N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

Objective To explore the impact of national volume-based procurement policies on the use of medicines in treatment of benign prostatic hyperplasia （BPH） and provide data support for the rational clinical use of medicines in BPH treatment. Methods Data on the use of BPH treatment medications from 2019 to 2023 were extracted from the Chinese Medicine Economic Information Network （CMEI）, covering 892 hospitals （including 645 tertiary hospitals and 247 secondary hospitals）. The changes in various indicators, including the consumption sum, Defined daily doses （DDDs）, Defined daily dose cost （DDDc）, and the ranking ratio （B/A） of these drugs were analyzed and compared. Results From 2019 to 2023, due to the influence of relevant policies, the overall consumption sums of medicines used in the sample hospitals in BPH treatment showed a trend of decreasing first and then rising steadily. The DDDs showed an overall upward trend, while the DDDc demonstrated a gradual decline. Tamsulosin and finasteride consistently ranked first and second in DDDs. The B/A value for tamsulosin was significantly higher than that of other BPH treatment medications. Conclusion The implementation of national centralized drug volume-based procurement policies and other policies from 2019 to 2023 had effectively reduced the economic burden of patients with benign prostatic hyperplasia. Tamsulosin and finasteride, which had the highest B/A in the two categories of α-blockers and 5α-reductase inhibitors, dominated the market for BPH treatment. The clinical use of BPH treatment medications was relatively rational.

OBJECTIVE To investigate the ameliorating effect and mechanism of the effective substance groups from Artemisia ordosica（Abbreviated as HSH） on rheumatoid arthritis （RA） based on cluster of differentiation 4/lymphocyte cell-specific protein- tyrosine kinase/zeta-chain-associated protein kinase of 70 kDa/interleukin-17（CD4/LCK/ZAP70/IL-17） signaling pathway. METHODS The rats were divided into normal group， model group， HSH low-dose， medium-dose and high-dose groups （2.7， 10.8， 21.6 mg/kg） and positive control group （Tripterygium glycosides tablet， 6.3 mg/kg）， with 10 rats in each group. Except for normal group， RA rat model was induced by complete Freund’s adjuvant in other groups. After modeling， each group was given relevant medicine or normal saline intragastrically， once a day， for 28 consecutive days. The changes in ankle joint swelling and arthritis index in rats were determined； the pathological changes of ankle joint tissue were observed； the levels of inflammatory factors [IL-1β， IL-21， IL-17A， IL-2， interferon-γ （IFN-γ） and IL-6] in serum and joint fluid of rats were determined； the levels of Th1， Th17 and Treg cells in the whole blood and spleen of rats were detected； protein and mRNA expressions of LCK， proto-oncogene tyrosine-protein kinase Fyn （Fyn）， ZAP70， CD45， RAR-related orphan receptor γt （RORγt）， and forkhead box protein 3 （Foxp3） in ankle synovial tissue were determined. RESULTS Compared with normal group， the changes in ankle joint swelling， arthritis index， the levels of IL-1β， IL-21， IL-17A， IL-2， IFN-γ and IL-6 in serum and joint fluid， the levels of Th1， Th17 cells and Th17/Treg value in whole blood and spleen， and the protein and mRNA expression levels of LCK， Fyn， ZAP70， CD45， and RORγt in ankle joint synovium were all significantly increased/elevated （P＜0.05）. The level of Treg cells in the spleen， as well as the protein and mRNA expression levels of Foxp3 in the ankle joint synovium were significantly decreased （P＜0.05）. Compared with model group， most of the above-mentioned indicators were significantly reversed in the positive control group and all dose groups of HSH （P＜0.05）. The degree of pathological changes in ankle joint tissues was markedly improved， and inflammation was alleviated. CONCLUSIONS HSH can regulate the cascade reactions in the CD4/LCK/ZAP70/IL-17 pathway within the T-cell receptor signaling pathway， thereby modulating the Th17/Treg balance. This leads to the suppression of inflammatory responses and the alleviation of synovial tissue damage in rats with RA.

ObjectiveTo investigate the influenza virus infection status of influenza-like illness (ILI) at a sentinel hospital in Baoshan District of Shanghai, to explore the seasonal patterns of influenza, so as to provide a scientific basis for influenza prevention and control in Baoshan District of Shanghai. MethodsSurveillance data and pathogenic testing results of ILI from the monitoring year of 2015 to 2023 were collected from the sentinel hospital to describe the seasonal epidemic characteristics of influenza in this district. ResultsThe proportion of ILI visits to sentinel hospital in Baoshan District of Shanghai showed an upward trend from 2015 to 2023 (Z=2.598, P=0.09). The positive rate of influenza virus in ILI was 20.43% (1 761/8 621), of which 14.17% were positive for influenza A virus, including 8.43% for influenza A/H3N2 and 5.74% for influenza A/H1N1. The positive rate of influenza B virus was 6.25%, of which the positive detection rate of influenza B/Victoria virus was 5.35%, while that of influenza B/Yamagata virus was 0.90%. Influenza B/Yamagata virus was not detected in 2019‒2023. The highest positivity rate was observed in the 5‒<15 years age group (25.57%). The positive rate of ILI was lower in males (19.90%) than that in females (20.90%). There were three patterns of influenza epidemic in the district: with year-round circulation in 2016‒2017 and 2021‒2022; with bimodal peaks in 2015‒2016, 2017‒2018 and 2022‒2023; and with one peak in 2018‒2019 and 2019‒2020. The positive rate of influenza virus exhibited seasonal variations, with influenza A virus predominated in summer and autumn. However, influenza B virus showed an increase in spring and winter. ConclusionThe influenza epidemic in Baoshan District, Shanghai exhibits diverse patterns with heterogeneous epidemiological characteristics across different age groups and seasons. Notably, children and adolescents aged 5‒<15 years constitute the key target population for influenza prevention and control. Enhanced surveillance and targeted control measures against influenza A/H3N2 lineage viruses are particularly warranted during summer and autumn seasons.

ObjectiveTo explore the mechanism of Huoxue Rongluo prescription （HXRLP） in repairing the blood-brain barrier （BBB） after ischemic stroke （IS）. MethodsMale C57BL/6 mice were randomly divided into sham operation （Sham） group， cerebral infarction model （MCAO） group， environmental circadian disruption with cerebral infarction model （ECD-MCAO） group， low-， medium-， and high-dose HXRLP （HXRLP-L， M， and H） groups （8.5， 17， 34 g·kg^-1·d^-1， respectively）， and positive drug butylphthalide （NBP） group （0.23 mL·d^-1）. In the Sham group， only the exposed blood vessels were isolated without suture insertion. In the other groups， the middle cerebral artery occlusion （MCAO） model of mice was prepared. In the ECD-MCAO group， HXRLP groups， and NBP group， the environmental circadian disruption （ECD） model was prepared. The mice in the Sham group， MCAO group， and ECD-MCAO group were given the same volume of soybean oil by gavage， while those in the other groups were given the corresponding drugs by gavage. Samples were collected after 7 consecutive days of administration. The mNSS score was used to evaluate the repair effect of HXRLP on neurological deficits after IS. Hematoxylin-eosin （HE） staining was used to assess the impact of HXRLP on the pathological damage of brain tissue after IS. 2，3，5-Triphenyltetrazolium chloride （TTC） staining and cerebral blood perfusion status were used to evaluate the repair effect of HXRLP on brain tissue damage after IS. Evans blue staining and transmission electron microscopy were used to evaluate the improvement effect of HXRLP on the permeability injury of BBB after IS. Immunofluorescence （IF） staining was used to observe the expression of von Willebrand Factor （vWF）， brain and muscle Arnt-like 1 （Bmal1）， and Occludin in brain tissue. Western blot was used to detect the protein expression of Bmal1， Occludin， tight junction protein （Claudin-5）， vascular endothelial growth factor （VEGF）， and angiopoietins（Ang）， and related analysis was conducted. ResultsCompared with the Sham group， the MCAO group exhibited significantly aggravated neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01） and significantly reduced cerebral blood perfusion （P0.01）. The expression of Bmal1， vWF， vascular endothelial growth factor A （VEGFA）， and Ang in brain tissue was significantly enhanced （P0.01）， while the expression of Occludin and Claudin-5 was significantly weakened （P0.01）. Compared with the MCAO group， the ECD-MCAO group showed significantly aggravated neurological deficits， cerebral infarction volume， and BBB leakage （P0.01）， obviously worsened brain pathological damage （P0.05）， significantly reduced cerebral blood perfusion （P0.01）， and significantly decreased expression of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. Compared with the ECD-MCAO group， the HXRLP groups of all doses presented significantly improved neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01）， significantly increased cerebral blood perfusion （P0.01）， and enhanced expression levels of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. ConclusionHXRLP can regulate the clock protein Bmal1 and promote the expression of VEGFA， Ang， Occludin， and Claudin-5， thereby improving BBB damage after IS.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Gastric cancer and esophagogastric junction cancer (EGJC) are one of the world 's most common types of malignant tumors. Traditional treatment methods mainly include radiotherapy, chemotherapy, and surgery, but the patients ' prognosis is limited. In recent years, with the development in treatment methods, immunotherapy and targeted therapy are gradually recognized as the first-line treatment methods. In immunotherapy, nivolumab and pabolizumab have shown clear efficacy in patients with programmed deathligand 1 positive, while other immunotherapies (such as tumor vaccine, engineered T cells, and non-specific immunomodulators) are still being tested or developed. In addition, targeted therapy has only shown comparatively large therapeutic potential in certain specific populations or in second-line treatment. For instance, tratuzumab has a clear curative effect on patients with positive human epidermal growth factor receptor 2, but has suboptimal efficacy in patients with amplification of other molecular targets. An in-depth discussion of the research progress of immunotherapy and targeted therapy in gastric cancer and EGJC will help to improve the prognosis of patients and provide a reference for accurate treatment of tumors.