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.

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 the correlation between blood glucose variability index(GLUCV)and postoperative delirium(POD)in elderly patients undergoing knee arthroplasty.Methods A total of 112 elderly patients undergoing elective knee arthroplasty were analyzed retrospectively,16 males and 96 females,aged 65-80 years,BMI 22.0-28.0 kg/m2,ASA physical status Ⅰ or Ⅱ.They were di-vided into two groups according to whether they had POD within 5 days after operation:POD group and non-POD group.The score of the last preoperative mini-mental state examination(MMSE),operation time,the duration of the intraoperative regional cerebral oxygen saturation(rScO2)value decreased by more than 13％of the rScO2 basic value(△rScO2＞13％),the preoperative hemoglobin(Hb)and C-reactive protein(CRP)concentration,the fingertip blood glucose concentration before entry,before anesthesia induction,5 minutes after anesthesia induction,1 minute after skin incision,and before leaving the chamber were col-lected,and the GLUCV was calculated.The risk factors of POD in elderly patients undergoing knee arthro-plasty were analyzed by univariate and multivariate logistic regression,and the odds ratio(OR)and 95％confidence interval(CI)were calculated.The receiver operating characteristic(ROC)curve was drawn to calculate the area under the curve(AUC)and analyze the predictive value of GLUCV.Results Thirty patients(26.8％)showed POD symptoms within 5 days after surgery.Compared with the non-POD group,the operation time and duration of intraoperative △rScO2＞13％in the POD group were significantly prolonged(P＜0.05),the CRP concentration and GLUCV were significantly increased(P＜0.05).Multi-variate logistic regression analysis showed that prolonged time of △rScO2＞13％(OR=3.542,95％CI 1.380-9.093,P=0.011),elevated CRP concentration(OR=1.984,95％CI 1.078-3.650.P=0.015),and elevated GLUCV(OR=5.257,95％CI 1.690-16.353,P=0.008)were risk factors of POD in elderly patients undergoing knee arthroplasty.ROC curve analysis showed that the area under the AUC of GLUCV in predicting POD in elderly patients undergoing knee arthroplasty was 0.747(95％CI 0.650-0.844,P＜0.001),while the optimal cutoff value was 23.4％,the sensitivity was 71.4％,and the specificity was 63.3％.Conclusion GLUCV is closely related to POD,and GLUCV level has a good pre-dictive effect on POD in elderly patients undergoing knee arthroplasty.

Objective To observe the value of intratumoral and peritumoral CT radiomics for evaluating KRAS gene status in patients with colorectal adenocarcinoma.Methods Totally 245 patients with colorectal adenocarcinoma were retrospectively enrolled and divided into mutant group(n=139)and wild group(n=106)according to KRAS gene status,also divided into training set(n=171)and test set(n=74)at a ratio of 7∶3.Clinical data were compared between groups,and clinical factors were screened with logistic regression analysis to establish a clinical model.Based on enhanced venous phase CT images,intratumoral volume of interest(VOI),peritumoral VOI,and intratumoral+peritumoral VOI were delineated,radiomics features were extracted,and radiomics models were constructed.The combination model was constructed based on the best radiomics model combined with clinical factors.The value of each model for evaluating KRAS gene status in patients with colorectal adenocarcinoma was analyzed.Results Significant differences of patients’gender and carcinoembryonic antigen(CEA)were found between mutant group and wild group(both P＜0.05),which were independent impact factors of KRAS gene status in patients with colorectal adenocarcinoma(both P＜0.05).The area under the curve(AUC)of clinical model for evaluating KRAS gene status in patients with colorectal adenocarcinoma in training set and test set was 0.633 and 0.658,respectively.Intratumoral+peritumoral 3 mm model was the best radiomics model,with AUC of 0.921 and 0.894 in training set and test set,respectively.AUC of the combination model in training set and test set was 0.949 and 0.956,respectively.In training set,significant differences of AUC were found between clinical model and intratumoral+peritumoral 3 mm model,also between clinical model and combination model(both P＜0.001),while in test set,significant differences of AUC were found between each two models(all P＜0.05).Conclusion Intratumoral+peritumoral 3 mm radiomics based on enhanced venous phase CT could help to evaluate KRAS gene status in patients with colorectal adenocarcinoma.Combining with patients’gender and CEA could further improve efficacy of this model.

Objective To observe the value of contrast-enhanced CT radiomics combined with clinical and hematology indicators for predicting lymph node(LN)metastasis(LNM)of esophageal squamous cell carcinoma(ESCC).Methods Totally 218 ESCC patients were retrospectively enrolled.Stage pN1 and pN2 were clustering as LNM(n=90),while stage pN0 were taken as non-LNM(n=128).The patients were divided into training set(n=174)and test set(n=44)at the ratio of 8∶2.In training set,clinical and LN imaging features which could be used to independently judge LNM were screened and a clinical-imaging model was constructed.The hematological indicators that might be associated with ESCC LNM were screened,and a hematological model was constructed.Radiomics features in LN ROI and ESCC volume of interest(VOI)were extracted based on venous-phase contrast-enhanced CT images,and those might be associated with LNM were screened,and a radiomics model was constructed.Finally a combined model was constructed based on all the above features.The efficacy of each model for diagnosing LNM was evaluated with the area under the curve(AUC)of receiver operating characteristic curves,and the clinical net benefit was evaluated using decision curve analysis(DCA).Results Body mass index(BMI)and internal necrosis of target LN were both independent judging factors for ESCC LNM(both P＜0.05),and AUC of clinical-imaging model for diagnosing LNM in training and test sets was 0.747 and 0.687,respectively.Seven hematological indicators were included in hematological model,and AUC in training and test sets was 0.623 and 0.583,respectively.Ten LN radiomics features and 15 ESCC radiomics features were included in radiomics model,and AUC in training and test sets was 0.769 and 0.745,respectively.AUC of the combined model for diagnosing LNM in training and test sets was 0.822 and 0.739,respectively,better than other models in training set(all P＜0.05),but no significantly different in test set(all P＞0.05).DCA showed that combined model had higher net gain than the other models in 0.55-0.80 threshold probability interval.Conclusion Combined model based on venous-phase contrast-enhanced CT radiomics and clinical and hematology indicators could relatively effectively evaluate ESCC LNM,which might bring some promotions in clinical benefit.

OBJECTIVE: This study investigated the association between household chemical use and respiratory disease (RD) in older Chinese adults. METHODS: The data were from the 2018 China Longitudinal Health and Longevity Survey (CLHLS) database, which included 12,866 participants aged ≥ 65 years. The prevalence of RD was based on self-reported medical history, and patients were divided into diseased and non-diseased groups. The frequency of household chemical usage was divided into four categories, and a total score for eight household chemical usage categories was constructed. Binary logistic regression was used to determine the relationship between the frequency of household chemical use and RD, and a restricted cubic spline was used to determine the dose-response association. RESULT: After adjusting for all covariates, regular use of repellents [odds ratios ( OR) = 1.28, 95% CI 1.06-1.55] and oil removers ( OR = 1.28, 95% CI 1.03-1.58) were associated with RD. There was a dose-response association between the total score of household chemicals usage and RD risk ( P non-linearity > 0.05, P for trend < 0.01). Using patients with the total score below 9 as a reference, the OR for patients with the total score ranging from 25 to 32 is 2.33 (95% CI 1.25-4.09). CONCLUSION Regular use of repellents and oil removers increased the risk of RD, and the dose-dependent relationship was also observed.
Humans ; China/epidemiology* ; Aged ; Male ; Female ; Respiratory Tract Diseases/chemically induced* ; Aged, 80 and over ; Household Products/adverse effects* ; Prevalence

Objective:To seek the effect of group education under the BOPPPS model(bridge-in, objective, pre-assessment, participatory learning, post-assessment, summary) on the breastfeeding competency of first gestation women, to improve the breastfeeding competency of first gestation women and promote the realization of postpartum breastfeeding.Methods:Eighty-one first gestation women were chosen from the gestation class of the First Affiliated Hospital of Shanxi Medical University, the quasi-experimental research method was adopted, 40 women from January to February 2022 were involved in the control group and 41 women from May to June 2022 were involved in the intervention group. The control group was assigned common education, while the intervention group was assigned group education based on BOPPPS model. Breastfeeding Competency Scale (BCS) and breastfeeding family support questionnaire were used to compare breastfeeding competency and family support level of the two groups before and after intervention, and the skin contact rate at 1 hour after delivery and the pure breastfeeding rate at 42 days after delivery were compared between the two groups.Results:Before intervention, there was no significant difference in breastfeeding competency and family support level between the two groups (all P>0.05). After 4 weeks of intervention, the scores of breastfeeding competency and family support were (147.59 ± 13.50), (3.16 ± 0.18) points in the intervention group, more than those in the control group (125.48 ± 16.87), (2.87 ± 0.22) points, the differences were statistically significant between the two groups ( t=-6.52, -6.30, both P<0.05). The skin contact rate at 1 hour after delivery and the pure breastfeeding rate at 42 days postpartum were 75.6%(31/41), 53.7%(22/41) in the intervention group, more than those in the control group 52.5%(21/40), 30.0%(12/40), the differences were statistically significant between the two groups ( χ 2=4.71, 4.65, both P<0.05). Conclusions:Group education based on BOPPPS model can improve the level of breastfeeding competency and family support of gestation women. It increases the skin contact rate, and plays a good role in promoting the increase of pure breastfeeding rate.

Background Non-occupational carbon monoxide (CO) poisoning is a public health problem that seriously affect people’s health and lives. Objective To describe the prevalence of non-occupational CO poisoning during 2007—2018 in Shanghai, analyze its epidemiological characteristics and potential influencing factors, and explore effective prevention and control measures. Methods Daily reported non-occupational CO poisoning cases and meteorological factors from 2007 to 2018 were collected in Shanghai, epidemiological characteristics were analyzed by descriptive epidemiology methods, and a distributed lag nonlinear model was used to assess the association between temperature and non-occupational CO poisoning. Results A total of 2264 non-occupational CO poisoning events and 3866 cases from 2007 to 2018 were reported in Shanghai, including 59 death cases. More than half of the poisoning cases were female (56.3%), and young adults accounted for more cases than any other age group (54.8%). The poisoning events mainly occurred in winter (from December to next February); however, cases reported in summer increased in recent years. The peak period of the events was from 20:00 to 24:00. Households (85.2%) and restaurants (8.0%) were the common places of non-occupational CO poisoning events, and the main cause was improper use of gas water heater (36.9%). A nonlinear curve was found between daily average temperature of current day and the occurrence of non-occupational CO poisoning. Temperature was negatively associated with the risk of non-occupational CO poisoning when the temperature was lower than 9.6 ℃, while a positive association was found during 9.7-26.0 ℃. Conclusion Winter is a high season for non-occupational CO poisoning in Shanghai, rising cases reported in summer is also worthy of attention. Supervision should be strengthened to ban sales of unqualified gas water heaters, and health education on CO poisoning prevention and control should be conducted through multiple channels, in order to reduce the incidence of CO poisoning.