Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Ultrasonography（US）is the first-line imaging modality recommended by domestic and international guidelines for liver tumor screening，owing to its non-invasive nature，real-time dynamic imaging capability，cost-effectiveness，and operational convenience. In recent years，the integration of artificial intelligence（AI）and medical imaging has emerged as a major research focus. By leveraging large-scale data training，AI models can automatically recognize and analyze input imaging data and generate predictive outcomes. Notably，AI-based ultrasound imaging technology has achieved breakthrough advancements in the diagnosis and treatment of liver tumors. These innovations significantly improve diagnostic accuracy，optimize treatment strategies，predict disease progression and prognosis，and monitor therapeutic response. This article provides a comprehensive review of the latest applications and research progress of AI in ultrasound-based diagnosis and treatment of liver tumors.

The profound integration of novel qualitative productive forces throughout the entire process of diagnosing and treating gastrointestinal cancer has catalyzed innovative advance-ments in surgical techniques and postoperative rehabilitation. In the field of minimally invasive resection, technological innovations, from laparoscopic surgery to robot-assisted surgical systems that transcend traditional visual and operational limitations, and further to the integration of artificial intelligence and 5G technologies that overcome spatiotemporal barriers for real-time decision-making and telemedicine, have significantly enhanced the precision and safety of gastrointestinal tumor surgery. Concurrently, the development of innovative medical devices plays a pivotal role in improving perioperative and postoperative rehabilitation efficiency. Functional device design focuses on addressing the holistic needs of patients throughout their clinical journey, systematically resolving efficiency and safety bottlenecks inherent in conventional diagnostic and therapeutic approaches. Technological progress has further enabled non-invasive, convenient remote health management for patients. Novel qualitative productive forces not only redefine surgical paradigms but also deliver efficient, safe, and patient-centered diagnostic and therapeutic experiences through comprehensive innovation across all treatment phases. This evolution marks a critical breakthrough in modern medicine's transition toward intelligence and systematization, heralding a new era of intelligent healthcare delivery.

Background and Aims:Biliary tract cancers(BTCs)are highly aggressive malignancies with dismal prognosis,for which radical resection remains the only potentially curative treatment.Laparoscopic surgery has demonstrated superiority over open surgery in perioperative safety and recovery,yet it is technically limited in complex operations.Robot-assisted laparoscopy,with its high-definition three-dimensional vision and enhanced instrument dexterity,may overcome these limitations.However,comparative evidence balancing baseline differences between laparoscopic and robot-assisted laparoscopic radical resections for BTCs is still lacking.This study aimed to evaluate and compare their short-term safety using propensity score matching(PSM).Methods:A total of 151 patients with biliary tract cancers who underwent radical resection were retrospectively enrolled from the Chinese Biliary Tract Tumor Collaborative Group database,including 128 in the laparoscopic group and 23 in the robotic-assisted laparoscopic group.To balance baseline differences,an initial 1∶1 PSM was performed,yielding 19 laparoscopic and 19 robotic cases.Subsequently,using the robotic group as the reference,a 1∶2 PSM was conducted,resulting in 36 laparoscopic and 18 robotic cases.Primary outcomes(conversion to open surgery,ICU admission,and postoperative complications)and secondary outcomes(operative time,intraoperative blood loss,transfusion,postoperative hospital stay,reoperation,readmission,and hospitalization costs)were compared between the two groups.Multivariate regression analyses were performed to explore factors associated with conversion to open surgery and postoperative hospital stay.Results:After matching,baseline characteristics were well balanced between groups.For primary outcomes,the conversion rate to open surgery was significantly higher in the laparoscopic group than in the robotic group(41.7％vs.0,P=0.001),while ICU admission,overall postoperative complications,and Clavien-Dindo graded complications showed no significant differences(all P＞0.05).For secondary outcomes,the postoperative hospital stay was significantly more extended in the laparoscopic group compared with the robotic group(18.5 d vs.8.0 d,P=0.005),whereas operative time,intraoperative blood loss,transfusion,reoperation,readmission,and hospitalization costs were comparable(all P＞0.05).Logistic regression for conversion did not identify statistically significant predictors,but moderately differentiated tumors,elevated preoperative CA19-9,and higher harvested lymph node counts showed trends toward increased risk.Multivariate linear regression revealed that robotic-assisted surgery was an independent factor for reduced postoperative hospital stay(P=0.024),while preoperative total bilirubin(P=0.020),longer operative time(P=0.000),postoperative complications(P=0.006),and reoperation(P=0.005)were found to be associated with a prolonged hospital stay.Conclusion:Robot-assisted laparoscopic radical resection for BTCs is not inferior to conventional laparoscopy in short-term safety and may further reduce conversion rates and hospital stay.Its technical advantages may be particularly valuable in anatomically complex or challenging cases.Nonetheless,cost-effectiveness and resource allocation should be considered for wider adoption.

Objective To investigate the effects of different anesthesia depths on stress states and inflammatory mediators in patients undergoing video-assisted thoracoscopic lobectomy.Methods A total of 89 lung cancer patients who underwent video-assisted thoracoscopic lobectomy were selected as study subjects.Based on intraoperative bispectral index(BIS)range,the patients were divided into deep anesthesia group(BIS of 40 to＜50,n=45)and shallow anesthesia group(BIS of 50 to＜60,n=44).Vital signs(mean arterial pressure,heart rate and blood oxygen saturation),anesthesia re-covery time,extubation time,dosage of vasoactive drugs,postoperative pain intensity[Visual Ana-logue Scale(VAS)],postoperative analgesic dosage,perioperative stress state[prostaglandin E2(PGE2),nerve growth factor(NGF)and substance P(SP)],levels of inflammatory mediators[neuron-specific enolase(NSE),tumor necrosis factor-α(TNF-α)and S100β protein]at different time points(before anesthesia induction,immediately after intubation,before lesion resection and at the end of surgery)and the incidence of anesthesia-related adverse reactions were compared between the two groups.Results Before lesion resection and at the end of surgery,the mean arterial pressure and heart rate in the deep anesthesia group were significantly lower than those in the shallow anesthe-sia group(P＜0.05).The anesthesia recovery time and extubation time in the deep anesthesia group were significantly longer than those in the shallow anesthesia group(P＜0.05).At the end of surgery and on postoperative day one,the levels of PGE2,NGF and SP in the deep anesthesia group were significantly lower than those in the shallow anesthesia group,while the levels f NSE,TNF-α and S100β protein were significantly higher than those in the shallow anesthesia group(P＜0.05).There were no significant differences in the dosage of vasoactive drugs,VAS scores,sufentanil dos-age and the incidence of anesthesia-related adverse reactions between thetwo groups(P＞0.05).Conclusion During one-lung ventilation in patients undergoing video-assisted thoracoscopic surgery lobectomy,deep anesthesia can effectively control surgical stress and maintain stability of intraopera-tive hemodynamics,but it is associated with delayed postoperative awakening and more pronounced inflammatory response.Shallow anesthesia results in faster postoperative awakening and lower levels of inflammatory mediators,but it is associated with more significant intraoperative stress response and unstable hemodynamics.

Objective To evaluate the efficacy of elastic appliances in the early correction of Class Ⅱmalocclusions in the replacement dentition.Methods A total of 15 children aged 7-9 years who were admit-ted to the Affiliated Stomatology Hospital of Southwest Medical University from June 2018 to August 2023 were selected as the observation group,and 15 children who were consulted but not treated in the hospital dur-ing the same period were selected as the control group.The changes of bone tissue,dental and alveolar tissue,soft tissue and occlusal relationship before and after treatment were evaluated in the two groups.In addition,X-ray images of the observation group were collected every 8 to 10 months for the whole process dynamic mo-nitoring.Results Before treatment,there was no significant difference in all indexes between the two groups(P＞0.05).After treatment,there were statistical significances in the upper and lower alveolar base Angle(ANB),mandibular branch length(GO-CO),mandibular height(ANS-Me),mandibular position(S-GO),up-per central incisor inclination(U1-NA Angle),upper central incisor inclination convexity(U1-NA),lower central incisor process distance(L1-APo),the Z Angle and FH-N'Pg'Angle of soft tissue between the two groups(P＜0.05).After treatment,the covering OB and covering OJ in the observation group were lower than those in the control group,and the proportion of ClassⅠ patients in molar relationship was higher than that in the control group,with statistical significance(P＜0.05).After 3-4 years of treatment,ANB gradual-ly decreased,and the anterior-basilar plane-mandibular plane Angle(SN-MP)remained basically stable,and had a slight decreasing trend in the later period.The U1-NA Angle and the lower central incisor inclination(L1-NB Angle)were close to the normal mean during the whole treatment.Conclusion Using elastic appli-ances to treat patients with early replacement Class Ⅱ malocclusion,after 3-4 years monitoring and guid-ance,it can effectively improve the molar relationship,promote forward jaw growth,and create a harmonious and aesthetically pleasing facial soft tissue.

Objective To screen long non-coding RNA(lncRNA)associated with lymph node metasta-sis in papillary thyroid carcinoma(PTC)and verify its function in vitro,so as to provide a theoretical basis for elucidating the molecular mechanism of lymph node metastasis in PTC.Methods lncRNA+mRNA microar-ray was used to detect the differential expression of lncRNA and mRNA in PTC cancer tissues with and with-out lymph node metastasis.Real time fluorescence quantitative PCR(qPCR)verified target differential lncR-NAs.Lentivirus was used as vector to construct high and low lncRNA expression PTC cell lines.Cell counting kit-8(CCK-8),cell scratches assay,Transwell assay,cell clone formation assay were used to detect the effects of target lncRNA on proliferation,migration,invasion,clonal formation of PTC cells.Results Compared with 5 cases of PTC tissues without lymph node metastasis,gene chips detected 119 lncRNA and 53 mRNA expres-sion levels upregulated,while 263 lncRNA and 198 mRNA expression levels down regulated in 5 cases of PTC tissues with lymph node metastasis.Furthermore,21 lncRNAs were selected for validation in the original 10 PTC samples,and the results showed that,compared with PTC tissues without lymph node metastasis,lncR-NAs FLJ20444,DPP10-AS1 and ENST00000567197 were highly expressed in PTC tissues with lymph node metastasis,while uc021thd.1,LNC00944,ENST00000429730 and BLNK were lowly expressed(P＜0.05).In addition,qPCR results of another 30 fresh PTC tissues showed that compared with PTC tissues without lymph node metastasis,DPP10-AS1 was highly expressed and LNC00944 was lowly expressed in PTC tissues with lymph node metastasis(P＜0.05).Cell function experiments showed that the proliferation,migration,invasion,and colony formation abilities of PTC cells in the DPP10-AS1 high expression group were higher than those in the DPP10-AS1 low expression group,and the differences were statistically significant(P＜0.05).Conclusion lncRNA DPP10-AS1 may play a role in PTC metastasis through certain signaling pathways.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans ; Liver/drug effects* ; Animals ; Chemical and Drug Induced Liver Injury/metabolism* ; Membrane Transport Proteins/metabolism* ; Biological Transport ; Liver Diseases/drug therapy* ; Pharmaceutical Preparations/metabolism*

Ultrasonography（US）is the first-line imaging modality recommended by domestic and international guidelines for liver tumor screening，owing to its non-invasive nature，real-time dynamic imaging capability，cost-effectiveness，and operational convenience. In recent years，the integration of artificial intelligence（AI）and medical imaging has emerged as a major research focus. By leveraging large-scale data training，AI models can automatically recognize and analyze input imaging data and generate predictive outcomes. Notably，AI-based ultrasound imaging technology has achieved breakthrough advancements in the diagnosis and treatment of liver tumors. These innovations significantly improve diagnostic accuracy，optimize treatment strategies，predict disease progression and prognosis，and monitor therapeutic response. This article provides a comprehensive review of the latest applications and research progress of AI in ultrasound-based diagnosis and treatment of liver tumors.