OBJECTIVES: To investigate the expression levels of marginal zone B and B1-cell-specific protein (MZB1) in pan-cancer and its association with patient prognosis and tumor microenvironment (TME). METHODS: MZB1 expression data, clinicopathological parameters, and survival data from 33 cancer types were extracted from the UCSC database for analyzing the correlations of MZB1 with clinical stage, patient prognosis, immunomodulatory genes, immune checkpoint genes, tumor stemness, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). MZB1 gene mutations in pan-cancer were assessed using cBioPortal online database, and the value of MZB1 for cancer diagnosis was evaluated using ROC curve analysis. MZB1 expression levels in myeloid leukemia and renal carcinoma cells were detected using RT-qPCR and Western blotting, and the effect of MZB1 knockdown on cell proliferation was examined using EdU assay. RESULTS: MZB1 was significantly overexpressed in 20 cancer types, including kidney renal clear cell carcinoma (KIRC), breast invasive carcinoma, and acute myeloid leukemia. Its expression was associated with TNM stage, clinical stage, overall survival, and progression-free survival in multiple cancers. In most tumors, MZB1 expression was correlated significantly with immunomodulatory genes, immune checkpoint genes, tumor stemness, immune cell infiltration, TMB, and microsatellite instability. Gene amplification was the predominant mutation type of MZB1 in pan-cancer, and MZB1 showed high diagnostic value for skin cutaneous melanoma, KIRC, and head and neck squamous cell carcinoma. MZB1 was highly expressed in different myeloid leukemia cell lines and renal carcinoma cell lines, and MZB1 knockdown significantly suppressed the proliferation of HL60 and 769-P cells. CONCLUSIONS MZB1 is highly expressed in a variety of tumors, and its aberrant expression affects the occurrence and prognosis of many tumors, suggesting its potential as a novel tumor biomarker and immunomodulatory target.
Humans ; Prognosis ; Tumor Microenvironment ; Neoplasms/pathology* ; Cell Line, Tumor ; Mutation ; Kidney Neoplasms ; Microsatellite Instability ; Cell Proliferation ; Carcinoma, Renal Cell

Objective     To explore the correlation between the imaging features of peripheral ground-glass pulmonary nodules and the invasion degree of lung adenocarcinoma, and the high risk factors for infiltrating lung adenocarcinoma under thin-slice CT, which provides some reference for clinicians to plan the surgical methods of pulmonary nodules before operation and to better communicate with patients, and assists in building a clinical predictive model for invasive adenocarcinoma. Methods    Clinical data of the patients with peripheral ground-glass pulmonary nodules (diameter≤3 cm) in thin-slice chest CT in the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were continuously collected. All patients underwent thin-slice CT scan and thoracoscopic surgery in our center. According to the pathological examination results, they were divided into two groups: an adenocarcinoma lesions before infiltration group, and an invasive lung adenocarcinoma group. The thin-slice CT imaging parameters of pulmonary nodules were collected. The nodular diameter, mean CT value, consolidation tumor ratio (CTR), nodular shape, vacuolar sign, bronchial air sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign and other clinical data were collected. Univariate and multivariate analyses were conducted to analyze the independent risk factors for the infiltrating lung adenocarcinoma, and to analyze the threshold value and efficacy of each factor for the identification of infiltrating lung adenocarcinoma. Results     Finally 190 patients were enrolled. There were 110 patients in the adenocarcinoma lesions before infiltration group, including 21 males and 89 females with a mean age of 53.57±10.90 years, and 80 patients in the invasive lung adenocarcinoma group, including 31 males and 49 females with a mean age of 56.45±11.30 years. There was a statistical difference in the mean CT value, nodular diameter, CTR, gender, smoking, nodular type, nodular shape, vacuolar sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign between the two groups (P<0.05). However, there was no statistical difference between the two groups in age (P=0.081), lesion site (P=0.675), and bronchial air sign (P=0.051). Multiple logistic regression analysis showed that nodular diameter, mean CT value, CTR and lobulation sign were independent risk factors for differentiating preinvasive adenocarcinoma from invasive adenocarcinoma. At the same time, the threshold value was calculated by Youden index, indicating that the CTR was 0.45, the nodal diameter was 10.5 mm and the mean CT value was –452 Hu. Conclusion     In the peripheral ground-glass pulmonary nodules, according to the patient's CT imaging features, such as mixed ground-glass nodules, irregular shapes, vacuoles, short burrs, clear boundaries, pleural indentations, and vascular clusters, have a certain reference value in the discrimination of the invasion degree of ground-glass pulmonary nodules. At the same time, it is found in this research that peripheral ground-glass pulmonary nodules with diameter greater than 10.5 mm, CT value greater than –452 Hu, CTR greater than 0.45 and lobulation sign are more likely to be infiltrating lung adenocarcinoma.

Objective:To explore the reasonable timing of radiotherapy for epidermal growth factor receptor ( EGFR) mutation-positive non-small cell lung cancer patients with brain metastasis in the era of third-generation targeted drugs. Methods:Clinical data of EGFR mutation-positive non-small cell lung cancer patients with brain metastasis who received first-line treatment with third-generation targeted drugs and stereotactic radiotherapy at Shanghai Armed Police Corps Hospital from September 2019 to May 2022 were retrospectively analyzed. According to the timing of radiotherapy before / after targeted drug resistance, all patients were divided into the early and salvage radiotherapy groups. The proportion of brain metastasis, physical fitness, complete response rate, objective response rate, delaying the progression of brain metastasis and overall survival (OS) were compared between two groups. Kaplan-Meier method was used for survival analysis, log-rank test was used for univariate prognostic analysis, and factors with P <0.1 were included in Cox multivariate analysis. Results:A total of 85 patients were included, including 51 (60%) cases receiving early radiotherapy. Patients who participated in early radiotherapy had a higher proportion of symptomatic brain metastasis (82% vs. 56%, P=0.013) and poorer physical fitness (Kanofsky performance score <70: 61% vs. 26%, P=0.002) compared to patients who underwent salvage radiotherapy. Early radiotherapy significantly improved the complete response rate of intracranial lesions (35% vs. 12%, P=0.015) and objective response rate (88% vs. 71%, P=0.041), delayed the progression of brain metastasis (median intracranial progression free survival: 23.0 months vs. 16.0 months, P=0.005; median intracranial secondary progression free survival: 31.0 months vs. 22.0 months, P=0.021), and improved OS (median OS: 44.0 months vs. 35.0 months, P=0.046). In multivariate analysis, diagnosis-specific graded prognostic assessment score <2.5, mutation of EGFR exon 21, and salvage brain radiotherapy were adverse prognostic factors for OS. Conclusion:In the era of third-generation targeted drugs therapy, early involvement of stereotactic radiotherapy in non-small cell lung cancer patients with brain metastasis can bring greater clinical benefits.

Wet age-related macular degeneration(wARMD)emerges as a primary contributor to irreversible vision impairment in the aging demographic. In clinical practice, anti-vascular endothelial growth factor(VEGF)therapies exhibit pronounced success in managing wARMD. However, in the actual clinical application, there are significant individual differences in the prognosis of anti-VEGF drug therapy, and some patients show poor response to the treatment, which may be related to the morphological differences of retinal layers in macular area, genetics, systemic conditions and other factors. It will help develop a more rational and individualized treatment plan to judge the prognosis of patients according to their different clinical manifestations in advance, so as to reduce overtreatment and the risk of retinal damage. In recent years, most studies on treatment response mainly focus on fundus morphology, genetics and so on. In this study, the relevant factors affecting adverse response to wARMD were reviewed, aiming to provide with more accurate treatment and prognostic monitoring programs for clinicians.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:This study aims to investigate the determinants influencing the efficacy of microsurgical sperm retrieval in individuals diagnosed with idiopathic non-obstructive azoospermia (iNOA).Methods:A retrospective analysis was performed on the clinical data of 757 patients diagnosed with iNOA who underwent microsurgical sperm extraction at Peking University Third Hospital between January 2019 and December 2021. The median age of patients was 31(29, 33)years, and the duration of infertility was 3(2, 5)years. A total of 169 patients (22.3%) received preoperative pharmacological treatment with agents such as follicle-stimulating hormone, human chorionic gonadotropin, or aromatase inhibitors. Additionally, 327 patients (43.2%) underwent testicular biopsy (TESA) prior to surgery. Among these, 51 cases (15.9%) exhibited sperm presence on smear microscopy, while 57 cases (17.8%) demonstrated sperm presence on pathological examination. The pathological classifications of the biopsies included 102 cases (31.9%) of reduced spermatogenic function, 66 cases (20.6%) of delayed sperm maturation, and 63 cases (19.7%) of sertoli cell-only syndrome.Preoperative median pituitary prolactin(PRL)was 9.1(6.5, 12.5)ng/ml, follicle-stimulating hormone (FSH)20.1(14.2, 28.5)U/L, luteinizing hormone (LH)7.9(5.5, 11.3)U/L, testosterone(T)117 .0(81.3, 154.0)nmol/L, estradiol(E2)8.7(6.3, 11.8)pmol/L. Under general anesthesia, patients underwent microsurgical testicular incision for sperm retrieval.The surgical testicular volume was measured at a median of 6(5, 10) ml. Among the cases studied, 59 patients (7.7%) underwent left testicular surgery, 213 patients (28.1%) underwent right testicular surgery, and 485 patients (64.0%) underwent bilateral testicular surgery. Furthermore, 44 patients (5.8%) underwent a second microsurgical sperm retrieval procedure, while 4 patients (0.5%) underwent a third procedure.Based on the presence of sperm identified during the surgical procedure, participants were categorized into a sperm retrieval group and a non-sperm retrieval group. Clinical data of these two groups were analyzed. A subgroup analysis was performed on the observed indicators. Both univariate and multivariate logistic regression analyses were employed to examine the factors influencing the micro sperm retrieval rate.Results:Among the 757 iNOA patients, 255(33.7%) obtained sperm through micro sperm retrieval, while 502(66.3%) did not obtain sperm through micro sperm retrieval. The age of sperm-receiving group was higher than that of the non-sperm-receiving group [32(30, 35)years vs. 30(28, 33)years, P<0.01], and the course of infertility was longer than that of the non-sperm-receiving group [3.0(2.0, 5.5)years vs. 3.0(2.0, 4.0)years, P=0.004]. There was no significant difference in the sperm acquisition rate in the subgroup with or without preoperative drug treatment [38.5%(65/169)vs. 32.7%(185/566), P=0.164]. There was statistical significance in the sperm collection rate of different TESA results in subgroups [85.7%(24/28)of sperm were detected by microscopic smear and pathological examination and 75.9%(22/29)of sperm were detected by pathological examination and no sperm were detected by microscopic smear and 17% of sperm were not detected by microscopic smear and pathological examination (42/247), P<0.01). The rate of spermatogenesis in the subgroup with low spermatogenic function was significantly higher than that in the subgroup with spermatogenic maturation retardation and sercell-only syndrome [47.1%(48/112), 12.1%(8/66)vs. 11.1%(7/63), P<0.01]. There was no significant difference in testicular volume between the seminal and non-seminal groups [6.0(5.0, 10.0)ml vs. 6.0(5.0, 9.5)ml, P=0.862]. Pituitary prolactin [8.3(5.8, 12.0)ng/ml vs. 9.3(7.5, 13.0)ng/ml, P=0.001] and FSH[18.3(11.8, 27.4)U/L vs. 20.7(15.2, 28.7)U/L, P=0.005] in spermated group were lower than those in non-spermated group. Luteinizing hormone [7.6(5.1, 11.0)U/L vs. 8.0(5.6, 11.5)U/L, P=0.126], testosterone [8.8(6.0, 11.8)nmol/L vs. 8.7(6.4, 11.7)nmol/L, P=0.607], estradiol [124.0(87.8, 156.0)nmol/L vs. 114.5(79.9, 151.3)nmol/L, P=0.105] had no significant difference. The recovery rate of the first operation was higher than that of the second operation [97.7%(43/44)vs. 81.8%(36/42), P=0.032]. The sperm retrieval rate of bilateral operation was significantly lower than that of unilateral operation [6.0% bilateral (29/485)vs. 86.4% left (51/59)vs. 82.2% right (175/213), P<0.01]. The proportion of no sperm on one side of bilateral operation and only 4.7%(23/485)on the opposite side were obtained. The results of multivariate analysis showed that >30 and ≤40 years old subgroup ( OR=2.226, 95% CI 1.364-3.632, P=0.001), >40 and ≤50 years old subgroup ( OR=4.282, 95% CI 1.457-12.588, P=0.008)was higher than that of >20 and ≤30 years old subgroup. The sperm acquisition rate of the sperm subgroup was significantly increased by smear microscopy and pathological examination ( OR=6.486, 95% Cl 1.444-29.127, P=0.015), while the sperm acquisition rate of the sperm subgroup was not significantly decreased by smear microscopy and pathological examination ( OR=0.420, 95% Cl 0.200-0.881, P=0.022). The pathological type of puncture was associated with lower spermatogenesis maturation block ( OR=0.099, 95% CI 0.019-0.509, P=0.006). Higher FSH (>7.6 U/L)was associated with lower sperm yield ( OR=0.324, 95% CI 0.122-0.856, P=0.023). Conclusions:Age, FSH level, results of testicular biopsy and pathologic type of biopsy are independent factors affecting the sperm retrieval rate of iNOA patients undergoing micro-TESE. The success rate of sperm retrieval diminished following multiple surgical procedures. Furthermore, for patients who did not have sperm successfully retrieved from one side, that the likelihood of sperm retrieval from contralateral surgery would also be low.

Objective:This study aims to investigate the determinants influencing the efficacy of microsurgical sperm retrieval in individuals diagnosed with idiopathic non-obstructive azoospermia (iNOA).Methods:A retrospective analysis was performed on the clinical data of 757 patients diagnosed with iNOA who underwent microsurgical sperm extraction at Peking University Third Hospital between January 2019 and December 2021. The median age of patients was 31(29, 33)years, and the duration of infertility was 3(2, 5)years. A total of 169 patients (22.3%) received preoperative pharmacological treatment with agents such as follicle-stimulating hormone, human chorionic gonadotropin, or aromatase inhibitors. Additionally, 327 patients (43.2%) underwent testicular biopsy (TESA) prior to surgery. Among these, 51 cases (15.9%) exhibited sperm presence on smear microscopy, while 57 cases (17.8%) demonstrated sperm presence on pathological examination. The pathological classifications of the biopsies included 102 cases (31.9%) of reduced spermatogenic function, 66 cases (20.6%) of delayed sperm maturation, and 63 cases (19.7%) of sertoli cell-only syndrome.Preoperative median pituitary prolactin(PRL)was 9.1(6.5, 12.5)ng/ml, follicle-stimulating hormone (FSH)20.1(14.2, 28.5)U/L, luteinizing hormone (LH)7.9(5.5, 11.3)U/L, testosterone(T)117 .0(81.3, 154.0)nmol/L, estradiol(E2)8.7(6.3, 11.8)pmol/L. Under general anesthesia, patients underwent microsurgical testicular incision for sperm retrieval.The surgical testicular volume was measured at a median of 6(5, 10) ml. Among the cases studied, 59 patients (7.7%) underwent left testicular surgery, 213 patients (28.1%) underwent right testicular surgery, and 485 patients (64.0%) underwent bilateral testicular surgery. Furthermore, 44 patients (5.8%) underwent a second microsurgical sperm retrieval procedure, while 4 patients (0.5%) underwent a third procedure.Based on the presence of sperm identified during the surgical procedure, participants were categorized into a sperm retrieval group and a non-sperm retrieval group. Clinical data of these two groups were analyzed. A subgroup analysis was performed on the observed indicators. Both univariate and multivariate logistic regression analyses were employed to examine the factors influencing the micro sperm retrieval rate.Results:Among the 757 iNOA patients, 255(33.7%) obtained sperm through micro sperm retrieval, while 502(66.3%) did not obtain sperm through micro sperm retrieval. The age of sperm-receiving group was higher than that of the non-sperm-receiving group [32(30, 35)years vs. 30(28, 33)years, P<0.01], and the course of infertility was longer than that of the non-sperm-receiving group [3.0(2.0, 5.5)years vs. 3.0(2.0, 4.0)years, P=0.004]. There was no significant difference in the sperm acquisition rate in the subgroup with or without preoperative drug treatment [38.5%(65/169)vs. 32.7%(185/566), P=0.164]. There was statistical significance in the sperm collection rate of different TESA results in subgroups [85.7%(24/28)of sperm were detected by microscopic smear and pathological examination and 75.9%(22/29)of sperm were detected by pathological examination and no sperm were detected by microscopic smear and 17% of sperm were not detected by microscopic smear and pathological examination (42/247), P<0.01). The rate of spermatogenesis in the subgroup with low spermatogenic function was significantly higher than that in the subgroup with spermatogenic maturation retardation and sercell-only syndrome [47.1%(48/112), 12.1%(8/66)vs. 11.1%(7/63), P<0.01]. There was no significant difference in testicular volume between the seminal and non-seminal groups [6.0(5.0, 10.0)ml vs. 6.0(5.0, 9.5)ml, P=0.862]. Pituitary prolactin [8.3(5.8, 12.0)ng/ml vs. 9.3(7.5, 13.0)ng/ml, P=0.001] and FSH[18.3(11.8, 27.4)U/L vs. 20.7(15.2, 28.7)U/L, P=0.005] in spermated group were lower than those in non-spermated group. Luteinizing hormone [7.6(5.1, 11.0)U/L vs. 8.0(5.6, 11.5)U/L, P=0.126], testosterone [8.8(6.0, 11.8)nmol/L vs. 8.7(6.4, 11.7)nmol/L, P=0.607], estradiol [124.0(87.8, 156.0)nmol/L vs. 114.5(79.9, 151.3)nmol/L, P=0.105] had no significant difference. The recovery rate of the first operation was higher than that of the second operation [97.7%(43/44)vs. 81.8%(36/42), P=0.032]. The sperm retrieval rate of bilateral operation was significantly lower than that of unilateral operation [6.0% bilateral (29/485)vs. 86.4% left (51/59)vs. 82.2% right (175/213), P<0.01]. The proportion of no sperm on one side of bilateral operation and only 4.7%(23/485)on the opposite side were obtained. The results of multivariate analysis showed that >30 and ≤40 years old subgroup ( OR=2.226, 95% CI 1.364-3.632, P=0.001), >40 and ≤50 years old subgroup ( OR=4.282, 95% CI 1.457-12.588, P=0.008)was higher than that of >20 and ≤30 years old subgroup. The sperm acquisition rate of the sperm subgroup was significantly increased by smear microscopy and pathological examination ( OR=6.486, 95% Cl 1.444-29.127, P=0.015), while the sperm acquisition rate of the sperm subgroup was not significantly decreased by smear microscopy and pathological examination ( OR=0.420, 95% Cl 0.200-0.881, P=0.022). The pathological type of puncture was associated with lower spermatogenesis maturation block ( OR=0.099, 95% CI 0.019-0.509, P=0.006). Higher FSH (>7.6 U/L)was associated with lower sperm yield ( OR=0.324, 95% CI 0.122-0.856, P=0.023). Conclusions:Age, FSH level, results of testicular biopsy and pathologic type of biopsy are independent factors affecting the sperm retrieval rate of iNOA patients undergoing micro-TESE. The success rate of sperm retrieval diminished following multiple surgical procedures. Furthermore, for patients who did not have sperm successfully retrieved from one side, that the likelihood of sperm retrieval from contralateral surgery would also be low.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

OBJECTIVE To evaluate the relationship and impact of long-term budesonide treatment results and medication compliance of children with asthma in Shaoxing through multidisciplinary precision medication nursing led by clinical pharmacists. METHODS Randomized controlled trial design was adopted. Children with asthma admitted to Shaoxing Maternity and Child Health Care Hospital from January 1, 2022 to December 1, 2022 were taken as the research objects. According to the inclusion and exclusion criteria, 106 patients were selected to be included in the group, and randomly divided into intervention group(multidisciplinary precision care group led by pharmacists) and control group(conventional care group). Compared the differences of lung function, Morisky Children’s Medication Compliance Scale, IgE, eosinophil count, drug information satisfaction scale and medication belief scale between the two groups. RESULTS The lung function level, Morisky score, lgE, eosinophil count and medication compliance of the intervention group were significantly better than those of the control group, and the differences had statistical significance. CONCLUSION A multidisciplinary nursing team led by clinical pharmacists has significantly improved the clinical outcomes and medication compliance of children with asthma.

OBJECTIVE To investigate the anti-tumor effects of the components of Ganoderma lucidum(Gc) based on the two-dimensional(2D) and three-dimensional(3D) culture of colorectal cancer HCT116 cells. METHODS The chemical compositional of the three components was identified by UPLC-Q-TOF-MS. An in vitro 3D culture model of HCT116 cells was established by using Matrigel as the matrix material, and the effects of Gc1, Gc2, Gc3, and 5-fluorouracil(5-FU) on the proliferation of HCT116 cells in 2D and 3D culture models were evaluated, and the effects of Gc3 on cell-cycle, apoptosis, drug resistance, lipid metabolism, and 5-FU's anti-tumor activity were evaluated. Cell viability was detected by CCK-8 assay. mRNA expression level of the cells was analyzed by Real-time PCR. Proteins expression level of the cells was analyzed by Western blotting. HPLC was used to detect the content of 5-FU in cells. RESULTS A total of 76, 69, and 17 compounds were identified from Gc1, Gc2, and Gc3, respectively. Compared with 2D culture, the proliferation rate of HCT116 cells was decreased in the 3D culture model, and the expression of cell cycle-promoters CDK2, CDK4, CDK6, and fatty acid synthesizer FASN, SREBP1 were significantly down-regulated. On the contrary, the expression of cell cycle-suppressor p21, p27, and lipid droplet breakdown proteins ATGL and drug resistance gene ITGB1, CDH1, ABCB1, and ABCC1 mRNA were significantly up-regulated. Gc1, Gc2, Gc3 and 5-FU inhibited the proliferation of both 2D and 3D cultured HCT116 cells in a dose dependent manner after incubation for 48 h, and the inhibitory effect of Gc3 was significantly stronger than Gc1 and Gc2. Gc3 could not only reduce the expression of CDK2, CDK4, Bcl-xl, ATGL, and LC3B proteins, but also increase the expression of p21, p27, Bax, Cleaved caspase-3, and Cleaved PARP1 proteins, and overexpression of LC3B or ATGL attenuated Gc3-induced cytotoxicity in 3D cultured HCT116 cells. In addition, Gc3 significantly inhibited the expression of ITGB1, CDH1, ABCB1, and ABCC1 mRNA, and increased the intracellular 5-FU content, and enhanced the anti-tumor activity. CONCLUSION Gc3 significantly inhibit the proliferation of 3D-cultured HCT116 cells by inhibiting cell autophagy and lipid droplet breakdown, and enhance the anti-cancer activity of 5-FU by inhibiting the expression of ITGB1, CDH1, ABCB1, and ABCC1 mRNA.