OPALIN is an LGI1 receptor promoting oligodendrocyte differentiation.

Leucine-rich glioma-inactivated protein 1 (LGI1), a secretory protein in the brain, plays a critical role in myelination; dysfunction of this protein leads to hypomyelination and white matter abnormalities (WMAs). Here, we hypothesized that LGI1 may regulate myelination through binding to an unidentified receptor on the membrane of oligodendrocytes (OLs). To search for this hypothetic receptor, we analyzed LGI1 binding proteins through LGI1-3 × FLAG affinity chromatography with mouse brain lysates followed by mass spectrometry. An OL-specific membrane protein, the oligodendrocytic myelin paranodal and inner loop protein (OPALIN), was identified. Conditional knockout (cKO) of OPALIN in the OL lineage caused hypomyelination and WMAs, phenocopying LGI1 deficiency in mice. Biochemical analysis revealed the downregulation of Sox10 and Olig2, transcription factors critical for OL differentiation, further confirming the impaired OL maturation in Opalin cKO mice. Moreover, virus-mediated re-expression of OPALIN successfully restored myelination in Opalin cKO mice. In contrast, re-expression of LGI1-unbound OPALIN_K23A/D26A failed to reverse the hypomyelination phenotype. In conclusion, our study demonstrated that OPALIN on the OL membrane serves as an LGI1 receptor, highlighting the importance of the LGI1/OPALIN complex in orchestrating OL differentiation and myelination.

A colorimetric biosensor with infrared sterilization based on CuSe nanoparticles for the detection of E. coli O157:H7 in food samples.

It is critical to develop quick, accurate, and efficient sterilization for detecting Escherichia coli O157:H7 in order to prevent infections and outbreaks of foodborne illnesses. Herein, we established a colorimetric biosensor with sterilizing properties using copper selenide nanoparticles to detect E. coli O157:H7. The sample was mixed with magnetic nanoprobes and nanozyme probes to form a sandwich structure, and then the unbound nanozyme probes were collected by magnetic separation. Finally, the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate)-hydrogen peroxide (H2O2) reporting system was added for signal amplification. The change from colorless to green can be seen with the naked eye. Under the optimal conditions, the detection range of E. coli O157:H7 was 102-106 CFU/mL, and the detection limit was 0.35 × 102 CFU/mL. The total detection time was 80 minutes, which can be successfully applied to milk and mineral water. In addition, the colorimetric sensor can kill the target bacteria by irradiating it under a 980-nm laser for 5 minutes. In conclusion, this sensor is a promising tool for rapidly detecting foodborne pathogens and promptly eliminating bacteria. IMPORTANCE: Escherichia coli O157:H7 is a major threat to public health. At present, the detection methods for E. coli O157:H7 mainly include traditional bacterial culture, immunology (enzyme-linked immune-sorbent assay) and molecular biology techniques (polymerase chain reaction). These methods have the limitations of professional operation, waste of time and energy, and high cost. Therefore, we have developed a simple, fast, bactericidal colorimetric biosensor to detect E. coli. O157:H7. The entire process was completed in 80 minutes. The method has been successfully applied to milk and mineral water samples with satisfactory results, proving that the method is an effective method for real-time detection and inactivation of bacteria.

Structural characterization of oligosaccharide from Dendrobium officinale and its properties in vitro digestion and fecal fermentation.

Oligosaccharides from Dendrobium officinale (DOO) is a kind of new potential prebiotic for health. In this study, structural characteristics, digestion properties and regulatory function on intestinal flora of DOO were investigated. An oligosaccharide, DOO 1-1, was purified by DEAE-Sepharose Fast Flow and Sephadex G-25, and its physicochemical properties were characterized as a glucomannan oligosaccharide with a molecular weight of 1560 Da (DP = 9). In vitro simulated digestion, it proved that the structure of DOO 1-1 was degraded hardly in the simulated gastric and small intestinal fluid. By evaluating the gas, short-chain fatty acids and intestinal microbiota in vitro fermentation, DOO has an excellent regulatory effect on intestinal microbiota, especially promoting the proliferation of Bacteroidetes and Actinobacteria. Therefore, DOO can be used as a potential prebiotic in functional foods.

Impact of task-oriented training based on acupuncture rehabilitation on upper extremity function and quality of life of patients with early stroke.

BACKGROUND: Eighty percent of stroke patients develop upper limb dysfunction, especially hand dysfunction, which has a very slow recovery, resulting in economic burden to families and society. AIM: To investigate the impact of task-oriented training based on acupuncture therapy on upper extremity function in patients with early stroke. METHODS: Patients with early stroke hemiplegia who visited our hospital between January 2021 and October 2022 were divided into a control group and an observation group, each with 50 cases. The control group underwent head acupuncture plus routine upper limb rehabilitation training (acupuncture therapy). In addition to acupuncture and rehabilitation, the observation group underwent upper limb task-oriented training (30 min). Each group underwent treatment 5 d/wk for 4 wk. Upper extremity function was assessed in both groups using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Wolf Motor Function Rating Scale (WMFT), modified Barthel Index (MBI), and Canadian Occupational Performance Measure (COPM). Quality of life was evaluated using the Short-Form 36-Item Health Survey (SF-36). Clinical efficacy of the interventions was also evaluated. RESULTS: Before intervention, no significant differences were observed in the FMA-UE, MBI, and WMFT scores between the two groups (P > 0.05). After intervention, the FMA-UE, WMFT, MBI, COPM-Functional Mobility and Satisfaction, and SF-36 scores increased in both groups (P < 0.05), with even higher scores in the observation group (P < 0.05). The observation group also obtained a higher total effective rate than the control group (P < 0.05). CONCLUSION: Task-oriented training based on acupuncture rehabilitation significantly enhanced upper extremity mobility, quality of life, and clinical efficacy in patients with early stroke.

Assembly of Homochiral Magneto-Optical Dy6 Triangular Clusters by Fixing Carbon Dioxide in the Air.

A new hydrazone Schiff base bridging ligand (H2LSchiff (E)-N'-((1-hydroxynaphthalen-2-yl)methylene)pyrazine-2-carbohydrazide) and L/D-proline were used to construct a pair of homochiral Dy6 cluster complexes, [Dy6(CO3)(L-Pro)6(LSchiff)4(HLSchiff)2]·5DMA·2H2O (L-1, L-HPro = L-proline; DMA = N,N-dimethylacetamide) and [Dy6(CO3)(D-Pro)6(LSchiff)4(HLSchiff)2]·5DMA·2H2O (D-1, D-HPro = D-proline), which show a novel triangular Dy6 topology. Notably, the fixation of CO2 in the air formed a carbonato central bridge, playing a key role in assembling L-1/D-1. Magnetic measurements revealed that L-1/D-1 displays intramolecular ferromagnetic coupling and magnetic relaxation behaviours. Furthermore, L-1/D-1 shows a distinct magneto-optical Faraday effect and has a second harmonic generation (SHG) response (1.0 × KDP) at room temperature. The results show that the immobilization of CO2 provides a novel pathway for homochiral multifunctional 4f cluster complexes.

Comprehensive quality control of silkworm chrysalis using chemical fingerprints combined with antioxidant activity and acetylcholine content.

In recent years, some insects have become foods due to their high nutritional value. In order to solve the problem of the lack of quality control methods for insect foods, this study proposes a comprehensive control model using silkworm chrysalis (SC) as an example. Firstly, five-wavelength mean fusion fingerprints (FWMFF) and UV quantum fingerprints of 21 batches of SC were established. And the 21 batches of SC were classified into different grades from different perspectives by using the comprehensive linear quantified fingerprint method (CLQFM) as a quality evaluation method for qualitative and quantitative analysis. Secondly, this paper fully considered the issue of the reliability of fingerprint evaluation, which guaranteed the accuracy of the evaluation results. On this basis, the antioxidant capacity of the samples was used in vitro 1,1-Diphenyl-2-picrylhydrazylradical (DPPH) scavenging assay using IC50. The relationship between fingerprints and antioxidant activity was also discussed. Finally, the content of endogenous neurotransmitter (ACh) in SC determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in the range of 0.25-2.11µg/g. Overall, the present study proposes a comprehensive quality control strategy for functional foods based on the quality assessment of SC.

High-throughput screening of 222 pesticides in road environments in a megacity of northern China: A new approach to urban population exposure.

A large number of pesticides have been widely manufactured and applied, and are released into the environment with negative impact on human health. Pesticides are largely used in densely populated urban environments, in green zones, along roads and on private properties. In order to characterize the potential exposure related health effects of pesticide and their occurrence in the urban environment, 222 pesticides were screened and quantified in 228 road dust and 156 green-belt soil samples in autumn and spring from Harbin, a megacity in China, using GC-MS/MS base quantitative trace analysis. The results showed that a total of 33 pesticides were detected in road dust and green-belt soil, with the total concentrations of 650 and 236 ng/g (dry weight = dw), respectively. The concentrations of pesticides in road dust were significantly higher than that in green-belt soil. Pesticides in the environment were influenced by the seasons, with the highest concentrations of insecticides in autumn and the highest levels of herbicides in spring. In road dust, the concentrations of highways in autumn and spring (with the mean values of 94.1 and 68.2 ng/g dw) were much lower than that of the other road classes (arterial roads, sub-arterial roads and branch ways). Whereas in the green-belt soil, there was no significant difference in the concentration of pesticides between the different road classes. A first risk assessment was conducted to evaluate the potential adverse health effects of the pesticides, the results showed that the highest hazard index (HI) for a single pesticide in dust and soil was 0.12, the hazard index for children was higher than that for adults, with an overall hazard index of less than 1. Our results indicated that pesticide levels do not have a significant health impact on people.

Thrombectomy improves functional independence in severe basilar artery occlusion with favorable collateral circulation.

BACKGROUND AND PURPOSE: This study aimed to investigate the effect of collateral circulation on the outcomes of thrombectomy versus medical management alone in basilar artery occlusion (BAO) patients with varying stroke severities. METHODS: Data from the ATTENTION cohort were used to perform a post-hoc analysis comparing the outcomes of thrombectomy with medical management in BAO patients with varying degrees of collateral circulation and stroke severity. Basilar Artery on Computed Tomography Angiography (BATMAN) scores were used to quantify the collateral circulation, and the effect was estimated through a primary outcome of 90-day functional independence (modified Rankin Scale score, mRS ≤2). Favorable versus unfavorable BATMAN scores were analyzed as both continuous and categorical variables, and an adjusted multivariate regression model was applied. RESULTS: Among 221 BAO patients, thrombectomy significantly improved functional independence compared to medical management in patients with favorable BATMAN scores (aOR 7.75, 95% CI 2.78-26.1), but not in those with unfavorable BATMAN scores (aOR 1.33, 95% CI 0.28-6.92; pinteraction = 0.028). When treated as a continuous variable, increased BATMAN score was found to be associated with a higher likelihood of functional independence in the thrombectomy group (aOR 1.97, 95% CI 1.44-2.81; pinteraction = 0.053). In severe stroke patients with higher BATMAN scores (National Institutes of Health Stroke Scale (NIHSS) ≥21), we identified a significant interaction for treatment effect with thrombectomy compared to medical management (pinteraction = 0.042). CONCLUSION: An increased BATMAN score was significantly associated with a higher probability of functional independence after thrombectomy than after medical management, particularly in patients with severe BAO.

Growth factor-functionalized titanium implants for enhanced bone regeneration: A review.

Titanium and titanium alloys are widely favored materials for orthopedic implants due to their exceptional mechanical properties and biological inertness. The additional benefit of sustained local release of bioactive substances further promotes bone tissue formation, thereby augmenting the osseointegration capacity of titanium implants and attracting increasing attention in bone tissue engineering. Among these bioactive substances, growth factors have shown remarkable osteogenic and angiogenic induction capabilities. Consequently, researchers have developed various physical, chemical, and biological loading techniques to incorporate growth factors into titanium implants, ensuring controlled release kinetics. In contrast to conventional treatment modalities, the localized release of growth factors from functionalized titanium implants not only enhances osseointegration but also reduces the risk of complications. This review provides a comprehensive examination of the types and mechanisms of growth factors, along with a detailed exploration of the methodologies used to load growth factors onto the surface of titanium implants. Moreover, it highlights recent advancements in the application of growth factors to the surface of titanium implants (Scheme 1). Finally, the review discusses current limitations and future prospects for growth factor-functionalized titanium implants. In summary, this paper presents cutting-edge design strategies aimed at enhancing the bone regenerative capacity of growth factor-functionalized titanium implants-a significant advancement in the field of enhanced bone regeneration.

Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Numerical Simulation Study on the Influence of Fracture on Borehole Wave Modes: Insights from Fracture Width, Filling Condition, and Acoustic Frequency.

Unconventional reservoirs, such as shale and tight formations, have become increasingly vital contributors to oil and gas production. In these reservoirs, fractures serve as crucial spaces for fluid migration and storage, making their precise assessment essential. Array acoustic logging stands out as a pivotal method for evaluating fractures. To investigate the impact of fracture width, fracture-filling conditions, and acoustic frequency on compressional and shear waves, a three-dimensional variable mesh finite difference program was employed for acoustic logging numerical simulation. Firstly, numerical models representing fractured formations with varying fracture widths and distinct fluid-filling conditions were established, and array acoustic logging numerical simulations were conducted at different frequencies. Subsequently, the waveform data were processed to extract acoustic characteristic parameters, such as velocities and amplitude attenuations of compressional and shear waves. Finally, a quantitative analysis was conducted to examine the variation patterns of characteristic parameters of refracted compressional and shear waves in relation to fracture properties. The research results indicate that amplitude attenuation information derived from borehole wave modes is particularly sensitive to the changes in fracture properties. As fracture width increased, we observed a significant amplitude attenuation in both compressional and shear waves, proportional to the logarithm of the attenuation coefficients. Furthermore, when the fracture width was constant, gas-filled fractures exhibited more prominent amplitude attenuation than water-filled fractures, with shear wave attenuation being more sensitive to the filling material. Moreover, from a quantitative perspective, the analysis revealed that the attenuation coefficients of refracted compressional and shear waves exhibited an exponential variation with gas saturation. Notably, once fracture width and filling conditions were established, the amplitudes of compressional and shear waves at the dominant frequency of 40 kHz were significantly reduced compared to those at 8 kHz, accompanied by increased attenuation. Subsequent quantitative analysis revealed that, when the product of fracture width and dominant frequency remains constant, the corresponding attenuation coefficient ratios approach 1. This indicates that the attenuation process of acoustic propagation in fractured media follows the principle of acoustic similarity. The findings of this study provide reference for further research on fracture property evaluation methods based on array acoustic logging data.

Biological functions and therapeutic potential of SRY related high mobility group box 5 in human cancer.

Cancer is a heavy human burden worldwide, with high morbidity and mortality. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Transcription factors, including SRY associated high mobility group box (SOX) proteins, are thought to be involved in the regulation of specific biological processes. There is growing evidence that SOX transcription factors play an important role in cancer progression, including tumorigenesis, changes in the tumor microenvironment, and metastasis. SOX5 is a member of SOX Group D of Sox family. SOX5 is expressed in various tissues of human body and participates in various physiological and pathological processes and various cellular processes. However, the abnormal expression of SOX5 is associated with cancer of various systems, and the abnormal expression of SOX5 acts as a tumor promoter to promote cancer cell viability, proliferation, invasion, migration and EMT through multiple mechanisms. In addition, the expression pattern of SOX5 is closely related to cancer type, stage and adverse clinical outcome. Therefore, SOX5 is considered as a potential biomarker for cancer diagnosis and prognosis. In this review, the expression of SOX5 in various human cancers, the mechanism of action and potential clinical significance of SOX5 in tumor, and the therapeutic significance of Sox5 targeting in cancer were reviewed. In order to provide a new theoretical basis for cancer clinical molecular diagnosis, molecular targeted therapy and scientific research.

A novel IRF6 gene mutation impacting the regulation of TGFß2-AS1 in the TGFß pathway: A mechanism in the development of Van der Woude syndrome.

Several mutations in the IRF6 gene have been identified as a causative link to VWS. In this investigation, whole-exome sequencing (WES) and Sanger sequencing of a three-generation pedigree with an autosomal-dominant inheritance pattern affected by VWS identified a unique stop-gain mutation-c.748C>T:p.R250X-in the IRF6 gene that co-segregated exclusively with the disease phenotype. Immunofluorescence analysis revealed that the IRF6-p.R250X mutation predominantly shifted its localization from the nucleus to the cytoplasm. WES and protein interaction analyses were conducted to understand this mutation's role in the pathogenesis of VWS. Using LC-MS/MS, we found that this mutation led to a reduction in the binding of IRF6 to histone modification-associated proteins (NAA10, SNRPN, NAP1L1). Furthermore, RNA-seq results show that the mutation resulted in a downregulation of TGFß2-AS1 expression. The findings highlight the mutation's influence on TGFß2-AS1 and its subsequent effects on the phosphorylation of SMAD2/3, which are critical in maxillofacial development, particularly the palate. These insights contribute to a deeper understanding of VWS's molecular underpinnings and might inform future therapeutic strategies.

[A controlled clinical study of vertebroplasty for the treatment of osteoporotic vertebral compression fractures after self-made spinal positioner and manual reduction].

OBJECTIVE: To explore clinical effect of manipulation reduction combined with vertebral plasty on osteoporotic compression fractures (OVCFs). METHODS: Totally 61 patients with OVCFs treated from January 2022 to March 2024 were randomly divided into self-made spinal locator positioning with manipulation reduction group (treatment group) and traditional Kirchner positioning group (control group). There were 30 patients in treatment group, including 4 males and 26 females, aged from 61 to 87 years old with an average of (73.61±7.17) years old;body mass index (BMI) ranged from 15.24 to 28.89 kg·m-2 with an average of (23.90±3.20) kg·m-2;bone mineral density T value ranged from -4.90 to -2.50 SD with an avergae of (-3.43±0.75) SD;fracture to operation time was 6.50 (4.00, 10.25) d;10 patients were gradeⅠ, 13 patients were gradeⅡ, and 7 patients were grade Ⅲ according to Genant classification of fracture compression. There were 31 patients in control group, including 7 males and 24 females, aged from 61 to 89 years old with an average of (73.63±8.77) years old;BMI ranged from 18.43 to 27.06 kg·m-2 with an average of (23.67±2.35) kg·m-2;bone mineral density T value ranged from -4.60 to -2.50 SD with an avergae of (-3.30±0.68) SD;fracture to operation time was 6.00 (3.00, 8.00) d;11 patients were gradeⅠ, 9 patients were gradeⅡ, and 11 patients were grade Ⅲ according to Genant classification of fracture compression. The puncture times, X-ray fluoroscopy times and puncture time between two groups were observed and compared. Visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and timed up and go test (TUGT) were observed and compared before operation, 3 d and 1 month after operation. RESULTS: All patients were followed up for 1 to 3 months with an average of (2.10±0.80) months. Puncture times, X-ray fluorosecopy times and puncture time in treatment group were 5.00(4.00, 6.00) times, (29.53±5.89) times and 14.83(12.42, 21.20) min, respectively, while those in control group were 7.00(6.00, 8.00) times, (34.58±5.33) times, 22.19(17.33, 27.01) min, treatment group was better than those of control group (P<0.05). There were no significant differences in preoperative VAS, JOA and TUGT between two groups(P>0.05). VAS, JOA and TUGT in both groups were significantly improved after opeation(P<0.05). On the third day after operation, JOA score of treatment group was 23.00 (20.75, 25.00), which was higher than that of control group 20.00(19.00, 23.00)(P<0.05). TUGT of treatment group was 6.26(5.86, 6.57) s, which was better than that of control group 6.90(6.80, 7.14) s (P<0.05). Bone cement leakage occurred with 1 patient in treatment group and 2 patients in control group. CONCLUSION: The optimal scheme of self-made spinal locators for locating descending verteboplasty combined with traditional Chinese medicine reduction manipulation for OVCF patients could reduce the number of intraoperative puncture times, shorten puncture times and reduce number of X-ray fluoroscopy times, and have advantages over the simple positioning of Kirschn's needle in restoring short-term lumbar function and standing and walking ability of postoperative patients.

In Vitro Digestion and Fermentation of Different Ethanol-Fractional Polysaccharides from Dendrobium officinale: Molecular Decomposition and Regulation on Gut Microbiota.

Polysaccharides from Dendrobium officinale have garnered attention for their diverse and well-documented biological activities. In this study, we isolated three ethanol-fractionated polysaccharides from Dendrobium officinale (EPDO) and investigated their digestive properties and effects on gut microbiota regulation in vitro. The results indicated that after simulating digestion in saliva, gastric, and small intestinal fluids, three EPDOs, EPDO-40, EPDO-60 and EPDO-80, with molecular weights (Mw) of 442.6, 268.3 and 50.8 kDa, respectively, could reach the large intestine with a retention rate exceeding 95%. During in vitro fermentation, the EPDOs were broken down in a "melting" manner, resulting in a decrease in their Mw. EPDO-60 degraded more rapidly than EPDO-40, likely due to its moderate Mw. After 24 h, the total production of short-chain fatty acids (SCFAs) for EPDO-60 reached 51.2 ± 1.9 mmol/L, which was higher than that of EPDO-80. Additionally, there was an increase in the relative abundance of Bacteroides, which are capable of metabolizing polysaccharides. EPDO-60 also promoted the growth of specific microbiota, including Prevotella 9 and Parabacteroides, which could potentially benefit from these polysaccharides. Most notably, by comparing the gut microbiota produced by different fermentation carbon sources, we identified the eight most differential gut microbiota specialized in polysaccharide metabolism at the genus level. Functional prediction of these eight differential genera suggested roles in controlling replication and repair, regulating metabolism, and managing genetic information transmission. This provides a new reference for elucidating the specific mechanisms by which EPDOs influence the human body. These findings offer new evidence to explain how EPDOs differ in their digestive properties and contribute to the establishment of a healthy gut microbiota environment in the human body.

Electronic health record-integrated questionnaires in colorectal surgery patients as a new standard: Could preoperative bowel function be used to predict postoperative patient-reported outcomes?

BACKGROUND AND OBJECTIVES: Patient-reported bowel function has been previously shown to correlate with quality of life and patient-reported outcomes (PROs) after colorectal surgery. We examined the relationship between preoperative patient-reported bowel function and postoperative symptom reporting using an electronic health record-integrated symptom management (eSyM). METHODS: Patients who underwent major abdominal surgery for colorectal cancer at a single institution were included. Preoperative bowel function was assessed prospectively using the validated colorectal functional outcome (COREFO) questionnaire. Patients with electronic portal access received automated eSyM questionnaires after discharge. Logistic regression was used to analyze the association between COREFO scores and eSyM use. RESULTS: 169 patients underwent surgery between April 2020 and June 2022 (median age 64, 46.7% female). 148 completed COREFO questionnaires preoperatively; 54 (36.5%) had scores ≥15. Of the 108 patients with portal access, 67.6% used eSyM postoperatively. Among users, 72.3% (47/73) reported severe symptoms. Those with COREFO scores ≥15 were more likely to use eSyM (80.0% vs. 62.7%) though this difference was not significant (p = 0.079). CONCLUSIONS: We found that eSyM utilization regardless of preoperative baseline bowel function was high in this cohort of colorectal surgery patients. This suggests that electronically captured PROs is an effective way for patients to communicate symptoms to their care teams in a postsurgical setting.

The Sustained Impact of the COVID-19 Pandemic on Vascular Surgical Care Delivery.

BACKGROUND: The COVID-19 pandemic necessitated postponement of vascular surgery procedures nationally. Whether procedure volumes have since recovered remains undefined. Therefore, our objective was to quantify changes in procedure volumes and determine whether surgical volume has returned to its prepandemic baseline. METHODS: This study was a retrospective cross-sectional study between 2018 and 2023 using the US Fee-for-Service Medicare 5% National Sample as part of the VA Disrupted Care National Project. We studied patients who underwent 1 of 3 procedures: abdominal aortic aneurysm (AAA) repair for intact aneurysms, carotid endarterectomy (CEA), and major lower extremity amputation (LEA). The case volume of each quarter of 2020-2023 was compared to its corresponding prepandemic quarter in 2019. We then performed a subanalysis of these trends by sex, age, and race. RESULTS: We identified 21,031 procedures: 4,411 AAA repair, 8,361 CEA, and 8,259 LEA. The average percent change during the baseline prepandemic period from 2018 to 2019 was -4.3% for AAA repair, -8.5% for CEA, and -2.6% for LEA. Compared to Q2 of 2019, Q2 of 2020 demonstrated that AAA repair procedures decreased by 47%, CEA by 40%, and LEA by 14%. While procedures initially rebounded in Q3 of 2020, volumes did not return to their prepandemic baseline, demonstrating a persistent volume reduction (-16% AAA, -22% CEA, and -11% LEA). Thereafter, procedure counts again declined in Q1 of 2022 (-25% AAA, -34% CEA, and -25% LEA). CONCLUSIONS: Despite a perception that vascular surgical care was singularly disrupted at the outset of the pandemic, there has been a sustained reduction in vascular surgical volume since 2019. Not only have procedure volumes not returned to prepandemic baseline but it also appears that there has been a cumulative incremental impact on overall procedure volume. The impact of these findings on long-term population health remains uncertain and necessitates a better understanding of postpandemic care delivery.

Atrial Natriuretic Peptide Alleviates Motion Sickness Potentially through Regulating Endolymph Volume in the Inner Ear Increased by Arginine Vasopressin.

INTRODUCTION: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. RESULTS: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. CONCLUSION: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

The fibrosis-4 index is a prognostic factor for cholangiocarcinoma patients who received immunotherapy.

Background: Research of immunotherapy for cholangiocarcinoma has yielded some results, but more clinical data are needed to prove its efficacy and safety. Moreover, there is a need to identify accessible indexes for selecting patients who may benefit from such treatments. Methods: The medical records of 66 cholangiocarcinoma patients who underwent immunotherapy were retrospectively collected. The effectiveness of immunotherapy was assessed by tumor response, progression-free survival (PFS), and overall survival (OS), while safety was evaluated by adverse events during treatment. Univariate and multivariate Cox regression analyses were performed to identify prognostic risk factors for PFS and OS, and Kaplan-Meier curves of potential prognostic factors were drawn. Results: Overall, in this study, immunotherapy achieved an objective response rate of 24.2% and a disease control rate of 89.4% for the included patients. The median PFS was 445 days, and the median OS was 772.5 days. Of the 66 patients, 65 experienced adverse events during treatment, but none had severe consequences. Multivariate Cox analysis indicated that tumor number is a prognostic risk factor for disease progression following immunotherapy in cholangiocarcinoma patients, while tumor differentiation and the fibrosis-4 (FIB-4) index are independent risk factors for OS. Conclusion: In general, immunotherapy for cholangiocarcinoma is safe, with adverse events remaining within manageable limits, and it can effectively control disease progression in most patients. The FIB-4 index may reflect the potential benefit of immunotherapy for patients with cholangiocarcinoma.