Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Objective:To assess the clinical value of digital PCR (dPCR) for the prenatal diagnosis of common fetal aneuploidies.Methods:A dPCR-based assay was developed for detecting trisomies 21, 18, and 13. A retrospective analysis was carried out on 173 amniotic fluid samples collected by the Prenatal Diagnosis Center of Taizhou Hospital between January 2017 and December 2023. By using chromosomal karyotyping as the gold standard, the diagnostic performance of the multiplex dPCR system was evaluated in a double-blind manner. This study has been approved by the Ethics Committee of Taizhou Hospital (Ethics No. K20250339).Results:Chromosomal karyotyping has identified 59 cases of trisomy 21, 5 cases of trisomy 18, 2 cases of trisomy 13, 6 cases with chromosomal structural abnormalities or mosaicisms, and 101 cases with a normal karyotype. The dPCR results ( Z-score cutoff = 4.0, CI = 99.997%) showed full concordance with karyotyping (sensitivity = 100%, specificity = 100%, Kappa = 1). Among the 6 structurally abnormal or mosaicism samples, dPCR has accurately detected 4 cases, but mis-classified 2 cases of trisomy 21 with very low-level mosaicisms (3.3%, 6.9%, respectively) as normal. Conclusion:The established multiplex dPCR system demonstrated high diagnostic accuracy for common chromosomal aneuploidies, with results available within 24 hours. It can serve as an efficient supplementary tool to conventional chromosomal karyotyping, providing reliable support for time-sensitive clinical decision-making in prenatal diagnosis.

Objective:To observe whether electroacupuncture(EA)can inhibit activation of JAK1/STAT3 signaling pathway and improve pulmonary inflammation in chronic obstructive pulmonary disease(COPD)by increasing expression of SOCS3.Methods:Atotal of 60 mice were randomly divided into normal group,model(COPD)group,COPD+EA group,COPD+si-SOCS3 group,COPD+si-SOCS3 NC group,COPD+si-SOCS3+EA group,with 10 mice in each group.Mice COPD model was replicated by simple cigarette smoking for three months.After modeling,SOCS3 siRNA was administered to lungs of mice in COPD+si-SOCS3 group and COPD+si-SOCS3+EA group,SOCS3 siRNA NC was administered to COPD+si-SOCS3 NC group.24 h after the first SOCS3 siRNA ad-ministration,mice in COPD+EA and COPD+si-SOCS3+EA groups were treated with EA in"Feishu"and"Zusanli",once every other day,30 min/times for 14 days.Lung function of mice in each group was detected;lung pathological changes were observed by HE staining;IL-6,IL-1β and TNF-α levels in mice broncho alveolar lavage fluid were detected by ELISA;protein expressions of SOCS3,JAK1,STAT3,p-JAK1 and p-STAT3 were detected by Western blot;SOCS3,JAK1 and STAT3 mRNA were detected by RT-PCR.Results:Compared with normal group,mice in COPD group showed decreased lung function,thickened alveolar walls,congestion and edema between tissues,significantly increased levels of inflammatory cytokines IL-6,TNF-α and IL-1β,decreased SOCS3 protein expres-sion,p-JAK1/JAK1 and p-STAT3/STAT3 significantly increased,JAK1 and STAT3 mRNA increased,SOCS3 mRNA decreased(P<0.05).Compared with COPD group,the above indexes of COPD+EA group were improved(P<0.05),and the above indexes of COPD+si-SOCS3 group were more serious(P<0.05),and COPD+si-SOCS3+EA group was improved compared with COPD+si-SOCS3 group(P<0.05).Conclusion:EA can inhibit overactivation of JAK1/STAT3 signaling pathway by up-regulating SOCS3 expression,and thus improve pulmonary inflammation in COPD.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

OBJECTIVE: To assess the clinical value of digital PCR (dPCR) for the prenatal diagnosis of common fetal aneuploidies. METHODS: A dPCR-based assay was developed for detecting trisomies 21, 18, and 13. A retrospective analysis was carried out on 173 amniotic fluid samples collected by the Prenatal Diagnosis Center of Taizhou Hospital between January 2017 and December 2023. By using chromosomal karyotyping as the gold standard, the diagnostic performance of the multiplex dPCR system was evaluated in a double-blind manner. This study has been approved by the Ethics Committee of Taizhou Hospital (Ethics No. K20250339). RESULTS: Chromosomal karyotyping has identified 59 cases of trisomy 21, 5 cases of trisomy 18, 2 cases of trisomy 13, 6 cases with chromosomal structural abnormalities or mosaicisms, and 101 cases with a normal karyotype. The dPCR results (Z-score cutoff = 4.0, CI = 99.997%) showed full concordance with karyotyping (sensitivity = 100%, specificity = 100%, Kappa = 1). Among the 6 structurally abnormal or mosaicism samples, dPCR has accurately detected 4 cases, but mis-classified 2 cases of trisomy 21 with very low-level mosaicisms (3.3%, 6.9%, respectively) as normal. CONCLUSION The established multiplex dPCR system demonstrated high diagnostic accuracy for common chromosomal aneuploidies, with results available within 24 hours. It can serve as an efficient supplementary tool to conventional chromosomal karyotyping, providing reliable support for time-sensitive clinical decision-making in prenatal diagnosis.
Humans ; Female ; Pregnancy ; Aneuploidy ; Prenatal Diagnosis/methods* ; Karyotyping ; Retrospective Studies ; Polymerase Chain Reaction/methods* ; Chromosome Disorders/genetics* ; Adult ; Trisomy 13 Syndrome/diagnosis* ; Trisomy 18 Syndrome/genetics* ; Down Syndrome/genetics*

OBJECTIVE: To assess the clinical value of non-invasive prenatal testing (NIPT) for identifying maternal malignant tumors. METHODS: A retrospective analysis was carried out on pregnant women undergoing Non-invasive prenatal testing (NIPT) at Taizhou Hospital in Zhejiang Province from January 2018 to December 2022. The criteria included maternal copy number variations for at least two chromosomes. Clinical follow-up data were obtained for the high-risk population of maternal malignant tumors through telephone follow-up and review of electronic medical records. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20250339). RESULTS: Among 45 141 NIPT samples, 6 (0.013%) were suggested to have maternal malignant tumors. Follow-up information was available for 5 patients (83.3%). Two cases were diagnosed with maternal malignant tumors, including 1 myelodysplastic syndrome and 1 pelvic malignant tumor. Two cases were found to have multiple uterine fibroids and 1 was lost during follow-up. CONCLUSION The abnormal copy number indicated by NIPT may serve as an early signal for maternal malignant tumors. To establish a systematic follow-up protocol and multidisciplinary collaboration are conducive to achieving early diagnosis of tumors and improving the prognosis of patients. Based on the results of this study, it is recommended that for pregnant women with unexplained copy number variations and suspected maternal tumors by NIPT, targeted tumor screening program should be implemented to optimize their clinical management.
Humans ; Female ; Pregnancy ; Adult ; Retrospective Studies ; DNA Copy Number Variations/genetics* ; Follow-Up Studies ; Neoplasms/diagnosis* ; Noninvasive Prenatal Testing/methods* ; Pregnancy Complications, Neoplastic/diagnosis* ; Prenatal Diagnosis/methods*

Objective:To investigate and assess the situation of popularization and promotion of domestically innovative medical devices in Liaoning Province,so as to provide a basis for promoting the allocation policy of domestically innovation medical devices.Methods:Self-made questionnaire and on-site filling survey were conducted to implement investigation and analysis for the allocation situation of newly medical equipment of 188 medical institutions in 9 demonstration regions of the Project on Regional Application and Demonstration of Innovative Medical Equipment in Liaoning Province from 2015 to 2020.The allocation data of medical equipment between before(from 2015 to 2017)and after the demonstration projects were implemented(from 2018 to 2020)were compared.The occupancy rate of domestically medical devices(referred as"occupancy ratio of domestic device")was used as an evaluation indicator to assess the status of equipment allocation and application before and after the projects of application and demonstration were implemented in the region of innovative equipment for diagnosis and treatment.Results:In the 9 demonstrational regions of Liaoning province,the number of newly added domestic medical devices during the period from 2018 to 2020 increased from 1,608 units between 2015 and 2017 to 1,703 units.The occupancy ratio of newly added domestic devices increased from 72.7%to 84.9%.The occupancy ratio of domestic devices of newly added key equipment increased from 63.0%to 83.4%,and the growth rate reached 20.4%.In different districts and different grades of medical institution,the increase and application of domestically medical devices appeared difference.Conclusion:The occupancy rate of newly added domestically medical devices in 9 demonstration regions in Liaoning province has generally increased.However,there are still imbalances between different regions and different grades of medical institutions.The manufacturers of domestically medical devices still need strengthen brand building and marketing promotion,so as to further enhance market competitiveness of domestically medical devices.

Objective:To observe whether electroacupuncture(EA)can inhibit activation of JAK1/STAT3 signaling pathway and improve pulmonary inflammation in chronic obstructive pulmonary disease(COPD)by increasing expression of SOCS3.Methods:Atotal of 60 mice were randomly divided into normal group,model(COPD)group,COPD+EA group,COPD+si-SOCS3 group,COPD+si-SOCS3 NC group,COPD+si-SOCS3+EA group,with 10 mice in each group.Mice COPD model was replicated by simple cigarette smoking for three months.After modeling,SOCS3 siRNA was administered to lungs of mice in COPD+si-SOCS3 group and COPD+si-SOCS3+EA group,SOCS3 siRNA NC was administered to COPD+si-SOCS3 NC group.24 h after the first SOCS3 siRNA ad-ministration,mice in COPD+EA and COPD+si-SOCS3+EA groups were treated with EA in"Feishu"and"Zusanli",once every other day,30 min/times for 14 days.Lung function of mice in each group was detected;lung pathological changes were observed by HE staining;IL-6,IL-1β and TNF-α levels in mice broncho alveolar lavage fluid were detected by ELISA;protein expressions of SOCS3,JAK1,STAT3,p-JAK1 and p-STAT3 were detected by Western blot;SOCS3,JAK1 and STAT3 mRNA were detected by RT-PCR.Results:Compared with normal group,mice in COPD group showed decreased lung function,thickened alveolar walls,congestion and edema between tissues,significantly increased levels of inflammatory cytokines IL-6,TNF-α and IL-1β,decreased SOCS3 protein expres-sion,p-JAK1/JAK1 and p-STAT3/STAT3 significantly increased,JAK1 and STAT3 mRNA increased,SOCS3 mRNA decreased(P<0.05).Compared with COPD group,the above indexes of COPD+EA group were improved(P<0.05),and the above indexes of COPD+si-SOCS3 group were more serious(P<0.05),and COPD+si-SOCS3+EA group was improved compared with COPD+si-SOCS3 group(P<0.05).Conclusion:EA can inhibit overactivation of JAK1/STAT3 signaling pathway by up-regulating SOCS3 expression,and thus improve pulmonary inflammation in COPD.

Objective:To investigate and assess the situation of popularization and promotion of domestically innovative medical devices in Liaoning Province,so as to provide a basis for promoting the allocation policy of domestically innovation medical devices.Methods:Self-made questionnaire and on-site filling survey were conducted to implement investigation and analysis for the allocation situation of newly medical equipment of 188 medical institutions in 9 demonstration regions of the Project on Regional Application and Demonstration of Innovative Medical Equipment in Liaoning Province from 2015 to 2020.The allocation data of medical equipment between before(from 2015 to 2017)and after the demonstration projects were implemented(from 2018 to 2020)were compared.The occupancy rate of domestically medical devices(referred as"occupancy ratio of domestic device")was used as an evaluation indicator to assess the status of equipment allocation and application before and after the projects of application and demonstration were implemented in the region of innovative equipment for diagnosis and treatment.Results:In the 9 demonstrational regions of Liaoning province,the number of newly added domestic medical devices during the period from 2018 to 2020 increased from 1,608 units between 2015 and 2017 to 1,703 units.The occupancy ratio of newly added domestic devices increased from 72.7%to 84.9%.The occupancy ratio of domestic devices of newly added key equipment increased from 63.0%to 83.4%,and the growth rate reached 20.4%.In different districts and different grades of medical institution,the increase and application of domestically medical devices appeared difference.Conclusion:The occupancy rate of newly added domestically medical devices in 9 demonstration regions in Liaoning province has generally increased.However,there are still imbalances between different regions and different grades of medical institutions.The manufacturers of domestically medical devices still need strengthen brand building and marketing promotion,so as to further enhance market competitiveness of domestically medical devices.

Objective:To assess the clinical value of digital PCR (dPCR) for the prenatal diagnosis of common fetal aneuploidies.Methods:A dPCR-based assay was developed for detecting trisomies 21, 18, and 13. A retrospective analysis was carried out on 173 amniotic fluid samples collected by the Prenatal Diagnosis Center of Taizhou Hospital between January 2017 and December 2023. By using chromosomal karyotyping as the gold standard, the diagnostic performance of the multiplex dPCR system was evaluated in a double-blind manner. This study has been approved by the Ethics Committee of Taizhou Hospital (Ethics No. K20250339).Results:Chromosomal karyotyping has identified 59 cases of trisomy 21, 5 cases of trisomy 18, 2 cases of trisomy 13, 6 cases with chromosomal structural abnormalities or mosaicisms, and 101 cases with a normal karyotype. The dPCR results ( Z-score cutoff = 4.0, CI = 99.997%) showed full concordance with karyotyping (sensitivity = 100%, specificity = 100%, Kappa = 1). Among the 6 structurally abnormal or mosaicism samples, dPCR has accurately detected 4 cases, but mis-classified 2 cases of trisomy 21 with very low-level mosaicisms (3.3%, 6.9%, respectively) as normal. Conclusion:The established multiplex dPCR system demonstrated high diagnostic accuracy for common chromosomal aneuploidies, with results available within 24 hours. It can serve as an efficient supplementary tool to conventional chromosomal karyotyping, providing reliable support for time-sensitive clinical decision-making in prenatal diagnosis.