OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Primary biliary cholangitis （PBC） is a cholestatic autoimmune liver disease characterized by the injury of small intrahepatic bile ducts， and at present， the pathogenesis of PBC remains unclear. Recent studies have shown that bile acid metabolism disorder and gut microbiota imbalance play a key role in the development and progression of PBC， and they form a complex and dynamic interaction network via the “gut-liver axis” and regulate core physiopathological processes such as immune response， metabolic homeostasis， and inflammatory response in a synergistic manner. This article systematically elaborates on the abnormal features of bile acid metabolism and gut microbiota in PBC， discusses their synergistic mechanisms in PBC， and then proposes a combined strategy of targeting bile acid receptors and modulating gut microbiota， in order to overcome the limitations of current treatment modalities and provide new insights and directions for the clinical management of PBC.

Objective: To evaluate the methodological quality and reporting quality of clinical practice guidelines or expert consensus on blood transfusion and blood use (BTBU) in China (hereinafter referred to as "guidelines/consensus"), providing reference for the development and updating of future BTBU guidelines/consensus. Methods: A systematic search was conducted in Chinese databases such as China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Data-base, relevant guideline release platforms, and professional association websites. BTBU-related guidelines/consensus published between January 2006 and December 2025 were included. According to the inclusion and exclusion criteria, after completing literature screening and data extraction, three evaluators independently assessed the quality of the included literature using the Scientificity, Transparency, and Applicability of Guidelines Rating Tool (STAR), the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ), and the International Practice Guideline Reporting Standards (RIGHT). Results: A total of 29 documents were included, including 5 guidelines, 22 consensus statements, and 2 protocols. The results of the STAR assessment showed that the total score was (21.7±8.8)%. The domain score ratios for registration, research protocol, funding, working group, conflict of interest, clinical question, evidence, consensus method, recommendation, accessibility and other domains were (2.2±12.1)%, 0, (36.7±25.1)%, (18.3±7.6)%, (19.2±15.3)%, (16.6±23.1)%, (15.1±6.3)%, (9.6±21.2)%, (54.3±18.4)%, (31.7±10.4)% and (10.3±31.0)%, respectively. For the AGREE Ⅱ assessment, the methodological quality of 26 articles was rated Grade B and 3 articles Grade C. The results of the RIGHT assessment indicated that the overall reporting rate of all guidelines/consensuses was (65.3±4.0)%. Conclusion: The methodological and reporting quality of current expert guidelines/consensus on BTBU in China still need improvement, and guidelines and consensus should be strictly formulated and standardized according to the standards of STAR, AGREE II and RIGHT.

Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Carbon ion radiotherapy(CIRT)is an advanced radiotherapy method with unique physical and biological properties.It increases the dose to the tumor target area while providing better protection to normal tissues.CIRT can be used for hypoxic tumors resistant to photon radiotherapy.It also has the potential superiority of inducing immune responses and can produce the"abscopal effect"when com-bined with different immunotherapies.Radioimmunotherapy can not only ablate tumors at the irradiated site but also partially control dis-tant metastases at the unirradiated site.However,the underlying mechanism has not been fully elucidated.Due to the protection of the tu-mor microenvironment,tumors can sometimes be difficult to completely clear through CIRT-mediated anti-tumor immunity;this can also in-dicate functional limitations of some immune organs after CIRT.Therefore,this study reviewed the impact of CIRT on both innate and adapt-ive immune responses.It also examined the relationship between different radiation doses/fractions and immune protein expression,as well as compared the differences in imaging techniques between carbon ion radiotherapy and traditional radiotherapy.We have also proposed future directions to enhance the superiority of CIRT.This study aimed to provide a strong theoretical basis for improving the efficacy of CIRT and its combination therapy,ultimately benefiting more patients with cancer.

ObjectiveTo evaluate the antipyretic effect of the Qingwen Baiduling prescription in a dry yeast-induced rat fever model and to investigate its antipyretic mechanism， providing a theoretical basis for its clinical application. MethodsSPF-grade male SD rats were randomly assigned to six groups （n=6 per group）： control， model， aspirin （20 mg·kg^-1）， and high-， medium-， and low-dose Qingwen Baiduling prescription groups （14.40， 7.20， 3.60 g·kg^-1）. The fever model was established by subcutaneous injection of dry yeast suspension on the back. After model induction， body temperature was recorded every 1 hour. Drugs were administered at 6 hours after modeling， and body temperature was continuously recorded hourly for 12 hours. Record the body temperature of rats to observe the trend of changes in body temperature. Serum interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） levels， as well as hypothalamic prostaglandin E₂ （PGE₂） and cyclic adenosine monophosphate （cAMP）， were measured using enzyme-linked immunosorbent assay （ELISA）. Hypothalamic tissue morphology was examined by hematoxylin and eosin （HE） staining. Western blot was used to detect hypothalamic expression of Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， nuclear factor-κB p65 （NF-κB p65）， inhibitor κBα （IκBα）， phosphorylated IκBα （p-IκBα）， IκB kinase α （IKKα）， IKKβ， phosphorylated IKKα/β （p-IKKα/β）， and cyclooxygenase-2 （COX2）. ResultsCompared with the control group， the model group showed a significant increase in body temperature 6 hours after modeling （P0.01）， confirming successful fever induction. Serum IL-6， IL-1β， TNF-α， and hypothalamic cAMP and PGE₂ levels were significantly elevated （P0.01）. Hypothalamic neurons exhibited irregular morphology and disordered distribution， accompanied by inflammatory cell infiltration and microglial aggregation. Expression levels of TLR4/NF-κB pathway-related proteins and phosphorylated proteins were significantly increased （P0.05， P0.01）. Compared with the model group， 2-3 hours after administration， all Qingwen Baiduling prescription dose groups significantly reduced body temperature （P0.01）. All dose groups significantly decreased serum IL-6， IL-1β， TNF-α， and hypothalamic cAMP and PGE₂ levels （P0.05， P0.01）. Neuronal morphology was markedly improved in the high- and medium-dose groups， with narrowed intercellular spaces and reduced inflammatory infiltration. The prescription effectively inhibited hypothalamic expression of TLR4， MyD88， NF-κB p65， p-IκBα， p-IKKα/β， and COX2 proteins （P0.05， P0.01）. ConclusionQingwen Baiduling prescription effectively reduces body temperature in rats by mitigating the further effects of inflammatory cytokines on the hypothalamic thermoregulatory center through the blood-brain barrier. Its antipyretic mechanism may be related to inhibition of NF-κB pathway activation.

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

Objective To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

Objective To investigate the efficacy and safety of compound cantharidis capsule combined with pemetrexed and platinum-based drugs in the treatment of elderly patients with advanced lungadenocarcinoma.Methods A total of 80 patients with advanced lung adenocarcinoma were retro-spectively selected as the study subjects.According to the treatment regimen,they were divided into chemotherapy group(treated with pemetrexed and platinum-based drugs)and traditional Chinese med-icine combined with chemotherapy group(treated with compound cantharidis capsule combined with-pemetrexed and platinum-based drugs),with 40 cases in each group.The short-term efficacy,serum tumor marker[carcinoembryonic antigen(CEA),carbohydrate antigen 72-4(CA72-4),carbohydrate antigen 125(CA125)]levels,and the incidence of adverse reactions were observed and compared between the two groups.The patients were followed up,and the progression-free survival(PFS)and overall survival(OS)of the two groups were recorded.Results The objective response rate(ORR)and disease control rate(DCR)in the traditional Chinese medicine combined with chemotherapy group were higher than those in the chemotherapy group,with statistically significant differences(P＜0.05).After treatment,the serum CEA,CA72-4 and CA125 levels in both groups were lower than those before treatment,and the levels in the traditional Chinese medicine combined with chemotherapy group were lower than those in the chemotherapy group,with statistically significant differences(P＜0.05).There was no statistically significant difference in the incidence of grade 3 to 4 adverse reac-tions between the two groups(P＞0.05).The progression-free survival rate and overall survival rate in the traditional Chinese medicine combined with chemotherapy group were higher than those in the chemotherapy group,with statistically significant differences(P＜0.05).Conclusion Compound cantharidis capsule combined with pemetrexed and platinum-based drugs can significantly improve the ORR and DCR,reduce serum tumor marker levels,prolong the survival of patients with ad-vanced lung adenocarcinoma,and has good safety.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.