OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Onco-critical care has emerged as an important subspecialty at the intersection of critical care medicine and oncology, attracting increasing attention in recent years. With continuous innovations in cancer therapies, patient survival has improved significantly; however, the incidence of associated critical complications has also increased. The reasons for cancer patients requiring intensive care unit admission are diverse and can be broadly categorized into three groups: progression of the underlying malignancy, treatment-related complications, and coexisting classical critical illnesses. Traditional critical care concepts and practices face limitations in addressing the multidimensional and heterogeneous challenges of onco-critical care. Based on the core mechanism of critical illness development—host/organ unregulated response (HOUR)—this article systematically elaborates on how this framework advances understanding and clinical practice into onco-critical care, with emphasis on its manifestations in neuroendocrine, immune-inflammatory, and coagulation-metabolic pathways. The review summarizes recent advances in clinical assessment and phenotyping systems for onco-critical illness and discusses a multidisciplinary, integrated management strategy centered on the "Disease Control, Host Response Modulation, Organ Support" triad. Finally, major challenges and future directions in this field are outlined. By integrating existing evidence and theoretical insights, this review aims to provide new perspectives and a theoretical foundation for the clinical management of onco-critical illness, thereby promoting its evolution toward precision and standardization.

OBJECTIVE To clarify the roles and functions of full-time pharmacists in the management of early-phase clinical trials of antineoplastic drugs， and to provide theoretical and practical support for their transformation from traditional drug managers to multi-dimensional roles in clinical research. METHODS Combined with relevant regulations such as the Good Clinical Practice （GCP） （2020 Edition）， and based on the clinical practice experience of the Phase Ⅰ Clinical Ward in our hospital， this study systematically sorted out full-time pharmacists’ roles and functions in early-phase clinical trials of antineoplastic drugs， and explored the core challenges and optimization pathways for role transformation and capacity-building of domestic full-time clinical trial pharmacists. RESULTS & CONCLUSIONS Full-time pharmacists assumed multiple roles in early-phase clinical trials of antineoplastic drugs， including providing pharmaceutical support for protocol design， implementing whole-process standardized management of clinical trial drugs， ensuring medication safety for clinical trial subjects/participants， conducting quality control throughout the clinical trial process， and serving as a bridge for interdisciplinary collaboration and communication. Currently， there are challenges in this field in China， such as unclear roles， an imperfect capacity building system， and insufficient regulatory support. This paper proposes that by establishing a standardized role framework， clarifying the core responsibilities and authorities of full-time pharmacists， and leveraging cutting-edge technologies to provide comprehensive support for their roles， so as to fully harness their pharmaceutical expertise and contribute to the standardization and efficiency of the antineoplastic new drug development process.

Objective To preliminary explore the imaging manifestations of digital breast tomosynthesis (DBT) and contrast-enhanced mammography (CEM) in triple-negative breast cancer (TNBC) patients with different levels of human epidermal growth factor receptor 2 (HER2) expression. Methods A retrospective analysis was conducted on TNBC patients who underwent preoperative DBT or CEM examinations at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2019 and Shanghai Second People’s Hospital from January 2022 to May 2025. Clinical data, pathological and immunohistochemical results, and imaging data were collected. Results A total of 69 TNBC patients pathologically confirmed as invasive ductal carcinoma were included, among which 34 underwent DBT and 35 underwent CEM. Among these patients, 34 (49.28%) had HER2-low expression and 35 (50.72%) had HER2-zero expression. DBT results showed that the proportion of spiculation signs in HER2-low group (n＝14) was significantly higher than that in HER2-zero group (n＝20; P＝0.009, P_adj＝0.045). However, there were no significant differences in breast density type, mass shape, or calcification between the two groups. CEM results showed that on low-energy images, the proportion of spiculation signs in the HER2-low group (n＝20) was higher than that in the HER2-zero group (n＝15; P＝0.011, P_adj＝0.077). Results of CEM showed that on reconstructed images, differences in background parenchymal enhancement and mass enhancement patterns between the two groups were not statistically significant; in both groups, heterogeneous enhancement was the most common, followed by homogeneous enhancement, with ring enhancement being the least common. Conclusions TNBC with low HER2 expression and TNBC with zero HER2 expression may have potential differences in the presentation of spiculation signs on DBT. However, the correlation between CEM manifestations and TNBC with different HER2 expression levels requires further research.

Background Pneumoconiosis remains a critical occupational disease in China. As a major industrial province, Hebei historically faced severe challenges regarding this condition. The 1986 national epidemiological survey ranked Hebei sixth in reported pneumoconiosis cases nationwide. Objective To analyze 76 years of pneumoconiosis data (1949–2024) in Hebei Province to provide evidence-based support for prevention and control strategies. Methods Occupational pneumoconiosis cases diagnosed in Hebei from 1949 to 2024 were included. Five-year intervals were used to analyze incidence composition, dust exposure duration, age at first diagnosis, and age at death. A hybrid model, integrating autoregressive integrated moving average (ARIMA) with generalized regression neural network (GRNN), was employed to predict case numbers for the 2025−2030 period. Results A total of 36107 cases of pneumoconiosis were recorded (2.10% female) in Hebei from 1949 to 2024. Stages I, II, and III accounted for 77.35%, 16.45%, and 6.20%, respectively. Silicosis (55.60%), coal workers’ pneumoconiosis (27.24%), and pottery workers’ pneumoconiosis (8.88%) were the predominant types. Observed trends included a shortened dust exposure duration [silicosis: (12.78±7.063) years in 2020–2024] and an increasing age at first diagnosis [(54.01±7.499) years in 2020–2024]. The case-fatality rate was 14.84%, with a rising age at death [(82.26±9.632) years in 2015–2019]. Three incidence peaks (1963, 1984, and 2014) correlated with national policies and industrialization phases. The number of pneumoconiosis cases showed a decreasing trend from 2015 to 2024. Chengde and Tangshan were identified as current high-risk areas. The ARIMA-GRNN model projected annual cases between 416 and 429 during 2025–2030. Conclusion In the past decade，the number of pneumoconiosis cases in Hebei Province had shown a decreasing trend, it is projected to plateau with no significant decline over the next five years. Furthermore, challenges such as the proportion of silicosis remaining high and shortened dust exposure duration remain severe. It is recommended to focus on key regions like Chengde (ore mining) and Tangshan (ceramics industry). A comprehensive strategy integrating stricter regulation, technological controls, model innovation, and targeted interventions should be implemented to achieve a further substantial reduction in pneumoconiosis incidence.

Background Pneumoconiosis remains a critical occupational disease in China. As a major industrial province, Hebei historically faced severe challenges regarding this condition. The 1986 national epidemiological survey ranked Hebei sixth in reported pneumoconiosis cases nationwide. Objective To analyze 76 years of pneumoconiosis data (1949–2024) in Hebei Province to provide evidence-based support for prevention and control strategies. Methods Occupational pneumoconiosis cases diagnosed in Hebei from 1949 to 2024 were included. Five-year intervals were used to analyze incidence composition, dust exposure duration, age at first diagnosis, and age at death. A hybrid model, integrating autoregressive integrated moving average (ARIMA) with generalized regression neural network (GRNN), was employed to predict case numbers for the 2025−2030 period. Results A total of 36107 cases of pneumoconiosis were recorded (2.10% female) in Hebei from 1949 to 2024. Stages I, II, and III accounted for 77.35%, 16.45%, and 6.20%, respectively. Silicosis (55.60%), coal workers’ pneumoconiosis (27.24%), and pottery workers’ pneumoconiosis (8.88%) were the predominant types. Observed trends included a shortened dust exposure duration [silicosis: (12.78±7.063) years in 2020–2024] and an increasing age at first diagnosis [(54.01±7.499) years in 2020–2024]. The case-fatality rate was 14.84%, with a rising age at death [(82.26±9.632) years in 2015–2019]. Three incidence peaks (1963, 1984, and 2014) correlated with national policies and industrialization phases. The number of pneumoconiosis cases showed a decreasing trend from 2015 to 2024. Chengde and Tangshan were identified as current high-risk areas. The ARIMA-GRNN model projected annual cases between 416 and 429 during 2025–2030. Conclusion In the past decade，the number of pneumoconiosis cases in Hebei Province had shown a decreasing trend, it is projected to plateau with no significant decline over the next five years. Furthermore, challenges such as the proportion of silicosis remaining high and shortened dust exposure duration remain severe. It is recommended to focus on key regions like Chengde (ore mining) and Tangshan (ceramics industry). A comprehensive strategy integrating stricter regulation, technological controls, model innovation, and targeted interventions should be implemented to achieve a further substantial reduction in pneumoconiosis incidence.

The advancement of microbiome technologies has facilitated a growing interest in the interactions between urinary microbiota and urinary stone formation. This article systematically reviews the technological evolution, and the reciprocal mechanism of microbiota involvement in lithogenesis and its clinical significance. It specifically highlights the changes within the urinary microbiota of calcium oxalate stone patients, notably a depletion of Lactobacillus populations and an enrichment of pathogenic taxa such as Enterobacteriaceae. Furthermore, it delineates the mechanisms whereby microbes participate in stone formation through metabolic regulation, physical adhesion, and inflammatory processes. The article also explores the influence exerted by distinct stone types on the structural composition and functional dynamics of the urinary microbiota. Integrated multi-omics analyses offer novel perspectives for unraveling the intricate microbiome-host interaction network. This approach is anticipated to facilitate significant advances in developing precision-focused prophylactic and therapeutic strategies for urinary stones from a microecological standpoint.

ObjectiveTo understand the epidemiological characteristics and post-exposure prophylaxis of rabies exposure cases in Suqian City of Jiangsu Province from 2021 to 2024, providing a reference for optimizing the allocation of health resources and formulating scientific prevention and control measures. MethodsData on individuals exposed to rabies and treated at Suqian’s rabies post-exposure prophylaxis (PEP) clinics from 2021 to 2024 were collected. Descriptive epidemiological methods were used to analyze patient characteristics, exposure classification, animal species responsible for injuries, wound management, and vaccination status. ResultsBetween 2021 and 2024, the number of outpatient visits for rabies PEP clinics in Suqian City totaled 333 450. The median age and the 25th and 75th percentiles of exposed individuals was 23 (9, 47) years. The highest proportion of exposed individuals was recorded in 2023 (27.09%); the majority were female (52.22%), aged 5‒9 years (17.49%), and in other occupations (37.05%). The rabies exposure rate in Suqian City from 2021 to 2024 was 16.75‰. The overall rabies exposure rate showed an upward trend (χtrend2=1 994.80, P<0.001). The exposure rate among males was lower than that among females (χ²=890.43, P<0.001). The highest exposure rate was observed in the 5‒9 age group (χ²=67 063.20, P<0.001). The number of individuals seeking medical care for rabies exposure exhibited a weak bimodal distribution, with the primary peak occurring in August and the secondary peak in January. The primary animal responsible for injuries was the cat (53.70%), and the source of these animals was predominantly domestic pets (88.90%). The proportion of exposed individuals bitten by cats showed an upward trend from 2021 to 2024 (χtrend2=548.44, P<0.001). Grade Ⅲ exposure accounted for the highest proportion (53.53%), and 301 652 cases (90.46%) presented within 24 hours of exposure. The coverage rate of rabies vaccine was 98.18% (13 625/13 877) for those with Grade Ⅰ exposure and 99.95% (319 413/319 573) for those with Grade Ⅱ and Ⅲ exposures; 64 042 individuals received rabies immunoglobulin or anti-rabies serum; 8 360 exposed individuals received tetanus vaccine, with the usage rate of tetanus vaccine among exposed individuals was only 2.51%, though the rate was on the rise (χtrend2=618.26, P<0.001). ConclusionBetween 2021 and 2024, the overall incidence of rabies exposure in Suqian City showed an upward trend, with a higher incidence among women than men. The incidence was particularly high among children and adolescents aged 14 and under, with the majority of injuries caused by cats; most injuries were inflicted by domestic animals. The overall uptake of tetanus vaccines showed an upward trend. Suqian City should step up health education on rabies exposure during January and August each year, with a particular focus on raising awareness of rabies exposure prevention among people aged 14 and under and women. It should also strengthen the management of domestic animals and ensure that they receive regular rabies vaccinations, particularly for pet cats. Preventive measures against tetanus should be strengthened for individuals exposed to rabies. Medical staff at rabies PEP clinics should receive enhanced training on the management of rabies exposures and the completion of information system reports to ensure the standardized operation of these clinics.

Objective:To explore the mechanism of TLR4/ERK1/2 signaling pathway in progesterone regulating expression of IL-8 in decidual stromal cells(DSCs).Methods:Human DSCs on early pregnancy were isolated and cultured in vitro.The cells were treated with 0.01 μmol/L,0.1 μmol/L and 1 μmol/L progesterone,respectively.Expressions of IL-8,TLR4,ERK1/2 and p-ERK1/2 were detected by Western blot.TLR4 inhibitor TAK-242 and ERK1/2 inhibitor U0126 were further treated,and expression of IL-8 in progesteron+inhibitor group,progesterone group and control group was detected by Western blot.Results:With the increase of pro-gesterone concentration,expression of IL-8 in DSCs decreased gradually.Expressions of DSCs IL-8,TLR4 and p-ERK1/2 in 0.01 μmol/L progesterone group were lower than those in control group(P=0.035 8,P=0.019 4 and P=0.047 1).Expressions of IL-8,TLR4 and p-ERK1/2 in DSCs in 0.1 μmol/L progesterone group were significantly lower than those in control group(P=0.003 5,P=0.004 0 and P=0.009 9).Expressions of IL-8,TLR4 and p-ERK1/2 in DSCs in 1 μmol/L progesterone group were significantly lower than those in control group(P=0.003 3,P=0.001 6 and P=0.005 0).Expression of IL-8 in progesterone+TAK-242 group was signifi-cantly lower than that in progesterone group(P=0.009 1),and expression of IL-8 in progesterone+U0126 group was significantly lower than that in progesterone group(P=0.004).Conclusion:TLR4/ERK1/2 signaling pathway is involved in the physiological process of progesterone regulating expression of IL-8 in DSCs,and progesterone reduces IL-8 expression by inhibiting expression of TLR4 and phosphorylation activation of ERK1/2.

Objective To evaluate the efficacy and safety of recombinant staphylokinase in patients with acute ST-segment elevation myocardial infarction(STEMI)by a multi-center,randomized,position-controlled,parallel post-marketing clinical trial.Methods This study was a multi-center,randomized,positive drug parallel control,non-inferiority clinical trial.From July 2019 to June 2022,a total of 251 patients with STEMI were enrolled in 31 hospitals.Patients were randomly assigned to receive intravenous staphylokinase or alteplase in a ratio of 1∶1.Vascular recanalization was evaluated by clinical indicators 30 minutes,60 minutes and 120 minutes after the initiation of thrombolysis.Coronary angiography was performed 90 to 120 minutes after the initiation of thrombolysis.The proportion of infarct-related artery(IRA)with thrombolysis in myocardial infarction(TIMI)grade Ⅱ and Ⅲ,corrected TIMI frame count(CTFC)and TIMI myocardial perfusion grade(TMPG)were analyzed Major adverse cardiac events(MACE,including all-cause death,rehospitalization,reinfarction,urgent target vessel revascularization)and bleeding events were followed up at 30 days(±2 days)after thrombolysis.Results After excluding 7 subjects who did not use thrombolytic drugs,244 subjects were finally eligibled from 31 hospitals(117 in trial group and 127 in control group),and 232 subjects completed the follow-up(111 in trial group and 121 in control group).The vascular recanalization rate evaluated by clinical indicators at 120 minutes after thrombolysis was 85.6％ in trial group and 83.5％ in control group(P=0.657).The difference between the two groups was 2.11(95％CI-7.19-11.41).Given that the lower confidence limit of the 95％CI was greater than-12％,the non-inferiority of the vascular recanalization rate was established based on clinical judgment.Coronary angiography showed that the total patency rate of IRA(TIMIⅡ-Ⅲ)was 77.5％ in trial group and 77.7％ in control group(P=0.970).The difference between the two groups was-0.21(95％CI-10.95-10.54),with the lower bound of the 95％CI exceeding-12％.Therefore,the non-inferiority of the TIMI blood flow grade was confirmed,indicating that the total patency rate of IRA in the trial group was not inferior to that in the control group.The CTFC was(32.7±17.6)frames in trial group and(37.6±16.6)frames in control group,with no statistically significant difference between the two groups(P=0.054).The difference between the two groups was-4.9(95％CI-10.0-0.1).As the lower limit of the 95％CI exceeded-12％,the noninferiority of CTFC was successfully demonstrated.The proportions of TMPG 0-Ⅲ were 20.7％,6.3％,2.7％and 69.4％in trial group,and 22.3％,4.1％,6.6％ and 66.9％ in control group,respectively.There was no significant difference in TIMI myocardial perfusion grade between the two groups(P=0.086).The incidence of MACE was 7.7％ in trial group and 7.1％ in control group within 30 days after the initiation of thrombolysis,and there was no significant difference between the two groups(P=0.857).Further analysis showed that there was no significant difference in cardiovascular mortality(3.4％ vs.4.7％,P=0.751).All 244 subjects were included in the safety analysis set.There was no significant difference in the total incidence of bleeding events between the two groups(22.2％ vs.15.0％,P=0.144).There was no significant difference in the incidence of major bleeding(1.7％ vs.0.8％,P=0.609).Conclusions Recombinant staphylokinase is simple to use and has a rapid onset of action.The efficacy and safety of recombinant staphylokinase are not inferior to alteplase in the treatment of acute STEMI.