Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Methods: Fifty patients who underwent UBE-TLIF and 50 patients who underwent W-TLIF, each with >2 years of follow-up, were retrospectively analyzed. Outcomes included operative parameters, time to postoperative mobilization, paravertebral muscle atrophy and fat infiltration rates, clinical scores (Visual Analog Scale [VAS], Oswestry Disability Index [ODI], Japanese Orthopaedic Association [JOA]), modified Macnab criteria, fusion rates, and complications. Results: Compared with W-TLIF, the UBE-TLIF group had significantly less intraoperative blood loss, shorter operative times, and lower postoperative drainage volumes (p <0.05). The UBE-TLIF group showed faster postoperative recovery and shorter hospital stays. At 6 months, 1 year, and 2 years, W-TLIF patients had higher multifidus and erector spinae atrophy, and greater paravertebral muscle fat infiltration (p <0.05). The UBE-TLIF group also had lower VAS and ODI scores at 1 year and 2 years (p <0.05) and fewer surgical complications (6% vs. 10%). Fusion rates (94% vs. 92%) and modified Macnab outcomes (88% vs. 86%) were comparable (p >0.05). Conclusions UBE-TLIF is associated with reduced intraoperative trauma, quicker recovery, and fewer complications. In the long-term, it better preserves paravertebral muscle integrity and provides superior pain and functional outcomes.

Background: Cerebral hypoxia-ischemia impairs brain development in extremely preterm infants and is associated with poor neurological outcomes. Near-infrared spectroscopy (NIRS) is a noninvasive continuous monitoring method for regional cerebral oxygen saturation (rcSO2).Purpose: This study evaluated the clinical feasibility and neurological impact of a neurocritical care bundle that incorporates prolonged multidisciplinary hemodynamic monitoring and a stepwise management algorithm. Methods: Preterm infants with a gestational age (GA) ≤28 weeks or birth weight (BW) ≤1,000 g were prospectively enrolled in a bundle group subjected to NIRS for rcSO2, electrical cardiometry for cardiac output, and daily brain and cardiac echography during the first 72 hours of life. Monitoring was repeated weekly in the first month and then monthly until discharge or the term-equivalent age (TEA) was reached. We implemented a stepwise management algorithm for treating cerebral hypoxia. The primary outcome was a composite of mortality and adverse neurological events (structural abnormalities or electroencephalogram-confirmed seizures) before discharge. The secondary outcomes were the physiological pattern of rcSO2 within the initial 72 hours and up to discharge or TEA. Results: Thirty preterm infants (GA, 27.1±2.0 weeks; BW, 830±225 g) were enrolled in the bundle group. The mean time-averaged rcSO2 (66.8%±10.3%) was not associated with GA or BW. However, postnatal age appeared to influence physiological rcSO2 changes, given that rcSO2 values were higher during the initial 72 hours than at subsequent intervals. Seven infants (23.3%) had poor outcomes and significantly lower time-averaged rcSO2 (51.1% [50.0%–65.2%] vs. 71.8% [67.1%–73.1%], P=0.002). Multivariate regression indicated that a lower rcSO2 was an independent risk factor, and a 65% threshold showed an optimal predictive value for poor outcomes. Conclusion The neurocritical care bundle helped identify preterm infants at risk of cerebral hypoxia, and lower rcSO2 was an independent risk factor for composite mortality and adverse neurological outcomes.

The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

Alzheimer’s disease (AD) is pathologically characterized by cerebral amyloid β‑protein (Aβ) aggregation, neurofibrillary tangles and progressive cognitive deterioration. There is an urgent clinical demand for targeted therapeutic agents against AD, whereas the blood-brain barrier (BBB) acts as a critical physical barrier that blocks over 98% small-molecule drugs and nearly all biomacromolecules from entering brain parenchyma. Nanomedicine-based drug delivery systems (NDDSs) with tunable physicochemical properties can cross the BBB via multiple transcytosis pathways including adsorptive-mediated, receptor-mediated and transporter-mediated routes, opening a promising avenue for targeted AD treatment. A core academic viewpoint proposed herein is that robust in vitro endothelial penetration of nanocarriers cannot guarantee effective accumulation in brain target cells. Comprehensive evaluation of BBB-crossing delivery efficiency should not merely rely on in vitro permeability tests, but cover the full multi-step transcytosis cascade, cellular tropism in brain tissues and in vivo therapeutic outcomes. This review systematically sorts out diverse nanoplatforms applicable to BBB penetration for AD intervention. Inorganic nanomaterials such as gold and ceria nanoparticles possess large specific surface areas and intrinsic antioxidant capacity, which eliminate reactive oxygen species and hinder Aβ fibrillization. Liposomal formulations and solid lipid nanoparticles exhibit superior biocompatibility with biomimetic phospholipid bilayer architectures, capable of co-loading hydrophilic nucleic acids for Tau regulation and lipophilic Aβ inhibitors; relying on receptor-mediated transcytosis, they achieve sustained drug retention in the brain. Polymeric nanocarriers including nanogels and polyamidoamine dendrimers enable multi-target combinatorial therapy, and can be engineered to release cargo in response to inflammatory microenvironments, thereby suppressing excessive microglial activation and protecting neuronal mitochondria. Beyond conventional nanocarriers, this work elaborates two cutting-edge BBB-crossing delivery platforms: biomimetic nanosystems and metal-organic frameworks (MOFs). Biomimetic nanoparticles camouflaged with erythrocyte, platelet or macrophage membranes, as well as natural exosomes, evade immune clearance, prolong systemic circulation and inherently home to inflammatory lesions. Serving as “nano-decoys”, they neutralize Aβ neurotoxins and remodel cerebral inflammatory microenvironments simultaneously. MOFs feature high porosity and customizable pore channels for co-delivery of multiple therapeutics, and can be integrated with near-infrared photothermal and photooxidation modalities to facilitate focal brain lesion therapy. This review highlights a transformative paradigm shift in the field of BBB-targeted AD therapy: research focus has shifted from simply maximizing cerebral drug penetration toward active modulation and functional restoration of the BBB. Impaired BBB transporters intrinsically impede endogenous Aβ clearance. Accordingly, BBB-regulating nanocarriers are designed to remodel the low-density lipoprotein receptor-related protein 1 (LRP1) trafficking cascade, redirecting endocytic vesicles from lysosomal degradation to non-degradable transcytosis and restoring the intrinsic Aβ efflux capacity of the BBB. Distinct from conventional strategies that only exert local lesion inhibition, this systemic clearance strategy eliminates cerebral Aβ deposits by accelerating peripheral excretion.

Aim To investigate the effect of Huangqi injection(HI)and Huangqi oral solution(HO)on cisplatin-induced nephrotoxicity(CIN)based on un-targeted metabolomics technology and the underlying mechanisms.Methods Sprague Dawley(SD)rats were randomly divided into the blank group,cisplatin(CDDP)model group,HI treatment group,and HO treatment group,then the CIN model was built with low dose multiple intraperitoneal injections of CDDP.Pre-liminary evaluation of the renal protective efficacy of HI and HO was performed by measuring serum creatinine(Scr),blood urea nitrogen(BUN),and organ indi-ces.Further screening and identification of potential biomarkers(PBs)related to CIN and HI/HO pharma-cological effects were attained through metabolomics studies of renal tissues,and pathway enrichment analy-sis was conducted.Results HI and HO significantly restored the abnormal increase in renal function indica-tors and abnormal decrease in organ indices caused by CDDP,as well as significantly improved the abnormal renal metabolic profile induced by CDDP,indicating that both HI and HO had good alleviating effects on CIN.HI significantly reversed 47 out of 54 CIN related PBs,mainly involving metabolic pathways such as glycerophospholipid metabolism,tryptophan metabo-lism,pantothenate and CoA biosynthesis;HO signifi-cantly reversed 18 out of 54 CIN related PBs,mainly involving metabolic pathways such as taurine and hypo-taurine metabolism,ascorbate and aldarate metabo-lism,pentose and glucuronate interconversions.Con-clusions Both HI and HO have significant alleviating effects on CIN.In the short term,HI salleviating effect is superior to that of HO.Overall,the mechanisms by which both alleviate CIN are mainly related to regula-ting lipid metabolism,amino acid metabolism.

Objective To investigate the role and clinical significance of Calpain activity and 145 kDa cleavage fragments of αⅡ-spec-trin breakdown products(SBDP145)in systemic lupus erythematosus(SLE).Methods 124 patients with confirmed SLE and de-tailed clinical data were collected as the SLE group,and 75 healthy individuals who underwent physical examination during the same period were selected as the control group.Their serum samples were collected,and serum SBDP145 levels and Calpain activity were de-tected by the enzyme-linked immunosorbent assay(ELISA)and substrate-based method,respectively.The Mann-Whitney U test,Spearman rank correlation,univariate and multivariate Logistic regression,and receiver operating characteristic(ROC)curve were used to evaluate the clinical value of Calpain activity and SBDP145 in the diagnosis and assessment of SLE.Results Compared with healthy controls,serum Calpain activity([17.000[8.5000,33.500]RFU vs 7.500[4.000,12.500]RFU)and SBDP145 levels(5.283[3.532,9.463]ng/mL vs 1.472[0.994,2.212]ng/mL)in SLE patients were significantly increased(Z=-9.229,P<0.001;Z=-6.881,P<0.001).Furthermore,the Calpain activity was significantly correlated with SLE disease activity index(SLEDAI-2K)score(r=0.349,P<0.001).Logistic regression analysis showed that the increased Calpain activity and SBDP145 levels were significantly associated with the occurrence of SLE(OR=1.164,95％CI:1.016-1.334,P=0.029;OR=3.822,95％CI:1.928-7.574,P<0.001).The ROC curve analysis showed that the area under the ROC curve(AUCROC)of serum Calpain activity in distin-guishing SLE and healthy controls was 0.762(95％CI:0.697-0.827).When the cut-off value was 13.75 RFU,its sensitivity and speci-ficity were 63.1％and 81.1％,respectively.The AUCROC of serum SBDP145 levels in distinguishing SLE and healthy controls was 0.891(95％CI:0.845-0.936).When the cut-off value was 2.377 ng/mL,its sensitivity and specificity were 88.7％and 80.0％,re-spectively.The AUCROC,sensitivity,and specificity of combining the two with traditional SLE clinical indicators,including complement C3,erythrocyte sedimentation rate,and anti-dsDNA antibodies,in the diagnosis of SLE reached 0.986(95％CI:0.972-1.000),93.3％,and 96.0％,respectively.The Spearman correlation analysis results showed that the organ damage index(SDI)score of SLE patients was positively correlated with serum Calpain activity and SBDP145 levels(r=0.342,P<0.001;r=0.250,P=0.005).Con-clusion The elevated Calpain activity and SBDP145 levels are closely related to the occurrence and development of SLE,suggesting that they may be served as potential biomarkers for the diagnosis and assessment of SLE patients.

Aim To investigate the effect of Huangqi injection(HI)and Huangqi oral solution(HO)on cisplatin-induced nephrotoxicity(CIN)based on un-targeted metabolomics technology and the underlying mechanisms.Methods Sprague Dawley(SD)rats were randomly divided into the blank group,cisplatin(CDDP)model group,HI treatment group,and HO treatment group,then the CIN model was built with low dose multiple intraperitoneal injections of CDDP.Pre-liminary evaluation of the renal protective efficacy of HI and HO was performed by measuring serum creatinine(Scr),blood urea nitrogen(BUN),and organ indi-ces.Further screening and identification of potential biomarkers(PBs)related to CIN and HI/HO pharma-cological effects were attained through metabolomics studies of renal tissues,and pathway enrichment analy-sis was conducted.Results HI and HO significantly restored the abnormal increase in renal function indica-tors and abnormal decrease in organ indices caused by CDDP,as well as significantly improved the abnormal renal metabolic profile induced by CDDP,indicating that both HI and HO had good alleviating effects on CIN.HI significantly reversed 47 out of 54 CIN related PBs,mainly involving metabolic pathways such as glycerophospholipid metabolism,tryptophan metabo-lism,pantothenate and CoA biosynthesis;HO signifi-cantly reversed 18 out of 54 CIN related PBs,mainly involving metabolic pathways such as taurine and hypo-taurine metabolism,ascorbate and aldarate metabo-lism,pentose and glucuronate interconversions.Con-clusions Both HI and HO have significant alleviating effects on CIN.In the short term,HI salleviating effect is superior to that of HO.Overall,the mechanisms by which both alleviate CIN are mainly related to regula-ting lipid metabolism,amino acid metabolism.

Objective To develop a precise and efficient single-disease management model to reduce the intensity of antibiotic use.Methods Data was collected from surgical inpatient admissions at the Shanghai Pulmonary Hospital between Jan 2022 and Mar 2024.The study focused on the six most prevalent types of malignant tumors within single-disease management.Surgical patients who did not receive single-disease quality management from Jan 2022 to Jun 2023 were designated as the control group,while surgical patients who received single-disease quality management from Jul 2023 to Mar 2024 served as the management group.By formulating and implementing standardized policies and guidelines for antibiotic use,supervision and effect evaluation were conducted across departments.Results A total of 21 746 individuals were included in the control group and 15 635 in the management group.Following the introduction of the single-disease management model,the proportion of non-restricted antibiotics used in various single diseases increased from 73.2%-77.0%before management to 78.3%-84.4%after management,while the usage of restricted antibiotics significantly decreased(P<0.001).The intensity of antibiotic use,measured in defined daily doses(DDDs),fell significantly from 113.0-159.9 before management to 36.0-44.0 after management(P<0.001).Moreover,compared with the control group,the average length of stay in the intervention group did not change considerably,although the length of stay increased for some diseases,possibly due to more precise medication adjustments.Conclusion The single-disease management model optimizes antibiotic use,reduces the intensity of antibiotic use,and enhances overall medical quality and patient safety.