Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

OBJECTIVE: To investigate the clinical characteristics and prognostic of venetoclax (VEN) combined targeted therapy in acute leukemia (AL) patients with PICALM∷MLLT10 fusion gene positivity. METHODS: A retrospective analysis was conducted on 16 PICALM∷MLLT10-positive AL patients treated at the First Affiliated Hospital of Soochow University from January 2021 to August 2024. These patients were diagnosed by targeted RNA sequencing (RNA-seq) or reverse transcription multiplex PCR, including newly diagnosed and relapsed/refractory (R/R) cases. The immunophenotypes, genetic features, gene mutations, and the efficacy of VEN combination targeted therapy of patients were evaluated. RESULTS: Among the 16 cases, 3 were confirmed by reverse transcription multiplex PCR, and 13 were detected through targeted RNA-seq among 528 AL patients, with a detection rate of 2.46%. The averge age of patients was (28.0±8.58) years. Patients exhibited diverse immunophenotypes, including 7 cases of acute myeloid leukemia, 5 of acute T-lymphoblastic leukemia, 1 of acute B-lymphoblastic leukemia, 1 of acute undifferentiated leukemia, and 2 of mixed-phenotype acute leukemia. Among them, 11 had extramedullary disease (EMD), 14 expressed CD7, and 12 expressed CD33. Major co-occurring mutations included PHF6 (6 cases), NOTCH1 (5 cases), and 7 cases with complex karyotypes. Of the 12 patients who received standard induction therapy, 7 did not achieve remission (PR+NR). All 4 patients treated with VEN combination therapy achieved complete remission (CR). Among the 7 induction failure cases, 4 achieved CR upon re-induction with VEN, while the remaining 3 re-induced with standard therapy, did not achieve CR. Thirteen patients received allogeneic hematopoietic stem cell transplantation, including 6 who received maintenance therapy with hypomethylating agents (HMA) alone or in combination with VEN, and seven were followed up. Survival analysis showed that the overall survival was better in the maintenance therapy group (P =0.044). CONCLUSION PICALM∷MLLT10-positive AL involves multiple lineages and demonstrates poor response to conventional chemotherapy. VEN combination therapy shows promising efficacy in both newly diagnosed and R/R patients. Post-transplant maintenance therapy with HMA alone or combined with VEN may extend survival; however, further clinical validation is required.
Humans ; Sulfonamides/therapeutic use* ; Retrospective Studies ; Prognosis ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Adult ; Male ; Female ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

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*

3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.

ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Objective To explore the differences of regional homogeneity(ReHo)between overweight and normal weight male patients with type 2 diabetes mellitus(T2DM)during rest and their correlations with clinical features.Methods Twenty-five untreated male overweight T2DM(OW-T2DM)patients,25 untreated male normal weight T2DM(NW-T2DM)patients and 25 healthy controls(HC)were enrolled.The brain structure and resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from all subjects.The brain structure and rs-fMRI data were preprocessed,and ReHo values of all brain regions were calculated for all subjects.ReHo values were compared among three groups and between groups respectively via the methods of one-way analysis of variance and two-sample t-test.To address the problem of multiple comparisons,the method of AlphaSim was performed(the threshold was set at P<0.005,the number of voxel clusters was>12).In addition,Pearson correlation analysis was performed to explore the relationships between ReHo values of the abnormal brain regions and clinical features in patients.Results(1)The brain regions showed differences of ReHo values among three groups were mainly distributed in the right hemisphere,including the superior parietal gyrus,superior marginal gyrus and superior occipital gyrus;(2)Compared with HC,NW-T2DM patients showed significantly decreased ReHo values in the right medial superior frontal gyrus,right middle cingulate gyrus and left anterior cingulate gyrus;(3)Compared with HC,OW-T2DM patients showed significantly decreased ReHo values in the bilateral postcentral gyrus and bilateral middle cingulate gyrus;(4)Compared with NW-T2DM patients,OW-T2DM patients showed significantly decreased ReHo values in the right superior parietal gyrus,right superior occipital gyrus and left cuneus;(5)ReHo values of the right medial superior frontal gyrus and right superior parietal gyrus were negatively correlated with hemoglobinA1c(HbA1c)level and body mass index(BMI),respectively,in all patients.Conclusion The occurrence of T2DM in male patients may lead to the declined activity of brain regions located in the default mode network(DMN),while overweight may further lead to decreased brain activity within the attention and visual recognition network in male T2DM patients.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.