ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids （SCFAs） and high mobility group protein B1 （HMGB1）/receptor of advanced glycation end products （RAGE） signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group，model group，low-dose modified Sini San group （7.34 g·kg^-1·d^-1），high-dose modified Sini San group （14.68 g·kg^-1·d^-1），and Fructo-oligosaccharides group （3.15 g·kg^-1·d^-1），with 10 rats in each group. Except for the control group，all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling，each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors，body weight，Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin （HE） staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry （GC-MS）. Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1，Occludin，and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay （ELISA）. ResultsCompared with the model group，the sucrose preference rate，total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased （P<0.05， P<0.01），and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced （P<0.05， P<0.01）. Meanwhile，the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased （P<0.05）. The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased，with a obviously increase in the content of acetic acid，propionic acid，butyric acid，and isovaleric acid （P<0.05， P<0.01） and the expression levels of HMGB1，RAGE，Toll-like receptor 2（TLR2），Toll-like receptor 4（TLR4），tumor necrosis factor-α（TNF-α），and nuclear factor kappa-B p65（NF-κB p65） proteins in cecal tissue were significantly decreased （P<0.05， P<0.01） in low-dose group of modified Sini San. Meanwhile，the contents of ZO-1，Occludin，and Claudin-1 in the cecal tissue were obviously increased （P<0.01） in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.

low transit constipation （STC） is a common functional intestinal disorder caused by impaired colonic transit function， characterized by reduced bowel movement frequency， hard stools， and difficulty in defecation. The mitogen-activated protein kinase （MAPK） signaling pathway， which mainly includes extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and p38 subtypes， plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine （TCM） intervention.At the mechanistic level， the MAPK signaling pathway promotes the progression of STC through the following links：（1） Activation of p38 upregulates the expression of aquaporin 3 （AQP3）/AQP4 in the colon， leading to excessive reabsorption of water in the intestinal lumen； （2） It forms a positive feedback loop with nuclear factor-κB （NF-κB） to maintain low-grade intestinal inflammation， releases inflammatory factors such as tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and inhibits smooth muscle contraction； （3） Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2， thereby disrupting the mucosal barrier； （4） The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells， neurons， and interstitial cells of Cajal； （5） Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion， ultimately resulting in impaired colonic transit function.At the intervention level， TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent：yin-nourishing formulas （Zengye Chengqi Tang， Tongbian Tang） mainly regulate the ERK/AQP axis； yang-warming formulas （Jichuan Jian） target both ERK/JNK and anti-apoptosis； heat-clearing formulas （Sanren Tang） focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism， inflammation， barrier function， apoptosis， and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets， establish disease-syndrome integrated STC models， and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”， so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.

Objective To explore the effect of sex on the incidence of immune-related cutaneous adverse event (ircAE) during immunotherapy for gastric cancer, and to further analyze the correlation between sex, ircAE and prognosis. Methods A retrospective analysis was conducted on patients with advanced gastric cancer who received immune checkpoint inhibitors at the Department of Oncology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, from February 1, 2022, to December 31, 2024. Clinicopathological characteristics, occurrence of ircAE, and survival data were collected. The incidence of ircAE was compared between male and female patients. Kaplan-Meier method was used to plot survival curves, and univariate Cox regression analysis was performed to assess prognostic factors. Results A total of 116 patients with advanced gastric cancer were enrolled, including 76 males (65.5%) and 40 females (34.5%). The overall incidence of ircAE was 23.28%, with a higher incidence in male patients than in female patients (28.95% vs 12.50%, P＝0.046). Kaplan-Meier survival analysis on 86 patients with complete follow-up data indicated that patients with ircAE had longer overall survival (OS) than those without ircAE (P＝0.045). Univariate Cox regression analysis showed that male (HR＝0.43, 95%CI 0.22–0.83, P＝0.012) was associated with prolonged OS. Conclusions In gastric cancer immunotherapy, male patients are more likely to develop ircAE and have longer OS than female patients, and the occurrence of ircAE may be related to prolonged OS.

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation （NMES） in the treatment of dysphagia in Wilson disease （WD） with combined phlegm and stasis. MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy， the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group， with 40 patients in each group. In addition， 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days， and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study （VFSS） before and after treatment. During the examination， contrast agents with 4 different characters were used for the swallowing action， and the passing time was recorded. The TCM syndrome score， water swallow test score， standard swallowing assessment （SSA） score， and 24-h urinary copper level before and after treatment were analyzed. ResultsWhen performing VFSS， the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group （P<0.01）， while it had no significant difference in the pharyngeal stage. After treatment， the passing time in the oral stage shortened in the control and observation groups （P<0.01）， and the observation group outperformed the control group （P<0.01）. After treatment， both the control and observation groups showed declines in TCM syndrome score and SSA score （P<0.01） and an increase in water swallow test score （P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.01）. In addition， the treatment in the control and observation groups elevated the 24-h urinary copper level （P<0.01）， and the elevation in the observation group was more obvious than that in the control group （P<0.01）. Neither group showed obvious adverse reaction. ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score， water swallow test score， and SSA score， demonstrating definite clinical efficacy and high safety.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Lipid droplets (LDs) are dynamic organelles that are ubiquitous across most organisms, including animals, plants, protists, and microorganisms. Their core consists of neutral lipids, surrounded by a phospholipid monolayer adorned with a specific set of proteins. As critical intracellular hubs of metabolic regulation, lipid droplets play essential roles in maintaining physiological homeostasis and contributing to the progression of various pathological processes. They store neutral lipids for energy production during periods of starvation or for membrane biosynthesis, and they sequester fatty acids to mitigate lipotoxicity. Clinically, dysregulation of lipid droplet function is associated with a wide range of diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, type 2 diabetes mellitus (T2DM), neurodegenerative disorders, and cancer. Research into the biological functions of lipid droplets—as dynamic organelles and their links to multiple diseases—has emerged as a cutting-edge focus in cell biology. In recent years, significant advances have been made in understanding lipid droplet biogenesis. Researchers have developed a more refined framework that elucidates how LDs are assembled in the endoplasmic reticulum (ER). Triacylglycerols and sterol esters are synthesized between the inner and outer leaflets of the ER bilayer, and when they exceed the critical nucleation concentration (CNC), they coalesce to form neutral lipid lenses. These then bud from the ER under the coordinated action of key proteins such as Seipin, fat storage-inducing transmembrane protein 2 (FIT2), and the peroxisomal membrane protein Pex30. This budding process is driven by changes in membrane curvature and surface tension, induced by the asymmetric distribution of phospholipids. Nascent lipid droplets recruit lipid-synthesizing enzymes via ER-LD bridging structures, enabling localized lipid production and surface expansion, ultimately resulting in the formation of mature LDs. Biochemical and biophysical approaches have revealed important features of this process, underscoring the critical roles of ER membrane biophysical properties and specific phospholipids. Structural biology and proteomic studies have identified key regulators—particularly Seipin and FIT2—as central players in LD biogenesis. This review systematically summarizes recent advances in the molecular mechanisms of LD biogenesis. It delves into the processes of LD nucleation, membrane budding, and expansion in eukaryotic cells, with a special focus on how core factors such as Seipin and FIT2 dynamically regulate LD morphology. In addition, it examines the mechanisms and pathways by which class I and class II proteins are targeted to LDs, compares LD biogenesis involving different neutral lipid cores, and discusses the disease relevance of specific regulatory proteins. Finally, the review outlines critical unresolved questions in the field of LD biogenesis, offering clear directions for future research and providing a comprehensive framework for deepening our understanding of LD formation and its implications for disease intervention.