Background: The gut microbiome is increasingly recognized as a key modulator of frailty. a systematic bibliometric assessment of this rapidly evolving research domain has been lacking. This study aimed to conduct a comprehensive bibliometric analysis to map the research landscape, intellectual structure, and thematic trends in the field of gut microbiota and frailty. Methods: 1,405 publications indexed in the Web of Science Core Collection(from 2010 to 2025) using bibliometric tools (VOSviewer and CiteSpace). The analysis evaluated annual publication outputs, international collaborations, journal contributions, and thematic evolution, with particular focus on microbiota-specific methodologies (e.g., 16S rRNA sequencing, metagenomics) and interventions (e.g., probiotics, fecal microbiota transplantation). Results: 1405 publications related to gut bacteria and aging have been published.Publication output exhibited exponential growth, increasing from 16 in 2010 to 248 in 2024 (R² = 0.994). The United States(386 papers) and China (n = 364 papers) were the most productive countries, whereas European nations—particularly the Netherlands and France—achieved the highest average citation impact. Thematic progression revealed an evolution from early descriptive studies of microbiome composition to mechanistic investigations of host–microbe interactions and, more recently, clinical trials involving dietary and other interventions. Keyword analysis identified central mechanistic themes such as the gut–brain axis, short-chain fatty acids, and inflammatory biomarkers, alongside emerging topics including post-COVID-19 frailty and exercise-based microbiota modulation. Conclusion: Research investigating the association between gut microbiota composition and frailty is expanding rapidly. To advance mechanistic understanding and support clinical translation, future studies should prioritize the integration of multi-omics data and the implementation of rigorously designed randomized controlled trials to establish causal inference and inform evidence-based interventions.

Abstract Hepatocellular carcinoma (HCC) remains a significant therapeutic challenge due to multiple bottlenecks, including low early diagnosis rates, rapid disease progression, and limited efficacy of monotherapy. Against this backdrop, multimodal integrated treatment has emerged as a core solution. Here, we reported a tumor-microenvironment (TME)-activatable “nano-cocktail” (UMDCAc) that synchronizes photodynamic (PDT), chemodynamic (CDT), and starvation (ST) therapies for synergistic HCC eradication. UMDCAc was engineered by growing hollow MnO2 (HMnO2) on upconversion nanoparticles (UCNPs), coloading dihydroartemisinin (DHA) and the photosensitizer chlorin e6 (Ce6), and in situ anchoring ultrasmall gold nanoparticles (AuNPs) that mimic glucose oxidase (GOx). Surface modification with cyclic RGD peptides enabled active targeting of αvβ3 integrin. The targeting strategy synergizes with near-infrared (NIR) light-activated catalysis to enhance therapeutic efficacy. Invitro and invivo data demonstrate that UMDCAc achieves tumor suppression through synergistically amplified reactive oxygen species (ROS) generation, hypoxia relief, and targeted delivery, while maintaining favorable biocompatibility and safety and exhibiting superior efficacy over monotherapy. The synergistically generated ROS compromise cellular antioxidant defenses, induce lipid peroxidation, and double the apoptosis rate, thereby producing effective antitumor effects. Therefore, this innovative multimodal strategy offers opportunities for collaborative cancer therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated infections remain a formidable clinical challenge, owing to limited antibiotic penetration, an immunosuppressive microenvironment, and recurrent biofilm regeneration. Effective long-term immunomodulatory strategies to prevent reinfection are still lacking. To address this issue, we have constructed a biomimetic cascade nanoplatform (MACP@DG@CM) that integrates a photothermal nanozyme core, surface-anchored DNase I-functionalized gold nanoclusters (DNase I-GNCs), and a pre-activated macrophage membrane camouflage. This design enables synergistic biofilm eradication and immune microenvironment modulation. Under an 808 nm near-infrared (NIR) irradiation, the nanoplatform triggers a cascade radical storm, including photothermal hyperthermia, a peroxidase-like hydroxyl radical (·OH) burst, nitric oxide (NO) release, and DNase I-mediated extracellular DNA (eDNA) degradation. Concurrently, it depletes glutathione (GSH), disrupts bacterial redox homeostasis, and causes severe membrane damage. Transcriptomic analysis reveals that the nanoplatform perturbs bacterial two-component systems, d-amino acid metabolism, and antimicrobial peptide resistance pathways. Enzyme-linked immunosorbent assay (ELISA) further confirms up-regulated pro-inflammatory cytokines and down-regulated anti-inflammatory cytokines, indicating an activated inflammatory response. In an MRSA-infected wound model, it accelerates wound closure, promotes collagen deposition, and modulates inflammation. Collectively, this biomimetic cascade nanoplatform provides a synergistic strategy for biofilm eradication and immune activation against drug-resistant infections.

Bacterial biofilms play a crucial role in the emergence of antibiotic resistance and the persistence of chronic infections. The challenge of effectively eradicating bacterial biofilms while ensuring minimal toxicity to normal cells persists. Carbon-based artificial nanoenzymes have attracted considerable attention as emerging nanotheranostic agents, owing to their biocompatibility, cost-effectiveness, and straightforward synthesis. In this study, we have developed a multifunctional carbon dots (CDs) system, specifically CDs functionalized with 1-(3-aminopropyl) imidazole (API), termed CDs-API. This system demonstrates acid-activated antibiofilm activity. The CDs-API were synthesized from chlorogenic acid (ChA), a bioactive compound naturally occurring in coffee, and subsequently functionalized with API to achieve charge-switchable properties under acidic conditions. This distinctive feature enables CDs-API to efficiently penetrate bacterial biofilms and selectively target the colonized bacteria. The enzyme-like activity of CDs-API effectively consumes high levels of glutathione (GSH) within the biofilm, leading to the accumulation of reactive oxygen species (ROS). Consequently, this process degrades the extracellular polymeric substance (EPS) matrix, damages bacterial DNA and protein structures, and disrupts the redox balance, ultimately leading to bacterial cell death. Experimental results demonstrated that CDs-API effectively inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAE) while promoting wound healing with minimal damage to healthy tissues. The acid-activated charge-switchable capability of CDs-API provides superior antibacterial efficacy compared to traditional antibiotics, rendering it a promising candidate for the treatment of bacterial biofilm infections.

Complete hepatitis B virus (HBV) cure is hindered primarily by the stable persistence of covalently closed circular DNA (cccDNA). Gene editing approaches to eradicate HBV by targeting cccDNA face challenges and limitations due to suboptimal editing efficiency and substantial off-target effects. Herein, a combinatorial therapeutic strategy is developed that integrates CRISPR/Cas9-mediated cccDNA disruption with an antisense oligonucleotide (ASO)-targeted degradation of pregenomic RNA (pgRNA). To overcome delivery challenges, a hepatocyte-targeting nanocarrier (UACPG) is engineered, featuring low immunogenicity, high payload capacity, and dual-stimuli responsiveness. The UACPG platform enabled liver-specific delivery through surface-conjugated targeting ligands, followed by on-demand release of Cas9 ribonucleoprotein complexes and ASO via RNase H-dependent degradation and near-infrared (NIR) light activation. The results demonstrated that UACPG can effectively reduce HBV replication and viral antigen levels, while significantly lowering cccDNA in hydrodynamic HBV-infected mouse models, with no significant off-target effects observed. This nanocarrier achieved the spatiotemporally controlled release of gene-editing systems in vitro and in vivo, significantly inhibiting the replication of HBV, thereby establishing an innovative technological platform for developing curative HBV therapies.

Background: Comprehensive data on the economic burden of cervical cancer treatment remain scarce in China’s less developed regions, necessitating this study on hospitalization costs and expenditure trends in these areas. Methods: Employing a multi-stage stratified cluster sampling approach, this study enrolled 10,070 cervical cancer inpatients from 72 healthcare facilities in Gansu Province. Clinical and expenditure data were extracted from hospital information systems. Rank sum tests and Spearman correlation analyses were performed for univariate assessment, while quantile regression and random forest models were applied to identify determinant factors. Results: From 2019 to 2023, the average hospitalization duration for cervical cancer patients in Gansu Province was 16.12 days, with an average hospitalization cost of USD 3862.08 (2023 constant prices, converted from CNY at 1:7.0467). During these five years, the average inpatient costs per hospitalization increased from USD 3473.45 to USD 4202.57, and the average daily hospitalization cost rose from USD 230.53 to USD 241.77. The average drug cost decreased from USD 769.06 to USD 640.16. The main factors influencing hospitalization costs included the length of hospital stay, whether cervical cancer surgery was performed, hospital type, hospital level, and the proportion of medications. Conclusions: Our findings indicate that cervical cancer is a considerable economic burden on both families and society. This highlights the need to control the length of hospital stay and optimize the allocation of medical resources, in addition to strengthening cervical cancer screening and HPV vaccination in underdeveloped areas, in order to enhance the efficiency of prevention and treatment and ensure medical equity.

Numerous studies over the past few decades have shown that RNAs are multifaceted, multifunctional regulators of most cellular processes, contrary to the initial belief that they only act as mediators for translating DNA into proteins. LncRNAs, which refer to transcripts longer than 200nt and lack the ability to code for proteins, have recently been identified as central regulators of a variety of biochemical and cellular processes, particularly cancer. When they are abnormally expressed, they are closely associated with tumor occurrence, metastasis, and tumor staging. Therefore, through searches on Google Scholar, PubMed, and CNKI, we identified five five recently characterized lncRNAs-Lnc-SLC2A12-10:1, LncRNA BCRT1, lncRNA IGFBP4-1, LncRNA PCNAP1, and LncRNA CDC6-that have been linked to the promotion of cancer cell proliferation, invasion, and metastasis. Consequently, this review encapsulates the existing research and molecular underpinnings of these five newly identified lncRNAs across various types of cancer. It suggests that these novel lncRNAs hold potential as independent biomarkers for clinical diagnosis and prognosis, as well as candidates for therapeutic intervention. In parallel, we discuss the challenges inherent in the research on these five newly discovered lncRNAs and look forward to the avenues for future exploration in this field.

Objective: Endometrioid ovarian cancer (EnOC) accounts for approximately 10%-15% of epithelial ovarian cancer cases. There are no effective tools for predicting the prognosis of EnOC in clinical work. The aim of this study was to construct and validate a nomogram to predict overall survival and cancer-specific survival (CSS) in patients with EnOC.Methods: Data regarding patients diagnosed with primary EnOC between 2004 and 2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. LASSO Cox regression and Cox regression analyses were performed to screen for prognostic factors, which were used to construct nomograms. In addition, we performed subgroup analyses of the prognostic value of chemotherapy and lymph node surgery.Results: In total, 3957 patients with primary EnOC were included in the analysis: 2770 in a training cohort and 1187 in a validation cohort. Age, stage, grade, lymph node surgery, and race were significantly and independently correlated with overall survival and CSS. Nomograms were constructed to predict 3- and 5-year overall survival and CSS. Nomograms have good predictive ability and clinical practicability. Subgroup analysis showed that lymph node surgery improved the prognosis of patients with EnOC (P < 0.05) except for patients with grade III-IV and Stage I disease (overall survival P = 0.272, CSS P = 0.624). Chemotherapy did not improve survival time in most patients (P > 0.05) except for patients with grade I-II and Stage II-IV disease (overall survival P = 0.008, CSS P = 0.046).Conclusion: We constructed predictive nomograms and a risk classification system to evaluate overall survival and CSS in EnOC patients. For most patients with EnOC, chemotherapy did not improve the prognosis. In contrast to chemotherapy, lymph node surgery improved prognosis in most patients with EnOC.

Schematic illustration of (A) Acr-Bis polymerization catalyzed by HRP /H2O2/ACAC ternary initiation system and (B) the polymerization of Acr-Bis causes AIE phenomenon of BSA-Au NCs.

Bovine serum albumin-stabilized Au nanoclusters (BSA-Au NCs) have emerged as promising contenders for imaging agents and highly sensitive fluorescence sensors due to their biocompatibility and strong photoluminescence. Optimizing the synthesis conditions of BSA-Au NCs is crucial for enhancing fluorescence imaging and other nanocluster applications. In this study, for the first time, we systematically investigated the effects of BSA concentration and Au3+ on both particle size and optical characteristics of BSA-Au NCs. When the two components achieved a suitable concentration ratio, it was beneficial to form BSA-Au NCs with a high quantum yield (QY = 74.30%) and good fluorescence stability. In contrast, an inappropriate concentration ratio would lead to the formation of gold nanoparticles (Au NPs), and their internal filtration effect (IFE) would attenuate the fluorescence emission of BSA-Au NCs. The BSA-Au NCs were then employed as efficient fluorescence sensors for detecting Hg2+. Furthermore, the growth mechanism of BSA-Au NCs was elucidated by monitoring fluorescence changes during different incubation times. The BSA-Au NCs with a high quantum yield introduce a novel synthetic concept for sensitive fluorescent probes and expanding versatile applications of BSA-Au NCs in catalysis, chemical sensing and biomedicine.

Perfluoroalkyl substances (PFASs) are a classic environmental endocrine disruptor with carcinogenic risk. Epidemiological studies have shown that PFASs contamination is associated with breast cancer development, but the mechanism remains largely unknown. This study first obtained complex biological information about PFASs-induced breast cancer through the comparative toxicogenomics database (CTD). The Protein-Protein Interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were utilized to investigate molecular pathways. The ESR1 and GPER expression levels at different pathological stages and the prognosis of Breast Cancer patients were confirmed using the Cancer Genome Atlas (TCGA) database. Furthermore, we verified this by cellular experiments and the results showed breast cancer cell migration and invasion were promoted by PFOA. Two estrogen receptors (ER), ERα and G protein-coupled estrogen receptor (GPER), mediated the promoting effects of PFOA by activating MAPK/Erk and PI3K/Akt signaling pathways. These pathways were regulated by ERα and GPER in MCF-7 cells or independently by GPER in MDA-MB-231 cells. Overall, our study provides a better overview of the mechanisms associated with PFASs-induced breast cancer development and progression.

Background:Regional anesthesia have been successfully performed for pain management in breast cancer surgery, but it is unclear which is the best regional anesthesia technique. The aim of the present network meta-analysis was to assess the analgesic efficacy and disadvantages of regional anesthesia techniques.Methods:Multiple databases were searched for randomized controlled trials (RCTs). The association between regional anesthesia and analgesic efficacy was evaluated by Bayesian network meta-analysis.Results:We included 100 RCTs and 6639 patients in this study. The network meta-analysis showed that paravertebral nerve block, pectoral nerve-2 block, serratus anterior plane block, erector spinae plane block, rhomboid intercostal block, and local anesthetic infusion were associated with significantly decreased postoperative pain scores, morphine consumption and incidence of postoperative nausea and vomiting compared with no block. Regarding the incidence of chronic pain, no significance was detected between the different regional anesthesia techniques. In the cumulative ranking curve analysis, the rank of the rhomboid intercostal block was the for postoperative care unit pain scores, postoperative 24-hour morphine consumption, and incidence of postoperative nausea and vomiting.Conclusion:Regional anesthesia techniques including, paravertebral nerve block, pectoral nerve-2 block, serratus anterior plane block, erector spinae plane block, rhomboid intercostal block, and local anesthetic infusion, can effectively alleviate postoperative acute analgesia and reduce postoperative morphine consumption, but cannot reduce chronic pain after breast surgery. The rhomboid intercostal block might be the optimal technique for postoperative analgesia in breast cancer surgery, but the strength of the evidence was very low.Systematic review registration:https://www.crd.york.ac.uk/prospero/(PROSPERO), identifier CRD 42020220763.

Hepatitis B virus (HBV) infection is a serious global public health threat. It remains elusive to achieve a functional HBV cure with currently available antivirals. Herein, a photo-responsive delivery vehicle composed of Nd3+-sensitized core-shell upconversion nanoparticle (UCNP), mesoporous silica nanoparticle (MSN), antisense oligonucleotides (ASOs), and capsid-binding inhibitor C39 was established, which was named UMAC according to the initials of its components. Subsequently, the as-synthesized delivery vehicle was encapsulated by beta-D-galactopyranoside (Gal) modified red blood cell (RBC) membrane vesicles, which enabled precise targeting of the liver cells (UMAC-M-Gal). Both in vitro and in vivo experiments demonstrated that this biomimetic system could successfully achieve controlled drug release under light conditions at 808 nm, leading to effective suppression of HBV replication in this dual-targeted therapeutic approach. Together, these results substantiate the system has huge prospects for application to achieve functional HBV cure, and provides a promising novel strategy for drug delivery.

Protein-stabilized gold nanoclusters (Prot-Au NCs) have been widely used in biosensing and cell imaging owing to their excellent optical properties and low biotoxicity. However, several Prot-Au NCs reported in the literature do not retain the biological role of the protein, which greatly limits their ability to directly detect biomarkers. This study demonstrated for the first time the successful synthesis of dual-function avidin-stabilized gold nanoclusters (Av–Au NCs) using a one-pot method. The resulting Av–Au NCs exhibited intense blue and red emissions under 374 nm excitation. Furthermore, the Av–Au NCs retained the native functionality of avidin to bind to biotin. When DNA strands modified with biotin at both ends (i.e., linker chains) were mixed with Av–Au NCs, large polymers were formed, indicating that Av–Au NCs could achieve fluorescence signal amplification by interacting with biotin. Taking advantage of the aforementioned properties, we constructed a novel enzyme-free fluorescent biosensor based on the Av–Au NCs-biotin system to detect DNA. The designed fluorescent biosensor could detect target DNA down to 0.043 nM, with a wide line range from 0.2 nM to 20 µM. Thus, these dual-functional Av–Au NCs were shown to be an excellent fluorescent material for biosensing.

The overuse of antibiotics has contributed to the emergence of multidrug-resistant bacteria, which poses a challenging task for clinical therapy. Thus, new agents with antibiotic efficacy against multidrug-resistant infections are needed. The traditional Dong ethnic minority medicines have emerged as a new source for prodrug selection. Among them, Madeng'ai (PotentillafreynianaBornm) is widely used by the folk for anti-infection and wound healing, although the mechanisms remain unclear. In this study, the antimicrobial activities of Dong medicine Madeng'ai were evaluated both in vitro and in vivo. S. aureus, E. coli, E. faecalis, P. aeruginosa, K. pneumoniae, and A. baumannii were cultured in LB media, different concentrations of Madeng'ai powder solution were added to the LB agar plates to evaluate minimal inhibitory concentration. An animal study was performed on a mouse excisional wound model combined with bacterial solution injection in the wound area. After Madeng'ai or PBS treatment, hematoxylin and eosin analysis were used for pathological analysis of skin tissues from the infected area. Madeng'ai powder solution over 2 mg/mL concentration completely inhibited E. coli growth. At 4.0 mg/mL, Madeng'ai significantly inhibited the growth of E. faecalis, Pseudomonas aeruginosa (PAE), Klebsiella pneumoniae, and Acinetobacter baumannii. The mouse model revealed that Madeng'ai could suppress the growth of MRSA and PAE and accelerate healing of cutaneous wounds. Madeng'ai, a newly discovered Dong ethnic minority medicine possesses considerable antimicrobial activity against both human normal pathogenic bacteria and multiresistance bacteria such as Pseudomonas aeruginosa, S. aureus, and Acinetobacter baumannii. Therefore, Madeng'ai has great potential for further study and clinical application.

Background Inherent limitations of single cancer therapy are overcome by multi-therapy modality, which integrates characteristics of each therapeutic modality and material chemistry. The multi-modal method has the potential for becoming one of the next generation options for cancer treatments. Photothermal therapy (PTT) is an efficient, non-invasive treatment method that can be used on various cancer types. We propose an acid-triggered self-destructing nano-biocatalyst integrated starvation/chemical/photothermal triple therapy that is based on design principles and biomedical applications of GOx cancer treatment methods. Methods Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potentials were used to analyze the physical as well as chemical properties of MoS 2 @DOX/GOx@MnO 2 (M@D/G@M). Further, Fourier transform infra-red (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) were used to assess the compositions of the nanocatalysts. The biological effects of M@D/G@M on cells were studied in vitro by inverted fluorescence microscopy, confocal laser scanning microscopy (CLSM), flow cytometry, CCK-8 test, and hemolysis test. Treatment effects of the nanocatalysts were evaluated in MHCC-97H tumor BALB/c mice, whose body weights, tumor local temperature, tumor volumes, and tumor histological changes were evaluated. Results There was a high DOX encapsulation efficiency of M@D/G@M (90.233%). The photothermal conversion efficiency (η) of M@D/G@M is 25.2%, and its oxygen production within 5 min reached 27.5 mg L −1 . Cell internalization analysis showed that within 4 h, M@D/G@M was almost completely absorbed by HepG2 cells. Further, the highest red fluorescence and apoptosis effects of dead cells (59.07% apoptosis) as well as the lowest tumor volume index of mice (0.2862%) were observed in the M@D/G@M + pH6.0 + NIR treatment group. Conclusions Our findings inform the development and applications of multi-modal methods in tumor therapy.

Abstract Pulmonary mucoepidermoid carcinoma (PMEC) is uncommon. The purpose of this study was to evaluate the clinicopathological features, diagnostic criteria, treatment options, and prognostic factors relating to primary PMEC. Clinical data on 45 patients with primary PMEC were collected and analyzed retrospectively at Tianjin Medical University General Hospital and the First People’ Hospital of Longquanyi District Chengdu from January 2008 to December 2020. The 45 patients (25 males and 20 females) ranged in age from 22 to 72 years, with a median age of 49 and an average age of 47.7. All the patients underwent surgery, with 32 receiving only surgery and 13 receiving both surgery and postoperative chemotherapy. A total of 34 instances of low‐grade tumors and 11 cases of high‐grade tumors were discovered during postoperative pathological diagnosis. Forty‐five patients were followed for 13 to 78 months, and four died during this period. In all four instances, a lung infection unrelated to the tumor was determined to be the cause of death. The MAML2 gene translocation was detected in 40 of 45 patients, with 34 of them testing positive. Radical surgery with lymph node dissection is an efficient treatment for PMEC. The prognosis is poor for patients with advanced disease, a negative MAML2 gene translocation, lymph node metastases, and high‐grade tumors.

Exposure to ethephon (ETH), a plant growth regulator commonly used for several purposes, can potentially decrease sperm numbers and viability. Occasional findings regarding ETH effects on female reproduction during early pregnancy have also been reported. During early pregnancy, endometrial decidualization is a critical event for embryo implantation and pregnancy maintenance. Thus, we aimed to explore the effect and mechanism of ETH on endometrial decidualization both in vivo and in vitro. Mice were gavaged with 0 and 285 mg/kg b.w. ETH from gestational days (GD)1 until sacrifice, whereas pseudopregnant mice from pseudopregnant day 1 (PPD-1) until PPD-8. Primary mouse endometrial stromal cells (mESCs) received 640 ug/ml ETH and added E2 and P4 to induce decidualization. Results indicated female albino CD1 mice exposed to high dose of ETH (285 mg/kg b.w.) by oral gavage, the number of embryo implantation sites on GD6 and GD8 were significantly decreased, the levels of serum E2 and P4 on GD8 were significantly decreased. Compared with the control group, the decidualization response artificially induced by corn oil in pseudopregnant mice and by E2 and P4 in primary mouse endometrial stromal cells (mESCs) was weakened in the high dose of ETH treated group. The high dose, 285 mg/kg b.w ETH treated group altered the expression of endometrial decidual markers on GD6 and GD8. The triglyceride and fatty acid metabolism-related genes were significantly increased after female albino CD1 mice exposed to high does, 285 mg/kg b.w ETH on GD6 and GD8. GPR120 was substantially reduced after ETH treatment. When overexpression of GPR120, the compromised decidualization induced by ETH treatment was rescued. Furthermore, molecular docking presented Thr234 and His251 of GPR120 as preferred binding sites for ETH. Mutation of these two sites rescued the compromised decidualization induced by ETH. In conclusion, we demonstrated that ETH exposure could impair decidualization during early pregnancy. GPR120 expression and binding between GPR120 and ETH are crucial for impaired decidualization mediated via ETH.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. This study aimed to investigate the therapeutic efficacy of puerarin on PD in rats and the mechanism. The rat model of PD was established by injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra. The modeled rats were randomly divided into model, low-dose puerarin (puerarin-L), middle-dose puerarin (puerarin-M), and high-dose puerarin (puerarin-H) groups. The latter three groups were treated with 25, 50, and 100 mg/kg puerarin by gavage, respectively, for four continuous weeks. After treatment, when comparing to Model group, in Puerarin-M and Puerarin-H groups the escape latency was obviously decreased (p < 0.05), the platform crossing times were obviously increased, the serum and substantia nigra tissue superoxide dismutase and glutathione peroxidase levels were obviously increased (p < 0.05), the malondialdehyde level was obviously decreased (p < 0.05), and the substantia nigra tissue nuclear factor E2-related factor 2 (Nrf2) and Kelch-like epichlorohydrin-associated protein 1 (Keap1) protein expression levels were significantly increased (p < 0.05). In conclusion, puerarin can reduce the oxidative stress injury, thus protecting the substantia nigra in rats with 6-OHDA-induced PD. The mechanism may be related to its regulation of Nrf2-keap1 signal pathway in substantia nigra.

Background: With the increasing incidences of papillary thyroid cancer(PTC), it is important to risk-stratify patients who may have more aggressive tumor biology. This study aimed to evaluate the risk factors for lymph node metastasis with PTC in Southwest China Patients which may provide a substantial reference for clinical diagnosis and treatment. Methods: 1045 PTCs (313 PTMC and 732 non-PTMC) between August 2016 and August 2019 were examined totally (including one Tibetan). BRAF V600E mutation was tested in all samples. The clinical data (gender, age, tumor location, sample source and pathological features) were retrospectively analyzed. Logistic regression analysis was performed to evaluate independent risk factors for LNM. Results: 181 out of 313 PTMC cases (57.8%), 145 out of 732 non-PTMC cases (19.8%) had BRAF V600E mutation, the Tibetan had a double mutation of BRAF L597Q and V600E in two separate lesions. In PTMC, significant difference in gender and sample source was found (BRAF V600E mutation vs. wild-type). In non-PTMC, significant difference in gender was found (BRAF V600E mutation vs. wild-type). The female (OR=1.952; 95% CI= 1.373-2.774; P= 0.00), age (31-59 years) and diameter of tumor ≤1cm (OR=3.273; 95% CI= 2.417-4.432; P=0.000) were significant independent predictors of LNM in all PTCs. In PTMC, the female (OR= 3.002; 95% CI= 1.654-5.446; P= 0.00) was a significant independent predictor of LNM. The tumor in left and right lobes simultaneously was an independent protective factor of LNM in each group (PTCs: OR=0.287; PTMC: OR=0.170; non-PTMC: OR=0.441, respectively). The BRAF V600E mutation rate of US-FNAC was much higher than FFPE in PTMC (P=0.018). Conclusions: Unlike previous research, our findings suggested that the female patients and diameter of tumor ≤1cm were risk factors for LNM and the BRAF V600E wild-type of PTMC might be more aggressive than others. Interestingly, the position of tumor in bilateral thyroid simultaneously was an independent protective factor for LNM. The US-FNA should be recommended for gene analysis (BRAF V600E) in PTMC. The BRAF L597Q mutation may be an independent aggressive factor in the Chinese Tibetan population. Hence, clinicians should consider an individualized treatment according to gene mutation, gender, age, tumor size and location of tumor in order to achieve a better therapeutic efficacy.