Objective To describe the spatiotemporal distribution characteristics of Severe Fever with Thrombocytopenia Syndrome (SFTS) in Zibo City and identify its environmental influencing factors and potential high-risk areas, and to propose targeted strategies for SFTS prevention and control. Methods Data on SFTS incidence from 2010 to 2024 were collected. Spatiotemporal scan statistics were used to identify the time and area of SFTS clustering. The maximum entropy (MaxEnt) model was used to analyze environmental influencing factors and predict high-risk areas. Results From 2010 to 2024, a total of 459 cases of SFTS were reported in Zibo. The number of SFTS cases increased yearly, with a peak incidence from April to October each year. Spatiotemporal scan statistics showed the existence of one class I cluster and one class II cluster areas in Zibo. The class I cluster was in Yiyuan District and southern Boshan District, from April to September 2024. The class II cluster was in the center of Zichuan District, from July to September 2024. The MaxEnt model showed that yearly average atmospheric pressure (PRS), yearly average evaporation (EVP), yearly average sunshine duration (SSD) and goat density (Goat) were the key factors influencing the occurrence of SFTS. The predicted risk map showed that the area of high prevalence was 1116 km2, accounting for 18.71% of the total area of the city. Conclusion The spatiotemporal distribution of SFTS exhibits heterogeneity and is influenced by multidimensional environmental factors. This should be considered as a basis for delineating SFTS risk areas and developing SFTS prevention and control measures.

ObjectiveTo compare the differences in fungal community composition between lesional and non-lesional scalp areas in patients suffering from severe alopecia areata （AA）， and compare these with healthy scalp areas in control subjects. Additionally， to preliminarily explore the changes in scalp fungal communities in severe AA patients and their potential underlying immunological mechanisms. MethodsA total of 20 severe AA patients and 18 healthy controls were enrolled. Skin swab samples were collected from lesional and non-lesional scalp areas of severe AA patients， as well as from the normal scalp of healthy controls. The fungal internal transcribed spacer （ITS） region was amplified and analyzed using high-throughput sequencing. ResultsThe lesional scalp areas of severe AA patients exhibited higher α-diversity and species richness in fungal communities. Notably， the relative abundance of Ascomycota， along with genera such as Mycosphaerella， Aspergillus， Penicillium， and Wallemia， significantly increased in the bald regions. In contrast， Acremonium and Schizophyllum were more predominant in the non-lesional areas of severe AA patients. ConclusionDistinct region-specific differences in scalp fungal microbiota in severe AA patients suggests that fungal dysbiosis may play a potential role in the pathogenesis of alopecia areata. These findings provide new insights into the disease characteristics of severe AA from the perspective of scalp microecology.

ObjectiveTo examine the effects of Chaihu Jia Longgu Muli Tang （CLMT）-containing serum on Neuro-2A cell damage when exposed to conditioned medium from lipopolysaccharide （LPS）-stimulated microglia （BV-2） and explore the underlying mechanism. MethodsBV-2 cells were activated by LPS at a concentration of 1 mg·L^-1 to generate conditioned medium. Concurrently， a blank control group， a model group and groups treated with varying concentrations of CLMT （5%， 10%， and 15%）， dexamethasone （2.5 μmol·L^-1）， stimulator of interferon genes （STING） agonist （MSA-2， 10 μmol·L^-1）， and STING inhibitor （STING-IN-4， 4 μmol·L^-1） were established. Neuro-2A cells were subsequently cultured in the conditioned medium from each treatment group. The viability of BV-2 cells following interventions was assessed by the cell counting kit-8 （CCK-8） assay. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the supernatant of Neuro-2A cells from each group were measured through enzyme linked immunosorbent assay （ELISA）. Additionally， the expression of tyrosine hydroxylase （TH） in Neuro-2A cells was evaluated through immunohistochemistry （IHC）， while the expression of phosphorylated alpha-synuclein （p-α-Syn） was assessed by immunofluorescence （IF） assay. The expression levels of STING， interferon regulatory factor 3 （IRF3）， phosphorylated interferon regulatory factor 3 （p-IRF3）， nuclear transcription factor-kappa B p65 （NF-κB p65）， and phosphorylated nuclear transcription factor-kappa B p65 （p-NF-κB p65） in Neuro-2A cells were determined by Western blot. ResultsIn comparison to the control group， both the model group and the MSA-2 group exhibited reduced viability of Neuro-2A cells （P<0.01）， elevated concentrations of TNF-α， IL-1β， and IL-6 in the cell supernatant （P<0.01）， reduced expression of TH （P<0.01）， increased expression of p-α-Syn （P<0.01）， and upregulated relative protein levels of STING， p-IRF3， and p-NF-κB p65 （P<0.01）. Compared with the model group， medium- and high-dose CLMT enhanced the viability of Neuro-2A cells （P<0.01）， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted TH expression， and suppressed p-α-Syn expression （P<0.01）. In the dexamethasone group， the levels of IL-6， TNF-α， and IL-1β were reduced （P<0.05， P<0.01）. In the STING-IN-4 group， the levels of TNF-α and IL-1β were decreased （P<0.01）. The expression of TH was increased in both the dexamethasone group and the STING-IN-4 group （P<0.01）， while the expression of p-α-Syn was reduced （P<0.01）. The relative protein levels of p-IRF3， STING， and p-NF-κB p65 were reduced in medium- and high-dose CLMT groups （P<0.05， P<0.01）. Similarly， the dexamethasone group exhibited decreases in the expression levels of STING， p-IRF3， and p-NF-κB p65 （P<0.01）. In the STING-IN-4 group， the expression levels of p-NF-κB p65， STING， and p-IRF3 were also diminished （P<0.05， P<0.01）. However， no statistically significant differences were observed in the expression of IRF3 or NF-κB p65 across the groups. ConclusionCLMT has the potential to suppress the activation of BV-2 microglial cells， consequently mitigating the inflammatory response induced by LPS and further preventing inflammation-mediated damage to Neuro-2A cells. The underlying mechanism is likely associated with the modulation of the STING/NF-κB signaling pathway， which results in reduced inflammation and confers neuroprotective effects.

Objective To retrieve,evaluate and summarize the evidence on prevention and management of hypothermia in war trauma patients at high altitudes so as to provide data for related prevention and management.Methods Clinical decisions,practices recommended,summaries of evidence,guidelines,expert consensus,systematic reviews and randomized controlled trials concerning the prevention and management of hypothermia in patients with war trauma at high altitudes that were published between the inception and February 2024 were retrieved from related websites and Chinese and English databases.Results A total of fifteen articles were included,including 4 guidelines,1 clinical decision,3 summaries of evidence,1 recommended practice,2 systematic reviews,and 4 randomized controlled trials.Finally,29 pieces of evidence were made available,involving 6 themes:hypothermia assessment,risk factors,rewarming processes,rewarming methods,body temperature monitoring,and considerations.Conclusion This study has summed up the evidence on hypothermia management in patients with war trauma at high altitudes.It is recommended that nurses take into consideration the actual conditions and clinical scenarios and formulate personalized rewarming plans based on the results of assessment of patients when using evidence.

Objective To explore the predictive value of serum high-mobility group box protein B1(HMGB1)and soluble receptor for advanced glycation end-products(sRAGE)in the occurrence and short-term prognosis of sepsis-associated encephalopathy(SAE).Methods Clinical data of 228 patients with sepsis were retrospectively analyzed.According to the presence of SAE,patients were divided into the SAE group(96 cases)and the non-SAE group(132 cases).General clinical data,laboratory test results,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)scores,Sequential Organ Failure Assessment(SOFA)scores and serum HMGB1 and sRAGE levels were compared between the two groups.Multivariate Logistic regression analysis was performed to determine factors influencing SAE occurrence.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive ability of HMGB1,sRAGE and the HMGB1/sRAGE ratio to predict the occurrence and short-term prognosis of SAE.Kaplan-Meier survival curves were used to compare the 28-day mortality rates of SAE patients with different HMGB1 and sRAGE expression levels.Results Compared to the non-SAE group,patients in the SAE group exhibited elevated serum HMGB1 levels,decreased sRAGE levels and an increased HMGB1/sRAGE ratio(P＜0.05).The areas under the curve(AUC)for predicting SAE using HMGB1,sRAGE and the HMGB1/sRAGE ratio were 0.826(95%CI:0.770-0.872),0.682(95%CI:0.617-0.742)and 0.895(95%CI:0.848-0.932),respectively,indicating predictive value.Among the 96 SAE patients,52(54.2%)died within 28 days.There were no statistically significant differences in HMGB1,sRAGE and the HMGB1/sRAGE ratio between surviving and deceased patients(P＞0.05).Similarly,there were no significant differences in 28-day mortality rates between SAE patients with different HMGB1 or sRAGE expression levels.Conclusion Elevated serum HMGB1 and reduced sRAGE are of significant value in the auxiliary diagnosis of SAE,but have limited clinical predictive value for short-term prognosis.

Objective:To develop a quality control model for anal sphincter ultrasound images and validate its diagnostic performance across multiple centers.Methods:A retrospective analysis was conducted on anal sphincter ultrasound images from seven medical centers in China between May 2019 and June 2022. A total of 7 040 images from 3 116 patients were included and divided into a training set（4 912 images）and a validation set（2 128 images）. The images were classified as standard or non-standard images by three experts. Three models were developed based on different image feature extraction methods：a single-branch model，a multi-branch weighted model，and a multi-branch ensemble model. The diagnostic performance of each model was evaluated using the area under the ROC curve（AUC），sensitivity，specificity，accuracy，positive predictive value，and negative predictive value，respectively. The optimal model was selected and compared with the performance of 4 doctors with varying experience levels. Sixty days later，the images with the assistance of the model's output were reassessed by the doctors to evaluate its impact on manual quality control.Results:① Among the 3 models，the multi-branch ensemble model demonstrated the highest AUC and sensitivity，with an AUC of 0.966（95% CI=0.958 - 0.974），a sensitivity of 91.83%，and a specificity of 91.41%. This model was named M quality. ② M quality's AUC was slightly lower than that of Senior A and B（0.966 vs. 0.976，0.976，and P<0.05），its sensitivity was slightly lower than that of Senior A（91.83% vs. 95.61%， P<0.001）but comparable to Senior B（91.83% vs. 92.89%， P=0.315），its specificity was slightly lower than Senior A and B（91.41% vs. 94.44%，98.18%，and P<0.05）. However，M quality significantly outperformed Junior A and B in AUC and sensitivity（AUC：0.966 vs. 0.850，0.818；sensitivity：91.83% vs. 84.90%，61.46%；all P<0.001），its specificity was higher than that of Junior A（91.41% vs. 80.28%， P<0.001）but lower than that of Junior B（91.41% vs. 95.96%， P<0.001）. ③ With model assistance，Senior B's sensitivity（92.89% vs. 94.20%， P=0.001）and Senior A's specificity（94.44% vs. 96.56%， P<0.001）improved significantly. Junior A and B showed significant improvements in AUC and sensitivity（AUC：0.931 vs. 0.850，0.914 vs. 0.818；sensitivity：91.83% vs. 84.90%，89.53% vs. 61.46%；all P<0.001）. After model assistance，Junior A's specificity increased（93.62% vs. 80.28%， P<0.001），while Junior B's specificity decreased（91.60% vs. 95.96%， P=0.013）. Conclusions:This study develops a quality control model for anal sphincter ultrasound images with robust diagnostic performance，approaching the level of seniors. The model significantly enhances the image quality assessment capabilities of juniors，demonstrating promising clinical application potential.

Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

Objective To explore the predictive value of serum high-mobility group box protein B1(HMGB1)and soluble receptor for advanced glycation end-products(sRAGE)in the occurrence and short-term prognosis of sepsis-associated encephalopathy(SAE).Methods Clinical data of 228 patients with sepsis were retrospectively analyzed.According to the presence of SAE,patients were divided into the SAE group(96 cases)and the non-SAE group(132 cases).General clinical data,laboratory test results,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)scores,Sequential Organ Failure Assessment(SOFA)scores and serum HMGB1 and sRAGE levels were compared between the two groups.Multivariate Logistic regression analysis was performed to determine factors influencing SAE occurrence.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive ability of HMGB1,sRAGE and the HMGB1/sRAGE ratio to predict the occurrence and short-term prognosis of SAE.Kaplan-Meier survival curves were used to compare the 28-day mortality rates of SAE patients with different HMGB1 and sRAGE expression levels.Results Compared to the non-SAE group,patients in the SAE group exhibited elevated serum HMGB1 levels,decreased sRAGE levels and an increased HMGB1/sRAGE ratio(P＜0.05).The areas under the curve(AUC)for predicting SAE using HMGB1,sRAGE and the HMGB1/sRAGE ratio were 0.826(95%CI:0.770-0.872),0.682(95%CI:0.617-0.742)and 0.895(95%CI:0.848-0.932),respectively,indicating predictive value.Among the 96 SAE patients,52(54.2%)died within 28 days.There were no statistically significant differences in HMGB1,sRAGE and the HMGB1/sRAGE ratio between surviving and deceased patients(P＞0.05).Similarly,there were no significant differences in 28-day mortality rates between SAE patients with different HMGB1 or sRAGE expression levels.Conclusion Elevated serum HMGB1 and reduced sRAGE are of significant value in the auxiliary diagnosis of SAE,but have limited clinical predictive value for short-term prognosis.