Autosomal dominant polycystic kidney disease （ADPKD） is a systemic hereditary renal disorder and can affect multiple organs， and congenital hepatic fibrosis is one of the manifestations of liver involvement and is an important complication of ADPKD. Symptomatic management is currently the main treatment method for this disease， and disease-specific drugs such as tolvaptan have limited indications and cannot correct the underlying genetic defect. This article reports a case of ADPKD with congenital hepatic fibrosis， and sirolimus was identified as the individualized treatment regimen based on peripheral blood functional genomic analysis and drug sensitivity prediction platform. The patient achieved significant improvements in symptoms and quality of life after treatment， with a stable kidney volume. This case shows that functional genomics has a potential value in guiding individualized treatment of rare genetic disorders， which provides new treatment ideas and practice paths for similar patients.

ObjectiveTo investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsAnimal experiments were conducted with 50 female SD rats， which were randomized into a sham operation group （10 rats） and a modeling group （40 rats）. An autologous endometrial transplantation method was used for the modeling of EMs. The 36 successfully modeled rats were randomly allocated into four groups （n=9 each）： The model group， the low-dose （7.87 g·kg^-1） Luoshi Neiyi prescription group， the high-dose （15.74 g·kg^-1） Luoshi Neiyi prescription group， and the dienogest （0.20 mg·kg^-1） group. The physiological status and ectopic lesion volumes of rats in each group were observed. Hematoxylin-eosin （HE） staining was used to observe the morphology of the eutopic endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory factors including interleukin-1β （IL-1β） and prostaglandin E₂ （PGE₂） in the serum of EMs rats. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor A （VEGFA） in the eutopic endometrial tissue. Western blot was adopted to determine the protein levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated nuclear factor-κB （p-NF-κB）/NF-κB， MMP-9， and VEGFA in the eutopic endometrial tissue. In the cell experiments， the cell-counting kit-8 （CCK-8） assay was employed to screen the optimal concentration of Luoshi Neiyi prescription-containing serum， and a scratch assay was performed to assess the migration ability of iheESCs cells. Interventions with Luoshi Neiyi prescription-containing serum， resatorvid （TAK-242， a TLR4 inhibitor）， and lipopolysaccharides （LPS， a TLR4 agonist） were conducted， and Western blot was used to detect the expression of proteins related to the TLR4/NF-κB signaling pathway. ResultsThis experiment successfully replicated 36 EMs rat models. Compared with the sham operation group， the model group exhibited visible ectopic lesions on the abdominal wall and an increase in the writhing response score （P<0.01）. Furthermore， HE staining revealed the model group exhibited a thickened eutopic epithelium， stromal cell disarrangement， and evident infiltration of inflammatory cells. In addition， the model group showed elevated serum levels of IL-1β and PGE₂ （P<0.05， P<0.01）， increased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.01）， and up-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. Compared with the model group， all treatment groups exhibited a reduction in the ectopic lesion volume （P<0.01）. Furthermore， the writhing response scores were decreased in the high-dose Luoshi Neiyi prescription group and the dienogest group （P<0.05， P<0.01）. The pathological state of the ectopic endometrial tissue was alleviated to varying degrees in the treatment groups. Low-dose Luoshi Neiyi prescription reduced serum PGE₂ levels， and high-dose Luoshi Neiyi prescription and dienogest decreased serum IL-1β and PGE₂ levels in EMs rats （P<0.05， P<0.01）. The treatment groups showed decreased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01） and down-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. The cell experiments showed that 5%， 10%， and 20% Luoshi Neiyi prescription-containing sera significantly reduced the viability and inhibited the migration of iheESCs. Compared with the control group， 5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups and the TAK-242 group showed reduced protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA （P<0.01）. Compared with the control group， the LPS group showed increased expression of the above proteins （P<0.01）. Compared with the LPS group， the LPS+5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups showed reduced expression of the above proteins （P<0.05， P<0.01）. ConclusionLuoshi Neiyi prescription may modulate the TLR4/NF-κB signaling pathway to reduce the inflammatory response and histopathological damage in the eutopic endometrium and suppress the adhesive， invasive， and angiogenic biological processes in the ectopic endometrial tissue， thereby exerting its therapeutic effect on EMs.

Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.

OBJECTIVE To investigate the regulatory effect of Rasfonin on SOS1(Son of Seven-less,one of the major guanylate exchange factors)expressions and the underlying mechanism.METHODS① Human cancer cells MCF-7(breast cancer cells,KRASWT wild-type),Calu-1(non-small cell lung cancer,KRASG12C mutation),and UM-UC-3(bladder metastatic cell carcinoma,KRASG12C mutation)were divided into the control group and Rasfonin(1,5,10 and 15 μmol·L-1)treated groups.CCK-8 assay was used to observe the effects of Rasfonin on the proliferation of MCF-7,Calu-1,and UM-UC-3 cells after 24 h of Rasfonin treatment.In addition,these cells were divided into the control group,EGF stimulation group(EGF 50 μg·L-1,stimulated for 5 min),and Rasfonin treated groups(pretreated with 5 and 10 μmol·L-1 Rasfonin before 5 min EGF stimulation).Quantitative real-time PCR(real-time fluores-cence PCR)and Western blotting were employed to identify the expression levels of SOS1 mRNA and protein in MCF-7,Calu-1 and UM-UC-3 cells.② The co-expression systems of KRAS and SOS1 were established by transfecting plasmids(KRAS-NC,KRASWT,KRASG12C and SOS1)into 293T cells that were divided into the control group and Rasfonin(1,5 and 10 μmol·L-1)treated group.The dual luciferase reporter gene assay was used to evaluate the effects of Rasfonin on activities of the SOS1 promoter.Moreover,293T cells were divided into the EGF stimulation group(EGF 50 μg·L-1,stimulated for 5 min)and Rasfonin treated groups(12 h of treatment with 10 μmol·L-1 Rasfonin before 5 min EGF stimula-tion).Western blotting was performed to determine the role of KRASG12C protein in the inhibition of Rasfonin on SOS1 expression.RESULTS ① Compared with the control group,Rasfonin inhibited the prolifera-tion of Calu-1 and UM-UC-3 cells at concentrations of 5,10 and 15 μmol·L-1(IC50 was 8.22 and 4.94 μmol·L-1).But for MCF-7 cells,only 15 μmol·L-1 Rasfonin could decrease their viability(IC50 was 45.15 μmol·L-1).Compared with the EGF stimulation group,mRNA expressions of SOS1 were increased after Rasfonin treatment of 1 h.mRNA expressions of SOS1 were decreased in Calu-1 cells after 3 h of Rasfonin treatment.These changes also occurred after Rasfonin treatment of 3 h and 6 h in UM-UC-3 cells.Further-more,Rasfonin treatment did not influence SOS1 protein expressions in MCF-7 cells,but can signifi-cantly inhibit SOS1 expression of in UM-UC-3 and Calu-1 cells.② Rasfonin had no significant effects on the activity of SOS1 promoter and its protein level in 293T cells when only SOS1 was expressed,but significantly inhibited its activity and its protein level when SOS1 was co-expressed with KRAS protein.CONCLUSION One of the anti-tumor mechanisms of Rasfonin is to inhibit the activity of SOS1 promoter to decrease mRNA and protein expressions of SOS1 through KRASG12C protein.

OBJECTIVE To investigate the regulatory effect of Rasfonin on SOS1(Son of Seven-less,one of the major guanylate exchange factors)expressions and the underlying mechanism.METHODS① Human cancer cells MCF-7(breast cancer cells,KRASWT wild-type),Calu-1(non-small cell lung cancer,KRASG12C mutation),and UM-UC-3(bladder metastatic cell carcinoma,KRASG12C mutation)were divided into the control group and Rasfonin(1,5,10 and 15 μmol·L-1)treated groups.CCK-8 assay was used to observe the effects of Rasfonin on the proliferation of MCF-7,Calu-1,and UM-UC-3 cells after 24 h of Rasfonin treatment.In addition,these cells were divided into the control group,EGF stimulation group(EGF 50 μg·L-1,stimulated for 5 min),and Rasfonin treated groups(pretreated with 5 and 10 μmol·L-1 Rasfonin before 5 min EGF stimulation).Quantitative real-time PCR(real-time fluores-cence PCR)and Western blotting were employed to identify the expression levels of SOS1 mRNA and protein in MCF-7,Calu-1 and UM-UC-3 cells.② The co-expression systems of KRAS and SOS1 were established by transfecting plasmids(KRAS-NC,KRASWT,KRASG12C and SOS1)into 293T cells that were divided into the control group and Rasfonin(1,5 and 10 μmol·L-1)treated group.The dual luciferase reporter gene assay was used to evaluate the effects of Rasfonin on activities of the SOS1 promoter.Moreover,293T cells were divided into the EGF stimulation group(EGF 50 μg·L-1,stimulated for 5 min)and Rasfonin treated groups(12 h of treatment with 10 μmol·L-1 Rasfonin before 5 min EGF stimula-tion).Western blotting was performed to determine the role of KRASG12C protein in the inhibition of Rasfonin on SOS1 expression.RESULTS ① Compared with the control group,Rasfonin inhibited the prolifera-tion of Calu-1 and UM-UC-3 cells at concentrations of 5,10 and 15 μmol·L-1(IC50 was 8.22 and 4.94 μmol·L-1).But for MCF-7 cells,only 15 μmol·L-1 Rasfonin could decrease their viability(IC50 was 45.15 μmol·L-1).Compared with the EGF stimulation group,mRNA expressions of SOS1 were increased after Rasfonin treatment of 1 h.mRNA expressions of SOS1 were decreased in Calu-1 cells after 3 h of Rasfonin treatment.These changes also occurred after Rasfonin treatment of 3 h and 6 h in UM-UC-3 cells.Further-more,Rasfonin treatment did not influence SOS1 protein expressions in MCF-7 cells,but can signifi-cantly inhibit SOS1 expression of in UM-UC-3 and Calu-1 cells.② Rasfonin had no significant effects on the activity of SOS1 promoter and its protein level in 293T cells when only SOS1 was expressed,but significantly inhibited its activity and its protein level when SOS1 was co-expressed with KRAS protein.CONCLUSION One of the anti-tumor mechanisms of Rasfonin is to inhibit the activity of SOS1 promoter to decrease mRNA and protein expressions of SOS1 through KRASG12C protein.

Objective:To investigate the effectiveness and safety of ultrasound-guided endovascular therapy for autogenous arteriovenous fistula (AVF) thrombosis.Methods:It was a single-center retrospective cohort study. Data of patients undergoing ultrasound-guided intravascular therapy due to AVF thrombosis in the First Hospital of Hebei Medical University from August 2018 to June 2021 were analyzed. According to different surgical procedures, the patients were divided into two groups. Patients treated with percutaneous transluminal angioplasty (PTA) + drilling thrombectomy were in group A, and patients treated with PTA only were in group B. After 1 year of follow-up, the surgical technique success rate, primary patency rate, secondary patency rate and complications were compared between the two groups.Results:A total of 152 patients were enrolled, including 74 in group A and 78 in group B. There were no significant differences in gender, age, proportion of patients with diabetes and hypertension, and thrombosis time of AVF between the two groups (all P>0.05). Compared with group B, the diameter and length of thrombus in group A were larger [13.0(9.0, 16.0) mm vs. 6.0(5.0, 6.5) mm, Z=-9.362, P<0.001; 12(8, 15) cm vs. 3(3, 4) cm, Z=-10.061, P<0.001], and the establishment time of AVF was longer [5(2, 7) years vs. 2(1, 5) years, Z=-2.698, P=0.007]. Among the overall patients, the success rate of surgery was 96.7% (147/152), and the success rate of surgery was 95.9% (71/74) in group A and 97.4% (76/78) in group B respectively, with no statistical difference ( χ2=0.004, P=0.952). Kaplan-Meier survival analysis showed that, overall, the primary patency rate at 3rd, 6th and 12th month after operation was 87.1%, 71.4% and 56.6%, and the secondary patency rate was 97.1%, 96.4% and 94.1%, respectively. The primary patency rate of group A at 3rd, 6th and 12th month was 82.4%, 66.7% and 53.6%, and the secondary patency rate was 95.7%, 94.2% and 89.7%, respectively. The primary patency rate of group B at 3rd, 6th and 12th month was 91.5%, 73.2% and 59.7%, and the secondary patency rate was 98.6%, 98.6% and 98.5%, respectively. There was no significant difference in the primary and secondary patency rate between group A and group B at 3rd, 6th and 12th month (all P>0.05). The duration of operation in group A was longer than that in group B [2.0(1.9, 2.0) h vs. 2.0(1.0, 2.0) h, Z=-5.181, P<0.001], but no serious complications occurred in both groups. Conclusion:The two surgical methods are effective, safe and reliable in the treatment of AVF thrombosis, and have high clinical application value.

Objective:To study the distribution and changes of dopamine transporter (DAT) in guinea pig eyes under different light patterns.Methods:Thirty-six 3-week-old white ordinary-grade guinea pigs were randomly selected and divided into groups of 10 000 lx, 5 000 lx, and 500 lx, with 12 guinea pigs in each group exposed to strong light, medium strong light, and normal light, respectively.Each group was randomly divided into 3 subgroups, with 4 guinea pigs in each subgroup.The 3 subgroups of 500 lx group received light exposure for 5, 20, and 40 minutes, respectively.The 3 subgroups of 5 000 lx group received light exposure for 2, 4, and 40 minutes, respectively.The 3 subgroups of 10 000 lx group received light exposure for 2, 5, and 20 minutes, respectively.After light treatment, each group of guinea pigs was injected with 99mTc-TRODAT-1 for SPECT DAT imaging, and image data were collected by Micro-SPECT.The region of interest (ROI) of guinea pig retinas was analyzed using Micro-CT software.The counts of ROI were expressed as Sum, which reflected the relative distribution or density of DAT.The DAT density between experimental and control eyes of guinea pigs after light exposure, the differences in DAT density between guinea pig eyes under different light intensities, the differences in DAT density between guinea pig eyes after different light durations, and the cumulative and interactive effects of light intensity and light duration on DAT aggregation in guinea pigs were compared.Another 3 guinea pigs were selected, and after light exposure, the 3 guinea pigs' eyes underwent continuous image acquisition for 6 hours at 20-minute intervals, and 18 images per guinea pig were acquired to analyze the trend of DAT density in guinea pig eyes over time.This study was approved by the Ethics Committee of Shanghai General Hospital (No.2020SQ196). Results:The DAT density (Sum value) of experimental eyes at 500, 5 000, and 10 000 lx were 5 598.97±3 159.38, 8 636.78±2 503.16, and 7 407.39±2 053.41, respectively, significantly higher than 4 388.89±2 902.90, 5 981.92±3 057.44, and 5 091.32±2 039.36 of control eyes ( t=5.31, 4.69, 11.80; all at P<0.001). At 500 lx, there was a statistically significant difference in DAT density between the experimental and control eyes of guinea pigs at different light exposure durations ( F=14.01, P<0.01), while no significant difference was found at other light intensities at different light exposure durations (both at P>0.05). When the light exposure time was 5 minutes, the difference in DAT density between the experimental and control eyes of guinea pigs was significantly greater in the 10 000 lx group than in the 500 lx group ( t=-13.22, P<0.001). There was no statistically significant difference between different groups at other light exposure durations (all at P>0.05). No cumulative or interactive effects of light intensity and light duration were found on the differences in DAT density (all at P>0.05). Continuous scanning after illumination showed that DAT density in guinea pig retinas first increased to a peak over time and then gradually returned to normal values. Conclusions:Light, even under moderate or normal light levels, can cause an increase in the secretion of DAT in the retina and stimulate the production of DAT.Light intensity and duration have no cumulative or interactive effects on the distribution and density of retinal DAT.

Artificial intelligence(AI)is a strategic technology leading a new round of technological revolution and industrial transformation.It is forward-looking,important and necessary to apply AI technology to the medical field.At present,the research and development of intelligent data monitoring equipment,intelligent medical instruments,disease auxiliary diagnosis and treatment platforms,auxiliary diagnosis and treatment integrated systems and other technologies have been widely carried out,and related products are gradually used in auxiliary medical prevention,diagnosis,treatment,and rehabilitation.Based on the recent development of AI technology in the medical field,the application status of intelligent auxiliary diagnosis and treatment equipment in three fields of intelligent monitoring equipment,virtual psychological diagnosis and treatment platforms,and traditional Chinese medicine auxiliary diagnosis and treatment instruments was summarized to provide reference for AI to connect disease and health,and realize the intersection of AI and medical disciplines.

Objective To investigate the effects of metoprolol succinate sustained-release tablets on acute phase ventricular pacing threshold and intracardiac electrical signal amplitude in a leadless pacemaker(Micra).Methods A total of 100 patients implanted with a leadless pacemaker were selected and divided into a study group(n=43)and a control group(n=57)according to whether oral metoprolol succinate sustained release tablets were postoperatively administered.The patients with underlying diseases including hypertension,coronary heart disease,or diabetes were treated with antihypertensive drugs,hypoglycemic drugs,or anti-platelet aggregation drugs.The study group received oral metoprolol succinate sustained release tablets within one to three days after implantation of a leadless pacemaker;while the control group received no metoprolol succinate sustained release tablets.Changes in ventricular pacing threshold and intracardiac electrical signal amplitude were observed in two groups one week,one month and three months after implantation.Results No serious complications occurred in the patients at the three time points after implantation.Ventricular pacing thresholds were stable in both groups,and there was no statistical significance between the two groups as compared with the same time period(P>0.05).In terms of amplitude of ventricular intracardiac electrical signal,theamplitude of ventricular R-wave did not differ significantly between the two groups at the three time points after implantation(P>0.05).Conclusions Oral administration of metoprolol succinate sustained release tablets had no significant effects on acute phase ventricular pacing threshold and intracardiac electrical signal amplitude in a leadless pacemaker(Micra).

Objective To investigate the correlation between abdominal obesity and autoimmune thyroid disease in the view point of helper T cells and cytokines.Methods Clinical and laboratory data were collected from 108 pa-tients with Hashimoto's thyroiditis(HT)plus abdominal obesity and 122 patients of Hashimoto's thyroiditis without abdominal obesity who visited the People's Hospital of Xinjiang Uygur Autonomous Region and also from the control population.Abdominal circumference was measured,and patients in the HT patients were grouped according to whether they were abdominally obese or not.The thyroglobulin antibody(TgAb)and thyroid peroxidase antibody(TPOAb)were detected,and the ratio of helper T cells and related cytokines were detected by flow cytometry and enzyme-linked immunosorbent assay.Results The abdominal circumference of the TgAb-positive group was higher than that of the TgAb-negative group(P＜0.05).Correlation analysis suggested that abdominal circumference was significantly and positively correlated with TgAb and IL-4 but negatively correlated with Th1.After correcting for gender and age,and abdominal obesity and IL-4 were risk factors for TgAb antibody positivity OR=3.080(95％CI:1.022-9.284)and OR=1.296(95％CI:1.022-9.284),both with P＜0.05.Conclusions Abdominal obesity may be an influential factor in TgAb antibody positivity,with larger abdominal circumference having higher TgAb antibody titers,lower Th1 levels,and higher IL-4 levels.Visceral adiposity may exacerbate autoimmune dam-age of thyroid tissue by disruption of helper T cell pathway.