Therapy Research Articles

Identifying the quality markers and optimizing the processing of Gastrodiae rhizoma to treat brain diseases

BackgroundGastrodiae rhizoma (GR) refers to the dried tuber of Gastrodia elata Bl. and has been used for many centuries to treat brain diseases, such as Alzheimer’s disease, major depressive disorder, and cerebral ischemia. However, the processing of GR is complex and varied, resulting in unstable clinical treatment effects. The processing protocols significantly affect the active ingredients and curative effects of GR. We can optimize the processing of GR by identifying quality markers to treat brain diseases.MethodsFresh tubers of G. elata Bl. were processed under eight different protocols, and their resulting contents of potentially bioactive compounds were compared using liquid chromatography mass spectrometry to screen the potential quality markers of GR through stoichiometric analysis. The potential quality markers of GR targeting Alzheimer’s disease, major depressive disorder, and cerebral ischemia were identified by network pharmacology, and the potentially neuroprotective effects of these components were validated through simulated docking to likely protein targets. Finally, a fit degree analysis was carried out using different composition ratios and proportions of the disease component degree value, and the therapeutic effects of different processing methods on Alzheimer’s disease, major depressive disorder, and cerebral ischemia were outlined clearly.ResultsWe identified 32 potential therapeutic components and screened 13 quality markers in GR, of which five quality markers (galactinol, glucosyringic acid, parishins C and E, and S-(4-hydroxybenzyl)-glutathione) showed efficacy against all three brain diseases. Furthermore, steaming and microwave-drying during processing can optimize the components of these quality markers for treating the three diseases.ConclusionProcessing protocols significantly affect the therapeutic components of GR and may also impact its effectiveness in treating brain diseases. Accordingly, optimizing the processing methods of GR to correspond to different therapeutic purposes may improve its efficacy against brain diseases.

ECC at LLETZ—An Exploratory Retrospective Cohort Study

Background: The aim of this study is to evaluate the distribution of the histological results of the endocervical curettage (ECC) at large loop excision of the transformation zone (LLETZ) as well as the additional diagnostic information and its impact on further clinical treatment recommendations in accordance with national guidelines. The ECC in addition to LLETZ can serve to detect (pre)cancerogenic lesions above the endocervical cone margin, although its predictive value as well as diagnostic accuracy remains vague due to limited studies performed on this topic. Methods: In this retrospective cohort study, 1121 patients who underwent LLETZ and concomitant ECC during a twelve-year period (2009–2021) were analyzed. The main outcome parameters were the histological diagnosis and incidence of adequate or inadequate ECC specimens. Results: In 1.7% of the specimens, ECC performed at the completion of LLETZ yielded additional diagnostic information. The histological result of the ECC had an impact on subsequent therapeutic approach in 2 of the 1121 patients (0.2%). Furthermore, a negative ECC yielded a low negative predictive value (NPV) of 43.8% for the detection of residual disease. Conclusions: As current guidelines increasingly support the performance of an HPV test six months after LLETZ as an indicator of treatment success irrespective of the margin status, the routine performance of an ECC at LLETZ remains questionable.

Neurocognitive dysfunction in adolescents with recent onset major depressive disorder: a cross-sectional comparative study.

The aim of this study was to examine the neurocognitive deficits associated with the first episode of major depressive disorder (recent onset depression, ROD) in adolescents as compared to adult patients. Cross-sectional neurocognitive data from the baseline assessments of the PRONIA study with N = 650 (55.31% females) were analyzed. Based on a principal component analysis of eleven neurocognitive tests, we constructed an overall neurocognitive performance (NP) score. We examined mean score differences in NP between the groups of healthy controls (HC) and ROD and between adolescents (15-21years) and adults (22-40years) within a GLM approach. This accounts for unbalanced data with focus on interaction effects while controlling for effects of medication and educational years. Our results show lower NP for the ROD as compared to the HC group (d = -0.29, p = .046) and lower NP for the adolescent group as compared to the adult group (d = -0.29; p < .039). There was no interaction between these two group effects (F = 1.11; p = .29). Our findings suggest that the detrimental effect of ROD on neurocognitive functioning is comparable in adolescent and adult patients, since lower scores in adolescent patients are explained by effects of age and education. Neurocognitive impairment is an under addressed issue in clinical treatment guidelines for adolescent MDD. We suggest efficient monitoring in clinical practice by using an aggregate of the Digit Symbol Substitution Test and the Trail Making Test B, which highly correlated with the overall score of NP (r = 0.82).

Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body’s inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby blocking the synthesis of prostaglandins (PGs), which play a role in inflammation, cancer, and various cardiovascular conditions. However, long-term COX inhibition and reduced PGs synthesis can result in serious side effects. Recent studies have increasingly shown that some selective COX-2 inhibitors and NSAIDs, such as Meloxicam, may exert effects beyond COX inhibition. This emerging understanding prompts a re-evaluation of the mechanisms by which NSAIDs operate, suggesting that their benefits in cancer and CVD treatment may not solely depend on COX targeting. In this review, we will explore the potential COX-independent mechanisms of Meloxicam and other NSAIDs in addressing oncology and cardiovascular health.

An Integrated TCN-CrossMHA Model for Predicting circRNA-RBP Binding Sites.

Circular RNA (circRNA) has the capacity to bind with RNA binding protein (RBP), thereby exerting a substantial impact on diseases. Predicting binding sites aids in comprehending the interaction mechanism, thereby offering insights for disease treatment strategies. Here, we propose a novel approach based on temporal convolutional network (TCN) and cross multi-head attention mechanism to predict circRNA-RBP binding sites (circTCA). First, we employ two distinct encoding methodologies to obtain two raw matrices of circRNA sequences. Then, two parallel TCN blocks extract shallow and abstract features of the two matrices separately. The fusion of the two is achieved through cross multi-head attention mechanism and after this, global expectation pooling assigns weights to the concatenated feature. Finally, the task of classifying the input sequence is entrusted to a fully connected (FC) layer. We compare circTCA with other five methods and conduct ablation experiments to demonstrate its effectiveness. We also conduct feature visualization and assess the motifs extracted by circTCA with existing motifs. All in all, circTCA is effective for binding sites prediction of circRNA and RBP.

Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases

Neddylation, a type of protein post-translational modification that links the ubiquitin-like protein NEDD8 to substrate proteins, can be involved in various significant cellular processes and generate multiple biological effects. Currently, the best-characterized substrates of neddylation are the Cullin protein family, which is the core subunit of the Cullin-RING E3 ubiquitin ligase complex and controls many important biological processes by promoting ubiquitination and subsequent degradation of various key regulatory proteins. The normal or abnormal process of protein neddylation in the central nervous system can lead to a series of occurrences of normal functions and the development of diseases, providing an attractive, reasonable, and effective targeted therapeutic strategy. Therefore, this study reviews the phenomenon of neddylation in the central nervous system and summarizes the corresponding substrates. Finally, we provide a detailed description of neddylation involved in CNS diseases and treatment methods that may be used to regulate neddylation for the treatment of related diseases.

An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts

Malignant fibroblasts (MFs) are widely present in various diseases and are characterized by connective tissue proliferation; these cells act as a physical barrier that severely limits drug delivery and affects disease outcomes. Based on this, we constructed the smart, integrated, theranostic, targeted lipid nanoprobe HMME-RG3@PFH to overcome the bottleneck in the early diagnosis and treatment of MF-related diseases. The protein glucose transporter protein 1 (GLUT-1) is overexpressed on MFs, and its ideal substrate, ginsenoside RG3 (RG3), significantly enhances the targeted uptake of HMME-RG3@PFH by MFs in a hypoxic environment and endows the nanomaterial with stealthiness to prolong its circulation. Perfluorohexane (PFH), a substance that can undergo phase change, was encapsulated in the lipid core and vaporized for ultrasound-enhanced imaging under low-intensity focused ultrasound (LIFU) irradiation. Moreover, hematoporphyrin monomethyl ether (HMME) was loaded into the lipid bilayer for photoacoustic molecular imaging and sonodynamic therapy (SDT) of MFs under the combined effects of LIFU. Additionally, HMME-RG3@PFH instantaneously burst during visualization to promote targeted drug delivery. In addition, the increased number of exposed RG3 fragments can regulate the MFs to enter a quiescent state. Overall, this nanoplatform ultimately achieves dual-modal imaging with targeted and precise drug release for visualization and synergistic amplification therapy, providing a new possibility for the early diagnosis and precise treatment of MF-related diseases.

Nanoemulsion and nanoemulgel-based carriers as advanced delivery tools for the treatment of oral diseases.

Oral diseases rank among the most widespread ailments worldwide posing significant global health and economic challenges affecting around 3.5billion people, impacting the quality of life for affected individuals. Dental caries, periodontal disease, bacterial and fungal infections, tooth loss and oral malignancies are among the most prevalent global clinical disorders contributing to oral health burden. Traditional treatments for oral diseases often face challenges such as poor drug bioavailability, breakdown of medication in saliva, inconsistent antibiotic levels at the site of periodontal infection as well as higher side effects. However, the emergence of nanoemulgel (NEG) as an innovative drug delivery system offers promising solutions where NEG combines the advantages of both nanoemulsions (NEs) and hydrogels providing improved drug solubility, stability, and targeted delivery. Due to their minuscule size and ability to control drug release, NEGs hold promise for improving treatment of oral diseases, where versatility of these delivery systems makes them suitable for various applications, including topical delivery in dentistry. This review concisely outlines the anatomy of the oral environment and investigates the therapeutic potential of NE-based gels in oral disorder treatment. It thoroughly examines the challenges of drug delivery in the oral cavity and proposes strategies to improve therapeutic efficacy, drawing attention to previous research reports for comparison. Through comprehensive analysis, the review highlights the promising role of NEGs as a novel therapeutic approach for oral health management via research advancements and their clinical translation. Additionally, it provides valuable insights into future research directions and development opportunities in this area.

Efficacy of domestic single-hole robotic surgery system in the treatment of pediatric urological diseases

To explore the efficacy of domestic single-hole robotic surgery system in the treatment of pediatric urological diseases. A prospective review of clinical data of children who underwent laparoscopic surgery in the Department of Urology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, was conducted from July to November 2023. All surgeries were performed using the sharp single-port serpentine arm robotic surgery system, with an umbilical access route. All surgeries are performed by the same chief physician. Operative time, intraoperative blood loss, incision size, and postoperative complications were recorded. A total of 12 patients were included, consisting of 8 males and 4 females, aged 8.0-17.0 (13.5±2.7) years. The procedures included 5 pyeloplasties (1 case of bilateral pyeloplasty), with a unilateral operative time [M (Q1, Q3) ]of 180 (145, 200) minutes and a blood loss of 5 (5, 10) ml. Oral mucosa ureteroplasty was performed in 1 patient, taking 3 hours and 52 minutes with a blood loss of 10 ml. Renal cyst decortication was conducted in 1 case in 85 minutes with a blood loss of 20 ml. High ligation of the spermatic vein was conducted in 3 patients, with an average operative time of 97 minutes and no intraoperative blood loss. Bilateral gonadectomy was completed in 80 minutes with a blood loss of 5 ml. Ovarian cystectomy (1 case) was performed in 69 minutes with a blood loss of 5 ml. All surgeries were successfully completed without conversion to open surgery. Except for the oral mucosa ureteroplasty, which required an additional 5 mm auxiliary port, all procedures were performed through a 3 cm umbilical incision. Among the patients who underwent pyeloplasty, 1 case of urinary leak was identified and successfully treated conservatively with adequate drainage over 25 days. Re-stenosis was experienced by 1 patient with a long segment ureteral stricture postoperatively, while no Clavien-Dindo grade≥2 complications were observed in other patients. All umbilical wounds were concealed, and satisfactory postoperative appearances were noted. The domestic single-hole robotic surgery system is effective in treating pediatric urological diseases.

Nanomedicine-based strategies for the treatment of vein graft disease.

Autologous saphenous veins are the most frequently used conduits for coronary and peripheral artery bypass grafting. However, vein graft failure rates of 40-50% within 10 years of the implantation lead to poor long-term outcomes after bypass surgery. Currently, only a few therapeutic approaches for vein graft disease have been successfully translated into clinical practice. Building on the past two decades of advanced understanding of vein graft biology and the pathophysiological mechanisms underlying vein graft disease, nanomedicine-based strategies offer promising opportunities to address this important unmet clinical need. In this Review, we provide deep insight into the latest developments in the rational design and applications of nanoparticles that have the potential to target specific cells during various pathophysiological stages of vein graft disease, including early endothelial dysfunction, intermediate intimal hyperplasia and late-stage accelerated atherosclerosis. Additionally, we underscore the convergence of nanofabricated biomaterials, with a particular focus on hydrogels, external graft support devices and cell-based therapies, alongside bypass surgery to improve local delivery efficiency and therapeutic efficacy. Finally, we provide a specific discussion on the considerations, challenges and novel perspectives for the future clinical translation of nanomedicine for the treatment of vein graft disease.

Nanomotors as Therapeutic Agents: Advancing Treatment Strategies for Inflammation-Related Diseases.

Inflammation is a physiological response of the body to harmful stimuli such as pathogens, damaged cells, or irritants, involving a series of cellular and molecular events. It is associated with various diseases including neurodegenerative disorders, cancer, and atherosclerosis, and is a leading cause of global mortality. Key inflammatory factors, such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), RANTES (CCL5), and prostaglandins, play central roles in inflammation and disease progression. Traditional treatments such as NSAIDs, steroids, biologic agents, and antioxidants have limitations. Recent advancements in nanomaterials present promising solutions for treating inflammation-related diseases. Unlike nanomaterials that rely on passive targeting and face challenges in precise drug delivery, nanomotors, driven by chemical or optical stimuli, offer a more dynamic approach by actively navigating to inflammation sites, thereby enhancing drug delivery efficiency and therapeutic outcomes. Nanomotors allow for controlled drug release in response to specific environmental changes, such as pH and inflammatory factors, ensuring effective drug concentrations at disease sites. This active targeting capability enables the use of smaller drug doses, which reduces overall drug usage, costs, and potential side effects compared to traditional treatments. By improving precision and efficiency, nanomotors address the limitations of conventional therapies and represent a significant advancement in the treatment of inflammation-related diseases. This review summarizes the latest research on nanomotor-mediated treatment of inflammation-related diseases and discusses the challenges and future directions for optimizing their clinical translation.

DIGITAL STETHOSCOPE – NEW ERA OF AUSCULTATION

This review is devoted to electronic and digital stethoscopes. We performed analysis of publications within last 10 years in databases e-LIBRARY, PubMed, Google Scholar. Key words for the search were «auscultation», «electronic stethoscope», «digital stethoscope», «telemedicine». Review contains an information about new possibilities in auscultation by using digital stethoscopes. We provided an information about brief characteristics of the products of the most popular manufacturers on the Market. Increasing of functionality and versatility (the ability to analyze heart, lungs and intestine sounds) of digital stethoscope and also increasing of noise reduction and sound filtration will make these devices more attractable for everyday use. When these tasks will be solved, the digital stethoscope will definitely become an indispensable tool in the diagnosis, monitoring and treatment of diseases, as well as patients’ self-monitoring. Contemporary models of digital stethoscopes can be used in telemonitoring of the patients with cardiovascular and respiratory diseases. In this case it is possible to estimate the results of auscultation in dynamics, during long term follow up. This can contribute to early evaluation of complications and decompensations in patients with chronic non-infectious diseases such as chronic obstructive pulmonary diseases, asthma, myocardial infarction, etc.

Collagen triple helix repeat-containing 1 protein: an emerging biomarker and its influence on the clinical and sonographic disease severity in Egyptian medicated female rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of synovial joints, with a multifactorial etiology. Collagen triple helix repeat-containing 1 protein (CTHRC1) is a biomarker produced by fibroblast-like synoviocytes, which was shown to be highly expressed in RA patients. The study aimed to measure serum CTHRC1 level in female RA patients currently on medical treatment and its influence on the clinical and sonographic severity of the disease.ResultsThe patients’ mean age was 43.39 ± 8.55 years and median RA disease duration of 5.5 (0.33–20) years. RA patients showed significantly higher serum CTHRC1 level [89.71 ng/ml (53.95–353.45)] in comparison to controls [87.38 ng/ml (44.47–110.3)] (U = 430, P = 0.014). Furthermore, higher serum CTHRC1 levels were recorded in seropositive versus seronegative patients (U = 76, P = 0.022) and in RA patients with severe disease activity compared to those with lower disease activity (H = 9.79, P = 0.007). Furthermore, serum CTHRC1 levels were lower in RA patients receiving biological therapy compared to those receiving conventional therapy; however, this difference did not reach statistical significance.Significant positive correlations were found between CTHRC1 and disease activity, acute-phase reactants, serological markers, functional assessment, fatigue, and erosions detected by ultrasound, while a significant negative correlation was recorded between CTHRC1 and duration of biologic intake (rs = − 0.45, P = 0.036). Furthermore, on multivariate linear regression analysis, serum CTHRC1 was the only significant predictor for higher disease activity (P = 0.028, B = 0.009, 95% CI 0.001 to 0.017).ConclusionRA patients showed higher CTHRC1 serum levels compared to healthy controls, especially those with seropositivity and highly active disease. Furthermore, it was positively associated with poor patient functional outcome, fatigability, and erosive findings by ultrasound, thus suggesting that serum CTHRC1 can be a good predictor for high RA disease activity and possibly severity. Moreover, biological therapy could influence serum CTHRC1 levels in these patients.

Approaches to developing mechanisms for medical care centralization at the interterritorial level

Background. As new high-tech methods of treatment and diagnostics are introduced into the basic compulsory health insurance program, the focus on creating separate regional healthcare systems is becoming less effective. The creation of the necessary infrastructure requires disproportionately large investments, while the needs of the population in most regions do not provide adequate loading of newly created facilities. A promising solution to these problems is the centralization of delivering certain types of medical care (MC) on the basis of interregional medical centers.Objective: development of approaches to identifying medical interventions that are appropriate to provide in specialized interregional centers.Material and methods. The criteria for selection of medical interventions including MC profiles and diagnosis-related groups (DRGs) of diseases, which potentially require centralization were developed. On the basis of statistical analysis, data on specialized MC provided in inpatient settings by “Pediatric surgery” and “Traumatology and orthopedics” profiles were analyzed to identify regions with low and high levels of hospitalizations in order to determine the need for centralization or the creation of interregional centers.Results. The analysis enabled to identify the territorial subjects of the Russian Federation (RF) where the issue of MC centralization would be relevant to increase its availability to the insured population in the territory of certain subject. Besides, the study identified regions, in which the number of hospitalizations significantly exceeded the average indicators in the RF. It is advisable to create interregional MC centers on the basis of such subjects.Conclusion. The presented analysis of individual profiles and DRGs across the territorial subjects of the RF showed the objective differences in the extent of provided MC. The proposed methodology for determining DRGs and identifying subjects of the RF that have a surplus or deficit in the provision of MC can form the basis for approaches to identifying “MC centralization points”.

Forced stability studies and estimation of encapsulated ellagic acid in nano-formulations using UV-spectroscopy

Abstract There is a growing interest in dietary materials to explore their therapeutic activities. Ellagic acid is considered as a dietary supplement and is naturally present in fruits and other foods. It has anticancer, antimalarial, antiviral, antioxidant, and anti-inflammatory activities. These activities can be enhanced with nanoformulations, which can increase its oral bioavailability. However, there is a need for an economical, simple, sensitive, and robust analytical method for the estimation of entrapped ellagic acid in the nanoformulations. Therefore, the present study presents the development and validation of a UV–visible spectroscopy method for the estimation of EA in nanoformulations. The phosphate buffer (pH 7.2) and the detection wavelength of 253.5 nm were used for the method development, and its validation was performed according to the ICH Q2A (R1) guidelines. The coefficient of determination value of the developed method was found to be 0.9988 in the concentration range of 1 μg mL−1 to 6 μg mL−1. The method was found to be linear, precise, sensitive, and robust. This method can be used for the estimation of EA in nanoformulations, bulk dosage forms, and other pharmaceutical formulations.

Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation

Uveal melanoma (UM) is a rare aggressive intraocular tumour that spreads most commonly to the liver in tumours with loss of one copy of chromosome 3 (HR-M3); current treatments for metastatic disease remain largely ineffective. Pre-clinical research is increasingly using three-dimensional models that better recapitulate the tumour microenvironment (TME). One aspect of the TME is the acellular extracellular matrix (ECM) that influences cell proliferation, migration and response to therapy. Although commercial matrices are used in culture, the composition and biochemical properties may not be representative of the tumour ECM in vivo. This study identifies UM metastatic risk specific ECM proteins by developing methodology for decellularisation of low- and high- metastatic risk tissue samples (LR-D3 vs. HR-M3). Proteomic analysis revealed a matrisome signature of 34 core ECM and ECM-associated proteins upregulated in HR-M3 UM. Combining additional UM secretome and whole cell iTRAQ proteomic datasets revealed enriched GO and KEGG pathways including ‘regulating ECM binding’ and ‘PI3K/Akt signalling’. Structural analyses of decellularised matrices revealed microarchitecture of differing fibre density and expression differences in collagen 4, collagen 6A1 and nidogen 1, between metastatic risk groups. This approach is a powerful tool for the generation of ECM matrices relevant to high metastatic risk UM.

Insights of gut-liver axis in hepatic diseases: Mechanisms, clinical implications, and therapeutic potentials

With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.

ADVANCES IN LAPAROSCOPIC SURGERY

Laparoscopic surgery has established itself as an innovative and effective approach to treating acute abdominal diseases, revolutionizing traditional surgical practices. With the advancement of medical technologies and the growing demand for less invasive procedures, laparoscopy offers significant advantages, such as reduced postoperative pain, shorter recovery time and lower complication rates. This paper explores recent advances in the laparoscopic technique, highlighting its role in the future of minimally invasive surgery. This paper sets out to explore the main advances in laparoscopic surgery, its applications in the treatment of acute abdominal diseases and the future prospects of this minimally invasive approach, discussing how these developments can positively impact surgical practice and the patient experience. This is a literature review with a qualitative approach, using the PubMed, Google Scholar and Scielo databases. To refine the search, the health descriptors “laparoscopic surgery”, “minimally invasive surgery”, “surgical training”, and “inequalities in surgical access” were applied, with a time frame between 2020 and 2022. The methodology adopted for this analysis involves a comprehensive literature review of recent scientific articles, systematic reviews and clinical guidelines. The study examines innovations such as the use of robotics, advanced surgical instruments and improved visualization techniques, which have broadened the indications for laparoscopic surgery. In addition, the research highlights the importance of continuing education for surgeons, emphasizing the need for specific skills to successfully perform laparoscopic procedures. The data shows that laparoscopy not only improves clinical outcomes, but also promotes a more comfortable surgical experience for patients. Therefore, advances in laparoscopic surgery represent a significant milestone in the approach to acute abdominal diseases, establishing a promising future for minimally invasive surgery. The integration of new technologies and techniques, together with the proper training of professionals, is crucial to maximizing the benefits of this approach. Laparoscopy not only transforms surgical treatment, but also redefines patients’ expectations regarding recovery and quality of life. Continued development in this field promises not only better clinical results, but also a positive impact on the efficiency of health services.

Deep learning based highly accurate transplanted bioengineered corneal equivalent thickness measurement using optical coherence tomography

Corneal transplantation is the primary treatment for irreversible corneal diseases, but due to limited donor availability, bioengineered corneal equivalents are being developed as a solution, with biocompatibility, structural integrity, and physical function considered key factors. Since conventional evaluation methods may not fully capture the complex properties of the cornea, there is a need for advanced imaging and assessment techniques. In this study, we proposed a deep learning-based automatic segmentation method for transplanted bioengineered corneal equivalents using optical coherence tomography to achieve a highly accurate evaluation of graft integrity and biocompatibility. Our method provides quantitative individual thickness values, detailed maps, and volume measurements of the bioengineered corneal equivalents, and has been validated through 14 days of monitoring. Based on the results, it is expected to have high clinical utility as a quantitative assessment method for human keratoplasties, including automatic opacity area segmentation and implanted graft part extraction, beyond animal studies.

The activation of inflammatory responses in the brain is potentiated by over-expressing acetylcholinesterase in myeloid lineage of transgenic mice.

Acetylcholinesterase (AChE) has functions in neuroinflammation, beyond its classical role in neurotransmission. Understanding the role of AChE in neuroinflammation is of great significance, as it highlights the potential therapeutic targets for the treatment of neurodegenerative diseases. In an invitro study, the expression of AChE was up-regulated in lipopolysaccharide (LPS)-induced microglia/macrophage and contrarily potentiated the inflammatory responses via disturbing the cholinergic anti-inflammatory pathway (CAP). However, the regulation of AChE in neuroinflammation has not been revealed invivo yet. Here, we aim to uncover the inflammatory roles of microglial AChE in LPS-induced neuroinflammation by using the conditional AChE over-expression mouse model. AChE was specifically over-expressed in the myeloid cell linkage of mouse by applying CRISPR/cas9 combined with Cre-LoxP system. LPS was intraperitoneally injected into the mice to induce inflammation. The results showed that the inflammation, induced by LPS, was aggravated in the brain of transgenic mice having over-expression of AChE in microglia. The expressions of pro-inflammatory cytokines were robustly up-regulated in the brains of LPS-treated transgenic mice, as compared to the LPS-treated wildtypes. In parallel, the activations of microglia and astrocytes in hippocampus were enhanced significantly in AChE transgenic mice. Transcriptomics analysis further confirmed the severer inflammation in the transgenic mice than the wildtype after LPS administration. These findings shed light on the regulation of microglial AChE in neuroinflammation invivo for the first time, presenting another angle to understand the role of AChE in neurodegenerative diseases.