Comparison of suture-bridge and independent double-row techniques for medium to massive posterosuperior cuff tears: a two-year retrospective study.

BACKGROUND: Transosseous-equivalent suture-bridge (TOE-SB) and independent double-row (IDR) repair techniques were developed to treat rotator cuff tears. The study was designed to prove that both TOE-SB and IDR techniques provided comparable clinical results and retear rate for medium to massive posterosuperior rotator cuff tears, while the surgical time and number of suture anchor used were less in the IDR group. STUDY DESIGN: Level of evidence: level III, Retrospective comparative study. METHODS: Patients with medium to massive posterosuperior rotator cuff tears receiving arthroscopic TOE-SB and IDR between November 2016 to October 2019 were retrospectively enrolled. All patients were confirmed to have grade ≤ 2 fatty infiltration in the muscles of the torn tendons. Revision, concomitant subscapularis tear, acromiohumeral distance < 7 mm, glenohumeral osteoarthritis, partial repair, incomplete repair, partial thickness, or irreparable posterosuperior cuff tear were excluded. Surgical time, number of suture anchor used for the surgery, pre-operative, and post-operative clinical scores such as Constant-Murley score, subjective shoulder value (SSV), and visual analog scale (VAS) were compared. The retear rates between groups were evaluated by ultrasound. RESULTS: Thirty-five IDR and thirty-five TOE-SB repairs were enrolled. The IDR technique required much fewer anchors than TOE-SB did to complete the cuff repair. The mean operation time in IDR and TOE-SB group were 86(18.23), and 114(18.7) (min), respectively (P <  0.01). The mean number of anchors used to complete the cuff repair was 2(0.17) in IDR and 3(0.61) in TOE-SB (P <  0.01). The Constant-Murley score improved from 34.9 ± 6.6 to 80.6 ± 9.4 in the IDR group, and 37.4 ± 6 to 81.9 ± 4.6 in the TOE-SB group (both P <  0.001). SSV improved from 24.6 ± 9.6 to 79.3 ± 10.6 in the IDR, and 27.9 ± 9 to 82.9 ± 6.9 in the TOE-SB group (both P <  0.001). VAS improved from 7.9 ± 0.6 to 1.5 ± 0.7 in the IDR, and 8 ± 0.5 to 1.3 ± 0.6 in the TOE-SB group (both P <  0.001) at final follow-up. No significant difference was found between the retear rates (14.3% in the IDR vs. 17.1% in the TOE-SB, respectively) in the 2-year follow-up. CONCLUSIONS: Both IDR and TOE-SB group provided comparable clinical results and retear rates for medium to massive posterosuperior rotator cuff tears. The surgical time and number of anchors used were less in the IDR group than in the TOE-SB group.

CFTR Modulators: From Mechanism to Targeted Therapeutics.

People with cystic fibrosis (CF) suffer from a multi-organ disorder caused by loss-of-function variants in the gene encoding the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Tremendous progress has been made in both basic and clinical sciences over the past three decades since the identification of the CFTR gene. Over 90% of people with CF now have access to therapies targeting dysfunctional CFTR. This success was made possible by numerous studies in the field that incrementally paved the way for the development of small molecules known as CFTR modulators. The advent of CFTR modulators transformed this life-threatening illness into a treatable disease by directly binding to the CFTR protein and correcting defects induced by pathogenic variants. In this chapter, we trace the trajectory of structural and functional studies that brought CF therapies from bench to bedside, with an emphasis on mechanistic understanding of CFTR modulators.

Open the Technical Black Box of Tumor Mutational Burden (TMB): Factors Affecting Harmonization and Standardization of Panel-Based TMB.

As tumor mutational burden (TMB) has been approved as a predictive biomarker for immune checkpoint inhibitors (ICIs), next-generation sequencing (NGS) TMB panels are being increasingly used clinically. However, only a few of them have been validated in clinical trials or authorized by administration. The harmonization and standardization of TMB panels are thus essential for clinical implementation. In this review, preanalytic, sequencing, bioinformatics and interpretative factors are summarized to provide a comprehensive picture of how the different factors affect the estimation of panel-based TMB. Among the factors, poor DNA quality, improper formalin fixation and residual germline variants after filtration may overestimate TMB, while low tumor purity may decrease the sensitivity of the TMB panel. In addition, a small panel size leads to more variability when comparing with true TMB values detected by whole-exome sequencing (WES). A panel covering a genomic region of more than 1Mb is more stable for harmonization and standardization. Because the TMB estimate reflects the sum of effects from multiple factors, deliberation based on laboratory and specimen quality, as well as clinical information, is essential for decision making.

Genetic and Functional Effects of Adiponectin in Type 2 Diabetes Mellitus Development.

Diabetes mellitus (DM) is a common chronic metabolic disease, and the C57BLKsJ-db/db mice are good animal models for type 2 diabetes mellitus (T2DM). In this study, Western blotting and immunohistochemistry (IHC) were employed to examine the protein expression of adiponectin in the liver tissues of T2DM mice with different disease courses (4, 16, and 32 weeks). Adiponectin expression reduced in the liver tissues of T2DM mice in different disease courses. The genotypic and allelic frequencies of the adiponectin gene rs1063538 and rs2241766 single nucleotide polymorphisms (SNPs) in a Taiwanese population (570 T2DM patients and 1700 controls) were investigated. Based on the genetic distribution of the rs2241766 locus, the distribution frequency of the T allele in the T2DM group (72.8%) was higher than in the control group (68.8%). Individuals carrying the G allele had a 0.82-fold greater risk of developing T2DM than individuals carrying the T allele. Differences were evident in the genotypic and allelic distributions (p < 0.05). Enzyme-linked immunosorbent assay (ELISA) was used to measure changes in serum adiponectin protein concentrations in the healthy population and in patients with T2DM. Serum adiponectin concentration in patients with T2DM was lower than in the control group. In summary, adiponectin was determined to be a T2DM susceptibility gene and may be involved in T2DM progression.

Increasing arsenic accumulation as an implication of climate change: a case study using red algae.

Climate change due to an increasing concentration of carbon dioxide in the atmosphere is a global issue. It can impact aquatic environments by affecting water flow, pollutant transformation and migration, and other toxicant-related effects. We assessed the interactive effects of temperature warming and pH changes on variations in accumulation of total arsenic (AsT) in the red alga Sarcodia suae at different levels of arsenite (AsIII). Result showed that AsT variations in the alga were moderated by significant joint effects of warming temperature and/or increasing pH levels and their interactions with increasing AsIII concentrations. Our study suggests possible deleterious impacts on macroalgal populations due to toxicological effects associated with prevailing environmental conditions. Therefore, improved pollution management, climate change adaptation, and mitigation strategies are needed to deal with current environmental issues and As aggravation.

Functional stability of CFTR depends on tight binding of ATP at its degenerate ATP-binding site.

Opening of the cystic fibrosis transmembrane conductance regulator (CFTR) channel is coupled to the motion of its two nucleotide-binding domains: they form a heterodimer sandwiching two functionally distinct ATP-binding sites (sites 1 and 2). While active ATP hydrolysis in site 2 triggers rapid channel closure, the functional role of stable ATP binding in the catalysis-incompetent (or degenerate) site 1, a feature conserved in many other ATP-binding cassette (ABC) transporter proteins, remains elusive. Here, we found that CFTR loses its prompt responsiveness to ATP after the channel is devoid of ATP for tens to hundreds of seconds. Mutants with weakened ATP binding in site 1 and the most prevalent disease-causing mutation, F508del, are more vulnerable to ATP depletion. In contrast, strengthening ligand binding in site 1 with N6 -(2-phenylethyl)-ATP, a high-affinity ATP analogue, or abolishing ATP hydrolysis in site 2 by the mutation D1370N, helps sustain a durable function of the otherwise unstable mutant channels. Thus, tight binding of ATP in the degenerate ATP-binding site is crucial to the functional stability of CFTR. Small molecules targeting site 1 may bear therapeutic potential to overcome the membrane instability of F508del-CFTR. KEY POINTS: During evolution, many ATP-binding cassette transporters - including the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, whose dysfunction causes cystic fibrosis (CF) - lose the ability to hydrolyse ATP in one of the two ATP-binding sites. Here we show that tight ATP binding at this degenerate site in CFTR is central for maintaining the stable, robust function of normal CFTR. We also demonstrate that membrane instability of the most common CF-causing mutant, F508del-CFTR, can be rescued by strengthening ATP binding at CFTR's degenerate site. Our data thus explain an evolutionary puzzle and offer a potential therapeutic strategy for CF.

Analytical validation of human epidermal growth factor receptor 2 immunohistochemistry by the use of the A0485 antibody versus the 4B5 antibody and breast versus gastric scoring guidelines in ovarian clear cell carcinoma.

AIMS: The aim of this study was to evaluate human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) in ovarian clear cell carcinoma (OCCC) by using two antibodies and two scoring guidelines in correlation with HER2 amplification and clinicopathological features. METHODS AND RESULTS: A tissue microarray was constructed by use of a total of 71 OCCC cases for IHC (the A0485 antibody and the 4B5 antibody) and dual-colour silver in-situ hybridisation (DISH). Two pathologists independently scored the IHC according to the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) breast cancer guidelines (breast guidelines) and the 2016 ASCO/CAP gastro-oesophageal adenocarcinoma guidelines (gastric guidelines). IHC concordances between A0485 and 4B5 were 87.3-93.0%. Three to 16 (4.2-22.5%) cases had an IHC score of 2+/3+ with frequent basolateral/lateral membranous staining. The 4B5 antibody yielded fewer IHC 2+ cases than the A0485 antibody (n = 2-6 versus n = 5-12). Five (7.0%) cases had HER2 amplification as determined with DISH. Cases with papillary-predominant growth patterns were significantly more likely to have HER2 amplification (P = 0.0051). In predicting DISH results, IHC scored according to the gastric guidelines yielded 100%/100% sensitivity and 83.3-95.5%/98.2-100% specificity, and IHC scored according to the breast guidelines yielded 60-80%/33.3-66.7% sensitivity and 95.5-100%/100% specificity (including/excluding IHC 2+ cases). One case had intratumoral heterogeneity, with discordant results between primary and metastatic tumour specimens. CONCLUSION: We demonstrated HER2 amplification in 7% of OCCC cases, and the molecular change is significantly associated with papillary-predominant growth patterns. In predicting HER2 amplification, a combination of 4B5 IHC and gastric guidelines provides the best sensitivity and fewer equivocal (IHC 2+) cases. Given the intratumoral heterogeneity, assessment of HER2 status on whole tissue sections and on both primary and metastatic tumour specimens is recommended.

Extraction Procedure, Characteristics, and Feasibility of Caulerpa microphysa (Chlorophyta) Polysaccharide Extract as a Cosmetic Ingredient.

The green alga Caulerpa microphysa, which is native to Taiwan, has a relatively high economic value and a well-developed culture technique, and is used mainly as a foodstuff. Its extract has been shown to exhibit antitumor properties, but the polysaccharide content of the extract and its anti-inflammatory and wound-healing effects and moisture-absorption and -retention capacity remain unknown. Hence, the objective of this study was to evaluate the potential of the polysaccharides in C. microphysa extract (CME) for use in cosmetics. The overall polysaccharide yield from the CME was 73.93% w/w, with four molecular weight fractions. The polysaccharides comprised 59.36 mol% mannose, 27.16 mol% glucose, and 13.48 mol% galactose. In addition, the CME exhibited strong antiallergic, wound-healing, transdermal-delivery, and moisture-absorption and -retention effects. In conclusion, the results suggested that CME potentially has anti-inflammatory and wound-healing effects and a good moisture capacity, which can be used in cosmetic applications.

Immunostimulatory effects of Sarcodia suiae water extracts on Nile tilapia Oreochromis niloticus and its resistance against Streptococcus agalactiae.

In this study, water extracts of the red seaweed Sarcodia suiae were obtained using solid-liquid extraction (SLE) or pressurized liquid extraction (PLE) methods. The extracts were used to investigate immunostimulatory activity by measuring the phagocytic activity of Nile tilapia (Oreochromis niloticus) hepatic and splenic macrophages and the tilapia head kidney (THK) cell line, and modulation of immune-related genes in primary head kidney (HK) cells and THK cells. At 10 µg/ml, both extracts promoted the proliferation of hepatic and splenic macrophages. Expression levels of proinflammatory cytokines (IL-1ß and IL-8), antimicrobial peptides (TP2 and TP4), and pattern recognition receptors (TLR5) were elevated in SLE extracts-treated primary HK leukocytes. Similarly, IL-1ß, IL-8, and TNFα expression was also induced by SLE extract in THK cells. Phagocytic activity in primary HK cells and THK cells was induced by SLE extract 12 h and 24 h post-stimulation, while PLE extract only induced phagocytic activity in THK cells at early time points. SLE extract (100 µg/g body weight) increased the expression of IL-1ß, IL-8, TNFα, TP2, TP4, TLR2 and TLR5 in the spleen and immunoprotective efficiency against Streptococcus agalactiae infection. Taken together, these results show that S. suiae can differentially stimulate the immune response of tilapia in vitro and in vivo and could potentially be used as an immunomodulator in tilapia culture.

Effects of Casein Kinase 2 Alpha 1 Gene Expression on Mice Liver Susceptible to Type 2 Diabetes Mellitus and Obesity.

Diabetes mellitus (DM) is a chronic disease found worldwide. Notably, BKS.Cg- Dock7m +/+ Leprdb/JNarl mice are useful animal models for studying type 2 diabetes mellitus (T2DM). In this study, we investigated casein kinase 2 alpha 1 (CSNK2A1) gene and protein expression in the liver tissues of mice at different ages (4, 16, and 32 weeks) using real-time quantitative polymerase chain reactions, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay. Our data paved the way for exploring BKS.Cg- Dock7m +/+ Leprdb/JNarl in the mouse model by demonstrating a significant increase in gene and protein expression in T2DM (+Leprdb/+Leprdb) mouse liver when compared to control (+Dock7m/+Dock7m) mouse liver. We also observed that CSNK2A1 protein level in the serum of T2DM patient group was higher than that of the control group, although the data was not statistically significant. Based on our findings, we can now understand the role of CSNK2A1 gene upregulation when encountering T2DM pathologies.

The impact of robotic total mesorectal excision on survival of patients with rectal cancer-a propensity matched analysis.

INTRODUCTION: Robotic surgery can overcome some limitations of laparoscopic total mesorectal excision (L-TME), improving the quality of the surgery. We aim to compare the medium-term oncological outcomes of L-TME vs. robotic total mesorectal excision (R-TME) for rectal cancer. METHODS: A retrospective analysis was performed including patients who underwent L-TME or R-TME between 2011 and 2017. Patients presenting with metastatic disease or R1 resection were excluded. From a total of 680 patients, 136 cases of R-TME were matched based on age, gender, stage and time of follow-up with an equal number of patients who underwent L-TME. We compared 3-year disease-free survival (DFS) and overall survival (OS). RESULTS: Major complications were lower in the robotic group (13.2% vs. 22.8%, p = 0.04), highlighting the anastomotic leakage rate (7.4% vs. 16.9%, p = 0.01). The 3-year DFS rate for all stages was 69% for L-TME and 84% for R-TME (p = 0.02). For disease stage III, the 3-year DFS was significantly higher in the R-TME group. OS was also significantly superior in the robotic group for every stage, reaching 86% in stage III. In the multivariate analysis, R-TME was a significant positive prognostic factor for distant metastasis (OR 0.2 95% CI 0.1, 0.6, p = 0.001) and OS (OR 0.2 95% CI 0.07, 0.4, p = 0.000). Moreover, major complications were also found to have a negative impact on OS (OR 8.3 95% CI 3.2, 21.6, p = 0.000). CONCLUSION: R-TME for rectal cancer can achieve better oncological outcomes compared with L-TME, especially in stage III rectal cancers. However, a longer follow-up period is needed to confirm these findings.

Loss of Response Gene to Complement 32 (RGC-32) in Diabetic Mouse Retina Is Involved in Retinopathy Development.

Diabetic retinopathy (DR) is a severe and recurrent microvascular complication in diabetes. The multifunctional response gene to complement 32 (RGC-32) is involved in the regulation of cell cycle, proliferation, and apoptosis. To investigate the role of RGC-32 in the development of DR, we used human retinal microvascular endothelial cells under high-glucose conditions and type 2 diabetes (T2D) mice (+Leprdb/ + Leprdb, db/db). The results showed that RGC-32 expression increased moderately in human retinal endothelial cells under hyperglycemic conditions. Histopathology and RGC-32 expression showed no significant changes between T2D and control mice retina at 16 and 24 weeks of age. However, RGC-32 expression was significantly decreased in T2D mouse retina compared to the control group at 32 weeks of age, which develop features of the early clinical stages of DR, namely reduced retinal thickness and increased ganglion cell death. Moreover, immunohistochemistry showed that RGC-32 was predominantly expressed in the photoreceptor inner segments of control mice, while the expression was dramatically lowered in the T2D retinas. Furthermore, we found that the level of anti-apoptotic protein Bcl-2 was decreased (approximately 2-fold) with a concomitant increase in cleaved caspase-3 (approximately 3-fold) in T2D retina compared to control. In summary, RGC-32 may lose its expression in T2D retina with features of DR, suggesting that it plays a critical role in DR pathogenesis.

Cadmium-Free InP/ZnSeS/ZnS Heterostructure-Based Quantum Dot Light-Emitting Diodes with a ZnMgO Electron Transport Layer and a Brightness of Over 10 000 cd m-2.

Cadmium-free thick-shelled InP/ZnSeS/ZnS quantum dot (QD) was synthesized using the heating-up approach. This quantum dots was used in inverted quantum dots light emitting diode (QLED) devices. The brightness of the inverted QLED device can reach a brightness of over 10 000 cd m-2 , low turn-on voltage (2.2 V), and high power efficiency (4.32 lm W-1 ).

Optimizing inorganic carbon and salinity for enhanced biomass and pigment production in Colaconema formosanum: Implications for sustainable carbon sequestration and stress responses.

This study investigates a cultivation strategy for the macroalga Colaconema formosanum by determining optimal inorganic carbon concentration and salinity for maximizing biomass and photosynthetic pigment production while also facilitating carbon sequestration. The response surface method was used with a central composite design (CCD-RSM) to determine the optimal conditions. Results showed that adding 1.2 g/L of carbon increased the specific growth rate to 18%-19% per day. The maximum amount of pigment, including phycobiliprotein and chlorophyll, was achieved by adjusting both carbon content and salinity. This strategy enables mass pigment production and offers an eco-friendly approach to carbon sequestration while reducing culture period. This study also sheds light on algal mechanisms against enriched inorganic carbon and salinity content, contributing to an enhanced understanding of these vital processes.

No association of postoperative opioid usage with long-term surgery outcomes in patients with liver cancer: a population-based retrospective cohort study.

ABSTRACT: Hepatocellular carcinoma (HCC) is a fatal cancer worldwide, and surgical resection remains the standard treatment. Postoperative opioid prescription has been believed to affect cancer recurrence through complex biological pathways. We conducted a retrospective cohort study using the Longitudinal Health Insurance Database of Taiwan to evaluate the relationship between postoperative opioid use and long-term surgical outcomes of patients with HCC. This study had a retrospective cohort design. In total, 812 patients older than 20 years who underwent hepatectomy because of HCC were included. The exposure group comprised patients who used opioids during hospitalization postoperatively. The comparison group included those who never used opioids during hospitalization postoperatively. A Cox proportional hazards model was used to evaluate the overall survival or recurrence-free survival rate between the opioid group and the nonopioid group. A total of 530 patients received opioids postoperatively and 282 patients did not. The hazard ratios of overall survival and recurrence-free survival were 1.10 (95% confidence interval [CI], 0.85-1.41) and 1.15 (95% CI, 0.91-1.46), respectively. Total postoperative opioids were converted into oral morphine milligram equivalents and then divided into 3 equal subgroups: low dose, <40 mg; medium dose, 40 to 144 mg; and high dose, ≥145 mg. The hazard ratios of overall survival were 0.88 (95% CI, 0.63-1.24) for the low-dose group, 1.27 (95% CI, 0.92-1.74) for the medium-dose group, and 1.14 (95% CI, 0.83-1.58) for the high-dose group. Postoperative opioids do not affect overall and recurrence-free survival in patients undergoing hepatectomy or liver transplantation because of HCC. Cancer recurrence should not be a clinical concern regarding postoperative opioid prescription.

Association of Glaucoma with the Risk of Peripheral Arterial Occlusive Disease: A Retrospective Population-Based Cohort Study.

This study aimed to investigate the potential association between glaucoma and peripheral arterial occlusive disease. The study recruited patients, including 101,309 with glaucoma and 1,860,528 without a glaucoma diagnosis, from a population of 2 million patients in the Longitudinal Health Insurance Database. Propensity score matching was performed between the two groups, matching for age, sex, and comorbidities. In total, 95,575 patients with glaucoma and 95,575 patients without glaucoma were analyzed for their risk of developing peripheral arterial occlusive disease. The analysis of the data revealed that the glaucoma group had a higher incidence density (ID = 4.13) of peripheral arterial occlusive disease than the non-glaucoma group (ID = 3.42). The relative risk for the glaucoma group was 1.21 (95% C.I. = 1.15-1.28). Cox proportional hazard model analysis indicated that the glaucoma group had a higher risk of developing peripheral arterial occlusive disease (HR = 1.18; 95% C.I. = 1.12-1.25). The subgroup analysis of the risk of PAOD showed that the glaucoma group had a higher risk of developing peripheral arterial occlusive disease in the age group of 20 to 39 (p for interaction = 0.002). In conclusion, patients with glaucoma were associated with a higher risk of subsequent peripheral arterial occlusive disease compared with those without a diagnosis of glaucoma.

Robust Nanoparticle-Derived Lubricious Antibiofilm Coating for Difficult-to-Coat Medical Devices with Intricate Geometry.

A major medical device-associated complication is the biofilm-related infection post-implantation. One promising approach to prevent this is to coat already commercialized medical devices with effective antibiofilm materials. However, developing a robust high-performance antibiofilm coating on devices with a nonflat geometry remains unmet. Here, we report the development of a facile scalable nanoparticle-based antibiofilm silver composite coating with long-term activity applicable to virtually any objects including difficult-to-coat commercially available medical devices utilizing a catecholic organic-aqueous mixture. Using a screening approach, we have identified a combination of the organic-aqueous buffer mixture which alters polycatecholamine synthesis, nanoparticle formation, and stabilization, resulting in controlled deposition of in situ formed composite silver nanoparticles in the presence of an ultra-high-molecular-weight hydrophilic polymer on diverse objects irrespective of its geometry and chemistry. Methanol-mediated synthesis of polymer-silver composite nanoparticles resulted in a biocompatible lubricious coating with high mechanical durability, long-term silver release (∼90 days), complete inhibition of bacterial adhesion, and excellent killing activity against a diverse range of bacteria over the long term. Coated catheters retained their excellent activity even after exposure to harsh mechanical challenges (rubbing, twisting, and stretching) and storage conditions (>3 months stirring in water). We confirmed its excellent bacteria-killing efficacy (>99.999%) against difficult-to-kill bacteria (Proteus mirabilis) and high biocompatibility using percutaneous catheter infection mice and subcutaneous implant rat models, respectively, in vivo. The developed coating approach opens a new avenue to transform clinically used medical devices (e.g., urinary catheters) to highly infection-resistant devices to prevent and treat implant/device-associated infections.

Genomic and tumour microenvironmental biomarkers of immune checkpoint inhibitor response in advanced Taiwanese melanoma.

Objective: Genomic biomarkers predicting immune checkpoint inhibitor (ICI) treatment outcomes for Asian metastatic melanoma have been rarely reported. This study presents data on next-generation sequencing (NGS) and tumour microenvironment biomarkers in 33 cases. Methods: Thirty-three patients with advanced melanoma, who underwent ICI treatment at the Chang Gung Memorial Hospital in Taiwan, were recruited. The study evaluated clinical outcomes, including response rate, disease control rate, progression-free survival (PFS) rate and overall survival (OS) rate. Archived tissue samples from 33 cases were subjected to NGS by ACTOnco, and ACTTME was employed in 25 cases. Results: The most prevalent driver mutations were BRAF mutations (24.2%), followed by NRAS (15.2%), KIT (12.1%), KRAS (9.1%) and NF1 (9.1%) mutations. Acral/mucosal melanomas exhibited distinct mutation patterns compared to non-acral melanomas. Tumour mutational burden estimated using ACTOnco was not associated with ICI efficacy. Notably, genetic alterations in the p53 pathway (CDKNA2 loss, MDM2 gain/amplification and TP53 mutation) accounted for 36.4% and were significantly associated with unfavourable PFS (median PFS 2.7 months vs. 3.9 months, P = 0.0394). Moreover, 26 genes were identified as differentially expressed genes that were upregulated in patients with clinical benefits compared to those without benefits. Four genes, GZMH, GZMK, AIM2 and CTLA4, were found to be associated with both PFS and OS. Conclusion: Genetic alterations in the p53 pathway may be critical in Asian patients with melanoma undergoing ICI treatment. Further investigation is required to explore this mechanism and validate these findings.