COVID-19 epidemic investigation study of a follow-up cohort of patients with diabetic kidney disease.

Introduction: The impact of coronavirus disease 2019 (COVID-19) on diabetic kidney disease (DKD) patients in China is not fully understood. This study aimed to investigate infection status in a DKD cohort post-renal biopsy and analyze vaccination and infection rates, as well as symptom severity, across various renal pathologies in DKD patients. Methods: This epidemiological survey, centered on COVID-19, employed a Chinese DKD and renal puncture follow-up cohort. A customized questionnaire enabled standardized data gathering. It collected data on clinical characteristics, vaccination and infection statuses, and diverse pathological types. The study analyzed the relationship between vaccination and infection statuses across various pathological types, evaluating characteristics and treatment outcomes in patients with infections. Results: In total, 437 patients with DKD from 26 Chinese provinces were followed up for a median of 44.6 ± 20 months. COVID-19 infection, vaccination, and novel coronavirus pneumonia (NCP) rates were 73.68%, 59.3%, and 6.63%, respectively. Ten patients with NCP had severe pneumonia or died of COVID-19. Renal pathology revealed that 167 (38.22%) patients had diabetic nephropathy (DN), 171 (39.13%) had non-diabetic renal disease (NDRD), and 99 had DN and NDRD (22.65%). The DN group had the lowest vaccination (54.5%), highest all-cause mortality (3.6%), and highest endpoint rates (34.10%). Compared to patients who were not vaccinated pre-infection (117 cases), vaccinated patients (198 cases) had reduced NCP (6.6% vs. 13.7%), severity (1.0% vs. 3.4%), and endpoint (9.10% vs. 31.60%) rates. Conclusion: Vaccination can prevent infection and diminish COVID-19 severity in patients with DKD; therefore, increasing vaccination rates is particularly important. Clinical Trial registration: ClinicalTrails.gov, NCT05888909.

The biphasic role of Hspb1 on ferroptotic cell death in Parkinson's disease.

Rationale: Ferroptosis-driven loss of dopaminergic neurons plays a pivotal role in the pathogenesis of Parkinson's disease (PD). In PD patients, Hspb1 is commonly observed at abnormally high levels in the substantia nigra. The precise consequences of Hspb1 overexpression in PD, however, have yet to be fully elucidated. Methods: We used human iPSC-derived dopaminergic neurons and Coniferaldehyde (CFA)-an Nrf2 agonist known for its ability to cross the blood-brain barrier-to investigate the role of Hspb1 in PD. We examined the correlation between Hspb1 overexpression and Nrf2 activation and explored the transcriptional regulation of Hspb1 by Nrf2. Gene deletion techniques were employed to determine the necessity of Nrf2 and Hspb1 for CFA's neuroprotective effects. Results: Our research demonstrated that Nrf2 can upregulate the transcription of Hspb1 by directly binding to its promoter. Deletion of either Nrf2 or Hspb1 gene abolished the neuroprotective effects of CFA. The Nrf2-Hspb1 pathway, newly identified as a defense mechanism against ferroptosis, was shown to be essential for preventing neurodegeneration progression. Additionally, we discovered that prolonged overexpression of Hspb1 leads to neuronal death and that Hspb1 released from ruptured cells can trigger secondary cell death in neighboring cells, exacerbating neuroinflammatory responses. Conclusions: These findings highlight a biphasic role of Hspb1 in PD, where it initially provides neuroprotection through the Nrf2-Hspb1 pathway but ultimately contributes to neurodegeneration and inflammation when overexpressed. Understanding this dual role is crucial for developing therapeutic strategies targeting Hspb1 and Nrf2 in PD.

ßAR-mTOR-lipin1 pathway mediates PKA-RIIß deficiency-induced adipose browning.

Background: Enhancing white adipose tissue (WAT) browning combats obesity. The RIIß subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIß gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored. Methods: This study investigates the mechanisms underlying WAT browning in RIIß-KO mice. Genetic approaches such as ß3-adrenergic receptors (ß3ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 in vitro, while AAV-shRNAs were used for the same purpose in vivo. Results: We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RIIß-KO mice. The WAT browning can be dampened by ß3ARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RIIß-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, ß3AR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally, in vivo knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity. Conclusions: The ß3AR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity.

Structural Comparisons, Fluorescence Properties, and Glass-to-Crystal Transformations of Heat-Cooled and Melt-Quenched Zeolitic Imidazolate Framework Glass.

As a representative of zeolitic imidazolate framework glass, agZIF-62 has been reported to be synthesized using a melt-quenching method in which the ZIF-62 crystal is heated to a temperature above the melting point. Interestingly, we unexpectedly found that agZIF-62 can also be synthesized by simple heating at temperatures lower than the melting point, which may be assisted by the release of encapsulated solvent molecules. The structural differences between melt-quenched agZIF-62 (MQ-agZIF-62) and heat-cooled agZIF-62 (HC-agZIF-62) were investigated. The results indicated that MQ-agZIF-62 is closer to the liquid state, while HC-agZIF-62 is closer to the crystal state. Interestingly, their luminescent emissions exhibit significant differences. Compared with the ZIF-62 crystal, MQ-agZIF-62 showed a blue-shift of 14 nm, whereas HC-agZIF-62 showed a red-shift of 9 nm. The emission intensity of agZIF-62 is also significantly stronger than that of ZIF-62; thus, rapid semiquantitative detection of the content of the MOF glass in glass and crystal mixtures can be achieved. In addition, HC-agZIF-62 and MQ-agZIF-62 can transform into ZIF-62 crystals via a solvent-media mechanism. This study provides new insights into ZIF-62 glass.

SORBS2-Mediated inhibition of malignant behaviors in esophageal squamous cell carcinoma through TIMP3.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is characterized by high invasiveness and poor prognosis. The role of Sorbin and SH3 domain-containing protein 2 (SORBS2) in ESCC remains largely unexplored. METHODS: The expression levels of SORBS2 in ESCC were detected using RNA-seq and proteomics data. The biological functions of SORBS2 in ESCC were investigated through in vivo and in vitro experiments. The mechanism of SORBS2 was explored using RIP-seq technology, which identified the key downstream molecule metalloproteinase-3 (TIMP3). The interaction between SORBS2 and TIMP3, including specific binding sites, was validated through RIP-qPCR and RNA pull-down assays. The impact of altered SORBS2 expression in ESCC on HUVECs was assessed using endothelial tube formation assays. RESULTS: SORBS2 expression was significantly downregulated in ESCC tissues, and its decreased expression was associated with poor prognosis. Overexpression of SORBS2 in ESCC cell lines inhibited cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, SORBS2 bound to the 3' UTR of TIMP3 mRNA, enhancing its stability and thereby regulating TIMP3 expression. Rescue experiments demonstrated that increased TIMP3 expression could reverse the promotive effects of SORBS2 knockdown on ESCC, confirming TIMP3 as a critical downstream molecule of SORBS2. Furthermore, downregulation of SORBS2 in ESCC cells was associated with activation of HUVEC functions, whereas upregulation of TIMP3 could reverse this effect. The SORBS2/TIMP3 axis may exert tumor suppressive effects by influencing extracellular matrix degradation. CONCLUSION: This study confirms that SORBS2 inhibits ESCC tumor progression by regulating extracellular matrix degradation through TIMP3, providing a potential therapeutic target for future treatment interventions.

Experience in the diagnosis and treatment of non-invasive bilateral carotid cavernous sinus fistula based on CT image examination.

Carotid cavernous fistula is a rare but clinically important vascular abnormality that is challenging to diagnose and treat. The clinical data of a patient with bilateral carotid cavernous fistula diagnosed by CT images were retrospectively analyzed. Through the analysis of CT images, the patient was accurately located and the diagnosis was confirmed. CT images can provide detailed anatomical information and accurately show the location, morphology and hemodynamic characteristics of carotid cavernous fistula. Through CT image examination, we successfully diagnosed bilateral carotid cavernous fistula patients, and can provide an important reference for surgical treatment. Therefore, CT image examination can provide accurate diagnosis and surgical planning information, and provide support for the formulation of individual treatment plans for patients. The application of this method is helpful to improve the early diagnosis rate and treatment effect of carotid cavernous fistula.

The muscular-deep fascial system: new findings on the anatomy of the structure attached to the superior orbital margin.

Studies on the muscular-deep fascial system which connects the upper eyelid, brow, and glabella, are lacking. This study aimed to explore the fine anatomy of the muscular-deep fascial system in the region between the eyebrow and the superior orbital margin. We included eight formalin-phenol-embalmed cadavers (16 sides of specimens), and categorized them into anatomical dissections and histological sections. Five cadavers (10 sides) were dissected for gross anatomical observation, whereas all soft tissues of the other three cadavers (6 sides) were dissected for tissue sectioning and histological analysis. Three tissue blocks and 16 strips in each block were trimmed, numbered, and sliced into these specimens. Hematoxylin-Eosin and Masson's Trichrome staining were performed. In the region between the eyebrow and the superior orbital margin, the frontalis was covered by the orbicularis oculi. Fibers of the frontalis muscle penetrated into the orbicularis oculi muscle bundles, and crosslinked around the eyebrow level. Both the frontalis and the orbicularis oculi were attached to the thickened multilayered deep fascia in this region, which could be regarded as the muscular-deep fascial system. The muscular-deep fascial system connects the frontalis deep fascia and deep forehead compartments down to the orbicularis-supporting ligament. The precise anatomy of the muscular-deep fascial system in the region between the eyebrow and the superior orbital margin may provide a valuable reference for soft-tissue fixation and suspension in facial surgery.

Self-Standing Chiral Covalent Organic Framework Thin Films with Full-Color Tunable Guest-Induced Circularly Polarized Luminescence.

Exploring self-standing chiral covalent organic framework (CCOF) thin films with controllable circularly polarized luminescence (CPL) is of paramount significance but remains challenging. Herein, we demonstrate the first example of self-standing CCOF films employing a polymerization-dispersion-filtration strategy. Pristine, low-quality CCOF films were produced by interfacial polymerization and then re-dispersed into COF colloidal solutions. Via vacuum assisted assembly, these COF colloids were densely stacked and assembled into self-standing, pure chiral COF films (L-/D-CCOF-F) that were transparent, smooth, crack-free and highly crystalline. These films were tunable in thicknesses, areas, and roughness, along with strong diffuse reflectance circular dichroism (DRCD) and cyan CPL signals, showing an intrinsic luminescence asymmetric factor (glum) of 4.3×10-3. Furthermore, these COF films served as host adsorbents to load various achiral organic dye guests through adsorption. The effective chiral transfer and energy transfer between CCOF-F and achiral fluorescent dyes endowed the dyes with strong chirality and tunable DRCD, resulting in intense, full-color-tunable solid-state CPL. Notably, the ordered arrangement of dye guest molecules within the preferentially oriented chiral pores of CCOF-F contributed to an amplified |glum| factor of 7.2×10-2, which is state-of-the-art for COF-based CPL materials. This work provides new insights into the design and fabrication of self-standing chiral COF films.

Correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 diabetic nephropathy.

Background: Diabetic nephropathy (DN) and diabetic retinopathy (DR) are common microvascular complications of diabetes. The purpose of this study was to investigate the correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 DN and to determine the capacity of retinal vascular geometric parameters in differentiating DN from non-diabetic renal disease (NDRD). Methods: The study participants were adult patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who underwent a renal biopsy. Univariate and multivariable regression analyses were performed to evaluate associations between retinal vessel geometry parameters and pathologically diagnosed DN. Multivariate binary logistic regression analyses were performed to establish a differential diagnostic model for DN. Results: In total, 403 patients were examined in this cross-sectional study, including 152 (37.7%) with DN, 157 (39.0%) with NDRD and 94 (23.3%) with DN combined with NDRD. After univariate logistic regression, total vessel fractal dimension, arteriolar fractal dimension and venular fractal dimension were all found to be associated with DN. In multivariate analyses adjusting for age, sex, blood pressure, diabetes, DR and other factors, smaller retinal vascular fractal dimensions were significantly associated with DN (P < .05). We developed a differential diagnostic model for DN combining traditional clinical indicators and retinal vascular geometric parameters. The area under the curve of the model established by multivariate logistic regression was 0.930. Conclusions: Retinal vessel fractal dimension is of great significance for the rapid and non-invasive differentiation of DN. Incorporating retinal vessel fractal dimension into the diagnostic model for DN and NDRD can improve the diagnostic efficiency.

Candesartan Cilexetil Formulations in Mesoporous Silica: Preparation, Enhanced Dissolution In Vitro, and Oral Bioavailability In Vivo.

Candesartan cilexetil (CC) is one of well-tolerated antihypertensive drugs, while its poor solubility and low bioavailability limit its use. Herein, two mesoporous silica (Syloid XDP 3150 and Syloid AL-1 FP) and the corresponding amino-modified products (N-XDP 3150 and N-AL-1 FP) have been selected as the carriers of Candesartan cilexetil to prepare solid dispersion through solvent immersion, and characterized through using powder X-ray diffraction analysis, infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and solid-state nuclear magnetic resonance spectroscopy, etc. The state of CC changed from crystalline to amorphous after loading onto the silica carriers, in which no interactions between CC and silica existed. Then, the dissolution behaviors in vitro were studied through using flow-through cell dissolution method. CC-XDP 3150 sample exhibited the most extensive dissolution, and the cumulative release of CC from it was 1.88-fold larger than that of CC. Moreover, the pharmacokinetic results in rats revealed that the relative bioavailability of CC-XDP 3150 and CC-N-XDP 3150 solid dispersions were estimated to be 326 % % and 238 % % in comparison with CC, respectively. Clearly, pore size, pore volume, and surface properties of silica carrier have remarkable effect on loading, dissolution and bioavailability of CC. In brief, this work will provide valuable information in construction of mesoporous silica-based delivery system toward poorly water-soluble drugs.

STING coordinates resolution of inflammation during wound repair by modulating macrophage trafficking through STAT3.

Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-α+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING-STAT3-chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts. STING regulates the macrophage trafficking through STAT3 in wound healing.

Preparation and Research on Mechanical Properties of Eco-Friendly Geopolymer Grouting Cementitious Materials Based on Industrial Solid Wastes.

Red mud (RM), a hazardous solid waste generated in the alumina production process, of which the mineral composition is mainly hematite, is unable to be applied directly in the cement industry due to its high alkalinity. With the rise of geopolymers, RM-based grouting materials play an essential role in disaster prevention and underground engineering. To adequately reduce the land-based stockpiling of solid wastes, ultrafine calcium oxide, red mud, and slag were utilized as the main raw materials to prepare geopolymers, the C-R-S (calcium oxide-red mud-slag) grouting cementitious materials. The direct impact of red mud addition on the setting time, fluidity, water secretion, mechanical properties, and rheological properties of C-R-S were also investigated. In addition, a scanning electron microscope (SEM), X-ray diffraction (XRD), three-dimensional CT (3D-CT), Fourier transform infrared spectroscopy (FT-IR), and other characterization techniques were used to analyze the microstructure and polymerization mechanism. The related results reveal that the increase in red mud addition leads to an enhanced setting time, and the C-R-S-40 grouting cementitious material (40% red mud addition) exhibits the best fluidity of 27.5 cm, the lowest water secretion rate of 5.7%, and a high mechanical strength of 57.7 MPa. The C-R-S polymer grout conforms to the Herschel-Bulkley model, and the fitted value of R2 is above 0.99. All analyses confirm that the preparation process of C-R-S grouting cementitious material not only substantially improves the utilization rate of red mud, but also provides a theoretical basis for the high-volume application of red mud in the field of grouting.

Relationship Between Asymmetry of Transverse Sinus and Difference in Intraocular Pressure.

BACKGROUND AND OBJECTIVE: This study used two-dimensional time-of-flight magnetic resonance venography (2D TOF MRV) to show the shape of the transverse sinus and to determine whether there is a correlation between the asymmetry of the transverse sinus morphology and the intraocular pressure (IOP) of the two eyes. METHODS: In this study, 63 male and 42 female volunteers were included. Those with obvious neurological diseases and eye diseases were excluded. According to the morphology of the transverse sinus scanned with 2D TOF MRV, subjects were divided into five groups. The IOP of the volunteers was measured separately. RESULTS: The difference between group I and group V is statistically significant (Z = 6.78, P < 0.01). Statistically, significant differences also existed among the IOP of each group, including the mean values of both eyes and the difference between the right eye and the left eye. The asymmetry of the transverse sinus maintained a negative correlation with the right IOP (r = 0.51, P < 0.01) and the difference between the right eye and the left eye (r = 0.79, P < 0.01). The asymmetry and the left IOP had no statistical correlation. CONCLUSION: The preliminary conclusion of this study is that if one side of the transverse sinus is thicker, the drainage-related ocular veins are relatively coarser, and the IOP is relatively lower. The 2D TOF MRV examination can be used as an examination to show the shape of the transverse sinus. It is a display method to provide a feasible means of inspection for a reasonable interpretation.

DNA methylation and whole-genome transcription analysis in CD4+ T cells from systemic lupus erythematosus patients with or without renal damage.

BACKGROUND: Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. METHODS: Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. RESULTS: We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. CONCLUSION: Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Development and Validation of a Predictive Model for Postoperative Intracranial Infections in Neurosurgery with Risk Factor Analysis.

BACKGROUND: Currently, the diagnosis of postneurosurgical intracranial infection is mainly dependent on cerebrospinal fluid (CSF) bacterial culture, which has the disadvantages of being time-consuming, having a low detection rate, and being easily affected by other factors. These disadvantages bring some difficulties to early diagnosis. Therefore, it is very important to construct a nomogram model to predict the risk of infection and provide a basis for early diagnosis and treatment. METHODS: This retrospective study analyzed postneurosurgical patient data from the Fourth Affiliated Hospital of Harbin Medical University between January 2019 and September 2023. The patients were randomly assigned in an 8:2 ratio into the training cohort and the internal validation cohort. In the training cohort, initial screening of relevant indices was conducted via univariate analysis. Subsequently, the least absolute shrinkage and selection operator logistic regression identified significant potential risk factors for inclusion in the nomogram model. The model's discriminative ability was assessed using the area under the receiver operating characteristic curve, and its calibration was evaluated through calibration plots. The clinical utility of the model was determined using decision curve analysis and further validated by the internal validation cohort. RESULTS: Multivariate logistic regression analysis of the training cohort identified 7 independent risk factors for postoperative intracranial infection: duration of postoperative external drainage (odds ratio [OR] 1.19, P = 0.005), continued fever (OR 2.11, P = 0.036), CSF turbidity (OR 2.73, P = 0.014), CSF pressure (OR 1.01, P = 0.018), CSF total protein level (OR 1.26, P = 0.026), CSF glucose concentration (OR 0.74, P = 0.029), and postoperative serum albumin level (OR 0.84, P < 0.001). Using these variables to construct the final model. The area under the receiver operating characteristic curve value of the model was 0.868 in the training cohort and 0.900 in the internal validation cohort. Calibration and the decision curve analysis indicated high accuracy and clinical benefit of the nomogram, findings that were corroborated in the validation cohort. CONCLUSIONS: This study successfully developed a novel nomogram for predicting postoperative intracranial infection, demonstrating excellent predictive performance. It offers a pragmatic tool for the early diagnosis of intracranial infection.

Orchestration of Macrophage Polarization Dynamics by Fibroblast-Secreted Exosomes during Skin Wound Healing.

Macrophages undertake pivotal yet dichotomous functions during skin wound healing, mediating both early proinflammatory immune activation and late anti-inflammatory tissue remodeling processes. The timely phenotypic transition of macrophages from inflammatory M1 to proresolving M2 activation states is essential for efficient healing. However, the endogenous mechanisms calibrating macrophage polarization in accordance with the evolving tissue milieu remain undefined. In this study, we reveal an indispensable immunomodulatory role for fibroblast-secreted exosomes in directing macrophage activation dynamics. Fibroblast-derived exosomes permitted spatiotemporal coordination of macrophage phenotypes independent of direct intercellular contact. Exosomes enhanced macrophage sensitivity to both M1 and M2 polarizing stimuli, yet they also accelerated timely switching from M1 to M2 phenotypes. Exosome inhibition dysregulated macrophage responses, resulting in aberrant inflammation and impaired healing, whereas provision of exogenous fibroblast-derived exosomes corrected defects. Topical application of fibroblast-derived exosomes onto chronic diabetic wounds normalized dysregulated macrophage activation to resolve inflammation and restore productive healing. Our findings elucidate fibroblast-secreted exosomes as remote programmers of macrophage polarization that calibrate immunological transitions essential for tissue repair. Harnessing exosomes represents a previously unreported approach to steer productive macrophage activation states with immense therapeutic potential for promoting healing in chronic inflammatory disorders.

The impact of deep-inspiration breath-hold total-body PET/CT imaging on thoracic 18F-FDG avid lesions compared with free-breathing.

OBJECTIVES: To investigate PET/CT registration and quantification accuracy of thoracic lesions of a single 30-second deep-inspiration breath-hold (DIBH) technique with a total-body PET (TB-PET) scanner, and compared with free-breathing (FB) PET/CT. METHODS: 137 of the 145 prospectively enrolled patients finished a routine FB-300 s PET/CT exam and a 30-second DIBH TB-PET with chest to pelvis low dose CT. The total-body FB-300 s, FB-30 s, and DIBH-30 s PET images were reconstructed. Quantitative assessment (SUVmax and SUVmean of lung and other organs), PET/CT registration assessment and lesion analysis (SUVmax, SUVpeak, SUVmean and tumor-background ratio) were compared with Wilcoxon signed-rank tests. RESULTS: The SUVmax and SUVmean of the lung with DIBH-30 s were significantly lower than those with FB. The distances of the liver dome between PET and CT were significantly smaller with DIBH-30 s than with FB. 195 assessable lesions in 106 patients were included, and the detection sensitivity was 97.9 % and 99.0 % in FB-300 s, and DIBH-30 s, respectively. For both small co-identified lesions (n = 86) and larger co-identified lesions with a diameter ≥ 1 cm (n = 91), the lesion SUVs were significantly greater with DIBH-30 s than with FB-300 s. Regarding lesion location, the differences of the SUVs for the lesions in the lower thorax area (n = 97, p < 0.001) were significant between DIBH-30 s and FB-300 s, while these differences were not statistically significant in the upper thorax (n = 80, p > 0.05). The lesion tumor-to-surrounding-background ratio (TsBR) was significantly increased, both in the upper and lower thorax. CONCLUSION: The TB DIBH PET/CT technique is feasible in clinical practice. It reduces the background lung uptake and achieves better registration and lesion quantification, especially in the lower thorax.

Cerebrospinal fluid efflux through dynamic paracellular pores on venules as a missing piece of the brain drainage system.

The glymphatic system plays a key role in the clearance of waste from the parenchyma, and its dysfunction has been associated with the pathogenesis of Alzheimer's disease (AD). However, questions remain regarding its complete mechanisms. Here, we report that efflux of cerebrospinal fluid (CSF)/interstitial fluid (ISF) solutes occurs through a triphasic process that cannot be explained by the current model, but rather hints at the possibility of other, previously undiscovered routes from paravenous spaces to the blood. Using real-time, in vivo observation of efflux, a novel drainage pathway was discovered, in which CSF molecules enter the bloodstream directly through dynamically assembled, trumpet-shaped pores (basolateral ϕ<8 µm; apical ϕ < 2 µm) on the walls of brain venules. As Zn2+ could facilitate the brain clearance of macromolecular ISF solutes, Zn2+-induced reconstruction of the tight junctions (TJs) in vascular endothelial cells may participate in pore formation. Thus, an updated model for glymphatic clearance of brain metabolites and potential regulation is postulated. In addition, deficient clearance of Aß through these asymmetric venule pores was observed in AD model mice, supporting the notion that impaired brain drainage function contributes to Aß accumulation and pathogenic dilation of the perivascular space in AD.

Safety and efficacy of ultrasound-guided percutaneous flexor retinaculum release of the ankle: an anatomical study.

Background: Tarsal tunnel syndrome (TTS) is a condition in which the tibial nerve (TN) (or its terminal branches) is compressed by the flexor retinaculum (FR) and the deep fascia of the abductor hallucis muscle at the tarsal tunnel, causing symptoms that negatively impact the patient's quality of life, including numbness, a sensation of a foreign object, coldness, and pain. FR release via microtrauma using needle-knife has proven to be effective in China and is widely used by clinicians. The traditional acupotomy, however, is the "blind knife" treatment, which cannot guarantee patient safety due to risk of injury to important structures, particularly the neurovascular bundle. Compared with the conventional treatments, ultrasound-guided percutaneous FR release possesses noteworthy advantages including high efficacy and safety. Methods: Percutaneous release of the FR was performed on 51 formalin-fixed specimens. The specimens were divided into two groups: an ultrasound-guided acupotomy pushing group comprising 20 legs (group U) and a nonultrasound-guided acupotomy pushing group comprising 31 legs (group N). After high-frequency ultrasound exploration, those with clear vascular imaging were included in group U; otherwise, they were included in group N. The FR was released percutaneously, soft tissue was dissected layer by layer, and anatomical data were recorded. Results: There no cases of injury in group U (0%) and four in group N (12.9%). Among the different intervention methods, there were no significant differences in tissue injury types (χ2=2.80; P=0.09). The percentage of released FR in group U was 80.00% while that in group N was 61.29% (χ2=1.977; P=0.16), which did not represent a significant difference between the two groups. However, group U had a significantly greater release length than that in the group N (t=3.359; P=0.002), indicating that the flexor release length guided by ultrasound is significantly greater than the unguided one. Conclusions: Ultrasound-guided percutaneous release of the FR using a needle-knife can provide greater length and percentage of released FR while maintaining a comparable safety rate to the unguided procedure.

Machine learning model for cardiovascular disease prediction in patients with chronic kidney disease.

Introduction: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). This study aimed to develop CVD risk prediction models using machine learning to support clinical decision making and improve patient prognosis. Methods: Electronic medical records from patients with CKD at a single center from 2015 to 2020 were used to develop machine learning models for the prediction of CVD. Least absolute shrinkage and selection operator (LASSO) regression was used to select important features predicting the risk of developing CVD. Seven machine learning classification algorithms were used to build models, which were evaluated by receiver operating characteristic curves, accuracy, sensitivity, specificity, and F1-score, and Shapley Additive explanations was used to interpret the model results. CVD was defined as composite cardiovascular events including coronary heart disease (coronary artery disease, myocardial infarction, angina pectoris, and coronary artery revascularization), cerebrovascular disease (hemorrhagic stroke and ischemic stroke), deaths from all causes (cardiovascular deaths, non-cardiovascular deaths, unknown cause of death), congestive heart failure, and peripheral artery disease (aortic aneurysm, aortic or other peripheral arterial revascularization). A cardiovascular event was a composite outcome of multiple cardiovascular events, as determined by reviewing medical records. Results: This study included 8,894 patients with CKD, with a composite CVD event incidence of 25.9%; a total of 2,304 patients reached this outcome. LASSO regression identified eight important features for predicting the risk of CKD developing into CVD: age, history of hypertension, sex, antiplatelet drugs, high-density lipoprotein, sodium ions, 24-h urinary protein, and estimated glomerular filtration rate. The model developed using Extreme Gradient Boosting in the test set had an area under the curve of 0.89, outperforming the other models, indicating that it had the best CVD predictive performance. Conclusion: This study established a CVD risk prediction model for patients with CKD, based on routine clinical diagnostic and treatment data, with good predictive accuracy. This model is expected to provide a scientific basis for the management and treatment of patients with CKD.