Global hotspots and trends in diabetic peripheral neuropathy research from 2011 to 2023.

Diabetic peripheral neuropathy (DPN) is a prevalent disease, and the relevant literature has been increasingly investigated over the past years. Consequently, it is imperative to conduct a scientific and comprehensive DPN research field bibliometric analysis. This study aims to summarize and visualize the literature distribution laws, the research hotspots, and the development trends in DPN using bibliometric methods. We searched all relevant documents published from 2011 to 2023 in the Web of Science Core Collection. Bibliometric analysis and network visualization were performed using VOSviewer, R-bibliometrix, and CiteSpace tools, focusing on countries, institutions, authors, journals, highly cited papers, references, and keywords. This study included a total of 2708 documents. The annual number of publications in the field has notably increased. China, the USA, and the UK take on critical significance in DPN research. The University of Manchester in the UK has the highest number of publications (109). Malik has the most publications (86). Tesfaye literature has been most frequently cited by scholars of DPN research. The Journal of Diabetes and its Complications and Frontiers in Endocrinology have the most publications (45 each). Diabetes Care stands out with the highest impact factor (16.200), number of citations (2516), and H-index (27) among the number of publications top 10 journals. The paper "Colloca, L. et al Neuropathic pain. Nature Reviews Disease Primers. 2017, 3 (1):1-19" has the highest number of citations (1224 times). The most critical co-cited reference is "Tesfaye S, 2010, DIABETES CARE, V33, P2285" (cited 408 times). Keywords like "type 2 diabetes," "diagnosis," "association," "retinopathy," "risk factors," "progression," "corneal confocal microscopy," "nephropathy," "balance," "microvascular complications," "inflammation," "disease," and "insulin resistance" represent the recent research hotspots. The development, research hotspots, and future trends of the global DPN domain from 2011 to 2023 were summarized and visualized in this study. This study can present more insights into the general situation of DPN research and provide a useful reference for clinical decision-making and directions of subsequent research.

Melatonin Improves Oxidative Stress Injury in Retinopathy of Prematurity by Targeting miR-23a-3p/Nrf2.

PURPOSE: Melatonin has promising protective effects for retinopathy. However, its roles in retinopathy of prematurity (ROP) and the underlying mechanisms remain unknown. We aimed to explore its roles and mechanisms in a ROP model. METHODS: Hematoxylin and eosin staining were used to observe the morphology of the retina. Immunofluorescence was used to detect positive (Nrf2+ and VEGF+) cells. Immunohistochemistry was used to detect the level of nuclear expression of PCNA in retinal tissue. Transmission electron microscope (TEM) was used to observe the morphology and structure of pigment cells. qRT-PCR was used to assay the expression of miR-23a-3p, Nrf2, and HO-1. Western blotting was used to detect the expression of Nrf2, HO-1, ß-actin, and Lamin B1. RESULTS: Melatonin or miR-23a-3p antagomir treatment could ameliorate the Oxygen-induced pathological changes, increased the expression of Nrf2 and HO-1, SOD, and GSH-Px, and decreased the expression of VEGF, miR-23a-3p, MDA and the apoptosis in the ROP model. Further target prediction and luciferase reporter assays confirmed the targeted binding relationship between miR-23a-3p and Nrf2. CONCLUSION: Our study showed that melatonin could ameliorate H2O2-induced apoptosis and oxidative stress injury in RGC cells by mediating miR-23a-3p/Nrf2 signaling pathway, thereby improving retinal degeneration.

Lignin nanoparticles formation by multiscale structure control to regulate morphology and their adsorption, nucleation, and growth on chitin nanofibers.

The lignin nanoparticles (LNPs) synthesis relies on lignin polymers with heterogeneous molecules and properties, which impose significant limitations on the preparation and property regulation. The multiscale structure of lignin from monomers to oligomers, provides a potential pathway for precise regulation of its physical and chemical properties. The study addresses this challenge by employing coniferyl alcohol and sinapyl alcohol as monomers and separately utilizing the Zulaufverfaren (ZL) and Zutropfverfaren (ZT) methods to synthesize different types of lignin dehydrogenation polymers (DHPs) including guaiacyl (G)-ZL-DHP, G-ZT-DHP, syringyl (S)-ZL-DHP, and S-ZT-DHP. The investigation highlights the chemical bonds as essential components of lignin primary structure. Additionally, the secondary structure is influenced by branched and linear molecular structures. G unit provides some branching points, which are utilized and amplified in the ZL process of DHPs synthesis. The branched DHPs aggregate at the edge and form rod-like LNPs. While linear DHPs aggregate around the center, presenting polygonal LNPs. The study identifies that the branched LNPs, characterized by more surface charges and lower steric hindrance, can form a stable complex with chitin nanofibers. Emulsions with varying oil-to-water ratios were subsequently prepared, opening a new window for the application of LNPs in fields such as food and cosmetics.

A dual heterostructure enables the stabilization of 1T-rich MoSe2 for enhanced storage of sodium ions.

Electron injection effectively induces the formation of a 1T-rich phase to address the low conductivity of MoSe2. Nevertheless, overcoming the inherent metastability of the 1T phase (particularly during the conversion reactions that entail the decomposition-reconstruction of MoSe2 and volume expansion) remains a challenge. Guided by DFT results, we designed a composite with bimetal selenides-based heterostructures anchored on reduced graphene oxide (rGO) nanosheets (G-Cu2Se@MoSe2) to obtain stabilized 1T-rich MoSe2 and enhanced ion transfer. The construction of 1T-rich MoSe2 and built-in electric fields (BiEF) through electron transfer at the heterointerfaces were realized. Moreover, the rGO-metal selenides heterostructures with in situ-formed interfacial bonds could facilitate the reconstruction of the 1T-rich MoSe2-involved heterostructure and interfacial BiEF. Such a dual heterostructure endowed G-Cu2Se@MoSe2 with an excellent rate capability with a capacity of 288 mA h g-1 at 50 A g-1 and superior cycling stability with a capacity retention ratio of 89.6% (291 mA h g-1) after 15 000 cycles at 10 A g-1. Insights into the functional mechanism and structural evolution of the 1T MoSe2-involved dual heterostructure from this work may provide guidelines for the development of MoSe2 and phase-engineering strategies for other polymorphistic materials.

Detection of muscular system adverse reaction signals in sacubitril/valsartan treatment combined with statins.

Objective: To detect muscular system adverse reaction signals of sacubitril/valsartan treatment combined with statins (atorvastatin, rosuvastatin, simvastatin) to provide a reference for clinical administration. Methods: Multiplicative and additive models were used to mine the FDA's spontaneous reports database to detect signals of drug-drug interactions between sacubitril/valsartan and statins. SAS 9.4 software was used to conduct statistical tests for suspicious signals to determine whether the signals were statistically significant. Results: A total of 8,883,870 adverse reaction reports were analyzed. The combinations "sacubitril/valsartan - simvastatin - musculoskeletal muscle pain" had statistically significant correlation signals in both models (P < 0.05). The combination "sacubitril/valsartan - atorvastatin - myopathy" and "sacubitril/valsartan-simvastatin - myopathy" had statistically significant correlation signal in the multiplicative model (P < 0.05). Conclusion: Compared with a single drug, coadministration of sacubitril/valsartan with atorvastatin may increase safety risks to myopathy, with simvastatin may increase safety risks to the musculoskeletal pain and myopathy, which should be closely monitored in clinical practice.

Endothelial dysfunction: Pathophysiology and therapeutic targets for sepsis-induced multiple organ dysfunction syndrome.

Sepsis and septic shock are critical medical conditions characterized by a systemic inflammatory response to infection, significantly contributing to global mortality rates. The progression to multiple organ dysfunction syndrome (MODS) represents the most severe complication of sepsis and markedly increases clinical mortality. Central to the pathophysiology of sepsis, endothelial cells play a crucial role in regulating microcirculation and maintaining barrier integrity across various organs and tissues. Recent studies have underscored the pivotal role of endothelial function in the development of sepsis-induced MODS. This review aims to provide a comprehensive overview of the pathophysiology of sepsis-induced MODS, with a specific focus on endothelial dysfunction. It also compiles compelling evidence regarding potential small molecules that could attenuate sepsis and subsequent multi-organ damage by modulating endothelial function. Thus, this review serves as an essential resource for clinical practitioners involved in the diagnosing, managing, and providing intensive care for sepsis and associated multi-organ injuries, emphasizing the importance of targeting endothelial cells to enhance outcomes of the patients.

New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation.

Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

An unusual presentation of solitary ovarian metastasis from colorectal cancer in an elderly woman: a case report.

Background: There have been cases of colorectal cancer (CRC) metastasizing into the ovary. This study reports a case involving solitary ovarian metastasis (OM) from CRC, which is very rare in the absence of other pelvic and peritoneal metastases. This atypical clinical presentation added to the complexity of the diagnosis. Case Description: We report a case of solitary OM-CRC in a 48-year-old woman. The patient underwent CRC surgery and refused follow-up after three rounds of chemotherapy. Approximately 14 months later, the patient presented with vaginal bleeding for 2 months. The magnetic resonance imaging (MRI) showed a huge solid cystic mass in the right adnexa. Intraoperatively, the right ovary was found to be enlarged and smooth without adhesions. By careful examination of the abdominal cavity, no metastatic lesions were found in the left ovary and uterus, and no seedings were found in the rest of the pelvis and abdomen. After removal of the uterus and bilateral adnexa, the histologic examination revealed metastatic adenocarcinoma of the right ovary with a considered rectal carcinoma of origin. Positive staining for multiple tumor-associated markers, which further established the primary nature of CRC. These findings support a possible diagnosis of primary CRC and ovarian metastases. The patient recovered well after the operation and no recurrence or metastasis was seen 18 months after the operation. Conclusions: Solitary ovarian metastases from CRC can be better managed and treated by increasing clinicians' vigilance for this rare condition. This helps to improve the patient's prognosis and quality of life.

Neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence.

AIMS: Abuse of methamphetamine has aroused concern worldwide. Stimulant use and sexual behaviours have been linked in behavioural and epidemiological studies. Although methamphetamine-related neurofunctional differences are reported in previous studies, only few studies have examined neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence. METHODS: Neurofunctional changes were measured using a cue-reactivity task involving methamphetamine, sexual, and neutral cues in 20 methamphetamine abusers who were evaluated after a short- (1 week to 3 months) and long-term (10-15 months) abstinence. RESULTS: Five brain regions mainly involved in the occipital lobe and the parietal lobe were found with the group-by-condition interaction. Region-of-interest analyses found higher sexual-cue-related activation than other two activations in all five brain regions in the long-term methamphetamine abstinence group while no group differences were found. Negative relationships between motor impulsivity and methamphetamine- or sexual-cue-related activations in the left middle occipital gyrus, the superior parietal gyrus and the right angular gyrus were found. CONCLUSIONS: The findings suggested that methamphetamine abstinence may change the neural response of methamphetamine abusers to methamphetamine and sexual cues, and the neurofunction of the five brain regions reported in this study may partly recover with long-term methamphetamine abstinence. Given the use and relapse of methamphetamine for sexual purposes, the findings of this study may have particular clinical relevance.

The association of non-severe COVID-19 infection and progression to frailty among robust older veterans.

BACKGROUND: Studies have shown that frailty was increased in hospitalized COVID-19 patients. However, it is not clear whether non-severe COVID-19 increases the risk for pre-frailty and frailty development. Our study aimed to determine the risk of developing frailty and pre-frailty in robust veterans who contracted non-severe COVID-19. METHODS: We conducted a retrospective cohort study to assess the association of SARS-CoV-2 infection with the development of pre-frailty and frailty status among robust U.S. veterans using VA COVID-19 Shared Data Resource. We included patients 55 years and older who had at least one SARS-CoV-2 testing between March 15, 2020, and November 30, 2020, had been active patients in the past 12 months, and had a VA frailty index of zero (robust status) at the time of testing. Cox proportional hazard model was used to assess the association between COVID-19 infection and developing frailty or pre-frailty and frailty. We also assessed the association by patients' age groups, sex, and race. FINDINGS: We identified 82070 veterans mean age 68.3 ± 7.8, 74738 (91.1%) male, 53899 (65.7%) white, 7557 (9.2%) with mild COVID-19 infection. Over the follow up period of 36 months, testing positive for COVID-19 was associated with a 66% increase in the hazard of becoming frail (adjusted HR = 1.66, 95%CI: 1.32-2.08), and a 68% increase in the hazard of becoming pre-frail (adjusted HR = 1.68, 95%CI: 1.45-1.94). Among male patients, mild COVID-19 infection was associated with a 54% increase in the hazard of becoming frail (adjusted HR = 1.54, 95% CI: 1.21-1.96), while among female patients there was a 330% increase (adjusted HR = 4.30, 95% CI: 2.13-8.64). CONCLUSIONS AND RELEVANCE: Non-severe COVID-19 infection that occurred in robust older adults increased the risk of developing frailty. Further multi-center prospective cohort studies evaluating the mechanism of action and clinical trials of treatment options for post-COVID frailty are indicated in Veterans to support clinical care.

Human Pharmacokinetic and CYP3A Drug-Drug Interaction Prediction of GDC-2394 Using Physiologically Based Pharmacokinetic Modeling and Biomarker Assessment.

Physiologically based pharmacokinetic (PBPK) modeling was used to predict the human pharmacokinetics and drug-drug interaction (DDI) of GDC-2394. PBPK models were developed using in vitro and in vivo data to reflect the oral and intravenous PK profiles of mouse, rat, dog, and monkey. The learnings from preclinical PBPK models were applied to a human PBPK model for prospective human PK predictions. The prospective human PK predictions were within 3-fold of the clinical data from the first-in-human study, which was used to optimize and validate the PBPK model and subsequently used for DDI prediction. Based on the majority of PBPK modeling scenarios using the in vitro CYP3A induction data (mRNA and activity), GDC-2394 was predicted to have no-to-weak induction potential at 900 mg twice daily (BID). Calibration of the induction mRNA and activity data allowed for the convergence of DDI predictions to a narrower range. The plasma concentrations of the 4ß-hydroxycholesterol (4ß-HC) were measured in the multiple ascending dose study to assess the hepatic CYP3A induction risk. There was no change in plasma 4ß-HC concentrations after 7 days of GDC-2394 at 900 mg BID. A dedicated DDI study found that GDC-2394 has no induction effect on midazolam in humans, which was reflected by the totality of predicted DDI scenarios. This work demonstrates the prospective utilization of PBPK for human PK and DDI prediction in early drug development of GDC-2394. PBPK modeling accompanied with CYP3A biomarkers can serve as a strategy to support clinical pharmacology development plans. SIGNIFICANCE STATEMENT: This work presents the application of physiologically based pharmacokinetic modeling for prospective human pharmacokinetic (PK) and drug-drug interaction (DDI) prediction in early drug development. The strategy taken in this report represents a framework to incorporate various approaches including calibration of in vitro induction data and consideration of CYP3A biomarkers to inform on the overall CYP3A-related DDI risk of GDC-2394.

Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease.

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

Physical and oxidative stability of flaxseed oil-in-water emulsions prepared by natural lignin-carbohydrate complex.

Flaxseed oil, rich in α-linolenic acid, plays a crucial role in various physiological processes. However, its stability presents certain challenges. In this study, the natural lignin-carbohydrate complex (LCC) was used to prepare the physical and oxidative stability of flaxseed oil-in-water emulsions. The LCC was characterized by HPLC, GPC, and FT-IR. The stability of emulsions was evaluated by viscosity, modulus, and micro-morphology changes. Then, the oxidation products were monitored by UV-vis spectrophotometer and HPLC. The results revealed that the high internal phase emulsion (HIPE) was successfully prepared with 2.5 wt% LCC at an oil/water ratio of 75/25 (v/v). Small droplet size (13.361 µm) and high viscosity (36,500 mPa·s) were found even after 30-day storage. Steric interactions of the LCC play a crucial role in ensuring stability, intricately linked to the interfacial properties of the emulsion. Meanwhile, the oxidative stability of α-linolenic acid in the encapsulated flaxseed oil was significantly higher than that in the bulk flaxseed oil. The results revealed that the LCC as a suitable emulsifier opens a new window for the storage of functional lipids rich in polyunsaturated fatty acids.

Building and validating an artificial intelligence model to identify tracheobronchopathia osteochondroplastica by using bronchoscopic images.

BACKGROUND: Given the rarity of tracheobronchopathia osteochondroplastica (TO), many young doctors in primary hospitals are unable to identify TO based on bronchoscopy findings. OBJECTIVES: To build an artificial intelligence (AI) model for differentiating TO from other multinodular airway diseases by using bronchoscopic images. DESIGN: We designed the study by comparing the imaging data of patients undergoing bronchoscopy from January 2010 to October 2022 by using EfficientNet. Bronchoscopic images of 21 patients with TO at Anhui Chest Hospital from October 2019 to October 2022 were collected for external validation. METHODS: Bronchoscopic images of patients with multinodular airway lesions (including TO, amyloidosis, tumors, and inflammation) and without airway lesions in the First Affiliated Hospital of Guangzhou Medical University were collected. The images were randomized (4:1) into training and validation groups based on different diseases and utilized for deep learning by convolutional neural networks (CNNs). RESULTS: We enrolled 201 patients with multinodular airway disease (38, 15, 75, and 73 patients with TO, amyloidosis, tumors, and inflammation, respectively) and 213 without any airway lesions. To find multinodular lesion images for deep learning, we utilized 2183 bronchoscopic images of multinodular lesions (including TO, amyloidosis, tumor, and inflammation) and compared them with images without any airway lesions (1733). The accuracy of multinodular lesion identification was 98.9%. Further, the accuracy of TO detection based on the bronchoscopic images of multinodular lesions was 89.2%. Regarding external validation (using images from 21 patients with TO), all patients could be diagnosed with TO; the accuracy was 89.8%. CONCLUSION: We built an AI model that could differentiate TO from other multinodular airway diseases (mainly amyloidosis, tumors, and inflammation) by using bronchoscopic images. The model could help young physicians identify this rare airway disease.

Chemical Structures, Biological Activities, and Biosynthetic Analysis of Secondary Metabolites from Agaricus Mushrooms: A Review.

Agaricus mushrooms are an important genus in the Agaricaceae family, belonging to the order Agaricales of the class Basidiomycota. Among them, Agaricus bisporus is a common mushroom for mass consumption, which is not only nutritious but also possesses significant medicinal properties such as anticancer, antibacterial, antioxidant, and immunomodulatory properties. The rare edible mushroom, Agaricus blazei, contains unique agaricol compounds with significant anticancer activity against liver cancer. Agaricus blazei is believed to expel wind and cold, i.e., the pathogenic factors of wind and cold from the body, and is an important formula in traditional Chinese medicine. Despite its nutritional richness and outstanding medicinal value, Agaricus mushrooms have not been systematically compiled and summarized. Therefore, the present review compiles and classifies 70 natural products extracted from Agaricus mushrooms over the past six decades. These compounds exhibit diverse biological and pharmacological activities, with particular emphasis on antitumor and antioxidant properties. While A. blazei and A. bisporus are the primary producers of these compounds, studies on secondary metabolites from other Agaricus species remain limited. Further research is needed to explore and understand the anticancer and nutritional properties of Agaricus mushrooms. This review contributes to the understanding of the structure, bioactivity, and biosynthetic pathways of Agaricus compounds and provides insights for the development of functional foods using these mushrooms.

Recent advance in preparation of lignin nanoparticles and their medical applications: A review.

BACKGROUND: Lignin has attracted a lot of attention because it is non-toxic, renewable and biodegradable. Lignin nanoparticles (LNPs) have high specific surface area and specific surface charges. It provides LNPs with good antibacterial and antioxidant properties. LNPs preparation has become clear, however, the application remains in the early stages. PURPOSE: A review centric research has been conducted, reviewing existing literature to accomplish a basic understanding of the medical applications of LNPs. METHODS: Initially, we extensively counseled the heterogeneity of lignin from various sources. The size and morphology of LNPs from different preparation process were then discussed. Subsequently, we focused on the potential medical applications of LNPs, including drug delivery, wound healing, tissue engineering, and antibacterial agents. Lastly, we explained the significance of LNPs in terms of antibacterial, antioxidant and biocompatibility, especially highlighting the need for an integrated framework to understand a diverse range of medical applications of LNPs. RESULTS: We outlined the chemical structure of different type of lignin, and highlighted the advanced methods for lignin nanoparticles preparation. Moreover, we provided an in-depth review of the potential applications of lignin nanoparticles in various medical fields, especially in drug carriers, wound dressings, tissue engineering components, and antimicrobial agents. CONCLUSION: This review provides a detailed overview on the current state and progression of lignin nanoparticles for medical applications.

Modified superior bleb needling of rare hypertrophic bleb after trabeculectomy: A case series.

BACKGROUND: Hypertrophic bleb is a rare complication of glaucoma filtration surgery characterized by an elevated bleb extended through the nasal 180 degrees of the eye and usually with a normal IOP. Currently, there is little experience and no existing standardized treatment. We describe a new method called modified superior bleb needling and evaluate the clinical outcomes in affected eyes. METHODS: In this retrospective, consecutive interventional case series, patients who developed hypertrophic blebs after trabeculectomy from November 2015 to August 2020 at West China Hospital were enrolled. We innovatively adopted a modified superior bleb needling to allow aqueous humor to outflow into the superior subconjunctival space. Repeat needlings were performed if necessary. The technical and clinical success rate and complications were reported. RESULTS: At the time of the last follow-up, complete success was achieved in 8/10 patients, qualified success was achieved in 9/10 patients, and failure was achieved in 1/10 patients. Eight patients had a low filtering bleb and IOP ≤21 mmHg. There was no statistically significant difference between the preneedling and postneedling IOP (p > 0.05). CONCLUSION: Modified superior bleb needling is effective for hypertrophic blebs after trabeculectomy, and there was no significant impact on anterior chamber depth or IOP, making it a viable or preferred alternative option. It is worthy of further study and wider usage.

Recurrent neural network for predicting absence of heterozygosity from low pass WGS with ultra-low depth.

BACKGROUND: The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). RESULTS: Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. CONCLUSIONS: Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

Retreatment with immunotherapy in a patient with hepatocellular carcinoma who received immune checkpoint inhibitors after primary curative treatment: a case report.

Hepatocellular carcinoma (HCC) presents a malignant pathology known for its high early recurrence rate following curative treatment, significantly impacting patient prognosis. Currently, effective strategies to mitigate early HCC recurrence remain undetermined. In this report, we document a case of HCC managed with curative radiofrequency ablation (RFA), particularly in a patient facing a high risk of early recurrence due to a substantial tumor size. In an effort to forestall recurrence, immune checkpoint inhibitors (ICIs) were preemptively administered for 6 months post-RFA. Despite this, early recurrence ensued upon ICIs cessation. Traditionally, the approach to advanced HCC has been conservative, yet recent years have seen promising outcomes with ICIs in advanced HCC. However, research on ICIs retreatment is limited. In the short term, this patient experienced widespread metastases post-ICIs discontinuation, yet exhibited prompt regression upon ICIs reinitiation. Notably, this represents the initial documented instance of employing ICIs to forestall recurrence subsequent to curative RFA in HCC. Following ICIs discontinuation, diffuse recurrence with multiple metastases emerged, with successful resolution upon ICIs retreatment.