Hydrogen therapy: recent advances and emerging materials.

Hydrogen therapy, leveraging its selective attenuation of hydroxyl radicals (˙OH) and ONOO-, has emerged as a pivotal pathophysiological modulator with antioxidant, anti-inflammatory, and antiapoptotic attributes. Hydrogen therapy has been extensively studied both preclinically and clinically, especially in diseases with an inflammatory nature. Despite the substantial progress, challenges persist in achieving high hydrogen concentrations in target lesions, especially in cancer treatment. A notable breakthrough lies in water/acid reactive materials, offering enhanced hydrogen generation and sustained release potential. However, limitations include hydrogen termination upon material depletion and reduced bioavailability at targeted lesions. To overcome these challenges, catalytic materials like photocatalytic and sonocatalytic materials have surfaced as promising solutions. With enhanced permeability and retention effects, these materials exhibit targeted delivery and sustained stimuli-reactive hydrogen release. The future of hydrogen therapy hinges on continuous exploration and modification of catalytic materials. Researchers are urged to prioritize improved catalytic efficiency, enhanced lesion targeting effects, and heightened biosafety and biocompatibility in future development.

Comprehensive evaluation and screening of phytochemical compounds and their hypolipidemic activities of lotus leaf based on HPLC-Q-TOF-MS and spectral-effect analysis.

This study aimed to identify and quantify the primary components in lotus leaf and to explore the hypolipidemic components through spectral-effect relationships and chemometric methods. Utilizing a data-dependent acquisition-diagnostic fragment ion/characteristic neutral loss screening strategy (DFI-NLS), a reliable HPLC-Q-TOF-MS analysis was conducted, identifying 77 compounds, including 36 flavonoids, 21 alkaloids, 3 terpenoids, 11 organic acids, 4 phenols, 1 lignin and 1 unsaturated hydrocarbon. A straightforward HPLC-DAD method was developed for the simultaneous determination of seven major components in lotus leaf, and quercetin-3-O-glucuronide (Q3GA) was identified as the most abundant component. The HPLC fingerprints of 36 lotus leaf sample batches were assessed using chemometric approaches such as principal component analysis and hierarchical cluster analysis. The hypolipidemic effect of these samples was analyzed by measuring total cholesterol (TC) and total triglycerides (TG) levels in palmitic acid (PA) and oleic acid (OA)-induced lipid modeling in HepG-2 cells, employing partial least squares regression and grey relation analysis to investigate the spectral-effect relationship of the lotus leaf. The in vivo hypolipidemic effect of these compounds was assessed using an egg yolk powder-induced high-fat zebrafish model. The findings indicated that peak No.11 (Q3GA) in the chemical fingerprint was significantly associated with hypolipidemic activity, suggesting it as a potential hypolipidemic compound in lotus leaf. In summary, this study facilitates the exploration of the phytochemical compounds and their bioactive properties in the lotus leaf.

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1ß pathway.

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.

Characteristics of Bacteria in Urine and Stones from Patients Treated with Percutaneous Nephrolithotomy and Association with Postoperative Infection.

Background: The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS). Methods: Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed. Results: Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients. Conclusion: The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.

In Situ Construction of Highly Dispersed Pd on Cobalt Nanoparticle on Hollow Functional Cubic Graphene by Double Framework for ORR.

Developing advanced functional carbon materials is essential for electrocatalysis, caused by their vast merits for boosting many key energy conversion reactions. Herein, the covalent organic frameworks (COFs) is utilized on metal-organic frameworks (MOFs) as the template, under the controllable metal atoms thermal migration process successfully in situ constructs Pd-Co alloy nanoparticles on hollow cubic graphene. The electrocatalytic oxygen reduction reaction (ORR) evaluation showed excellent performances with a half-wave potential of 0.866 V, and a limited current density of 4.975 mA cm-2, that superior to the commercial Pt/C and Co nanoparticles. The contrast experiments and X-ray absorption spectrum demonstrated the aggregated electrons at highly dispersed Pd atoms on Co nanoparticle that promoted the main activities. This work not only enlightens the novel carbon materials designing strategies but also suggests heterogeneous electrocatalysis.

GC-MS Combined with Fast GC E-Nose for the Analysis of Volatile Components of Chamomile (Matricaria chamomilla L.).

Chamomile has become one of the world's most popular herbal teas due to its unique properties. Chamomile is widely used in dietary supplements, cosmetics, and herbal products. This study aimed to investigate the volatile aromatic components in chamomile. Two analytical techniques, gas chromatography-mass spectrometry (GC-MS) and an ultra-fast gas chromatography electronic nose, were employed to examine samples from Xinjiang (XJ), Shandong (SD), and Hebei (HB) in China, and imported samples from Germany (GER). The results revealed that all chamomile samples contained specific sesquiterpene compounds, including α-bisabolol, bisabolol oxide, bisabolone oxide, and chamazulene. Additionally, forty potential aroma components were identified by the electronic nose. The primary odor components of chamomile were characterized by fruity and spicy notes. The primary differences in the components of chamomile oil were identified as (E)-ß-farnesene, chamazulene, α-bisabolol oxide B, spathulenol and α-bisabolone oxide A. Significant differences in aroma compounds included geosmin, butanoic acid, 2-butene, norfuraneol, γ-terpinene. This study demonstrates that GC-MS and the ultra-fast gas chromatography electronic nose can preliminarily distinguish chamomile from different areas, providing a method and guidance for the selection of origin and sensory evaluation of chamomile. The current study is limited by the sample size and it provides preliminary conclusions. Future studies with a larger sample size are warranted to further improve these findings.

Polyvinylpyrrolidone-curcumin nanoparticles with immune regulatory and metabolism regulatory effects for the treatment of experimental autoimmune uveitis.

Uveitis comprises a cluster of intraocular inflammatory disorders characterized by uncontrolled autoimmune responses and excessive oxidative stress leading to vision loss worldwide. In the present study, curcumin (CUR) was conjugated with polyvinylpyrrolidone (PVP) to form PVP-CUR nanoparticles with significantly elevated solubility and outstanding multiple radical scavenging abilities. In vitro studies revealed that PVP-CUR nanoparticles markedly mitigated oxidative stress and reduced apoptosis in a H2O2-induced human retinal pigment epithelial cell line (ARPE-19) and promoted phenotypic polarization from M1 to M2 in an LPS-induced human microglial cell line (HMC3). Further in vivo studies demonstrated the prominent therapeutic effects of PVP-CUR nanoparticles on experimental autoimmune uveitis (EAU), which relieved clinical and pathological progression, improved perfusion and tomographic manifestations of retinal vessels, and reduced blood-retinal barrier (BRB) leakage; these effects may be mediated by mitigating oxidative stress and attenuating macrophage/microglia-elicited inflammation. Notably, treatment with PVP-CUR nanoparticles was shown to regulate metabolite alterations in EAU rats, providing novel insights into the underlying mechanisms involved. Additionally, the PVP-CUR nanoparticles showed great biocompatibility in vivo. In summary, our study revealed that PVP-CUR nanoparticles may serve as effective and safe nanodrugs for treating uveitis and other oxidative stress- and inflammation-related diseases.

Transcriptome and metabolome analysis revealed the dynamic change of bioactive compounds of Fructus Ligustri Lucidi.

BACKGROUND: The Fructus Ligustri Lucidi, the fruit of Ligustrum lucidum, contains a variety of bioactive compounds, such as flavonoids, triterpenoids, and secoiridoids. The proportions of these compounds vary greatly during the different fruit development periods of Fructus Ligustri Lucidi. However, a clear understanding of how the proportions of the compounds and their regulatory biosynthetic mechanisms change across the different fruit development periods of Fructus Ligustri Lucidi is still lacking. RESULTS: In this study, metabolite profiling and transcriptome analysis of six fruit development periods (45 DAF, 75 DAF, 112 DAF, 135 DAF, 170 DAF, and 195 DAF) were performed. Seventy compounds were tentatively identified, of which secoiridoids were the most abundant. Eleven identified compounds were quantified by high performance liquid chromatography. A total of 103,058 unigenes were obtained from six periods of Fructus Ligustri Lucidi. Furthermore, candidate genes involved in triterpenoids, phenylethanols, and oleoside-type secoiridoid biosynthesis were identified and analyzed. The in vitro enzyme activities of nine glycosyltransferases involved in salidroside biosynthesis revealed that they can catalyze trysol and hydroxytyrosol to salidroside and hydroxylsalidroside. CONCLUSIONS: These results provide valuable information to clarify the profile and molecular regulatory mechanisms of metabolite biosynthesis, and also in optimizing the harvest time of this fruit.

Integrated analysis of tertiary lymphoid structures and immune infiltration in ccRCC microenvironment revealed their clinical significances: a multicenter cohort study.

BACKGROUND: Tertiary lymphoid structures (TLSs) serve as organized lymphoid aggregates that influence immune responses within the tumor microenvironment. This study aims to investigate the characteristics and clinical significance of TLSs and tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC). METHODS: TLSs and TILs were analyzed comprehensively in 754 ccRCC patients from 6 academic centers and 532 patients from The Cancer Genome Atlas. Integrated analysis was performed based on single-cell RNA-sequencing datasets from 21 ccRCC patients to investigate TLS heterogeneity in ccRCC. Immunohistochemistry and multiplex immunofluorescence were applied. Cox regression and Kaplan-Meier analyses were used to reveal the prognostic significance. RESULTS: The study demonstrated the existence of TLSs and TILs heterogeneities in the ccRCC microenvironment. TLSs were identified in 16% of the tumor tissues in 113 patients. High density (>0.6/mm2) and maturation of TLSs predicted good overall survival (OS) (p<0.01) in ccRCC patients. However, high infiltration (>151) of scattered TILs was an independent risk factor of poor ccRCC prognosis (HR=14.818, p<0.001). The presence of TLSs was correlated with improved progression-free survival (p=0.002) and responsiveness to therapy (p<0.001). Interestingly, the combination of age and TLSs abundance had an impact on OS (p<0.001). Higher senescence scores were detected in individuals with immature TLSs (p=0.003). CONCLUSIONS: The study revealed the contradictory features of intratumoral TLSs and TILs in the ccRCC microenvironment and their impact on clinical prognosis, suggesting that abundant and mature intratumoral TLSs were associated with decreased risks of postoperative ccRCC relapse and death as well as favorable therapeutic response. Distinct spatial distributions of immune infiltration could reflect effective antitumor or protumor immunity in ccRCC.

YOLO-ISTD: An infrared small target detection method based on YOLOv5-S.

Infrared target detection is widely used in industrial fields, such as environmental monitoring, automatic driving, etc., and the detection of weak targets is one of the most challenging research topics in this field. Due to the small size of these targets, limited information and less surrounding contextual information, it increases the difficulty of target detection and recognition. To address these issues, this paper proposes YOLO-ISTD, an improved method for infrared small target detection based on the YOLOv5-S framework. Firstly, we propose a feature extraction module called SACSP, which incorporates the Shuffle Attention mechanism and makes certain adjustments to the CSP structure, enhancing the feature extraction capability and improving the performance of the detector. Secondly, we introduce a feature fusion module called NL-SPPF. By introducing an NL-Block, the network is able to capture richer long-range features, better capturing the correlation between background information and targets, thereby enhancing the detection capability for small targets. Lastly, we propose a modified K-means clustering algorithm based on Distance-IoU (DIoU), called K-means_DIOU, to improve the accuracy of clustering and generate anchors suitable for the task. Additionally, modifications are made to the detection heads in YOLOv5-S. The original 8, 16, and 32 times downsampling detection heads are replaced with 4, 8, and 16 times downsampling detection heads, capturing more informative coarse-grained features. This enables better understanding of the overall characteristics and structure of the targets, resulting in improved representation and localization of small targets. Experimental results demonstrate significant achievements of YOLO-ISTD on the NUST-SIRST dataset, with an improvement of 8.568% in mAP@0.5 and 8.618% in mAP@0.95. Compared to the comparative models, the proposed approach effectively addresses issues of missed detections and false alarms in the detection results, leading to substantial improvements in precision, recall, and model convergence speed.

Unveiling the enigma of acute kidney disease: predicting prognosis, exploring interventions, and embracing a multidisciplinary approach.

Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury is approximately 33.6%, and it can occur without identifiable preceding acute kidney injury. The development of AKD is associated with increased risks of chronic kidney disease, dialysis, and mortality. Biomarkers and subphenotypes are promising tools to predict prognosis in AKD. The complex clinical situations in patients with AKD necessitate a comprehensive and structured approach, termed "KAMPS" (kidney function check, advocacy, medications, pressure, sick day protocols). We introduce "MAND-MASS," an acronym devised to summarize the reconciliation of medications during episodes of acute illness, as a critical component of the sick day protocols at AKD. A multidisciplinary team care, consisting of nephrologists, pharmacists, dietitians, health educators, and nurses, is an optimal model to achieve the care bundle in KAMPS. Although the evidence for patients with AKD is still lacking, several potential pharmacological agents may improve outcomes, including but not limited to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists. In conclusion, accurate prognosis prediction and effective treatment for AKD are critical yet unmet clinical needs. Future studies are urgently needed to improve patient care in this complex and rapidly evolving field.

Micro-flow cell washing technique combined with single-cell Raman spectroscopy for rapid and automatic antimicrobial susceptibility test of pathogen in urine.

Facing the rapid spread of antimicrobial resistance, methods based on single-cell Raman spectroscopy have proven their advances in reducing the turn-around time (TAT) of antimicrobial susceptibility tests (AST). However, the Raman-based methods are still hindered by the prolonged centrifugal cell washing procedure, which may require complex labor operation and induce high mechanical stress, resulting in a pretreatment time of over 1 h as well as a high cell-loss probability. In this study, we developed a micro-flow cell washing device and corresponding Raman-compatible washing chips, which were able to automatically remove the impurities in the samples, retain the bacterial cell and perform Raman spectra acquisition in situ. Results of washing the 5- and 10-µm polymethyl methacrylate (PMMA) microspheres showed that the novel technique achieved a successful removal of 99 % impurity and an 80 % particle retention rate after 6 to 10 cycles of washing. The micro-flow cell washing technique could complete the pretreatment for urine samples in a 96-well plate within 10 min, only taking 15 % of the handling time required by centrifugation. The AST profiles of urine sample spiked with E. coli 25922, E. faecalis 29212, and S. aureus 29213 obtained by the proposed Raman-based approach were found to be 100 % consistent with the results from broth micro-dilution while reducing the TAT to 3 h from several days which is required by the latter. Our study has demonstrated the micro-flow cell washing technique is a reliable, fast and compatible approach to replace centrifuge washing for sample pretreatment of Raman-AST and could be readily applied in clinical scenarios.

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

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

The Effectiveness of Acupuncture for Low Back Pain: An Umbrella Review and Meta-Analysis.

Recommendations on the use of acupuncture in managing low back pain (LBP) vary across different guidelines. The methodological quality of existing systematic reviews and meta-analyses on this topic also demonstrates considerable diversity, potentially leading to biased conclusions. Therefore, we comprehensively searched PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Chinese National Knowledge Infrastructure (CNKI) databases and conducted an umbrella review. Scrutiny was performed to ascertain whether primary studies within the systematic reviews and meta-analyses adhered to our inclusion criteria, followed by a meticulous reanalysis of pertinent data. Participant numbers, heterogeneity, publication bias, and excessive significance were taken into account when assessing the credibility of the evidence. For robustness, sensitivity analysis was performed using the leave-one-out method. The results of the umbrella review yielded highly suggestive evidence in favor of the immediate and short-term analgesic effects of acupuncture, with suggestive evidence supporting intermediate-term analgesic effects. However, the effectiveness of acupuncture on disability improvement has demonstrated weak to suggestive evidence. Evidence supporting the enhancement of quality of life by acupuncture is limited. The leave-one-out analysis corroborated the robustness of the meta-analysis, further confirming the credibility of the findings. This umbrella review indicated that the most significant advantage of acupuncture for LBP is its capacity to reduce pain.

TAK1 inhibition mitigates intracerebral hemorrhage-induced brain injury through reduction of oxidative stress and neuronal pyroptosis via the NRF2 signaling pathway.

Introduction: Intracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-ß-activated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis. Methods: Adult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays. Results: Our study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis. Discussion: Our findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH.

Effects of meditation on neural responses to pain: A systematic review and meta-analysis of fMRI studies.

This systematic review investigates the impact of meditation on neural responses to pain, as measured by functional magnetic resonance imaging (fMRI). Up to March 2024, we conducted searches across four databases for human studies implementing fMRI to assess the efficacy of meditation for pain relief. Eighteen studies met the inclusion criteria. Our systematic review indicates that activation of the insula, anterior cingulate cortex, and orbitofrontal cortex is positively associated with meditation for pain relief, while activity in regions like the amygdala and medial prefrontal cortex is negatively correlated with pain relief. Meta-analyses consistently reveal the involvement of various brain regions, including the insula, putamen, amygdala, anterior cingulate cortex, precentral gyrus, postcentral gyrus, inferior parietal lobule, superior temporal gyrus, inferior frontal gyrus, and caudate nucleus, in meditation-induced alleviation of pain. These findings suggest ccthat meditation acts on specific brain regions related to pain, mood, and cognition, providing insight into the potential mechanisms underlying the pain-alleviating effects of meditation on both pain sensations and emotional experiences.

Advancing mid-rectal cancer surgery: Unveiling the potential of natural orifice specimen extraction surgery in comparison to conventional laparoscopic-assisted resection.

BACKGROUND: Mid-rectal cancer treatment traditionally involves conventional laparoscopic-assisted resection (CLAR). This study aimed to assess the clinical and therapeutic advantages of Natural Orifice Specimen Extraction Surgery (NOSES) over CLAR. AIMS: To compare the clinical outcomes, intraoperative metrics, postoperative recovery, complications, and long-term prognosis between NOSES and CLAR groups. MATERIALS & METHODS: A total of 136 patients were analyzed, with 92 undergoing CLAR and 44 undergoing NOSES. Clinical outcomes were evaluated, and propensity score matching (PSM) was employed to control potential biases. RESULTS: The NOSES group exhibited significant improvements in postoperative recovery, including lower pain scores on days 1, 3, and 5 (p < .001), reduced need for additional analgesics (p = .02), shorter hospital stays (10.8 ± 2.3 vs. 14.2 ± 5.3 days; p < .001), and decreased intraoperative blood loss (48.1 ± 52.7 mL vs. 71.0 ± 55.0 mL; p = .03). Patients undergoing NOSES also reported enhanced satisfaction with postoperative abdominal appearance and better quality of life. Additionally, the NOSES approach resulted in fewer postoperative complications. CONCLUSION: While long-term outcomes (overall survival, disease-free survival, and local recurrence rates) were comparable between the two methods, NOSES demonstrated superior postoperative outcomes compared to CLAR in mid-rectal cancer treatment, while maintaining similar long-term oncological safety. These findings suggest that NOSES could serve as an effective alternative to CLAR without compromising long-term results.

Immunomodulatory Precision: A Narrative Review Exploring the Critical Role of Immune Checkpoint Inhibitors in Cancer Treatment.

An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an immune response. These checkpoints play a pivotal role in suppressing excessive immune responses and maintaining immune homeostasis against viral or microbial infections. There are several FDA-approved immune checkpoint inhibitors (ICIs), including ipilimumab, pembrolizumab, and avelumab. These ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1). Furthermore, ongoing efforts are focused on developing new ICIs with emerging potential. In comparison to conventional treatments, ICIs offer the advantages of reduced side effects and durable responses. There is growing interest in the potential of combining different ICIs with chemotherapy, radiation therapy, or targeted therapies. This article comprehensively reviews the classification, mechanism of action, application, and combination strategies of ICIs in various cancers and discusses their current limitations. Our objective is to contribute to the future development of more effective anticancer drugs targeting immune checkpoints.