ObjectiveTo investigate the inhibitory effect of Biejiajian Pills （BJJW） on the growth of liver cancer， as well as its potential mechanism in mediating the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group， BJJW group （2.2 g/kg）， and metformin group （250 mg/kg）， and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment； HE staining was used to observe histopathological changes； the levels of reactive oxygen species （ROS） and adenosine triphosphate （ATP） in tumor tissue were measured； immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Tukey’s test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group， the BJJW group had a tumor inhibition rate of 45.73%， with significant reductions in both tumor volume and weight （P<0.01）. Pathological examination showed that compared with the model group， the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group， the BJJW group had a significant increase in ROS level （P<0.001） and a significant reduction in ATP level （P<0.001）， as well as significant increases in p-AMPK/AMPK ratio （0.81±0.20 vs 0.13±0.04， P<0.01） and p-ULK1/ULK1 ratio （0.69±0.17 vs 0.18±0.13， P<0.01） and a significant reduction in p-mTOR/mTOR ratio （1.34±0.16 vs 3.20±0.62， P<0.01）. ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction， increasing the level of ROS， reducing the level of ATP， and activating the AMPK/mTOR signaling pathway.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

ObjectiveTo investigate the correlation between neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， systemic immune-inflammation index （SII） and the severity of intrauterine adhesions （IUA）. MethodsThe retrospective study included 380 patients who underwent transcervical resection of adhesions （TCRA） from December 2019 to March 2025. Based on the American Fertility Society （AFS） classification， patients were divided into mild （n=61）， moderate （n=225）， and severe （n=94） groups. NLR， PLR， and SII were calculated from preoperative blood tests. Statistical analyses included Kruskal-Wallis test and ordinal Logistic regression. ResultsNLR， PLR， and SII were significantly higher in the severe IUA group compared to the mild group （P<0.05）， with SII showing the strongest predictive ability （OR=1.004， P=0.001）. The number of intrauterine procedures was an independent risk factor （OR=1.27/level， P=0.016）. The predictive model ［Logit（P）=-0.676+0.241×operation times+0.004×SII］ effectively identified severe IUA cases. ConclusionInflammatory markers （particularly SII） are correlated with IUA severity and may serve as non-invasive tools for clinical assessment.

Transdermal drug delivery offers advantages such as safety, convenience, and high patient compliance. However, the complex structure of the skin and significant individual variability, particularly the barrier function of the stratum corneum, result in generally low bioavailability for topical formulations. The formulation of topical drug products is complex, with numerous factors influencing quality, which requires strict control of product quality. Raman spectroscopy, as a non-destructive vibrational technique, combined with chemometric methods, imaging technology, and other spectroscopic techniques, can be applied to study the key quality attributes of topical drug formulations. The applications of Raman spectroscopy in studies of the crystal form, particle size distribution, excipient research, and in vitro transdermal experiments of topical drug formulations were summarized. In particular, it focused on the use of Raman spectroscopy in the selection of skin samples for in vitro permeation tests, the study of drug spatial distribution in the skin, and the interactions between drugs and the skin.

Both hyperlipidemic acute pancreatitis and fatty liver disease are associated with lipid metabolism disorders and are commonly comorbid with each other in clinical practice. The pathogenesis of such comorbidity involves the interaction between multiple factors such as hypertriglyceridemia， metabolic syndrome， obesity， and insulin resistance， and these factors may form a vicious cycle and jointly promote disease progression. In clinical practice， hyperlipidemic acute pancreatitis is characterized by severe disease conditions， a high incidence rate of complications， a high mortality rate， and a tendency for recurrence， and it can easily lead to multi-organ damage and even multiple organ failure without timely treatment， posing a serious threat to the life of patients. Starting from the various signaling pathways associated with hyperlipidemic acute pancreatitis comorbid with fatty liver disease， this article discusses the potential molecular mechanisms of synergistic pathogenesis between hyperlipidemic acute pancreatitis and fatty liver disease， so as to provide a reference for the early prevention and treatment of such comorbidity.

Objective To evaluate the efficacy of combining the replenishing qi and nourishing yin empirical formula with anti-vascular endothelial growth factor (VEGF) in diabetic macular edema (DME). Methods A retrospective analysis was conducted on 59 patients diagnosed with DME at Tongji Hospital of Tongji University or Shanghai Nanxiang Hospital, Jiading District from June 2019 to December 2022. Among them, 29 cases received intravitreal injection of ranibizumab (anti-VEGF group), while 30 cases received both intravitreal injection of ranibizumab and oral administration of the replenishing qi and nourishing yin empirical formula (combined treatment group). The best corrected visual acuity (BCVA), central macular thickness (CMT), and the traditional Chinese medicine (TCM) syndrome score were compared between the two groups before treatment and at 4, 8, 12, 16, 20, and 24 weeks after treatment. Results Compared with before treatment, BCVA significantly improved (P＜0.05) and CMT significantly decreased (P＜0.05) at different time points after treatment in both groups. At 16, 20, and 24 weeks after treatment, BCVA in the combined treatment group was superior to that in the anti-VEGF group (P＜0.01). At 12, 16, 20, and 24 weeks after treatment, CMT in the combined treatment group was lower than that in the anti-VEGF group (P＜0.01). Starting from week 8 after treatment, the TCM syndrome scores in the combined treatment group were lower than those in the anti-VEGF group (P＜0.01). Conclusions The replenishing qi and nourishing yin empirical formula could improve the efficacy of anti-VEGF therapy in DME patients, indicating that integrating traditional Chinese and Western medicine has certain clinical application value in treating DME.

ObjectiveTo investigate the role of Ras-GTPase-activating protein SH3 domain-binding protein 2 （G3BP2） in regulating the activation， proliferation， and migration of hepatic stellate cells （HSCs）. MethodsThe mouse HSCs （JS-1 cell line） were treated with 5 μg/L transforming growth factor-beta 1（TGF-β1） for 24 hours to establish an HSC activation and proliferation model. A G3BP2 knockdown system was constructed using siRNA interference technology. The experiment was divided into four groups： Control， TGF-β1 treatment， TGF-β1+si-NC， and TGF-β1+ G3BP2-siRNA. The expression levels of key fibrosis indicators， including type I collagen （Collagen I）， α-smooth muscle actin （α-SMA）， and G3BP2， were detected by Western blot and RT-qPCR. Cell proliferation activity was assessed using the CCK-8 proliferation assay kit and EdU fluorescence labeling technology. Cell migration ability was analyzed by scratch wound healing assay and Transwell migration assay. The formation level of stress granules was quantified by immunofluorescence microscopy to investigate the effects of G3BP2 on stress granule formation in activated HSCs. ResultsStimulation with TGF-β1 upregulated the expression of G3BP2 in JS-1 cells （RT-qPCR： P0.000 1； Western blot： P0.000 1）， while a downward trend in its expression was observed in the G3BP2‑silenced group （RT-qPCR： P0.01； Western blot： P0.000 1）. Compared with the control group， the TGF-β1 group exhibited increased protein expression levels of α-SMA and Collagen I （RT-qPCR： both P0.01； Western blot： P0.01 and P0.05， respectively）， concomitant with an increased number of stress granules and enhanced cell proliferation and migration capacity （all P0.001）. The experimental results demonstrated that G3BP2 knockout effectively reversed the aforementioned phenotypes， with the G3BP2-silenced group showing reduced expression of fibrotic markers （all P0.01）， decreased stress granule formation （P0.01）， and reduced cell proliferation and migration capacity （all P0.05）， compared to the negative control group. ConclusionG3BP2 enhances the activation， proliferation， and migration of HSCs by promoting the formation of stress granules， thereby accelerating the pathological progression of liver fibrosis. This suggests that stress granules may serve as important regulators in controlling the activation， proliferation， and migration of HSCs.

ObjectiveTo investigate the synergistic promotion of malignant phenotypes in gastric cancer cells by tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs） and polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） through crosstalk， and the intervention mechanism of the intestinal absorption solution containing Banxia Xiexintang （BXT）. MethodsGastric cancer MFC cells were treated with conditioned medium （co-culture-CM） prepared from a co-culture system of TA-BMSCs and PMN-MDSCs. Groups included control， co-culture-CM model， stromal cell-derived factor 1 （SDF1） inhibitor （LY2510924）， α₄β₁ inhibitor （BIO5192）， dual inhibitor combination， and different concentrations （55%， 70%， 85%） of BXT-containing intestinal absorption solutions. MFC cell proliferation， migration， invasion， and apoptosis were assessed via cell counting kit-8 （CCK-8） assay， wound-healing assay， Transwell assay， and flow cytometry. The SDF-1， α₄β₁， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA） levels in culture supernatants， along with the protein levels of intracellular macrophage migration inhibitory factor （MIF）， chemokine （C-X-C motif） receptor 4 （CXCR4）， CD106， MMP-9， and VEGFA in MFC cells， were measured by enzyme-linked immunosorbent assay （ELISA） and Western blot， respectively. ResultsCompared with the control group， co-culture-CM promoted the proliferation， migration， and invasion of MFC cells （P<0.01）， elevated the levels of SDF-1， α₄β₁， MMP-9， and VEGFA （P<0.01）， and upregulated the protein levels of MIF （P<0.05）， MMP-9 （P<0.01）， and VEGFA （P<0.01）. Compared with co-culture-CM， BXT-containing intestinal absorption solutions at various concentrations significantly reversed the phenotypic effects on cells， inhibited malignant phenotypes， lowered the levels of MMP-9 and SDF1， and reduced the expression of proteins in the crosstalk axis. Compared with the SDF1+α₄β₁ inhibitor group， the SDF1 inhibitor group and the α₄β₁ inhibitor group showed no differences in the inhibition of proliferation， scratch healing， and cytokine levels. The SDF1 inhibitor increased the apoptosis rate and downregulated the protein levels of MIF and CD106， while the α₄β₁ inhibitor increased the number of migrated cells and the expression of various proteins. Compared with the SDF1 inhibitor group， the α₄β₁ inhibitor group showed reduced inhibitory effect on proliferation， decreased apoptosis rate， increased number of invasive cells， decreased α₄β₁ content， and increased expression of various proteins （P<0.01）. The 55%， 70%， and 85% intestinal absorption solutions increased the inhibitory effect on proliferation， decreased the number of invasive cells， and increased the apoptosis rate （P<0.01）. The 55% BXT-containing intestinal absorption solution group showed increased wound healing rate and upregulated protein levels of VEGFA， CD106， and MMP-9 （P<0.05）. The 70% intestinal absorption solution group showed upregulated protein level of MIF （P<0.05）， and the 85% intestinal absorption solution group showed upregulated protein level of VEGFA （P<0.01） and downregulated the protein level of CXCR4 （P<0.01）. ConclusionTA-BMSCs and PMN-MDSCs synergistically activate the MIF/SDF-1/CXCR4 and MMP-9/α₄β₁/CD106 axes through crosstalk， significantly enhancing gastric cancer cell invasion and migration. BXT-containing intestinal absorption fluid effectively inhibits the malignant progression of gastric cancer cells by multi-targeted intervention in this crosstalk process.

ObjectiveTo explore whether the intestinal absorption solution containing Banxia Xiexintang （BXT） can inhibit the invasion and migration of gastric cancer cells by interfering with the stromal cell-derived factor 1 （SDF1）-CXC chemokine receptor 4 （CXCR4） axis in tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs）. MethodsThe intestinal absorption solution containing BXT was prepared， and the optimal intervention concentration and duration for MFC cells were determined through the cell counting kit-8 （CCK-8） assay. A co-culture system was established comprising TA-BMSCs conditioned medium （TA-BMSCs-CM） and gastric cancer MFC cells. The experiment was conducted with a blank control group， a TA-BMSCs-CM group， an SDF1 inhibitor （LY2510924） group， and intervention groups with varying concentrations （55%， 70%， 85%） of the intestinal absorption solution containing BXT. Cell proliferation was assessed by the CCK-8 assay. Horizontal and vertical cell migration were evaluated via scratch and Transwell assays， respectively. Cell invasion was examined by a Transwell assay with Matrigel. Cell apoptosis was detected by flow cytometry. The levels of factors such as SDF1， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）， as well as the protein levels of macrophage migration inhibitory factor （MIF）， CXCR4， VEGFA， and MMP-9， were quantified by ELISA and Western blot， respectively. ResultsThe CCK-8 assay results indicated that compared with the 24 h intervention， the 48 h interventions with all concentrations of the intestinal absorption solution containing BXT increased the inhibition rate on MFC cells （P<0.01）. The half-maximal inhibitory concentration （IC₅₀） of the intestinal absorption solution containing BXT at the time point of 48 h was 68.51%， and subsequent intervention concentrations were selected as 55%， 70%， and 85%. Compared with the TA-BMSCs-CM group， the intestinal absorption solution containing BXT （particularly at concentrations of 70% 85%） suppressed the proliferation， migration， and invasion of MFC cells， promoted the cell apoptosis （P<0.05， P<0.01）， decreased the levels of SDF1， MMP-9， and VEGFA， and downregulated the protein levels of MIF， CXCR4， VEGFA， and MMP-9 （P<0.05， P<0.01）. The inhibitory effects of the intestinal absorption solution containing BXT were comparable to or superior to those of the SDF1 inhibitor （P<0.01）. ConclusionThe intestinal absorption solution containing BXT can inhibit the invasion and migration of gastric cancer cells by interfering with the SDF1-CXCR4 axis in TA-BMSCs. The underlying mechanism may involve the regulation of the MIF/SDF1/CXCR4 signaling pathway and its downstream effector molecules.

ObjectiveTo investigate the synergistic promotion of malignant phenotypes in gastric cancer cells by tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs） and polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） through crosstalk， and the intervention mechanism of the intestinal absorption solution containing Banxia Xiexintang （BXT）. MethodsGastric cancer MFC cells were treated with conditioned medium （co-culture-CM） prepared from a co-culture system of TA-BMSCs and PMN-MDSCs. Groups included control， co-culture-CM model， stromal cell-derived factor 1 （SDF1） inhibitor （LY2510924）， α₄β₁ inhibitor （BIO5192）， dual inhibitor combination， and different concentrations （55%， 70%， 85%） of BXT-containing intestinal absorption solutions. MFC cell proliferation， migration， invasion， and apoptosis were assessed via cell counting kit-8 （CCK-8） assay， wound-healing assay， Transwell assay， and flow cytometry. The SDF-1， α₄β₁， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA） levels in culture supernatants， along with the protein levels of intracellular macrophage migration inhibitory factor （MIF）， chemokine （C-X-C motif） receptor 4 （CXCR4）， CD106， MMP-9， and VEGFA in MFC cells， were measured by enzyme-linked immunosorbent assay （ELISA） and Western blot， respectively. ResultsCompared with the control group， co-culture-CM promoted the proliferation， migration， and invasion of MFC cells （P<0.01）， elevated the levels of SDF-1， α₄β₁， MMP-9， and VEGFA （P<0.01）， and upregulated the protein levels of MIF （P<0.05）， MMP-9 （P<0.01）， and VEGFA （P<0.01）. Compared with co-culture-CM， BXT-containing intestinal absorption solutions at various concentrations significantly reversed the phenotypic effects on cells， inhibited malignant phenotypes， lowered the levels of MMP-9 and SDF1， and reduced the expression of proteins in the crosstalk axis. Compared with the SDF1+α₄β₁ inhibitor group， the SDF1 inhibitor group and the α₄β₁ inhibitor group showed no differences in the inhibition of proliferation， scratch healing， and cytokine levels. The SDF1 inhibitor increased the apoptosis rate and downregulated the protein levels of MIF and CD106， while the α₄β₁ inhibitor increased the number of migrated cells and the expression of various proteins. Compared with the SDF1 inhibitor group， the α₄β₁ inhibitor group showed reduced inhibitory effect on proliferation， decreased apoptosis rate， increased number of invasive cells， decreased α₄β₁ content， and increased expression of various proteins （P<0.01）. The 55%， 70%， and 85% intestinal absorption solutions increased the inhibitory effect on proliferation， decreased the number of invasive cells， and increased the apoptosis rate （P<0.01）. The 55% BXT-containing intestinal absorption solution group showed increased wound healing rate and upregulated protein levels of VEGFA， CD106， and MMP-9 （P<0.05）. The 70% intestinal absorption solution group showed upregulated protein level of MIF （P<0.05）， and the 85% intestinal absorption solution group showed upregulated protein level of VEGFA （P<0.01） and downregulated the protein level of CXCR4 （P<0.01）. ConclusionTA-BMSCs and PMN-MDSCs synergistically activate the MIF/SDF-1/CXCR4 and MMP-9/α₄β₁/CD106 axes through crosstalk， significantly enhancing gastric cancer cell invasion and migration. BXT-containing intestinal absorption fluid effectively inhibits the malignant progression of gastric cancer cells by multi-targeted intervention in this crosstalk process.