Objective To investigate the heterogeneity and key molecular features of epithelial cells in triple-negative breast cancer (TNBC), identify prognostic biomarkers, and develop a robust survival prediction model. Methods Using TNBC single-cell transcriptomic data, epithelial cells were extracted, normalized, and subclustered to characterize their molecular signatures and functional differences. High-dimensional weighted gene co-expression network analysis (hdWGCNA) was applied to establish co-expression modules in epithelial cells. Multiple machine learning algorithms were integrated to select key prognostic genes and develop a risk-score model, whose performance was evaluated using receiver operating characteristic (ROC) curves and Kaplan-Meier (K-M) survival analysis. In addition, the immune microenvironment features and potential drug-response differences between the high- and low-risk groups were systematically assessed. Finally, PCR was performed to validate the expression differences of the key genes between tumor and normal tissues. Results We characterized the composition and molecular features of TNBC epithelial subpopulations and identified a TNBC-associated epithelial subset. By integrating hdWGCNA with machine learning approaches, 10 key genes were selected to construct a prognostic model, which effectively stratified patients into distinct survival-risk groups and demonstrated favorable predictive performance in ROC and K-M analyses. Immune profiling revealed the differences in the infiltration levels of seven immune cell types and immune function-related features between the high- and low-risk groups. Drug-sensitivity analysis suggested potential differential responses to eight agents across the risk groups. PCR validation further confirmed the differential expression of the ten signature genes between tumor and normal tissues. Conclusion This study reveals epithelial heterogeneity in TNBC at single-cell resolution and establishes a 10-gene prognostic model, which may facilitate the stratification of TNBC risk and the evaluation of immune characteristics and potential therapeutic strategies.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

OBJECTIVES: To investigate the etiological characteristics of bacterial meningitis (BM) in infants aged <90 days. METHODS: A retrospective analysis was conducted on the etiology and outcomes of BM in infants aged <90 days admitted to five collaborating hospitals between January 2007 and December 2021. The overall etiological profile was described, and pathogen distributions were compared across different age groups, regions, and years. The prognosis of BM caused by common pathogens was also evaluated. RESULTS: A total of 197 infants with bacteriologically confirmed BM were included. The most common pathogens were Escherichia coli (E. coli) (72 cases, 36.5%), group B Streptococcus (GBS) (49 cases, 24.9%), and Listeria monocytogenes (LM) (11 cases, 5.6%). The detection rate of E. coli was significantly higher in the neonatal group than in the infant group (40.2% vs 18.2%, P<0.05). E. coli was the predominant pathogen in Beijing (31.7%) and Kunming (54.1%), while GBS and E. coli were equally prevalent in Shenzhen (33.3%). From 2018 to 2021, the detection rates of E. coli were 46.4%, 47.2%, 45.2%, and 36.8%, respectively, whereas those of GBS were 25.0%, 27.8%, 22.6%, and 31.6%. No significant difference was observed in the overall complication rates among BM cases caused by E. coli, GBS, and LM (P>0.05). However, ventriculitis and hydrocephalus were more frequent in LM meningitis than in GBS meningitis (P<0.017). CONCLUSIONS E. coli is the most common pathogen in BM among young infants, particularly neonates. GBS is predominant in Shenzhen, with an increasing trend. LM meningitis accounts for a notable proportion of cases and is associated with poorer outcomes.
Humans ; Meningitis, Bacterial/microbiology* ; Infant ; Retrospective Studies ; Infant, Newborn ; Male ; Female