Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Objective To investigate the clinical manifestations of traditional Chinese medicine(TCM)and their associations with TCM constitutions in individuals who have migrated to plateau areas,and to provide a scientific basis for plateau health management.Methods Migrants living in areas above 3000 m were selected as research subjects.Data were collected by using TCM symptom assessment scales and constitution assessment scales.Descriptive statistical analysis was conducted to determine the incidence and severity of symptoms among individuals with different migration durations,and core symptoms were identified.Factor analysis was performed by using SPSS software to extract symptom clusters and explore the correlation between core symptoms and TCM constitutions.Results Among individuals who migrated to plateau areas,the incidence of discomfort symptoms was 83.44％.The five most common symptoms were dry skin(67.94％),forgetfulness(56.03％),dry mouth(52.06％),yellow urine(48.73％),and insomnia(47.14％).In the top 10 symptoms with the highest increase in incidence,yellow urine(33.51％)and forgetfulness(26.33％)were both present in the top 10 symptoms across different migration durations.Factor analysis extracted 5,2,4,and 6 symptom clusters from the overall population,individuals who migrated within 1 year,those who migrated for 1-2 years,and those who migrated over 2 years,respectively.Qi-deficiency constitution(QDC),blood stasis constitution(BSC),qi stagnation constitution(QSC),phlegm-dampness constitution(PDC),and dampness-heat constitution(DHC)were significantly positively correlated with forgetfulness.Conclusion Migrating to plateau areas can induce discomfort symptoms,and both the number and incidence of symptoms increase with longer migration durations.The number and incidence of high-frequency symptoms(incidence≥30％)increase with prolonged migration time.There are differences in the composition and severity of symptom clusters across different migration durations.QDC,BSC,QSC,PDC,and DHC are closely related to forgetfulness and can be considered risk constitutions for forgetfulness.Timely attention to changes in symptom clusters and constitutions can help prevent and mitigate the occurrence and development of symptoms.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

To enhance the understanding of familial erythrocytosis type 2 (ECYT2) resulting from compound heterozygous mutations in the VHL gene.Methods:We conducted a retrospective analysis of the case data from a patient with ECYT2 to investigate its pathogenesis, clinical features, diagnosis and treatment options, as well as prognosis, while also reviewing the relevant literature.Results:A 31-year-old man was admitted to the hospital due to facial and hand flushing that had persisted for 29 years. Whole exome sequencing revealed compound heterozygous mutations in VHL p.P81L and p.N90T. Both of his parents were found to carry only one of these heterozygous mutations, yet they exhibited normal phenotypes. Based on the patient's hematological tests, a clear diagnosis of ECYT2 was established. Following treatment with erythrocytapheresis and daily administration of aspirin at a dosage of 100 mg, the patient experienced relief from dizziness and headaches associated with blood hyperviscosity, without any thrombotic or bleeding complications during this period.Conclusions:ECYT2 is a rare group of autosomal recessive genetic disorders. This case of ECYT2, resulting from compound heterozygous mutations in the VHL gene, represents the first report in China. Clinically, it is characterized by elevated red cell mass, normal or increased serum erythropoietin levels, and normal hemoglobin oxygen affinity levels. These factors contribute to thrombotic and bleeding complications that can lead to early mortality.

Objective:To analyze the clinical characteristics, therapeutic responses, and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) .Methods:We retrospectively reviewed clinical data from 16 consecutive patients diagnosed with L-HES at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and October 2024. A control group of 65 patients with idiopathic hypereosinophilic syndrome (iHES), diagnosed during the same period, was used for comparison. Clinical and laboratory characteristics, therapeutic responses, and survival outcomes were compared between the two groups.Results:The most frequently involved organs at presentation in patients with L-HES were the skin (75.0%), gastrointestinal tract (25.0%), respiratory tract (18.8%), lymph nodes (18.8%), heart (12.5%), and spleen (6.3%). Compared with iHES patients, patients with L-HES had a significantly higher incidence of skin involvement ( P=0.016), with no statistically significant differences observed in the involvement of other organs. No statistically significant differences were found in complete blood count parameters between the two groups. Multiparameter flow cytometry revealed that the median percentage of CD3 -CD4 + T cells in the peripheral blood of patients with L-HES was 4.08% ( IQR: 1.64%-32.78%), with a median absolute count of 0.10 (0.05-0.55) ×10 9/L. Serum immunoglobulin E (IgE) levels were significantly higher in the L-HES group than in the iHES group ( P<0.001). Clonal rearrangement of T-cell receptor genes was detected in 75.0% of patients with L-HES. After diagnosis, 14 patients with L-HES received glucocorticoids as first-line therapy, yielding an overall response rate of 92.9%. During glucocorticoid tapering, 11 patients experienced recurrent eosinophilia or worsening of clinical symptoms. Three patients received interferon-alpha as a second-line therapy, with two achieving complete remission. After a median follow-up of 16 months ( IQR: 8-28 months), one patient died of cardiac insufficiency 8 months after diagnosis, and no cases of lymphoma transformation were observed. The 2-year overall survival rate was (91.7±8.0) %, which did not significantly differ from that of the iHES group (96.2±2.6) % ( P=0.746) . Conclusions:Patients with L-HES generally have a favorable prognosis and are often characterized by skin involvement and significantly elevated serum IgE levels at diagnosis. They typically respond well to glucocorticoid therapy, although relapse is common during dose tapering. Interferon-alpha may serve as an effective second-line therapeutic option.

To enhance the understanding of familial erythrocytosis type 2 (ECYT2) resulting from compound heterozygous mutations in the VHL gene.Methods:We conducted a retrospective analysis of the case data from a patient with ECYT2 to investigate its pathogenesis, clinical features, diagnosis and treatment options, as well as prognosis, while also reviewing the relevant literature.Results:A 31-year-old man was admitted to the hospital due to facial and hand flushing that had persisted for 29 years. Whole exome sequencing revealed compound heterozygous mutations in VHL p.P81L and p.N90T. Both of his parents were found to carry only one of these heterozygous mutations, yet they exhibited normal phenotypes. Based on the patient's hematological tests, a clear diagnosis of ECYT2 was established. Following treatment with erythrocytapheresis and daily administration of aspirin at a dosage of 100 mg, the patient experienced relief from dizziness and headaches associated with blood hyperviscosity, without any thrombotic or bleeding complications during this period.Conclusions:ECYT2 is a rare group of autosomal recessive genetic disorders. This case of ECYT2, resulting from compound heterozygous mutations in the VHL gene, represents the first report in China. Clinically, it is characterized by elevated red cell mass, normal or increased serum erythropoietin levels, and normal hemoglobin oxygen affinity levels. These factors contribute to thrombotic and bleeding complications that can lead to early mortality.

Objective:To analyze the clinical characteristics, therapeutic responses, and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) .Methods:We retrospectively reviewed clinical data from 16 consecutive patients diagnosed with L-HES at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and October 2024. A control group of 65 patients with idiopathic hypereosinophilic syndrome (iHES), diagnosed during the same period, was used for comparison. Clinical and laboratory characteristics, therapeutic responses, and survival outcomes were compared between the two groups.Results:The most frequently involved organs at presentation in patients with L-HES were the skin (75.0%), gastrointestinal tract (25.0%), respiratory tract (18.8%), lymph nodes (18.8%), heart (12.5%), and spleen (6.3%). Compared with iHES patients, patients with L-HES had a significantly higher incidence of skin involvement ( P=0.016), with no statistically significant differences observed in the involvement of other organs. No statistically significant differences were found in complete blood count parameters between the two groups. Multiparameter flow cytometry revealed that the median percentage of CD3 -CD4 + T cells in the peripheral blood of patients with L-HES was 4.08% ( IQR: 1.64%-32.78%), with a median absolute count of 0.10 (0.05-0.55) ×10 9/L. Serum immunoglobulin E (IgE) levels were significantly higher in the L-HES group than in the iHES group ( P<0.001). Clonal rearrangement of T-cell receptor genes was detected in 75.0% of patients with L-HES. After diagnosis, 14 patients with L-HES received glucocorticoids as first-line therapy, yielding an overall response rate of 92.9%. During glucocorticoid tapering, 11 patients experienced recurrent eosinophilia or worsening of clinical symptoms. Three patients received interferon-alpha as a second-line therapy, with two achieving complete remission. After a median follow-up of 16 months ( IQR: 8-28 months), one patient died of cardiac insufficiency 8 months after diagnosis, and no cases of lymphoma transformation were observed. The 2-year overall survival rate was (91.7±8.0) %, which did not significantly differ from that of the iHES group (96.2±2.6) % ( P=0.746) . Conclusions:Patients with L-HES generally have a favorable prognosis and are often characterized by skin involvement and significantly elevated serum IgE levels at diagnosis. They typically respond well to glucocorticoid therapy, although relapse is common during dose tapering. Interferon-alpha may serve as an effective second-line therapeutic option.

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 analyze the clinical characteristics, pregnancy outcomes and factors affecting live birth of patients undergoing multifetal pregnancy reduction (MFPR), in order to provide reference for clinical strategies.Methods:A retrospective cohort study was conducted on all patients who underwent multifetal pregnancy reduction among polychorionic multifetal pregnancy patients at the Center for Reproductive Medicine, Department of Obstetrics and Gynecology of Peking University Third Hospital during a period of 12 years from January 1, 2009 to December 31, 2020. The overall and annual clinical characteristics were analyzed, pregnancy outcomes were followed up. Patients were divided into live birth group ( n=1 555) and not live birth group ( n=205), and factors affecting live birth were analyzed by multivariate logistic. Through further subgroup analysis, multiple pregnancies were divided into three subgroups: dichorionic diamniotic twin, triplet pregnancy, and four or more high sequence multiple pregnancy. Results:A total of 1 925 patients who underwent MFPR were included, and 1 760 pregnancy outcomes were followed up. In the past 12 years, there had been an increase in dizygotic twins, and the proportion of transabdominal fetal reduction had significantly increased, from 3% in 2009 to 77% in 2020. The annual live birth rate of reduction patients fluctuated between 83% and 94%. The live birth rate of patients with MFPR was related with the type of multiple pregnancies, the method of reducing pregnancies, and the number of retained embryos. The live birth rate of four or more high sequence multiple pregnancies [75.8% (72/95)] was lower than that of dichorionic diamniotic twins [90.0% (796/884), P<0.001], the dichorionic diamniotic twins [89.9% (241/268), P<0.001], the trichorionic triamniotic triplet pregnancy [86.9% (446/513), P=0.005]. The live birth rate of transabdominal fetal reduction [91.4% (655/717)] was higher than that of transvaginal fetal reduction with fetal cardiac activity area injection of KCl [84.9% (304/358), P=0.001], and vaginal embryo aspiration [87.0% (596/685), P=0.009]. There was no statistically significant difference in the live birth rate between vaginal KCl injection and vaginal aspiration ( P=0.351). The survival rate of patients with retained singletons [89.7% (1 062/1 184)] was higher than that of patients with retained twins [85.6% (493/576), P=0.012]. After adjusting for confounding factors such as age, assisted pregnancy method, type of multiple pregnancies, and number of retained embryos, transabdominal fetal reduction was an independent protective factor for live birth rate ( P=0.040, OR=1.604, 95% CI: 1.021-2.519). Conclusion:With the change of transplantation strategy, the proportion of dichorionic diamniotic twins increased, and the proportion of transabdominal fetal reduction increased, which pregnancy outcomes might be better. There was no difference in pregnancy outcomes between those who underwent vaginal aspiration and transvaginal fetal reduction with fetal cardiac activity area injection of KCl. The outcomes of four or more high sequence multiple pregnancies were poor, and it was necessary to strictly control the number of embryo transfers and optimize ovulation promotion plans in clinical practice.