use of the EORTC QLQ-STO22 to assess health-related quality of life of patients with gastric cancer: incorporating updated treatment options and cross-cultural perspectives.

BACKGROUND: The EORTC QLQ-STO22 (QLQ-STO22) is a firmly established and validated measure of health-related quality of life (HRQoL) for people with gastric cancer (GC), developed over two decades ago. Since then there have been dramatic changes in treatment options for GC. Also, East Asian patients were not involved in the development of QLQ-STO22, where GC is most prevalent and the QLQ-STO22 is widely used. A review with appropriate updating of the measure was planned. This study aims to capture HRQoL issues associated with new treatments and the perspectives of patients and health care professionals (HCPs) from different cultural backgrounds, including East Asia. METHODS: A systematic literature review and open-ended interviews were preformed to identify potential new HRQoL issues relating to GC. This was followed by structured interviews where HCPs and patients reviewed the QLQ-STO22 alongside new issues regarding relevance, importance, and acceptability. RESULTS: The review of 267 publications and interviews with 104 patients and 18 HCPs (48 and 9 from East Asia, respectively) generated a list of 58 new issues. Three of these relating to eating small amounts, flatulence, and neuropathy were recommended for inclusion in an updated version of the QLQ-STO22 and covered by five additional questions. CONCLUSIONS: This study supports the content validity of the QLQ-STO22, suggesting its continued relevance to patients with GC, including those from East Asia. The updated version with additional questions and linguistic changes will enhance its specificity, but further testing is required.

Value of spectral CT parameters in predicting the efficacy of neoadjuvant chemotherapy for gastric cancer.

AIM: To investigate the value of pre-chemotherapy spectral computed tomography (CT) parameters in predicting neoadjuvant chemotherapy (NAC) response in gastric cancer (GC). MATERIALS AND METHODS: Sixty patients with GC who received NAC and underwent spectral CT examination before chemotherapy were enrolled retrospectively and divided into a responsive group and a non-responsive group according to the postoperative pathological tumour regression grade. Clinical characteristics were collected. The iodine concentration (IC), water concentration (WC), and effective atomic number (Eff-Z) of the portal venous phases were measured before chemotherapy, and IC was normalised to that of the aorta to provide the normalised IC (NIC). An independent samples t-test, Mann-Whitney U-test, or chi-square test was used to analyse the differences between the two groups, and the receiver operating curve (ROC) was used to evaluate the predictive performance of different variables. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was lower in the responsive group than in the non-responsive group (p<0.05). IC, NIC, and Eff-Z values were significantly higher in the responsive group than in the non-responsive group (p<0.01). The areas under the ROC curves for the NLR, IC, NIC, and Eff-Z were 0.694, 0.688, 0.799, and 0.690, respectively. The combination of NIC, Eff-Z, and NLR values showed good diagnostic performance in predicting response to NAC in GC, with an area under the ROC curve of 0.857, 76.92% sensitivity, 80% accuracy, and 85.71% specificity. CONCLUSION: Spectral CT parameters may serve as non-invasive tools for predicting the response to NAC in patients with GC.

Preoperative CT histogram analysis to predict the expression of Ki-67 in solid pseudopapillary tumours of the pancreas.

AIM: To explore the value of preoperative computed tomography (CT) histogram features in predicting the expression status of Ki-67 in patients with solid pseudopapillary pancreatic tumours (SPTP). MATERIALS AND METHODS: This retrospective study analysed venous phase CT images of 39 patients with SPTP confirmed at surgery and histopathology and measured using the Ki-67 proliferation index from November 2015 to February 2022. According to the Ki-67 proliferation index, they were divided into high expression (Ki-67 ≥ 4%) and low expression (Ki-67 < 4%) groups. The histogram features of quantitative parameters were extracted using MaZda software, and the quantitative parameters of CT histograms were compared between groups. The receiver operating characteristic (ROC) curves of the patients were plotted according to the parameters, with statistically significant differences. The area under the curve (AUC), sensitivity, and specificity were calculated, and the effectiveness of the histogram parameters in predicting Ki-67 expression was analysed and evaluated. RESULTS: In total, 27 SPTP patients were enrolled, including 11 with high expression of Ki-67 and 16 with low expression. Comparative analysis of the Ki-67 high- and low-expression groups revealed a statistically significant in necrosis and variance (p<0.05). ROC curve analysis showed that the AUC of necrosis and variance predicting Ki-67 expression status were 0.753 and 0.841, the sensitivities were 81.8% and 81.3%, and the specificities were 68.7% and 81.8%, respectively. CONCLUSION: Preoperative CT histogram features help predict Ki-67 expression status in patients with SPTP.

18F-FDG PET/CT-based radiomics model for predicting the degree of pathological differentiation in non-small cell lung cancer: a multicentre study.

AIM: To explore the value of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)-based radiomics model for predicting the degree of pathological differentiation in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Clinical characteristics of 182 NSCLC patients from four centres were collected, and radiomics features were extracted from 18F-FDG PET/CT images. Three logistic regression prediction models were established: clinical model; radiomics model; and nomogram combining radiomics signatures and clinical features. The predictive ability of the models was assessed using receiver operating characteristics curve analysis. RESULTS: Patients from centre 1 were assigned randomly to the training and internal validation cohorts (7:3 ratio); patients from centres 2-4 served as the external validation cohort. The area under the curve (AUC) values for the clinical model in the training, internal validation, and external validation cohort were 0.74 (95% confidence interval [CI] = 0.64-0.84), 0.64 (95% CI = 0.46-0.81), and 0.74 (95% CI = 0.60-0.88), respectively. In the training (AUC: 0.84 [95% CI = 0.77-0.92]), internal validation (AUC: 0.81 [95% CI = 0.67-0.95]), and external validation cohorts (AUC: 0.74 [95% CI = 0.58-0.89]), the radiomics model showed good predictive ability for differentiation. Compared to the clinical and radiomics models, the nomogram has relatively better diagnostic performance, and the AUC values for nomogram in the training, internal validation, and external validation cohort were 0.86 (95% CI = 0.78-0.93), 0.83 (95% CI = 0.70-0.96), and 0.77 (95% CI = 0.62-0.92), respectively. CONCLUSIONS: The 18F-FDG PET/CT-based radiomics model showed good ability for predicting the degree of differentiation of NSCLC. The nomogram combining the radiomics signature and clinical features has relatively better diagnostic performance.

Multiphase computed tomography angiography combined with inflammation index to predict clinical functional prognosis in patients with acute ischemic stroke.

AIM: In this study, we investigated the feasibility of the Alberta Stroke Program Early CT Score (ASPECTS) and multiphase computed tomography angiography (mCTA) lateral branch circulation grading combined with clinical and laboratory indicators to predict the clinical prognosis of patients with acute ischemic stroke after 90 days. MATERIALS AND METHODS: The clinical data of 80 patients with acute anterior circulation ischemic stroke were retrospectively analyzed and divided into the good prognosis (37 cases) and poor prognosis groups (43 cases) according to their clinical function score at 90 days after discharge. Various factors, including basic imaging parameters (ASPECTS), occluded vessel location, affected side location and clinical indicators (time from onset to computed tomography examination, height, weight, body mass index, previous hypertension, and degree of hypertension and diabetes mellitus), laboratory blood rutine, and biochemical tests (white blood count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, hematocrit test, platelet count, international normalized ratio, blood glucose, triglycerides, uric acid, and D-dimer) were considered in the analysis. RESULTS: Logistic regression analysis showed that the mCTA score, hypertension, and neutrophil count were significant independent predictors. CONCLUSION: A nomogram of the mCTA score, hypertension, and neutrophil count may predict functional recovery after 90 days in patients with acute ischemic stroke.

"Very early" intrahepatic cholangiocarcinoma (≤ 2.0 cm): MRI manifestation and prognostic potential.

AIMS: To explore the MRI characteristics and clinical outcome of the "very early" intrahepatic cholangiocarcinoma (iCCA) ≤2.0cm. MATERIALS AND METHODS: Totally 213 pathologically confirmed iCCAs (44 ≤ 2.0cm and 169 of 2.0-5.0cm) from two institutes were included. Forty-four matching non-iCCA malignancies ≤2.0cm were also enrolled. Recurrence-free survival (RFS) was estimated and compared between iCCAs ≤2.0cm and 2.0-5.0cm. MRI features were analyzed and compared between iCCAs ≤2.0cm and 2.0-5.0cm, as well as between iCCAs ≤2.0cm and non-iCCAs ≤2.0cm. Univariate and multivariate regression analyses were performed to identify independent imaging features for discrimination. An MRI-based diagnostic model for iCCA ≤2.0cm was constructed by incorporating the independent imaging features. RESULTS: ICCAs ≤2.0cm had a significantly longer RFS than those of 2.0-5.0cm (log rank P=0.014). Imaging features of homogeneous signal (odds ratio (OR) = 6.677, P<0.001) and lack of vessel invasion (OR=7.56, P<0.001) were more frequently displayed in iCCAs ≤2.0cm compared to iCCAs of 2.0-5.0cm independently. In the small lesions ≤2.0cm, imaging features of progressive or persistent enhancement pattern (OR=27.78, P=0.002) and rim diffusion restriction (OR=5.70, P=0.027) were independent imaging features suggestive of iCCA over non-iCCA malignancy; their combination yielded an area under the curve value of 0.824, with a sensitivity of 97.73%. CONCLUSION: The "very early" iCCA ≤2.0cm was associated with a favorable outcome after surgery, it displayed different and relatively atypical imaging manifestations compared with those of 2.0-5.0cm. Furthermore, in the small lesions ≤ 2.0cm, MRI can be served as a useful non-invasive diagnostic tool for iCCA in clinical screening with high sensitivity.

Role of oedema and shrinkage patterns for prediction of response to neoadjuvant chemotherapy and survival outcomes in luminal breast cancer.

AIMS: To explore the independent and additional value of oedema and shrinkage patterns for predicting the disease-free survival (DFS) and neoadjuvant chemotherapy (NAC) response in luminal breast cancer (BC). MATERIALS AND METHODS: Patients with luminal BC who underwent NAC were enrolled in this study from 2017 to 2022. Traditional MRI features include BI-RADS-based MRI descriptors, tumor size, and ADC values, while emerging MRI features include oedema and shrinkage patterns, all of which were evaluated before, early, and after NAC. The changes in features during NAC were also evaluated. The value of features was evaluated through univariate, multivariate analyses. RESULTS: A total of 258 patients were enrolled in this study, of which 77 responded to NAC. Diffuse oedema, stable or increased oedema during early NAC were adverse predictors for treatment response, while a greater reduction in tumor size and increase in ADC value were favorable predictors (all P<0.05). Furthermore, 20 of 60 patients who were followed up experienced recurrence. Diffuse oedema, pre-pectoral or subcutaneous oedema, and non-concentric shrinkage patterns after NAC were risk factors for DFS, whereas a greater increase in ADC value was a protective factor. Incorporating oedema and shrinkage patterns into traditional MRI features improved the predictive performance for treatment response (AUC from 0.76-0.78 to 0.80-0.83) and DFS (C-index from 0.67-69 to 0.75-0.80). CONCLUSIONS: Oedema is an unfavorable predictor for treatment response and survival outcomes, while shrinkage patterns contribute more to the prognostic value, both of which could offer supplementary benefits for clinical outcomes in luminal BC.

Correlation between left atrial appendage morphology based on fractal dimension quantification and its hemodynamic parameters in patients with atrial fibrillation.

AIMS: To investigate the relationship between left atrial appendage (LAA) morphology, quantified based on fractal dimension (FD), and LAA hemodynamic parameters in patients with atrial fibrillation (AF), in an effort to reveal the effect of LAA shape on blood flow. MATERIALS AND METHODS: 225 patients with AF who underwent cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) were enrolled. LAA morphology was quantified based on FD on cardiac CTA images, and LAA hemodynamic parameters, including injection fraction (EF), filling peak flow velocity (FV), maximum speed of emptying (PEV), and wall motion velocity (WMV), were assessed using TEE. RESULTS: We divided the patients with AF into two groups based on a mean LAA FD of 1.32: the low FD group (n=124) and the high FD group (n=101). Compared to the low FD group, there were more patients with LAA circulatory stasis/thrombus (P=0.008) in the high FD group, as well as lower LAA FV (P=0.004), LAA PEV (P=0.007), and LAA WMV (P=0.007). LAA FD was an independent and significant determinant of LAA EF (ß = -11.755, P=0.001), LAA FV (ß = -17.364, P=0.004), LAA PEV (ß = -18.743, P<0.001), and LAA WMV (ß = -7.740, P=0.001) in multiple linear regression analysis. CONCLUSIONS: LAA FD is an essential determinant of LAA hemodynamic parameters, suggesting that the relatively complex morphology of the LAA may influence its hemodynamics, which can correlate with embolic events.

Relationship between pericoronary fat-attenuation values quantified by coronary computed tomography angiography and coronary artery disease severity.

AIM: To explore the relationship between pericoronary fat-attenuation index (FAI) values and coronary artery disease (CAD) severity measured using coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study retrospectively included 428 patients with CAD who were eligible and underwent CCTA at our hospital. CAD severity on CCTA images including obstructive stenosis and extensive lesions, and segment stenosis and involvement score (SSS, SIS), and CAD-RADS classification were assessed. FAI values for left anterior descending (LAD), left circumflex (LCX) branches, and right coronary artery (RCA) were quantified using fully automated software. The relationship between FAI values and CAD severity was assessed using univariate and multivariate regression models. RESULTS: Univariate analyses showed that sex and current smoking were associated with elevated FAILAD and FAILCX values (all P<0.05), whereas CAD severity was not relevant (all P>0.05). Not only clinical factors such as sex, current smoking, and hypertension were associated with elevated FAIRCA, but also indicators to assess CAD severity including obstructive stenosis, SIS, and SSS were related to it (all P<0.05). Multivariate analysis demonstrated that after correcting for the effects of other conventional cardiovascular risk factors and CCTA imaging features, current smoking was an independent risk factor for elevated FAI values (odds ratio [OR] = 0.569, 0.458, and 0.517; all P<0.05), whereas that SSS (OR=1.041, P=0.027) for elevated FAIRCA values. CONCLUSION: Following correction for conventional cardiovascular risk factors and imaging characteristics, current smoking was an independent clinical risk factor for elevated FAI values, and SSS was an independent risk factor for elevated FAIRCA values.

Added value of spectral computed tomography quantitative parameters for differentiating tuberculosis-associated fibrosing mediastinitis from endobronchial lung cancer: initial results.

OBJECTIVE: The objective of this study was to explore the added value of spectral computed tomography (CT) parameters to conventional CT features for differentiating tuberculosis-associated fibrosing mediastinitis (TB-associated FM) from endobronchial lung cancer (EBLC). METHODS: Chest spectral CT enhancement images from 109 patients with atelectasis were analyzed retrospectively. These patients were divided into two distinct categories: the TB-associated FM group (n = 77) and the EBLC group (n = 32), based on bronchoscopy and/or pathological findings. The selection of spectrum parameters was optimized with the least absolute shrinkage and selection operator regression analysis. The relationship between the spectrum parameters and conventional parameters was explored using Pearson's correlation. Multivariate logistic regression analysis was used to build spectrum model. The spectrum parameters in the spectrum model were replaced with their corresponding conventional parameters to build the conventional model. Diagnostic performances were evaluated using receiver operating characteristic curve analyses. RESULTS: There was a moderate correlation between the parameters ㏒(L-AEFNIC) - ㏒(L-AEFC) (r= 0.419; p< 0.0001), ㏒(O-AEF40KeV) - ㏒(O-AEFC) (r= 0.475; p< 0.0001), [L-A-hydroxyapatite {HAP}(I)] - (L-U-CT) (r= 0.604; p< 0.0001), {arterial enhancement fraction (AEF) derived from normalized iodine concentration (NIC) of lymph node (L-AEFNIC), AEF derived from CT40KeV of bronchial obstruction (O-AEF40KeV), arterial-phase Hydroxyapatite (Iodine) concentration of lymph node [L-A-HAP(I)], AEF derived from conventional CT (AEFC), unenhanced CT value (U-CT)}. Spectrum model could improve diagnostic performances compared to conventional model (area under curve: 0.965 vs 0.916, p= 0.038). CONCLUSION: There was a moderate correlation between spectrum parameters and conventional parameters. Integrating conventional CT features with spectrum parameters could further improve the ability in differentiating TB-associated FM from EBLC.

Vesical Imaging-Reporting and Data System (VI-RADS) as a grouping imaging biomarker combined with a decision-tree mode to preoperatively predict the pathological grade of bladder cancer.

AIM: To investigate whether the Vesical Imaging-Reporting and Data System (VI-RADS) could be used to develop a new non-invasive preoperative grade-prediction system to partially predict high-grade bladder cancer (HG-BC). MATERIALS AND METHODS: The present study enrolled 89 primary BC patients prospectively from March 2022 to June 2023. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of VI-RADS for predicting HG-BC and muscle-invasive bladder cancer (MIBC) in the entire group. In the low VI-RADS (≤2) group, the decision tree-based method was used to obtain significant predictors and construct the decision-tree model (DT model). The performance of the DT model and low VI-RADS scores for predicting HG-BC was determined using ROC, calibration, and decision curve analyses. RESULTS: At a cut-off of ≥3, the specificity and positive predictive value of VI-RADS for predicting HG-BC in the entire group was 100%, and the area under the ROC curve (AUC) was 0.697. Among 65 patients with low VI-RADS scores, the DT model showed an AUC of 0.884 in predicting HG-BC compared to 0.506 for low VI-RADS scores. Calibration and decision curve analyses showed that the DT model performed better than the low VI-RADS scores. CONCLUSION: Most VI-RADS scores ≥3 correspond to HG-BCs. VI-RADS could be used as a grouping imaging biomarker for a pathological grade-prediction procedure, which in combination with the DT model for low VI-RADS (≤2) populations, would provide a potential preoperative non-invasive method of predicting HG-BC.

CT quantification of pulmonary vessels in lung aging.

AIM: To evaluate the effect of aging on pulmonary vessels based on computed tomography (CT) quantification and analyse the correlation between quantitative pulmonary vascular volume and pulmonary function during aging. MATERIALS AND METHODS: A total of 330 healthy adult volunteers, including 161 men (53 aged 20-39 years, 61 aged 40-59 years, and 47 aged ≥60 years) and 169 women (53 aged 20-39 years, 63 aged 40-59 years, and 53 aged ≥60 years) were recruited in this study. AVIEW software was used to quantitatively measure pulmonary vascular volume, including pulmonary total blood vessel volume (TBV) and small blood vessel volume with a cross-sectional area of <5 mm2 (BV5). Pulmonary vascular volume parameters were standardised using the ratio of vascular volume to the body surface area (BSA; TBV/BSA and BV5/BSA). Subsequently, the effect of aging on the pulmonary vessels was analysed. RESULTS: The pulmonary vascular volume parameters TBV/BSA and BV5/BSA of the whole lung, right lung, and left lung decreased significantly with increasing age (p<0.05). Additionally, TBV/BSA and BV5/BSA of the whole lung were higher in men than in women. The declining trend of pulmonary vascular volume was consistent in men and women and increased with age. CONCLUSIONS: The pulmonary vascular volume parameters, TBV/BSA and BV5/BSA, decreased with age and were weakly positively correlated with pulmonary function.

Sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis.

BACKGROUND: The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated. OBJECTIVE: This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer. METHODS: We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24 weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0. RESULTS: A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03). CONCLUSION: SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.

The complexity of glucose time series is associated with short- and long-term mortality in critically ill adults: a multi-center, prospective, observational study.

BACKGROUND: The wealth of data taken from continuous glucose monitoring (CGM) remains to be fully used. We aimed to evaluate the relationship between a promising new CGM metric, complexity of glucose time series index (CGI), and mortality in critically ill patients. METHODS: A total of 293 patients admitted to mixed medical/surgical intensive care units from 5 medical centers in Shanghai were prospectively included between May 2020 and November 2021. CGI was assessed using intermittently scanned CGM, with a median monitoring period of 12.0 days. Outcome measures included short- and long-term mortality. RESULTS: During a median follow-up period of 1.7 years, a total of 139 (47.4%) deaths were identified, of which 73 (24.9%) occurred within the first 30 days after ICU admission, and 103 (35.2%) within 90 days. The multivariable-adjusted HRs for 30-day mortality across ascending tertiles of CGI were 1.00 (reference), 0.68 (95% CI 0.38-1.22) and 0.36 (95% CI 0.19-0.70), respectively. For per 1-SD increase in CGI, the risk of 30-day mortality was decreased by 51% (HR 0.49, 95% CI 0.35-0.69). Further adjustment for HbA1c, mean glucose during hospitalization and glucose variability partially attenuated these associations, although the link between CGI and 30-day mortality remained significant (per 1-SD increase: HR 0.57, 95% CI 0.40-0.83). Similar results were observed when 90-day mortality was considered as the outcome. Furthermore, CGI was also significantly and independently associated with long-term mortality (per 1-SD increase: HR 0.77, 95% CI 0.61-0.97). CONCLUSIONS: In critically ill patients, CGI is significantly associated with short- and long-term mortality.

DACH1 attenuated PA-induced renal tubular injury through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway.

BACKGROUND: Palmitic acid (PA), the major saturated fatty acid in the blood, often induces the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. DACH1 is an important regulator of kidney functions. Herein, we investigated the roles of DACH1 in PA-induced kidney injury. METHODS: Clinical data from the NHANES database were subjected to analyse the association between serum PA (sPA), blood glucose and kidney function. Molecular docking of PA was performed with DACH1. Immunohistochemistry, cell viability, annexin V/7-AAD double staining, TUNEL assay, immunofluorescent staining, autophagic flux analysis, qRT-PCR and western blot were performed. RESULTS: Clinical data confirmed that sPA was increased significantly in the pathoglycemia individuals compared with controls and correlated negatively with renal function. Our findings suggested that PA could dock with DACH1. DACH1 enhances cell viability by inhibiting apoptosis and attenuating autophagy blockage induced by PA. Furthermore, the results demonstrated that DACH1 ameliorated inflammation and fibrosis through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway in PA-treated renal tubular epithelial cell line (HK-2). CONCLUSIONS: This study proved that sPA presents a risk factor for kidney injuries and DACH1 might serve as a protective target against renal function deterioration in diabetic patients.

Parent-child interaction, appetite self-regulation, and BMIz in Chinese preschoolers: a mediation analysis.

OBJECTIVES: Research on parent-child interaction (PCI) and its impact on children's weight status is a thriving study area. However, their potential pathways have not been established. This study investigated the association between PCI and children's body-mass index z score (BMIz) examining the role of appetite self-regulation (ASR) as a mediator. STUDY DESIGN: Mediation analysis. METHODS: We included children from 33 kindergartens in Wuhan with parents' consent, measuring children's height and weight, and calculating BMIz. To assess the PCI quality, we utilized the Brigance Parent-Child Interactions Scale. Additionally, children's ASR was tested by satiety responsiveness (SR) and food responsiveness (FR) using the Children's Eating Behavior Questionnaire. Quantile regression was employed to examine the PCI-BMIz association, while mediation analysis was conducted to explore ASR's mediating effect on the relationship between PCI and BMIz. RESULTS: Of 3973 children (53.88% boys) included in the analysis, the mean BMIz was 0.24 ± 1.13. The results revealed that children with poorer PCI quality have higher BMIz across all selected BMIz percentiles, except for the 5th percentile. Furthermore, these associations were significant across most percentiles, whether for boys or girls. Mediation analysis suggested that these associations were partially mediated by children's ASR (indFR = -0.026, PFR < 0.001; indSR = -0.058, PSR < 0.001), with stronger effects observed among boys. CONCLUSION: The variation in how strongly BMIz was linked to PCI across different percentiles suggests that children with poorer PCI have higher BMIz. The link is partially mediated through children's ASR. It's important to pay attention to the PCI quality in children with higher BMIz levels, especially in boys.