Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

OBJECTIVE: To investigate the short-term efficacy and safety of low-dose venetoclax combined with CHG (cytarabine+homoharringtonine+G-CSF) priming regimen in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy. METHODS: The data of 14 patients with AML or high-risk MDS admitted to the department of hematology/oncology of the First Hospital of Tsinghua University and 2 cooperative institutions from July 2022 to August 2023 were retrospectively analyzed. All the patients were treated with low-dose venetoclax combined with CHG priming regimen and the early induction (one course) efficacy and adverse reactions were observed. RESULTS: Among the 14 patients, 10 were males and 4 were females, with a median age of 69.5 (46-83) years. After 1 cycle of induction chemotherapy, the complete remission (CR) rate was 64.3% (9/14) and overall response rate (ORR) was 78.6% (11/14). Among the 10 patients with adverse prognosis according to cytogenetics and molecular genetics, the CR rate was 50.0% (5/10), and ORR was 70.0% (7/10). In 7 patients with TP53 mutation, the CR rate was 42.9% (3/7) and ORR was 71.4% (5/7). In the 6 patients with complex karyotype, CR rate was 33.3% (2/6) and ORR was 66.7% (4/6). While the CR rate and ORR of 8 non-complex karyotype patients were both 87.5% (7/8), and the difference in CR rate between patients with complex karyotype and non-complex karyotype was statistically significant ( P < 0.05). The adverse reactions of chemotherapy were tolerable, without early treatment-related deaths. CONCLUSION Low-dose venetoclax combined with CHG priming regimen can be used as an effective treatment for AML and high-risk MDS patients who are ineligible for intensive chemotherapy, and it is safe and worthy of clinical application.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Male ; Female ; Sulfonamides/therapeutic use* ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Aged, 80 and over ; Retrospective Studies ; Cytarabine/administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Homoharringtonine/therapeutic use*

OBJECTIVE: To investigate the significance of serum β₂-microglobulin (β₂-MG) for survival and relapse of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. METHODS: Clinical data of 92 patients with DLBCL admitted from December 2003 to July 2015 were retrospectively analyzed. The optimal cutoff value of β₂-MG levels for predicting prognosis of the DLBCL patients was determined using receiver operating characteristic (ROC) curve. KaplanMeier analysis was used to estimate progression-free survival (PFS) and overall survival (OS). Cox logistic regression analysis was used to explore potential prognostic factors associated with survival. Binary logistic regression analysis was used to analyze the relationship between various factors and relapse. RESULTS: The most discriminative cutoff value for β₂-MG level was determined to be 2.25 mg/L by the ROC curve. Subgroup analysis showed that patients in the elevated β₂-MG (＞2.25 mg/L) group had significantly worse PFS(P =0.006) and a trend toward worse OS compared with those in the low β₂-MG (≤2.25 mg/L) group(P =0.053). Univariate analysis showed that elevated β₂-MG, age>60 years, Ann Arbor stage III-IV, as well as IPI score ≥3 were associated with worse PFS. Binary logistic regression analysis showed that age＞60 years and β₂-MG＞2.25 mg/L were potential influencing factors for relapse of DLBCL patients. CONCLUSION Serum β ₂-MG might be an important predictor for the survival and relapse of DLBCL patients in the rituximab era.
Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; beta 2-Microglobulin/blood* ; Rituximab ; Retrospective Studies ; Prognosis ; Female ; Male ; Middle Aged ; Recurrence ; ROC Curve

Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo (TXL) capsule to treat atherosclerosis. However, clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable. In response, we developed this study to investigate the hypothesis that on the basis of statin therapy, treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome (ACS). The TXL-CAP study was an investigator-initiated, randomized, double-blind clinical trial conducted across 18 medical centers in China. Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness (FCT) < 100 μm and lipid arc > 90° as defined by optical coherence tomography (OCT) were recruited. A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL (n = 110) or placebo (n = 110) for a duration of 12 months. The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up. Secondary endpoints included: (1) changes of the maximum lipid arc and length of the target plaque, and the percentage of lipid, fibrous, and calcified plaques at the end of the 12-month period; (2) the incidence of composite cardiovascular events and coronary revascularization within the 12 months; (3) changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society (CCS) grading system and Seattle angina questionnaire (SAQ) score, respectively; and (4) changes in hs-CRP serum levels. The results of the TXL-CAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

OBJECTIVE To provide a reference for the implementation and high-quality development of hospital medication reconciliation. METHODS A semi-structured questionnaire was designed to investigate the implementation of drug reconciliation services in medical institutions before and after the release of 5 standards such as Standard for Medication Reconciliation Services in Medical Institutions（“standards” for short，in 2021 and 2022）. Descriptive statistical analysis was conducted on the survey results. RESULTS After the promulgation of the standards， the medication reconciliation service rate of all types of medical institutions increased from 15.10% （434/2 874） in 2021 to 27.84%（363/1 304） in 2022. In 2022， in the 363 medical institutions providing drug reconciliation services， the median number of pharmacists involved in drug reconciliation was 6. The participation rate of pharmacists in standardized training for drug reconciliation services was 75.00%， among which the participation rate of third-class hospitals was higher， reaching 85.71%. The main stages covered by medication reconciliation services included patient admission， transfer between departments， and discharge. The main problems found in the service included repeated medication （252， 69.42%）， inappropriate usage and dosage （228， 62.81%）， drug interactions and adverse reactions （218， E-mail：cputianxin@163.com 60.06%）. Only 69 institutions （19.01%） had a separate electronic information recording system， while 48 institutions 58516003。E-mail：zhenjiancun@vip.163.com （13.22%） had established comprehensive quality management and evaluation improvement systems. In terms of value embodiment， 141 institutions （38.84%） did not provide any form of compensation to relevant pharmacists. “Closely linked to enhancing patient satisfaction and improving services” was the most significant experience influencing medication reconciliation work（192， 52.89%）， while “the shortage of talent which meet the relevant requirements” stands as the primary challenge faced by medical institutions at all levels（238， 65.56%）. CONCLUSIONS The release of the standards has effectively improved the development rate of medication reconciliation in national medical institutions. However， there is still room for improvement in various aspects， including the allocation of personnel for medication reconciliation services， service content， information management， and the construction of quality control and evaluation systems.

Objective:To explore the levels of regulatory T cells(Tregs)and cytokines IL-35,TGF-β and IL-10 in peripheral blood of hemophilia A(HA)patients with F Ⅷ inhibitor and their clinical significance.Methods:43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected,including 6 cases with F Ⅷ inhibitor and 37 cases without FⅧ inhibitor.In addition,20 healthy males who underwent physical examinations were selected as healthy controls.Flow cytometry was used to detect the levels of CD4+CD25+CD127-Tregs in peripheral blood of the HA patients and healthy controls,and ELISA assay was used to detect the expression levels of IL-35,TGF-β and IL-10 in serum,and their differences between different groups were compared.Results:Compared with the healthy control group,the level of Tregs in HA patients was decreased,and the level of Tregs in the FⅧ inhibitor positive group was the lowest,the difference was statistically significant(P＜0.05).There was no significant difference in the expression level of Tregs in HA patients of different severity levels.The serum IL-35,TGF-β,and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group,and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group(all P＜0.05).Conclusion:The decrease of Tregs,IL-35,TGF-β,and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Objective:To analyze the application value of MCV,MCH and HbA2 in screening for thalassemia in the population of childbearing age in Quanzhou area,and to determine the optimal screening cut-off value of relevant indicators in this area. Methods:2725 couples of childbearing age were included in the study and underwent routine blood test,capillary hemoglobin electrophoresis,and α and β thalassemia gene test. Statistical methods were used to analyze the distribution of thalassemia genotypes,and compare the performance of MCV,MCH,and HbA2 in screening various types of thalassemia. According to the ROC curve,the best cut-off values of MCV,MCH and HbA2 in screening for thalassemia in this area were determined. Results:In this study,a total of 1801 thalassemia carriers were detected,including 1341 cases of α-thalassemia,420 cases of β-thalassemia,and 40 cases of αβ compound thalassemia. The most common genotypes of α-thalassemia and β-thalassemia were--SEA/αα and β654/βN,respectively. ROC curves were drawn to evaluate the performance of MCV,MCH and HbA2 in screening for α-thalassemia,mild β-thalassemia,αβ compound thalassemia,silent α-thalassemia,mild α-thalassemia,and intermediate α-thalassemia. The maximum areas under the curves (AUC) were 0.747,0.865,0.724,0.486,0.812,0.841;0.747,0.846,0.703,0.479,0.796,0.903;0.613,0.980,0.909,0.465,0.674,0.996,respectively;and the best cut-off values corresponding to the three screening indicators were 76.15fl,71.95fl,77.35fl,86.15fl,75.41fl,61.15fl;24.35pg,21.51pg,25.45pg,28.65pg,24.01pg,20.51pg;2.45％,3.05％,3.55％,3.25％,2.45％,1.65％,respectively. Conclusion:The levels of MCV,MCH and HbA2 are correlated with the phenotype of thalassemia,and the detection of these indicators is of great significance for the prevention and control of thalassaemia.