Percutaneous Image-Guided Microwave Ablation for Treating Postsurgical Intrapulmonary Oligometastases or Oligorecurrence.

OBJECTIVE: To assess the clinical efficacy of microwave ablation (MWA) in treating tumour patients with postsurgical intrapulmonary oligometastases or oligorecurrence (PIORO). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Departments of Thoracic Surgery and Oncology, Jinan Central Hospital and Qilu Hospital, Jinan, China, from January 2014 to June 2023. METHODOLOGY: Clinical data of 31 patients with PIORO receiving treatment with MWA were retrospectively analysed. After undergoing MWA, the patients were followed up for computed tomography (CT) examination on the 7th day, 1st month, and every 3 months, respectively. The Kaplan-Meier method was conducted to evaluate the clinical outcomes; overall survival (OS), progression-free survival (PFS), and time to local progression (TTLP). RESULTS: All patients with PIORO were successfully treated with MWA. The 3-year survival rate of patients was 35.5%. The median OS was 26.0 months, the median PFS was 11.1 months, and the median TTLP was 14.4 months. Patients with oligometastatic or oligorecurrent tumours ≤3 cm in diameter showed better PFS (≤3 cm, 14.261 m vs. >3 cm, 7.786 m; p <0.01) and TTLP (≤3 cm, 19.522 m vs. >3 cm, 12.214 m; p <0.05) than those with tumours >3 cm in diameter. Clinical characteristics of the patients were not significantly correlated with OS. CONCLUSION: MWA, as a topically therapeutic method, is an effective procedure for tumour patients with PIORO, especially in cases of oligometastatic or oligorecurrent tumours ≤3 cm in diameter. KEY WORDS: Microwave ablation, Thermal ablation, Oligometastases, Oligorecurrence, Progression-free survival, Survival.

Cellular and molecular mechanisms of oroxylin A in cancer therapy: Recent advances.

Seeking an effective and safe scheme is the common goal of clinical treatment of tumor patients. In recent years, traditional Chinese medicine has attracted more and more attention in order to discover new drugs with good anti-tumor effects. Oroxylin A (OA) is a compound found in natural Oroxylum indicum and Scutellaria baicalensis Georgi plants and has been used in the treatment of various cancers. Studies have shown that OA has a wide range of powerful biological activities and plays an important role in neuroprotection, anti-inflammation, anti-virus, anti-allergy, anti-tumor and so on. OA shows high efficacy in tumor treatment. Therefore, it has attracted great attention of researchers all over the world. This review aims to discuss the anti-tumor effects of OA from the aspects of cell cycle arrest, induction of cell proliferation and apoptosis, induction of autophagy, anti-inflammation, inhibition of glycolysis, angiogenesis, invasion, metastasis and reversal of drug resistance. In addition, the safety and toxicity of the compound were also discussed. As a next step, to clarify the benefits and adverse effects of Oroxylin A in cancer patients further experiments, especially clinical trials, are needed.

Pan-cancer and single-cell analysis reveal THRAP3 as a prognostic and immunological biomarker for multiple cancer types.

Background: Thyroid hormone receptor-associated protein 3 (THRAP3) is of great significance in DNA damage response, pre-mRNA processing, and nuclear export. However, the biological activities of THRAP3 in pan-cancer remain unexplored. We aimed to conduct a comprehensive analysis of THRAP3 and validate its expression levels in lung cancer. Methods: A pan-cancer analysis was conducted to study the correlation of THRAP3 expression with clinical outcome and the tumor microenvironment based on the available bioinformatics databases. The protein levels of THRAP3 were explored in lung cancer by immunohistochemistry (IHC) analysis. Single-cell sequencing (ScRNA-seq) analysis was employed to investigate the proportions of each cell type in lung adenocarcinoma (LUAD) and adjacent normal tissues, along with the expression levels of THRAP3 within each cell type. Results: THRAP3 is upregulated in multiple cancer types but exhibits low expression in lung squamous cell carcinoma (LUSC). immunohistochemistry results showed that THRAP3 is a lowly expression in LUAD and LUSC. THRAP3 elevation had a poor prognosis in kidney renal clear cell carcinoma and a prolonged survival time in kidney chromophobe, brain lower-grade glioma and skin cutaneous melanoma, as indicated by the KM curve. Single-cell analysis confirmed that the proportions of T/B cells, macrophages, and fibroblasts were significantly elevated in LUAD tissues, and THRAP3 is specifically overexpressed in mast cells. Conclusion: Our findings uncover that THRAP3 is a promising prognostic biomarker and immunotherapeutic target in multiple cancers, but in LUAD and LUSC, it may be a protective gene.

Recent Advances in Natural Products with Anti-Leukemia and Anti-Lymphoma Activities.

Leukemia and lymphoma are the most common blood cancers, which pose a critical threat to the health of adults and children. The total incidence and mortality rates of both are approximately 6% globally. Compared with the expensive cost of CAR T cell therapy, natural products from animals, plants and microorganisms have the characteristics of wide-range sources and costeffectiveness in the treatment of cancer. Moreover, the drug resistance that emerged in leukemia and lymphoma treatments shows an urgent need for new drugs. However, in addition to the natural products that have been marketed in the treatment of leukemia and lymphoma, there have been a large number of studies on natural products that fight blood cancer in recent years. This review summarized the recent studies on natural compounds with anti-lymphoma and anti-leukemia activities, hoping to provide novel weapons into the drug development arsenal.

Recent Advances in Xanthine Oxidase Inhibitors.

Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives, and imidazole derivatives, hoping to provide valuable information for the research and development of novel xanthine oxidase inhibitors.

The effectiveness of problem-based learning compared with lecture-based learning in surgical education: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted to systematically evaluate the impact of problem-based learning (PBL) and lecture-based learning (LBL) teaching models on students' learning in surgical education. METHODS: We systematically searched the publications related to the application of PBL and LBL in surgical courses in PubMed, Embase, Web of Science and Cochrane Library databases, the last retrieval time is September 20, 2022. After screening the literature according to the inclusion and exclusion criteria, extracting data and evaluating the methodological treatment of the included studies, Stata 17.0 software was used to perform meta-analysis. RESULTS: Nine studies were included totally. The results showed that compared with LBL, PBL was superior in clinical competence (SMD = 0.81, 95% CI: 0.12 ~ 1.49, P = 0.020) and student satisfaction (SMD = 2.13, 95% CI: 1.11 ~ 3.15, P < 0.0001) with significant differences. But the comprehensive scores (SMD = 0.26, 95% CI: -0.37 ~ 0.89, P = 0.421) and theoretical knowledge (SMD=-0.19, 95% CI: -0.71 ~ 0.33, P = 0.482) to PBL and LBL had no significant difference. CONCLUSION: This study showed that the PBL teaching model is more effective than the LBL teaching model in surgical education on the aspects of enhancing clinical competence and student satisfaction. However, further well-designed studies are needed to confirm our findings.

Mucin 1 expression correlation with lymph node metastasis and micrometastasis and poor prognosis in patients with esophageal squamous cell carcinomas.

Introduction: Lymph node metastasis (LNM) and lymph node micrometastasis (LNMM) are prognostic factors in esophageal squamous cell carcinoma (ESCC) patients. The purpose of this research is to investigate whether mucin 1 expression detected by immunohistochemistry in lymph nodes correlates with LNM, LNMM and prognosis in ESCC patients. Material and methods: There were 92 ESCC patients enrolled in the research, and 1382 lymph nodes were obtained from these 92 patients. All lymph nodes were immunohistochemically analyzed using an anticytokeratin and mucin 1 antibody cocktail. Results: In the pN1-2 patients' group, 68 lymph nodes from 15 patients had tumor metastasis. All these 68 tumor metastatic lymph nodes were positive for mucin 1. Mucin 1 was detected in another 231 lymph nodes and among them, 3 (3/231 1.3%) lymph nodes from 2 (2/15 13.3%) patients were positive for mucin 1. In 77 pN0 patients, mucin 1 was detected in 1083 lymph nodes from the 77 patients; 17 (17/1083 1.6%) lymph nodes from 15 (15/77 19.5%) patients were positive for mucin 1. The 5-year survival rate was 39.1%, and it was significantly related to tumor invasion (pT, p < 0.05), lymph node metastasis (pN, p < 0.01), pTNM stage (p < 0.01) and mucin 1 expression (p < 0.01). Cox regression of multivariate analysis demonstrated that mucin 1 expression and pT were independent prognostic factors. Conclusions: Mucin 1 expression was related to LNM and LNMM and poor prognosis in ESCC patients. Immunohistochemistry for mucin 1 can be applied for the detection of LNM and LNMM.

Association between CD8+ tumor-infiltrating lymphocytes and prognosis of non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis.

BACKGROUND: A meta-analysis method was used to investigate the prognostic value of CD8+ tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors. METHODS: A database search of PubMed, Embase, Web of Science and Cochrane Library up until 7 February, 2023. A clinical study on the relationship between CD8+ TILs and PD-1/PD-L1 inhibitors in the therapeutics of NSCLC. RevMan 5.3 and StataMP 17.0 software were used for meta-analysis. The outcome indicators incorporated overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). RESULTS: Nineteen articles with 1488 patients were included. The analysis results showed that high CD8+ TILs were associated with better OS (HR = 0.60, 95% CI: 0.46-0.77; P < 0.0001), PFS (HR = 0.68, 95% CI: 0.53-0.88; P = 0.003) and ORR (OR = 2.26, 95% CI: 1.52-3.36; P < 0.0001) in NSCLC patients treated with PD-1/PD-L1 inhibitors. Subgroup analysis indicated that patients with high CD8+ TILs had good clinical prognostic benefits whether the location of CD8+ TILs was intratumoral or stromal, and compared with East Asian, high CD8+ TILs in Caucasians showed a better prognosis. High CD8+ TILs in peripheral blood did not improve OS (HR = 0.83, 95% CI: 0.69-1.01; P = 0.06) and PFS (HR = 0.93, 95% CI: 0.61-1.14; P = 0.76) in NSCLC patients receiving PD-1/PD-L1 inhibitors. CONCLUSION: In spite of the location of CD8+ TILs, high densities of CD8+ TILs were predictive of treatment outcomes in NSCLC patients treated with PD-1/PD-L1 inhibitors. However, high CD8+ TILs in peripheral blood had no predictive effect.

Clinical and prognostic features of E-cadherin in adenocarcinoma of the esophagogastric junction patients.

OBJECTIVE: The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value. METHODS: A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan-Meier survival curves and multifactorial Cox regression analysis. RESULTS: In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade ( P = 0.013), infiltration depth ( P = 0.033), and clinicopathological stage ( P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression ( P = 0.037), tumor differentiation ( P = 0.010), lymph node metastasis ( P < 0.001), and clinicopathological stage ( P = 0.037). Tumor differentiation ( P = 0.033) and lymph node metastasis ( P = 0.001) were independent risk factors for shorter overall survival. CONCLUSION: E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.

The enhanced effect of magnetism on the thermoelectric performance of a CrI3 monolayer.

The effect of magnetism on the thermoelectric (TE) transformation efficiency has recently attracted a lot of attention. A CrI3 monolayer is a two-dimensional (2D) ferromagnetic (FM) semiconductor with a Curie temperature of 45 K. In this work, we employed first-principles calculations within the framework of density functional theory (DFT) combined with the non-equilibrium Green's function (NEGF) method and Landauer-Buttiker theory to study the effect of magnetism on the TE performance of a CrI3 monolayer. The stability, electronic structures, density of states (DOS) and TE parameters of a CrI3 monolayer are calculated. Our calculation results indicate that the TE performance of a CrI3 monolayer in a FM state is superior to that in a non-magnetic (NM) state. Namely, magnetism is beneficial to improving the TE performance. To further investigate the physical mechanism, the phonon group velocity, the electronic and phonon transmission spectra and the effective mass of a CrI3 monolayer in FM and NM states are analyzed in detail. For a CrI3 monolayer in a NM state, the maximum ZT value at 40 K is 0.09 and 0.16 for p-type and n-type doping, respectively. Relative to that in a NM state, the maximum ZT of a CrI3 monolayer in a FM state is largely improved, and can reach 0.23 and 1.58 for p-type and n-type doping. Our research provides a valuable reference by showing that magnetism is a possible factor for improving the TE efficiency.

Clinicopathological Significance of STAT3 and p-STAT3 among 91 Patients with Adenocarcinoma of the Esophagogastric Junction.

Adenocarcinoma of the esophagogastric junction (AEG) has increased rapidly worldwide during the last few decades. The purpose of this study is to investigate the clinical and prognostic characteristics of signal transduction and activator of transcription factor 3(STAT3) and phosphorylated STAT3 (p-STAT3) expression in AEG patients. We retrospectively analyzed the immunohistochemical results of 61 AEG patients and followed up for 5 years, while Western blot was performed on tissues from another 30 AEG patients. The results showed that STAT3 and p-STAT3 were overexpressed in AEG tissues (P < 0.05, P < 0.01). The high expression of STAT3 was significantly associated with the pTNM stage (P < 0.05), and the increased expression of p-STAT3 was significantly associated with depth of invasion (pT), lymph node metastasis (pN), and pTNM stage (P < 0.05, P < 0.05, P < 0.05). The 5-year survival rate for AEG patients was 41.0% and was significantly associated with tumor differentiation, pN, pTNM, and p-STAT3 (P < 0.05, P < 0.01, P < 0.05, P < 0.01). Cox regression analysis confirmed that tumor differentiation, pN, and high expression of p-STAT3 were independent risk factors for the 5-year survival rate in patients with AEG (P < 0.05, P < 0.01, P < 0.05). Our study showed that STAT3 and p-STAT3 play a critical role in AEG development.

Molecular mechanism, regulation, and therapeutic targeting of the STAT3 signaling pathway in esophageal cancer (Review).

Esophageal cancer (EC) is the seventh most common cancer globally, and the overall 5­year survival rate is only 20%. Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in EC, and its activation is associated with a poor prognosis. STAT3 can be activated by canonical pathways such as the JAK/STAT3 pathway as well as non­canonical pathways including the Wnt/STAT3 and COX2/PGE2/STAT3 pathways. Activated STAT3, present as phosphorylated STAT3 (p­STAT3), can be transported into the nucleus to regulate downstream genes, including VEGF, cyclin D1, Bcl­xL, and matrix metalloproteinases (MMPs), to promote cancer cell proliferation and induce resistance to therapy. Non­coding RNAs, including microRNAs (miRNAs/miRs), circular RNAs (circRNAs), and long non­coding RNAs (lncRNAs), play a vital role in regulating the STAT3 signaling pathway in EC. Several miRNAs promote or suppress the function of STAT3 in EC, while lncRNAs and circRNAs primarily promote the effects of STAT3 and the progression of cancer. Additionally, various drugs and natural compounds can target STAT3 to suppress the malignant behavior of EC cells, providing novel insights into potential EC therapies.

Comparison of the BOPPPS model and traditional instructional approaches in thoracic surgery education.

BACKGROUND: BOPPPS (bridge-in, learning objective, pretest, participatory learning, posttest, and summary) is a student-centered modular teaching model that improves classroom teaching effectiveness. This study's primary aim was to explore whether the BOPPPS model has advantages over traditional instructional approaches in teaching lung cancer courses to clinical medical interns. METHODS: A total of 88 students majoring in clinical medicine of Shandong First Medical University and Shandong University, who had clinical practice in thoracic surgery from January 2018 to December 2019, were divided into two groups, receiving the same lung cancer teaching content. The experimental group (n = 44) utilized the BOPPPS model, while the control group (n = 44) used the traditional instructional approach. A questionnaire was used to attain the students' satisfaction and self-evaluation of the course, and a post-study examination was used to assess end-of-course performance. RESULTS: The experimental group's theoretical examination scores with the BOPPPS teaching model were significantly higher than those in the control group. Students preferred the BOPPPS model more than the traditional instructional approach in course satisfaction, student-teacher interaction, learning initiative, analytical ability, clinical thinking ability, and self-study ability (p < 0.05). CONCLUSIONS: Compared with the traditional instructional approach. The BOPPPS model can better inspire clinical medical students' enthusiasm for thoracic surgery and enhance the students' comprehensive ability. In a word, the BOPPPS model has better teaching effectiveness in the clinical teaching practice of thoracic surgery, which is worthy of reference and popularization.

Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.

According to the latest statistics from the International Agency for Research on Cancer (IARC), lung cancer is one of the most lethal malignancies in the world, accounting for approximately 18% of all cancer-associated deaths. Yet, even with aggressive interventions for advanced lung cancer, the five-year survival rate remains low, at around 15%. The hedgehog signaling pathway is highly conserved during embryonic development and is involved in tissue homeostasis as well as organ development. However, studies have documented an increasing prevalence of aberrant activation of HH signaling in lung cancer patients, promoting malignant lung cancer progression with poor prognostic outcomes. Inhibitors targeting the HH pathway have been widely used in tumor therapy, however, they still cannot avoid the occurrence of drug resistance. Interestingly, natural products, either alone or in combination with chemotherapy, have greatly improved overall survival outcomes for lung cancer patients by acting on the HH signaling pathway because of its unique and excellent pharmacological properties. In this review, we elucidate on the underlying molecular mechanisms through which the HH pathway promotes malignant biological behaviors in lung cancer, as well as the potential of inhibitors or natural compounds in targeting HH signaling for clinical applications in lung cancer therapy.

The molecular mechanism of METTL3 promoting the malignant progression of lung cancer.

Lung cancer remains one of the major causes of cancer-related death globally. Recent studies have shown that aberrant m6A levels caused by METTL3 are involved in the malignant progression of various tumors, including lung cancer. The m6A modification, the most abundant RNA chemical modification, regulates RNA stabilization, splicing, translation, decay, and nuclear export. The methyltransferase complex plays a key role in the occurrence and development of many tumors by installing m6A modification. In this complex, METTL3 is the first identified methyltransferase, which is also the major catalytic enzyme. Recent findings have revealed that METTL3 is remarkably associated with different aspects of lung cancer progression, influencing the prognosis of patients. In this review, we will focus on the underlying mechanism of METT3 in lung cancer and predict the future work and potential clinical application of targeting METTL3 for lung cancer therapy.

[Characteristics of VOCs and Formation Potentials of O3 and SOA in Autumn and Winter in Tongchuan, China].

Volatile organic compounds (VOCs) are the main precursors of tropospheric O3 and secondary organic aerosol (SOA), which can enhance atmospheric oxidation, promote the formation of secondary pollutants, and affect regional air quality and human health. In order to gain insights on VOCs characteristics and their potentials for O3 and SOA formation, the volume fraction of 102 VOCs in autumn and winter in the urban area of Tongchuan were monitored using the TH-300B online monitoring system. The maximum incremental reactivity (MIR) coefficient and the fractional aerosol coefficient (FAC) were used to estimate the ozone formation potential (OFP) and SOA formation potential (SOAFP), respectively. The φ(TVOC, total VOCs) were (50.52±16.81)×10-9 in autumn and (63.21±35.24)×10-9 in winter. The OFPs were 138.43×10-9 in autumn and 137.123×10-9 in winter, and the SOAFPs were 3.098 µg·m-3 and 0.612 µg·m-3, respectively. Alkanes (26.19%) and aromatics (26.04%) were the most abundant species in autumn, and alkanes (48.88%) were the most abundant species in winter. Trans-2-pentene, toluene, and m/p-xylene were the most reactive species in terms of OFPs in autumn, and ethylene, acetylene, and propylene were the top three species contributing to the total OFPs in winter. Toluene, m/p-xylene, and ethylbenzene contributed the most to the total SOAFPs in both of autumn and winter. Traffic emissions were considered as the major source of VOCs in both seasons. VOCs from biomass/coal combustion emissions showed seasonal differences, which were more prominent in winter. The results can provide references for the "one city, one policy" to mitigate regional VOCs pollution and improve ambient air quality.

Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis.

BACKGROUND: N6-methyladenosine (m6A) is a dynamic and reversible internal RNA structure of eukaryotic mRNA. YTH domain family 2 (YTHDF2), an m6A-specific reader YTH domain family, plays fundamental roles in several types of cancer. However, the function of YTHDF2 in lung squamous cell carcinoma (LUSC) remains elusive. METHODS: The knockdown and overexpression of YTHDF2 in LUSC cells were conducted to detect the biological characteristics of YTHDF2. In vivo assays, the role of YTHDF2 in tumor growth was further uncovered. In vitro assays, YTHDF2 was confirmed to be involved in activating the mTOR/AKT signaling and YTHDF2 overexpression induced the EMT process in LUSC. Clinically, immunohistochemical staining revealed the relationship between YTHDF2 expression levels and the clinicopathological characteristics of lung squamous cell carcinoma patients. Moreover, quantitative PCR (qPCR), western blot, CCK8 assay, transwell assay, and wound-healing assay were used to detect the expression level and function of YTHDF2 under hypoxia exposure in LUSC cells. RESULTS: The results showed that hypoxia-mediated YTHDF2 overexpression promotes cell proliferation and invasion by activating the mTOR/AKT axis, and YTHDF2 overexpression induces the EMT process in LUSC. Moreover, YTHDF2 is closely associated with pN (pN- 37.0%, pN + 73.9%; P = 0.002) and pTNM stage (pI 50.0%, PII 43.3%, pIIIa 80.6%; P = 0.007), ultimately resulting in poor survival for LUSC patients. CONCLUSION: In brief, the results highlight high-YTHDF2 expression predicted a worse prognosis of LUSC, while hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT signaling pathway.

Recent Developments of Flavonoids with Various Activities.

Flavonoids, a series of compounds with a C6-C3-C6 structure, mostly originate from plant metabolism. Flavonoids have shown beneficial effects on many aspects of human physiology and health. Recently, many flavonoids with various activities have been discovered, which has led to more and more studies focusing on their physiological and pharmacodynamic activities. The anticancer and anti-viral activities especially have gained the attention of many researchers. Therefore, the discovery and development of flavonoids as anti-disease drugs has great potential and may make a significant contribution to fighting diseases. This review focus on the discovery and development of flavonoids in medicinal chemistry in recent years.

Promising Enzymes for Inhibitors Development Against COVID-19.

After the emergence of COVID-19 in 2019, it has now become a pandemic. COVID-19 has brought painful disasters to people all over the world. It not only threatens lives and health but also induces economic crises. At present, promising methods to eradicate COVID-19 mainly include drugs and vaccines. Enzyme inhibitors have always been a reliable strategy for the treatment of related diseases. Scientists worldwide have worked together to study COVID-19, obtained the structure of key SARS-CoV-2 associated enzymes, and reported the research of inhibitors of these enzymes. This article summarizes COVID-19-related enzyme inhibitors' recent development, mainly including 3CLpro, PLpro, TMPRSS2, and RdRp inhibitors, hoping to provide valuable weapons in the ensuing battle against COVID-19.