Vitrectomy combined with inverted internal limiting membrane flap insertion or single-layered flap covering technique for highly myopic macular holes with macular retinoschisis.

PURPOSE: To investigate the anatomical and visual outcomes of inverted internal limiting membrane (i-ILM) flap insertion versus single-layered i-ILM flap covering in highly myopic macular holes (HMMHs) associated with macular retinoschisis (MRS). METHODS: A retrospective study compared 23G vitrectomy with i-ILM flap insertion (30 eyes) or covering (31 eyes) in HMMH patients. Pre- and postoperative optical coherence tomography images and best-corrected visual acuity (BCVA) were evaluated. Macular hole schisis (MHS) was classified into three types based on the extent of outer layer schisis. Regression analysis identified predictors of closure rate and postoperative BCVA. RESULTS: The baseline data of the two groups were matched, including BCVA, axial length, and minimum linear diameter, except for a higher hole height in insertion group (P=0.038). After a mean follow-up of 11.7 months, type I closure rates were 83.3% (25/30) in the insertion group and 90.3% (28/31) in the covering group (P=0.335), respectively. The intact external limiting membrane in the covering group (7/28) was higher compared to the insertion group (1/28) finally (P=0.026). Final BCVA improved significantly in both groups (P<0.001), the BCVA was better in closed HMMHs in the covering group (P=0.011). Multivariate linear regression analysis revealed that preoperative BCVA (ß=0.386, P=0.001) and MHS stage (ß=0.309, P=0.004) were independent predictive factors for the final BCVA. CONCLUSION: The single-layered i-ILM flap covering favored foveal structure recovery and provided a better visual prognosis in closed HMMHs compared with insertion. The preoperative BCVA and MHS stage were independent predictors of visual outcomes in patients with HMMHs.

Anomalous Non-Hermitian Open-Boundary Spectrum.

For a long time, it was presumed that continuum bands could be readily encompassed by open-boundary spectra, irrespective of the system's modest dimensions. However, our findings reveal a nuanced picture: under open-boundary conditions, the proliferation of complex eigenvalues progresses in a sluggish, oscillating manner as the system expands. Consequently, even in larger systems, the overlap between continuum bands and open-boundary eigenvalues becomes elusive, with the surprising twist that the count of these complex eigenvalues may actually diminish with increasing system size. This counterintuitive trend underscores that the pursuit of an ideal, infinite-sized system scenario does not necessarily align with enlarging the system size. Notably, despite the inherent non-Hermiticity of our system, the eigenstates distribute themselves in a manner reminiscent of Bloch waves. These discoveries hold potential significance for both theoretical explorations and experimental realizations of non-Hermitian systems.

Associations between multi-metal joint exposure and decreased estimated glomerular filtration rate (eGFR) in solar greenhouse workers: A study of a unique farmer group.

BACKGROUND: Solar greenhouse workers, a unique farmer group, have been reported to have a higher risk of chronic kidney disease (CKD) compared to the general population, possible due to exposure to multiple metals. OBJECTIVE: This study aimed to investigate the associations between exposure to multiple metals and the estimated glomerular filtration rate (eGFR). METHODS: A cross-sectional study was conducted in the Northwest China. Urine samples were tested for concentration of 14 metals, including chromium, manganese, iron et al. Blood creatinine was measured to calculate eGFR, which was to evaluate the kidney function. Linear model and the Bayesian Kernel Machine Regression (BKMR) models were used to evaluate the associations between metals exposure and eGFR. RESULT: The study included 281 solar greenhouse workers, with 128 (45.6%) males and 153 (54.4%) females. The highest median concentrations of metals were zinc (418.55 µg/L), strontium (368.77 µg/L), and iron (55.73 µg/L), respectively. The linear model analysis showed that urinary levels of copper and zinc were negatively associated with eGFR [ß = -0.021, 95% CI (-0.048, -0.007); ß = -0.018, 95% CI (-0.068, -0.005)] considering a false discovery rate. BKMR results indicated a significant overall negative effect of 14 metals exposure on the eGFR when all metal levels were above the 50th percentile compared to the median value. CONCLUSIONS: The decrease in eGFR among solar greenhouse workers was related to mixed metal exposure. Reducing exposure to the metals of copper, zinc, and lead could effectively protects kidney function. Further prospective studies are needed to resolve concerns about reverse causality.

Single-cell virology: On-chip, quantitative characterization of the dynamics of virus spread from one single cell to another.

Virus spread at the single-cell level is largely uncharacterized. We have designed and constructed a microfluidic device in which each nanowell contained a single, infected cell (donor) and a single, uninfected cell (recipient). Using a GFP-expressing poliovirus as our model, we observed both lytic and non-lytic spread. Donor cells supporting lytic spread established infection earlier than those supporting non-lytic spread. However, non-lytic spread established infections in recipient cells substantially faster than lytic spread and yielded higher rates of genome replication. While lytic spread was sensitive to the presence of capsid entry/uncoating inhibitors, non-lytic spread was not. Consistent with emerging models for non-lytic spread of enteroviruses using autophagy, reduction of LC3 levels in cells impaired non-lytic spread and elevated the fraction of virus in donor cells spreading lytically. The ability to distinguish lytic and non-lytic spread unambiguously will enable discovery of viral and host factors and host pathways used for non-lytic spread of enteroviruses and other viruses as well.

Artificial intelligence software for assessing brain ischemic penumbra/core infarction on computed tomography perfusion: A real-world accuracy study.

BACKGROUND: With the increasingly extensive application of artificial intelligence (AI) in medical systems, the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation. AIM: To investigate the accuracy of AI diagnostic software (Shukun) in assessing ischemic penumbra/core infarction in acute ischemic stroke patients due to large vessel occlusion. METHODS: From November 2021 to March 2022, consecutive acute stroke patients with large vessel occlusion who underwent mechanical thrombectomy (MT) post-Shukun AI penumbra assessment were included. Computed tomography angiography (CTA) and perfusion exams were analyzed by AI, reviewed by senior neurointerventional experts. In the case of divergences among the three experts, discussions were held to reach a final conclusion. When the results of AI were inconsistent with the neurointerventional experts' diagnosis, the diagnosis by AI was considered inaccurate. RESULTS: A total of 22 patients were included in the study. The vascular recanalization rate was 90.9%, and 63.6% of patients had modified Rankin scale scores of 0-2 at the 3-month follow-up. The computed tomography (CT) perfusion diagnosis by Shukun (AI) was confirmed to be invalid in 3 patients (inaccuracy rate: 13.6%). CONCLUSION: AI (Shukun) has limits in assessing ischemic penumbra. Integrating clinical and imaging data (CT, CTA, and even magnetic resonance imaging) is crucial for MT decision-making.

Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

Autodelineation of Treatment Target Volume for Radiation Therapy Using Large Language Model-Aided Multimodal Learning.

PURPOSE: Artificial intelligence-aided methods have made significant progress in the auto-delineation of normal tissues. However, these approaches struggle with the auto-contouring of radiation therapy target volume. Our goal was to model the delineation of target volume as a clinical decision-making problem, resolved by leveraging large language model-aided multimodal learning approaches. METHODS AND MATERIALS: A vision-language model, termed Medformer, has been developed, employing the hierarchical vision transformer as its backbone and incorporating large language models to extract text-rich features. The contextually embedded linguistic features are seamlessly integrated into visual features for language-aware visual encoding through the visual language attention module. Metrics, including Dice similarity coefficient (DSC), intersection over union (IOU), and 95th percentile Hausdorff distance (HD95), were used to quantitatively evaluate the performance of our model. The evaluation was conducted on an in-house prostate cancer data set and a public oropharyngeal carcinoma data set, totaling 668 subjects. RESULTS: Our Medformer achieved a DSC of 0.81 ± 0.10 versus 0.72 ± 0.10, IOU of 0.73 ± 0.12 versus 0.65 ± 0.09, and HD95 of 9.86 ± 9.77 mm versus 19.13 ± 12.96 mm for delineation of gross tumor volume on the prostate cancer dataset. Similarly, on the oropharyngeal carcinoma dataset, it achieved a DSC of 0.77 ± 0.11 versus 0.72 ± 0.09, IOU of 0.70 ± 0.09 versus 0.65 ± 0.07, and HD95 of 7.52 ± 4.8 mm versus 13.63 ± 7.13 mm, representing significant improvements (P < 0.05). For delineating the clinical target volume, Medformer achieved a DSC of 0.91 ± 0.04, IOU of 0.85 ± 0.05, and HD95 of 2.98 ± 1.60 mm, comparable with other state-of-the-art algorithms. CONCLUSIONS: Auto-delineation of the treatment target based on multimodal learning outperforms conventional approaches that rely purely on visual features. Our method could be adopted into routine practice to rapidly contour clinical target volume/gross tumor volume.

Synthesis and Biological Evaluation of Novel Chlorogenic Acid-Apigenin Conjugates as Anti-acute Gout Agents.

Gout is the second largest metabolic disease worldwide after diabetes, with acute gouty arthritis as most common symptom. Xanthine oxidase (XOD) and the NOD like receptor-3 (NLRP3) inflammasome are the key targets for acute gout treatment. Chlorogenic acid has been reported with a good anti-inflammatory activity, and Apigenin showed an excellent potential in XOD inhibition. Therefore, a series of chlorogenic acid-apigenin (CA) conjugates with varying linkers were designed and synthesized as dual XOD/NLRP3 inhibitors, and their activities both in XOD and NLRP3 inhibition were evaluated. An in vitro study of XOD inhibitory activity revealed that the majority of CA conjugates exhibited favorable XOD inhibitory activity. Particularly, the effects of compounds 10c and 10d, with an alkyl linker on the apigenin moiety, were stronger than that of allopurinol. The selected CA conjugates also demonstrated a favorable anti-inflammatory activity in RAW264.7 cells. Furthermore, compound 10d, which showed the optimal activity both in XOD inhibition and anti-inflammatory, was chosen and its inhibitory ability on NLRP3 and related proinflammatory cytokines was further tested. Compound 10d effectively reduced NLRP3 expression and the secretion of interluekin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) with an activity stronger than the positive control isoliquiritigenin (ISL). Based on these findings, compound 10d exhibits dual XOD/NLRP3 inhibitory activity and, therefore, the therapeutic effects on acute gout is worthy of further study.

Construction of a mitophagy-related prognostic signature for predicting prognosis and tumor microenvironment in lung adenocarcinoma.

Background: Mitophagy is the selective degradation of mitochondria by autophagy. It becomes increasingly clear that mitophagy pathways are important for cancer cells to adapt to their high-energy needs. However, which genes associated with mitophagy could be used to prognosis cancer is unknown. Methods: We created a clinical prognostic model using mitophagy-related genes (MRGs) in lung adenocarcinoma (LUAD) patients for the first time, and we employed bioinformatics methods to search for biomarkers that affect the progression and prognosis of LUAD. Transcriptome data for LUAD were obtained from The Cancer Genome Atlas (TCGA) database, and additional expression data from LUAD patients were sourced from the Gene Expression Omnibus (GEO) database. Furthermore, 25 complete MRGs were identified based on annotations from the MSigDB database. Results: A comparison of the mitophagy scores between the groups with high and low scores was done using receiver operating characteristic (ROC) curves, which also revealed the differential gene expression patterns between the two groups. Using Kaplan-Meier analysis, two prognostic MRGs from the groups with high and low mitophagy scores were identified: TOMM40 and VDAC1. Using univariate and multivariate Cox regression, the relationship between the expression levels of these two genes and prognostic clinical features of LUAD was examined further.The prognosis of LUAD patients was shown to be significantly correlated (P < 0.05) with the expression levels of these two genes. Conclusions: Our prognostic model would improve the prognosis of LUAD and guide clinical treatments.

Stability and Controller Research of Double-Wing FMAV System Based on Controllable Tail.

This study aimed to enhance the stability and response speed of a passive stabilized double-wing flapping micro air vehicle (FMAV) by implementing a feedback-controlled biomimetic tail. A model for flapping wings accurately calculated the lift force with only a 2.4% error compared to the experimental data. Experimental tests established the relationship between control torque and tail area, swing angle, and wing-tail spacing. A stability model for the double-wing FMAV was developed, incorporating stabilizing sails. Linearization of the hovering state facilitated the design of a simulation controller to improve response speed. By adjusting the feedback loops of velocity, angle, and angular velocity, the tail controller reduced the angle simulation response time from 4 s to 0.1 s and the velocity response time from 5.64 s to 0.1 s. In take-off experiments, a passive stabilized prototype with an adjustable tail angle exhibited enhanced flight stability compared to fixed tails, reducing standard deviation by 72.96% at a 0° take-off angle and 56.85% at a 5° take-off angle. The control axis standard deviation decreased by 38.06% compared to the passive stability axis, confirming the effectiveness of the designed tail angle controller in reducing angular deflection and improving flight stability.

Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo.

Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.

MpANT regulates meristem development in Marchantia polymorpha.

Meristems are crucial for organ formation, but our knowledge of their molecular evolution is limited. Here, we show that AINTEGUMENTA (MpANT) in the euANT branch of the APETALA2-like transcription factor family is essential for meristem development in the nonvascular plant Marchantia polymorpha. MpANT is expressed in the thallus meristem. Mpant mutants show defects to maintain meristem identity and undergo meristem duplication, while MpANT overexpressers show ectopic thallus growth. MpANT directly upregulates MpGRAS9 in the SHORT-ROOT (SHR) branch of the GRAS family. In the vascular plant Arabidopsis thaliana, the euANT-branch genes PLETHORAs (AtPLTs) and AtANT are involved in the formation and maintenance of root/shoot apical meristems and lateral organ primordia, and AtPLTs directly target SHR-branch genes. In addition, euANTs bind through a similar DNA-binding motif to many conserved homologous genes in M. polymorpha and A. thaliana. Overall, the euANT pathway has an evolutionarily conserved role in meristem development.

Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque.

BACKGROUND: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition. METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria. RESULTS: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice. CONCLUSIONS: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques.

Single-Frame Supervision for Spatio-Temporal Video Grounding.

Spatio-Temporal Video Grounding (STVG) aims at localizing the spatio-temporal tube of a specific object in an untrimmed video given a free-form natural language query. As the annotation of tubes is labor intensive, researchers are motivated to explore weakly supervised approaches in recent works, which usually results in significant performance degradation. To achieve a less expensive STVG method with acceptable accuracy, this work investigates the "single-frame supervision" paradigm that requires a single frame labeled with a bounding box within the temporal boundary of the fully supervised counterpart as the supervisory signal. Based on the characteristics of the STVG problem, we propose a Two-Stage Multiple Instance Learning (T-SMILE) method, which creates pseudo labels by expanding the annotated frame to its contextual frames, thereby establishing a fully-supervised problem to facilitate further model training. The innovations of the proposed method are three-folded, including 1) utilizing multiple instance learning to dynamically select instances in positive bags for the recognition of starting and ending timestamps, 2) learning highly discriminative query features by incorporating spatial prior constraints in cross-attention, and 3) designing a curriculum learning-based strategy that iterative assigns dynamic weights to spatial and temporal branches, thereby gradually adapting to the learning branch with larger difficulty. To facilitate future research on this task, we also contribute a large-scale benchmark containing 12,469 videos on complex scenes with single-frame annotation. The extensive experiments on two benchmarks demonstrate that T-SMILE significantly outperforms all weakly-supervised methods. Remarkably, it also performs better than some fully-supervised methods associated with much more annotation labor costs. The dataset and codes are available at https://github.com/qumengxue/T-SMILE.

Inhibiting the self-discharging process of quantum batteries in non-Markovian noises.

One of the main challenges in developing high-performance quantum batteries is the self-discharging process, where energy is dissipated from a quantum battery into the environment. In this work, we investigate the influence of non-Markovian noises on the performance of a quantum battery. Our results demonstrate that adding auxiliary qubits to a quantum battery system can effectively suppress the self-discharging process, leading to an improvement in both the steady-state energy and extractable work. We reveal that the physical mechanism inhibiting the self-discharging process is the formation of system-environment bound states, rather than an increase in non-Markovianity. Our results could be of both theoretical and experimental interest in exploring the ability of quantum batteries to maintain long stored energy in the environment.

Del Nido cardioplegia versus cold blood cardioplegia in adult cardiac surgery: a meta-analysis of randomized clinical trials.

OBJECTIVE: Systematic evaluation of the safety of del Nido cardioplegia compared to cold blood cardioplegia in adult cardiac surgery. METHODS: We systematically searched PubMed, EMbase, The Cochrane Library and ClinicalTrials.gov for randomized clinical trials (published by 14 January 2024) comparing del Nido cardioplegia to cold blood cardioplegia in adult. Our main endpoints were myocardial injury markers and clinical outcomes. We assessed pooled data by use of a random-effects model or a fixed-effects model. RESULTS: A total of 10 studies were identified, incorporating 889 patients who received del Nido cardioplegia and 907 patients who received cold blood cardioplegia. The meta-analysis results showed that compared with the cold blood cardioplegia, the del Nido cardioplegia had less volume of cardioplegia, higher rate of spontaneous rhythm recovery after cross clamp release, lower levels of postoperative cardiac troponin T and creatinine kinase-myocardial band, all of which were statistically significant. However, there was no statistically significant difference in postoperative troponin I and postoperative left ventricular ejection fraction. The clinical outcomes including mechanical ventilation time, intensive care unit stay time, hospital stay time, postoperative stroke, postoperative new-onset atrial fibrillation, postoperative heart failure requiring intra-aortic balloon pump mechanical circulation support, and in-hospital mortality of both are comparable. CONCLUSION: Existing evidence suggests that del Nido cardioplegia reduced volume of cardioplegia administration and attempts of defibrillation. The superior postoperative results in CTnT and CK-MB may provide a direction for further research on improvement of the composition of cardioplegia.

Clinical efficacy of high-voltage pulsed radiofrequency combined with stellate ganglion block in the acute phase of thoracic and dorsal herpes zoster neuralgia under dual guidance of ultrasound and C-arm.

OBJECTIVES: A single therapeutic approach is not always successful in the treatment of herpes zoster neuralgia, and the appropriate combination of different treatments deserves further exploration. In this study, we investigated the clinical efficacy of high-voltage long-duration pulsed radiofrequency (PRF) combined with stellate ganglion block (SGB) in the acute phase of thoracic and dorsal herpes zoster neuralgia under dual guidance of ultrasound and C-arm. METHODS: 79 cases of acute zoster neuralgia were grouped premised upon differing therapeutic approaches: standard voltage PRF (group S, the temperature, duration, pulse width, frequency and voltage were set to 42 °C, 300 s, 20 ms, 2 Hz, and 45 V), high-voltage long-duration PRF (group H, parameters of PRF were set to 42 °C, 900 s, 20 ms, 2 Hz, and 90 V, respectively), and high-voltage long-duration PRF combined with SGB (group C, parameter settings for PRF are the same as those for group H). The therapeutic outcomes were assessed utilizing the numeric rating scale (NRS), Pittsburgh sleep quality index (PSQI), and Hamilton anxiety rating scale (HAMA). The incidence of clinically significant postherpetic neuralgia post-treatment had been documented. RESULTS: Compared to baseline, scores of NRS, PSQI, and HAMA at each time point post-treatment decreased across all groups, and the decrease was more significant in the C group than in the S group. At the later stage of treatment, the consumption of pregabalin and tramadol and the plasma levels of interleukin-6 and galectin-3 in the C group were significantly lower than those in the S group. The incidence of PHN in the C group was significantly lower than in the S group. CONCLUSIONS: The combination of high-voltage long-duration PRF combined with SGB under dual guidance of ultrasound and C-arm represents a safe, effective, environmentally friendly, and cost-efficient method for treating AZN, significantly improving sleep quality, alleviating anxiety, and reducing the risk of PHN occurrence.

Bifidobacterium animalis subsp. lactis LPL-RH improves postoperative gastrointestinal symptoms and nutrition indexes by regulating the gut microbiota in patients with valvular heart disease: a randomized controlled trial.

Gastrointestinal symptoms constitute a frequent complication in postoperative patients with valvular heart disease (VHD), impacting their postoperative recovery. Probiotics contribute to regulating human gut microbiota balance and alleviating postoperative gastrointestinal symptoms. Our objective involved assessing the potential of Bifidobacterium animalis subsp. lactis LPL-RH to alleviate postoperative gastrointestinal symptoms and expedite patient recovery. Adult patients diagnosed with VHD scheduled for valve surgery were enrolled. 110 patients were randomly divided into two groups and received LPL-RH or a placebo for 14 days. Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptoms Questionnaire. An analysis of the time to recovery of bowel function and various postoperative variables was conducted in both study groups. Variations in the intestinal microbiota were detected via 16S rRNA sequencing. The study was completed by 105 participants, with 53 in the probiotic group and 52 in the placebo group. Compared to the placebo group, LPL-RH significantly reduced the total gastrointestinal symptom score after surgery (p = 0.004). Additionally, LPL-RH was found to significantly reduce abdominal pain (p = 0.001), bloating (p = 0.018), and constipation (p = 0.022) symptom scores. Furthermore, LPL-RH dramatically shortened the time to recovery of bowel function (p = 0.017). Moreover, LPL-RH administration significantly enhanced patients' postoperative nutrition indexes (red blood cell counts, hemoglobin level, p < 0.05). Microbiome analysis showed that the composition and diversity of the postoperative intestinal microbiota differed between the probiotic and placebo groups. No adverse incidents associated with probiotics were documented, emphasizing their safety. This study initially discovered that oral B. animalis subsp. lactis LPL-RH can assist in regulating intestinal microbiota balance, alleviating gastrointestinal symptoms, promoting intestinal function recovery, and enhancing nutrition indexes in patients with VHD after surgery. Regulating the intestinal microbiota may represent a potential mechanism for LPL-RH to exert clinical benefits.

Efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil monotherapy for refractory metastatic colorectal cancer: a retrospective cohort study.

Background: Several studies demonstrated trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) had better efficacy than the monotherapy of TAS-102 in refractory metastatic colorectal cancer (mCRC). However, it remains unclear whether Chinese population can benefit from this combination or not. Hence, we conducted this retrospective cohort study to compare the efficacy and safety between TAS-102 plus BEV with TAS-102 monotherapy in refractory mCRC. Methods: This retrospective cohort study enrolled patients (any age) with refractory mCRC from Hunan Cancer Hospital. The main inclusion criteria were histopathologically and/or radiographically confirmed refractory mCRC, World Health Organization (WHO) performance status of 0 to 2, adequate organ function, and initial treatment of TAS-102 with or without BEV between November 2020 and October 2022. Previous therapy with fruquintinib or regorafenib was allowed but not mandatory. Baseline demographic and clinical characteristics were collected appropriately. Every 2 or 3 treatment cycles, the patients were assessed by computed tomography (CT) scans and clinical assessments until disease progression or loss to follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI-CTCAE 5.0) were presented as n (%). The primary endpoint was investigator-evaluated overall survival (OS). As this is a retrospective cohort study, sample size calculation was not performed. Eligible patients would be enrolled as many as possible. Results: A total of 90 patients were enrolled, including 58 patients who received TAS-102 plus BEV and another 32 patients who received TAS-102 monotherapy. The known baseline characteristics were comparable (P<0.05). With a median follow-up of 4.60 months (range, 0.20-22.80), the median OS (mOS) time in the TAS-102 plus BEV group was longer than that in the TAS-102 monotherapy group (10.83 vs. 7.43 months), but the difference was not significant (P=0.79). The median progression-free survival (mPFS) time was comparable between the two groups (4.67 vs. 4.30 months, P=0.96). Multivariate Cox regression analysis demonstrated that undergoing therapy after TAS-102 either with or without BEV was an independent risk factor for OS [hazard ratio (HR) =0.25; 95% confidence interval (CI): 0.09-0.71, P<0.01], and previous treatment with cetuximab was an independent protective factor for PFS (HR =0.17; 95% CI: 0.03-0.91, P=0.04). Of the 70 patients who were evaluated, those receiving TAS-102 plus BEV showed trend of a higher objective response rate (ORR) and disease control rate (DCR) than those who received TAS-102 monotherapy (P=0.16 and P=0.29, respectively). Adverse events (AEs) were similar between the two groups, except that the incidence of platelet count decrease (grade ≥3) was significantly higher in the TAS-102 plus BEV group. Conclusions: There was a trend in favor of the combination of BEV plus TAS-102 regarding OS and DCR, without reaching statistical significance, and it means that there was no clear advantage of one over the other in terms of efficacy. Further prospective studies are still necessary to draw a definite conclusion.