Objective To design and synthesize novel Hsp90 inhibitors with dual functions of synergistically enhancing the antifungal activity of fluconazole （FLC） against drug-resistant fungi and anti-tumor activity based on the Hsp90 inhibitor Ganetespib. Methods The previous research found that Ganetespib had a good synergistic anti-resistant fungal activity with FLC, with a fractional inhibitory concentration index （FICI） of 0.023 to 0.039. In this study, structural modifications were made to Ganetespib by replacing its indole ring with a phenyl ring containing different substituents to design and synthesize a series of new compounds. The in vitro synergistic anti-resistant fungal activity against C. albicans 0304103 in combination with FLC, anti-tumor activity （against HEL, HL60 and A549 cells）, and Hsp90α inhibition activity were determined to explore their structure-activity relationship and mechanism of action. Results The chemical structures of 19 new compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. Most of the compounds exhibited strong Hsp90α inhibitory activity, good synergistic activity against drug-resistant fungi in combination with FLC and anti-tumor activity. The substitution of electron-donating groups on the benzene ring was beneficial to enhancing the synergistic activity against drug-resistant fungi in combination with FLC. Among them, compounds F3 and F5 showed excellent synergistic activity against drug-resistant fungi in combination with FLC （FICI were both 0.047） and anti-tumor activity （IC₅₀ were 0.025 to 0.15 μmol/L and 0.021 to 0.23 μmol/L respectively）, and could down-regulate the expression levels of drug resistance genes and efflux pump genes in fungi, inhibit the formation of fungal biofilms, and arrest the cell cycle of HEL cells at G0/G1 phase. Conclusion The novel Hsp90 inhibitors such as F3 and F5 could both effectively exert the dual activities of synergizing with FLC to combat drug-resistant fungi and fight against tumors, which provided a new idea for the development of new drugs with dual functions of synergizing with FLC to combat drug-resistant fungi and fight against tumors.

Background: Healthcare-associated infections impose a significant burden on antibiotic usage, healthcare expenditures, and morbidity. Therefore, it is crucial to revise policies to minimize such losses. This nationwide survey aimed to evaluate infection prevention and control (IPC) components in healthcare facilities and encourage improvements in acute care hospitals with inadequate infection prevention settings. This study aims to enhance the infection control capabilities of healthcare facilities. Methods: From December 27, 2021, to May 13, 2022, we conducted a survey of 1,767 acute care hospitals in the Republic of Korea. A survey was conducted to evaluate the infection control components in 1,767 acute care hospitals. Infection control officers provided direct responses to a systematically developed questionnaire. Subsequently, 10% of the respondents were randomly selected for the site investigation. Results: Overall, 1,197 (67.7%) hospitals responded to the online survey. On-site investigations were conducted at 125 hospitals. Hospitals with ≥ 150 beds are advised to have an IPC team under Article 3 of the Medical Service Act; however, only 87.0% (598/687) of hospitals with ≥ 100 beds had one. Conversely, 22.7% (116/510) of hospitals with < 100 beds had an IPC team. Regulations for hand hygiene, waste management, healthcare worker protection and safety, environmental cleaning, standard precautions, and prevention of the transmission of multidrug-resistant pathogens were present in 84.2%, 80.1%, 77.4%, 76.2%, 75.8%, and 63.5% of the hospitals, respectively. Hospitals with < 100 beds had low availability of all categories of standard operating procedures. Conclusion This study is the first national survey of acute care hospitals in the Republic of Korea. The data presented in the current study will improve the understanding of IPC status and will help establish a survey system. Our survey provides a basis for improving policies related to IPC in healthcare facilities.

Background: Healthcare-associated infections impose a significant burden on antibiotic usage, healthcare expenditures, and morbidity. Therefore, it is crucial to revise policies to minimize such losses. This nationwide survey aimed to evaluate infection prevention and control (IPC) components in healthcare facilities and encourage improvements in acute care hospitals with inadequate infection prevention settings. This study aims to enhance the infection control capabilities of healthcare facilities. Methods: From December 27, 2021, to May 13, 2022, we conducted a survey of 1,767 acute care hospitals in the Republic of Korea. A survey was conducted to evaluate the infection control components in 1,767 acute care hospitals. Infection control officers provided direct responses to a systematically developed questionnaire. Subsequently, 10% of the respondents were randomly selected for the site investigation. Results: Overall, 1,197 (67.7%) hospitals responded to the online survey. On-site investigations were conducted at 125 hospitals. Hospitals with ≥ 150 beds are advised to have an IPC team under Article 3 of the Medical Service Act; however, only 87.0% (598/687) of hospitals with ≥ 100 beds had one. Conversely, 22.7% (116/510) of hospitals with < 100 beds had an IPC team. Regulations for hand hygiene, waste management, healthcare worker protection and safety, environmental cleaning, standard precautions, and prevention of the transmission of multidrug-resistant pathogens were present in 84.2%, 80.1%, 77.4%, 76.2%, 75.8%, and 63.5% of the hospitals, respectively. Hospitals with < 100 beds had low availability of all categories of standard operating procedures. Conclusion This study is the first national survey of acute care hospitals in the Republic of Korea. The data presented in the current study will improve the understanding of IPC status and will help establish a survey system. Our survey provides a basis for improving policies related to IPC in healthcare facilities.

Background: Healthcare-associated infections impose a significant burden on antibiotic usage, healthcare expenditures, and morbidity. Therefore, it is crucial to revise policies to minimize such losses. This nationwide survey aimed to evaluate infection prevention and control (IPC) components in healthcare facilities and encourage improvements in acute care hospitals with inadequate infection prevention settings. This study aims to enhance the infection control capabilities of healthcare facilities. Methods: From December 27, 2021, to May 13, 2022, we conducted a survey of 1,767 acute care hospitals in the Republic of Korea. A survey was conducted to evaluate the infection control components in 1,767 acute care hospitals. Infection control officers provided direct responses to a systematically developed questionnaire. Subsequently, 10% of the respondents were randomly selected for the site investigation. Results: Overall, 1,197 (67.7%) hospitals responded to the online survey. On-site investigations were conducted at 125 hospitals. Hospitals with ≥ 150 beds are advised to have an IPC team under Article 3 of the Medical Service Act; however, only 87.0% (598/687) of hospitals with ≥ 100 beds had one. Conversely, 22.7% (116/510) of hospitals with < 100 beds had an IPC team. Regulations for hand hygiene, waste management, healthcare worker protection and safety, environmental cleaning, standard precautions, and prevention of the transmission of multidrug-resistant pathogens were present in 84.2%, 80.1%, 77.4%, 76.2%, 75.8%, and 63.5% of the hospitals, respectively. Hospitals with < 100 beds had low availability of all categories of standard operating procedures. Conclusion This study is the first national survey of acute care hospitals in the Republic of Korea. The data presented in the current study will improve the understanding of IPC status and will help establish a survey system. Our survey provides a basis for improving policies related to IPC in healthcare facilities.

Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

Background: Healthcare-associated infections impose a significant burden on antibiotic usage, healthcare expenditures, and morbidity. Therefore, it is crucial to revise policies to minimize such losses. This nationwide survey aimed to evaluate infection prevention and control (IPC) components in healthcare facilities and encourage improvements in acute care hospitals with inadequate infection prevention settings. This study aims to enhance the infection control capabilities of healthcare facilities. Methods: From December 27, 2021, to May 13, 2022, we conducted a survey of 1,767 acute care hospitals in the Republic of Korea. A survey was conducted to evaluate the infection control components in 1,767 acute care hospitals. Infection control officers provided direct responses to a systematically developed questionnaire. Subsequently, 10% of the respondents were randomly selected for the site investigation. Results: Overall, 1,197 (67.7%) hospitals responded to the online survey. On-site investigations were conducted at 125 hospitals. Hospitals with ≥ 150 beds are advised to have an IPC team under Article 3 of the Medical Service Act; however, only 87.0% (598/687) of hospitals with ≥ 100 beds had one. Conversely, 22.7% (116/510) of hospitals with < 100 beds had an IPC team. Regulations for hand hygiene, waste management, healthcare worker protection and safety, environmental cleaning, standard precautions, and prevention of the transmission of multidrug-resistant pathogens were present in 84.2%, 80.1%, 77.4%, 76.2%, 75.8%, and 63.5% of the hospitals, respectively. Hospitals with < 100 beds had low availability of all categories of standard operating procedures. Conclusion This study is the first national survey of acute care hospitals in the Republic of Korea. The data presented in the current study will improve the understanding of IPC status and will help establish a survey system. Our survey provides a basis for improving policies related to IPC in healthcare facilities.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*