Reconstruction of Allen's type IV fingertip amputation via bilateral unequal-sized hallux osteo-onychocutaneous free flaps: A retrospective study with 5-year follow-up.

PURPOSE: The reconstruction of Allen's type IV fingertip amputation is a clinical challenge. Our team designed bilateral unequal-sized hallux osteo-onychocutaneous free flaps for the long-term reconstruction of Allen's type IV fingertip amputation and conducted a retrospective study with a 5-year follow-up aims to evaluate the effects of this technique. METHODS: A retrospective analysis with a 5-year follow-up including 13 patients with Allen's type IV fingertip amputation who were admitted to our hospital from January 2010 to January 2017 was conducted. The patients were treated with bilateral unequal-sized hallux osteo-onychocutaneous free flaps. The operation time, intraoperative blood loss, and complications were recorded, and the survival rate of the transplanted flaps was calculated. During the 5-year follow-up after operation, the nail growth time was recorded and the finger appearance was observed. At the last follow-up appointment, the length, width, and girth of the reconstructed fingertip and contralateral normal fingertip, range of motion of the reconstructed fingertip and contralateral normal fingertip, Semmes-Weinstein test (for the evaluation of tactile sensation), and two-point discrimination testing results were recorded. SPSS 22.0 software was used for the statistical analysis and the data are presented as mean ± SD. RESULTS: The mean operation time was (5.62 ± 0.51) h, the mean intraoperative blood loss was (34.15 ± 3.13) mL, and the survival rate of the transplanted flaps was 100%. During the 5-year follow-up, the average nail growth time was (10.14 ± 1.98) months and the average bone union time was (3.78 ± 0.91) months. The length, width, and girth of the reconstructed fingertip were (31.52 ± 3.73) mm, (17.82 ± 1.74) mm, and (59.75 ± 3.04) mm, respectively, which did not differ from those of the contralateral normal fingertip. The range of motion of the reconstructed fingertip was (12.15 ± 2.79) degrees which is different from that of the contralateral normal fingertip. The average tactile sensation evaluated via the Semmes-Weinstein test and the average two-point discrimination test of the reconstructed fingertip were (0.39 ± 0.17) g and (7.46 ± 1.14) mm, respectively, which were not different from those of the contralateral normal fingertip. The average Maryland score of feet in the donor area was 87.66 ± 7.39, which was satisfactory. CONCLUSION: Bilateral unequal-sized hallux osteo-onychocutaneous free flaps are an effective method to reconstruct Allen's type IV fingertip amputations with a satisfactory appearance and good sensory function.

Assessment of perioperative cardiac risk using preoperative quantitative flow ratio in patients with coronary artery disease undergoing noncardiac surgery: a retrospective cohort study.

Background: Quantitative flow ratio (QFR) is a novel diagnostic modality for the functional testing of coronary artery stenosis, but evidence concerning the postoperative prognostic implication of QFR in noncardiac surgery (NCS) of patients with coronary artery disease (CAD) is limited. The purpose of this study was to examine the role of QFR in perioperative risk prediction in patients with coronary heart disease. Methods: This retrospective cohort study was conducted in The First Affiliated Hospital of Wenzhou Medical University between 2013 and 2022, and consecutively included patients with CAD who had undergone NCS <1 year after coronary angiography. The primary endpoint was major adverse cardiovascular events (MACEs), which were defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, cardiopulmonary arrest, malignant ventricular arrhythmia (MVA), congestive heart failure, and revascularization. Univariate and multifactorial Cox regression was used to identify the independent risk factors for perioperative cardiovascular events and to construct new models. The area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to compare the newly constructed model with existing traditional models. Results: Among the 929 participants enrolled (median age 68 years; 72.0% male), the primary endpoint was met in 67 (7.2%) patients within 30 days of follow-up. There was no significant difference in the incidence of the primary endpoint between patients with QFR <0.75 and those with "gray zone" lesions (0.75≤ QFR ≤0.8) (log-rank P=0.325). Patients with QFR <0.75 and those with "gray zone" lesions (0.75≤ QFR ≤0.8) had a higher incidence of primary endpoint events compared to patients with QFR >0.8. [QFR <0.75 vs. QFR >0.8: adjusted hazard ratio (HR) =20.70, P<0.001; 0.75≤ QFR ≤0.8 vs. QFR >0.8: HR =15.99, P<0.001]. The independent predictors of MACEs events within 30 days after NCS were albumin level [HR =0.92, 95% confidence interval (CI): 0.87-0.98; P=0.008], emergency surgery (HR =4.12, 95% CI: 1.66-10.23; P=0.002), and QFR ≤0.8 (HR =15.92, 95% CI: 5.96-42.51; P<0.001). In addition, adjusting the original Revised Cardiac Risk Index (RCRI) with QFR ≤0.8 as a risk factor significantly improved the risk stratification of postoperative adverse events, with the adjusted AUC rising from 0.574 to 0.740 (P<0.001). Conclusions: QFR ≤0.8 could independently predict perioperative cardiovascular adverse events in patients with CAD undergoing NCS and improve the predictive value of original predictive index. Gray-zone lesions (0.75≤ QFR ≤0.8) should be actively treated.

CTAC Self-Assembled Alkylated ß-Cyclodextrin Loaded onto Functionalized MWCNTs Electrochemical Sensor for NP Detection.

Nonylphenol (NP) is an important fine chemical raw material and intermediate that is widely utilized in industry and may be distributed in aquatic ecosystems. Following its entry into the food and water cycles, it can subsequently enter the human body and potentially harm the human reproductive system. For the purpose of monitoring NP in water, it is thus essential to build a straightforward, affordable, and robust electrochemical sensor. Based on a two-step chemical modification proceeding and an electrostatic self-assembly effect, a double-modified ß-cyclodextrin functionalized multiwalled carbon nanotube sensor (HE-ß-CD-CTAC/F-MWCNTs) has been successfully constructed. It incorporates the excellent host-guest interaction ability of ß-cyclodextrin and the high chemical activity of cetyltrimethylammonium chloride (CTAC), and the carbon nanotubes have an enormous particular surface area and strong electrical conductivity. The electrochemical oxidation reaction of NP with the sensor is controlled by a surface adsorption process of equal numbers of protons and electrons. In accordance with the optimized experimental parameters, the limit of detection (LOD) for the sensor is 0.13 µM, and it responds linearly to NP in the concentration range of 1-200 µM. Meanwhile, the sensor has excellent repeatability, stability, and immunity to interference. For the detection of NP in real water samples, the sensor also showed an excellent recovery rate (92.8%-98.5%) and relative standard deviation (1.16%-3.26%).

Distribution network insulator detection based on improved ant colony algorithm and deep learning for UAV.

Under the background of the accelerating speed of urban and rural construction, the geographical environment of overhead transmission lines has also changed greatly. Using unmanned aerial vehicle (UAV) to realize intelligent line inspection can significantly shorten inspection time and improve inspection efficiency. In this paper, the intelligent power inspection of UAVs is studied from two levels: path planning and UAV control, and the insulator is identified through actual image recognition. At the path planning level, the improved swarm intelligence algorithm is used to conduct simulation experiments on the UAV flight path to find a safe and effective route. Insulator identification and defect location of overhead transmission lines are trained on the insulator dataset collected by deep learning technology to achieve accurate insulator identification and improve the efficiency of UAV inspection, which has great application prospects in engineering.

Realization of double uniform line self-focusing of elliptical Airyprime beams.

Double line self-focusing characteristics of elliptical Airyprime beams (EAPBs) with different elliptical vertical-axis factor ß are investigated by varying the main ring radius r0. Overly large or small r0 results in the inhomogeneous distribution of light intensity at one linear focus of the double line self-focusing. Only when r0 is appropriate and ß is within a certain range, can double uniform line self-focusing happen to the EAPB. Moreover, the self-focusing ability of the second line self-focusing is weaken than that of the first line self-focusing. Under the premise of our selected values of beam parameters, the EAPB can achieve double uniform line self-focusing when r0 = 0.3 mm and ß = 0.58∼0.71. The focal length of the first line self-focusing, the lengths of double linear focus, and the self-focusing abilities of the double uniform line self-focusing can be regulated by varying ß within the range of 0.58∼0.71. If ß is smaller than 0.58 or larger than 0.71, it will lead to nonuniform line self-focusing. An explanation of the physical mechanism behind the double uniform line self-focusing of the EAPB is proposed. Finally, the experimental measurements of the line self-focusing of the EAPB confirm the validity of the above conclusions. This research provides a new solution on how to generate double uniform line self-focusing and new insights into the practical application of elliptical self-focusing beams.

Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model.

Retinitis pigmentosa (RP) is an inherited retinal disease in which there is a loss of cone-mediated daylight vision. As there are >100 disease genes, our goal is to preserve cone vision in a disease gene-agnostic manner. Previously we showed that overexpressing TXNIP, an α-arrestin protein, prolonged cone vision in RP mouse models, using an AAV to express it only in cones. Here, we expressed different alleles of Txnip in the retinal pigmented epithelium (RPE), a support layer for cones. Our goal was to learn more of TXNIP's structure-function relationships for cone survival, as well as determine the optimal cell type expression pattern for cone survival. The C-terminal half of TXNIP was found to be sufficient to remove GLUT1 from the cell surface, and improved RP cone survival, when expressed in the RPE, but not in cones. Knock-down of HSP90AB1, a TXNIP-interactor which regulates metabolism, improved the survival of cones alone and was additive for cone survival when combined with TXNIP. From these and other results, it is likely that TXNIP interacts with several proteins in the RPE to indirectly support cone survival, with some of these interactions different from those that lead to cone survival when expressed only in cones.

Use of pressure muscle index to predict the contribution of patient's inspiratory effort during pressure support ventilation: a prospective physiological study.

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support. Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort. Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort. Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

Silver nanowires/waterborne polyurethane composite film based piezoresistive pressure sensor for ultrasensitive human motion monitoring.

Flexible piezoresistive pressure sensors are gaining significant attention, particularly in the realm of flexible wearable electronic skin. Here, a flexible piezoresistive pressure sensor was developed with a broad sensing range and high sensitivity. We achieved this by curing polydimethylsiloxane (PDMS) on sandpaper, creating a PDMS film as the template with a micro-protrusion structure. The core sensing layer was formed using a composite of silver nanowires (AgNWs) and waterborne polyurethane (WPU) with a similar micro-protrusion structure. The sensor stands out with its exceptional sensitivity, showing a value of 1.04 × 106kPa-1with a wide linear range from 0 to 27 kPa. It also boasts a swift response and recovery time of 160 ms, coupled with a low detection threshold of 17 Pa. Even after undergoing more than 1000 cycles, the sensor continues to deliver stable performance. The flexible piezoresistive pressure sensor based on AgNWs/WPU composite film (AWCF) can detect small pressure changes such as pulse, swallowing, etc, which indicates that the sensor has great application potential in monitoring human movement and flexible wearable electronic skin.

Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model.

Retinitis pigmentosa (RP) is a prevalent inherited retinal degenerative disease worldwide, affecting 1 in 4,000 people. The disease is characterized by an initial loss of night vision followed by a loss of daylight and color vision. Many of the RP disease genes are expressed in the rod photoreceptors, the cell type that initiates dim light vision. Following loss of rods, the cone photoreceptors, which initiate daylight vision, also are affected and can die leading to total loss of vision. The reasons for loss of cone vision are not entirely clear, but appear to be due to loss of the rods. Previously we showed that overexpressing Txnip, an α-arrestin protein, in mouse models of RP using AAV gene therapy prolonged the survival of RP cones (Xue et al., 2021). At least part of the mechanism for cone survival was a switch in the fuel source, from glucose to lactate. In addition, the mitochondria of cones were both morphologically and functionally improved by delivery of Txnip. We have gone on to test several alleles of Txnip for the ability to prolong cone survival in rd1, a mouse model of RP. In addition, proteins that bind to Txnip and/or have homology to Txnip were tested. Five different deletion alleles of Txnip were expressed in cones or the retinal pigmented epithelium (RPE). Here we show that the C-terminal half of Txnip (149-397aa) is sufficient to remove GLUT1 from the RPE cell surface, and improved rd1 cone survival when expressed specifically in the RPE. Overexpressing Arrdc4, an α-arrestin that shares 60% similar protein sequence to Txnip, reduced rd1 cone survival. Reduction of the expression of HSP90AB1, a protein that interacts with Txnip and regulates metabolism, improved the survival of rd1 cones alone and was additive for cone survival when combined with Txnip. However, full length Txnip with a single amino acid change, C247S, as we tested in our original study, remains the most highly efficacious form of the gene for cone rescue. The above observations suggest that only a subset of the hypothesized and known activities of Txnip play a role in promoting RP cone survival, and that the activities of Txnip in the RPE differ from those in cone photoreceptors.

Realization of a circularly transformed Airyprime beam with powerful autofocusing ability.

The reported autofocusing ability of a ring Airyprime beam array reaches up to 8632.40, while the strongest autofocusing ability of a circular Airyprime beam (CAPB) is only 1822.49. How can the autofocusing ability of a single beam reach the autofocusing ability of a beam array? To achieve this goal, a circularly transformed Airyprime beam (CTAPB) is introduced by following two steps. First, a circular equation transformation on the two transverse coordinates in the electric field expression of a propagating Airyprime beam is performed. Then, the electric field expression of a propagating Airyprime beam is integrated over the angle. The intensity profile of a CTAPB on the initial plane changes significantly with varying the primary ring radius r0. With increasing r0, therefore, the autofocusing ability of a CTAPB undergoes a process of first increasing and then decreasing, while the focal length always increases. A CTAPB exhibits more powerful autofocusing ability than a CAPB. The maximum autofocusing ability of a CTAPB can reach up to 8634.76, which is 4.74 times that of a CAPB, while the corresponding focal length is 95.11% of a CAPB. A CTAPB on the initial plane can be approximately characterized by a ring Airyprime beam array with sufficient number of Airyprime beams. Due to the better symmetry, a CTAPB has a slightly stronger autofocusing ability than a ring Airyprime beam array and almost the same focal length as a ring Airyprime beam array. The CTAPB is also experimentally generated, and the experimental results indicate that the CTAPB has powerful autofocusing ability. As a replacement of a CAPB and a ring Airyprime beam array, this introduced CTAPB can be applied to the scenes which involve abruptly autofocusing effect.

Macroscale intrinsic dynamics are associated with microcircuit function in focal and generalized epilepsies.

Epilepsies are a group of neurological disorders characterized by abnormal spontaneous brain activity, involving multiscale changes in brain functional organizations. However, it is not clear to what extent the epilepsy-related perturbations of spontaneous brain activity affect macroscale intrinsic dynamics and microcircuit organizations, that supports their pathological relevance. We collect a sample of patients with temporal lobe epilepsy (TLE) and genetic generalized epilepsy with tonic-clonic seizure (GTCS), as well as healthy controls. We extract massive temporal features of fMRI BOLD time-series to characterize macroscale intrinsic dynamics, and simulate microcircuit neuronal dynamics used a large-scale biological model. Here we show whether macroscale intrinsic dynamics and microcircuit dysfunction are differed in epilepsies, and how these changes are linked. Differences in macroscale gradient of time-series features are prominent in the primary network and default mode network in TLE and GTCS. Biophysical simulations indicate reduced recurrent connection within somatomotor microcircuits in both subtypes, and even more reduced in GTCS. We further demonstrate strong spatial correlations between differences in the gradient of macroscale intrinsic dynamics and microcircuit dysfunction in epilepsies. These results emphasize the impact of abnormal neuronal activity on primary network and high-order networks, suggesting a systematic abnormality of brain hierarchical organization.

Bio-mechanical effects of femoral neck system versus cannulated screws on treating young patients with Pauwels type III femoral neck fractures: a finite element analysis.

INTRODUCTION: As a novel internal fixation for femoral neck fractures, the femoral neck system has some advantages for young Pauwels type III femoral neck fractures without clear biomechanical effects and mechanisms. Thus, the objection of the study is to realize the biomechanical effects and mechanism of FNS cannulated screws on treating young patients with Pauwels type III femoral neck fractures compared to cannulated screws which are commonly used for femoral neck fractures by finite element analysis. METHODS: Firstly, the model of young Pauwels type III femoral neck fractures, femoral neck system (FNS), and three cannulated screws (CS) arranged in an inverted triangle were established, and the internal fixations were set up to fix young Pauwels type III femoral neck fractures. Under 2100 N load, the finite element was performed, and the deformation, peak von Mises stress (VMS), and contact at fracture segments were recorded to analyze the biomechanical effects and mechanism of FNS and three-CS fixing young Pauwels type III femoral neck fractures. RESULTS: Compared to three-CS, the deformation of the whole model, internal fixation, and fracture segments after FNS fixation were lower, and the peak VMS of the whole model and the internal fixation after FNS were higher with lower peak VMS of the distal femur and the fracture segments. With a sticking contact status, the contact pressure at fracture segments after FNS fixation was lower than that of three-CS. CONCLUSIONS: FNS can provide better mechanical effects for young patients with Pauwels type III femoral neck fractures, which may be the mechanical mechanism of the clinical effects of FNS on femoral neck fracture. Although there is high stress on FNS, it is still an effective and safe internal fixation for young patients with Pauwels type III femoral neck fractures.

The role of intestinal flora on tumor immunotherapy: recent progress and treatment implications.

Immunotherapy, specifically immune checkpoint inhibitors, has emerged as a promising approach for treating malignant tumors. The gut, housing approximately 70 % of the body's immune cells, is abundantly populated with gut bacteria that actively interact with the host's immune system. Different bacterial species within the intestinal flora are in a delicate equilibrium and mutually regulate each other. However, when this balance is disrupted, pathogenic microorganisms can dominate, adversely affecting the host's metabolism and immunity, ultimately promoting the development of disease. Emerging researches highlight the potential of interventions such as fecal microflora transplantation (FMT) to improve antitumor immune response and reduce the toxicity of immunotherapy. These remarkable findings suggest the major role of intestinal flora in the development of cancer immunotherapy and led us to the hypothesis that intestinal flora transplantation may be a new breakthrough in modifying immunotherapy side effects.

Effects of the excitation wavelength and temperature on the zero-phonon emission line of Cr:YAG.

In this work, a detailed study was conducted of the temperature and excitation wavelength-dependent photoluminescence (PL) spectra of the chromium-doped yttrium aluminum garnet (Cr:YAG) transparent ceramic. Focusing on the two sets of zero-phonon lines (ZPLs) of the 2 E→4 A 2 transition in this material, the PL spectra are discovered to evolve significantly with respect to temperature and be highly dependent on the excitation wavelength. Compared to the continuous variation behavior with temperature, an increase in the excitation wavelength leads to a blueshift of the peak position within the regions of 450 nm to 465 nm, 465 nm to 490 nm, and 490 nm to 500 nm, and a sharp change in the PL position at the excitation wavelengths of 465 nm and 490 nm. The electron-phonon coupling (EPC) effect is believed to be more sensitive to the excitation wavelength. Different excitation wavelengths involve different electronic levels participating in the light emission processes, which explains the evolution behavior of the PL peak position with respect to the excitation wavelength. Moreover, the emergence of weak peaks next to the ZPLs at particular temperatures and excitation wavelengths is also observed. This work compares the influence of the temperature and excitation wavelength to the PL properties of the Cr:YAG transparent ceramic, which promotes an advanced understanding of the luminescence behavior of the Cr:YAG transparent ceramics.

Visualization and Experimental Characterization of Wrapping Layer Using Planar Laser-Induced Fluorescence.

Droplets on nanotextured oil-impregnated surfaces have high mobility due to record-low contact angle hysteresis (∼1-3°), attributed to the absence of solid-liquid contact. Past studies have utilized the ultralow droplet adhesion on these surfaces to improve condensation, reduce hydrodynamic drag, and inhibit biofouling. Despite their promising utility, oil-impregnated surfaces are not fully embraced by industry because of the concern for lubricant depletion, the source of which has not been adequately studied. Here, we use planar laser-induced fluorescence (PLIF) to not only visualize the oil layer encapsulating the droplet (aka wrapping layer) but also measure its thickness since the wrapping layer contributes to lubricant depletion. Our PLIF visualization and experiments show that (a) due to the imbalance of interfacial forces at the three-phase contact line, silicone oil forms a wrapping layer on the outer surface of water droplets, (b) the thickness of the wrapping layer is nonuniform both in space and time, and (c) the time-average thickness of the wrapping layer is ∼50 ± 10 nm, a result that compares favorably with our scaling analysis (∼50 nm), which balances the curvature-induced capillary force with the intermolecular van der Waals forces. Our experiments show that, unlike silicone oil, mineral oil does not form a wrapping layer, an observation that can be exploited to mitigate oil depletion of nanotextured oil-impregnated surfaces. Besides advancing our mechanistic understanding of the wrapping oil layer dynamics, the insights gained from this work can be used to quantify the lubricant depletion rate by pendant droplets in dropwise condensation and water harvesting.

Lifetime cumulative effect of reproductive factors on ischaemic heart disease in a prospective cohort.

OBJECTIVE: This study aimed to examine the association between lifetime oestrogen exposure and ischaemic heart disease (IHD), based on the hypothesis that higher lifetime oestrogen exposure is linked to lower cardiovascular risk. METHODS: In 2004-2008, lifetime cumulative exposure to reproductive factors was assessed among postmenopausal females from the China Kadoorie Biobank using reproductive lifespan (RLS), endogenous oestrogen exposure (EEE) and total oestrogen exposure (TEE). EEE was calculated by subtracting pregnancy-related and contraceptive use duration from RLS, while TEE by adding up the same components except for lactation. Incident IHD during follow-up (2004-2015) was identified. Stratified Cox proportional hazards models estimated the HRs and 95% CIs of IHD for RLS, EEE and TEE. RESULTS: Among 118 855 postmenopausal females, 13 162 (11.1%) developed IHD during a median follow-up of 8.9 years. The IHD incidence rates were 13.0, 12.1, 12.5, 13.8 per 1000 person-years for RLS Q1-Q4, 15.8, 12.6, 11.3, 12.1 per 1000 person-years for EEE Q1-Q4 and 13.7, 12.3, 12.2, 13.4 per 1000 person-years for TEE Q1-Q4. The highest quartile (Q4) of RLS and TEE were associated with lower risks of IHD (adjusted HR (aHR) 0.95, 95% CI 0.91 to 1.00 and 0.92, 95% CI 0.88 to 0.97, respectively) compared with the lowest quartile (Q1). Longer EEE showed progressively lower risks of incident IHD (aHR 0.93, 95% CI 0.88 to 0.97; 0.88, 95% CI 0.84 to 0.93; 0.87, 95% CI 0.83 to 0.92 for Q2-Q4 vs Q1). CONCLUSIONS: Longer RLS, TEE and EEE were associated with lower risks of IHD among Chinese postmenopausal females.

Olaparib enhances radiation-induced systemic anti-tumor effects via activating STING-chemokine signaling in hepatocellular carcinoma.

Although Poly (ADP-ribose) polymerase (PARP) inhibitors have been clinically approved for cancers with BRCA mutations and are known to augment radiotherapy responses, their roles in promoting the abscopal effect and mediating immunotherapy in BRCA-proficient hepatocellular carcinoma (HCC) remain underexplored. Our study elucidates that olaparib enhances the radio-sensitivity of HCC cells. Coadministration of olaparib and irradiation induces significant DNA damage by generating double-strand breaks (DSBs), as revealed both in vitro and in immune-deficient mice. These DSBs activate the cGAS-STING pathway, initiating immunogenic cell death in abscopal tumors. STING activation reprograms the immune microenvironment in the abscopal tumors, triggering the release of type I interferon and chemokines, including CXCL9, CXCL10, CXCL11, and CCL5. This in turn amplifies T cell priming against tumor neoantigens, leading to an influx of activated, neoantigen-specific CD8+ T-cells within the abscopal tumors. Furthermore, olaparib attenuated the immune exhaustion induced by radiation and enhances the responsiveness of HCC to immune checkpoint inhibitors. Collectively, our data advocate that a synergistic regimen of PARP inhibitors and radiotherapy can strategically reinforce both local (primary) and systemic (abscopal) tumor control, bolstering HCC susceptibility to immunotherapy.

A Bioorthogonal Antidote Against the Photosensitivity after Photodynamic Therapy.

As an effective and non-invasive treatment modality for cancer, photodynamic therapy (PDT) has attracted considerable interest. With the recent advances in the photosensitizing agents, the fiber-optic systems, and other aspects, its application is extended to a wide range of superficial and localized cancers. However, for the few clinically used photosensitizers, most of them suffer from the drawback of causing prolonged photosensitivity after the treatment. As a result, post-PDT management is also a crucial issue. Herein, a facile bioorthogonal approach is reported that can effectively suppress this common side effect of PDT in nude mice. It involves the use of an antidote that contains a black-hole quencher BHQ-3 conjugated with a bicyclo[6.1.0]non-4-yne (BCN) moiety and a tetrazine-substituted boron dipyrromethene-based photosensitizer. By using tumor-bearing nude mice as an animal model, it is demonstrated that after PDT with this photosensitizer, the administration of the antidote can effectively quench the photodynamic activity of the residual photosensitizer by bringing the BHQ-3 quencher close to the photosensitizing unit through a rapid click reaction. It results in substantial reduction in skin damage upon light irradiation. The overall results demonstrate that this simple and facile strategy can provide an effective means for minimizing the photosensitivity after PDT.

Use of airway pressure-based indices to detect high and low inspiratory effort during pressure support ventilation: a diagnostic accuracy study.

BACKGROUND: Assessment of the patient's respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (Paw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation. METHODS: In this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative Paw generated during the first 100 ms (P0.1) and the maximal negative swing of Paw (∆Pocc) were measured. After an end-inspiratory airway occlusion, Paw reached a plateau, and the magnitude of change in plateau from peak Paw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (Pmus) and Pmus-time product per minute (PTPmus/min) were used as the reference standard for the patient's effort. High and low effort was defined as Pmus > 10 and < 5 cmH2O, or PTPmus/min > 200 and < 50 cmH2O s min-1, respectively. RESULTS: A total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective Pmus and PTPmus/min criterion. The receiver operating characteristic area of the three Paw-based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83-0.96), specificity (0.74-0.88), and positive (0.80-0.91) and negative predictive values (0.78-0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using Pmus and PTPmus/min criterion, respectively. High receiver operating characteristic areas of the three Paw-based indices by the two criteria were found (0.93-0.95). A high sensitivity (0.80-1.00) and negative predictive value (0.97-1.00) were found with a low positive predictive value (0.23-0.64). CONCLUSIONS: By performing simple airway occlusion maneuvers, the Paw-based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort.

Delta radiomics analysis for prediction of intermediary- and high-risk factors for patients with locally advanced cervical cancer receiving neoadjuvant therapy.

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann-Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models-the clinical model, the radiomics model, and the combined clinic and radiomics model-were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.