ObjectiveBased on traditional quality evaluation of Gardeniae Fructus（GF） recorded in historical materia medica， this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics， microscopic features， and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length， diameter and individual fruit weight of wild and cultivated GF， and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF， and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently， the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China， the starch content was measured by anthrone colorimetric method， the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method， the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection（HPLC-ELSD）， and the contents of representative components in them were measured by ultra-performance liquid chromatography（UPLC）. Finally， correlation analysis was conducted between quality traits and phenotypic traits， combined with multivariate statistical analysis methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， key differential components between wild and cultivated GF were screened. ResultsIn terms of traits， the wild GF fruits were smaller， exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger， displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF， while the blue-yellow value（b^*） of wild GF was significantly higher than that of cultivated GF. In the microstructure， the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals， while the endocarp contained stone cell class round， polygonal or tangential prolongation， undeveloped seeds were visible within the fruit. In contrast， the mesocarp of cultivated GF contained few calcium oxalate cluster crystals， or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like， with the innermost layer arranged in a grid pattern. Seeds were basically mature， and only a few immature seeds existed in some batches. Regarding primary metabolite content， wild GF exhibited significantly higher total polysaccharide level than cultivated GF（P<0.01）. In category-specific component content， wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF（P<0.01）. Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside， deacetyl asperulosidic acid methyl ester， gardenoside and chlorogenic acid compared to cultivated GF（P<0.01）. Conversely， the contents of genipin 1-gentiobioside， geniposide and genipin were significantly lower in wild GF（P<0.01）. ConclusionThere are significant differences between wild and cultivated GF in terms of traits， microstructure， and contents of primary and secondary metabolites. At present， the quality evaluation system of cultivated GF remains incomplete， and this study provides a reference for guiding the production of high-quality GF medicinal materials.

Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.

Purpose: This study aimed to evaluate the impact of postoperative adjuvant chemotherapy (AC) on survival outcomes in breast cancer (BC) patients who have already undergone neoadjuvant chemotherapy (NAC) followed by surgery. Materials and Methods: Data from a population-based cohort (2010-2020) were analyzed for BC patients treated with NAC and surgery. Univariate and multivariate Cox regression identified prognostic factors for overall survival (OS), and a nomogram was developed and validated. Personalized scores from the nomogram were used for risk stratification to assess the effect of postoperative AC. Results: A total of 15,921 BC patients were analyzed, with 11,144 in the training cohort and 4,777 in the validation cohort. The key prognostic indicators for OS included age, race, marital status, histological grade, BC subtype, T category, N category, type of surgery, and response to NAC (all p < 0.05). The nomogram effectively predicted individualized OS rates and stratified patients into various risk categories. Postoperative AC was found to significantly enhance OS in the high-risk subgroup (p=0.011 in the training cohort, p=0.012 in the overall population). However, for the low-risk subgroup, there was no significant survival benefit from postoperative AC (p=0.130 for the training cohort, p=0.588 for the overall population), suggesting that some patients might safely forgo unnecessary postoperative AC. Conclusion This study efficiently differentiates between varying levels of risk, enabling clinicians to identify patients unlikely to benefit from postoperative AC and thus reduce the likelihood of overtreatment.

Objective To investigate the effect and mechanism of long non-coding RNA(lncRNA)NRON on myocardial fibrosis in mice with myocardial infarction(MI).Methods Thirty-two C57/BL6 mice were randomly assigned to a Sham group,MI group,MI+shNRON group or MI+NC group,with eight mice in each group.The expression level of lncRNA NRON in myocardial tissue of mice was detected by real-time quantitative PCR.Hematoxylin and eosin staining,Masson's trichrome staining,and immunohistochemistry were used to detect the degree of myocardial injury,myocardial fibrosis,and the expression level of collagen Type Ⅰ(col Ⅰ).Western blotting was used to detect the protein expression levels of TGF-β1,p-Smad2,and p-Smad3 in myocardial tissue of the mice.Results Compared with the Sham group,the expression of NRON,col Ⅰ,TGF-β1,p-Smad2,and p-Smad3 proteins were increased in the MI group.Compared with the MI group,the expression of NRON,the degree of myocardial damage and fibrosis,the expression of col Ⅰ,TGF-β1,p-Smad2,and p-Smad3 proteins were decreased in the MI+shNRON group.Conclusion Down-regulation of lncRNA NRON can alleviate myocardial injury and inhibit myocardial fibrosis in mice with MI,and the molecular mechanism may be related to inhibition of the TGF-β/Smad signaling pathway.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective:To explore the application effect of integrated root cause analysis (RCA) in the analysis of approximate administration error events, and to provide reference for the management of clinical approximate administration error events.Methods:A non-synchronous pre-and post-control study was conducted. The data of 3 cases of approximate error events of drug administration in the Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University from January to September 2021 were retrospectively analyzed. The integrated RCA was used to find out the proximal causes, and the system diagram and problem tree analysis were used to determine the root causes. The improvement measures were formulated through barrier analysis, including improving the safety barrier of hospital information system (HIS), updating the database of drug instructions in the Department of Cardiology, standardizing the barrier of nurses′ treatment and examination of medical orders, and visual management barrier. The integrated RCA improvement measures were applied to the management of approximate error events of drug administration. The improvement effect was evaluated by comparing the number of adverse events of medication errors before improvement (January to September 2021) and after improvement (September 2023 to May 2024), the error rate of HIS drug orders, the number of drug interceptions in pharmacies, the processing time of doctors′ HIS orders, and the qualified rate of medical staff 's drug knowledge assessment.Results:There were 32 medical staff in the department of cardiology before improvement, including 6 males and 26 females, aged (31.03 ± 4.29) years old. After improvement, 30 medical staff, 6 males and 24 females, aged (31.20 ± 4.37) years old. After the implementation of integrated RCA improvement, the number of adverse events of medication errors decreased from 3 cases before improvement to 0 cases after improvement. The error rate of HIS drug orders decreased from 11.83%(11/93) before improvement to 2.74%(2/73) after improvement. Improve the pre-audit system without pharmacy drug delivery interception function, improve the pre-application drug information 6 990, the number of drug interception was 0; after improvement, 7 782 pieces of drug information were claimed, and the number of drug interceptions was 78. The difference before and after improvement was statistically significant ( χ2=68.54, P<0.05). After the improvement, the doctor′s HIS doctor′s order processing time including admission, discharge, preoperative, postoperative, examination and medication, and temporary doctor′s order processing time were (1.14 ± 0.41), (1.37 ± 0.30), (0.43 ± 0.11), (0.51 ± 0.11), (0.40 ± 0.10) and (0.51 ± 0.14) min, respectively. They were lower than (4.07 ± 0.70), (3.69 ± 0.60), (1.44 ± 0.24), (2.10 ± 0.45), (1.41 ± 0.28) and (1.44 ± 0.29) min before improvement, and the differences were statistically significant ( t values were 15.21-21.42, all P<0.05). The qualified rate of drug knowledge examination of medical staff increased from 81.25%(26/32) before improvement to 100.00%(30/30) after improvement, and the difference was statistically significant ( P<0.05). Conclusions:The application of integrated RCA to analyze the approximate error events of drug administration is helpful to identify the system defects in the workflow of electronic medical order administration more comprehensively, improve work efficiency and ensure the quality and safety of medical care.

The Gram-negative bacteria Escherichia coli Nissle 1917(EcN)is a probiotic that has been widely applied in clinical practice.With its notable tolerance,safety,and antimicrobial proper-ties,EcN demonstrates the capacity to colonize the intestine and establish a symbiotic relationship with the host,thereby balancing the intestinal microbiota.Extensive studies have elucidated the mechanisms through which EcN regulates the host's innate immune response enhancing the host's ability to combat pathogenic invasions.On one hand,EcN strengthens the integrity of the intestinal mucosal barrier by upregulating the expression of tight junction proteins.On the other hand,EcN's diverse array of secreted,and released components,including lipopolysaccharides,K5 capsule,fla-gellum proteins,and fimbria,play roles in modulating the host's innate immune response.These components interact with host cell receptors and modulate the activities of immune cells and cyto-kines production.By consolidating the current understanding of EcN's probiotic properties,this ar-ticle provides a comprehensive overview of the intricate mechanisms underlying EcN-mediated reg-ulation of the host's innate immune response.Such insights offer theoretical support for leveraging EcN's advantages and improving immune function and overall health maintenance in the host.

The incidence of apoplexy remains persistently high among the older population.Based on the traditional Chinese medicine principle of"treating the elderly by focusing on the fu",this paper explores the holistic connotation of"fu".It proposes that the onset of apoplexy in the elderly is characterized by obstruction,stagnation,depression,and sluggishness,which should be treated from six fu viscera,xuanfu,and collaterals.The interconnected hierarchical network of these three systems,serving as macro-and micro-channels for qi and fluid metabolism,plays a central role in both disease development and treatment.The failure of the six fu viscera to descend and the upward invasion of turbid yin are identified as prerequisites for apoplexy onset,whereas yang qi stagnation and xuanfu blockage act as key pathogenic drivers,and the core mechanisms involve phlegm-stasis-toxin accumulation,and dysfunction of the collaterals and fu.In the treatment,acute phase requires unblocking fu viscera and restoring xuanfu patency;chronic phase focuses on dredging collaterals and opening xuanfu;and recovery phase emphasizes tonifying combined with regulating xuanfu.The understanding of"treating the elderly by focusing on the fu"emphasizes that the pathogenesis of the disease should be changed to individual conditions;"six fu viscera-xuanfu-collaterals"exhibits a pathological mechanism characterized by the transmission and reception of pathogenic factors,as well as progressive mutual involvement;in clinical practice,treatment should meticulously assess the severity and nuances of the condition,prioritizing method that emphasizes unobstructed flow;additionally,therapy should be essential to protect stomach qi and integrate therapeutic attacks within a framework of supplementation.These principles offer valuable reference for the differentiation and treatment of apoplexy.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.