ObjectiveTo investigate the efficacy and safety of lenvatinib combined with sintilimab versus atezolizumab combined with bevacizumab in patients with unresectable hepatocellular carcinoma （uHCC）， aims to provide real-world evidence for clinical personalized treatment. MethodsA retrospective analysis was performed for 78 patients with uHCC who were admitted to Beijing Ditan Hospital， Capital Medical University， from January 1， 2023， to May 31， 2025， and according to the treatment modality， they were divided into lenvatinib+sintilimab group （L+S group with 49 patients） and atezolizumab+bevacizumab group （A+T group with 29 patients）. The primary endpoints were progression-free survival （PFS） and overall survival （OS）， and the secondary endpoints included objective response rate （ORR）， disease control rate （DCR）， and the incidence rate of adverse events. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used for survival analysis， and the log-rank test was used for comparison between groups. ResultsThe 78 patients had a median PFS of 9 months and a median OS of 15 months. The median PFS was 11 months in the L+S group and 7 months in the A+T group， with no significant difference between the two groups （χ²=0.247， P=0.619）； the median OS was 19 months in the L+S group and 12 months in the A+T group， with a significant difference between the two groups （χ²=6.565， P=0.010）. There were no significant differences between the two groups in complete remission， partial remission， stable disease， disease progression， DCR， and ORR （all P>0.05）. The L+S group had a significantly higher incidence rate of adverse events than the A+T group （95.9% vs 75.9%， P=0.007）， and there was a significant difference in the incidence rate of grade ≥3 adverse events between the L+S group and the A+T group （65.3% vs 34.5%， P=0.008）. ConclusionCompared with atezolizumab combined with bevacizumab， lenvatinib combined with sintilimab can improve the OS of patients with uHCC， while atezolizumab combined with bevacizumab has a better safety profile.

Objective:To investigate the causal relationship between plasma proteins and spontaneous abor-tion using a two-sample Mendelian randomization method.Methods:Using genome-wide association study(GWAS)data from an Icelandic population as an exposure factor and spontaneous abortion data from the Finn-ish Genetic Research Project(FinnGen)as an outcome,the causal relationship between plasma proteins and the risk of developing spontaneous abortion was analyzed using a Mendelian randomization(MR)study.The inverse variance weighting(IVW)method was used as the primary study method,with MR-Egger,weighted median and weighted mode complementing the results;and sensitivity analyses were performed using Cochrane's Q test,MR-Egger intercept testand leave-one-out method to validate the reliability of the data.Results:Seven plasma proteins were identified as potentially correlated with the risk of spontaneous abortion of which fucosyltransferase 10(FUT10)(OR 0.955,95％CI 0.915-0.996,P=0.034),plexin B2(PLXNB2)(OR 0.947,95％CI 0.902-0.995,P=0.030),and interleukin-11 receptor alpha(IL-11Rα)(OR0.905,95％CI 0.848-0.966,P=0.003)were associ-ated with a reduced risk of SA development,while plasma proteins soluble L-selectin(SL-selectin)(OR 1.076,95％CI 1.021-1.134,P=0.006),Cripto protein(OR 1.039,95％CI 1.008-1.071,P=0.012),dendritic cell-specif-ic intercellular adhesion molecule 3-grabbing non-integrin(DC-SIGN)(OR 1.051,95％CI 1.022-1.082,P=0.001),and protein Z-dependent protease inhibitor(ZPI)(OR 1.035,95％CI 1.001-1.071,P=0.045)levels were positively associated with the risk of developing SA.No heterogeneity or horizontal pleiotropy was detected(Co-chrane's Q test and MR-Egger intercept test,P＞0.05),and leave-one-out analysis showed that there were no individual single-nucleotide polymorphisms that had a large impact on the overall data.Conclusions:This Mende-lian randomization analyses confirmed the causal relationship between multiple plasma proteins and spontaneous abortion,which is potentially clinically valuable for studying the correlation between plasma proteins and spontane-ous abortion.

Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.

Objective To investigate the anti-inflammatory protective effects of remimazolam on microglial cells and elucidates the potential molecular mechanisms underlying these effects. Methods The mouse microglial cell line (BV2) was selected as the research object. The following groups were set up:the control group (complete medium),the Rema group (200 μg/mL remimazolam),the model group (1 μg/mL lipopolysaccharide,LPS),and different-concentration administration groups (1 μg/mL LPS+50,100,200 μg/mL remimazolam). In the Rema group,cells were treated with 200 μg/mL remimazolam alone for 26 h. In the model group,cells were treated with LPS for 24 h. In the different-concentration administration groups,cells were pre-treated with different concentrations of remimazolam for 2 h,and then treated with LPS for 24 h. The effects of LPS and remimazolam on the morphology of BV2 cells were observed and evaluated using an optical microscope. Cell viability was determined using the CCK-8 assay,while the expression and secretion of inflammatory cytokines were quantified by quantitative real-time PCR and ELISA. Reactive oxygen species (ROS) levels were measured using a fluorescent probe. Additionally,malondial-dehyde (MDA) content,superoxide dismutase (SOD) activity,and glutathione peroxidase (GSH) activity were evaluated using respective assay kits. Western blot analysis was conducted to examine the protein expression levels of Bax,Bcl-2,IL-1β,RAGE,NF-κB,p-NF-κB,IκBα,p-IκBα,iNOS,and Arg-1. Immunofluorescence staining was employed to visualize NF-κB nuclear translocation and M1/M2 polarization in the cells. Results Compared to the control group,LPS-treated BV2 cells demonstrated significantly reduced cell viability,elevated expression and se-cretion of inflammatory cytokines (TNF-α,IL-6,IL-1β),decreased activities of SOD and GSH,and increased in-tracellular levels of MDA and ROS. Additionally,RAGE protein levels were upregulated,along with enhanced phos-phorylation of IκBα and NF-κB,leading to observable NF-κB nuclear translocation. The expression of the M1 marker iNOS was upregulated,while that of the M2 marker Arg-1 was downregulated. In contrast,in the LPS+Rema group,cell viability was restored,expression and secretion of inflammatory cytokines were attenuated,SOD and GSH activities were improved,and levels of MDA and ROS were reduced compared to the LPS group. Furthermore,RAGE protein expression and phosphorylation levels of IκBα and NF-κB were diminished,inhibiting NF-κB nuclear translocation. The expression of the M1 marker iNOS was downregulated,while that of the M2 marker Arg-1 was up-regulated. Conclusion Remimazolam mitigates LPS-induced inflammation by facilitating the transition of microglial cells from the M1 to the M2 phenotype via modulation of the NF-κB pathway and reduction of ROS production.

The female reproductive system is essential for sustaining reproductive endocrine homeostasis,however,its vulnerability to various endogenous and exogenous insults,including pathological conditions,pharmacological agents,genetic predispositions,and environmental factors,often results in compromised fertility.The existing protective approaches(including surgical interventions,hormonal replacement therapies,and assisted reproductive techniques)are constrained by several limitations,such as adverse therapeutic effects,technical complexities,and their incapacity to reverse ovarian senescence.Artemisinin and its derivatives(ARTs),characterized by their unique endoperoxide bridge configuration,have exhibited outstanding therapeutic performance across multiple domains including malaria treatment,anticancer therapy,inflammation modulation,and parasitic infection control.Emerging research has identified their novel protective capabilities against various reproductive system pathologies.This comprehensive review systematically elucidates the molecular mechanisms underlying artemisinin-based interventions in reproductive pathologies and evaluates their clinical translation prospects,thereby proposing innovative strategies for the development of next-generation fertility-protective agents with enhanced safety and efficacy profiles.

Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson tumor, is a rare vascular benign tumor of blood vessels. It may occur in any part of the body, especially the deep dermis and subcutaneous tissue of the head, neck, fingers and trunk. The imaging and histopathology of IPEH are similar to hemangiosarcoma, especially in the case of active vascular endothelial hyperplasia. IPEH is a reactive proliferative lesion of vascular intima. The etiology is still unclear. After some studies showed that IPEH was a benign lesion, few reports on the etiology of it were reported. IPEH is usually limited to the thrombotic vessels or lumens of vascular malformations, usually accompanied by a clear history of trauma. IPEH usually does not cause any symptoms. It looks like a slow-growing lump. Some cases have been reported with pain and swelling. Although IPEH is relatively rare, its accurate diagnosis is crucial because it may be similar to malignant angiogenic lesions in clinical practice. There were few reports of cases related to intravascular papillary endothelial hyperplasia located in the sternocleidomastoid muscle after reviewing the domestic and foreign literature in recent 10 years. This case reports that a young male, who was admitted to the hospital one month after finding a subcutaneous tumor in the left neck. After admittance, relevant preoperative examinations were completed. After multi-disciplinary discussion and elimination of surgical contraindications, a specific surgical plan was formulated. The tumor was removed under local anesthesia on the second day after admission. During the operation, it was found that the tumor was located between the sternocleidomastoid muscle bundles, and it was sent for pathologic examination. Paraffin section pathology was reported after operation. Histological examination showed that the morphology was consistent with vascular endothelial papillary hyperplasia. There were no related surgical complications and recurrence in the 3-month follow-up. The purpose of this paper is to provide clinicians with a certain understanding of this rare disease through the report of this case of IPEH, and to identify it in later clinical work, and at the same time, to avoid confusion with malignant diseases, such as hemangiosarcoma, leading to unnecessary treatment and increase the cost of treatment.
Humans ; Male ; Endothelium, Vascular/pathology* ; Hemangioendothelioma/surgery* ; Hyperplasia/pathology* ; Neck Muscles/surgery* ; Vascular Neoplasms/pathology*

OBJECTIVES: The core pathology of osteoporosis lies in bone resorption exceeding bone formation; thus, promoting osteogenesis is a key therapeutic strategy. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) forms the biological basis of bone formation. Astragaloside IV (A-IV), a major active component of Astragalus membranaceus, is known to enhance osteogenesis, but its precise molecular mechanisms remain unclear. This study aims to investigate the effects of A-IV on the proliferation and osteogenic differentiation of BMSCs from osteoporotic rats and to elucidate its molecular mechanism through the regulation of microRNA-21 (miR-21) and Notch2 expression. METHODS: After 1 week of adaptive feeding, mature female SD rats were randomly divided into a sham-operated (Sham) group (n=4) and an ovariectomized (OVX) group (n=8) to establish an osteoporosis model. Twelve weeks after surgery, BMSCs were isolated from femoral bone marrow and cultured. Cells were divided into a S-BMSCs group (from Sham), an O-BMSCs group (from OVX), and an A-BMSCs group (from OVX-derived BMSCs treated with A-IV). S-BMSCs and O-BMSCs were induced for osteogenic differentiation using osteogenic induction medium, whereas A-BMSCs were treated with A-IV before induction. Flow cytometry was used to identify mesenchymal stem cell surface markers (CD29) and hematopoietic stem cell marker (CD34) to confirm BMSC characteristics. Cell proliferation was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Alizarin red staining was performed to quantify calcium nodule formation, and alkaline phosphatase (ALP) activity assays were used to evaluate osteogenic differentiation. Real-time reverse transcription PCR (real-time RT-PCR) was used to detect changes in osteogenic-related genes, runt-related transcription factor 2 (Runx2) and osteopontin (OPN), as well as miR-21 expression. Western blotting was performed to assess Runx2, OPN, and Notch2 protein expression. RESULTS: Flow cytometry confirmed that O-BMSCs retained the phenotypic characteristics of mesenchymal stem cells. A-IV significantly enhanced the proliferation of BMSCs from osteoporotic rats (P<0.05), increased ALP activity, and upregulated the mRNA and protein expression of Runx2 and OPN (P<0.05). Bioinformatic and experimental analyses demonstrated that miR-21 directly targeted Notch2. A-IV treatment increased miR-21 expression while suppressing Notch2 protein expression and inhibiting activation of the Notch signaling pathway (P<0.05). CONCLUSIONS Astragaloside IV promotes the osteogenic differentiation of BMSCs derived from osteoporotic rats by upregulating miR-21 expression and inhibiting the key Notch signaling protein Notch2, thereby relieving the Notch2-mediated suppression of osteogenesis.
Animals ; Triterpenes/pharmacology* ; Saponins/pharmacology* ; Osteogenesis/drug effects* ; MicroRNAs/metabolism* ; Rats, Sprague-Dawley ; Female ; Cell Differentiation/drug effects* ; Mesenchymal Stem Cells/drug effects* ; Signal Transduction/drug effects* ; Osteoporosis/pathology* ; Rats ; Cells, Cultured ; Receptor, Notch2/metabolism* ; Receptors, Notch/metabolism* ; Ovariectomy ; Cell Proliferation/drug effects*