This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective: To investigate the protective effect of dulaglutide on lipopolysaccharide (LPS)-induced inju- ry in MLE-12 cells. Methods: An in vitro model of acute lung injury was established by inducing MLE-12 cells with LPS ( 1 μg/mL) , followed by treatment with dulaglutide for 24 hours. The cells were divided into four groups : CON group , LPS group , LPS + 100 nmol/L dulaglutide group , and LPS + 200 nmol/L dulaglutide group. Protein and RNA were extracted from each group. The mRNA levels of inflammatory factors , including interleukin (IL)-6 , tumor necrosis factor-α (TNF-α ) , IL-1β , monocyte chemotactic protein 1 (CCL2) , C-X-C motif chemokine lig- and (CXCL) 1 and CXCL2 , were detected by qRT-PCR. Cell apoptosis was assessed by TUNEL assay , and the expression levels of phosphorylated protein kinase B (P-Akt) and phosphorylated extracellular signal-regulated ki- nase (P-Erk) were measured by Western blot. Results: Compared with the CON group , the LPS group showed in- creased mRNA levels of inflammatory mediators (TNF-α , IL-6 , IL-1β , CCL2 , CXCL1 , and CXCL2) , increased TUNEL-positive cells , and elevated expression of P-Akt and P-Erk proteins. Compared with the LPS group , the LPS + 100 nmol/L dulaglutide treatment group exhibited reduced mRNA levels of TNF-α , IL-6 , IL-1β , CCL2 , CXCL1 , and CXCL2 , decreased TUNEL-positive cells , and downregulated expression of P-Akt and P-Erk pro- teins. However, the LPS + 200 nmol/L dulaglutide treatment group showed less pronounced improvement in inflam- matory factors compared to the LPS + 100 nmol/L dulaglutide group. Conclusion Dulaglutide has a protective effect on LPS-induced injury in MLE-12 cells , potentially through inhibiting Akt and Erk phosphorylation , thereby reducing the expression of inflammatory mediators and alleviating inflammatory damage , ultimately protecting the lungs.

Objective:To explore the clinical characteristics and prognosis risk factors of aggressive NK-cell leukemia(ANKL).Methods:The clinical and laboratory data of 34 patients with ANKL and 15 patients with chronic lymphoproliferative disorders of NK cells(CLPD-NK)admitted to the First Affiliated Hospital of Zhengzhou University from September 2019 to December 2024 were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,and the Cox proportional hazards regression model was used to analyze prognostic factors.Results:Compared with CLPD-NK patients,ANKL patients had a younger median age of onset,a higher proportion patients with EBV-DNA≥500 copies/ml,hepatosplenomegaly and hemophagocytic syndrome.They also presented with a higher peak of fever,a shorter median survival time,lower WBC count,PLT count,ALB and Fib values,while having higher LDH,AST,TG,ferritin,CRP and PCT levels.There were statistically significant differences in the morphology and expression of HLA-DR,CD56,CD57,CD16 and CD158 on abnormall cells between ANKL patients and CLPD-NK patients.Multivariate survival analysis revealed that combined with asparaginase treatment could improve patients' survival,and CRP≥ 15 mg/L and Fib＜2.0 g/L were independent risk factors affecting the overall survival of patients with ANKL.Conclusion:The differences in clinical features and laboratory tests between patients with ANKL and CLPD-NK aid in the diagnosis of ANKL.CRP and Fib levels can be used to predict the prognosis of patients,and combined asparaginase therapy can enhance the overall survival of patients.

Objective:To systematically evaluate the current status of research on the development of indicators for entrustable professional activities (EPAs) of residents in China.Methods:We searched the China National Knowledge Infrastructure, Wanfang Data, Airiti Library, PubMed, Embase, and Web of Science databases for literature on the development of EPA indicators for residents in China published between January 1, 2005 and February 28, 2025. Two researchers independently screened the literature and extracted data, followed by descriptive analysis. The quality of the studies was assessed using the Joanna Briggs Institute critical appraisal tool for expert opinion. Quantitative data were presented as medians (ranges) and qualitative data were presented as frequencies (percentages).Results:A total of eight articles were included, in which two general EPA indicator systems and six specialty-specific EPA indicator systems were developed for residents. The overall quality of the research was high, with the main shortcomings related to the methods used in the process of constructing the consensus indicators. The number of experts recruited ranged from 22 to 45, with 100.00% response rate, high authority coefficients (0.820-0.914), and high coordination coefficients (0.157-0.741). Most of the studies used literature reviews as one source for the indicator pool (8 studies, 100.00%), employed the Delphi method to reach consensus (6 studies, 75.00%), and provided inclusion criteria for the indicators (7 studies, 87.50%). However, only one study (12.50%) explored the practical application of the developed indicators, and none of the studies set indicator weights or conducted quality assessments. The number of EPA indicators developed ranged from 10 to 38 per study. The reporting of EPA indicators was included in most studies regarding titles (8 studies, 100.00%) and the expected levels of entrustment at various stages of training (6 studies, 75.00%), but the reporting on other aspects was lacking. Among the specialty-specific EPA indicators, 38.39% overlapped with the general EPAs indicators.Conclusions:The research on the development of EPA indicators for residents in China is still in its early stages, and there is room for improvement in methodological quality and reporting coverage. There is partial overlap between specialty-specific and general EPA indicators, failing to fully reflect the unique characteristics of different specialties.

Objective:To compare the accuracy of a Chinese large language model (LLM) and radiologists in Chinese middle level professional qualification examination of radiology, and evaluate the quality of answer reasoning provided by the Chinese LLM.Methods:In this study, 100 high-quality questions were selected using stratified random sampling to form a test set. We asked the ERNIE Bot by dialogues on the website to provide the correct answers and answer reasoning for these questions. These questions were also answered by 15 radiologists with different levels of experience. The accuracy of Chinese LLM and that of radiologists were compared. Two radiologists evaluated the quality of answer reasoning using a 5-point semi-quantitative scale.Results:The accuracy of ERNIE Bot was 60.00%, which was lower than the median (interquartile) accuracy of 67.00% (64.00%, 73.00%) for radiologists, and the difference was statistically significant ( W=2.47, P=0.013). The word count of the reasoning provided by Ernie Bot was (196.44±99.25) words, with no significant difference in word count between correct and incorrect answer reasoning, which were (211.03±107.53) words and (174.55±81.84) words, respectively ( t=1.82, P=0.072). Among the correct answers, the quality of reasoning was scored as follows: 1 point for 3 questions, 2 points for 9 questions, 3 points for 12 questions, and 4 points for 36 questions. No reasoning received a score of 5. Conclusions:Chinese LLM demonstrates a certain level of medical knowledge and clinical reasoning ability, which can assist clinical teachers in educational activities. However, it is not yet able to independently tutor residents and lacks the ability of invitational and heuristic teaching.

Objective:To investigate the current status of Chinese-foreign cooperative education programs for medical majors, and to discuss the potential problems and development trends of this field.Methods:Related data were collected from the information platform of Chinese-Foreign Cooperation in Running Schools by Ministry of Education of the People's Republic of China, and the characteristics of Chinese-foreign cooperative education programs for medical majors were extracted for analysis. Categorical data were expressed as frequency (percentage), and continuous data were expressed as mean±standard deviation.Results:A total of 83 Chinese-foreign cooperative education programs for medical majors were included in the study, accounting for only 3.45% (83/2 406) of all programs. Chinese partners in these cooperative programs were mainly from East China (41 programs, 49.40%), while foreign partners were mainly from Europe (39 programs, 46.99%). The mean duration of these programs was (3.61±0.88) years, with an enrollment of (87.08±35.52) students. Most of the students were included in National General Higher Education Enrollment Plan (79 programs, 95.18%), and the main majors included nursing (39 programs, 46.99%), medical technology (19 programs, 22.89%), and clinical medicine (11 programs, 13.25%), with the main enrollment level of junior college (45 programs, 54.22%). Chinese partners in the cooperative programs mainly issued academic certificate (45 programs, 54.22%) or academic certificate plus degree certificate (36 programs, 43.37%), while most foreign partners did not issue such certificates (44 programs, 53.01%).Conclusions:There are several problems in Chinese-foreign cooperative education programs for medical majors, such as a limited number of programs, a significant regional difference, an imbalanced distribution of specialties, a low level of education, and inconsistency in issuance of certificates, which still requires further improvement and standardization. However, there are also high-level and high-quality programs for reference.

Objective:To explore the clinical characteristics and prognosis risk factors of aggressive NK-cell leukemia(ANKL).Methods:The clinical and laboratory data of 34 patients with ANKL and 15 patients with chronic lymphoproliferative disorders of NK cells(CLPD-NK)admitted to the First Affiliated Hospital of Zhengzhou University from September 2019 to December 2024 were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,and the Cox proportional hazards regression model was used to analyze prognostic factors.Results:Compared with CLPD-NK patients,ANKL patients had a younger median age of onset,a higher proportion patients with EBV-DNA≥500 copies/ml,hepatosplenomegaly and hemophagocytic syndrome.They also presented with a higher peak of fever,a shorter median survival time,lower WBC count,PLT count,ALB and Fib values,while having higher LDH,AST,TG,ferritin,CRP and PCT levels.There were statistically significant differences in the morphology and expression of HLA-DR,CD56,CD57,CD16 and CD158 on abnormall cells between ANKL patients and CLPD-NK patients.Multivariate survival analysis revealed that combined with asparaginase treatment could improve patients' survival,and CRP≥ 15 mg/L and Fib＜2.0 g/L were independent risk factors affecting the overall survival of patients with ANKL.Conclusion:The differences in clinical features and laboratory tests between patients with ANKL and CLPD-NK aid in the diagnosis of ANKL.CRP and Fib levels can be used to predict the prognosis of patients,and combined asparaginase therapy can enhance the overall survival of patients.

Objective:To systematically evaluate the current status of research on the development of indicators for entrustable professional activities (EPAs) of residents in China.Methods:We searched the China National Knowledge Infrastructure, Wanfang Data, Airiti Library, PubMed, Embase, and Web of Science databases for literature on the development of EPA indicators for residents in China published between January 1, 2005 and February 28, 2025. Two researchers independently screened the literature and extracted data, followed by descriptive analysis. The quality of the studies was assessed using the Joanna Briggs Institute critical appraisal tool for expert opinion. Quantitative data were presented as medians (ranges) and qualitative data were presented as frequencies (percentages).Results:A total of eight articles were included, in which two general EPA indicator systems and six specialty-specific EPA indicator systems were developed for residents. The overall quality of the research was high, with the main shortcomings related to the methods used in the process of constructing the consensus indicators. The number of experts recruited ranged from 22 to 45, with 100.00% response rate, high authority coefficients (0.820-0.914), and high coordination coefficients (0.157-0.741). Most of the studies used literature reviews as one source for the indicator pool (8 studies, 100.00%), employed the Delphi method to reach consensus (6 studies, 75.00%), and provided inclusion criteria for the indicators (7 studies, 87.50%). However, only one study (12.50%) explored the practical application of the developed indicators, and none of the studies set indicator weights or conducted quality assessments. The number of EPA indicators developed ranged from 10 to 38 per study. The reporting of EPA indicators was included in most studies regarding titles (8 studies, 100.00%) and the expected levels of entrustment at various stages of training (6 studies, 75.00%), but the reporting on other aspects was lacking. Among the specialty-specific EPA indicators, 38.39% overlapped with the general EPAs indicators.Conclusions:The research on the development of EPA indicators for residents in China is still in its early stages, and there is room for improvement in methodological quality and reporting coverage. There is partial overlap between specialty-specific and general EPA indicators, failing to fully reflect the unique characteristics of different specialties.