Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective: To investigate the effects of platelet-derived PD-L1 released during storage on T cell proliferation, apoptosis, and cytokine expression. Methods: Apheresis platelets were stored with agitation at 22℃. Platelet supernatant was collected on days 1, 3, 5, and 7 of storage, and then co-cultured with human CD4 and CD8 mixed T cells isolated by magnetic bead sorting. CCK8 assay was used to detect T cell proliferation; flow cytometry was applied to determine T cell apoptosis as well as the expression levels of IFN-γ and GZMB. Additionally, Western blot was employed to examine alterations in downstream signaling molecules of the PD-1 receptor. Results: With the prolongation of platelet storage time, the inhibitory effect of platelet storage medium on T cell proliferation was gradually enhanced, accompanied by suppressed expression of IFN-γ and GZMB, whereas the apoptosis level of T cells increased progressively. Treatment with PD-1 antibody or PD-L1 antibody partially blocked the regulatory effects of platelet storage medium on T cell proliferation, apoptosis, and the expression of IFN-γ and GZMB. Western blot results showed that the phosphorylation levels of p-SHP1 and p-SHP2 were significantly upregulated, whereas p-AKT expression was downregulated in T cells co-cultured with platelet storage medium. Intervention with PD-1 or PD-L1 antibody could partially reverse the above changes in protein expression. Conclusion: During platelet storage, platelet-derived PD-L1 in the storage medium promotes T cell apoptosis and inhibits T cell proliferation as well as the expression of related cytokines in a time-dependent manner. Therefore, platelet-derived PD-L1, as an important immune regulatory mediator, may be involved in transfusion-related immunomodulation (TRIM).

Objective To investigate the effects of different administration times on the efficacy and safety of subcutaneous immunotherapy using dual mite extracts in patients with allergic rhinitis(AR).Methods This study was designed as a retrospective cohort analysis.Thirty-nine mite-sensitized AR patients who completed three years of standardized dual-mite subcutaneous immunotherapy(SCIT)were included.Based on self-selected and consistently maintained injection schedules,patients were non-randomly assigned to either a morning dosing group(MD group,8:00-12:00,n=19)or an afternoon dosing group(AD group,14:00-18:00,n=20),with further subgroup stratification conducted at 2-hour intervals.Nasal and ocular symptoms were evaluated before and after treatment using the visual analog scale(VAS),and all adverse reactions were systematically recorded.Results The AD group exhibited significantly greater improvement in nasal itching compared to the MD group(median difference:-2 vs.0,U=118.5,P=0.04,effect size r=0.33).The AD group also demonstrated favorable trends toward improved sneezing,nasal congestion,rhinorrhea,and total VAS score,although these differences did not reach statistical significance.In the subgroup analysis by 2-hour intervals,the 16:00-18:00 subgroup showed greater symptom relief than the 8:00-10:00 subgroup,though the difference was not statistically significant.No significant differences were observed between the two groups in the incidence of total,local,or systemic adverse reactions(P>0.05),and no moderate or severe systemic adverse events occurred.Conclusions This preliminary retrospective analysis indicates that afternoon administration of dual-mite SCIT,particularly between 16:00 and 18:00,may enhance the improvement of nasal symptoms without elevating safety concerns.The timing of SCIT administration could therefore represent a promising avenue for treatment optimization.

Objective:To construct an evaluation system for the risk factors of PICC catheter malposition in patients with hematological diseases, providing a reference for the prevention of central venous access malposition in these patients.Methods:From July 2022, a literature review was conducted to retrieve literature published in database and website such as PubMed, Web of Science domestically and internationally related to the risk assessment system of PICC catheter malposition in hematology patients. After full-text screening and extraction, the articles were included in the system′s item pool. Through further discussions among the research group′s experts, in conjunction with evidence-based findings, the system′s consultation items were formulated. Using the Delphi expert consultation method, a standard for PICC catheter malposition risk assessment system applicable to hematology patients was ultimately formulated.Results:In this study, 25 experts were invited for consultation: 24 females and 1 male, with an average age of (48.36 ± 6.82) years. After two rounds of expert consultations and revisions, the risk factors for PICC catheter malposition in hematology patients were identified to include 4 first-level indicators: patient factors, treatment factors, catheter-related factors, and operational factors, along with 11 second-level indicators and 25 third-level indicators. The positive coefficients of the experts in the two rounds of consultations were 84% and 100%, respectively; the Kendall coordination coefficients were 0.22 and 0.55 (both P<0.05); and the expert authority coefficient was 0.93. Conclusions:The risk assessment scale for PICC catheter malposition in patients with hematological diseases has high expert recognition and good consistency, and has clinical practice and guiding value.

Objective:To investigate the longitudinal trajectories of symptom clusters in elderly patients with laparoscopic surgery for colon cancer, and explore the predictive factors for each trajectories subgroup.Methods:Using a longitudinal survey, elderly patients with laparoscopic surgery for colon cancer patients from Shanxi Bethune Hospital from January 2021 to January 2024 were collected by convenient sampling method. The Chinese Version of the MD Anderson Symptom Inventory Gastrointestinal Cancer Module was used to conduct follow-up surveys of the selected patients at 2 weeks, 1 month, 3 months and 6 months after surgery. The symptom cluster was extracted by exploratory factor analysis, and the latent category growth model was conducted to identify the trajectory subgroups of each symptom cluster, the predictive factors of each trajectory subgroup was analyzed by multiple Logistic regression analysis.Results:A total of 118 cases were concluded in the present study, there were 69 males and 49 females with an age of (74.85 ± 3.29) years old. There were 4 symptom clusters after surgery, which were named as energy deficit symptom cluster, digestive tract symptom cluster, sleep mental symptom cluster, and psychological fatigue symptom cluster, the variance contribution rates were respectively 62.486%, 71.209%, 73.937%, 63.476%. The results from latent class growth model showed that there were 3 trajectory subgroups in the symptom cluster: high level-slow decline group accounted for 33.0% (39/118), moderate level-stable decline group accounted for 39.0% (46/118), low level-rapid decline group accounted for 28.0% (33/118). College education or above tends to developed into low level-rapid decline group ( OR=0.365, 95% CI 0.083-0.603, P<0.05), while patients undergoing traditional laparoscopic surgery ( OR=3.679, 95% CI 1.297-4.432, P<0.05) and primary tumor stages of Ⅲ-Ⅳ were more likely to developed into high level-slow decline group ( OR=0.333, 95% CI 0.120-0.920, P<0.05). Conclusions:There are 4 symptom clusters in elderly patients with laparoscopic surgery for colon cancer, and the characteristics of postoperative symptom cluster changes demonstrate significant heterogeneity, medical staff should pay attention to the management of symptom clusters trajectory categories, dynamically adjust intervention plans to improve nursing quality.

Objective To investigate the effects of different administration times on the efficacy and safety of subcutaneous immunotherapy using dual mite extracts in patients with allergic rhinitis(AR).Methods This study was designed as a retrospective cohort analysis.Thirty-nine mite-sensitized AR patients who completed three years of standardized dual-mite subcutaneous immunotherapy(SCIT)were included.Based on self-selected and consistently maintained injection schedules,patients were non-randomly assigned to either a morning dosing group(MD group,8:00-12:00,n=19)or an afternoon dosing group(AD group,14:00-18:00,n=20),with further subgroup stratification conducted at 2-hour intervals.Nasal and ocular symptoms were evaluated before and after treatment using the visual analog scale(VAS),and all adverse reactions were systematically recorded.Results The AD group exhibited significantly greater improvement in nasal itching compared to the MD group(median difference:-2 vs.0,U=118.5,P=0.04,effect size r=0.33).The AD group also demonstrated favorable trends toward improved sneezing,nasal congestion,rhinorrhea,and total VAS score,although these differences did not reach statistical significance.In the subgroup analysis by 2-hour intervals,the 16:00-18:00 subgroup showed greater symptom relief than the 8:00-10:00 subgroup,though the difference was not statistically significant.No significant differences were observed between the two groups in the incidence of total,local,or systemic adverse reactions(P>0.05),and no moderate or severe systemic adverse events occurred.Conclusions This preliminary retrospective analysis indicates that afternoon administration of dual-mite SCIT,particularly between 16:00 and 18:00,may enhance the improvement of nasal symptoms without elevating safety concerns.The timing of SCIT administration could therefore represent a promising avenue for treatment optimization.

Objective:To compare the diagnostic value of semi-quantitative parameters of fluorine 18-labelled prostate-specific membrane antigen( 18F-PSMA)positron emission tomography /computed tomography(PET/CT)and the Prostate-specific Membrane Antigen Reporting and Data System(PSMA-RADS)score for identifying benign and malignant oligo-PSMA-avid bone lesions(1-5 lesions)in elderly patients with prostate cancer. Methods:A retrospective analysis was conducted on 157 prostate cancer patients who underwent 18F-PSMA PET/CT examinations at Beijing Hospital from October 2022 to August 2024.According to the inclusion and exclusion criteria, a total of 63 patients were selected.All patients underwent 18F-PSMA PET/CT examination for the purpose of initial staging or detecting lesions with biochemical recurrence.PSMA-avid bone lesions were evaluated using the PSMA-RADS version 2.0 scoring system and the semi-quantitative parameters were measured on PSMA PET/CT images.According to the comprehensive diagnostic criteria, PSMA-avid bone lesions were divided into metastatic group and non-metastatic group.The differences in PSMA-RADS scores, semi-quantitative parameters, bone density abnormalities, and lesion distribution were compared between the two groups.Multivariate logistic regression analysis was performed to determine the factors related to the bone metastasis in prostate cancer.By plotting the receiver operating characteristic(ROC)curves and calculating the area under the curve(AUC), factors with better diagnostic performance were evaluated and screened, and the optimal diagnostic threshold for each factor in diagnosing bone metastasis was determined. Results:There were a total of 129 PSMA-avid bone lesions for 63 patients(aged 60-84 years, median age 69 years), including 35 lesions(27.1%)in the metastatic group and 94 lesions(72.9%)in the non-metastatic group.The differences between metastatic group and non-metastatic group in PSMA-RADS scores[5(4, 5) vs.3(3, 3)], maximum standardized uptake value(SUV max)[12.6(7.0, 18.4) vs.4.7(3.5, 5.9)], lesion SUV max/mediastinal blood pool SUV max ratio(lesion-to-blood pool ratio, LBR)[5.4(3.0, 8.3) vs.1.7(1.4, 2.2)], lesion SUV max/liver SUV max ratio(lesion-to-liver ratio, LLR)[2.6(1.6, 4.1) vs.0.8(0.7, 1.1)], PSMA receptor expressing tumor volume(PSMA-TV)[0.6(0.3, 1.0) vs.1.0(0.7, 1.5)], total lesion of PSMA(TL-PSMA)[4.4(2.4, 7.0) vs.2.4(1.7, 3.9)], proportion of changes in osteogenic bone density[77.1%(27/35) vs.2.1%(2/94)], proportion of lesions located in the ribs[14.3%(5/35) vs.46.8%(44/94)], and proportion of lesions located in the pelvis[54.3%(19/35) vs.20.2%(19/94)]were all statistically significant(all P<0.05). Multivariate logistic regression analysis indicated that none of the variables with statistically significant differences between groups above were independent risk factors for osseous metastasis in prostate cancer(all P>0.05). Among them, The PSMA-RADS score, LLR, LBR, and SUV max all had good diagnostic efficacy for osseous metastasis, with 0.995(95% CI: 0.987-1.000), 0.923(95% CI: 0.869-0.977), 0.898(95% CI: 0.828-0.967), and 0.890(95% CI: 0.820-0.961), respectively.The cut-off values for diagnosing osseous metastasis were 4 score for PSMA-RADS score, 0.934 for LLR, 1.990 for LBR, and 5.47 for SUV max, respectively.According to Delong's test, there were statistically significant differences in AUC between PSMA-RADS score and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)( Z-values were 2.677, 2.776, and 2.929, respectively, and P-values were 0.007, 0.006, and 0.003, respectively). Conclusions:The PSMA-RADS score(Version 2.0)and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)both have good diagnostic value in differentiating benign and malignant PSMA-avid bone lesions in elderly patients with prostate cancer, among which the PSMA-RADS score has the best diagnostic efficacy.

Objective:To explore the gait and eye movement parameters in early Parkinson's disease(PD)with sleep disorders, and analyze their association with underlying pathophysiological mechanisms.Methods:This study was a cross-sectional single-center design that included 82 early PD patients with Hoehn-Yahr(H-Y)staging ≤2.5 who visited Beijing Hospital from October 2023 to May 2025.Patients were divided into two groups according to the PDSS-2 score(total score ≤15 for the no sleep disorder group and total score >15 for the sleep disorder group). Gait and eye movement parameters were collected respectively through the ReadyGo system and the EyeKnow eye movement system, and analyzed in combination with clinical scales.Multivariate logistic regression was employed to identify independent characteristic parameters associated with sleep disorders.Results:In terms of gait, the sleep disorder group had significantly lower step speed, left-right stride speed, and left-right swing speed(all P<0.05), and significantly higher variability of left-right stride time( P=0.017, 0.026). Regarding eye movements, the sleep disorder group had significantly more vertical smooth pursuit offsets[(56.24±2.87)times vs.(45.98±18.18)times, P=0.040], significantly higher maximum real-time variability of the right eye in response to light stimuli(90.75 vs.67.95%, P=0.006), and a longer latency to error responses in the counter-scanning task(337.06 vs.286.63 ms, P=0.005). To precisely control for confounding factors, key covariates such as mood and disease severity were included in the multivariate logistic regression model.After comprehensive adjustment, higher anxiety levels(Hamilton Anxiety Rating Scale, HAMA)( OR=1.32, P<0.001)and an increased number of vertical smooth pursuit offsets( OR=1.06, P=0.010)were independent factors associated with sleep disorders in early PD patients. Conclusions:In early PD patients, sleep disorders are closely associated with specific abnormalities in gait and eye movement parameters.In particular, vertical smooth pursuit offsets may serve as an objective biomarker independent of emotional status, reflecting the dysfunction of shared neural circuits.However, further mechanism studies are needed to verify whether they reflect the dysfunction of shared neural circuits.

[Objective]To investigate a simple method for the rapid detection and precise analysis of trace triptolide(TP)in vitro.[Methods]Initially,4-carboxy-4'-methyl-2,2'-bipyridine(Me-bpy-COOH)and cis-bis(2,2'-bipyridine)dichlororuthenium(Ⅱ)(cis-Ru(bpy)2CL2)were used as raw materials to synthesize tripyridine ruthenium monocarboxylic acid fluorescent reagent,namely bis(2,2'-bipyridyl)(4-methyl-4'-carboxy-2,2'-bipyridyl)ruthenium(Ⅱ)bishexafluorophosphate[Ru(bpy)2(bpy-COOH)2PF6].Subsequently,the pre-column derivatization reaction conditions of Ru(bpy)2(bpy-COOH)2PF6 with TP was optimized through orthogonal test and a methodological evaluation of the high performance liquid chromatography-fluorescence detection(HPLC-FLD)of triptolide-terpyridine ruthenium derivative(TTRD)was conducted.Taking commercially available Kunxian Capsules as object,the newly established evaluation method was adopted for detection.[Results]A fluorescent derivative of TP,TTRD was obtained and was characterized by proton nuclear magnetic resonance(1H-NMR)and ultra high performance liquid chromatography-mass spectrometry(UPLC-MS).The optimized pre-column derivatization reaction conditions were a 4:1 molar ratio of Ru(bpy)2(bpy-COOH)2PF6 to TP,a reaction time of 2 hours and a reaction temperature of 45℃.This study presented a HPLC-FLD method for the pre-column derivatization of TP.The method demonstrated a good linear relationship within the range of 50 to 1 200 μg·L-1.The TP content in Kunxian Capsules was measured by using this method,yielding a result of 78.78 μg·g-1,which fell within the prescribed range of national drug standards.[Conclusion]The pre-column-derived HPLC-FLD method for TP exhibited good sensitivity,accuracy and reliability,expanding the HPLC detection range for TP.

Objective:To investigate the clinical characteristics of patients with hepatitis B virus（HBV）-related primary hepatocellular carcinoma（HCC）who were treated in a multidisciplinary team（MDT）for liver cancer，so as to provide a basis for clinical optimization of the diagnosis and treatment of patients with chronic hepatitis B（CHB）.Methods:A retrospective analysis was performed for 482 HBV-related HCC patients who were treated with HCC-MDT every Thursday afternoon in The First Affiliated Hospital of the Army Medical University from January 2022 to May 2024，aged 18-87（55.54±10.84）years，86.93%（419/482）males and 13.07%（63/482）females. According to the different underlying liver diseases at the time of initial medical treatment and the different prognostic outcomes at the later follow-up，the differences in clinical characteristics between groups under different conditions were compared and analyzed，and the influencing factors of HCC prognosis were understood by Logistic regression analysis. Results:At the time of MDT presentation，the differences in HBeAg status（ χ2=6.311 ，P=0.043），γ-glutamyl traspeptidase（GGT）（ Z=6.277， P=0.043），alkaline phosphatase（ALP）（ Z=7.236 ，P=0.027），and model for end-stage liver disease（MELD）scores（ Z=6.111， P=0.047）among patients with different underlying liver diseases were statistically significant. At follow-up，6.75%（11/163）of HBV-related HCC patients who presented to MDT had a family history of HCC，and their cumulative mortality rate was as high as 60.8%（205/337）at least for 1 year. Mulitivariate Logistic regression analysis showed that different underlying liver disease at the time of initial medical treatment，HBV DNA replication level，MELD score and choice of anti-cancer treatment regimen were the influencing factors for the prognosis of HCC（all P<0.05）. The worse the degree of cirrhosis at the initial presentation，the higher the level of HBV DNA replication，and the higher the MELD score，the worse the prognosis for HCC. Conclusion:Advancing the diagnosis and treatment of CHB，maximizing the inhibition of HBV DNA replication，reducing the MELD score，and optimizing the anti-cancer treatment regimen can reduce the mortality rate of HBV-related HCC.