Whether physical activity independently relates to kidney disease or modifies associations with sleep duration remains uncertain. We followed 4,845 CHARLS participants aged ≥ 45 years without reported doctor-diagnosed kidney disease in 2011 through 2020. Nighttime sleep was classified as < 7, 7–9 or > 9 h, and physical activity as sufficient or insufficient at 600 MET-min/week. Weighted Cox models used community-clustered robust standard errors. During 38,604.2 person-years, 456 participants first reported doctor-diagnosed kidney disease. Compared with 7–9 h sleep plus sufficient activity, < 7 h sleep plus sufficient activity was associated with a higher rate (hazard ratio 1.39, 95% confidence interval 1.09–1.77), although the six-category omnibus test was not significant (P = 0.094). In mutually adjusted models, hazard ratios were 1.34 (1.07–1.67) for short sleep, 1.61 (1.01–2.56) for long sleep and 1.08 (0.81–1.45) for insufficient activity. The overall sleep association was significant (P = 0.016); the sleep-by-activity interaction was not (P = 0.666). Short sleep was associated with a higher rate of newly reported doctor-diagnosed kidney disease, whereas physical activity showed neither an independent association nor multiplicative effect modification.

PurposeTo investigate the therapeutic effect and mechanism of Shenge Powder (SGS) on myocardial hypertrophy and cardiac lymphangiogenesis using a transverse aortic constriction (TAC) mouse model and a TNF-α-induced lymphatic endothelial cell (LEC) proliferation model.MethodsC57BL/6J mice were randomly divided into sham surgery group and model group (Build molds for 2, 4, 6, 8 weeks respectively) for dynamic observation. Based on this, 4-week C57BL/6J mice were randomly divided into model group, SGS group (low-, medium-, high-dose group), and positive control drug (LCZ696) group. Evaluate lymphangiogenesis and ventricular remodeling through echocardiography, histopathology, transcriptomics, proteomics, and in vitro measurement of LECs function.ResultsThe heart function and epicardial lymphatic vessels of the model group mice showed a compensatory increase in the 2-week and a significant decrease in the 4-week. As the modeling time prolongs, myocardial cell hypertrophy, inflammatory infiltration, interstitial fibrosis, and reduced lymphangiogenesis appear. SGS intervention significantly improves heart function and lymphatic regeneration, reduces myocardial hypertrophy and fibrosis. Transcriptomic analysis revealed that heart failure changes a series of biological functions from compensatory to decompensated phase, affecting multiple signaling pathways including ECM receptor interactions and TGF-β signaling. After TAC modeling, the RT-qPCR results showed that the mRNA expression levels of BNP, α-SMA, Collagen I, Collagen III, TGF-β1, Smad3, VEGFC, and VEGFR-3 were significantly increased. Western blot results showed that the protein expression levels of TGF-β1, P-Smad3, and Smad3 were increased, VEGFC and VEGFR-3 increased in the 2-week and then decreased. After administration of SGS, the mRNA expression of BNP, α-SMA, Collagen I, Collagen III, TGF-β1, and Smad3 was downregulated, while VEGFC and VEGFR-3 was upregulated. The protein expression of TGF-β1, P-Smad3/Smad3 was downregulated, while VEGFC and VEGFR-3 was upregulated. In vitro experiments showed that SGS could promote LEC migration, and upregulate the mRNA and protein expression of VEGFC and VEGFR-3.ConclusionEarly compensatory cardiac function enhancement and increased lymphangiogenesis were observed in TAC model mouse, followed by cardiac dysfunction, myocardial hypertrophy, myocardial fibrosis, and decreased lymphangiogenesis. SGS can significantly improve ventricular remodeling and lymphangiogenesis, and its mechanism may be related to inhibiting the TGF-β1/Smad3 pathway and promoting the VEGFC/VEGFR-3 pathway.

Atractylodes chinensis (DC.) Koidz is a pharmacologically significant medicinal plant that produces various bioactive metabolites, including β-eudesmol, which largely determines its medicinal quality and clinical efficacy. Treatment of A. chinensis hairy roots with 5-methoxyindole (5-MI), a chemical homolog of melatonin, revealed that 0.5 mmol·L−1 5-MI significantly enhanced β-eudesmol production. To investigate the underlying mechanism, we performed integrated transcriptomic and metabolomic analyses. Comprehensive targeted metabolomics identified ten upregulated terpenoids among the differentially expressed metabolites following 5-MI treatment in A. chinensis hairy roots, including β-eudesmol. The 5-MI treatment significantly influenced the expression levels of genes associated with metabolic regulation and secondary metabolite synthesis in A. chinensis hairy roots, particularly promoting the upregulation of genes involved in terpenoid biosynthesis. Notably, a putative sesquiterpene synthase gene, AcTPS1, was significantly upregulated after 5-MI treatment and was a strong candidate gene correlated with β-eudesmol. AcTPS1 belongs to the TPS-a subfamily and exhibits tissue-specific expression, with high transcript levels in root tissues, especially in one-year-old roots of A. chinensis. This study demonstrates that 5-MI serves as an effective elicitor, providing valuable insights for the production of medicinally active compounds and enhancing our understanding of the molecular mechanism by which 5-MI regulates plant secondary metabolism.

Ethnopharmacological relevance: Shenqi Yanshen Decoction (SQYSD) is a traditional Chinese herbal formula clinically used for chronic kidney disorders and kidney-related bone complications under the traditional concept that “the kidney governs bone.” However, experimental evidence demonstrating its coordinated protective effects on renal and skeletal injury in chronic kidney disease–mineral and bone disorder (CKD-MBD) remains limited.Aim of the study: This study aimed to evaluate the therapeutic effects of SQYSD on renal dysfunction, mineral metabolism disorder, and bone injury in CKD-MBD, and to explore whether its actions are associated with regulation of Wnt5a/RhoA/Pkn3-mediated osteoclast activation.Materials and methods: The chemical profile of SQYSD was characterized by UPLC-Q/TOF-MS, and representative constituents were quantified by UPLC-MS/MS. A CKD-MBD mouse model was established by 5/6 nephrectomy combined with a low-calcium, high-phosphate diet. Mice were orally treated with SQYSD for 10 weeks, with cinacalcet hydrochloride used as a clinically relevant positive control. Renal function, calcium–phosphate metabolism, and bone turnover markers were assessed biochemically. Renal and femoral pathological changes were evaluated by histological staining, transmission electron microscopy, and micro-computed tomography. Transcriptomic analysis, qPCR, Western blotting, immunofluorescence, and immunohistochemistry were performed to investigate potential mechanisms. RANKL-induced osteoclast differentiation in RAW264.7 cells, together with Wnt5a overexpression, was used for in vitro validation.Results:UPLC-Q/TOF-MS identified 71 phytochemicals in SQYSD, and 12 representative constituents were quantified, with icariin, epimedin B, chlorogenic acid, and epimedin A being abundant components. In CKD-MBD mice, SQYSD improved body weight, reduced serum creatinine and blood urea nitrogen levels, corrected calcium–phosphate imbalance, and attenuated renal inflammatory infiltration, fibrosis, calcification, and ultrastructural injury. SQYSD also alleviated bone deterioration, as evidenced by improved bone mineral density, BV/TV, trabecular number and thickness, reduced trabecular separation, restored bone turnover markers, and decreased osteoclast accumulation. Compared with cinacalcet, SQYSD showed broader protective effects on both renal and skeletal lesions. Transcriptomic analysis indicated that SQYSD markedly regulated the Wnt signaling pathway, and subsequent validation showed that SQYSD suppressed Wnt5a/RhoA/Pkn3-related signaling in renal and bone tissues. In vitro, SQYSD inhibited RANKL-induced osteoclast differentiation and F-actin ring formation, accompanied by downregulation of Wnt5a, RhoA, Pkn3, and cytoskeleton-associated proteins. Wnt5a overexpression partially reversed the inhibitory effects of SQYSD on osteoclastogenesis.Conclusion:SQYSD exerts coordinated renal and skeletal protective effects in CKD-MBD, involving improvement of renal dysfunction, correction of mineral metabolic disorder, preservation of bone microarchitecture, and inhibition of osteoclast activation. These effects may be partly associated with suppression of Wnt5a/RhoA/Pkn3-related signaling. The findings provide pharmacological evidence supporting the traditional use of SQYSD in kidney-related bone disorders and suggest its potential as a complementary multi-target herbal intervention for CKD-MBD.

Objective The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a critical unsolved clinical problem. Mitochondrial homeostasis and macrophage function are pivotal in this process. This study aimed to investigate whether glycine amidinotransferase (GATM), a key enzyme in creatine biosynthesis, mediates mitophagy and macrophage function to participate in AKI-to-CKD progression.Methods A renal ischemia-reperfusion (I/R) model was established in myeloid-specific GATM knockout (LysM-cre+/GATMfl/fl) and control (LysM-cre+/GATM+/+) mice (n = 3 per group, 3 independent replicates). Renal pathological injury and fibrosis were evaluated by hematoxylin-eosin (HE) and Masson staining. Serum creatinine (Cr), blood urea nitrogen (BUN), and renal biomarkers (Kim-1, NGAL, creatine, IL-1 beta, TNF-alpha) were quantified via ELISA. Gene and protein expressions of GATM, Collagen I, alpha-SMA, and mitophagy-related molecules were assessed by RT-qPCR and immunohistochemistry/western blot. Macrophage polarization, mitochondrial ROS levels, and efferocytosis efficiency were analyzed by flow cytometry. In vitro, bone marrow-derived macrophages (BMDMs) were differentiated with macrophage colony-stimulating factor (m-CSF), and polymorphonuclear neutrophils (PMNs) were induced to apoptosis by serum-free starvation. Functional rescue experiments were performed using ALDH2 overexpression plasmids. Statistical analyses were conducted with t-test and one-way ANOVA.Results GATM deficiency significantly exacerbated the pathological damage induced by AKI and promoted the AKI-to-CKD progression, as evidenced by elevated serum creatinine and blood urea nitrogen levels, along with increased expression of Kim-1, NGAL, and fibrotic markers (Collagen I, alpha-SMA). The absence of GATM led to a reduction in creatine levels within BMDMs, downregulation of ALDH2 expression, inhibition of mitophagy, and an elevation of ROS in mitochondria. Concurrently, there was an enhanced polarization of BMDMs towards the M1 phenotype, accompanied by a diminished efferocytic capacity. Notably, in vitro overexpression of ALDH2 partially revived mitophagy activity, reset the polarization balance of BMDMs, and rejuvenated their efferocytic function.Conclusion Data suggest that GATM may regulate ALDH2-linked mitophagy via creatine, influencing macrophage polarization and efferocytosis during AKI-to-CKD transition. Targeting the GATM-ALDH2 pathway represents a promising novel therapeutic strategy for mitigating CKD development after acute kidney injury.

Cisplatin causes nephrotoxicity by accumulating in renal tubular epithelial cells (RTECs). Astragaloside IV (ASIV) shows renoprotective potential, but its mechanisms remain poorly understood. Cisplatin induced nephrotoxicity was established in 8-week-old male C57BL/6 mice via intraperitoneal administration of cisplatin at 20 mg/kg for 48 h. For in vitro studies, HK-2 human proximal tubular epithelial cells were exposed to 50 μM cisplatin for 24 h. Multi-omics approaches were employed to identify novel mechanisms by which ASIV ameliorates cisplatin-induced proximal tubular injury. ASIV markedly reduced serum creatinine and urea nitrogen levels in mice, and ameliorated cisplatin-induced proximal tubular injury both in vivo and in vitro. Moreover, ASIV restored mitochondrial damage, upregulated protein expression of PGC-1α, TOMM20, and PINK1 in RTECs. Mechanistically, RNA-seq and scRNA-seq revealed that cisplatin predominantly affected ADRA1A-mediated mitochondrial biogenesis and mitophagy in proximal tubular cells, accompanied by suppression of the AMPK/FOXO3A pathway. Notably, ASIV upregulated ADRA1A expression, thereby facilitating AMPK and FOXO3A phosphorylation and consequently enhancing mitochondrial biogenesis and mitophagy. Furthermore, dabuzalgron (a selective ADRA1A agonist) recapitulated the protective effects of ASIV. In contrast, the renoprotective action of ASIV against cisplatin-induced proximal tubular injury was largely abrogated by the ADRA1A antagonist tamsulosin in vivo and by ADRA1A-specific siRNA in vitro. These findings identify ASIV as a highly promising renoprotective agent that upregulates ADRA1A expression and activates the AMPK/FOXO3A axis to enhance mitochondrial biogenesis and mitophagy, thereby counteracting cisplatin-induced proximal tubular injury.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, and its exact pathogenesis has not been fully studied. Hydrogen sulfide (H2S) is the third gas signaling molecule discovered in mammals, following nitric oxide and carbon monoxide. It has the effects of anti-inflammation, anti-apoptosis, and so on, thereby playing an important role in many diseases. However, the role and mechanism of exogenous H2S in NAFLD are not fully understood. In this study, we constructed in vitro and in vivo NAFLD models by feeding mice a high-fat diet and stimulating hepatocytes with palmitic acid, respectively, to investigate the improvement effect and mechanism of exogenous H2S on NAFLD. The results showed that NaHS (a donor of H2S) treatment alleviated lipid accumulation, inflammation, apoptosis and pyroptosis, and downregulated endoplasmic reticulum (ER) stress and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NRRP3) inflammasome in NAFLD. The activation of NLRP3 inflammasome weakened NaHS improvement of NAFLD, indicating that exogenous H2S ameliorated NAFLD by inhibiting NLRP3 inflammasome-mediated lipid synthesis, inflammation, apoptosis and pyroptosis. Similarly, the activation of ER stress weakened NaHS improvement of NAFLD and NaHS inhibition of NLRP3 inflammasome, indicating that exogenous H2S suppressed NLRP3 inflammasome by downregulating ER stress, thus improving NAFLD. Additionally, the protein expressions of NLRP3 and cleaved caspase-1 were downregulated after inhibiting the reactive oxygen species (ROS)/extracellular signal-regulated kinases (ERK) and ROS/thioredoxin-interacting protein (TXNIP) pathways, indicating that ER stress activated NLRP3 inflammasome through the ROS/ERK and ROS/TXNIP pathways. In conclusion, our results indicated that exogenous H2S inhibited NLRP3 inflammasome-mediated hepatocytes inflammation, lipid synthesis, apoptosis and pyroptosis by downregulating ER stress, thereby improving NAFLD; Furthermore, ER stress activated NLRP3 inflammasome through the ROS/ERK and ROS/TXNIP pathways in NAFLD. ER stress/NLRP3 inflammasome is expected to become a new target of H2S for treating NAFLD.

Higenamine Hydrochloride (HGN) is an alkaloid derived from the traditional Chinese medicinal herb Aconite, possesses pharmacological activities such as anti-inflammatory and antioxidant properties. Its specific role in diabetic nephropathy (DN) remains unknown. The purpose of this work was to investigate the protective impact of HGN against streptozotocin (STZ)-induced renal inflammation and fibrosis in DN mice, as well as to investigate its probable mechanism of action in vitro using high glucose (HG)-treated HK-2 cells. We constructed a mouse model of DN by intraperitoneal injection of STZ and a HK-2 cell model using HG treatment, followed by administration of HGN. Tissue distribution experiments, biochemical analysis, real-time PCR, immunoblotting, and histopathological examination were used to assess the effects of HGN on renal histopathology, inflammation, and fibrosis in DN mice and its molecular mechanisms. The results demonstrated that in the renal tissues of DN mice, HGN had the highest concentration. HGN treatment led to body weight increase, and blood glucose levels fell as well as the improvement in metabolic abnormalities. It further proved that HGN alleviated renal function damage by lowering serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (Cys-C), and renal index values. Moreover, HGN improved kidney histopathology, reduced renal tubular damage, and decreased interstitial inflammation. The kidneys had less collagen accumulation. At the same time, HGN decreased the expression of markers associated with inflammation (iNOS, IL-1β, IL-6, MCP-1) and fibrosis (Collagen-I, MMP9, α-SMA, CTGF). Mechanistic studies have shown that, in vitro, HGN inhibits STAT3 phosphorylation, thereby inhibiting the expression of inflammatory (iNOS, IL-1β, IL-6, and MCP-1) and fibrosis-related cytokines (Collagen-I, MMP9, α-SMA, and CTGF) in HK-2 cells under HG conditions. To summarize, HGN inhibits renal inflammation and fibrosis in DN mice by inhibiting the STAT3 pathway, and this discovery offers a new possible target for DN treatment.

OBJECTIVE:With the rising incidence of MASLD, extensive drug research has been conducted in clinical trials. The study examined the design principles and research objectives of MASLD therapeutics, in order to offer guidance to clinical trial participants and decision makers. METHODS:By searching the clinical research trial data registered on clinicaltrials.gov platform, 1209 interventional clinical trials were screened. These trials were subsequently evaluated based on clinical stage, trial design, intervention modalities, outcome metrics, and other pertinent factors. RESULTS:A total of 1,209 trials were included, of which 199 were registered from 2000 to 2012 (16.46%) and 1010 were registered from 2013 to 2024 (83.54%), reflecting the growing body of research on MASLD. Regarding the intervention model type, single-group designs were employed in 232 (19.19%) trials, and parallel designs were employed in 873(72.21%). A total of 13 trials were early phase 1 (1.08%), 152 (12.57%) were phase 1, 34 (2.81%) were phase 1/phase 2, 301 were phase 2 (24.90%), 19 (1.57%) were phase 2/phase 3, 72 (5.96%) were phase 3, and 84 (6.95%) were phase 4. Within these trials, the three primary clinical outcomes for drug interventions were hepatic histological improvement, hepatic fat content and adverse events. Furthermore, 140 drug interventional trials with results for therapeutic purposes (This accounted for 88.61% of the 158 drug interventional trials with results) primarily aimed to improve MASLD through mechanisms such as metabolic and energy balance, inflammatory and immunomodulatory, and lipid reduction, targeting primarily PPAR, FXR, ACC and GLP-1. CONCLUSION:This study suggests the basic characteristics of global MASLD clinical trial design, and the current global interventional clinical trials are mainly focused on drug-related treatments, and drugs to improve inflammation and metabolism are still the first choice for MASLD drug intervention studies.

Stroke is the second leading cause of death worldwide. Organoids, as disease models that closely mimic human physiology and pathology, are highly suitable for investigating the role of neural cells in brain diseases. However, there are few reports on circRNA research based on cerebral organoid stroke models. In this study, we established a human cerebral organoid ischemic stroke model induced by iPSCs and performed transcriptome sequencing. We found that at Days 31 and 52 of organoid development, the microglial marker Iba1, neuronal marker NeuN, and astrocytic marker GFAP exhibited strong fluorescent signals and showed co-localization with the proliferation marker KI67. The organoids showed high levels of the vascular marker CD31 and α-SMA, with co-localization between them. Transcriptome sequencing identified a total of 18 differentially expressed circRNAs (DEcircRNAs) and 2,111 differentially expressed genes (DEGs) in the human cerebral organoid stroke model. KEGG pathway enrichment analysis and WGCNA showed that these DEcircRNAs were involved in the pyroptosis pathway. Furthermore, we identified a pyroptosis-associated circRNA circFGFR2 who was up-regulated in astrocytes and promoted astrocyte pyroptosis. In summary, this study identified a highly expressed pyroptosis-associated circFGFR2 in the human cerebral organoid ischemic stroke model and demonstrated that circFGFR2 promoted astrocyte pyroptosis. This study provides new insights into the pathogenic mechanisms of ischemic stroke.

Ondansetron orally soluble pellicle can serve as an alternative option for preventing nausea and vomiting in patients who receive chemotherapy. However, there is a lack of clinical evidence regarding ondansetron. This study aimed to explore the efficacy and safety of ondansetron in patients with malignant tumours who received chemotherapy drugs with a moderate-to-high emetic risk. In total, 163 patients with malignant tumours received 24 mg of ondansetron via orally soluble pellicles at 30 min before chemotherapy (8 mg each time for three consecutive administrations). The incidence rates of nausea and vomiting in the three days after chemotherapy were recorded. Regarding the effect of ondansetron on vomiting, the complete response (zero episodes of vomiting), major response (1–2 episodes of vomiting), minor response (3–5 episodes of vomiting), and failure (> 5 episodes of vomiting) rates were 96.9

Objective:Patients with chronic kidney disease (CKD) exhibit increased vascular calcification (VC) risks, worsened by high-dose erythropoietin (EPO). While EPO treats anemia, its role in VC pathogenesis remains unclear. Ginsenoside Rb1 (Rb1), a Panax ginseng compound with anti-calcification properties, may counteract EPO-induced VC through the GATA binding protein 6 (GATA6)/bone morphogenetic protein 2 (BMP2)/Smad1/5/9 pathway. This article aims to explore whether Rb1 could counteract EPO-induced VC through the GATA6/BMP2/Smad1/5/9 pathway. Material and Methods:Adenine-induced CKD rats and b-glycerophosphate-treated vascular smooth muscle cells (VSMCs) received EPO ± Rb1. Calcification was assessed through von Kossa/alizarin red staining. Smooth muscle protein 22-a (SM22a)/a-Smooth muscle actin (a-SMA) expression was measured by immunofluorescence and real-time-quantitative polymerase chain reaction (RT-qPCR). GATA6/BMP2/Smad1/5/9 activation was analyzed using RT-qPCR/Western blot. Rb1-BMP2 interactions were tested through biotin pulldown, micro-thermophoresis, and Co-immunoprecipitation (Co-IP). GATA6 knockdown validated pathway roles. Results:High-dose EPO significantly worsened CKD-associated calcification and VSMC calcification (P < 0.01), suppressed SM22a and a-SMA expression levels, and activated the GATA6/BMP2/Smad1/5/9 pathway (P < 0.01). GATA6 knockdown reduced EPO-exacerbated calcification and modulated BMP2/Smad1/5/9 signaling (P < 0.01). Rb1 increased SM22a and a-SMA expression levels and inhibited Smad 1/5/9 phosphorylation (P < 0.01), without affecting GATA6 or BMP2 expression (P > 0.05). Molecular docking and Co-IP experiments revealed that Rb1 binds directly to BMP2, blocking its interaction with bone morphogenetic protein receptor and inhibiting Smad 1/5/9 phosphorylation (P < 0.01). Conclusion:Rb1 mitigates EPO-aggravated VC in CKD by disrupting BMP2/Smad1/5/9 signaling, positioning it as a promising molecular intervention strategy to reduce EPO-induced vascular toxicity.

BACKGROUND:Chronic kidney disease (CKD) is a long-term progressive condition characterized by a decline in renal function, for which effective treatment strategies remain limited. This study aimed to evaluate the effectiveness of ligustrazine for CKD and elucidate its underlying molecular mechanisms. METHODS:A CKD rat model was established using a 2.5% adenine suspension for two consecutive weeks via intragastric administration, followed by a two-week intervention with ligustrazine from day 15. In vitro, primary proximal straight tubule cells (PSTCs) were treated with adenine for 48 h to simulate chronic kidney injury. Biotin-labeled ligustrazine was subjected to LC-MS/MS analysis to identify the target proteins. Single-cell sequencing was performed on rats in the control, CKD, and ligustrazine groups to identify the key genes and characteristic cell subpopulations involved in CKD treatment. Additionally, overexpression and knockdown plasmids of Ornithine Decarboxylase 1 (Odc1) and methyltransferase like 3 (Mettl3) were constructed to investigate their roles in alleviating CKD through cellular and animal experiments. RESULTS:Ligustrazine intervention significantly alleviated kidney damage in CKD rats. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was identified as an intracellular target of ligustrazine. Odc1 was confirmed as a potential key gene, and PST cells were identified as a characteristic cell subset in the treatment of CKD with ligustrazine. Compared to adenine treatment, ligustrazine intervention inhibited the mRNA and protein expression of Odc1, while promoting the mRNA and protein expression of Glutathione Peroxidase 4 (Gpx4), without affecting the expression of IGF2BP1. Additionally, ligustrazine intervention reduced PSTCs apoptosis and lowered the expression of 4-HNE. Notably, Odc1 promoted adenine-induced PSTCs ferroptosis, whereas ligustrazine intervention weakened the binding of IGF2BP1 to m6A-modified Odc1 mRNA, shortening the half-life of Odc1 mRNA, thus inhibiting ferroptosis. CONCLUSIONS:Ligustrazine reduced the binding of IGF2BP1 to Odc1 mRNA, downregulated Odc1 protein expression, thereby decreasing ferroptosis, and restoring renal function.

Metabolic and Bariatric Surgery (MBS) is an effective treatment for severe obesity and its related complications. However, perioperative nutritional management is essential for the patient's surgical outcome and postoperative recovery. This article reviews the research progress in perioperative nutritional management of MBS. Preoperative nutritional assessment and optimization are essential, including monitoring and correction of micronutrient deficiencies, such as vitamin D, iron, folic acid, to reduce the risk of postoperative complications. In terms of preoperative dietary management, the use of a low-carbohydrate ketogenic diet (LCKD) and ready-to-eat low-carbohydrate ketogenic product (RLCKP) showed the potential to promote weight loss and liver volume reduction, creating favorable conditions for surgery. Strategies for preoperative weight loss (WL) need to be cautious, and moderate preoperative WL may help to reduce surgical difficulty and postoperative complications. In addition, the application of preoperative carbohydrate load can reduce postoperative insulin resistance and protein loss and promote postoperative recovery of patients. In terms of postoperative nutritional management, the risk of postoperative micronutrient deficiency is significantly increased. At the same time, the adjustment of postoperative dietary structure and rational use of nutritional supplements are important to maintain the nutritional status of patients and promote weight management. In conclusion, perioperative nutritional management of MBS is a multifaceted and multi-level comprehensive process that requires a multidisciplinary approach involving medical staff, dietitians, and patients. A tailor-made approach based on the patient's unique characteristics, such as nutritional status, surgical type, and personal preferences, is essential to achieve the best surgical results and improvement of patients' quality of life. Major challenges remain in perioperative nutritional management, such as the high prevalence of preoperative malnutrition and the complexity of postoperative nutritional deficiencies. In the future, more accurate preoperative nutritional assessment tools and personalized postoperative nutritional supplementation strategies should be developed.

Chronic kidney disease (CKD) is a progressive disorder characterized by renal fibrosis, inflammation, and dysregulated autophagy and apoptosis. High-mobility group box 1 (HMGB1) plays a crucial role in regulating autophagy in CKD. Hirudin, a potent thrombin inhibitor, has demonstrated antifibrotic and anti-inflammatory properties, but its effects on autophagy and apoptosis in CKD remain unclear. In this study, a rat model of renal interstitial fibrosis (RIF) and an HK-2 cell culture model were established to assess the effects of varying doses of hirudin and HMGB1 interference. Molecular and histological analyses, including RTqPCR, Western blot, TUNEL staining, hematoxylin-eosin (H&E) staining, immunofluorescence, and immunohistochemistry (IHC), were performed to assess renal injury, fibrosis, apoptosis, and autophagy-related markers. Hirudin treatment significantly reduced the expression of LC3, ATG12, ATG5, α-SMA, COL1A1, caspase-3, and caspase-9 while increasing P62 levels (p<0.05). It also lowered the renal coefficient (p<0.001) and apoptosis levels. The optimal effective concentration of hirudin in vitro was determined to be 4.8 ATU/mL (p<0.001). HMGB1 interference suppressed autophagy and apoptosis, as indicated by decreased LC3-II/LC3-I, ATG12, ATG5, caspase-3, and caspase-9 levels, increased P62 expression (p<0.001), and reduced apoptosis. However, simultaneous HMGB1 interference in hirudin-treated cells weakened the therapeutic effects of hirudin, leading to increased autophagy and apoptosis markers, decreased P62 levels, and a higher renal coefficient. These findings indicate that hirudin exerts protective effects in CKD by modulating autophagy and apoptosis, potentially through HMGB1 regulation. These findings highlight the therapeutic potential of targeting these mechanisms in renal dysfunction and underscore the necessity for further research to support clinical applications.

Diabetic nephropathy (DN) is characterized by renal lipid accumulation, often driven by proteoglycan (PG) interactions with lipoproteins. To investigate the effects of Shen-Qi-Yan-Shen Formula (SQYSF) on DN. Db/db mice were used as an experimental model and divided into different groups: db/m normal control, db/db model, SQYSF-treated, captopril-treated, and SQYSF + captopriltreated groups. Mice were treated with saline, SQYSF, captopril, or SQYSF + captopril for 12 weeks. SQYSF significantly reduced blood glucose, lipid levels, and markers of renal damage (blood urea nitrogen, serum creatinine, urinary albumin) in db/db mice compared to controls. SQYSF downregulated the expression of proteoglycan (PG), apolipoprotein B (apoB), and LDL-receptor in the kidney, suggesting a mechanism that involves reduced lipid accumulation. The protective effects of SQYSF were enhanced when combined with captopril. SQYSF may prevent lipid deposition by modulating PG expression, suggesting its potential as an innovative therapeutic agent for DN.

Acanthopanax senticosus (AS) is a well-known traditional herbal medicine in China that can invigorate the spleen, tonify the qi and kidney, tranquilize the mind, and possess diverse bioactive functions. However, comprehensive and simultaneous analysis of the main active constituents from AS and in vivo metabolites remains underexplored, which severely impedes its further clinical application. In this study, AB-8 macroporous resin column chromatography was used to enrich the AS extract. Furthermore, ultrahigh performance liquid chromatography with quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS/MS) and UPLC-Q-Orbitrap MS techniques were utilized to identify and characterize the chemical constituents and in vivo metabolites of AS extract, respectively. As a result, a total of 60 components were characterized in the AS extract, including 33 phenylpropanoids, 13 lignans, 4 coumarins, and 10 other substances. Additionally, a total of 29 prototype components and 226 metabolites were detected. Specifically, 91 metabolites were discovered in plasma, 19 in brain tissue, 111 in urine, and 76 in feces. The metabolic reactions included Phase I reactions (demethylation, deglucose, oxidation, and hydration) and Phase II reactions (methylation, sulfate esterification, glucuronidation, glucose conjugation, glycine conjugation, and acetylation). In conclusion, our findings provided basic data and a method for further investigations into the relationship between the chemical composition and pharmacological effects of AS. These results are valuable for revealing the material basis, illustrating the mechanism of medical action, and guiding the clinical applications of AS.

BackgroundThe effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation.Hypothesis/PurposeThis study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial.Study DesignA total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24.ResultsBoth QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p< 0.05). Compared to DFLG, QSHY treatment improved ALT (β, -0.128 [95% CI, -0.25, -0.005], p= 0.041), aspartate transaminase (β, -0.134 [95% CI, -0.256 to -0.012], p= 0.032), and fibrosis-4 score (β, -0.129 [95% CI, -0.254 to -0.003], p= 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid.ConclusionOur results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD.

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion's analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Background Little is known about the effect of electroacupuncture (EA) on cerebral blood flow. We investigated this question in patients undergoing laparoscopic cholecystectomy, hypothesizing that EA would increase cerebral blood flow during surgery. Methods Eighty-two patients undergoing laparoscopic cholecystectomy were randomly divided into receiving electroacupuncture and intravenous anesthesia (EA+IA) and receving intravenous anesthesia alone (IA). The patients in EA+IA were treated with EA at Baihui (GV 20), Shuigou (GV 26), unilateral Neiguan (PC 6) and unilateral Zusanli (ST 36) points 20 min before anesthesia until the end of the operation. The patients in IA received intravenous anesthesia alone. The internal carotid artery blood flow (Q), mean arterial pressure (MAP), end-tidal carbon dioxide pressure (PETCO2) and heart rate (HR) were recorded respectively before anesthesia induction (T1), 2 min after anesthesia induction (T2), 1 min after pneumoperitoneum (T3), 1 min after head-up tilt (T4) and after anesthesia resuscitation (T5). Results The internal carotid artery blood flow was significantly higher in EA+IA (mean [SD], T3, 294.0 [89.6] ml min-1; T4, 303.8 [90.6] ml min-1) than in IA (mean [SD], T3, 246.4 [80.9] ml min-1; T4, 253.5 [78.4] ml min-1) at T3 and T4 (P < 0.05). There was no difference in blood flow between the two groups at T2 and T5. As compared with baseline (T1), the internal carotid artery blood flow decreased at T2-T4 in two groups (P < 0.05). There were no differences in MAP, PETCO2, and HR between the two groups. Conclusion Electroacupuncture intervention could reduce the decline of internal carotid artery blood flow in patients undergoing laparoscopic cholecystectomy. Trial registration ChiCTR: 2,100,041,761.