Objective:To explore the effects of anlotinib on the proliferation, apoptosis, and migration of thyroid cancer cells, and investigate its role in inducing redifferentiation and enhancing iodine uptake capacity, providing a preliminary evaluation of its efficacy in tumor treatment.Methods:(1)The cell proliferation was detected by cell counting kit-8 (CCK-8) assay, and different concentrations (0, 1/4 half maximal inhibitory concentration (IC 50), 1/2IC 50, IC 50) of anlotinib were used to treat CAL62 and FTC133 thyroid cancer cells for 24h. The clonogenic formation experiment, cellular activity and drug toxicity staining, scratch healing assay, and apoptosis in situ fluorescence staining were employed to assess cell clonogenicity, apoptosis, and migration abilities. (2) CAL62 and FTC133 cells were treated with various concentrations of anlotinib, and changes in the expression levels of iodine metabolism-related proteins (sodium/iodide symporter (NIS), thyroid peroxidase (TPO), and thyroid-stimulating hormone receptor (TSHR)) were detected using Western blot. (3) Iodine uptake experiments were conducted to observe changes in the iodine uptake functionality of thyroid cancer cells following treatment with different concentrations of anlotinib for 24 h. (4) The thyroid cancer xenograft nude mouse models were established and divided into control group (physiological saline), low-dose group (1mg/kg), medium-dose group (2mg/kg), and high-dose group (4mg/kg). Mice were treated with varying doses of the drug, the therapeutic effects and the changes in iodine harvesting function on tumors were evaluated. One-way analysis of variance was used for comparison among groups. Results:Anlotinib treatment resulted in significantly reduced cell viability, decreased clonogenic formation, increased apoptosis rates, and reduced scratch healing rates in CAL62 and FTC133 cells ( F values: 53.75-211.90, all P<0.001). After anlotinib treatment, the levels of iodine metabolism-related proteins (NIS, TPO and TSHR) significantly increased ( F values: 21.14-710.00, all P<0.001), and iodine uptake rates in thyroid cancer cells also increased significantly ( F values: 36.45, 32.34, both P<0.001). The nude mouse treatment experiment showed tumor growth in the anlotinib treatment group was inhibited, and tumors iodine uptake rates were increased, both were statistically significant ( F values: 74.09, 38.22, both P<0.001). Conclusions:Anlotinib can inhibit thyroid cancer proliferation and growth, promote apoptosis, reduce cell migration capabilities, induce thyroid cancer cells redifferentiation, and enhance iodine uptake capacity. Anlotinib can induce the redifferentiation of thyroid cancer at the animal level and has better efficacy.

Objective:To investigate the effects of 177Lu-prostate specific membrane antigen (PSMA)-I&T combined with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor (PARPi) fluzoparib on the proliferation and migration of prostate cancer cells and the tumor inhibitory effects. Methods:177Lu-PSMA-I&T was synthesized. Cytotoxicity assay, colony formation assay, 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation assay, Transwell cell migration assay, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, flow cytometry were performed to detect apoptosis and cell cycles. 22RV1 tumor-bearing mice models ( n=16) were established, and were randomly divided into 4 groups: control group (no treatment; n=4), fluzoparib monotherapy group (6mg/kg; n=4), 177Lu-PSMA-I&T monotherapy group (14.8MBq; n=4) and combination group (14.8MBq 177Lu-PSMA-I&T+ 6mg/kg fluzoparib; n=4). All mice were treated for 14 d. Tumor volume and body mass changes of tumor-bearing mice were observed and recorded. After the treatment, 18F-FDG PET/CT was performed to evaluate the tumor′s uptake of 18F-FDG. Effects of 177Lu-PSMA-I&T combined with fluzoparib on cell and tumor-bearing mice were observed. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:At half maximal inhibitory concentrations (IC 50) of 177Lu-PSMA-I&T (13.06MBq/ml) and fluzoparib (72.13μmol/L), compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment significantly enhanced the anti-tumor effect on 22RV1 cells, inhibited the DNA synthesis rate and colony-forming ability of 22RV1 cells, reduced cell migration rate, increased the percentage of DNA damage, resulted in a higher proportion of cells arrested in the G2/M phase and increased the apoptosis rate ( F values: 9.77-162.20, t values: 2.98-21.60, all P<0.05). Compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment resulted in a significant reduction in relative tumor volume (RTV%) 14 d post-administration and markedly decreased 18F-FDG uptake ( F values: 25.28 and 67.42, t values: 4.64-8.61, P values: 0.001-0.009). Conclusion:The combination of 177Lu-PSMA-I&T and fluzoparib can inhibit prostate cancer cell proliferation and migration, suppress tumor growth and metabolism, and demonstrates synergistic effects more effectively.

Objective:To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation.Methods:A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlations were analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children′s Medical Center (Ethics No.: 2022-406B00).Results:The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c. 2668C>T; p. Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case reports has associated it with this phenotypic spectrum. It was not observed in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. Conclusion:This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c. 2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies in prenatal diagnostics. Above findings have advanced our understanding of pleiotropic effects in type Ⅱ collagen disorders and lay the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities in high-risk families.

Bacillus velezensis DJ1 exhibits broad-spectrum antagonistic activity against diverse phytopathogenic fungi, while its biocontrol mechanisms against Fusarium graminearum, the causal agent of maize stalk rot, remain poorly characterized. In this study, we integrated genomics and transcriptomics to elucidate the antifungal mechanisms of strain DJ1. The results demonstrated that DJ1 inhibited F. graminearum with the efficacy of 64.4%, while its polyketide crude extract achieved the control efficacy of 55% in pot experiments against this disease. Whole-genome sequencing revealed a single circular chromosome (3 929 792 bp, GC content of 47%) harboring 12 biosynthetic gene clusters for secondary metabolites, six of which encoded known antimicrobial compounds (macrolactin H, bacillaene, difficidin, surfactin, fengycin, and bacilysin). Transcriptomic analysis identified 243 differentially expressed genes (152 upregulated and 91 downregulated, P < 0.05), which were potentially associated with the antagonistic activity against F. graminearum. KEGG enrichment analysis highlighted activation (P < 0.05) of cysteine/methionine metabolism, pentose phosphate pathway, and polyketide biosynthesis pathways, indicating that DJ1 employed synergistic strategies involving antimicrobial compound synthesis, energy metabolism enhancement, and nutrient competition to suppress pathogens. This study provides a theoretical foundation for developing novel microbial resources and application technologies to combat phytopathogenic fungi.
Fusarium/drug effects* ; Bacillus/metabolism* ; Plant Diseases/prevention & control* ; Antifungal Agents/pharmacology* ; Genomics ; Zea mays/microbiology* ; Transcriptome ; Gene Expression Profiling ; Antibiosis ; Multigene Family ; Multiomics

OBJECTIVE: To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation. METHODS: A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00). RESULTS: The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C>T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. CONCLUSION This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis. Above findings have advanced our understanding of the pleiotropic effects in type Ⅱ collagen disorders and laid the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities for high-risk families.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Arthritis/genetics* ; Collagen Type II/genetics* ; Connective Tissue Diseases/genetics* ; Exome Sequencing ; Genetic Association Studies ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Retinal Detachment/genetics* ; East Asian People/genetics*

Objective:To establish the method of bacterial endotoxin detection for raw materials and injections of paliperidone palmitate.Methods:Paliperidone palmitate was dissolved with tetrahydrofuran and polysorbate 20 as solvent,and then diluted with BET H2O.According to bacterial endotoxin test in Chinese Pharmacopoeia 2020 Vol general charpters 1143,methodology validation of chromogenic substrate method in bacterial endotoxin test was con-ducted and then the interference experiment of solubilizer was added.Results:Paliperidone palmitate did not pre-cipitate during the experimental process,and then diluted to 0.007 mg·mL-1 with BET H2O.There was no inter-ference for chromogenic substrate method,while the bacterial endotoxin recovery of the solubilizer does not interfere with endotoxin testing.Conclusion:The method established in this paper is suitable for bacteria endotoxin test of raw materials and injections of paliperidone palmitate.

Objective To investigate the association between gout-related gene polymorphisms and clinical phenotypic heterogeneity among gout patients in the Foshan region,thereby providing a scientific basis for stratified clinical management.Methods A total of 125 gout patients diagnosed at the Foshan Hospital of Traditional Chinese Medicine between June 2022 and May 2025 were enrolled in this study.The collected data included demo-graphic characteristics,frequency of gout attacks,presence of tophi,levels of uric acid,creatinine,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),gout-related genes(ABCG2,SLC2A9,SLC22A12,MTHFR),and joint ultrasound findings.Group comparisons and rank correlation analyses were conducted to explore potential associations between gene polymorphisms and clinical heterogeneity.Results The male-to-female ratio was 11∶1;the mean age was(35.28±2.67)years;the mean disease duration was(6.03±0.68)years;and the mean frequency of acute attacks in the past 12 months was 4(2.0,7.25).Genotype distributions were as follows:ABCG2:wild-type(C/C),23.8%;heterozygous(C/A),53.2%;homozygous(A/A),23%.SLC2A9:wild-type(A/A),24.6%;heterozygous(A/G),50%;homozygous(G/G),25.4%.SLC22A12:wild-type(A/A),4.8%;heterozygous(A/C),31.7%;homozygous(C/C),63.5%.MTHFR:wild-type(C/C),68.3%;heterozygous(C/T),28.6%;homozygous(T/T),3.2%.Rank correlation analysis revealed that SLC2A9 polymorphisms were significantly correlated with tophi formation(ρ=0.193,P=0.031)and crystal deposition on ultrasound(ρ=0.202,P=0.025).SLC22A12 polymorphisms were associated with hypertension(ρ=0.269,P=0.003)and diabetes(ρ=0.200,P=0.026).MTHFR polymorphisms showed a correlation with diabetes(ρ=0.224,P=0.012).Conclusions Polymorphisms in SLC2A9,SLC22A12,and MTHFR are significantly linked to clinical phenotypic heterogeneity among gout patients.Genetic testing could facilitate the early identification of individuals at high risk for complications and support the development of stratified and individualized treatment approaches.

Objective:To establish the method of bacterial endotoxin detection for raw materials and injections of paliperidone palmitate.Methods:Paliperidone palmitate was dissolved with tetrahydrofuran and polysorbate 20 as solvent,and then diluted with BET H2O.According to bacterial endotoxin test in Chinese Pharmacopoeia 2020 Vol general charpters 1143,methodology validation of chromogenic substrate method in bacterial endotoxin test was con-ducted and then the interference experiment of solubilizer was added.Results:Paliperidone palmitate did not pre-cipitate during the experimental process,and then diluted to 0.007 mg·mL-1 with BET H2O.There was no inter-ference for chromogenic substrate method,while the bacterial endotoxin recovery of the solubilizer does not interfere with endotoxin testing.Conclusion:The method established in this paper is suitable for bacteria endotoxin test of raw materials and injections of paliperidone palmitate.

Objective To investigate the association between gout-related gene polymorphisms and clinical phenotypic heterogeneity among gout patients in the Foshan region,thereby providing a scientific basis for stratified clinical management.Methods A total of 125 gout patients diagnosed at the Foshan Hospital of Traditional Chinese Medicine between June 2022 and May 2025 were enrolled in this study.The collected data included demo-graphic characteristics,frequency of gout attacks,presence of tophi,levels of uric acid,creatinine,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),gout-related genes(ABCG2,SLC2A9,SLC22A12,MTHFR),and joint ultrasound findings.Group comparisons and rank correlation analyses were conducted to explore potential associations between gene polymorphisms and clinical heterogeneity.Results The male-to-female ratio was 11∶1;the mean age was(35.28±2.67)years;the mean disease duration was(6.03±0.68)years;and the mean frequency of acute attacks in the past 12 months was 4(2.0,7.25).Genotype distributions were as follows:ABCG2:wild-type(C/C),23.8%;heterozygous(C/A),53.2%;homozygous(A/A),23%.SLC2A9:wild-type(A/A),24.6%;heterozygous(A/G),50%;homozygous(G/G),25.4%.SLC22A12:wild-type(A/A),4.8%;heterozygous(A/C),31.7%;homozygous(C/C),63.5%.MTHFR:wild-type(C/C),68.3%;heterozygous(C/T),28.6%;homozygous(T/T),3.2%.Rank correlation analysis revealed that SLC2A9 polymorphisms were significantly correlated with tophi formation(ρ=0.193,P=0.031)and crystal deposition on ultrasound(ρ=0.202,P=0.025).SLC22A12 polymorphisms were associated with hypertension(ρ=0.269,P=0.003)and diabetes(ρ=0.200,P=0.026).MTHFR polymorphisms showed a correlation with diabetes(ρ=0.224,P=0.012).Conclusions Polymorphisms in SLC2A9,SLC22A12,and MTHFR are significantly linked to clinical phenotypic heterogeneity among gout patients.Genetic testing could facilitate the early identification of individuals at high risk for complications and support the development of stratified and individualized treatment approaches.

Objective:To explore the effects of anlotinib on the proliferation, apoptosis, and migration of thyroid cancer cells, and investigate its role in inducing redifferentiation and enhancing iodine uptake capacity, providing a preliminary evaluation of its efficacy in tumor treatment.Methods:(1)The cell proliferation was detected by cell counting kit-8 (CCK-8) assay, and different concentrations (0, 1/4 half maximal inhibitory concentration (IC 50), 1/2IC 50, IC 50) of anlotinib were used to treat CAL62 and FTC133 thyroid cancer cells for 24h. The clonogenic formation experiment, cellular activity and drug toxicity staining, scratch healing assay, and apoptosis in situ fluorescence staining were employed to assess cell clonogenicity, apoptosis, and migration abilities. (2) CAL62 and FTC133 cells were treated with various concentrations of anlotinib, and changes in the expression levels of iodine metabolism-related proteins (sodium/iodide symporter (NIS), thyroid peroxidase (TPO), and thyroid-stimulating hormone receptor (TSHR)) were detected using Western blot. (3) Iodine uptake experiments were conducted to observe changes in the iodine uptake functionality of thyroid cancer cells following treatment with different concentrations of anlotinib for 24 h. (4) The thyroid cancer xenograft nude mouse models were established and divided into control group (physiological saline), low-dose group (1mg/kg), medium-dose group (2mg/kg), and high-dose group (4mg/kg). Mice were treated with varying doses of the drug, the therapeutic effects and the changes in iodine harvesting function on tumors were evaluated. One-way analysis of variance was used for comparison among groups. Results:Anlotinib treatment resulted in significantly reduced cell viability, decreased clonogenic formation, increased apoptosis rates, and reduced scratch healing rates in CAL62 and FTC133 cells ( F values: 53.75-211.90, all P<0.001). After anlotinib treatment, the levels of iodine metabolism-related proteins (NIS, TPO and TSHR) significantly increased ( F values: 21.14-710.00, all P<0.001), and iodine uptake rates in thyroid cancer cells also increased significantly ( F values: 36.45, 32.34, both P<0.001). The nude mouse treatment experiment showed tumor growth in the anlotinib treatment group was inhibited, and tumors iodine uptake rates were increased, both were statistically significant ( F values: 74.09, 38.22, both P<0.001). Conclusions:Anlotinib can inhibit thyroid cancer proliferation and growth, promote apoptosis, reduce cell migration capabilities, induce thyroid cancer cells redifferentiation, and enhance iodine uptake capacity. Anlotinib can induce the redifferentiation of thyroid cancer at the animal level and has better efficacy.