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.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

BACKGROUND:Prostaglandin E1(PGE1)has been shown to play a regulatory role in vasodilatation,inflammation,and leukocyte migration and adhesion,but its effects on spinal cord microcirculation after traumatic spinal cord injury(SCI)remain poorly understood. OBJECTIVE:To investigate the mechanism underlying the protective effects of PGE1 administered during the acute phase of traumatic SCI in rats on the regulation of vascular-related factors and microcirculatory function. METHODS:Seventy-two female Sprague-Dawley rats were divided into three groups(n=24 per group):control group,SCI group,and PGE1 group.An in vivo SCI model was established using Allen's blow method.Rats in the PGE1 group were injected with PGE1(10 μg/kg)via the tail vein immediately after SCI.Spinal cord microcirculatory blood flow and oxygen saturation,spinal cord microvessel diameter and area,spinal cord water content,vascular function regulators(von Willebrand factor,thromboxane A2,prostacyclin,endothelin-1),and inflammatory factors(tumor necrosis factor-α,interleukin-1β)were measured at 2 and 24 hours after SCI. RESULTS AND CONCLUSION:At 2 hours after SCI,the diameter and area of spinal cord microvessels,spinal cord microcirculatory blood flow,and oxygen saturation in the PGE1 group were higher than those in the SCI group(P<0.05),the water content of the spinal cord was lower than that in the SCI group(P<0.05),and the level of plasma von Willebrand Factor,the ratio of thromboxane A2/prostacyclin of the spinal cord and the level of endothelin-1 were lower than those in the SCI group(P<0.05).At 24 hours after SCI,the spinal cord microvessel area,blood flow,and oxygen saturation of rats in the PGE1 group were higher than those in the SCI group(P<0.05),the spinal cord water content was lower than that in the SCI group(P<0.05),and the levels of plasma von Willebrand factor,spinal cord tissue thromboxane A2/prostacyclin ratio and the levels of endothelin-1,tumor necrosis factor-α and interleukin-1β were lower than those in the SCI group(P<0.05).The diameter and area of spinal cord microvessels,spinal cord microcirculatory blood flow and blood oxygen saturation of rats in the SCI group were higher than those in the SCI group at 24 hours post-injury(P<0.05),and the levels of plasma von Willebrand factor,spinal tissue thromboxane A2/prostacyclin ratio,tumor necrosis factor-α and interleukin-1β were higher than those at 2 hours post-injury(P<0.05),but the level of endothelin-1 in spinal cord tissue was lower than that at 2 hours(P<0.05).The blood flow and oxygen saturation of spinal cord microcirculation in the PGE1 group rats at 24 hours post-injury were lower than those at 2 hours post-injury(P<0.05),and the diameter and area of spinal cord microvessels and water content of the spinal cord were higher than those at 2 hours post-injury(P<0.05).The above results indicate that intravenous administration of PGE1 in SCI rats immediately after injury can regulate vascular function regulators,inflammatory factors and improve microcirculation of the spinal cord after SCI,which provides a potential basis for the search of drugs for the treatment of acute SCI.

Gouty arthritis （GA） is an inflammatory disorder caused by monosodium urate （MSU） crystal deposition， accompanied by elevated oxidative stress and aberrant release of inflammatory cytokines， resulting in joint tissue damage and intense pain. Nuclear factor E₂-related factor 2 （Nrf2）， a key transcription factor regulating the antioxidant defence system， exerts cytoprotective effects through dissociation from Kelch-like ECH-associated protein 1 （Keap1） and activates downstream antioxidant response element （ARE）-mediated pathways. It can upregulate the expression of heme oxygenase-1 （HO-1）， NADH quinone oxidoreductase 1 （NQO1）， superoxide dismutase （SOD）， and glutathione transferase （GST） to preserve redox homeostasis. Moreover， Nrf2 can suppress activation of NOD-like receptor protein 3 （NLRP3） inflammasomes， reduce pro-inflammatory cytokine production and release， modulate nuclear factor-κB （NF-κB） transcriptional activity， regulate gut microbiota balance， enhance mitophagy， and inhibit apoptosis， so as to reduce joint inflammation and pain and promote body recovery. This review systematically examined recent advancements in traditional Chinese medicine （TCM） for GA prevention and treatment via regulating the Nrf2 signaling pathway. It delineated Nrf2's molecular mechanisms and its role in GA pathogenesis and elucidated how TCM intervenes in multiple pathways including Keap1/Nrf2/ARE， Nrf2/HO-1（NQO1）， and Nrf2/NF-κB/NLRP3 to exert therapeutic effects. The study demonstrated that TCM monomers and compounds effectively counteract oxidative damage， attenuate inflammatory responses， promote autophagy， and inhibit apoptosis via regulating the Nrf2 signaling pathway. These findings not only clarify the scientific basis of TCM in GA treatment but also offer strategic insights for developing novel Nrf2-targeted anti-gout drugs.

Objective To analyze the acupoint selection law of acupuncture and moxibustion for pediatric cerebral palsy based on data mining techniques.Methods Clinical research literature about acupuncture and moxibustion for the treatment of pediatric cerebral palsy was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from the establishment of the databases to April 1,2024.Excel 2021 was used to establish a database of prescription acupoints.The frequency of use of acupoints,attributed to the meridians,parts and specific acupoints were under statistically analysis,and SPSS Modeler 18.0 and SPSS Statistics 27.0 were used to conduct the association rules analysis,factor analysis and clustering analysis of acupoints.Results A total of 579 articles were included,579 prescriptions were extracted,containing 245 acupoints with the frequency of 6 422 times.The high-frequency acupoints were Zusanli,Baihui,Hegu,Sanyinjiao and Quchi,etc.The commonly used meridians were Governor Vessel,gall bladder meridian,stomach meridian,large intestine meridian and bladder meridian;mostly used acupoints were in the lower limbs,head and neck,upper limbs,waist and back.The association rules analysis showed that the top combinations were"Hegu-Quchi","Zusanli-Quchi","Zusanli-Quchi-Hegu","Hegu-Quchi-Zusanli";clustering analysis showed that 6 valid clusters were extracted;factor analysis extracted 7 valid common factors.Conclusion Acupuncture and moxibustion treatment for pediatric cerebral palsy is based on the principle of strengthening the brain,improving intelligence and tonifying the five zang organs,reflecting the principle of matching acupoints far and near.The core combination of acupoints is"Zusanli-Quchi-Hegu".

Objective To assess the level of research integrity awareness among clinical nursing personnel in Yunnan Province,analyze the influencing factors,and identify related risks.Methods From June 2025 to July 2025,a research integrity awareness questionnaire was conducted on 697 clinical nursing personnel from a university-affiliated tumor hospital and children's hospital using the Questionnaire Star platform.The survey content included basic information,research integrity awareness status,research integrity construction awareness,and the causes of research misconduct.Data were analyzed using SPSS 27.0.Results The research integrity awareness score of clinical nursing personnel was(47.49±11.06),with an overall awareness rate of 51.48%.Univariate analysis showed statistically significant differences in awareness scores based on nursing categories(t=-2.45),marital status(F=5.557),age(F=2.735),work experience(F=4.775),highest education level(F=13.11),whether serving as a master's supervisor(t=2.693),participation in research projects(t=4.95),whether they had published papers as the first author or corresponding author(t=5.11),and attendance of research integrity training(t=12.48)(P<0.05).Multivariate linear regression analysis indicated that marital status,highest education level,and participation in research integrity training were significant factors influencing clinical nursing personnel's research integrity awareness(P<0.05).The main reason for research misconduct was lack of research integrity awareness The(76.47%),and 92.37%of clinical nursing personnel believed further strengthening of research integrity construction was necessary.Conclusion The research integrity awareness level of clinical nursing personnel needs improvement.Hospitals should enhance research integrity training,improve research integrity management systems,and optimize scientific talent evaluation mechanisms.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

Objective To analyze the acupoint selection law of acupuncture and moxibustion for pediatric cerebral palsy based on data mining techniques.Methods Clinical research literature about acupuncture and moxibustion for the treatment of pediatric cerebral palsy was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from the establishment of the databases to April 1,2024.Excel 2021 was used to establish a database of prescription acupoints.The frequency of use of acupoints,attributed to the meridians,parts and specific acupoints were under statistically analysis,and SPSS Modeler 18.0 and SPSS Statistics 27.0 were used to conduct the association rules analysis,factor analysis and clustering analysis of acupoints.Results A total of 579 articles were included,579 prescriptions were extracted,containing 245 acupoints with the frequency of 6 422 times.The high-frequency acupoints were Zusanli,Baihui,Hegu,Sanyinjiao and Quchi,etc.The commonly used meridians were Governor Vessel,gall bladder meridian,stomach meridian,large intestine meridian and bladder meridian;mostly used acupoints were in the lower limbs,head and neck,upper limbs,waist and back.The association rules analysis showed that the top combinations were"Hegu-Quchi","Zusanli-Quchi","Zusanli-Quchi-Hegu","Hegu-Quchi-Zusanli";clustering analysis showed that 6 valid clusters were extracted;factor analysis extracted 7 valid common factors.Conclusion Acupuncture and moxibustion treatment for pediatric cerebral palsy is based on the principle of strengthening the brain,improving intelligence and tonifying the five zang organs,reflecting the principle of matching acupoints far and near.The core combination of acupoints is"Zusanli-Quchi-Hegu".