Urolithin A attenuates hexavalent chromium-induced small intestinal injury by modulating PP2A/Hippo/YAP1 pathway.

Hexavalent chromium (Cr(VI)) exposure has been linked with gastrointestinal toxicity, whereas the molecular pathways and key targets remain elusive. Computational toxicology analysis predicted the correlation between protein phosphatase 2A (PP2A) and genes regarding Cr(VI)-induced intestinal injury. Here, we generated a mouse model with intestinal epithelium-specific knock out of Ppp2r1a (encoding PP2A Aα subunit) to investigate the mechanisms underlying Cr(VI)-induced small intestinal toxicity. Heterozygous (HE) mice and matched WT littermates were administrated with Cr(VI) at 0, 5, 20, and 80 mg/l for 28 successive days. Cr(VI) treatment led to crypt hyperplasia, epithelial cell apoptosis, and intestinal barrier dysfunction, accompanied by the decline of goblet cell counts and Occludin expression in WT mice. Notably, these effects were aggravated in HE mice, indicating that PP2A Aα deficiency conferred mice with susceptibility to Cr(VI)-induced intestinal injury. The combination of data analysis and biological experiments revealed Cr(VI) exposure could decrease YAP1 phosphorylation at Ser127 but increase protein expression and activity, together with elevated transcriptional coactivator with PDZ-binding motif protein driving epithelial crypt cells proliferation following damage, suggesting the involvement of Hippo/YAP1 signaling pathway in Cr(VI)-induced intestinal toxicity. Nevertheless, the enhanced phosphorylation of YAP1 in HE mice resulted in proliferation/repair defects in intestinal epithelium, thereby exacerbating Cr(VI)-induced gut barrier dysfunction. Notably, by molecular docking and further studies, we identified urolithin A, a microbial metabolite, attenuated Cr(VI)-induced disruption of intestinal barrier function, partly by modulating YAP1 expression and activity. Our findings reveal the novel molecular pathways participated in Cr(VI)-caused small intestinal injury and urolithin A could potentially protect against environmental hazards-induced intestinal diseases.

Echinococcus multilocularis serpin regulates macrophage polarization and reduces gut dysbiosis in colitis.

Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin (Emu-serpin), within the larval stage of Echinococcus multilocularis. Our observations indicate that Emu-serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu-serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu-serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu-serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu-serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.

Use of Interfacial Interactions and Complexation of Carbon Dots to Construct Ultra-Robust and Efficient Photothermal Film From Micro-Carbonized Polysaccharides.

Solar energy conversion technologies, particularly solar-driven photothermal conversion, are both clean and manageable. Although much progress has been made in designing solar-driven photothermal materials, significant challenges remain, not least the photobleaching of organic dyes. To tackle these issues, micro-carbonized polysaccharide chains, with carbon dots (CDs) suspended from the chains, are conceived, just like grapes or tomatoes hanging from a vine. Carbonization of sodium carboxymethyl cellulose (CMC) produces just such a structure (termed CMC-g-CDs), which is used to produce an ultra-stable, robust, and efficient solar-thermal film by interfacial interactions within the CMC-g-CDs. The introduction of the CDs into the matrix of the photothermal material effectively avoided the problem of photobleaching. Manipulating the interfacial interactions (such as electrostatic interactions, van der Waals interactions, π-π stacking, and hydrogen bonding) between the CDs and the polymer chains markedly enhances the mechanical properties of the photothermal film. The CMC-g-CDs are complexed with Fe3+ to eliminate leakage of the photothermal reagent from the matrix and to solve the problem of poor water resistance. The resulting film (CMC-g-CDs-Fe) has excellent prospects for practical application as a photothermal film.

Cognitive impairment and neurocognitive profiles among people living with HIV and HIV-negative individuals older over 50 years: a comparison of IHDS, MMSE and MoCA.

We aimed to examine the l differences in the assessment of neurocognitive impairment (NCI) using cognitive screening tools between PLWH and HIV-negative individuals and further compare the neurocognitive profiles between the two groups. This was baseline evaluation of Pudong HIV Aging Cohort, including 465 people living with HIV (PLWH) and 465 HIV-negative individuals aged over 50 years matched by age (± 3 years), sex and education. NCI was assessed using the Chinese version of Mini-mental State Examination (MMSE), the International HIV Dementia Scale (IHDS) and Beijing version of Montreal Cognitive Assessment (MoCA). In total, 258 (55.5%), 91 (19.6%), 273 (58.7%) of PLWH were classified as having NCI by the IHDS, MMSE and MoCA, compared to 90 (19.4%), 25 (5.4%), 135 (29.0%) of HIV-negative individuals, respectively (p < 0.05); such associations remained significant in multivariable analysis. PLWH showed a larger overlap of NCI detected by IHDS, MMSE, and MoCA. IHDS and MoCA detected almost all of the NCI detected by MMSE. IHDS-motor and psychomotor speeds and MoCA-executive function showed the greatest disparities between two groups. In multivariable analysis, older age and more depressive symptoms were positively associated with NCI regardless of the screening tools or HIV serostatus. PLWH over 50 years old display a higher prevalence of NCI and distinct neurocognitive profiles compared to HIV-negative individuals, despite viral suppression. Given the more considerable overlap in NCI classification in PLWH, it is advisable to choose one screening tool such as IHDS or MoCA to identify those potentially having NCI and then refer to more comprehensive neuropsychological assessment.

What is the impact of ferroptosis on diabetic cardiomyopathy: a systematic review.

Iron overload increases the production of harmful reactive oxygen species in the Fenton reaction, which causes oxidative stress in the body and lipid peroxidation in the cell membrane, and eventually leads to ferroptosis. Diabetes is associated with increased intracellular oxidative stress, inflammation, autophagy, microRNA alterations, and advanced glycation end products (AGEs), which cause cardiac remodeling and cardiac diastolic contractile dysfunction, leading to the development of diabetic cardiomyopathy (DCM). While these factors are also closely associated with ferroptosis, more and more studies have shown that iron-mediated ferroptosis is an important causative factor in DCM. In order to gain fresh insights into the functions of ferroptosis in DCM, this review methodically summarizes the traits and mechanisms connected with ferroptosis and DCM.

Establishment of a pMCAO model in SD rats and screening for behavioral indicators suitable for long-term monitoring.

OBJECTIVE: This study aimed to establish a permanent middle cerebral artery occlusion (pMCAO) model in rats to simulate the pathological process of stroke patients with no reperfusion. And screen highly sensitive items that could be used to detect long-term behavioral abilities in rat of intraluminal suture models. METHOD: Established the pMCAO model then tested the rats for the bilateral asymmetry, modified neurological severity score, grid-walking, cylinder, rotating, and water maze test from week 1 to week 16. RESULTS: The infarct volume of the model rats was stable (26.72% ±1.86%). The sensorimotor test of bilateral asymmetry, grid-walking, cylinder, and mNSS test showed significant differences from week 1 to week 16 after injury. The water maze test at week 16 showed significant differences in spatial exploration and learning ability between the two groups. We confirmed that there was no significant difference between MRI and TTC staining in detecting the degree of brain injury, which facilitated the diversity of subsequent detection methods. We also confirmed that at multiple time points, grid, cylinder and water maze test were significantly positively correlated with rat brain infarct volume. CONCLUSION: They are suitable for the long-term observation of behaviors in the sequela stage of stroke in rat.

Associations between HIV infection and frailty status and its individual components: Are frailty components disproportionally affected?

OBJECTIVE: We aimed to examine whether HIV infection was independently associated with frailty status and its individual components. METHODS: This cross-sectional investigation included people living with HIV (PLWH) and HIV-negative individuals from the baseline survey of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, China. Frailty phenotype was based on five components: weight loss, low physical activity, exhaustion, weak grip strength and slow gait speed. Frailty was defined as the presence of at least three components, and prefrailty was defined as one or two components. Logistic regression models were used to analyse the factors associated with frailty and its components. RESULTS: In all, 2475 people living with HIV (age 45.5 ± 14.9 years; 76.2% male) and 4948 HIV-negative individuals (age 45.5 ± 14.8 years; 76.3% male) were included. Among PLWH, median CD4 count was 395 cells/µL and 78% were currently on antiretroviral therapy (ART). Frailty and prefrailty were significantly more prevalent in PLWH (3.2% vs 1.9% and 32.9% vs 27.9%) overall and at ages 18-39 (1.4% vs 0.2% and 22.7% vs 19.0%), 40-59 (2.5% vs 0.9% and 30.9% vs 27.9%) and 60-90 years (8.4% vs 7.4% and 57.1% vs 45.8%). HIV infection was associated with frailty and prefrailty [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.06-2.08; and aOR = 1.18, 95% CI: 1.05-1.33, respectively] after adjusting for confounding variables, but were strengthened with further adjustment for multimorbidity (aOR = 1.62, 95% CI: 1.14-2.28; and aOR = 1.22, 95% CI: 1.09-1.37), and were no longer significant with further adjustment for depressive symptoms and sleep disorders (aOR = 1.02, 95% CI: 0.71-1.46; and aOR = 1.06, 95% CI: 0.94-1.20). Among individual components, HIV infection was positively associated with weak grip strength and slow gait speed, but negatively associated with low physical activity and exhaustion in all the adjusted models described. CONCLUSIONS: Frailty and prefrailty occur more often and earlier in PLWH. However, grip strength and gait speed are affected to a greater extent, highlighting their potential as screening and intervention targets to prevent or slow frailty among PLWH.

Generation and characterization of intense terahertz pulses from DSTMS crystal.

Matter manipulation in terahertz range calls for a strong-field broadband light source. Here, we present a scheme for intense terahertz generation from DSTMS crystal driven by a high power optical parametric chirped pulse amplifier. The generated terahertz energy is up to 175 µJ with a peak electric field of 17 MV/cm. The relationship between terahertz energy, conversion efficiency, and pump fluence is demonstrated. This study provides a powerful driving light source for strong-field terahertz pump-probe experimentation.

Using Machine Learning Methods to Assess Lymphovascular Invasion and Survival in Breast Cancer: Performance of Combining Preoperative Clinical and MRI Characteristics.

BACKGROUND: Preoperative assessment of lymphovascular invasion (LVI) in invasive breast cancer (IBC) is of high clinical relevance for treatment decision-making and prognosis. PURPOSE: To investigate the associations of preoperative clinical and magnetic resonance imaging (MRI) characteristics with LVI and disease-free survival (DFS) by using machine learning methods in patients with IBC. STUDY TYPE: Retrospective. POPULATION: Five hundred and seventy-five women (range: 24-79 years) with IBC who underwent preoperative MRI examinations at two hospitals, divided into the training (N = 386) and validation datasets (N = 189). FIELD STRENGTH/SEQUENCE: Axial fat-suppressed T2-weighted turbo spin-echo sequence and dynamic contrast-enhanced with fat-suppressed T1-weighted three-dimensional gradient echo imaging. ASSESSMENT: MRI characteristics (clinical T stage, breast edema score, MRI axillary lymph node status, multicentricity or multifocality, enhancement pattern, adjacent vessel sign, and increased ipsilateral vascularity) were reviewed independently by three radiologists. Logistic regression (LR), eXtreme Gradient Boosting (XGBoost), k-Nearest Neighbor (KNN), and Support Vector Machine (SVM) algorithms were used to establish the models by combing preoperative clinical and MRI characteristics for assessing LVI status in the training dataset, and the methods were further applied in the validation dataset. The LVI score was calculated using the best-performing of the four models to analyze the association with DFS. STATISTICAL TESTS: Chi-squared tests, variance inflation factors, receiver operating characteristics (ROC), Kaplan-Meier curve, log-rank, Cox regression, and intraclass correlation coefficient were performed. The area under the ROC curve (AUC) and hazard ratios (HR) were calculated. A P-value <0.05 was considered statistically significant. RESULTS: The model established by the XGBoost algorithm had better performance than LR, SVM, and KNN models, achieving an AUC of 0.832 (95% confidence interval [CI]: 0.789, 0.876) in the training dataset and 0.838 (95% CI: 0.775, 0.901) in the validation dataset. The LVI score established by the XGBoost model was an independent indicator of DFS (adjusted HR: 2.66, 95% CI: 1.22-5.80). DATA CONCLUSION: The XGBoost model based on preoperative clinical and MRI characteristics may help to investigate the LVI status and survival in patients with IBC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Prediction of early improvement of major depressive disorder to antidepressant medication in adolescents with radiomics analysis after ComBat harmonization based on multiscale structural MRI.

BACKGROUND: Due to individual differences and lack of objective biomarkers, only 30-40% patients with major depressive disorder (MDD) achieve remission after initial antidepressant medication (ADM). We aimed to employ radiomics analysis after ComBat harmonization to predict early improvement to ADM in adolescents with MDD by using brain multiscale structural MRI (sMRI) and identify the radiomics features with high prediction power for selection of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). METHODS: 121 MDD patients were recruited for brain sMRI, including three-dimensional T1 weighted imaging (3D-T1WI)and diffusion tensor imaging (DTI). After receiving SSRIs or SNRIs for 2 weeks, the subjects were divided into ADM improvers (SSRIs improvers and SNRIs improvers) and non-improvers according to reduction rate of the Hamilton Depression Rating Scale, 17 item (HAM-D17) score. Then, sMRI data were preprocessed, and conventional imaging indicators and radiomics features of gray matter (GM) based on surface-based morphology (SBM) and voxel-based morphology (VBM) and diffusion properties of white matter (WM) were extracted and harmonized with ComBat harmonization. Two-level reduction strategy with analysis of variance (ANOVA) and recursive feature elimination (RFE) was utilized sequentially to decrease high-dimensional features. Support vector machine with radial basis function kernel (RBF-SVM) was used to integrate multiscale sMRI features to construct models for early improvement prediction. Area under the curve (AUC), accuracy, sensitivity, and specificity based on the leave-one-out cross-validation (LOO-CV) and receiver operating characteristic (ROC) curve analysis were calculated to evaluate the model performance. Permutation tests were used for assessing the generalization rate. RESULTS: After 2-week ADM, 121 patients were divided into 67 ADM improvers (31 SSRIs improvers and 36 SNRIs improvers) and 54 ADM non-improvers. After two-level dimensionality reduction, 8 conventional indicators (2 VBM-based features and 6 diffusion features) and 49 radiomics features (16 VBM-based features and 33 diffusion features) were selected. The overall accuracy of RBF-SVM models based on conventional indicators and radiomics features was 74.80% and 88.19%. The radiomics model achieved the AUC, sensitivity, specificity, and accuracy of 0.889, 91.2%, 80.1% and 85.1%, 0.954, 89.2%, 87.4% and 88.5%, 0.942, 91.9%, 82.5% and 86.8% for predicting ADM improvers, SSRIs improvers and SNRIs improvers, respectively. P value of permutation tests were less than 0.001. The radiomics features predicting ADM improver were mainly located in the hippocampus, medial orbitofrontal gyrus, anterior cingulate gyrus, cerebellum (lobule vii-b), body of corpus callosum, etc. The radiomics features predicting SSRIs improver were primarily distributed in hippocampus, amygdala, inferior temporal gyrus, thalamus, cerebellum (lobule vi), fornix, cerebellar peduncle, etc. The radiomics features predicting SNRIs improver were primarily located in the medial orbitofrontal cortex, anterior cingulate gyrus, ventral striatum, corpus callosum, etc. CONCLUSIONS: These findings suggest the radiomics analysis based on brain multiscale sMRI after ComBat harmonization could effectively predict the early improvement of ADM in adolescent MDD patients with a high accuracy, which was superior to the model based on the conventional indicators. The radiomics features with high prediction power may help for the individual selection of SSRIs and SNRIs.

A nomogram risk prediction model for poor outcome of primary brainstem hemorrhage based on clinical data and radiographic features.

OBJECTIVE: Primary brainstem hemorrhage (PBSH) is a devastating acute neurological disorder with a poor prognosis. This study aimed to identify risk factors associated with poor outcomes in PBSH patients and develop a novel nomogram for predicting prognosis, with external validation. METHODS: A total of 379 patients with PBSH were included in the training cohort. The primary outcome of interest was a modified Rankin Scale score (mRS) of 4-6 at 90 days post-onset. Multivariable logistic regression was used to construct a nomogram based on relevant variables. Model performance was tested in the training cohort and externally validated for discriminatory ability, calibration, and clinical utility at a separate institution. The nomogram was also compared to the ICH score in terms of predictive ability. RESULTS: The poor outcome rate at 90 days was 57.26% (217/379) in the training cohort and 61.27% (106/173) in the validation cohort. Multivariable logistic regression analysis identified age, Glasgow Coma Scale (GCS) score, and hematoma size as significant risk factors for poor outcomes. Nomograms based on these variables demonstrated good discrimination, with an area under the curve (AUC) of 0.855 and 0.836 in the training and validation cohorts, respectively. Furthermore, the nomogram showed superior predictive value to the ICH score for the 90-day outcome in both cohorts. CONCLUSION: This study developed and externally validated a nomogram risk prediction model for predicting poor outcomes at 90 days in patients with PBSH, using age, GCS score, and hematoma size as predictors. The nomogram demonstrated good discrimination, calibration, and clinical validity, serving as a valuable assessment and decision-making tool.

Establishment of a method for detecting Trichinella spiralis in ovine muscle tissues using real-time fluorescence quantitative PCR.

Trichinellosis is caused by Trichinella spiralis, a meat-borne zoonotic disease transmitted to humans through the consumption of infected undercooked or raw meat. Surveillance using safe and precise diagnostic tools to diagnose T. spiralis in sheep is needed to assess the incidence and probability of transmission from sheep to humans. In this study, we developed a real-time PCR assay to detect T. spiralis DNA in ovine muscle samples that can be used as an alternative surveillance tool to ensure food safety using newly designed primers. The assay is specific for the Scfld4 gene of Trichinella (T1) and enables the detection of larvae in ovine muscle tissue samples with high sensitivity and specificity. Trichuris ovis, Oesophagostomum dentatum, Haemonchus contortus, and Bunostomum trigonocephalum showed no nonspecific amplification. The assay could detect Trichinella DNA concentrations as low as 0.0026 ng/µL, equivalent to 0.0064 larvae, indicating a high sensitivity for T. spiralis detection. We used this real-time PCR to detect 73 ovine muscle samples from an ovine abattoir, and five samples tested positive via real-time PCR but negative via microscopy. This assay may provide a more specific and sensitive method for rapidly detecting Trichinella larvae in ovine muscle tissues.

A retrospective study to examine the association of different pear-shaped balloons with efficacy and postoperative complications in percutaneous balloon compression for trigeminal neuralgia.

Percutaneous balloon compression is a safe and effective therapeutic modality for trigeminal neuralgia. It is widely recognized that the pear-shaped balloon is the key to the success of the procedure. This study aimed to analyze the effect of different pear-shaped balloons on the duration of the treatment outcome. In addition, the relationship between individual variables and the duration and severity of complications was analyzed. The clinical data and intraoperative radiographs of 132 patients with trigeminal neuralgia were reviewed. We classify pear-shaped balloons into type A, type B, and type C balloons depending on the size of their heads. The collected variables were correlated with prognosis by univariate and multivariate analyses. The efficiency of the procedure was 96.9%. There was no significant difference in pain relief rates between the different pear-shaped balloons. Median pain-free survival time was longer for type B and C balloons, which were significantly different from type A balloons. In addition, pain duration also was a risk factor for recurrence. There was no significant difference in the duration of numbness between the different types of pear-shaped balloons, but type C balloons resulted in longer-lasting masticatory muscle weakness. Duration of compression and balloon shape can also significantly influence the severity of complications. Different pear-shaped balloons have been shown to have a significant effect on the efficacy and complications of the PBC procedure, with type B balloons (head ratio: 10-20%) appearing to be the ideal pear shape. However, its clinical application remains to be validated.

Amorphous hollow manganese silicate nanosphere oxidase mimic for ultrasensitive and high-reliable colorimetric detection of biothiols.

Metal-based nanozymes with exceptional physicochemical property and intrinsic enzymatic properties have been widely used in industrial, medical, and diagnostic fields. However, low substrate affinity results in unsatisfying catalytic kinetic and instability in complicated conditions, which significantly decreases their sensitivity and reliability. Herein, an amorphous hollow manganese silicate nanosphere (defined as AHMS) has been successfully synthesized via a facile one-step hydrothermal method and utilized in the archetype for colorimetric detection of biothiols with high sensitivity and high reliability. The experimental data demonstrates that ultrafast affinity of the substrate contributes to enhanced sensitivity with outstanding catalytic kinetic features (Km = 27.1 µM) and low limit of detection (LODGSH = 20 nM). The designed sensor demonstrates a reliable applicability for analysis of biological liquids (fetal calf serum and Staphylococcus aureus) and design of visual logic gates. Therefore, AHMS provides a promising strategy for ultrasensitive and high-reliable biosensing.

Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions.

BACKGROUND: Genome-wide association studies (GWAS) have identified some variants associated with subclinical atherosclerosis (SCA) in general population but lacking sufficient validation. Besides traditional risk factors, whether and how would genetic variants associate with SCA among people with HIV (PWH) remains to be elucidated. METHOD: A large original GWAS and gene-environment interaction analysis of SCA were conducted among Chinese PWH (n = 2850) and age/sex-matched HIV-negative controls (n = 5410). Subgroup analyses by age and functional annotations of variants were also performed. RESULTS: Different from HIV-negative counterparts, host genome had a greater impact on young PWH rather than the elders: one genome-wide significant variant (rs77741796, P = 2.20 × 10-9) and eight suggestively significant variants (P < 1 × 10-6) were identified to be specifically associated with SCA among PWH younger than 45 years. Seven genomic loci and 15 genes were mapped to play a potential role on SCA among young PWH, which were enriched in the biological processes of atrial cardiac muscle cell membrane repolarization and molecular function of protein kinase A subunit binding. Furthermore, genome-wide interaction analyses revealed significant HIV-gene interactions overall as well as gene-environment interactions with alcohol consumption, tobacco use and obesity among PWH. The identified gene-environment interaction on SCA among PWH might be useful for discovering high-risk individuals for the prevention of SCA, particularly among those with tobacco use and alcohol consumption. CONCLUSION: The present study provides new clues for the genetic contribution of SCA among young PWH and is the starting point of precision intervention targeting HIV-related atherosclerosis.

Interaction of declined handgrip strength and HIV infection on neurocognitive impairment.

Neurocognitive impairment (NCI) persists among people living with HIV (PLWH) despite the success of combination antiretroviral therapy (cART). Although muscular waning or decreased handgrip strength has been widely reported to be associated with cognitive erosion in general elders, such association has not been examined in PLWH who commonly experience decreased handgrip strength and NCI. Furthermore, whether HIV infection modifies such association remains to be addressed. A cross-sectional analysis was conducted with 2808 HIV-positive and 5402 HIV-negative adults participating in the baseline survey of the CHART (Comparative HIV and Aging Research in Taizhou) cohort, China, 2017 - 2019. HIV-positive individuals showed weaker handgrip strength than HIV-negative controls (34.0 kg vs 37.7 kg). Multivariate logistic regression analysis indicated that both HIV infection (aOR = 4.35, p < 0.001) and every 5-kg decrease in "Handgrip strength" (aOR = 1.27, p < 0.001) were significantly associated with NCI, and there was a significant interaction between reduced handgrip strength and HIV infection on NCI (aOR = 1.14, p = 0.015). In stratified analyses adjusting for potential confounders, the association between reduced handgrip strength and NCI was significant among PLWH at all age groups but only significant among HIV-negative controls at 30 - 44 and 60 - 89 ages. Handgrip strength decline is significantly associated with the risk of NCI among PLWH. HIV infection may exacerbate the adverse effect of poor handgrip strength on NCI, especially at younger ages. Early detection of handgrip strength decline could facilitate delivery of compensatory strategies or assistive services to PLWH with or at high risk of NCI.

Preoperative serum CA19-9 should be routinely measured in the colorectal patients with preoperative normal serum CEA: a multicenter retrospective cohort study.

OBJECTIVE: Whether preoperative serum carbohydrate antigen 19-9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified. METHODS: Consecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale. RESULTS: A total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5-62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724). CONCLUSIONS: Preoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

MRI characteristics of breast edema for assessing axillary lymph node burden in early-stage breast cancer: a retrospective bicentric study.

OBJECTIVES: To investigate whether breast edema characteristics at preoperative T2-weighted imaging (T2WI) could help evaluate axillary lymph node (ALN) burden in patients with early-stage breast cancer. METHODS: This retrospective study included women with clinical T1 and T2 stage breast cancer and preoperative MRI examination in two independent cohorts from May 2014 to December 2020. Low (< 3 LNs+) and high (≥ 3 LNs+) pathological ALN (pALN) burden were recorded as endpoint. Breast edema score (BES) was evaluated at T2WI. Univariable and multivariable analyses were performed by the logistic regression model. The added predictive value of BES was examined utilizing the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 1092 patients were included in this study. BES was identified as the independent predictor of pALN burden in primary (n = 677) and validation (n = 415) cohorts. The analysis using MRI-ALN status showed that BES significantly improved the predictive performance of pALN burden (AUC: 0.65 vs 0.71, p < 0.001; IDI = 0.045, p < 0.001; continuous NRI = 0.159, p = 0.050). These results were confirmed in the validation cohort (AUC: 0.64 vs 0.69, p = 0.009; IDI = 0.050, p < 0.001; continuous NRI = 0.213, p = 0.047). Furthermore, BES was positively correlated with biologically invasive clinicopathological factors (p < 0.05). CONCLUSIONS: In individuals with early-stage breast cancer, preoperative MRI characteristics of breast edema could be a promising predictor for pALN burden, which may aid in treatment planning. KEY POINTS: • In this retrospective study of 1092 patients with early-stage breast cancer from two cohorts, the MRI characteristic of breast edema has independent and additive predictive value for assessing axillary lymph node burden. • Breast edema characteristics at T2WI positively correlated with biologically invasive clinicopathological factors, which may be useful for preoperative diagnosis and treatment planning for individual patients with breast cancer.

Health-care access and utilization among HIV-infected men who have sex with men in two Chinese municipalities with or without lockdown amidst early COVID-19 pandemic.

City lockdown is critical to successfully contain the COVID-19 pandemic. The impact of lockdown and COVID-19 pandemic on healthcare among vulnerable population has yet to be explicated. A cross-sectional survey was conducted among HIV-infected men who have sex with men (MSM) in Wuhan with city lockdown and Shanghai without lockdown, and healthcare interruptions were evaluated and compared. A logistic regression analysis was employed to examine associates of HIV-related healthcare interruptions and compromised mental health. Compared to participants in Shanghai (N = 440), HIV-infected MSM in Wuhan (N = 503) had significantly higher proportion of untimely availability of antiretroviral drugs (ARVs) (20.6% vs. 8.4%), obtaining ARVs from outside institutions (29.1% vs. 8.1%), postponed non-AIDS treatment (6.4% vs. 2.8%) and untimely follow-up appointments (33.4% vs. 14.5%). HIV-related healthcare interruptions were positively associated with lockdown (OR = 4.89, 95% CI: 3.49-6.85) and non-local residence (OR = 1.91, 95% CI: 1.37-2.64). Compromised mental health, including insomnia and generalized anxiety disorders, was associated with non-local residence (OR = 1.35, 95% CI: 1.01-1.81) and healthcare interruptions (OR = 1.34, 95% CI: 1.01-1.79). HIV-infected MSM are vulnerable to healthcare interruptions and mental health problems during the COVID-19 pandemic, underscoring the need for tailored intervention strategies to minimize deleterious health consequences.

Increased CD4+ T cell count is associated with lower anal human papillomavirus prevalence among HIV-positive male cohort in Taizhou, China: a cross-sectional study.

OBJECTIVES: This study aims to investigate the association between CD4+ T cell count and combined antiretroviral therapy (cART) with the prevalence of anal human papillomavirus (HPV) infection among HIV-positive male cohort in China. METHODS: A survey was conducted in men from a HIV cohort in Taizhou, China between 2016 and 2019. A face-to-face questionnaire interview was administered, and an anal-canal swab was collected for HPV genotyping. RESULTS: A total of 766 HIV-positive men were recruited. The HPV prevalence was lower among those with increased CD4+ T cell count than those with decreased or unchanged (46.5 vs. 56.6%, p = 0.033) from baseline. In multivariable models, having the current CD4+ T cell count of 350-499 cells/µL (aOR 0.28, 95% CI 0.13-0.64), and of ≥ 500 cells/µL (aOR 0.26, 95% CI 0.11-0.60) were associated with lower prevalence of any type HPV infection compared with those with < 200 cells/µL. Having taken NVP + 3TC + AZT was inversely associated with any high-risk (HR)-HPV (aOR 0.47, 95% CI 0.25-0.90) and any low-risk (LR)-HPV infection (aOR 0.40, 95% CI 0.18-0.88), compared with those taking EFV + 3TC + TDF. CONCLUSIONS: Increased CD4+ T cell count at follow-up was significantly associated with lower prevalence of anal HPV infection. Inverse associations between NVP + 3TC + AZT and HR-HPV or LR-HPV infecton were observed.