A Pilot Study for Effectiveness and Safety of Adjunctive Pharmacopuncture to Acupuncture Treatment for Rotator Cuff Diseases: A Pragmatic Randomized Controlled Trial.

Purpose: Pharmacopuncture therapy has been used in the conservative treatment of rotator cuff disease adjuvant to acupuncture treatment. Despite the increasing utilization of pharmacopuncture therapy, there is still a lack of high-quality research to support its effectiveness. This pilot study aimed to assess the feasibility of pharmacopuncture therapy adjuvant to acupuncture treatment for rotator cuff disease. Patients and Methods: This was a parallel-grouped, pragmatic randomized controlled, pilot study. Forty patients were randomly allocated to either the experimental or the control group. All patients received acupuncture treatment for four weeks, and pharmacopuncture was additionally administered to the experimental group. After eight treatments were delivered over four weeks, follow-up assessments were performed. The primary outcome was the mean change in the visual analog scale (VAS) score for shoulder pain from baseline to visit 8. Secondary outcomes included shoulder pain and disability index (SPADI) at visits 4, 8, and 9, shoulder range of motion (ROM) at visits 4, 8, and 9, EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at visits 8 and 9, patient global impression of change (PGIC) at visits 8 and 9, and mean rescue medication consumption at visits 8 and 9. Results: Both groups showed that each treatment effectively improved rotator cuff disease in most assessments. Particularly, the group that received acupuncture plus pharmacopuncture required fewer rescue medications than the group that received acupuncture alone. However, there was little statistically significant difference between the two groups. There were no serious adverse events experienced by patients in this study. Conclusion: Although there was little statistical difference between the two groups, the combination of acupuncture and pharmacopuncture for rotator cuff disease was associated with a reduction in the rescue medicine dosage compared with acupuncture alone. Also, it confirmed the safety of pharmacopuncture therapy. This pilot study would help design future research on the effectiveness of pharmacopuncture in rotator cuff disease.

Influence of the interaction between p53 and ZNF568 on mitochondrial oxidative phosphorylation.

The tumor suppressor p53 plays important roles in suppressing the development and progression of cancer by responding to various stress signals. In addition, p53 can regulate the metabolic pathways of cancer cells by regulating energy metabolism and oxidative phosphorylation. Here, we present a mechanism for the interaction between p53 and ZNF568. Initially, we used X-ray crystallography to determine the irregular loop structure of the ZNF568 KRAB domain; this loop plays an important role in the interaction between p53 and ZNF568. In addition, Cryo-EM was used to examine how the p53 DBD and ZNF568 KRAB domains bind together. The function of ZNF568 on p53-mediated mitochondrial respiration was confirmed by measuring glucose consumption and lactate production. These findings show that ZNF568 can reduce p53-mediated mitochondrial respiratory activity by binding to p53 and inhibiting the transcription of SCO2. SIGNIFICANCE: ZNF568 can directly bind to the p53 DBD and transcriptionally regulate the SCO2 gene. SCO2 transcriptional regulation by interaction between ZNF568 and p53 may regulate the balance between mitochondrial respiration and glycolysis.

Frequency-Selective, Multi-Channel, Self-Powered Artificial Basilar Membrane Sensor with a Spiral Shape and 24 Critical Bands Inspired by the Human Cochlea.

A spiral-artificial basilar membrane (S-ABM) sensor is reported that mimics the basilar membrane (BM) of the human cochlea and can detect sound by separating it into 24 sensing channels based on the frequency band. For this, an analytical function is proposed to design the width of the BM so that the frequency bands are linearly located along the length of the BM. To fabricate the S-ABM sensor, a spiral-shaped polyimide film is used as a vibrating membrane, with maximum displacement at locations corresponding to specific frequency bands of sound, and attach piezoelectric sensor modules made of poly(vinylidene fluoride-trifluoroethylene) film on top of the polyimide film to measure the vibration amplitude at each channel location. As the result, the S-ABM sensor implements a characteristic frequency band of 96-12,821 Hz and 24-independent critical bands. Using real-time signals from discriminate channels, it is demonstrated that the sensor can rapidly identify the operational noises from equipment processes as well as vehicle sounds from environmental noises on the road. The sensor can be used in a variety of applications, including speech recognition, dangerous situation recognition, hearing aids, and cochlear implants, and more.

Facile Fabrication of Multifunctional Hydrogel Nanoweb Coating Using Carboxymethyl Chitosan-Based Short Nanofibers for Blood-Contacting Medical Devices.

Blood-contacting medical devices (BCDs) require antithrombotic, antibacterial, and low-friction surfaces. Incorporating a nanostructured surface with the functional hydrogel onto BCD surfaces can enhance the performances; however, their fabrication remains challenging. Here, we introduce a straightforward method to fabricate a multifunctional hydrogel-based nanostructure on BCD surfaces using O-carboxymethyl chitosan-based short nanofibers (CMC-SNFs). CMC-SNFs, fabricated via electrospinning and cutting processes, are easily sprayed and entangled onto the BCD surface. The deposited CMC-SNFs form a robust nanoweb layer via fusion at the contact area of the nanofiber interfaces. The superhydrophilic CMS-SNF nanoweb surface creates a water-bound layer that effectively prevents the nonspecific adhesion of bacteria and blood cells, thereby enhancing both antimicrobial and antithrombotic performances. Furthermore, the CMC-SNF nanoweb exhibits excellent lubricity and durability on the bovine aorta. The demonstration results of the CMC-SNF coating on catheters and sheaths provide evidence of its capability to apply multifunctional surfaces simply for diverse BCDs.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

Structural identification and comprehension of human ALDH1L1-Gossypol complex.

The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO2. Non-small cell lung cancer cells (NSCLC) strongly express ALDH1L1. Gossypol binds to an allosteric site and disrupts the folate metabolism by preventing NADP+ binding. The Cryo-EM structures of tetrameric C-terminal aldehyde dehydrogenase human ALDH1L1 complex with gossypol were examined. Gossypol-bound ALDH1L1 interfered with NADP+ by shifting the allosteric site of the structural conformation, producing a closed-form NADP+ binding site. In addition, the inhibition activity of ALDH1L1 was targeted with gossypol in NSCLC. The gossypol treatment had anti-cancer effects on NSCLC by blocking NADPH and ATP production. These findings emphasize the structure characterizing ALDH1L1 with gossypol.

Beyond nanoparticle-based oral drug delivery: transporter-mediated absorption and disease targeting.

Various strategies at the microscale/nanoscale have been developed to improve oral absorption of therapeutics. Among them, gastrointestinal (GI)-transporter/receptor-mediated nanosized drug delivery systems (NDDSs) have drawn attention due to their many benefits, such as improved water solubility, improved chemical/physical stability, improved oral absorption, and improved targetability of their payloads. Their therapeutic potential in disease animal models (e.g., solid tumors, virus-infected lungs, metastasis, diabetes, and so on) has been investigated, and could be expanded to disease targeting after systemic/lymphatic circulation, although the detailed paths and mechanisms of endocytosis, endosomal escape, intracellular trafficking, and exocytosis through the epithelial cell lining in the GI tract are still unclear. Thus, this review summarizes and discusses potential GI transporters/receptors, their absorption and distribution, in vivo studies, and potential sequential targeting (e.g., oral absorption and disease targeting in organs/tissues).

Fabrication and evaluation of stable amorphous polymer-drug composite particles via a nozzle-free ultrasonic nebulizer.

We present a promising method for producing amorphous drug particles using a nozzle-free ultrasonic nebulizer with polymers, specifically polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA), and Eudragit® S 100 (EUD). Model crystalline phase drugs-Empagliflozin, Furosemide, and Ilaprazole-are selected. This technique efficiently produces spherical polymer-drug composite particles and demonstrates enhanced stability against humidity and thermal conditions, compared to the drug-only amorphous particles. The composite particles exhibit improved water dissolution compared to the original crystalline drugs, indicating potential bioavailability enhancements. While there are challenges, including the need for continuous water supply for ultrasonic component cooling, dependency on the solubility of polymers and drugs in volatile organic solvents, and mildly elevated temperatures for solvent evaporation, our method offers significant advantages over traditional approaches. It provides a straightforward, flexible process adaptable to various drug-polymer combinations and consistently yields spherical amorphous solid dispersion (ASD) particles with a narrow size distribution. These attributes make our method a valuable advancement in pharmaceutical drug formulation and delivery.

Three new species of the leafhopper genus Arboridia Zachvatkin (Hemiptera, Cicadellidae, Typhlocybinae), with a key and checklist to known species of China.

Three new species of the leafhopper genus ArboridiaZachvatkin 1946, Arboridia (Arboridia) furcata Han, sp. nov., Arboridia (Arboridia) rubrovittata Han, sp. nov., and Arboridia (Arboridia) robustipenis Han, sp. nov., are described and illustrated from fruit trees in Southwest China. A key and checklist to known species from China are provided.

Ribosomal S6 kinase 2-forkhead box protein O4 signaling pathway plays an essential role in melanogenesis.

Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4's transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis.

Efficacy and Safety of Acupoint Catgut Embedding for Knee Osteoarthritis: a Protocol for Systematic review and Meta-Analysis.

Background: Knee osteoarthritis causes physical dysfunction, and its prevalence increases with age. Although clinical studies examined acupoint catgut embedding in patients with knee osteoarthritis, no systematic reviews or meta-analyses have been conducted to date. We aim to comprehensively review the effects of acupoint catgut embedding on knee osteoarthritis. Methods: Eleven databases will be searched from inception to August 1, 2023, without language limitations. Additionally, two registration platforms-ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry-will be searched for ongoing trials. The primary outcomes will be assessed using the Visual Analog Scale and the Western Ontario and McMaster Universities Osteoarthritis Index. Secondary outcomes include the total effective rate, Lysholm Score, and adverse effects. Two reviewers will independently select the studies, extract data, and evaluate the risk of bias and the quality of evidence. Discussion: This systematic review will provide evidence regarding the safety and efficacy of acupoint catgut embedding in patients with knee osteoarthritis.

ELK3 destabilization by speckle-type POZ protein suppresses prostate cancer progression and docetaxel resistance.

Accumulating evidence demonstrates that the activity regulation of ELK3, a member of the E26 transformation-specific oncogene family, is critical to regulating cell proliferation, migration, and survival in human cancers. However, the molecular mechanisms of how ELK3 induces chemoresistance in prostate cancer (PCa) have not been elucidated. In this study, we found that SPOP and ELK3 are an interacting partner. The interaction between SPOP and ELK3 resulted in increased ELK3 ubiquitination and destruction, assisted by checkpoint kinase-mediated ELK3 phosphorylation. Notably, the modulation of SPOP-mediated ELK3 protein stability affected the c-Fos-induced cell proliferation and invasion of PCa cells. The clinical involvement of the SPOP-ELK3 axis in PCa development was confirmed by an immunohistochemical assay on 123 PCa tissues, with an inverse correlation between increased ELK3 and decreased SPOP being present in ~80% of the specimens. This observation was supported by immunohistochemistry analysis using a SPOP-mutant PCa specimen. Finally, docetaxel treatment induced cell death by activating checkpoint kinase- and SPOP-mediated ELK3 degradation, while SPOP-depleted or SPOP-mutated PCa cells showed cell death resistance. Notably, this observation was correlated with the protein levels of ELK3. Taken together, our study reveals the precise mechanism of SPOP-mediated degradation of ELK3 and provides evidence that SPOP mutations contribute to docetaxel resistance in PCa.

Boltzmann Switching MoS2 Metal-Semiconductor Field-Effect Transistors Enabled by Monolithic-Oxide-Gapped Metal Gates at the Schottky-Mott Limit.

A gate stack that facilitates a high-quality interface and tight electrostatic control is crucial for realizing high-performance and low-power field-effect transistors (FETs). However, when constructing conventional metal-oxide-semiconductor structures with two-dimensional (2D) transition metal dichalcogenide channels, achieving these requirements becomes challenging due to inherent difficulties in obtaining high-quality gate dielectrics through native oxidation or film deposition. Here, a gate-dielectric-less device architecture of van der Waals Schottky gated metal-semiconductor FETs (vdW-SG MESFETs) using a molybdenum disulfide (MoS2) channel and surface-oxidized metal gates such as nickel and copper is reported. Benefiting from the strong SG coupling, these MESFETs operate at remarkably low gate voltages, <0.5 V. Notably, they also exhibit Boltzmann-limited switching behavior featured by a subthreshold swing of ≈60 mV dec-1 and negligible hysteresis. These ideal FET characteristics are attributed to the formation of a Fermi-level (EF) pinning-free gate stack at the Schottky-Mott limit. Furthermore, authors experimentally and theoretically confirm that EF depinning can be achieved by suppressing both metal-induced and disorder-induced gap states at the interface between the monolithic-oxide-gapped metal gate and the MoS2 channel. This work paves a new route for designing high-performance and energy-efficient 2D electronics.

The anterior lobe of the parotid gland: a CT sialographic study.

OBJECTIVES: To investigate the imaging and anatomic features of the anterior lobe (AL) of the superficial parotid gland (SPG). METHODS: Computed tomographic sialography examinations were undertaken for 142 parotid glands in 77 patients. Whole computer tomography (CT) data were analyzed using multi-planar reformation and maximum intensity projection to generate sialographic CT images. The tributary ducts of the SPG were analyzed to classify the parotid morphology. Three-dimensional analyses were used to investigate the AL and its relationship with adjacent anatomic landmarks. RESULTS: Four major types (I-IV) and 2 minor types (V-VI) of the AL and the superficial parotid gland were observed. Type I AL (83/142) was contiguous and not separated from the retromandibular parotid gland. Type II AL (16/142) was detached from the retromandibular parotid gland with 1-4 tributary ducts. Type III AL (12/142) showed a small isolated lobe above the Stensen duct around the anterior edge of the masseter. Type IV (28/142) showed the absence of the AL. Type V (3/142) shows the absence of the retromandibular parotid gland. Type VI (3/142) showed the presence of ectopic salivary gland beneath the Stensen duct anterior to the retromandibular parotid gland. CONCLUSIONS: The AL gives rise to the morphological variations of the superficial parotid gland. AL also gives rise to the accessory parotid gland when it is detached from the retromandibular parotid gland.

Dysregulated CREB3 cleavage at the nuclear membrane induces karyoptosis-mediated cell death.

Cancer cells often exhibit resistance to apoptotic cell death, but they may be vulnerable to other types of cell death. Elucidating additional mechanisms that govern cancer cell death is crucial for developing new therapies. Our research identified cyclic AMP-responsive element-binding protein 3 (CREB3) as a crucial regulator and initiator of a unique cell death mechanism known as karyoptosis. This process is characterized by nuclear shrinkage, deformation, and the loss of nuclear components following nuclear membrane rupture. We found that the N-terminal domain (aa 1-230) of full-length CREB3 (CREB3-FL), which is anchored to the nuclear inner membrane (INM), interacts with lamins and chromatin DNA. This interaction maintains a balance between the outward force exerted by tightly packed DNA and the inward constraining force, thereby preserving INM integrity. Under endoplasmic reticulum (ER) stress, aberrant cleavage of CREB3-FL at the INM leads to abnormal accumulation of the cleaved form of CREB3 (CREB3-CF). This accumulation disrupts the attachment of CREB3-FL to the INM, resulting in sudden rupture of the nuclear membrane and the onset of karyoptosis. Proteomic studies revealed that CREB3-CF overexpression induces a DNA damage response akin to that caused by UVB irradiation, which is associated with cellular senescence in cancer cells. These findings demonstrated that the dysregulation of CREB3-FL cleavage is a key factor in karyoptotic cell death. Consequently, these findings suggest new therapeutic strategies in cancer treatment that exploit the process of karyoptosis.

Cryo-EM structure of Influenza A virus NS1 and antiviral protein kinase PKR complex.

Influenza A virus is the cause of a widespread human disease with high morbidity and mortality rates. The influenza virus encodes non-structural protein 1 (NS1), an exceedingly multifunctional virulence component. NS1 plays essential roles in viral replication and evasion of the cellular innate immune system. Protein kinase RNA-activated also known as protein kinase R (PKR) phosphorylates translation initiation factor eIF-2α on serine 51 to inhibit protein synthesis in virus-infected mammalian cells. Consequently, PKR activation inhibits mRNA translation, which results in the assert of both viral protein synthesis and cellular and possibly apoptosis in response to virus infection. Host signaling pathways are important in the replication of influenza virus, but the mechanisms involved remain to be characterized. Herein, the structure of NS1 and PKR complex was determined using Cryo-EM. We found the N91, E94, and G95 residues of PKR bind directly with N188, D125, and K126, respectively, of NS1. Furthermore, the study shows that PKR peptide offers a potential treatment for Influenza A virus infections.

Predicted Separation of Acid Gases from Gas Mixtures by Functionalized Porous Aromatic Frameworks.

The selective adsorption of target acid gas molecules from binary gas mixtures by porous aromatic frameworks (PAFs) with two identical functional groups per aromatic ring (PAF-R2) was computationally investigated using grand canonical Monte Carlo simulations. PAF-R2 adsorption was considered for three binary mixtures of small molecular concentrations of acid gas and abundant nitrogen gas (CO2/N2, SO2/N2, and H2S/N2). The results indicate that additional functional groups enhance acid gas loadings and selectivity, compared with pristine PAF and single-functionalized PAFs. Low pressures yield linearly increasing gas loadings and constant selectivity, while high pressures yield much higher adsorption and selectivity. In particular, SO2 loading and selectivity under high pressures are heavily influenced by the PAF's maximum adsorption limit, which can be linked back to the functional groups and their configuration. In summary, PAF-(3,5)-(COOH)2 (nomenclature of PAFs is provided in the Appendix in the Supporting Information) and many other PAF with the same two electron-withdrawing groups are predicted to have great acid gas adsorption and selectivity from gas mixtures, while PAF-(3,5)-(OH)2 (one of PAFs with two identical electron-donating groups) is predicted to have good adsorption and selectivity, especially under elevated pressures. The results of this work can provide insights into various types of PAFs with great selective adsorption ability and their corresponding conditions. The simulation procedures and results may inspire the exploration and screening of other types of PAFs or porous materials, for acid gas absorption.

Beyond Nanoparticle-Based Intracellular Drug Delivery: Cytosol/Organelle-Targeted Drug Release and Therapeutic Synergism.

Nanoparticle (NP)-based drug delivery systems are conceived to solve poor water-solubility and chemical/physical instability, and their purpose expanded to target specific sites for maximizing therapeutic effects and minimizing unwanted events of payloads. Targeted sites are also narrowed from organs/tissues and cells to cytosol/organelles. Beyond specific site targeting, the particular release of payloads at the target sites is growing in importance. This review overviews various issues and their general strategies during multiple steps, from the preparation of drug-loaded NPs to their drug release at the target cytosol/organelles. In particular, this review focuses on current strategies for "first" delivery and "later" release of drugs to the cytosol or organelles of interest using specific stimuli in the target sites. Recognizing or distinguishing the presence/absence of stimuli or their differences in concentration/level/activity in one place from those in another is applied to stimuli-triggered release via bond cleavage or nanostructural transition. In addition, future directions on understanding the intracellular balance of stimuli and their counter-stimuli are demonstrated to synergize the therapeutic effects of payloads released from stimuli-sensitive NPs.

Pharmacopuncture Therapy as an Adjunctive Treatment for Patients with Lumbar Spinal Stenosis: A Pragmatic Randomized Controlled Pilot Trial.

Purpose: Pharmacopuncture therapy (PPT) combines medicinal extracts with acupuncture and is widely used as an adjunct in clinical practice. This study assessed the safety and feasibility of PPT in addition to conventional Korean Medicine treatment (CKMT), including electroacupuncture, cupping and infra-red, for lumbar spinal stenosis (LSS). Patients and Methods: Forty patients diagnosed with LSS were randomly assigned to undergo PPT with CKMT (experimental group) or CKMT alone (control group) at a 1:1 ratio, receiving 10 sessions of each intervention over five weeks. The primary clinical outcome was measured using the 100-mm Visual Analog Scale (VAS) for buttock and leg pain five weeks post-treatment. Secondary outcomes included clinically important difference (CID), Zurich Claudication Questionnaire, self-reported walking capacity, Modified-Modified Schober test, EuroQol 5-dimension 5-level questionnaire, and the patient's global impression of change. The adverse events were assessed at each visit. The analysis of covariance was conducted to compare between two groups. Results: Intervention completion rates were 95% and 100% in the experimental and control groups, respectively. No statistically significant differences were found between groups regarding the primary outcome (adjusted mean difference: 8.0; 95% confidence interval: -1.4-17.4). The mean difference in the 100-mm VAS for low back pain at week 5 (adjusted mean difference: 12.9; 95% confidence interval: 2.4-23.4) and the proportion of patients who reached the minimum CID was higher in the experimental group than in the control group. However, no significant differences were observed with other secondary outcomes. One patient in the experimental group experienced a systemic skin rash that resolved the same day, whereas the adverse events in the other group were mild and transient. Conclusion: This trial demonstrated the feasibility of add-on effects and the safety of pharmacopuncture in patients with LSS. Further studies are warranted to evaluate the add-on effects of PPT in treating LSS. Trial Registration: Clinical Research Information Service (CRIS), KCT0007229; registered on April 26, 2022.

Clinical and financial impact of immune checkpoint inhibitors following platinum chemotherapy in patients with advanced or metastatic non-small cell lung cancer: a nationwide population-based study.

Background: Although various studies have demonstrated that the clinical efficacy of immune checkpoint inhibitors (ICIs) improves the prognosis of patients with non-small cell lung cancer (NSCLC), studies on the financial aspects based on large population-based data are needed. This study aimed to analyze the differences in medical expenses and the effect of ICIs on the prognosis of patients with advanced or metastatic NSCLC. Methods: Patients newly diagnosed with stage IIIB or IV NSCLC who received palliative chemotherapy between 2013 and 2020 were selected from the nationwide database of the population covered by the Korean National Health Insurance Service. Interrupted time-series analysis was performed to evaluate the effects of subsequent ICI use after platinum-based cytotoxic chemotherapy (CC) on overall mortality. Progression-free survival and medical expenditure were also assessed. Results: In the final study population, 2,485 and 4,812 patients were included in the ICI and non-ICI groups, respectively. ICI treatment significantly lowered the risk of death [adjusted hazard ratio, 0.79; 95% confidence interval (CI): 0.75-0.84]. And the ICI-treated patients were less likely to experience disease progression (adjusted odds ratios, 0.92; 95% CI: 0.85-0.99). Furthermore, after the introduction of ICIs, both total and cancer-related medical expenses per capita showed an increasing trend [ß: $4.56K, standard error (SE): $0.27K, P<0.0001 and ß: $4.54K, SE: $0.27K, P<0.0001, respectively]. Conclusions: Subsequent ICI use after platinum-based CC improved the overall survival rate of patients with advanced NSCLC. With the increasing burden of individual medical expenses, further research is required to identify patients for whom ICI treatment may be effective.