ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

The detection of coagulation function is helpful for the diagnosis of blood diseases,the assess-ment of bleeding and thrombus risks in patients,and the treatment of hemostasis and anticoagulation.It plays an important role in the diagnosis,treatment,and prevention of diseases.Solidification curve waveform analy-sis is a newly developed method for assessing coagulation function.It obtains more sensitive parameters for e-valuating the coagulation function of the body by taking the order derivative of the waveform reflecting the co-agulation process in routine coagulation experiments.Compared with traditional coagulation function tests,co-agulation cuvre waveform analysis curves is more comprehensive and effective in assessing the risk of bleeding and thrombosis.

Objective:To explore the relationship between memory bias, mental imagery, attention bias and depression in college students.Methods:From May to July 2024, a questionnaire was randomly distributed among 72 undergraduate students.The Beck depression inventory and Beck anxiety inventory were used to evaluate the depression and anxiety levels of all participants.The eye tracker was used to record the eye movement data of participants when observing emotional facial images.After the eye movement experiment, the scenario-based event completion task and prospective imagery task were used to collect the memory bias and mental imagery scores of all participants.SPSS 23.0 software was used for Spearman correlation analysis, and PROCESS 3.5 macro program was used for mediating effect test.Results:The scores of college students' negative memory bias, negative mental imagery, negative attention bias and depression were 0.40±0.15, 25.86±9.39, 0.41±0.14, 11.00(5.00, 20.00), respectively.Negative memory bias in college students was significantly and positively correlated with negative mental imagery, negative attention bias and depression ( r=0.832, 0.627, 0.834, all P<0.01).Negative mental imagery in college students was significantly and positively correlated with negative attention bias and depression ( r=0.692, 0.969, both P<0.01).Negative attention bias in college students was significantly and positively correlated with depression ( r=0.693, P<0.01).Negative mental imagery and negative attention bias had significant single chain mediating effect between negative memory bias and depression in college students, accounting for 16.61%(0.146/0.879), 15.70%(0.138/0.879)and 4.89%(0.043/0.879)of the total effect, respectively. Conclusion:There is a significant positive correlation between negative memory bias, negative mental imagery, negative attention bias and depression.Negative mental imagery and negative attention bias not only partially mediate the relationship between negative memory bias and depression in college students, but also have a chain mediating effect.

Objective To investigate the expression of leukocyte cell-derived chemotaxin 2(LECT2)and complement C3 in the serum of patients with autoimmune hepatitis(AIH),and their correlation with liver function grading and prognosis.Methods A total of 109 AIH patients admitted to our hospital from January 2022 to February 2024 were included as the observation group.According to the disease activity upon admission,they were grouped into the active group(59 cases)and the remission group(50 cases).According to the Child-Pugh grading,they were assigned into the grade A group(47 cases),the grade B group(40 cases),and the grade C group(22 cases).According to the prognosis,they were assigned into a poor prognosis group(35 cases)and a good prognosis group(74 cases),with 110 healthy volunteers who underwent physical checkup in our hospital as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to measure serum LECT2 level.Immunoturbidimetry was applied to detect serum complement C3 level.The correlation between LECT2,complement C3 and clinical indexes was analyzed by Pearson correlation analysis.Spearman correlation analysis was applied to analyze the relationship between serum LECT2,complement C3,and Child-Pugh grading.Receiver operating characteristic(ROC)curves were established to evaluate the predictive value of LECT2 and complement C3 levels for poor prognosis in AIH patients.Results The serum level of LECT2 in the observation group was higher than that in the control group,and the level of complement C3 was lower than that in the control group(P＜0.05).The expression level of ELECT2 in the grade C group was prominently higher than that in the grade B group and grade A group,while the expression level of complement C3 was prominently lower than that in the grade B group and grade A group(P＜0.05).The level of serum LECT2 in poor prognosis group was higher than that in good prognosis group,and the level of serum complement C3 was lower than that in good prognosis group(P＜0.05).Pearson correlation analysis showed that LECT2 was positively correlated with IgG,IL-6,TNF-α and Th17/Treg,and negatively correlated with TGF-β,while complement C3 was negatively correlated(all P＜0.05);Spearman correlation analysis showed that LECT2 level was positively correlated with Child-Pugh grading,while complement C3 level was negatively correlated with Child-Pugh grading(rs=0.803,-0.875,both P＜0.05).ROC curve reveled that the AUC of serum LECT2 and complement C3 levels in predicting poor prognosis of AIH patients was 0.802 and 0.805,respectively,the AUC of their combined detection was 0.905,which was higher than that of single indicator detection(P＜0.05).Conclusion Serum LECT2 level is elevated and complement C3 level is reduced in AIH patients,and they are correlated with liver function grading and disease severity.The combined detection of the two can serve as serological indicators for evaluating liver function and predicting prognosis.

Purpose To investigate the presence,proportion,clinical significance and origin of tumor cells with a macrophage phenotype in tumor tissues of patients with diffuse large B-cell lymphoma(DLBCL),and to explore wheth-er CD68 positive tumor cells can be induced in DLBCL cell lines in vitro.Methods The presence of CD68+CD163+CD20+PAX5-cells in the samples of DLBCL patients was first qualitatively detected by multiplex immunofluorescence staining,and then the proportion of CD79a+B lymphocytes,CD68+macrophages,and CD68+CD79a+double-positive cells were quantified.Patients were grouped according to the proportion of double-positive cells,and the differences in prognosis and clinicopathological features of DLBCL patients between subgroups were investigated.For cases with posi-tive BCL6 gene locus breaks,co-localization of CD68 with BCL6 gene breakapart was performed using combined immu-nofluorescence and immunological in situ hybridization to ascertain the tumor nature of B cell with a macrophage pheno-type.DLBCL cell lines(OCI-LY3,SU-DHL2)were treated with phorbol myristate acetate(PMA),and changes in the proteins levels of CD68 and PAX5 proteins were detected by flow cytometry.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA levels of PAX5,an important transcription factor for B cell differentiation and develop-ment,and macrophage-related genes(CD68,ARG1,CD163,CD206,Dectin-1,PU.1,C/EBPα,C/EBPβ).In ad-dition,PMA-treated DLBCL cell lines(OCI-LY3,SU-DHL2)were co-incubated with pH-sensitive fluorescent dye pHrodo to detect the phagocytosis ability of PMA-treated DLBCL cells.Results The percentage of CD68+B lympho-cytes in 50 patients with DLBCL varied from 0 to 9.3％,and the overall survival(OS)ranged from 0.008 2 to 4.2 years.Patients with the low CD68+B lymphocytes group exhibited a significantly lower OS compared to those in the high CD68+B lymphocytes group(P=0.039).There was a significant difference in the molecular typing of DLBCL patients(P=0.009 5)between different subgroups for the proportion of CD68+B lymphocytes.CD68+B lymphocytes were derived from tumor cells in DLBCL patients.The proportion of CD68+cells and CD68+PAX5-cells significantly increased in DLBCL after treatment with PMA(P＜0.05).The other macrophage markers CD68,ARG1,CD 163,CD206,Dectin-1,PU.1,C/EBPα,C/EBPβ,and the important B-cell transcription factor PAX5 were significantly different from the control group in terms of relative mRNA expression(P＜0.05).Cellular phagocytosis was enhanced after PMA treatment of DLBCL cells.Conclusion Diffuse large B-cell lymphoma tumor tissue contains a certain per-centage of CD68+neoplastic B lymphocytes.The proportion of CD68+B lymphocytes is correlated with patient progno-sis and molecular typing.DLBCL cell lines can be induced to differentiate into CD68+tumor cells in vitro.

Objective:To analyze the differences in clinicopathological features between non-elderly and elderly patients with melanoma, and to identify risk factors for prognosis in elderly patients with melanoma.Methods:A retrospective analysis was conducted on clinical and pathological data collected from non-elderly (aged < 60 years) and elderly (aged ≥ 60 years) patients with melanoma, who were confirmedly diagnosed according to clinical manifestations and histopathological findings at the People's Hospital of Xinjiang Uygur Autonomous Region from January 2008 to December 2023. The differences in clinical and pathological characteristics between the two groups were analyzed using the chi-square test and Wilcoxon rank-sum test. Survival curves were estimated using the Kaplan-Meier method and log-rank test. The relationship between clinicopathological variables and overall survival was analyzed using a Cox regression model.Results:A total of 233 patients with cutaneous melanoma were included, with the age being 60.3 ± 14.7 years, and the number of patients was highest in the age group of 60 - 69 years. There were 102 cases (43.8%) in the < 60 years old group and 131 cases (56.2%) in the ≥ 60 years old group. Compared with the < 60 years old group, the ≥ 60 years old group showed a significant increase in the proportion of patients with active tumor-infiltrating lymphocytes ( P = 0.040), proportion of those with Ki-67 index ≥ 30% ( P = 0.010), and Charlson comorbidity index ( P = 0.002), but a significant decrease in the proportion of patients with BRAF/KIT/NRAS mutations ( P = 0.003), proportion of those receiving surgical treatment ( P = 0.034), and proportion of those receiving adjuvant therapy ( P = 0.042). There was a significant difference in the overall survival between the two groups (log-rank test, χ2 = 6.10, P = 0.014). The gender, metastasis status, presence or absence of ulceration, distant metastasis status, American Joint Committee on Cancer staging, Charlson comorbidity index, and Breslow thickness were important prognostic indicators affecting the overall survival in the elderly patients with melanoma. Multivariate Cox regression analysis showed that males ( P = 0.015, HR = 4.622, 95% CI: 1.352 - 15.798), presence of distant metastasis ( P = 0.013, HR = 9.844, 95% CI: 4.621 - 59.763), and Charlson comorbidity index ≥ 3 ( P = 0.038, HR = 3.149, 95% CI: 1.067 - 9.294) were independent risk factors affecting the overall survival in the elderly patients with melanoma. Conclusions:Compared with the non-elderly patients with melanoma, a higher Ki-67 index, a higher Charlson comorbidity index, less surgical treatment, and less adjuvant therapy were more common in the elderly patients with melanoma. Males, the presence of distant metastasis, and Charlson comorbidity index ≥ 3 appeared to be independent risk factors affecting the overall survival in the elderly patients with melanoma.

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.

OBJECTIVES: To explore the effects of exogenous trigger (hCG/GnRHa) versus endogenous LH surge in natural cycle IVF/ICSI (NC-IVF/ICSI) for patients with diminished ovarian reserve (DOR). METHODS: A retrospective analysis was conducted on 1,118 NC-IVF/ICSI cycles from two reproductive centers between 2013 and 2024. Propensity score matching (PSM) and multivariate logistic regression were used to adjust for confounding factors. The trigger-day hormone threshold was determined using receiver operating characteristic (ROC) curve analysis. Outcome measures included oocyte retrieval rate, 2PN fertilization rate, clinical available embryo rate, high-quality embryo rate, fresh cycle clinical pregnancy rate (CPR), and live birth rate (LBR). RESULTS: After adjusting for confounders via PSM and logistic regression, the exogenous trigger group demonstrated significantly better outcomes across all the evaluated parameters (oocyte retrieval rate, 2PN fertilization rate, transferable embryo rate, high-quality embryo rate, fresh cycle CPR, and LBR) than the endogenous LH surge group (P<0.05). Age-stratified analysis revealed that for the entire cohort, exogenous triggering significantly increased the number of transferable embryos and high-quality embryos (P<0.001). In the 35-39 years old subgroup, exogenous triggering showed significant advantages in oocyte yield, high-quality embryo rate, CPR, and LBR (P<0.05) and resulted in the most pronounced improvement in LBR (OR=6.25, 95% CI: 1.34-29.23). ROC analysis established a decision-day LH threshold of 19.055 mIU/mL (AUC=0.945, specificity=93.3%) for precise stratification of the clinical pathways. CONCLUSIONS For DOR patients undergoing NC-IVF/ICSI, exogenous triggering comprehensively improves the treatment outcomes, particularly providing significant live birth benefits for women aged 35-40 years. An individualized protocol incorporating the LH threshold (19.055 mIU/mL) effectively enhances embryonic developmental potential and live birth rates.
Humans ; Female ; Ovarian Reserve ; Pregnancy ; Propensity Score ; Retrospective Studies ; Fertilization in Vitro ; Sperm Injections, Intracytoplasmic ; Chorionic Gonadotropin ; Pregnancy Rate ; Logistic Models ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone ; Adult ; Oocyte Retrieval