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 explore the correlation between serum angiotensin-converting enzyme(SACE),matrix metalloproteinase-9(MMP-9)and haptoglobin(HPT)with pulmonary infection in patients with schizophrenia.Methods A total of 83 patients with schizophrenia were selected and divided into the infected group(40 cases)and the non-infected group(43 cases)according to whether they had pulmonary infection.Data of antipsychotic drugs,length of hospital stay,course of disease and electroconvulsive therapy were collected.Serum SACE,MMP-9 and HPT levels were detected by enzyme-linked immunosorbent assay.Spearman correlation analysis was used to determine serum SACE,MMP-9 and HPT and pulmonary infection in patients with schizophrenia.Logistic regression was used to analyze risk factors for pulmonary infection in patients with schizophrenia,and receiver operating characteristic(ROC)curves were used to evaluate the predictive value of serum SACE,MMP-9 and HPT in patients with pulmonary infection.Results Before treatment,the types of antipsychotic drugs≥2,the proportion of electroconvulsive therapy,serum SACE,MMP-9 and HPT levels were higher in the infected group than those in the non-infected group(P＜0.05).After treatment,there were no significant differences in serum SACE,MMP-9 and HPT levels between the infected group and the non-infected group(P＞0.05).Serum SACE,MMP-9 and HPT were positively correlated with pulmonary infection in patients with schizophrenia(P＜0.05).More than 2 types of antipsychotic drugs,electroconvulsive therapy and elevated SACE,MMP-9 and HPT were risk factors for pulmonary infection in schizophrenia patients(P＜0.05).The ROC curve analysis showed that the combined serum SACE,MMP-9 and HPT for pneumonia in schizophrenic patients were better than each of these indicators alone in predicting pulmonary infection in patients with schizophrenia.Conclusion Serum SACE,MMP-9 and HPT are related with pulmonary infection in patients with schizophrenia,and which can be used as potential indicators for predicting pulmonary infection in patients with schizophrenia.

Objective:To study the results of detection of pulmonary nodules among military flying personnel and analyze the contributors to pulmonary nodules so as to provide data for early prevention and interventions.Methods:The physical examination data of 1 465 military flying personnel was retrospectively analyzed who had received the annual health checkup and undergone chest CT examinations at Lintong Rehabilitation and Recuperation Center. They were grouped by age (<40 years and ≥40 years), flying hour (<1 000 h and ≥1 000 h) and type of personnel [pilots and air support (technical) personnel]. The detection rates of pulmonary nodules among flying personnel were compared across groups, and a multivariate Logistic regression analysis was conducted to analyze the contributing factors to pulmonary nodules.Results:Among the 1 465 military flying personnel, 212 cases (14.47%) with pulmonary nodules were detected. A total of 230 pulmonary nodules were detected, including 35 pulmonary nodules (15.22%) in the left upper lung, 42 pulmonary nodules (18.26%) in the left lower lung, 52 pulmonary nodules (22.61%) in the right upper lung, 47 pulmonary nodules (20.43%) in the right middle lung, and 54 pulmonary nodules (23.48%) in the right lower lung. The detection rate of pulmonary nodules among military flying personnel in the ≥1 000 h group was higher than in the <1 000 h group, and the difference was statistically significant ( χ2=4.14, P=0.042). More pulmonary nodules were detected among military flying personnel who smoked than among those who did not, and the difference was statistically significant ( χ2=9.34, P=0.002). Age, types of personnel, body mass index, and complications with other lung diseases made no significant difference in the detection rate of pulmonary nodules (all P>0.05). Multivariate Logistic regression analysis showed that smoking was a risk factor for pulmonary nodules ( OR=1.692, 95% CI: 1.217-2.351). Conclusions:Among military flying personnel, pulmonary nodules are more likely to occur in the right lung. Smoking is an independent risk factor for pulmonary nodules, suggesting that routine chest CT screening should be carried out during the annual physical examinations of military flying personnel in order to exercise early interventions.

Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.

Objective:To analyze the survival outcomes and prognostic factors of patients with ovarian carcino-sarcoma(OCS)based on SEER database.Methods:The data of 1285 OCS patients from 2000 to 2018 in SEER database were retrospectively analyzed.Univariate and multivariate Cox proportional hazards models were used to evaluate the prognostic factors associated with overall survival(OS)and cancer specific survival(CSS).Kap-lan-Meier survival curve was drawn to evaluate the survival analysis of patients' prognosis after clinical treatment.Results:①The study cohort included a total of 1285 OCS patients,The mean age of these patients was 66.21±11.71 years.Most patients had already experienced regional(22.80％)or distant(72.22％)metastasis at the time of diagnosis.②Multivariate Cox regression revealed,SEER stage of regional or distant metastasis,no surger-y,no chemotherapy,and no lymphadenectomy were independent risk factors for both patient OS and CSS(HR＞1,P＜0.05).Age ≥67 years was an independent risk factor for OS(HR＞1,P＜0.05).Age ≥ 83 years was an in-dependent risk factors for CSS(HR＞1,P＜0.05).③Kaplan-Meier survival analysis showed that among surgical patients with adjacent tissue invasion or distant metastasis had significantly better overall survival rate after lymph node dissection than those without(P＜0.001);We didn't see the significantly different effects of lymphadenecto-my on patients with localized disease(P=0.266).Among all patients who underwent surgery,the overall survival rate of all patients who received adjuvant chemotherapy after surgery was significantly better than that of those who did not(P＜0.001).Conclusions:Prognosis of OCS patients is associated with age,SEER comprehensive stage,surgery status,chemotherapy status,lymphadenectomy status.Patients with OCS who underwent cytore-ductive surgery and adjuvant chemotherapy had a better prognosis.However,it is questionable whether lymph-adenectomy is necessary in OCS patients with very early stage.

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*

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.

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.