OBJECTIVE To compare the anti-hepatitis mechanisms of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. （AC） and Abrus pulchellus subsp. mollis（Hance） Verdc. （AM）. METHODS SD rats were randomly divided into blank group， AC- treated group， and AM-treated group， with each group consisting of 10 rats. The rats’ orbital venous blood was collected at 5， 15， 30 minutes， and 1， 1.5， 2， 4， 6， 8， 12 hours after gavage administration of 24 g/kg of the corresponding drug （calculated by crude drug） or water， respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology was utilized to identify the prototype components present in the serum. The network pharmacology method was adopted to predict the anti-hepatitis active components， key targets， and signaling pathways of AC and AM. Additionally， molecular docking technology was utilized to verify the binding activity of the core active components with key targets. RESULTS A total of 35 prototype components migrating to the blood of AC and AM were identified in the serum of administered rats， among which 24 were common components. The active components in AC， such as acetylanguidine， physcion， soyasaponin A3 and soyasaponin Ⅰ， as well as those in AM， including vicenin 3， acetylanguidine，soyasaponin Ⅰ and schaftoside， all acted on key targets such as steroid receptor coactivator， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha， epidermal growth factor receptor （EGFR）， and protein kinase B1（Akt1）. These components modulated pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the phosphoinositide 3-kinase （PI3K） -Akt pathway， thereby exerting anti-hepatitis effects. Furthermore， the binding energies between these active components and their key targets were all less than －5 kJ/mol. CONCLUSIONS There are differences in the active components of AC and AM against hepatitis， but their mechanisms of action are similar. Both may exert their anti-hepatitis effects through pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the PI3K-Akt pathway.

BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases. METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity. RESULTS: After a mean follow-up time of 11.8 years, over 20 International Classification of Diseases, 10th Revision ( ICD-10 ) codes were showed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR] = 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR = 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR = 1.58, 95% CI: 1.14-2.17), gastritis (K29: HR = 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR = 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR = 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR = 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR = 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR = 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR = 1.50, 95% CI: 1.17-1.94; K44: HR = 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR = 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL. CONCLUSIONS This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.
Humans ; Male ; Female ; Middle Aged ; Cohort Studies ; Leukocytes/metabolism* ; Telomere/genetics* ; Proportional Hazards Models ; Adult ; Digestive System Diseases/genetics* ; Aged ; Risk Factors ; Telomere Shortening

Objective:To compare the efficacy of gasless robotic surgery via transaxillary approach and combined axillary-retroauricular approach for unilateral N1b PTC, and to explore the safety and effectiveness of gasless robotic surgery via transaxillary approach for unilateral N1b PTC. Methods:Unilateral N1b PTC patients who underwent surgery in the Department of Otolaryngology, Sun Yat Sen Memorial Hospital, Sun Yat sen University between July 2016 and December 2024 were included and analyzed. According to the inclusion and exclusion criteria and the differences of surgical approaches, the patients were divided into the transaxillary approach（TA） group and the combined axillary-retroauricular approach（TARA） group. The demographic data, operation time, intraoperative blood loss, postoperative drainage volume, postoperative complications, shoulder function evaluation, postoperative visual analogue scale（VAS） of neck aesthetics and recurrence of the two groups were statistically analyzed. Results:A total of 88 patients undergoing gasless robotic surgery were included in this study, including 23 cases in the TA group and 65 cases in the TARA group. The proportion of males in the TA group was significantly higher than that in the TARA group（56.5% vs 21.5%, χ²=9.776, P=0.002）. The total operation time in the TA group was significantly lower than that in the TARA Group（180.00[155.00, 220.00]min vs 220.00[177.50, 272.50]min, z=-2.775, P=0.006）, and the postoperative blood loss in the TA group was significantly lower than that in the TARA Group（30.00[20.00, 50.00]ml vs 50.00[30.00, 60.00]ml, Z=-2.127, P=0.033）. The proportion of area Ⅱ-Ⅴ in the TA group and the TARA group was 87.0% and 70.8%, respectively, and there was no significant difference between the two groups（P>0.05）. There was no significant difference in lateral cervical lymph node dissection and central lymph node dissection between the two groups（P>0.05）. During the follow-up period, no recurrence was found in the two groups, and there was no significant difference in the incidence of complications between the two groups（P>0.05）. According to the stratification of dynamic recurrence risk assessment, it can be seen that the proportion of curative effect satisfaction in the TA group was as high as 95.7%, and that in the TARA group was as high as 81.5%, with no significant difference between the two groups. There was no significant difference in VAS score of neck, Constant Shoulder Score and NDⅡ scale between the two groups（P>0.05）. Conclusion:Gasless robotic surgery via transaxillary approach for unilateral N1b PTC is safe and feasible, and the amount postoperative lymph node acquisition is equivalent to that of combined axillary-retroauricular approach, which can provide a new choice for the treatment of unilateral N1b PTC patients.
Humans ; Robotic Surgical Procedures/methods* ; Axilla/surgery* ; Male ; Female ; Operative Time ; Middle Aged ; Adult ; Treatment Outcome ; Postoperative Complications

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.

Objective To compare the safety,effectiveness and affordability of robotic-assisted thoracic surgery and video-assisted thoracic surgery in the treatment of malignant pulmonary tumors,and provide ref-erences for the management of selection of different surgical strategies for malignant pulmonary tumors in hospitals and medical insurance departments.Methods The medical records homepages and information sys-tem data of patients with malignant pulmonary tumors who underwent major thoracic surgery in this hospital and discharged from January 1 to December 31,2022 were obtained.The patients were divided into the robotic-assistedthoracic surgery group and video-assisted thoracic surgery group according to the surgical methodolo-gies.After performing propensity score matching (PSM),no statistically significant difference was observed in baseline data between the two groups (117 cases in each group).Then the indicators of safety,effectiveness and affordability were compared between the two groups.Results Concerning the safety,the postoperative in-cision infection rate in the robotic-assisted thoracic surgery group was significantly lower than that in the vide-o-assisted thoracic surgery group (P<0.05),and the amount of intraoperative blood loss and postoperative complication rate were not significantly different between the two groups (P>0.05).Regarding the effective-ness,the average surgical duration in the robotic-assisted thoracic surgery group was appreciably shorter than that in the video-assisted thoracic surgery group (P<0.05),no patient in the two groups was converted to open thoracotomy,and there was no statistically significant difference in the average length of hospital stay and postoperative hospital stay between the two groups (P>0.05).With regard to the affordability,the aver-age inpatient expenditure per case and average daily inpatient expenditure per case in the robotic-assisted tho-racic surgery group were significantly higher than those in the video-assisted thoracic surgery group (P<0.05),and there were disparities in the cost structure between the two procedures.The medical cost,adminis-tration cost and consumables cost in the robotic-assisted thoracic surgery group were significantly higher than those in the video-assisted thoracic surgery group (P<0.05).The cost of medical technology in the robotic-assisted thoracic surgery group was significantly lower than that in the video-assisted thoracic surgery group (P<0.05).Conclusion Physicians should comprehensively consider the clinical efficacy and cost burden of patients when selecting the robotic-assisted thoracic surgery or the video-assisted thoracic surgery,and the monitoring and evaluation of the utilization of clinical robotic-assisted thoracic surgery should be strength-ened.

Objective:To compare the similarities and differences of macrophage activation syndrome（MAS）combined with systemic juvenile idiopathic arthritis（sJIA）versus with juvenile onset systemic lupus erythematosus（JSLE）.Methods:The clinical data of 48 children with MAS admitted to the Department of Nephrology and Immunology in Children's Hospital of Hebei Province from May 2015 to January 2023 were retrospectively analyzed. The patients were divided into sJIA-MAS and JSLE-MAS group，and the clinical manifestations，laboratory indicators and treatment of the two groups were compared.Results:Among the 48 children（14 males and 34 females）with MAS，the average age of onset was 9.5（3.0，11.8）years. There were 28 cases（11males and 17 females）of sJIA-MAS and 20 cases（3 males and 17 females）of JSLE- MAS. All the 48 children with MAS had fever and hyperferinemia，and the fever with sJIA-MAS was mostly continued fever or remittent fever. Respiratory tract infection was the most common trigger in sJIA-MAS［15 cases（53.6%）］，and disease activity was the most common trigger in JSLE-MAS［13 cases（65.0%）］.Additionally，viral infections（EB virus and cytomegalovirus）were also one of the triggers in MAS［sJIA：7 cases（25%），JSLE：4 cases（20%）］.Compared with JSLE-MAS，the number of days with fever［15.0（12.0，21.0）days vs. 6.0（4.0，9.5）days， Z=-3.812， P=0.001］and the length of hospital stay［29.0（26.3，39.8）days vs.26.0（19.3，30.8）days， Z=-1.958， P=0.049］were longer in sJIA. Compared with JSLE-MAS，ALT［（685.32±561.67）U/L vs.（139.61±124.44）U/L， t=4.973， P=0.001］，AST［784.00（235.25，1 251.25）U/L vs.189.50（53.25，374.08）U/L， Z=-3.283， P=0.001］，CRP［11.48（3.56，28.89）mg/L vs.1.91（0.53，8.98）mg/L， Z=-3.200， P=0.001］，ferritin［32 167.0（12 384.8，65 963.8）μg/L vs.2 003.5（922.5，11 430.0）μg/L， Z=-4.130， P=0.001］，ferritin max/ESR min［1 353.35（355.75，4 342.53）vs.91.92（34.94，291.53）， Z=-4.120， P=0.001］were higher in sJIA.The decrease of CRP was greater in sJIA［80.04（45.64，143.71）mg/L vs.10.20（6.27，25.64）mg/L， Z=-4.433， P=0.001］.Compared with sJIA-MAS，peripheral white blood cell counting［4.05（2.90，7.73）×10 9/L vs.1.56（1.15，3.47）×10 9/L， Z=-3.577， P=0.001］and platelet counting［（162.68±92.19）×10 9/L vs.（110.10±72.99）×10 9/L， t=2.118， P=0.040］were lower in JSLE-MAS. Kidney involvement was more common in JSLE-MAS［10 cases（50%）vs.0 cases（0%）， χ 2=17.684， P=0.001］.There was no significant difference in the incidence of sJIA-MAS and JSLE-MAS meeting the criteria of hemophagocytic lymphohistiocytosis［6 cases（21.4%）vs.5 cases（25.0%）， χ 2=0.084， P=0.772］. Conclusion:Compared with JSLE-MAS，sJIA-MAS is more dangerous and difficult to control，while JSLE-MAS involves more organs，among which the blood system and kidney are more common.

Objective:To investigate the effect of regional leptomeningeal collateral circulation (rLMC) score based on CT angiography (CTA) and onset-to-reperfusion time (OTR) on the outcome after endovascular treatment (EVT) in patients with anterior circulation acute large vessel occlusive stroke (ACA-LVOS).Methods:Patients with ACA-LVOS underwent EVT in the Department of Neurology, the Affiliated Hospital of Yangzhou University from July 2017 to July 2023 were included retrospectively. The rLMC score 0-10 was defined as poor collateral circulation, and 11-20 were defined as good collateral circulation. At 90 days after EVT, the modified Rankin Scale (mRS) was used to evaluate the outcome. A score of 0-2 was defined as a good outcome and 3-6 were defined as a poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of the outcome after EVT. Results:A total of 144 patients with ACA-LVOS underwent EVT were enrolled, including 78 males (54.2%), median aged 73 years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 16, the median baseline Alberta Stroke Program Early CT Score (ASPECTS) was 9, and the median OTR was 330.5 minutes. Eighty patients (55.6%) had good collateral circulation, 63 (43.8%) had poor outcome, including 13 deaths. Univariate analysis showed that there were significant differences in hypertension, previous stroke history, smoking, triglycerides, baseline NIHSS score, baseline ASPECTS, OTR, and collateral circulation status between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that good collateral circulation (odds ratio [ OR] 0.223, 95% confidence interval [ CI] 0.077-0.643; P=0.005) was an independent predictor of good outcome. In the poor collateral circulation group, longer OTR was an independent predictor of poor outcome ( OR 1.020, 95% CI 1.008-1.032; P=0.001). In the good collateral circulation group, longer OTR was not an independent risk factor for poor outcome ( OR 1.005, 95% CI 1.000-1.010; P=0.062). Conclusion:rLMC score based on CTA and OTR are the independent predictors of the outcome after EVT in patients with ACA-LVOS.

Objective To analyze the distribution of carbapenem-resistant strains and the transmission mode of resistance genes in the bacteria strains from urinary system of the individuals outside hospitals,and further explore the impacts of the antibiotics with different antibacterial mechanisms on the conjugation transfer of resistant plasmids.Methods The imipenem-resistant strains from 991 non-re-petitive urine samples of healthy individuals were screened for determining the carbapenem-resistance genotypes.Using the multilocus sequence typing(MLST)method,the main carbapenem-resistant strains were classified to determine the phylogenetic relationship be-tween different sequence types(STs)and reveal the transmission mode of resistance genes in the individuals outside hospitals.The conjugation experiment was used to analyze the effects of different sub-inhibitory concentrations of ampicillin,ciprofloxacin,and genta-micin on the conjugation efficiency of resistant plasmids in the bacteria of donor and/or recipient at different times.Results A total of 18 non-repetitive carbapenem-resistant strains(1.82％,18/991)were detected in healthy individuals outside hospitals,among which Escherichia coli(E.coli)(44.44％,8/18)was the main strain with main genotype being blaKPC-2(7/8).MLST showed that the 7 strains of E.coli with blaKPC-2 genotype belonged to ST-10,ST-101,ST-131,ST-405,ST-410,ST-1193,and ST-2562,respectively.Homologous clustering analysis showed that the type of the 7 E.coli strains exhibited high diversity.The range of joint efficiency was(1.59±0.20)× 10-4 to(4.01±1.31)× 10-4.The highest conjugation efficiency was observed in the donor bacteria treated with 1/8 of MIC of antibiotics for 9 hours,and the conjugation efficiency most significantly increased compared to the group without antibiotic treat-ment.Three antibiotics with different mechanisms of action could all improve conjugation efficiency,among which ampicillin exhibited the most significant improvement.Conclusion In this study,the genotype of carbapenem-resistant Escherichia coli(CREC)was mainly blaKPC-2 with a main mode of horizontal transmission.Antibiotics with sub-inhibitory concentrations could promote the conjugation transfer of the resistant plasmid.There may be significant differences in the effects of antibiotics with different mechanisms of action and different antibiotic stress conditions on the conjugation efficiency.