Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Heart failure is a complex clinical syndrome and pediatric heart failure (PHF) has a high mortality rate. Early diagnosis is crucial for treatment and management of PHF. In clinical practice, various tests and examinations play a key role in the diagnosis of PHF, including continuously updated biomarkers, echocardiography, and cardiac magnetic resonance imaging. This article focuses on summarizing relevant research on biomarkers, examinations, combined testing, clinical models, and the grading and staging of PHF diagnosis, aiming to provide insights and directions for the diagnosis of PHF.
Humans ; Heart Failure/diagnosis* ; Child ; Biomarkers/blood* ; Echocardiography ; Magnetic Resonance Imaging

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

New psychoactive substances(NPS)have the characteristics of rapid turnover,wide varieties,and high abuse potential.It has become a major threat to global public safety.Currently,the forensic identification of NPS faces certain challenges in detection methods for effectiveness,sensitivity,accu-racy and resistance to matrix interference.Novel functional materials(NFM),with their high specific surface area,designability,specific recognition capability and signal amplification effects,provide a new path for advancing rapid detection techniques for NPS.This paper systematically reviews the innova-tive applications of NFM in the rapid detection of NPS over the past decade.By summarizing and analyzing the research and applications of NFM in laboratory detection and on-site rapid screening,it outlines the characteristics and advantages of different types of materials.Combined with the develop-ment trends of NFM in intelligent material design,interdisciplinary integration and portable integrated devices,it provides theoretical references for the development of rapid detection methods for NPS,which is conducive to improving the rapid detection ability of NPS in"anti-drug combat".

Objective To investigate the effect of total paeony glycoside(TPG)on airway remodeling in bronchial asthma mice and its underlying mechanisms.Methods Forty-eight BALB/c mice were randomly divided into control group,model group,ovalbumin+budesonide group(OVA+BUD group),and OVA+TPG group,with 12 mice in each group.Except the control group,mice in other groups were sensitized by intraperitoneal injection of 10%OVA aluminum hydroxide suspension,and then stimulated by atomized inhalation of 1%OVA to establish mouse asthma model.One hour before each inhalation of OVA,mice in OVA+BUD group were atomized with 2 ml BUD suspension,and mice in OVA+TPG group were given 5 g/kg TPG by intragastric administration.Lung tissues and bronchoalveolar lavage fluid(BALF)of mice from each group were collected,and the pathological morphology of the lung tissues was detected by hematoxylin-eosin(HE)and periodic acid schiff(PAS)staining.Inflammatory cell counts[white blood cell(WBC),neutrophil(NEU),eosinophils(EOS),and leukomonocyte(LYM)]in BALF were detected by Wright-giemsa staining.The contents of inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in BALF were determined by ELISA.Airway remodeling proteins[fibronectin,α-smooth muscle actin(α-SMA),collagen Ⅰ]and NOD-like receptor protein 3(NLRP3)inflammasome-related proteins[NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein(ASC)]levels were detected by Western blotting.Human bronchial smooth muscle cells(HBSMCs)were divided into control group(normal culture),transforming growth factor(TGF)-β1 group(culture medium containing 10 ng/ml TGF-β1),and TGF-β1+TPG group(culture medium containing 10 ng/ml TGF-β1 and 50 μg/ml TPG).Cell proliferation was detected by CCK-8 method,and Western blotting was used to detect the expression of airway remodeling proteins and NLRP3 inflammasome-related proteins.Results Compared with control group,model group exhibited increased infiltration of inflammatory cell in lung tissues,mucosal epithelium hyperplasia,narrowed bronchial lumen narrowed,tube wall thickened,increased cup cells and mucus secretion,and an elevated pathological score of lung injury(P<0.05);the number of inflammatory cells(WBC,NEU,EOS,and LYM)and the levels of inflammatory factors(TNF-α,IL-1β,and IL-6)in BALF were increased(P<0.05),and the expressions of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC were elevated(P<0.05).Compared with model group,BUD or TPG treatment effectively reduced asthma symptoms,improved lung histopathology injury,inhibited bronchial wall thickening,significantly reduced the number of inflammatory cells(WBC,NEU,EOS,and LYM)and the content of inflammatory factors(TNF-α,IL-1β,and IL-6)in BALF,and inhibited expression of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC(P<0.05).Compared with control group,the proliferation rate of HBSMCs was increased,and the protein expression levels of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC were increased in TGF-β1 group(P<0.05).Compared with TGF-β1 group,TPG treatment decreased cell proliferation and inhibited the protein expression of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC(P<0.05).Conclusion TPG may alleviate airway remodeling and asthma symptoms by decreasing the expression of airway remodeling-related proteins,inhibiting NLRP3 inflammasome activation,and reducing the inflammatory response.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.