Ginsenoside Rg1 Suppresses Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway to Alleviate Chronic Atrophic Gastritis In Vitro and In Vivo.

Chronic atrophic gastritis (CAG) is characterized by the loss of gastric glandular cells, which are replaced by the intestinal-type epithelium and fibrous tissue. Ginsenoside Rg1 (Rg1) is the prevalent ginsenoside in ginseng, with a variety of biological activities, and is usually added to functional foods. As a novel form of programmed cell death (PCD), pyroptosis has received substantial attention in recent years. Despite the numerous beneficial effects, the curative impact of Rg1 on CAG and whether its putative mechanism is partially via inhibiting pyroptosis still remain unknown. To address this gap, we conducted a study to explore the mechanisms underlying the potential anti-CAG effect of Rg1. We constructed a CAG rat model using a multifactor comprehensive method. A cellular model was developed by using 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with Nigericin as a stimulus applied to GES-1 cells. After Rg1 intervention, the levels of inflammatory indicators in the gastric tissue/cell supernatant were reduced. Rg1 relieved oxidative stress via reducing the myeloperoxidase (MPO) and malonaldehyde (MDA) levels in the gastric tissue and increasing the level of superoxide dismutase (SOD). Additionally, Rg1 improved MNNG+Nigericin-induced pyroptosis in the morphology and plasma membrane of the cells. Further research supported novel evidence for Rg1 in the regulation of the NF-κB/NLRP3/GSDMD pathway and the resulting pyroptosis underlying its therapeutic effect. Moreover, by overexpression and knockout of GSDMD in GES-1 cells, our findings suggested that GSDMD might serve as the key target in the effect of Rg1 on suppressing pyroptosis. All of these offer a potential theoretical foundation for applying Rg1 in ameliorating CAG.

HIV-1 env gene mutations outside the targeting probe affects IPDA efficiency.

The intact proviral DNA assay (IPDA) based on droplet digital PCR was developed to identify intact proviral DNA and quantify HIV-1 latency reservoirs in patients infected with HIV-1. However, the genetic characteristics of different HIV-1 subtypes are non-consistent due to their high mutation and recombination rates. Here, we identified that the IPDA based on the sequences features of an HIV-1 subtype could not effectively detect different HIV-1 subtypes due to the high diversity of HIV-1. Furthermore, we demonstrated that mutations in env gene outside the probe binding site affect the detection efficiency of IPDA. Since mutations in env gene outside the probe binding site may also lead to the formation of stop codons, thereby preventing the formation of viruses and ultimately overestimating the number of HIV-1 latency reservoirs, it is important to address the effect of mutations on the IPDA.

A Chinese classical prescription Xuefu Zhuyu decoction in the treatment of coronary heart disease: An overview.

Background: Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide and is a hot topic in cardiovascular disease research. Western medicine treats CHD with stent implantation, anti-angina pectoris, anti-platelet aggregation and other operations or drugs. According to the whole concept and the characteristics of syndrome differentiation, traditional Chinese medicine (TCM) treats CHD according to different syndromes and points out that qi deficiency and blood stasis are the basic pathogenesis of CHD. Xuefu Zhuyu Decoction (XFZYD), as a classic prescription of TCM, has certain value in the treatment of CHD, with the effects of promoting qi, activating blood circulation, dredging collaterals and relieving pain. In addition, it also exhibits advantages in high efficiency, low toxicity, high cost performance, few side effects, and high patient acceptance. Objective: The therapeutic effect and mechanism of XFZYD in the treatment of CHD were searched by literature search, and the components and targets of XFZYD in the treatment of CHD were analyzed by computer simulation technology for molecular docking, providing theoretical basis for clinical treatment of CHD. Method: This study comprehensively searched CNKI, Wanfang, VIP, CBM, Pubmed, Embase, Web of science and other databases, included clinical studies with efficacy evaluation indicators in hospitals according to randomization, and excluded literatures with low quality and no efficacy evaluation indicators. Clinical cases and studies, molecular mechanisms and pharmacological effects of XFZYD in the treatment of CHD were searched, and the effective ingredients and core targets of XFZYD in the treatment of CHD were docked through molecular docking, providing theoretical support for clinical treatment of CHD. Results and Conclusion: Through this study, we found that XFZYD has a significant therapeutic effect in the clinical treatment of coronary heart disease, which can play a role in the treatment of CHD by inhibiting atherosclerosis, inhibiting cardiovascular remodeling, improving oxidative stress damage, improving hemorheology, improving myocardial fibrosis and other mechanisms. Through computer simulation, it was found that the main effective components of XFZYD treatment for CHD were quercetin, kaempferol and luteolin, and the key core targets were IL6, VEGFA and P53, and each component had a high VEGFA libdock score. It is speculated that VEGFA is the key target of XFZYD in the treatment of CHD. Kaempferol and VEGFA had the highest libdock score. kaempferol and IL6 have the highest number of hydrogen bonds, kaempferol and IL6 have the highest number of hydrogen bonds, which indicates that they are most stable, indicating that kaempferol is the key component of XFZYD in the treatment of CHD, which provides a theoretical basis for follow-up experimental research.

Lipid Nanoparticle-Based Delivery System-A Competing Place for mRNA Vaccines.

mRNA, as one of the foci of biomedical research in the past decade, has become a candidate vaccine solution for various infectious diseases and tumors and for regenerative medicine and immunotherapy due to its high efficiency, safety, and effectiveness. A stable and effective delivery system is needed to protect mRNAs from nuclease degradation while also enhancing immunogenicity. The success of mRNA lipid nanoparticles in treating COVID-19, to a certain extent, marks a milestone for mRNA vaccines and also promotes further research on mRNA delivery systems. Here, we explore mRNA vaccine delivery systems, especially lipid nanoparticles (LNPs), considering the current research status, prospects, and challenges of lipid nanoparticles, and explore other mRNA delivery systems.

Cytisine: State of the art in pharmacological activities and pharmacokinetics.

Cytisine is a naturally occurring bioactive compound, an alkaloid mainly isolated from legume plants. In recent years, various biological activities of cytisine have been explored, showing certain effects in smoking cessation, reducing drinking behavior, anti-tumor, cardiovascular protection, blood sugar regulation, neuroprotection, osteoporosis prevention and treatment, etc. At the same time, cytisine has the advantages of high efficiency, safety, and low cost, has broad development prospects, and is a drug of great application value. However, a summary of cytisine's biological activities is currently lacking. Therefore, this paper summarizes the pharmacological action, mechanism, and pharmacokinetics of cytisine by referring to numerous databases, and analyzes the new and core targets of cytisine with the help of computer simulation technology, to provide reference for doctors.

Modulation Engineering of Electromagnetic Wave Absorption Performance of Layered Double Hydroxides Derived Hollow Metal Carbides Integrating Corrosion Protection.

Layered double hydroxides (LDHs) with unique layered structure and atomic composition are limited in the field of electromagnetic wave absorption (EMA) due to their poor electrical conductivity and lack of dielectric properties. In this study, the EMA performance and anticorrosion of hollow derived LDH composites are improved by temperature control and composition design using ZIF-8 as a sacrifice template. Diverse regulation modes result in different mechanisms for EMA. In the temperature control process, chemical reactions tune the composition of the products and construct a refined structure to optimize the LDHs conductivity loss. Additionally, the different phase interfaces generated by the control components optimize the impedance matching and enhance the interfacial polarization. The results show that the prepared NCZ (Ni3ZnC0.7/Co3ZnC@C) has a minimum reflection loss (RLmin ) of -58.92 dB with a thickness of 2.4 mm and a maximum effective absorption bandwidth (EABmax ) of 7.36 GHz with a thickness of 2.4 mm. Finally, due to its special structure and composition, the sample exhibits excellent anticorrosion properties. This work offers essential knowledge for designing engineering materials derived from metal organic framework (MOF) with cutting-edge components and nanostructures.

Characterization of Fusarium verticillioides Med1 LxxLL Motif Involved in Fumonisin Biosynthesis.

The Med1 transcriptional coactivator is a crucial component of the Mediator middle complex, which regulates the expression of specific genes involved in cell development, differentiation, reproduction, and homeostasis. The Med1 LxxLL motif, a five-amino-acid peptide sequence, is essential for Med1-mediated gene expression. Our previous study revealed that the disruption of the Med1 subunit leads to a significant increase in fumonisin B1 (FB1) production in the maize pathogen Fusarium verticillioides. However, our understanding of how Med1 regulates FB1 biosynthesis in F. verticillioides, particularly through the Med1 LxxLL motifs, remains limited. To characterize the role of LxxLL motifs, we generated a series of Med1 LxxLL deletion and amino acid substitution mutants. These mutants exhibited impaired mycelial growth and conidia germination while demonstrating enhanced conidia production and virulence. Similar to the Med1 deletion mutant, Med1 LxxLL motif mutants also exhibited increased FB1 biosynthesis in F. verticillioides. Proteomic profiling revealed that the Med1 LxxLL motif regulated the biosynthesis of several key substances that affected FB1 production, including starch and carotenoid. Subsequent studies demonstrated that the production of amylopectin, which is strongly linked to FB1 biosynthesis, was significantly increased in Med1 LxxLL motif mutants. In addition, the disruption of carotenoid metabolic genes decreased carotenoid content, thus stimulating FB1 biosynthesis in F. verticillioides. Taken together, our results provide valuable insights into how the Med1 LxxLL motif regulates FB1 biosynthesis in the mycotoxigenic fungus F. verticillioides.

Banxia Xiexin decoction: A review on phytochemical, pharmacological, clinical and pharmacokinetic investigations.

Banxia Xiexin decoction (BXD), a famous traditional Chinese prescription constituted by Pinelliae Rhizoma, Zingiberis Rhizoma, Scutellariae Radix, Coptidis Rhizoma, Ginseng Radix et Rhizoma, Jujubae Fructus and Glycyrrhizae Radix et Rhizoma Praeparata Cum Mell, has notable characteristics of acrid-opening, bitter down-bearing and sweet-tonification, interfering with tumors, gastrointestinal diseases, central nervous system diseases and much more. Based on the wide clinical applications, current investigations of BXD focused on several aspects: chemical analysis to explore the underlying substrates responsible for the therapeutic effects; basic studies on pharmacological actions of the whole prescription or of those representative ingredients to demonstrate the intriguing molecular targets for specific pathological processes; pharmacokinetic feature studies of single or all components of BXD to reveal the chemical basis and synergistic actions contributing to the pharmacological and clinically therapeutic effects. In this review, we summarized the main achievements of phytochemical, pharmacological, clinical and pharmacokinetic profiles of BXD and its herbal or pharmacologically active chemicals, as well as discussions of our understanding which further reveals the significance of BXD clinically.

The Mechanism of bnAb Production and Its Application in Mutable Virus Broad-Spectrum Vaccines: Inspiration from HIV-1 Broad Neutralization Research.

Elite controllers among HIV-1-infected individuals have demonstrated a stronger ability to control the viral load in their bodies. Scientists have isolated antibodies with strong neutralizing ability from these individuals, which can neutralize HIV-1 variations; these are known as broadly neutralizing antibodies. The nucleic acid of some viruses will constantly mutate during replication (such as SARS-CoV-2), which will reduce the protective ability of the corresponding vaccines. The immune escape caused by this mutation is the most severe challenge faced by humans in the battle against the virus. Therefore, developing broad-spectrum vaccines that can induce broadly neutralizing antibodies against various viruses and their mutated strains is the best way to combat virus mutations. Exploring the mechanism by which the human immune system produces broadly neutralizing antibodies and its induction strategies is crucial in the design process of broad-spectrum vaccines.

Construction of Self-Assembly Based Tunable Absorber: Lightweight, Hydrophobic and Self-Cleaning Properties.

Although multifunctional aerogels are expected to be used in applications such as portable electronic devices, it is still a great challenge to confer multifunctionality to aerogels while maintaining their inherent microstructure. Herein, a simple method is proposed to prepare multifunctional NiCo/C aerogels with excellent electromagnetic wave absorption properties, superhydrophobicity, and self-cleaning by water-induced NiCo-MOF self-assembly. Specifically, the impedance matching of the three-dimensional (3D) structure and the interfacial polarization provided by CoNi/C as well as the defect-induced dipole polarization are the primary contributors to the broadband absorption. As a result, the prepared NiCo/C aerogels have a broadband width of 6.22 GHz at 1.9 mm. Due to the presence of hydrophobic functional groups, CoNi/C aerogels improve the stability in humid environments and obtain hydrophobicity with large contact angles > 140°. This multifunctional aerogel has promising applications in electromagnetic wave absorption, resistance to water or humid environments.

Pseudotyped Viruses.

Pseudotyped viruses have been constructed for many viruses. They can mimic the authentic virus and have many advantages compared to authentic viruses. Thus, they have been widely used as a surrogate of authentic virus for viral function analysis, detection of neutralizing antibodies, screening viral entry inhibitors, and others. This chapter reviewed the progress in the field of pseudotyped viruses in general, including the definition and the advantages of pseudotyped viruses, their potential usage, different strategies or vectors used for the construction of pseudotyped viruses, and factors that affect the construction of pseudotyped viruses.

Vacuole Proteins with Optimized Microtubule Assembly Is Required for Fum1 Protein Localization and Fumonisin Biosynthesis in Mycotoxigenic Fungus Fusarium verticillioides.

Fumonisin contamination of corn caused by Fusarium verticillioides is a major concern worldwide. While key genes involved in fumonisin biosynthesis are known, the location within the fungal cell where this process occurs has yet to be fully characterized. In this study, three key enzymes, i.e., Fum1, Fum8, and Fum6, associated with early steps of fumonisin biosynthesis pathway, were tagged with GFP, and we examined their cellular localization. Results showed that these three proteins co-localized with the vacuole. To further understand the role of the vacuole in fumonisin B1 (FB1) biosynthesis, we disrupted two predicted vacuole associated proteins, FvRab7 and FvVam7, resulting in a significant reduction of FB1 biosynthesis and a lack of Fum1-GFP fluorescence signal. Furthermore, we used the microtubule-targeting drug carbendazim to show that proper microtubule assembly is critical for proper Fum1 protein localization and FB1 biosynthesis. Additionally, we found that α1 tubulin is a negative regulator in FB1 biosynthesis. We concluded that vacuole proteins with optimized microtubule assembly play a crucial role in proper Fum1 protein localization and fumonisin production in F. verticillioides.

Substitution of gp120 C4 region compensates for V3 loss-of-fitness mutations in HIV-1 CRF01_AE co-receptor switching.

HIV-1 infection is mediated by a viral envelope subsequently binding to CD4 receptor and two main coreceptors, CCR5 (R5) for primary infection and CXCR4 (X4) in chronic infection. Switching from R5 to X4 tropism in HIV-1 infection is associated with increased viral pathogenesis and disease progression. The coreceptor switching is mainly due to variations in the V3 loop, while the mechanism needs to be further elucidated. We systematically studied the determinant for HIV-1 coreceptor switching by substitution of the genes from one R5 and one X4 pseudoviruses. The study results in successfully constructing two panels of chimeric viruses of R5 to X4 forward and X4 to R5 reverse switching. The determinants for tropism switching are the combined substitution of the V3 loop and C4 region of the HIV-1 envelope. The possible mechanism of the tropism switching includes two components, the V3 loop to enable the viral envelope binding to the newly switched coreceptor and the C4 region, to compensate for the loss of fitness caused by deleterious V3 loop mutations to maintain the overall viral viability. The combined C4 and V3 substitution showed at least an eightfold increase in replication activity compared with the pseudovirus with only V3 loop substitution. The site-directed mutations of N425R and S440-I442 with charged amino acids could especially increase viral activity. This study could facilitate HIV-1 phenotype surveillance and select right entry inhibitor, CCR5 or CXCR4 antagonists, for antiviral therapy.

Comparative pharmacokinetics of four major flavonoids in normal and chronic gastritis rats after oral administration of different combinations of Banxia Xiexin decoction.

Chronic gastritis (CG) has become a major threat to human health. Banxia Xiexin Decoction (BXXXD) has been used clinically to treat gastritis by acting on the spleen and stomach for thousands of years. Baicalin, wogonoside, liquiritin and liquiritigenin are the main bioactive flavonoids of BXXXD. A rapid, sensitive and selective HPLC-triple quadrupole (TQ)-MS/MS method was developed to simultaneously quantify the four flavonoids in rat plasma in this study. With salidroside as internal standard (IS), plasma samples were extracted and separated on a Welch HPLC XB-C18 column (2.1 × 50 mm, 1.8 µm) using gradient elution. The optimized gradient of the mobile phase consisted of water (containing 0.1% formic acid) (A) and methanol (B) was used. Detection was implemented in multiple reaction monitoring mode with an electrospray negative ionization source. The comparative pharmacokinetics of four analytes in normal and CG rats after oral administration of BXXXD or its different compatibilities were first investigated. The results indicated that the pharmacokinetic behaviors of analytes were obviously changed in CG rats. From the comparison between the whole prescription group and the compatibility groups, it was found that the pharmacokinetic behavior of analytes also changed to some extent. The pharmacokinetic alterations of analytes might be due to the pathological conditions of CG.

Gegen Qinlian Decoction Relieves Ulcerative Colitis via Adjusting Dysregulated Nrf2/ARE Signaling.

Objective: Oxidative stress has been proven to be essential in the pathogenesis of ulcerative colitis (UC). Therefore, this study was designed to investigate the effect of Gegen Qinlian decoction (GQ) on the Nrf2 pathway in the treatment of UC and explore the potential mechanism. Methods: The UC rat model was induced by 5% dextran sodium sulfate (DSS) aqueous solution, and UC rats were treated with GQ orally. The effect of GQ on UC rats was recorded. Human clonal colon adenocarcinoma cells (Caco-2) stimulated by tumor necrosis factor-α (TNF-α) were employed in this study. After being stimulated with TNF-α for 2 hours, Caco-2 cells were cultured with GQ or its major components (puerarin, baicalin, berberine, and liquiritin) for 22 hours. In addition, the Nrf2 gene of Caco-2 cells was silenced and then cultured with GQ for 22 hours. The contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in colonic tissues and Caco-2 cells were detected by assay kits. Reactive oxygen species (ROS) in Caco-2 cells were analyzed by flow cytometry. Quantitative real-time PCR and western blot were employed to detect the mRNA and protein expression of Nrf2 and its related target genes in colon tissues and Caco-2 cells. Results: GQ alleviated the injured colonic mucosa and activated the expression of Nrf2 in UC rats. In TNF-α stimulated Caco-2 cells and Nrf2 silenced Caco-2 cells, GQ also reversed the inhibitory effect of Nrf2. Furthermore, the major components of GQ could activate Nrf2 signaling in TNF-α stimulated cells as well. Moreover, the contents of SOD, GSH, MDA, and ROS were restored to normal after treatment with GQ or its major components. Among these components, puerarin, berberine, and liquiritin appear to have a better effect on activating Nrf2 in vitro. Overall, GQ can alleviate UC by increasing the activity of Nrf2/ARE signaling and enhancing the effect of antioxidant stress.

Distinct Function of Mediator Subunits in Fungal Development, Stress Response, and Secondary Metabolism in Maize Pathogen Fusarium verticillioides.

Mediator is a nucleus-localized, multisubunit protein complex highly conserved across eukaryotes. It interacts with RNA polymerase II transcription machinery as well as various transcription factors to regulate gene expression. However, systematic characterization of the Mediator complex has not been performed in filamentous fungi. In our study, the goal was to investigate key biological functions of Mediator subunits in a mycotoxigenic plant pathogen Fusarium verticillioides. Although there is some level of divergence in the constituent subunits, the overall structure was conserved between Saccharomyces cerevisiae and F. verticillioides. We generated 11 Mediator subunit deletion mutants and characterized vegetative growth, conidia formation, environmental stress response, carbon and fatty acid use, virulence, and fumonisin B1 (FB1) biosynthesis. Each Mediator subunit deletion mutant showed deficiencies in at least three of the phenotypes tested, suggesting that each subunit has different principal functions in F. verticillioides development, metabolism, and virulence. The deletion of FvMed1 led to increased FB1 production, and we confirmed that FvMed1 is transported from the nucleus to the cytoplasm under fumonisin-producing conditions. Taken together, our study characterized various important functional roles for Mediator subunits in F. verticillioides and suggests that select subunits can perform unique cytoplasmic functions independent of the core Mediator in fungal nucleus.

Long noncoding RNA RP11-909N17.2 presages a poor prognosis of non-small cell lung cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) were detected extraordinarily expressed in various tumors and could combine with microRNAs (miRNAs) to play important role in tumor cells. This study is to explore the role of lncRNA RP11-909N17.2 in NSCLC and discuss in what way it functions in NSCLC. METHODS: 120 NSCLC patients were enlisted in this study. Expression levels of lncRNA RP11-909N17.2 and miR-767-3p were detected and the correlation between lncRNA RP11-909N17.2 expression and the clinical data characteristics was analyzed. Prognosis potential of lncRNA RP11-909N17.2 was inferred with Kaplan-Meier and multivariate Cox regression assays. Biological functions of NSCLC cells were accessed by cell counting Kit-8, transwell migration and invasion assay. Mechanism of RP11-909N17.2 action on NSCLC cells was investigated by luciferase activity assay with wide-type or mutation. RESULTS: LncRNA RP11-909N17.2 has an ascendant expression while miR-767-3p has descended one in NSCLC tissue specimens and cells. Over-expression of lncRNA RP11-909N17.2 can shorten the overall survival period of NSCLC patients when compared with low expression. Knockdown of lncRNA RP11-909N17.2 suppressed biology function of NSCLC cell including proliferation, migration, and invasion. CONCLUSION: LncRNA RP11-909N17.2 can be developed into a prognostic index for NSCLC. LncRNA RP11-909N17.2 plays a promoting role in NSCLC cells possibly by binding miR-767-3p as a sponge.

Isolated Arthroscopic Partial Meniscectomy Is More Effective at Improving Meniscal Symptoms in Comparison With Mechanical Symptoms in Patients With Concomitant Untreated Chondral Lesions.

PURPOSE: To rank Knee Injury and Osteoarthritis Outcome Score (KOOS) questions from most to least improvement after arthroscopic partial meniscectomy (APM) and compare improvement of meniscal versus mechanical symptoms. METHODS: A secondary analysis of the Chondral Lesions and Meniscus Procedures (ChAMP) Trial was performed. Inclusion criteria were age 30 years or older with degenerative meniscal tear failing nonoperative management, with or without associated unstable chondral lesions. No chondral debridement was performed. Responses to the 42 KOOS questions ranged from 0 (extreme problems) to 4 (no problems), and were answered preoperatively and at 1 year after isolated APM. The 1-year mean change, or delta (Δ), was calculated for each KOOS question and the Δ for meniscal and mechanical symptoms were statistically compared. RESULTS: Greatest improvement in 135 eligible patients was observed for questions about (1) awareness of knee problems (Δ = 1.93, standard deviation [SD] = 1.38), (2) frequency of knee pain (Δ = 1.93, SD = 1.29), (3) degree of difficulty while twisting/pivoting on the injured knee (Δ = 1.88, SD = 1.13), (4) degree of difficulty while running (Δ = 1.67, SD = 1.30), and (5) being troubled by lack of confidence in the knee (Δ = 21.67, SD = 1.11). Least improvement was observed for questions about: (1) degree of difficulty while getting on/off the toilet (Δ = 0.94, SD = 0.96), (2) feel grinding or hear clicking when the knee moves (Δ= 0.90, SD = 1.25), 3) degree of difficulty while getting in/out of the bath (Δ= 0.88, SD = 1.00), (4) knee catches/hangs up during movement (Δ= 0.80, SD = 1.09), and (5) the ability to straighten the knee fully (Δ= 0.54, 1.44). There was greater improvement for the KOOS questions pertaining to meniscal versus mechanical symptoms (P < .00001). CONCLUSIONS: KOOS symptoms as reported by subjects' responses to the questions pertaining to the frequency of knee pain, twisting/pivoting, running, squatting, and jumping showed the most improvement 1 year after isolated APM, whereas those relating to mechanical symptoms improved the least. Focusing on meniscal rather than mechanical symptoms may help surgeons better identify patients expected to benefit from APM. LEVEL OF EVIDENCE: IV, retrospective analysis of prospectively collected data.

Better Outcomes but No Difference in Joint Space Narrowing at Five Years Among Patients Without Unstable Chondral Lesions Versus Those With Unstable Chondral Lesions (Left In Situ) at the Time of Arthroscopic Partial Meniscectomy.

PURPOSE: To compare 5-year outcomes among patients with and without unstable chondral lesions undergoing arthroscopic partial meniscectomy (APM). METHODS: Using data from the Chondral Lesions And Meniscal Procedures (ChAMP) Trial, we compared outcomes for patients with unstable chondral lesions found at the time of APM and left in situ (CL-noDeb, N = 71) versus patients without unstable chondral lesions (NoCL, N = 47) at 5 years after APM. Outcomes included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), visual analog pain scale, Short-form Health Survey (SF-36), physical knee measurements, progressive joint space narrowing on radiographs, and the rate of additional knee surgery. Multivariate linear regression was used to obtain mean differences (MDs) with corresponding 95% confidence intervals (CIs) adjusted for age, body mass index, and preoperative score (for postoperative scores). RESULTS: Compared with CL-noDeb, NoCL subjects had significantly greater improvement at 5 years in the KOOS score for function in sport and recreation (MD = 9.9 [95% CI, 0.7-19.1]), SF-36 pain (MD = 13.9 [95% CI, 5.5-22.3]), knee extension (MD = 0.8 [95% CI, 0.1-1.5]), and decreased quadriceps circumference at the mid-portion of the patella (MD = -1.5 [95% CI, -2.7 to -0.3). A greater proportion of patients in the NoCL group achieved the MCID for all outcome scores except for the WOMAC pain score (89% CL-NoDeb vs 87% NoCL) and SF-36 general (29% CL-NoDeb vs 23% NoCL). There were no significant group differences in measures of progressive radiographic joint space narrowing in any compartments of the operative knee and no significant difference in the rate of additional knee surgery within 5 years of the initial APM. CONCLUSIONS: Patients undergoing APM without unstable chondral lesions had statistically significantly better outcomes than patients with unstable chondral lesions at 5 years after surgery; however, there were no group differences in progressive radiographic joint space narrowing. LEVEL OF EVIDENCE: Level II, prospective comparative study.