ObjectiveTo investigate the liver-protecting and anti-liver fibrosis effects of astragaloside Ⅳ （AS-Ⅳ） in vitro and in vivo， as well as its mechanism of action in intervention against liver fibrosis. MethodsIn the animal experiment， C57BL/6J mice were divided into control group， model group， low-dose AS-Ⅳ （20 mg/kg） group， and high-dose AS-Ⅳ （80 mg/kg） group. The mice were given intraperitoneal injection of carbon tetrachloride for 6 weeks to induce liver fibrosis， and since week 3 of injection， the mice in the low-dose AS-Ⅳ group and the high-dose AS-Ⅳ group were given AS-Ⅳ by gavage at a dose of 20 mg/kg and 80 mg/kg， respectively. The serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured after 4 weeks of administration， as well as the serum levels of hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ N-terminal peptide （PⅢNP）， and collagen type Ⅳ （Col-Ⅳ）. HE staining， picrosirius red staining， and Masson staining were used to observe liver histopathology and collagen deposition； RT-qPCR was used to measure the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue， and Western blot was used to measure the protein expression levels of α-smooth muscle actin （α-SMA）， collagen type Ⅲ （Col-Ⅲ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated PI3K （pPI3K）， protein kinase B （Akt）， and phosphorylated AKT （p-Akt） in liver tissue； transcriptome sequencing was performed for liver tissue to identify differentially expressed genes and perform a bioinformatics analysis. In the cell experiment， transforming growth factor-β （TGF-β） was used to induce the activation of LX-2 cells， and the PI3K inhibitor LY294002 and the PI3K activator 740 Y-P were used for intervention. The cells were divided into control group， model group， AS-Ⅳ group， LY294002 group， and AS-Ⅳ+740 Y-P group， and the cells were harvested after 36 hours of intervention. Changes in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K/PI3K， and pAkt/Akt in LX-2 cells were measured， as well as changes in the relative mRNA expression levels of Acta2， Col1a1， and Col3a1. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the animal experiment， compared with the model group， the AS-Ⅳ treatment group had significant reductions in the serum levels of ALT， AST， HA， LN， PⅢNP， and Col-Ⅳ （all P<0.01）， the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue （all P<0.05）， and the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） in liver tissue （all P<0.05）. In the cell experiment， compared with the control group， the model group had significant increases in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） after TGF-β induction （all P<0.05）； compared with the model group， the AS-Ⅳ group had significant reductions in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） （all P<0.05）， and both the AS-Ⅳ group and the LY294002 group had significant reductions in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， Col1a1， and Col3a1 （all P<0.05）. Compared with the AS-Ⅳ group， there were significant increases in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， col1a1， and Col3a1 after 740 Y-P intervention （all P<0.05）. ConclusionAS-Ⅳ can inhibit hepatic stellate cell activation and improve liver fibrosis， possibly by inhibiting the PI3K/Akt signaling pathway.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Liuhetang is one of the classic prescriptions included in the Catalogue of Ancient Classic Prescriptions （the Second Batch）. This study adopts the method of literature review to systematically sort out the ancient literature about Liuhetang and obtained a total of 127 effective data records， involving 82 ancient books （including 2 Japanese books）. The origin， medicinal composition， compatibility， original plants and their processing methods， dosage， decocting method， usage， and indications of Liuhetang were analyzed. Liuhetang is first recorded in the Formulary of the Bureau of Taiping People's Welfare Pharmacy in the Song Dynasty， consisting of Amomi Fructus， Pinelliae Rhizoma， Armeniacae Semen Amarum， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， red Poria， Pogostemonis Herba， Lablab Semen Album， Chaenomelis Fructus， Moslae Herba， Magnoliae Officinalis Cortex， Zingiberis Rhizoma Recens， and Jujubae Fructus. The original plants of these herbal medicines follow those in the 2020 edition of the Pharmacopoeia of the People's Republic of China. The raw materials of Amomi Fructus， Armeniacae Semen Amarum， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， red Poria， Pogostemonis Herba， Chaenomelis Fructus， Moslae Herba， Magnoliae Officinalis Cortex， Zingiberis Rhizoma Recens， and Jujubae Fructus are used in this prescription. Pinelliae Rhizoma， Glycyrrhizae Radix et Rhizoma， Lablab Semen Album， and Magnoliae Officinalis Cortex are processed with alum， stir-fried， processed with Zingiberis Rhizoma Recens， and processed with Zingiberis Rhizoma Recens， respectively. The recommended formula is composed of 0.79 g Amomi Fructus， 0.79 g Pinelliae Rhizoma， 0.79 g Armeniacae Semen Amarum， 0.79 g Ginseng Radix et Rhizoma， 0.79 g Glycyrrhizae Radix et Rhizoma， 1.57 g red Poria， 1.57 g Pogostemonis Herba， 1.57 g Lablab Semen Album， 1.57 g Chaenomelis Fructus， 3.15 g Moslae Herba， and 3.15 g Magnoliae Officinalis Cortex. The above medicines should be pulverized to reach 10 meshes， mixed with 450 mL water， 3 g Zingiberis Rhizoma Recens， and 3 g Jujubae Fructus， and decocted to reach a volume of 240 mL. The filtrate should be taken three times a day. In ancient times， Liuhetang was mainly used to treat cholera， vomiting， diarrhea， phlegm， dyspnea， cough， chest distension， dizziness and pain in the head， swelling in the limbs， lethargy， loss of appetite， difficult urination and dark urine caused by heat and dampness damage to the spleen and disharmony between spleen and stomach. In modern times， Liuhetang is mainly used to treat the digestive system diseases such as gastroenteritis， hepatitis， stomach pain， and diarrhea. The above research confirmed the key information of Liuhetang， providing a basis for the clinical application of this prescription.

Objective:To reveal the differences in the transcriptome maps of brain tissues in mice subjected to Flash irradiation and conventional dose rate irradiation with electron beams and to explain the biological effect and mechanisms of Flash irradiation from multiple perspectives.Methods:Following the principle of grouping based on approximate body weights, 36 female C57BL/6J mice were divided into three groups, i. e., the control, conventional dose rate irradiation (CONV), and Flash irradiation (Flash) groups, with 12 mice in each group. Both the CONV and Flash groups received a single 15 Gy whole-brain irradiation with 9 MeV electron beams. At 3 d post-irradiation, the whole-brain tissue specimens were collected for hematoxylin-eosin (HE) staining to observe pathological changes. At 1, 3, and 10 weeks post-irradiation, the motion function, cognitive ability, depression level, and spatial memory capacity of the mice were assessed using ethology. At 1 and 10 weeks after behavioral experiments, brain tissue samples were collected and snap-frozen in liquid nitrogen for reference-based transcriptome sequencing. Accordingly, the differences in the transcriptome maps of radiation-induced brain injury between CONV and Flash groups were analyzed.Results:The HE staining-based pathological result revealed that compared to the CONV group, the Flash group exhibited reduced glial cell hyperplasia and inflammatory cell infiltration in brain tissues. Ethological research result at 1 week post-irradiation showed that the CONV group manifested a significantly decreased total traveled distance compared to the control and Flash groups ( t = 5.51, 2.38, P < 0.05) and a significantly increased immobility time compared to the control group ( t = 3.60, P < 0.05). Ethological research result at 3 weeks post-irradiation indicated that compared to the CONV group, the Flash group displayed significantly alleviated cognitive impairment ( t = 3.35, P < 0.05) and reduced depression levels ( t = 2.39, P < 0.05). Ethological research result at 10 weeks post-irradiation demonstrated that the CONV group showed the worst cognitive performance, significantly differing from the control group ( t = 4.53, P < 0.05). Transcriptome sequencing result revealed that besides immune-related pathways, the Flash group also exhibited multiple upregulated metabolic pathways and fibroblast growth factor (FGF)-related pathways compared to the CONV group. Conclusions:Compared to conventional dose rate irradiation, Flash irradiation can effectively alleviate radiation-induced brain injury in mice. This effect is associated with various metabolic pathways (including amino acid metabolism) and FGF-related pathways besides immune pathways.

Objective:To explore the effects of adenosine on learning and memory in rats thromboembolic stroke(TS)and its mechanism based on PI3K/Akt/CREB signaling pathway.Methods:36 male SD rats were randomly di-vided into sham group(Sham),TS group,TS+adenosine(TS+Ade)group and TS+adenosine+Akt inhibitor(TS+Ade+MK-2206)group.Preparation of rat TS model used autologous thrombus intravascular formation method.Mor-ris water maze(MWM)test was used to observe the learning and memory ability of rats.The morphological changes of hippocampal neurons were observed by Nissl staining.The expression of glutamate transporter 1(GLT-1)and glial fi-brillary acidic protein(GFAP)in CA1 region was determined by immunofluorescence.The protein expressions of PI3K,p-PI3K,Akt,p-Akt,CREB and p-CREB were determined by Western blot.Results:Through the rat TS mod-el,adenosine was able to improve the learning and memory ability,improve the hippocampal neuron cell morphological abpormality and vacuolation,nucleolar condensation and other phenomena in rats.Immunofluorescence results showed that GLT-1 and GFAP were co-localized,and adenosine could significantly enhance the fluorescence intensity of GFAP and GLT-1.Western blot results showed that adenosine can enhance the expression of p-PI3K,p-Akt,and p-CREB proteins,but the use of Akt inhibitors can to some extent inhibit the phosphorylation of PI3K,Akt,and CREB.Conclusion:Adenosine may enhance the expression of GLT-1 in astrocytes and increase the clearance of glutamate through activation of PI3K/Akt/CREB signaling pathway,thereby reducing the excitotoxicity and improving recognition and memory function.However,this effect is partially blocked by Akt inhibitors.

Background and Aims:Sleeve gastrectomy(SG)has become the most widely performed bariatric procedure worldwide,but postoperative gastroesophageal reflux disease(GERD)remains a major concern.This multicenter study aimed to identify independent risk factors associated with GERD after SG to guide preoperative assessment and intraoperative management.Methods:Clinical data of 672 patients who underwent SG between January 2020 and December 2022 in six bariatric centers and completed a 12-month follow-up were retrospectively analyzed.Demographic characteristics,esophagogastric junction(EGJ)integrity graded by the AFS system,operative parameters,and postoperative outcomes were compared between patients with and without GERD.Multivariate logistic regression was used to identify predictors of postoperative GERD.Results:The overall incidence of GERD after SG was 24.7%(166/672).Multivariate analysis revealed that a preoperative BMI>35 kg/m2(OR=1.68,P=0.033),EGJ integrity AFS grade>2(OR=2.90,P=0.006),and preoperative reflux symptoms(OR=2.44,P=0.030)were independent risk factors for GERD.A staple line more than 1 cm from the angle of His(OR=0.45,P<0.001)and a bougie size>36 Fr(OR=0.08,P=0.001)were protective factors.Conclusion:High BMI,impaired EGJ integrity,and preoperative reflux symptoms significantly increase the risk of GERD after SG,whereas adequate preservation of the His angle and appropriate bougie calibration may reduce it.Comprehensive preoperative EGJ assessment and standardized surgical techniques are essential for minimizing postoperative reflux.