Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears.

Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.

Evolutionary and biomedical insights from a marmoset diploid genome assembly.

The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes and diseases1. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an primate model system that is widely used in biomedical research2,3. The full spectrum of heterozygosity between the two haplotypes involves 1.36% of the genome-much higher than the 0.13% indicated by the standard estimation based on single-nucleotide heterozygosity alone. The de novo mutation rate is 0.43 × 10-8 per site per generation, and the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex-differentiation region and unique evolutionary changes in the marmoset Y chromosome. In addition, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain-related genes were highly conserved between marmosets and humans, although several genes experienced lineage-specific copy number variations or diversifying selection, with implications for the use of marmosets as a model system.

Deciphering the Role of Rapidly Evolving Conserved Elements in Primate Brain Development and Exploring Their Potential Involvement in Alzheimer's Disease.

Although previous studies have identified human-specific accelerated regions as playing a key role in the recent evolution of the human brain, the characteristics and cellular functions of rapidly evolving conserved elements (RECEs) in ancestral primate lineages remain largely unexplored. Here, based on large-scale primate genome assemblies, we identify 888 RECEs that have been highly conserved in primates that exhibit significantly accelerated substitution rates in the ancestor of the Simiiformes. This primate lineage exhibits remarkable morphological innovations, including an expanded brain mass. Integrative multiomic analyses reveal that RECEs harbor sequences with potential cis-regulatory functions that are activated in the adult human brain. Importantly, genes linked to RECEs exhibit pronounced expression trajectories in the adult brain relative to the fetal stage. Furthermore, we observed an increase in the chromatin accessibility of RECEs in oligodendrocytes from individuals with Alzheimer's disease (AD) compared to that of a control group, indicating that these RECEs may contribute to brain aging and AD. Our findings serve to expand our knowledge of the genetic underpinnings of brain function during primate evolution.

Integrative Omics Reveals Rapidly Evolving Regulatory Sequences Driving Primate Brain Evolution.

Although the continual expansion of the brain during primate evolution accounts for our enhanced cognitive capabilities, the drivers of brain evolution have scarcely been explored in these ancestral nodes. Here, we performed large-scale comparative genomic, transcriptomic, and epigenomic analyses to investigate the evolutionary alterations acquired by brain genes and provide comprehensive listings of innovatory genetic elements along the evolutionary path from ancestral primates to human. The regulatory sequences associated with brain-expressed genes experienced rapid change, particularly in the ancestor of the Simiiformes. Extensive comparisons of single-cell and bulk transcriptomic data between primate and nonprimate brains revealed that these regulatory sequences may drive the high expression of certain genes in primate brains. Employing in utero electroporation into mouse embryonic cortex, we show that the primate-specific brain-biased gene BMP7 was recruited, probably in the ancestor of the Simiiformes, to regulate neuronal proliferation in the primate ventricular zone. Our study provides a comprehensive listing of genes and regulatory changes along the brain evolution lineage of ancestral primates leading to human. These data should be invaluable for future functional studies that will deepen our understanding not only of the genetic basis of human brain evolution but also of inherited disease.

Association of triglyceride-glucose index and its combination with adiposity-related indices with the incidence of myocardial infarction: a cohort study from the UK Biobank.

BACKGROUND: The triglyceride-glucose (TyG) index performs better at reflecting insulin resistance when combined with waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHtR) than when used alone. This study aimed to prospectively examine the relationships between TyG, TyG-BMI, TyG-WC, and TyG-WHtR with the incidence of myocardial infarction (MI) and its subtypes. METHODS: This cohort study included 370,390 participants from the UK Biobank. The Cox proportional hazards model and restricted cubic spline regression model were used to assess the associations of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with MI, ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI). The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were employed to examine the predictive value of four indicators. RESULTS: The hazard ratios (HRs) and 95% confidence intervals (CIs) of MI in the highest quartiles for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.36 (1.28-1.44), 1.47 (1.39-1.56), 1.53 (1.43-1.64), and 1.58 (1.48-1.68) in the fully-adjusted model. Comparable findings were observed when the outcomes were reclassified as STEMI or NSTEMI. However, the associations of TyG-BMI, TyG-WC, and TyG-WHtR with the risk of STEMI were weaker than MI and NSTEMI. A linear dose-response association between TyG and the risk of MI and NSTEMI were demonstrated. TyG-BMI, TyG-WC, and TyG-WHtR all showed nonlinear patterns in their associations with the risk of MI, STEMI, and NSTEMI. TyG-WC was most effective in diagnosing MI (AUC: 0.648, 95% CI: 0.644-0.653), STEMI (AUC: 0.631, 95% CI: 0.622-0.639), and NSTEMI (AUC: 0.647, 95% CI: 0.641-0.654). CONCLUSION: The TyG index was linearly associated with increased risk of MI and NSTEMI, whereas TyG-BMI, TyG-WC, and TyG-WHtR were nonlinearly associated with increased risk of MI and NSTEMI. There were distinct patterns in the relationships between these indicators with STEMI. TyG-WC provided the best diagnostic effectiveness for MI, STEMI, and NSTEMI.

I2-Mediated [3 + 3] Annulation for the Construction of Indole-Pyrimidine-Pyrazole-Fused Tetracyclic Heteroarenes.

An I2-mediated annulation of 3-aminopyrazoles with indole-3-carboxaldehydes has been demonstrated for the first time. This tandem strategy allows the facile construction of indole-pyrimidine-pyrazole-fused tetracyclic heteroarenes that are otherwise inaccessible by the existing methods. These fused heterocycles exhibited enhanced antifungal activities against Valsa mali and Botryosphaeria dothidea compared with commercial Xemium fungicide.

Arylacryl amides: Design, synthesis and the protection against cisplatin-induced acute kidney injury via TLR4/STING/NF-κB pathway.

Arylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK2 cells. Furthermore, 9d can interact with TLR4 to inhibit TLR4/STING/NF-κB pathway in the RAW264.7 cell. In vivo AKI mice model, 9d significantly downregulated the level of serum creatinine (Scr), blood urea nitrogen (BUN) and the inflammatory factors (IL-1ß, IL-6, TNF-α) to improve kidney function. Morphological and KIM-1 analyses showed that 9d alleviated cisplatin-induced tubular damage. In a word, 9d was a promising lead compound for preventive and therapeutic of AKI.

Minimally Invasive Combined Medial and Lateral Approach for Treating Displaced Scapular Body and Neck Fractures.

BACKGROUND Traditional open surgery for displaced scapular body and neck fractures often results in significant trauma and complications. This study aimed to assess the efficacy of a combined medial and lateral minimally invasive approach compared with the traditional Judet approach. MATERIAL AND METHODS A retrospective analysis was conducted on 36 patients (22 men, 14 women; mean age 45.6 years) with displaced scapular body and neck fractures treated between May 2016 and May 2022. Nineteen patients underwent the minimally invasive approach, while 17 received the traditional Judet approach. Primary outcomes included surgical incision length, intraoperative blood loss, complication rate, time to postoperative pain relief (VAS score ≤3), and Constant-Murley shoulder score at 12 months. Statistical analysis was done using the t test and chi-square test. RESULTS The minimally invasive group had shorter incision lengths (mean difference: 10.0 cm; 95% CI: 8.1-11.9; P<0.001) and lower blood loss (mean difference: 129.4 mL; 95% CI: 119.0-139.8; P<0.001). They also experienced faster pain relief (mean difference: 3.0 days; 95% CI: 2.5-3.5; P<0.001) and higher Constant-Murley scores (mean difference: 7.4 points; 95% CI: 4.9-9.9; P<0.001). There were no significant differences in operative duration or fracture healing time. CONCLUSIONS The combined medial and lateral minimally invasive approach offers superior outcomes in reducing incision length, blood loss, complications, and pain, with enhanced shoulder function, making it a safe and effective alternative to the traditional Judet approach.

Health risk assessment of drinking groundwater in rural areas of Ru village and surrounding areas in Wutai County, China.

Nitrate pollution in groundwater is a global environmental problem that poses risks to human health. We investigate the health risks of nitrate in rural drinking groundwater in Rucun Township and surrounding areas of Wutai County, and provide a basis for healthy drinking water. By using statistical analysis software (SPSS19) and hydrogeochemical analysis software (AqQA), a qualitative and quantitative evaluation of nitrate health risks was conducted among populations of different ages and genders through water sample collection, chemical analysis, and construction of a human health risk model (HHRA). Through research, it was found that the average concentration of nitrate in the study area is 43.99 mg/L. Groundwater is severely polluted by NO3-, and nitrate pollution areas are mainly concentrated in the main human activity areas, especially in the main agricultural production areas. The Quaternary loess layer, as a permeable layer, cannot prevent groundwater from being polluted by NO3-. Through evaluation, it is believed that there is a health risk of nitrate pollution in rural drinking groundwater in Rucun Township and surrounding areas. Health risk level: infants>children>adult females>adult males. The discovery and evaluation results can provide a basis for the prevention and control of nitrate pollution in groundwater.

Del Nido versus conventional blood cardioplegia in patients with combined aortic root surgery: A retrospective study.

OBJECTIVE: This study aimed to compare the safety and efficacy of Del Nido cardioplegia (DNC) and conventional blood cardioplegia (CBC) in combined aortic surgery. METHODS: This retrospective study involved elective patients who underwent combined aortic root surgery between September 2017 and July 2023. Patients were divided into two groups: the DNC and the CBC group. The primary outcome was high-sensitivity cardiac troponin I and creatine kinase-MB levels at the 0, 1, 2, and three postoperative days. The secondary outcomes contained postoperative left ventricular ejection fraction, return to spontaneous rhythm after aortic de-clamping, postoperative myocardial infarction, new-onset atrial fibrillation, postoperative mechanical circulatory support, mechanical ventilation duration, intensive care unit stay, postoperative hospital stay, and the reduction of left ventricle end-diastolic diameter at 3 months after surgery. RESULTS: 223 patients were included and divided into the CBC (n = 111) and the DNC group (n = 112). There was no statistical difference in patients' demographics and preoperative parameters between the two groups. No in-hospital mortality. The total cardioplegia volume [35.25 (30.30,43.65) ml/kg versus 21.43 (18.42,25.62) ml/kg, p < 0.001] and infusion times [2 (2,3) times versus 1 (1,2) times, p < 0.001] were less and the incidence of return to spontaneous rhythm after de-clamping was higher in the DNC group [59.5% versus 83%, p < 0.001]. Postoperative high-sensitivity cardiac troponin I and creatine kinase-MB levels were comparable between the two groups. DNC is related to a shorter duration of mechanical ventilation, intensive care unit stay, and hospital stay than CBC. The rate of return to spontaneous rhythm after aortic de-clamping seemed to decrease with the prolongation of aortic cross-clamping (ACC) duration, and there was no difference between the two groups when the time exceeded 120 min. CONCLUSIONS: The safety and efficacy of using DNC were comparable to CBC in combined aortic surgery. The rate of return to spontaneous rhythm after aortic de-clamping seemed to decrease with the prolongation of ACC time. Further studies may be needed to fully elucidate the advantages of DNC in postoperative recovery and its long-term effects on patient outcomes.

A Novel Tongue Coating Segmentation Method Based on Improved TransUNet.

BACKGROUND: As an important part of the tongue, the tongue coating is closely associated with different disorders and has major diagnostic benefits. This study aims to construct a neural network model that can perform complex tongue coating segmentation. This addresses the issue of tongue coating segmentation in intelligent tongue diagnosis automation. METHOD: This work proposes an improved TransUNet to segment the tongue coating. We introduced a transformer as a self-attention mechanism to capture the semantic information in the high-level features of the encoder. At the same time, the subtraction feature pyramid (SFP) and visual regional enhancer (VRE) were constructed to minimize the redundant information transmitted by skip connections and improve the spatial detail information in the low-level features of the encoder. RESULTS: Comparative and ablation experimental findings indicate that our model has an accuracy of 96.36%, a precision of 96.26%, a dice of 96.76%, a recall of 97.43%, and an IoU of 93.81%. Unlike the reference model, our model achieves the best segmentation effect. CONCLUSION: The improved TransUNet proposed here can achieve precise segmentation of complex tongue images. This provides an effective technique for the automatic extraction in images of the tongue coating, contributing to the automation and accuracy of tongue diagnosis.

Association of statin use with osteoporosis risk: a drug-targeted Mendelian randomization study.

BACKGROUND: Hypercholesterolemia and the related inflammatory response promote the development of osteoporosis, but whether targeted interventions are protective against this bone metabolic disease remains unknown. The aim of this study was to investigate the association between the use of statins (one well-recognized cholesterol-lowering drug with anti-inflammatory properties) and the risk of osteoporosis using a drug-targeted Mendelian randomization (MR) approach. METHODS: Instrumental variables predicting three cholesterol-lowering target genes (including HGMCR) and the cholesterol effectors mediated by these genes (i.e., total cholesterol, LDL cholesterol, and non-HDL cholesterol) were extracted from expression quantitative trait loci and genome-wide association studies. Inverse variance-weighted (IVW), summary data-based MR (SMR), multivariate MR, and colocalization analysis were used to determine the association of the interventions represented by these instrumental variables with heel bone mineral density (one diagnostic indicator of osteoporosis). RESULTS: The IVW reported that increased levels of HGMCR-mediated total cholesterol, LDL cholesterol, and non-HDL cholesterol were associated with the decreased level of heel bone mineral density (P = 4.086e-10, P = 1.487e-09, P = 1.967e-09). The colocalization analysis supported the relationship between HGMCR-mediated non-HDL cholesterol and heel bone mineral density. The SMR reported that higher expression of HGMCR was associated with the decreased level of this osteoporosis indicator (P = 0.036). The multivariate MR further confirmed the role of HGMCR in the correlation between cholesterol traits and heel bone mineral density, and also reported that estrogen played a mediating role in the above correlations. CONCLUSION: These evidence supported a protective effect of HMGCR-mediated non-HDL cholesterol reduction or statin use against osteoporosis.

Protective effects of pulsed electromagnetic field therapy attenuates autophagy and apoptosis in osteoporotic osteoarthritis model rats by activating PPARγ.

Osteoporotic osteoarthritis (OPOA) is a specific phenotype of OA with high incidence and severe cartilage damage. This study aimed to explore the protective efficacy of PEMF on the progression of OPOA and observed the effects of PEMF on PPARγ, autophagy- and apoptosis-related proteins in OPOA rats. Rats were randomly divided into three groups: control group, OPOA group, and PEMF group (n = 6). One week after surgery, the rats in PEMF group were subjected to PEMF (3.82 mT, 8 Hz, 40 min/day and 5 day/week) for 12 weeks. Results showed that PEMF retarded cartilage degeneration and bone loss, as evidenced by pathological staining image, decreased MMP-13 expression and increased bone mineral density. PEMF inhibited the serum levels of inflammatory cytokines, and the expressions of caspase-3 and caspase-8, while upregulated the expression of PPARγ. Moreover, PEMF significantly improved the autophagy disorders, represented by decrease expressions of Beclin-1, P62, and LC3B. The research demonstrates that PEMF can effectively prevent cartilage and subchondral bone destruction in OPOA rats. The potential mechanism may be related to upregulation of PPARγ, inhibition of chondrocyte apoptosis and inflammation, and improvement of autophagy disorder. PEMF therapy thus shows promising application prospects in the treatment of postmenopausal OA.

Osteoporotic osteoarthritis (OPOA) is a very common combination disease, that characterized by chronic pain, swollen joints and susceptibility to fractures. It is particularly common in postmenopausal women. At present, drug therapy is the main treatment method, but the adverse reactions are serious and can not stop the progression of the disease. PEMF is a safe physical therapy that has been shown to increase bone density, reduce pain, and improve joints mobility. In this study, we aimed to explore the protective effect and potential mechanism of PEMF on OPOA. We found that PEMF significantly inhibited the inflammatory response, ameliorated the damaged cartilage and subchondral bone in OPOA rats, that maybe related to the regulation of chondrocyte autophagy and apoptosis. This study provided a new vision for PEMF' treatment on OPOA and has positive significance for the clinical promotion of PEMF.

Inhibition of Liver Cancer Cell Viability by Triazole through Up-regulation of p38 Phosphorylation and Targeting the Activation of p-ERK1/2 and Akt Protein Expression.

The present study was aimed to explore the effect of triazole on growth and viability of liver cancer cells. Cell growth was examined using the MTT test and expression of several proteins was assessed by western blotting assay. The Matrigel-coated Transwell assay was employed to examine the infiltration of cells. The data from MTT assay showed that MHCC97H and H4TG liver cancer cell viability was inhibited by triazole in a concentration-dependent manner. After treatment with 0.5, 1.0, 2.0, 4, 8, and 16 µM doses of triazole, the rate of H4TG cell viability was decreased to 96, 73, 58, 39, 29, and 28%, respectively. Treatment of MHCC97H cells with 0.5, 1.0, 2.0, 4, 8, and 16 µM doses of triazole resulted in a reduction in cell viability to 94, 70, 53, 35, 22, and 21%, respectively. Triazole treatment also led to a significant reduction in MHCC97H cell invasiveness compared to the control cells. In MHCC97H cells treated with triazole, there was a noticeable decrease in the levels of p-ERK1/2, and p-Akt protein expression. Treatment of MHCC97H cells with triazole resulted in a prominent increase in p-p38 level. In summary, triazole inhibits growth and viability of liver cancer cells through targeting the activation of p-ERK1/2 and Akt proteins. Therefore, triazole may be investigated further as a therapeutic agent for the treatment of liver cancer.

The 3,3'-dimethoxy-4,4'-dihydroxy-stilbene Triazole (STT) Inhibits Liver Cancer Cell Growth by Targeting Akt/mTOR Pathway.

The present study was aimed to investigate the proliferation inhibitory ability of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene triazole (STT) on SNU449 and Huh7 cells. Moreover, the mechanism associated with the suppression of liver cancer cell proliferation by STT was also studied. The results revealed that STT suppresses proliferation of SNU449 and Huh7 cells to 28 and 21%, respectively treatment with 20 µM. The clonogenic survival of SNU449 and Huh7 cells was also significantly reduced after incubation with STT compared to the control cultures. In comparison to the control, STT treatment significantly decreased the invasive potential of SNU449 cells. Treatment with STT led to a prominent suppression in p62 and increase in LC3B protein expression in SNU449 cells compared to the control cells. The STT treatment dramatically decreased p-Akt and p-mTOR protein expression in SNU449 cells. Docking study revealed that STT interacts via traditional hydrogen bonding with the glutamine, phenylalanine, leucine, serine, arginine, aspartic acid, and lysine residues of Akt protein. In summary, the current study demonstrates that STT effectively suppresses the viability of SNU449 and Huh7 liver cancer cells. Moreover, STT treatment of the liver cancer cells also significantly reduces the clonogenic survival and invasive potential of SNU449 cells. Treatment of liver cancer cells with STT increases the expression of autophagic, targets anti-autophagic protein expression and down-regulates Akt/mTOR pathway to inhibit cancer growth and proliferation. Thus, STT exhibits prominent anticancer effect and needs to be investigated further as a potential candidate for the treatment of liver cancer.

Negatively Curved Octagon-Incorporated Aza-nanographene and its Assembly with Fullerenes.

A negatively curved aza-nanographene (NG) containing two octagons was synthesized by a regioselective and stepwise cyclodehydrogenation procedure, in which a double aza[7]helicene was simultaneously formed as an intermediate. Their saddle-shaped structures with negative curvature were unambiguously confirmed by X-ray crystallography, thereby enabling the exploration of the structure-property relationship by photophysical, electrochemical and conformational studies. Moreover, the assembly of the octagon-embedded aza-NG with fullerenes was probed by fluorescence spectral titration, with record-high binding constants (Ka=9.5×103 M-1 with C60, Ka=3.7×104 M-1 with C70) found among reported negatively curved polycyclic aromatic compounds. The tight association of aza-NG with C60 was further elucidated by X-ray diffraction analysis of their co-crystal, which showed the formation of a 1 : 1 complex with substantial concave-convex interactions.

Self-Assemble Silk Fibroin Microcapsules for Cartilage Regeneration through Gene Delivery and Immune Regulation.

Effective treatments for cartilage defects are currently lacking. Gene delivery using proper delivery systems has shown great potential in cartilage regeneration. However, the inflammatory microenvironment generated by the defected cartilage severely affects the system's delivery efficiency. Therefore, this study reports a silk fibroin microcapsule (SFM) structure based on layer-by-layer self-assembly, in which interleukin-4 (IL-4) is modified on silk by click chemistry and loaded with lysyl oxidase plasmid DNA (LOX pDNA). The silk microcapsules display good biocompatibility and the release rate of genes can be adjusted by controlling the number of self-assembled layers. Moreover, the functionalized SFMs mixed with methacrylated gelatin (GelMA) exhibit good injectability. The IL-4 on the outer layer of the SFM can regulate macrophages to polarize toward the M2 type, thereby promoting cartilage matrix repair and inhibiting inflammation. The LOX pDNA loaded inside can be effectively delivered into cells to promote extracellular matrix generation, significantly promoting cartilage regeneration. The results of this study provide a promising biomaterial for cartilage repair, and this novel silk-based microcapsule delivery system can also provide strategies for the treatment of other diseases.

Synergistic Effect of Surface p-Doping and Passivation Improves the Efficiency, Stability, and Reduces Lead Leakage in All-Inorganic CsPbIBr2 -Based Perovskite Solar Cells.

Wide-bandgap inorganic cesium lead halide CsPbIBr2 is a popular optoelectronic material that researchers are interested in because of the character that balances the power conversion efficiency and stability of solar cells. It also has great potential in semitransparent solar cells, indoor photovoltaics, and as a subcell for tandem solar cells. Although CsPbIBr2 -based devices have achieved good performance, the open-circuit voltage (Voc ) of CsPbIBr2 -based perovskite solar cells (PSCs) is still lower, and it is critical to further reduce large energy losses (Eloss ). Herein, a strategy is proposed for achieving surface p-type doping for CsPbIBr2 -based perovskite for the first time, using 1,5-Diaminopentane dihydroiodide at the perovskite surface to improve hole extraction efficiency. Meanwhile, the adjusted energy levels reduce Eloss and improve Voc of the CsPbIBr2 PSCs. Furthermore, the Cs- and Br-vacancies at the interface are filled, reducing structural disorder and defect states and thus improving the quality of the perovskite film. As a result, the target device achieves a high efficiency of 11.02% with a Voc of 1.33 V, which is among the best values. In addition to the improved performance, the stability of the target device under various conditions is enhanced, and the lead leakage is effectively suppressed.

Deep-learning-based 3D super-resolution MRI radiomics model: superior predictive performance in preoperative T-staging of rectal cancer.

OBJECTIVES: To investigate the feasibility and efficacy of a deep-learning (DL)-based three-dimensional (3D) super-resolution (SR) MRI radiomics model for preoperative T-staging prediction in rectal cancer (RC). METHODS: Seven hundred six eligible RC patients (T1/2 = 287, T3/4 = 419) were retrospectively enrolled in this study and chronologically allocated into a training cohort (n = 565) and a validation cohort (n = 141). We conducted a deep-transfer-learning network on high-resolution (HR) T2-weighted imaging (T2WI) to enhance the z-resolution of the images and acquired the preoperative SRT2WI. The radiomics models named modelHRT2 and modelSRT2 were respectively constructed with high-dimensional quantitative features extracted from manually segmented volume of interests of HRT2WI and SRT2WI through the Least Absolute Shrinkage and Selection Operator method. The performances of the models were evaluated by ROC, calibration, and decision curves. RESULTS: ModelSRT2 outperformed modelHRT2 (AUC 0.869, sensitivity 71.1%, specificity 93.1%, and accuracy 83.3% vs. AUC 0.810, sensitivity 89.5%, specificity 70.1%, and accuracy 77.3%) in distinguishing T1/2 and T3/4 RC with significant difference (p < 0.05). Both radiomics models achieved higher AUCs than the expert radiologists (0.685, 95% confidence interval 0.595-0.775, p < 0.05). The calibration curves confirmed high goodness of fit, and the decision curve analysis revealed the clinical value. CONCLUSIONS: ModelSRT2 yielded superior predictive performance in preoperative RC T-staging by comparison with modelHRT2 and expert radiologists' visual assessments. KEY POINTS: • For the first time, DL-based 3D SR images were applied in radiomics analysis for clinical utility. • Compared with the visual assessment of expert radiologists and the conventional radiomics model based on HRT2WI, the SR radiomics model showed a more favorable capability in helping clinicians assess the invasion depth of RC preoperatively. • This is the largest radiomics study for T-staging prediction in RC.

A Systematic Review and Meta-analysis of Atherectomy Plus Balloon Angioplasty Versus Balloon Angioplasty Alone for Infrapopliteal Arterial Disease.

OBJECTIVE: The article aimed to compare the efficiency and safety of atherectomy plus balloon angioplasty (BA) with BA alone for the treatment of infrapopliteal arterial disease. METHODS: According to the inclusion and exclusion criteria, PubMed, Embase, and Cochrane Library database were searched for studies comparing atherectomy plus angioplasty and angioplasty alone in treating infrapopliteal artery lesions until November 2022. The endpoints included technical success, primary patency, clinically-driven target lesion revascularization (CD-TLR), periprocedural complications, distal embolization, target limb major amputation, and all-cause mortality. RESULTS: Ten studies met the requirements of our meta-analysis, including 7723 patients in the atherectomy plus BA group and 2299 patients in the BA alone group. The meta-analysis showed that atherectomy plus BA was associated with reduced CD-TLR (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.34, 0.78, p=0.002) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12-month follow-up. No statistically significant difference was found in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. Subgroup analysis found a higher rate of primary patency at 6 and 12 months (6 months: OR: 2.26, 95% CI: 1.11, 4.60, p=0.02; 12 months: OR: 2.38, 95% CI: 1.16, 4.86, p=0.02), and lower rates of CD-TLR (OR: 0.45, 95% CI: 0.25, 0.82, p=0.009) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12 months in patients treated with atherectomy plus drug-coated balloon (DCB) but not in patients treated with atherectomy plus plain old balloon angioplasty (POBA). CONCLUSIONS: This meta-analysis suggests that compared with BA alone, atherectomy plus BA may reduce the need for CD-TLR and the incidence of target limb major amputation at 12-month follow-up in the treatment of infrapopliteal artery occlusive lesions, even though there are no significant advantages in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. To go further, atherectomy plus DCB shows significant benefits in primary patency, CD-TLR, and target limb major amputation rate but atherectomy plus POBA does not'. However, due to the limitations of this article, more randomized controlled trials (RCTs) are needed to confirm these conclusions. CLINICAL IMPACT: According to our research, atherectomy combined with BA has the advantages of higher primary patency rate, lower CD-TLR and target limb significant amputation rate in treating infrapopliteal artery occlusive lesions, which may replace the current mainstream surgical method ---BA alone. For the clinician, although the surgery may take longer, it will significantly improve the prognosis and quality of life of patients and hold considerable significance for the management of patients with infrapopliteal arterial disease. Based on the characteristics of infrapopliteal artery disease, this study explored the feasibility of atherectomy combined with BA for infrapopliteal artery disease. Moreover, we found that atherectomy combined with DCB had better clinical efficacy, which should be the innovation of this study.