OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To explore the effect and mechanism of Slc1a2 overexpression on cognitive dysfunction in sleep-deprived mice.Methods A total of 130 mice were divided into five groups:normal sleep(NS),NS+ov-Slc1a2,sleep deprivation(SD),SD+ov-NC,and SD+ov-Slc1a2,with 26 mice in each group.The SD mice model was established using an automatic system based on a rotating rod,and overexpress Slc1a2 adenovirus was injected into the prefrontal cortex(PFC).Immunofluorescence and Western blotting were used to detect the expression of Slc1a2 in the mouse PFC.Electrophysiological tests were used to evaluate non-rapid eye movement(NREM)sleep time,rapid eye movement(REM)sleep time,and wakefulness time in mice.Real-time quantitative PCR was used to detect the expression of glutamate(Glu)and gamma-aminobutyric acid(GABA)metabolic enzymes in the mouse PFC.Whole-cell patch-clamp recording was used to detect the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSC)in mouse PFC.Immunofluorescence was used to detect the proportion of GABA-positive cells in the mouse PFC.The C11-BODIPY fluorescent probe was used to detect lipid reac-tive oxygen species(ROS)levels in mouse PFC.Commercial kits were used to detect Fe2+and malondialdehyde(MDA)levels in the mouse PFC.Cognitive function in mice was evaluated using the open field,novel object recognition,and Y-maze tests.Results Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index increased significantly,while wakefulness time decreased significantly in the NS+ov-Slc1a2 group(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD group and the SD+ov-NC group were significantly decreased,whereas wakefulness time was significantly increased(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the mouse PFC decreased significantly,whereas lipid ROS,Fe2+,and MDA levels increased significantly(all P＜0.05).Compared with the SD and SD+ov-NC groups,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD+ov-Slc1a2 group increased significantly,whereas the wakeful-ness time decreased significantly(all P＜0.05).The percentage of Slc1a2+GFAP+cells,the expression of Slc1a2 protein,the expression of Glul,Slc6a1,and Abat mRNA,the frequency and amplitude of mEPSC,and the proportion of GABA-positive cells in the mouse PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Conclusion Ectopic overexpres-sion of Slc1a2 in the PFC can improve sleep disorders in SD mice,reduce the damage caused by SD to excitatory synaptic transmission and GABAergic neuron function in the PFC,and alleviate cognitive impairment and anxiety-like behavior in these mice.Its mechanism may be related to the improvement of Glu/GABA metabolic imbalance in the PFC and inhibition of ferroptosis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To explore the effect and mechanism of Slc1a2 overexpression on cognitive dysfunction in sleep-deprived mice.Methods A total of 130 mice were divided into five groups:normal sleep(NS),NS+ov-Slc1a2,sleep deprivation(SD),SD+ov-NC,and SD+ov-Slc1a2,with 26 mice in each group.The SD mice model was established using an automatic system based on a rotating rod,and overexpress Slc1a2 adenovirus was injected into the prefrontal cortex(PFC).Immunofluorescence and Western blotting were used to detect the expression of Slc1a2 in the mouse PFC.Electrophysiological tests were used to evaluate non-rapid eye movement(NREM)sleep time,rapid eye movement(REM)sleep time,and wakefulness time in mice.Real-time quantitative PCR was used to detect the expression of glutamate(Glu)and gamma-aminobutyric acid(GABA)metabolic enzymes in the mouse PFC.Whole-cell patch-clamp recording was used to detect the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSC)in mouse PFC.Immunofluorescence was used to detect the proportion of GABA-positive cells in the mouse PFC.The C11-BODIPY fluorescent probe was used to detect lipid reac-tive oxygen species(ROS)levels in mouse PFC.Commercial kits were used to detect Fe2+and malondialdehyde(MDA)levels in the mouse PFC.Cognitive function in mice was evaluated using the open field,novel object recognition,and Y-maze tests.Results Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index increased significantly,while wakefulness time decreased significantly in the NS+ov-Slc1a2 group(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD group and the SD+ov-NC group were significantly decreased,whereas wakefulness time was significantly increased(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the mouse PFC decreased significantly,whereas lipid ROS,Fe2+,and MDA levels increased significantly(all P＜0.05).Compared with the SD and SD+ov-NC groups,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD+ov-Slc1a2 group increased significantly,whereas the wakeful-ness time decreased significantly(all P＜0.05).The percentage of Slc1a2+GFAP+cells,the expression of Slc1a2 protein,the expression of Glul,Slc6a1,and Abat mRNA,the frequency and amplitude of mEPSC,and the proportion of GABA-positive cells in the mouse PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Conclusion Ectopic overexpres-sion of Slc1a2 in the PFC can improve sleep disorders in SD mice,reduce the damage caused by SD to excitatory synaptic transmission and GABAergic neuron function in the PFC,and alleviate cognitive impairment and anxiety-like behavior in these mice.Its mechanism may be related to the improvement of Glu/GABA metabolic imbalance in the PFC and inhibition of ferroptosis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.