ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

Objective To explore the clinical characteristics and short-term prognosis of postoperative acute myocardial infarction (PAMI) after cardiac surgery. Methods A retrospective study was conducted on 45 PAMI patients who underwent coronary angiography after cardiac surgery at Zhongshan Hospital, Fudan University, from February 2015 to February 2025. General information, type of surgery, onset time and causes of PAMI, and in-hospital recovery condition were collected. Univariate logistic regression was used to analyze factors related to in-hospital survival. Results The patients’ age was (62.40±11.72) years, 31 cases (68.89%) were male, 21 cases (46.67%) had hypertension. Twenty-six patients (57.78%) underwent cardiac valve surgery, and 16 patients (35.56%) received coronary artery bypass grafting. The onset time of PAMI was 24 (0, 48) hours, with 38 cases (84.44%) developing within 48 hours after surgery. Twenty-eight patients (62.22%) presented with new lesions in coronary arteries/bypass grafts, and 20 patients (44.44%) were considered to have thrombus-induced PAMI. Nine patients died in hospital, 13 patients failed to recover and were discharged automatically, and 23 patients were discharged after recovery. Univariate logistic regression analysis showed that new lesion in coronary arteries/bypass grafts was risk factor for in-hospital survival (OR=0.235, P=0.036). Conclusions PAMI frequently occurs within 48 hours post-cardiac surgery, and thrombosis is the most common cause of PAMI. New lesions in coronary arteries/bypass grafts are closely correlated with poor short-term prognosis.

Metabolic associated fatty liver disease （MAFLD） is a highly prevalent chronic liver disease worldwide， and the mechanism underlying its progression to metabolic associated steatohepatitis and liver fibrosis remain unclear. Endoplasmic reticulum stress （ERS） and ferroptosis （Fer） are deeply involved in the pathological evolution of MAFLD. This article systematically reviews the core regulatory mechanisms of ERS and its role in regulating lipid metabolism， inflammation response， and cell apoptosis in MAFLD. It also analyzes the core mechanism of Fer and discusses the predisposing factors for Fer in the pathological microenvironment of MAFLD， as well as the role of Fer in exacerbating hepatocyte death and activating the progression of liver fibrosis. This article proposes that the crosstalk between ERS and Fer is a key driver for the progression of MAFLD， which provides new references and ideas for the clinical intervention of MAFLD.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

BACKGROUND:Eupatilin,a flavonoid active component derived from Artemisia sinensis,has been reported to relieve inflammation and improve neurological scores in rats with subarachnoid hemorrhage,but its role and mechanism in learning and memory remain unclear.OBJECTIVE:To investigate the effects of eupatilin on learning and memory abilities and P38 mitogen activated protein kinase(p38 MAPK)/signal transducer and activator of transcription-3(STAT3)pathway proteins in rats with subarachnoid hemorrhage.METHODS:A total of 50 Sprague-Dawley rats were randomly divided into sham surgery group,model group,eupatilin group,hesperetin group,eupatilin+hesperetin group,with 10 rats in each group.Except for the sham surgery group,the rats in the other groups were used to construct a subarachnoid hemorrhage model through intravascular perforation.Two hours after successful modeling,the eupatilin group was injected with 10 mg/kg eupatilin via the tail vein,the hesperetin group was injected with 50 mg/kg hesperetin(p38 MAPK/STAT3 signaling pathway activator)via the tail vein,the eupatilin+hesperetin group was injected with 10 mg/kg eupatilin and 50 mg/kg hesperetin via the tail vein,and the sham surgery group and the model group were injected with 10 mL/kg saline via the tail vein.The drug treatment lasted for 24 hours.The neurologic deficit score and Morris water maze experiment were applied to detect the neurological function and learning and memory abilities of rats.Hematoxylin-eosin staining was performed to detect the histopathological changes of the hippocampus.TUNEL method was used to detect neuronal apoptosis.Immunohistochemical staining was conducted to detect the number of doublecortin-positive cells in hippocampal tissue.Western blot was applied to detect the expression of p38 MAPK/STAT3 protein in hippocampal tissue.RESULTS AND CONCLUSION:Compared with the sham surgery group,rats in the model group had lower neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Compared with the model group,rats in the eupatilin group showed higher neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and lower neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05),while those in the nerolone group showed lower neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Compared with the eupatilin group,rats in the eupatilin+hesperetin group had lower neurological deficit scores,learning memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Hematoxylin-eosin staining showed that compared with the model group,the nerve cells were more neatly arranged in the eupatilin group,disorganized in the hesperetin group,and arranged in a similar way to the model group in the eupatilin+hesperetin group.To conclude,eupatilin may improve learning and memory abilities of rats with subarachnoid hemorrhage by inhibiting the p38 MAPK/STAT3 signaling pathway.

Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.