Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

Objective: To investigate the chemical compositions of Maxing Shigan Decoction (麻杏石甘汤, MXSGD) and elucidate its anti-influenza A virus (IAV) mechanism from prediction to validation. Methods: Ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the chemical compositions of MXSGD. Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV. A protein-protein interaction (PPI) network was then constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations. A total of 24 BALB/c mice were infected with IAV to build IAV mouse models. After successful modelling, the mouse models were randomly divided into model, MXSGD high-dose (2.8 g/kg), MXSGD low-dose (1.4 g/kg), and oseltamivir (20.14 mg/kg) groups, with an additional normal mice as control group (n = 6 per group). The treatments were administered by gavage daily between 8:00 a.m. and 10:00 a.m. for five consecutive days. Upon completion of the administration, the body weight ratio, lung index, protein content in the bronchoalveolar lavage fluid (BALF), and the levels of inflammatory factors including interleukin (IL)-6 and tumor necrosis factor (TNF)-α in mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection. Furthermore, the expression levels of mechanistic target of rapamycin (mTOR), hypoxia inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) proteins in the HIF-1 signaling pathway, which was enriched by network pharmacology, were detected by Western blot. Results: A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method. These chemical components can be classified into 9 primary categories and 31 secondary categories. After intersecting the chemical component targets with IAV-related targets, a total of 567 potential MXSGD components targeting IAV were identified. The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways, including apoptosis, TNF, HIF-1, and IL-17 signaling pathways. The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α, mTOR, and VEGF were all lower than – 5.0 kcal/mol. Furthermore, molecular dynamics simulations confirmed the structural stability of the resulting complexes. Animal experiments showed that compared with the normal controls, IAV-infected mice showed significantly reduced body weight ratio, markedly increased lung index, protein content in BALF, and the levels of inflammatory factors such as IL-6 and TNF-α (P < 0.01), thereby causing damage to the lung tissue; consequently, the expression levels of mTOR, HIF-1α, and VEGF proteins in the lung tissues of these mice were significantly elevated (P < 0.01). However, after MXSGD treatment, the mouse models presented a significant increase in body weight ratio, as well as marked decreases in lung index, protein content in BALF, and the levels of inflammatory factors including IL-6 and TNF-α (P < 0.01). Furthermore, the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR, HIF-1α, and VEGF proteins in lung tissues (P < 0.01 or P < 0.05). Conclusion MXSGD exerts anti-IAV effects through multi-component, multi-target, and multi-pathway synergism. Among them, 1-methoxyphaseollin is identified as a potential key component, which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway, providing experimental evidence for the clinical application of MXSGD.

OBJECTIVES: To investigate the synergistic inhibitory effects of AKBA and doxorubicin on malignant phenotype of triple-negative breast cancer (TNBC) MDA-MB-231 cells. METHODS: CCK-8 assay was used to determine the 48-h IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells, and SynergyFinder was employed to calculate the synergistic index and the optimal concentrations of the two agents. MDA-MB-231 cells treated with AKBA (22.5 μmol/L), doxorubicin (0.84 μmol/L) or their combination were examined for changes in cell proliferation, migration, invasion and apoptosis using Transwell migration, scratch assay, clone generation, RT-qPCR and Western blotting. Network pharmacology analysis was conducted to identify the downstream targets of AKBA in TNBC. In nude mouse models bearing subcutaneous MDA-MB-231 cell xenografts, the effects of normal saline, AKBA (50 mg/kg), doxorubicin (2.5 mg/kg), and AKBA combined with doxorubicin on xenograft growth and histopathology were observed. RESULTS: The IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells at 48 h was 45.15±0.97 μmol/L and 0.42±0.99 μmol/L, respectively. SynergyFinder confirmed the synergistic effect of AKBA and ADR with a ZIP>10. The combined treatment with AKBA and doxorubicin significantly inhibited the proliferation, migration and invasion, promoted apoptosis of MDA-MB-231 cells, and effectively suppressed xenograft growth in nude mice. Network pharmacology analysis predicted that AKBA affects the progression of TNBC through its downstream target AKBA. CONCLUSIONS AKBA combined with doxorubicin inhibits proliferation, migration and invasion, promotes apoptosis of MDA-MB-231 cells and suppresses MDA-MB-231 cell xenograft growth in nude mice. The combined use of AKBA can attenuate the toxic effects of doxorubicin in nude mice.
Animals ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/pathology* ; Mice, Nude ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Humans ; Female ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Xenograft Model Antitumor Assays ; Drug Synergism ; MDA-MB-231 Cells

Objective:A cohort of patients with oxaliplatin-associated portal hypertension was established and compared with patients with hepatitis B or schistosomiasis-associated cirrhotic portal hypertension to explore the course, disease features and prognosis of endoscopic treatment.Methods:From January 1, 2014 to December 31, 2021, patients diagnosed with portal hypertension and gastroesophageal varices after oxaliplatin chemotherapy at Zhongshan Hospital of Fudan University were selected (oxaliplatin general group). The patients who received endoscopic treatment for the first time because of esophagogastric variceal bleeding in the oxaliplatin general group were included in the oxaliplatin group. From January 1, 2014 to December 31, 2016, patients who initially received endoscopic treatment for the first time because of esophagogastric variceal bleeding due to hepatitis B or schistosomiasis-associated cirrhotic portal hypertension at Zhongshan Hospital of Fudan University were enrolled (hepatitis B group and schistosomiasis group). The history of oncology and chemotherapy, laboratory results, imaging and pathological findings were collected, and the clinical features were analyzed. Clinical data were collected, and the clinical features, 3-year cumulative non-bleeding rate and survival rate after endoscopic treatment of the 3 groups including oxaliplatin group, hepatitis B group and schistosomiasis group were compared. Kaplan-Meier survival curve was drawn to estimate treatment effects, and log-rank method was performed to test the differences in survival curves. Chi-square test and Mann-Whitney U test were used for statistical analysis. Results:There were 93 patients in oxaliplatin general group, with a median chemotherapy course of 8 (ranged from 6 to 10) cycles, and the median time from the end of chemotherapy to the diagnosis of gastroesophageal varices was 4 (ranged from 2 to 6) years. There were 55 patients in oxaliplatin group, 191 cases in hepatitis B group and 96 cases in schistosomiasis group. There were 78.5% (73/93) of patients in the oxaliplatin group classified as Child-Pugh grade A, and 33 patients (35.5%) with portal vein thrombosis. The abdominal imaging showed no obvious liver cirrhosis such as liver shrinkage and uneven surface. The pathology of 11 patients with liver biopsy in the oxaliplatin general group showed mainly vascular injury and fibrous deposition in the confluent area with lymphocytic infiltration, mild hepatocellular injury, and no pseudolobule formation. In terms of baseline characteristics, direct bilirubin, alanine transaminase, and aspartate transaminase levels of patients in the oxaliplatin group were all lower than those of the hepatitis B group and schistosomiasis group (4.8 (3.9, 6.5) μmol/L vs. 6.4 (4.7, 9.0) and 6.5 (4.4, 9.4) μmol/L; 17 (13, 22) U/L vs. 22 (15, 31) and 19 (15, 27) U/L; 22 (19, 25) U/L vs. 28 (22, 39) and 29 (22, 42) U/L), while albumin and prealbumin levels and the proportion of patients with Child-Pugh grade A were all higher than those of the hepatitis B group and schistosomiasis group (39.0 (35.0, 42.5) g/L vs. 34.0 (30.0, 38.3) and 33.8 (29.5, 36.0) g/L; 0.160 (0.130, 0.197) g/L vs. 0.120 (0.090, 0.150) and 0.110 (0.080, 0.140) g/L; 74.5% (41/55) vs. 55.5% (106/191) and 42.7% (41/96)), and the differences were all statistically significant ( U=3 298.50, 2 749.00, 2 159.00, 7 759.00, 5 822.50, χ2=6.92 and U=1 622.00, 1 878.50, 1 305.50, 3 989.00, 3 264.50, χ2=16.36; all P<0.05). The 3-year rebleeding risk in the oxaliplatin group was higher than that in the hepatitis B group ( HR=1.80, 95% confidence interval 1.07 to 3.02, P=0.026), but the difference was not statistically significant compared with that of the schistosomiasis group ( HR=1.04, 95% confidence interval 0.61 to 1.78, P=0.874). There were no statistically significant differences in the 3-year cumulative survival rate between the oxaliplatin group and the hepatitis B group and schistosomiasis group (96.4% (53/55) vs. 94.8% (181/191) and 95.8% (92/96), both P>0.05). Conclusions:The pathology of liver injury in patients with oxaliplatin-associated portal hypertension are mainly vascular injury and fibrous deposition in the confluent area. The efficacy of endoscopic treatment to prevent rebleeding in patients with oxaliplatin-associated portal hypertension is significantly inferior to that in patients with hepatitis B-associated portal hypertension, but comparable to that in patients with schistosomiasis-associated portal hypertension.

Objective:A cohort of patients with oxaliplatin-associated portal hypertension was established and compared with patients with hepatitis B or schistosomiasis-associated cirrhotic portal hypertension to explore the course, disease features and prognosis of endoscopic treatment.Methods:From January 1, 2014 to December 31, 2021, patients diagnosed with portal hypertension and gastroesophageal varices after oxaliplatin chemotherapy at Zhongshan Hospital of Fudan University were selected (oxaliplatin general group). The patients who received endoscopic treatment for the first time because of esophagogastric variceal bleeding in the oxaliplatin general group were included in the oxaliplatin group. From January 1, 2014 to December 31, 2016, patients who initially received endoscopic treatment for the first time because of esophagogastric variceal bleeding due to hepatitis B or schistosomiasis-associated cirrhotic portal hypertension at Zhongshan Hospital of Fudan University were enrolled (hepatitis B group and schistosomiasis group). The history of oncology and chemotherapy, laboratory results, imaging and pathological findings were collected, and the clinical features were analyzed. Clinical data were collected, and the clinical features, 3-year cumulative non-bleeding rate and survival rate after endoscopic treatment of the 3 groups including oxaliplatin group, hepatitis B group and schistosomiasis group were compared. Kaplan-Meier survival curve was drawn to estimate treatment effects, and log-rank method was performed to test the differences in survival curves. Chi-square test and Mann-Whitney U test were used for statistical analysis. Results:There were 93 patients in oxaliplatin general group, with a median chemotherapy course of 8 (ranged from 6 to 10) cycles, and the median time from the end of chemotherapy to the diagnosis of gastroesophageal varices was 4 (ranged from 2 to 6) years. There were 55 patients in oxaliplatin group, 191 cases in hepatitis B group and 96 cases in schistosomiasis group. There were 78.5% (73/93) of patients in the oxaliplatin group classified as Child-Pugh grade A, and 33 patients (35.5%) with portal vein thrombosis. The abdominal imaging showed no obvious liver cirrhosis such as liver shrinkage and uneven surface. The pathology of 11 patients with liver biopsy in the oxaliplatin general group showed mainly vascular injury and fibrous deposition in the confluent area with lymphocytic infiltration, mild hepatocellular injury, and no pseudolobule formation. In terms of baseline characteristics, direct bilirubin, alanine transaminase, and aspartate transaminase levels of patients in the oxaliplatin group were all lower than those of the hepatitis B group and schistosomiasis group (4.8 (3.9, 6.5) μmol/L vs. 6.4 (4.7, 9.0) and 6.5 (4.4, 9.4) μmol/L; 17 (13, 22) U/L vs. 22 (15, 31) and 19 (15, 27) U/L; 22 (19, 25) U/L vs. 28 (22, 39) and 29 (22, 42) U/L), while albumin and prealbumin levels and the proportion of patients with Child-Pugh grade A were all higher than those of the hepatitis B group and schistosomiasis group (39.0 (35.0, 42.5) g/L vs. 34.0 (30.0, 38.3) and 33.8 (29.5, 36.0) g/L; 0.160 (0.130, 0.197) g/L vs. 0.120 (0.090, 0.150) and 0.110 (0.080, 0.140) g/L; 74.5% (41/55) vs. 55.5% (106/191) and 42.7% (41/96)), and the differences were all statistically significant ( U=3 298.50, 2 749.00, 2 159.00, 7 759.00, 5 822.50, χ2=6.92 and U=1 622.00, 1 878.50, 1 305.50, 3 989.00, 3 264.50, χ2=16.36; all P<0.05). The 3-year rebleeding risk in the oxaliplatin group was higher than that in the hepatitis B group ( HR=1.80, 95% confidence interval 1.07 to 3.02, P=0.026), but the difference was not statistically significant compared with that of the schistosomiasis group ( HR=1.04, 95% confidence interval 0.61 to 1.78, P=0.874). There were no statistically significant differences in the 3-year cumulative survival rate between the oxaliplatin group and the hepatitis B group and schistosomiasis group (96.4% (53/55) vs. 94.8% (181/191) and 95.8% (92/96), both P>0.05). Conclusions:The pathology of liver injury in patients with oxaliplatin-associated portal hypertension are mainly vascular injury and fibrous deposition in the confluent area. The efficacy of endoscopic treatment to prevent rebleeding in patients with oxaliplatin-associated portal hypertension is significantly inferior to that in patients with hepatitis B-associated portal hypertension, but comparable to that in patients with schistosomiasis-associated portal hypertension.

Systemic lupus erythematosus(SLE)is a diffuse,systemic autoimmune disorder that can impact multiple organs and systems,with patients exhibiting abnormal levels of various autoantibodies and immune markers in their serum.It is currently understood that dysregulation of B cells activation plays a pivotal role in the pathogenesis of SLE,as aberrantly activated B cells produce autoantibodies that inflict damage on multiple organs through complement activation and antibody-dependent cell-mediated cyto-toxicity.Traditional therapies for SLE may prove ineffective for certain patients or lead to adverse reactions.In most instances,conventional treatment merely alleviates symptoms and necessitates lifelong immuno-therapy.A limited number of clinical cases have explored chimeric antigen receptor T cells(CAR-T)therapy as a potential treatment for autoimmune diseases such as SLE.Research indicates that CAR-T can specifically target CD 19 expressed on the surface of B cells and plasma cells,achieving profound de-pletion while minimizing drug-related side effects.This report details a female patient diagnosed with SLE and lupus nephritis who was successfully treated using dual-targeting B cells maturation antigen CAR-T by our research team;following treatment,she ceased steroid and immunomodulator use,attaining sustained remission without these medications.The patient was a 23-year-old female.Multiple examinations in other hospitals and in our hospital showed positive anti-double-stranded DNA(dsDNA)antibody and low complement C3.Renal biopsy in our hospital showed lupus nephritis Ⅳ-G(A/C),and National Institu-tes of Health(NIH)activity index(AI)score=4.She was diagnosed with"SLE,lupus nephritis(LN)".She was treated with hormones,immunosuppressants and Chinese medicine,but the effect was not good.After the CAR-T treatment,She stopped using hormones and immune agents and achieved con-tinuous remission with zero hormones and zero immune agents.She became pregnant six months after CAR-T infusion,and gave birth to a healthy full-term,full-weight baby successfully.She is the first pa-tient in China who successfully discontinued hormone,immune preparations and gave birth after CAR-T therapy.During the follow-up of the patient,we found that the immune indexes had basically returned to normal,and the safety was good.It indicates that CAR-T therapy may represent a promising and innova-tive therapeutic approach for the management of SLE.This offers hope and establishes a precedent for SLE women of childbearing age.

Malignant tumors of digestive system are highly prevalent malignant tumors that seriously threaten human health around the world. At present, the curative efficacy and prognosis of traditional treatment methods cannot reach the expectation, so it is urgent to find new targets for cancer treatment and realize targeted therapy for tumors. Abnormal energy metabolism in tumor cells is regarded as a hallmark of cancer, and malignant tumor cells absorb glucose through aerobic glycolysis pathway, and obtain a small amount of energy and produce lactate under the catalysis of a series of enzymes. Lactate dehydrogenase A (Lactate dehydrogenase A, LDHA), as a key enzyme in the aerobic glycolysis pathway of tumor cells, plays an important role in the metabolic changes of tumor cells. Studies have demonstrated that LDHA has high expression characteristics in a variety of tumor cells,and its high expression in clinic is often related to the poor prognosis and high metastasis rate of tumors, which is expected to be a new target for cancer therapy. This article reviews the role of LDHA in the development of digestive system tumors and the research progress of related drugs.

Objective:To investigate the correlation between thromboelastography (TEG) and portal vein thrombosis in patients with cirrhotic esophagogastric varices.Methods:210 hospitalized patients with cirrhotic esophagogastric varices treated in Zhongshan Hospital Affiliated to Fudan University from December 2016 to December 2017 were retrospectively included. They were divided into portal vein thrombosis group (PVT group) and non portal vein thrombosis group (NPVT group) according to whether they were complicated with portal vein thrombosis. The correlation between the results of TEG coagulation reaction time (R value), coagulation time (K value), αAngle, maximum amplitude (MA) and coagulation composite index (CI) and portal vein thrombosis was analyzed. The characteristics of coagulation status in patients with portal vein thrombosis in cirrhosis were compared.Results:A total of 91 patients (43.3%) were complicated with portal vein thrombosis. The R value in the PVT group was significantly lower than that of NPVT group [5.49(5.22-5.77) vs 5.98(5.76-6.20), P=0.006]. Logistic regression analysis showed that Child Pugh grade ( OR=2.883, 95% CI: 1.630-5.098, P<0.001) and R value ( OR=0.739, 95% CI: 0.575-0.950, P=0.018) were independently associated risk factors of PVT. The R value of patients was significantly correlated with Child Pugh grade ( r=0.147, P=0.034), platelet ( r=-0.358, P<0.001), prothrombin time (PT) ( r=0.334, P<0.001) and international standardized ratio (INR) ( r=0.328, P<0.001). Conclusions:The decrease of TEG-R value is closely related to PVT in liver cirrhosis.

Objective:This study aimed to evaluate the rebleeding risk and prognosis of patients being treated after acute esophageal varices bleeding by two different treatment strategies: sclerosing agent combined with tissue glue injection, esophageal varices ligation (EVL), through comparing the therapeutic effects and securities.Methods:A total of 76 patients who underwent endoscopy and received treatment in Zhongshan Hospital Affiliated to Fudan University due to acute esophageal variceal bleeding were included retrospectively. 6 patients with active bleeding and 70 patients with thrombus in esophagus varices under gastroscopy. Among them, 21 cases were treated with sclerosing agent combined with tissue glue injection (sclerosing tissue glue group), and 55 cases were treated with EVL (EVL group). The emergency endoscopic diagnosis and treatment of the two groups were compared, and the risk factors of rebleeding 6 months after endoscopic treatment were analyzed by univariate and multivariate analysis.Results:All patients received endoscopic treatment successfully. During the follow-up period of 6 months after endoscopic treatment, rebleeding occurred in 13 cases. Kaplan Meier analysis showed that the 6-month rebleeding rate in the sclerosing tissue glue group was significantly higher than that in the EVL group (41.6% vs 12.3%, P=0.011). There were 8 deaths in total. Kaplan Meier analysis showed that there was no significant difference in 6-month mortality between the two groups (17.5% vs 10.1%, P=0.616). Multivariate analysis further showed that malignant tumor ( HR=3.700, 95% CI: 1.187-11.536, P=0.024) and treatment mode of esophageal variceal bleeding ( HR=4.834, 95% CI: 1.443-16.193, P=0.011) were independent risk factors for rebleeding 6 months after endoscopic treatment of acute esophageal variceal bleeding. Conclusions:This study found that EVL and the combining injection of lauromacrogol and cyanoacrylate could be used in emergent hemostatic treatment for acute esophageal varices bleeding. Moreover, EVL is the prioritized approach in endoscopic emergency treatment with a lower rebleeding rate and fewer complications. Sclerotherapy combined with tissue glue can be used as one of the measures of emergency treatment, which is not better than ligation.

Objective:In this study, the liver, spleen, and hepatic portal vein in the portal venous phase images of abdominal enhanced computed tomography (CT) are artificially segmented and annotated, and the radiomics features are extracted from them. A model for predicting portal pressure in patients with hepatitis B virus (HBV) related cirrhosis is constructed by combining radiomics features with clinical indicators.Methods:A total of 171 patients who had abdominal enhancement CT examination and trans-jugular hepatic venous pressure gradient (HVPG) measurement at the same time were enrolled from January 2016 to May 2020 in the Zhongshan Hospital Affiliated to Fudan University. The liver, spleen, and hepatic portal vein in the portal venous phase images of the CT were manually labeled by using ITK-SNAP 3.8 software. The radiomics features of these three sites were extracted using Python programming, and an HVPG prediction model was established.Results:A total of 171 patients was included in the study. The average age was (51.1±10.3)years, of which 134(78.4%) were males, and the average HVPG was 16.87±5.695. A total of 2 553 radiomics features were extracted from three sites of the portal venous phase images of abdominal enhanced CT in each patient. The 2 553 features extracted were screened using LASSO, and by combing with clinical features and radiomics features, the predictive model of HVPG was obtained: m_HVPG=31.622+ 0.028 8T×total bile acids-6.31(portal venous wavelet-LHH_glcm_ClusterShade)=0.253(portal venous wavelet-LHL_glszm_LargeAreaLowGrayLevelEmphasis)-20.9(spleen wavelet-LLH_glcm_Correlation)-0.000 127(liver original_shape_SurfaceArea)+ 2.79(liver wavelet-LLH_glcm_ClusterShade). The coefficient of determination R2 was 0.345. Conclusions:The study suggests that radiomics features of the liver, spleen, and portal venous combined with clinical features may be used as a non-invasive method to assess the portal pressure in patients with HBV-related cirrhosis.