OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

Objective To evaluate the clinical efficacy of modified Rhinoceros Dihuang decoction in the treatment of children with henoch-sch?nlein purpura(HSP)of the"bleeding due to blood-heat syndrome"pattern in traditional Chinese medicine(TCM).Methods A total of 72 pediatric patients diagnosed with HSP and admitted to Zhengzhou Hospital of Traditional Chinese Medicine from June 2021 to June 2023 were enrolled and divided into two groups(n=36 each):control group and observation group.The control group received conveational Western medical treatment,while the observation group received additional treatment with modified Rhinoceros Dihuang decoction based on conventional therapy.The decoction was composed of:Herba Agrimoniae,Radix Rehmanniae,Radix Arnebiae seu Lithospermi,Radix Rubiae,15 g each;Cornu Bubali,30 g,Rhizoma Imperatae,20 g;Cortex Moutan and Radix Paeoniae Rubra,10 g each.The herbs were decocted once daily,dosed according to age:100 mL for ages 3-6,150 mL for 7-11,and 200 mL for 12-14 years old,administered twice daily for 10 days.Outcome measures included clinical efficacy,symptom scores(distribution,color,and morphology of purpura),inflammatory markers[interleukins(IL-17,IL-9),tumor necrosis factor-α(TNF-α)],immune function indicators[T lymphocyte subsets(CD4+,CD8+,CD4+/CD8+)and immunoglobulins(IgA,IgM,IgG)],quality of life,and adverse events.Results After treatment,the symptom scores,inflammatory factors,CD8+,IgA,and IgM levels in the observation group were significantly lower than those in the control group[purpura distribution score:1.03±0.20 vs.1.85±0.27,purpura color score:0.95±0.18 vs.1.76±0.31,purpura morphology score:0.94±0.16 vs.1.76±0.28;IL-17(ng/L):19.84±2.31 vs.26.12±2.63,IL-9(ng/L):20.40±4.19 vs.34.16±6.31,TNF-α(ng/L):13.61±2.05 vs.22.17±2.13;CD8+:0.259±0.040 vs.0.423±0.040,IgA(g/L):1.26±0.24 vs.1.81±0.32,IgM(g/L):1.24±0.19 vs.1.54±0.26,all P<0.05],CD4+,CD4+/CD8+,and IgG levels,as well as the pediatric quality of life inventory 4.0(PedsQL4.0)score were significantly higher in the observation group than in the control group[CD4+:0.461±0.046 vs.0.423±0.040,CD4+/CD8+:1.780±0.330 vs.1.450±0.270,IgG(g/L):11.22±1.75 vs.9.41±1.84,PedsQL4.0 score:83.62±6.54 vs.75.54±12.32,all P<0.05].The total clinical efficacy rate in the observation group was significantly higher than that in the control group[94.44%(34/36)vs.72.22%(26/36),P<0.05].No significant adverse reactions were observed in either group.Conclusion Modified Rhinoceros Dihuang decoction is effective and safe in alleviating clinical symptoms,reducing inflammatory responses,regulating immune function,and improving quality of life in children with HSP of the bleeding due to blood-heat pattern.

Objective:To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms.Methods:A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group ( n=6), FLASH irradiation groups ( n=90), and CONV irradiation groups ( n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results:After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group ( t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group ( P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy ( t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy ( t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant ( tcrypt=13.10, 23.80, 11.90; tmucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ2=5.39, P<0.05), with a median survival extension of 6 d ( HR=0.340, 95% CI: 0.115 4-0.999 9). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy ( P>0.05). Conclusions:FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.

Objective To understand the epidemiological characteristics of road traffic accident injuries in Beijing can provide a theoretical basis for improving the pre-hospital emergency service capabilities and levels,and increasing patient survival rates while reducing disability,mortality rates.Methods A retrospective analysis was conducted on the medical records of 9207 patients who made pre-hospital emergency calls due to road traffic accident injuries at the Beijing Emergency Medical Center in 2023 to understand the patients' age,gender,injury time,injury location,injury degree and other characteristics.Results Traumatic diseases ranked first in the classification of emergency medical conditions in Beijing.Among them,road traffic accidents account for 37％.The ratio of male to female patients was 1.32∶1.The largest number of patients were aged 31-40,accounting for nearly 25％.The proportion of underage patients and those aged 71 and above was 12.16％.The differences in gender and age distribution were statistically significant,while the differences in gender distribution among different age groups were not statistically significant.Road traffic accident injuries occured most frequently in September and least in January.There were more cases in summer and autumn,and fewer in winter and spring.The most common injury sites in road traffic accidents were limbs/skin and head and neck,accounting for 81.06％.The patients with moderate severity of injuries were the most numerous,accounting for 85.29％.Conclusion To avoid road traffic accidents,prevention should be the priority.It is necessary to strengthen the joint governance of multiple departments and minimize the occurrence of road traffic accident from the source.Pre-hospital emergency care must focus on key populations and key seasons,strengthen professional skills training and resource allocation,ensure efficient and smooth connection between pre-hospital and in-hospital care.Popularize and publicize the importance of self-rescue and mutual rescue,promote first aid knowledge and skills training for the public,and create a social atmosphere where"rescue is right beside us".

ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

BACKGROUND:Neuroinflammation is a major cause of exacerbation after spinal cord injury.In recent years,pyroptosis has received much attention due to its remarkable pro-inflammatory features.Some of these natural products can significantly inhibit the inflammatory response and improve the damaged nerve function by regulating the level of pyroptosis after spinal cord injury,which provides a new therapeutic idea for spinal cord injury.OBJECTIVE:To summarize the mechanism of action of natural products in regulating pyroptosis for the treatment of spinal cord injury,with a view to providing lessons and references for future research on the treatment of spinal cord injury.METHODS:The search terms"spinal cord injury,pyroptosis,inflammasome,natural products,natural compounds,traditional Chinese medicine"in Chinese and English were used to search for relevant literature since the establishment of the database up to September 2024 in the databases of PubMed,Web of Science,WanFang,and CNKI.According to the inclusion and exclusion criteria,75 relevant articles were finally obtained.RESULTS AND CONCLUSION:(1)Pyroptosis is an important pro-inflammatory pathway in spinal cord injury,and controlling pyroptosis is an effective way to improve damaged nerve function.(2)Some natural products can regulate pyroptosis via the NLRP3/Caspase-1 classical pyroptosis pathway,the NF-κB-related pathway,other upstream pathways such as Nrf2/HO-1,and autophagy,thereby affecting the level of tissue inflammation and accelerating neurological recovery after spinal cord injury.(3)The anti-pyroptosis effects of these natural products are mostly dependent on the NLRP3 classical pyroptosis pathway,and there is a lack of studies on other pyroptosis pathways.(4)There are still many problems in this field,such as the fact that these natural products are not currently supported by evidence from appropriate clinical studies.(5)The natural product has great potential in regulating pyroptosis and is expected to be a powerful weapon in the treatment of spinal cord injury.

Objective To explore the diagnostic value of ultrasonography in ischiofemoral impinge-ment syndrome(IFI).Methods Fifty-six patients who underwent hip MRI with confirmed IFI diagnosis and completed ultrasonography examinations were enrolled as the IFI group,including 44 females and 12 males.Twenty healthy volunteers were concurrently recruited as the control group,consisting of 10 females and 10 males.The control group underwent ultrasonography examinations of bilateral hip joints,whiletheischialfemoralspace(IFS)andquadratusfemoristhickness(QFT)of both groups were measured and recorded.Then measurements were compared within(by laterality and gender)and between the two groups using independent-samples t-tests.Moreover,receiver operating characteristic adults,males exhibited significantly higher IFS and QFT values than females(P<0.05).Within the IFI group,males with affected hips had significantly higher IFS than females(P<0.05),while no sig-nificant differences were observed in QFT between different genders(P>0.05).Moreover,affected hips in the IFI group showed significantly narrower IFS and thicker QFT compared to both contralateral hips and the control group(P<0.001).In addition,the diagnostic cut-off values of IFS and QFT for ultrasound diagnosis of IFI were 22.93 mm and 16.48 mm,respectively.At these thresholds,the ar-eas under the curve(AUC)were 0.997 and 0.977,with sensitivities of 97.8%and 91.8%,and speci-ficities of 98.4%and 97.8%,respectively.Conclusion Ultrasound can serve as a reliable diagnostic technique for IFI,where narrowing of the IFS and thickening of the QFT should raise suspicion of this condition.

Objective To analyze the research status,development trends and hotspots in the field of corticomuscular coherence(CMC).Methods Relevant literatures on CMC from 1999 to 2024 were retrieved from the Web of Science Core Collection.CiteSpace 6.3R1 was ued to evaluate publications across multiple dimensions,including publication volume,countries/regions,institutions,authors,cited journals,cited references and keywords.Research hotspots and fron-tier dynamics were identified through keyword co-occurrence,clustering and bursting.Results A total of 447 articles were included.The overall publication trend for CMC research showed a fluctuating up-ward trajectory,peaking in 2023.China led in publication volume but exhibited relatively low centrality and inter-national collaboration.Germany led the way in academic influence.Aalto University and the University of Lon-don served as academic hubs for CMC research.The most influential research team,led by Mathieu Bourgui-gnon,focused on the physiological mechanisms and motor control applications of CMC.The Journal of Physiolo-gy-London was identified as the most impactful journal in the CMC field.CMC research spaned from molecular mechanisms to system-level behavior,delving into the interdisciplinary nexus of neuroscience and motor science while gradually extending to foundational studies in psychology and biology.High-interest keywords included synchronization,motor cortex and precision grip task.Current research hotspots encompassed connectivity,reor-ganization and activation.Future research was predicted to focus on advancements in CMC technology,interven-tions for neurological disorders,brain-muscle interaction mechanisms and signal processing.Conclusion CMC research has rapidly progressed in recent years,becoming a pivotal direction in motor function assess-ment and neurorehabilitation.Future studies should focus on optimizing CMC analytical techniques to enhance their application in brain-computer interfaces and personalized rehabilitation.Additionally,interdisciplinary col-laboration and international exchange should be strengthened to improve research quality and global impact.

BACKGROUND:Slow bone repair and poor bone formation quality are still problems during masquelet technique in the treatment of large segment bone defects.H-type vessels can induce osteogenesis,enhance the local angiogenesis and osteogenesis coupling,and promote bone repair.However,there are few reports on the role of H-type blood vessels in the bone induced membrane.OBJECTIVE:To construct a large segment bone defect model of SD rat tibia,observe the expression characteristics of H-type blood vessels in the bone induced membrane,then to identify the expression peak point of H-type blood vessels in the bone induced membrane and determine the optimal period of bone grafting.METHODS:Sixty SD rats were randomly divided into a control group(n=30)and a model group(n=30)by random number table method.The two groups were further divided into three subgroups at 4,6,and 8 weeks after bone cement implantation,with 10 rats in each group.A 4 mm bone defect model of the right tibia was constructed in both the control and the model groups.Polymethyl methacrylate bone cement was implanted in the model group to induce bone biomembrane formation,while bone cement was not implanted in the control group.At 4,6,and 8 weeks after bone cement implantation,6 rats were randomly selected at each time point.The bone induction membrane tissue was cut from the model group,and the non-bone soft tissue of the corresponding part was cut from the control group.The dynamic expressions of H-type blood vessels in the bone induced membrane were identified by immunofluorescence.The morphological changes of the bone induced membrane were observed by hematoxylin-eosin staining.The formation of blood vessels in the bone induced membrane was observed by angiography.The expression levels of osteoblast-specific transcription factor in the bone induced membrane were detected by immunohistochemistry.Four rats remained at each time point.In the model group,the bone induced membrane was cut open and the bone cement was removed and autologous coccyx was implanted.In the control group,autologous coccyx was implanted in the bone defect area.Micro-CT evaluation of the tibial defect was performed 8 weeks after bone grafting.RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed that the expression of H-type vessels in the model group was most obvious 6 weeks after bone cement implantation,and the expression of H-type vessels in the model group at each time point after bone cement implantation was higher than that in the control group(P＜0.05).(2)Hematoxylin-eosin staining and angiography showed that the number and volume of new blood vessels at each time point after bone cement implantation in the model group were greater than those in the control group(P＜0.05).The order of the number and volume of new blood vessels in the model group was:8 weeks after bone cement implantation＞6 weeks after bone cement implantation＞4 weeks after bone cement implantation.(3)Immunohistochemical staining showed that the positive expression of osteoblast-specific transcription factors at each time point after bone cement implantation in the model group was higher than that in the control group(P＜0.05),and the positive expression of osteoblast-specific transcription factors in the model group was most obvious 6 weeks after bone cement implantation.(4)Micro-CT detection showed that the bone repair effect of the three subgroups in the model group was significantly better than that of the corresponding subgroups in the control group,and the bone repair effect of the subgroup in the model group 6 weeks after bone cement implantation was better than that of the subgroups 4 and 8 weeks after bone cement implantation.The results indicate that H-type blood vessels are dynamically expressed in the bone induced membrane and reached a peak 6 weeks after bone cement implantation.Good bone repair effects can be obtained by the bone induced membrane bone grafting 6 weeks after bone cement implantation.