Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Objective To explore the optimal ratio of Baitong decoction based on efficacy,clarify its spectrum-effect relationship,and identify its potential quality markers.Methods An ulcerative colitis(UC)model in mice was established using dextran sulfate sodium.The efficacy of Baitong decoction with varying drug ratios was assessed by evaluating the apparent score,pathological score and inflammatory factor changes of UC in each group of experimental animals.The fingerprints of Baitong decoction with different ratios were established by high performance liquid chromatography(HPLC),and the relationship between the content of each substance and its efficacy was analyzed by partial least squares regression to determine the potential quality markers of Baitong decoction.Results Baitong decoction was most effective in relieving ulcerative colitis when the mass ratio of Fuzi,Ganjiang and Congbai was 1∶2∶2.The fingerprinting identified 14 common peaks across 7 ratios,with 9 peaks were found to be associated with the remission of ulcerative colitis by partial least squares regression analysis.Conclusion The optimal ratio of Fuzi,Ganjiang and Congbai for treating UC is 1∶2∶2.The spectrum-effect relationship analysis suggested that the quality markers of Baitong decoction may be the substances represented by peak 2(benzoylaconine),3,5,6,8(mesaconine),9(aconitine),10(hypaconitine),13(10-gingerol)and 14.

Objective To study the effects of different implantation angles of bi-leaflet mechanical heart valve(BMHV)on swirling flow in the aorta.Methods Based on the aortic CT images of a healthy volunteer,the effects of 4 different valve implantation angles(0°,45°,90° and 135°)on the aortic swirling flow under constant flow conditions were studied by computational simulation.Results The implantation of BMHV could seriously interfere with the aortic swirling flow,affecting the structure and helicity distributions of the swirling flow in ascending aorta,thus resulting in disturbed blood flows distal to the valve.The 135° implantation angle caused the most disruption to the swirling flow,leading to the largest areas of reversed swirling flows,while the 0° and 45° implantation angles caused relatively smaller damage to the swirling flow.The areas with low wall shear stress(<0.5 Pa)were the smallest when the implantation angle of BMHV was 0°.Conclusions At the implantation angle of 0°-45°,the disruption of BMHV to the swirling flow in ascending aorta was relatively small.Therefore,for different patients,the selection of implantation angle should be individualized according to the spatial geometry of their aorta(including the aortic sinuses),and the implantation angle can be determined between 0°-45°.

Objective:To explore the clinical value of aspirin combined with atorvastatin in the prevention of new onset atrial fibrillation after off-pump coronary artery bypass grafting (OPCABG).Methods:208 patients with coronary artery bypass grafting in our hospital from June 2019 to June 2021 were selected as the research subjects and divided by a random number table method into groups. The control group (104 cases) was treated with aspirin before operation, and the observation group (104 cases) was treated with aspirin and atorvastatin before operation. ECG monitoring was carried out continuously for 7 days of patients in the two groups, and the occurrence and duration of AF were recorded. The clinical therapeutic efficacy, incidence and adverse reactions of AF, left atrial diameter and high-sensitivity C-reactive protein (hs-CRP) level were observed before and after treatment.Results:The incidence of AF in the observation group was significantly lower than that in the control group, the difference was statistically significant ( P<0.05). There was no statistical significant difference in the starting time of AF between the two groups after operation ( P>0.05). The duration of AF in the observation group was better than that in the control group, the difference was statistically significant ( P<0.05). Before treatment, there was no statistical significant difference in left atrial diameter and hs-CRP level between the two groups ( P>0.05). After treatment, the left atrial diameter in the observation group returned to that before treatment, and there was no statistical significant difference in the same group ( P>0.05). The left atrial diameter in the control group was higher than that before treatment, and there was statistical significant difference in the same group ( P<0.05). The level of hs-CRP was lower than that in the control group, the difference was statistically significant ( P<0.05). There were no adverse reactions in both groups. Conclusion:Aspirin combined with atorvastatin has a significant effect in preventing new onset AF after OPCABG. It can reduce the incidence of postoperative AF, shorten the duration of AF, effectively control the inner diameter of left atrium, reduce the degree of postoperative inflammatory reaction, and has no adverse effects. It is worthy of clinical application.

Objective:To describe a distal anastomosis support (DAS) technique, and retrospectively investigate the effect of DAS on the mid-term graft patency of patient with small posterior descending artery.Methods:Between January and December 2016, 100 patients with triple-vessel disease and small PDA who continuously underwent off-pump coronary artery bypass grafting (OPCABG) (OPCABG group, n=50) and OPCABG with DAS for anastomosis of PDA grafted by saphenous vein (SVG) (OPCABG+ DAS group, n=50) were evaluated retrospectively. The dynamic changes of electrocardiogram and TnI level were observed within 48h after the surgery. All patients came back to follow-up visit 6th, 12th, 24th and 36th postoperative month. The primary endpoint was the graft failure (FitzGibbon B or O) of SVG-PDA on the follow-up CTA.Results:There was no death during the operation. There was no acute inferior wall myocardial infarction confirmed by electrocardiogram. Peak TnI within 48h of surgery was 0.74(0.98)ng/ml vs. 0.92(1.29)ng/ml, P>0.05, and the number of patients with peak TnI≥70×ULN was 3(6%, 3/50) vs.5(10%, 5/50), P>0.05. There was no postoperative death, and all the patients were discharged 5-15 days postoperatively. We found significantly improved cumulative graft patency in OPCABG+ DAS group at 36 months after operation [85.7%(42/49) vs. 68.0%(34/50), P<0.05). In multivariate logistic regression analysis, PDA with atherosclerotic lesions ( OR=6.513, 95% CI: 1.279-33.180, P=0.024), and peak TnI≥70×ULN within 48 h of surgery ( OR=5.948, 95% CI: 1.128-31.368, P=0.036) were independent predictors of graft failure, whereas concomitant DAS ( OR=0.222, 95% CI: 0.069-0.713, P=0.011) was significant protective factor. Conclusion:Concomitant DAS conferred superior mid-term patency of SVG-PDA in patients with small PDA. Adding the DAS procedure to OPCABG may be a promising surgical option for small PDA with atherosclerotic lesions.

Objective:To explore the correlation between serum high mobility group protein B1 (HMGB1) and severity of coronary artery disease.Methods:From January 2018 to March 2019, 170 patients who underwent coronary angiography and were definitely diagnosed with coronary heart disease in Beijing Anzhen Hospital were divided into single-vessel lesion group(65 cases), double-vessel lesion group(55 cases) and three-vessel lesion group(50 cases) according to the results of coronary angiography.Sixty healthy persons in the same period were set as the control group.The serum levels of HMGB1, endothelin-1, C-reaction protein (CRP), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) were detected, and the severity of coronary artery disease was evaluated according to Gensini score standard.Results:The serum HMGB1 of patients with single vessel disease was (7.35±0.75) μg/L, that of double vessel disease group was (11.56±1.16) μg/L, that of three vessel disease group was (14.36±1.46) μg/L, and that of control group was (3.22±1.52) μg/L.The difference between the two groups was statistically significant ( F=14.235, P<0.001). The serum endothelin-1 in single vessel disease group was (198.56±19.86) ng/L, that in double vessel disease group was (226.54±22.64) ng / L, that in three vessel disease group was (435.65±43.95) ng/L, and that in control group was (120.47±13.27) ng/L.The difference between the two groups was statistically significant ( F=16.337, P<0.001). The serum CRP of patients with single vessel disease was (6.21±0.61) ng/L, that of double vessel disease group was (8.54±0.84) ng/L, that of three vessel disease group was (11.36±1.16) ng/L, and that of control group was (3.39±1.56) ng/L.The difference between the two groups was statistically significant ( F=15.206, P<0.001). Serum LDL-C was (3.23±0.33) mmol/L in single vessel disease group, 4.12±0.42 mmol/L in double vessel disease group, (6.23±0.63) mmol/L in three vessel disease group and (2.25±1.45) mmol/L in control group.The difference between the two groups was statistically significant ( F=22.017, P<0.001). Serum HDL-C was (4.02±0.42) mmol/L in single vessel disease group, (2.35±0.25) mmol/L in double vessel disease group, (1.79±0.29) mmol/L in three vessel disease group and (4.60±1.69) mmol/L in control group.The difference between the two groups was statistically significant ( F=18.564, P<0.001). The Gensini score of single vessel disease group was (10.36±2.26), that of double vessel disease group was (16.74±1.04) and that of three vessel disease group was (23.36±2.36). The difference between the two groups was statistically significant ( F=23.014, P<0.001). The levels of HMGB1, endothelin-1, CRP and LDL-C in patients with coronary heart disease were significantly higher than those in the control group, while the levels of HDL-C were significantly lower than those in the control group (all P<0.05). The higher the number of diseased vessels, the higher the levels of HMGB1, endothelin-1, CRP, LDL-C and Gensini score, the lower the level of HDL-C.Multiple linear regression analysis showed that HMGB1, endothelin-1, CRP and LDL-C were risk factors of Gensini score (standard coefficient was 0.480, 0.087, 0.173, 0.197, t=8.351, 9.047, 12.476, 11.692, all P<0.01); HDL-C level was a protective factor of Gensini score (standard coefficient -0.352, t value was 16.582, P<0.001). Pearson linear correlation analysis showed that serum HMGB1 level was positively correlated with endothelin-1, CRP and LDL-C ( r=0.536, 0.659, 0.724, all P<0.05), and negatively correlated with HDL-C ( r=-0.669, P<0.05). Conclusion:There are obvious inflammatory reaction and lipid metabolism disorder in patients with coronary heart disease.The level of HMGB1 in peripheral blood is closely related to the severity of coronary artery disease.

Objective To investigate the clinical effect of minimally invasive single locking plate combined with multiplanar screw internal fixation on pilon fracture of distal tibia. Methods A retrospective case control study was conducted to analyze the clinical data of 51 patients with pilon fracture involving distal tibial articular surface admitted to 81th Group Military Hospital of the Army from January 2013 to August 2017. Among the patients, 20 patients including 15 males and five females, aged (37. 5 ± 9. 9)years were treated with closed traction reduction or open joint reduction through minimally invasive incision and single main locking plate combined with multiplanar screw placement ( study group) . There were 13 patients with type II and seven patients with type III according to Ru edi-Allgwer classification of fracture. In addition, 31 patients were treated with open reduction and multi-plate internal fixation (control group), including 25 males and six females, aged (43. 4 ± 11. 3) years. There were 20 patients with type II and 11 with type III according to Ru edi-Allgwer classification. The operation time, fracture healing time, postoperative complications were compared between the two groups. Burwell-Charnley imaging evaluation criteria were used to assess the quality of fracture reduction. At the last follow-up, ankle function was assessed by the American Orthopedic Foot and Ankle Society ( AOFAS) ankle-hind foot functional score. Results All 51 patients were followed up for 6-24 months, with an average of 16 months. The operation time was (82. 5 ± 19. 2)minutes in the study group and (127. 7 ± 40. 8)minutes in the control group (P<0. 05). The fracture healing time was (10. 8 ± 1. 6)weeks in the study group and (11.0 ±1.5) weeks in the control group (P>0.05). Local skin necrosis (not above the plate) occurred in two patients in the study group and in three patients in the control group, with the wounds being healed within 3 months after dressing change and vacuum sealing drainage ( VSD) . In the control group, one patient had severe infection and recovered after treatment of steel plate removal, debridement and irrigation, and external fixator fixation. Three patients in the control group had skin necrosis resulting in plate exposure, who received transferred skin flaps to cover the wound. The incidence of postoperative complications were 10％ (2/20) and 23％ in the study group and the control group, respectively (7/31) (P >0. 05), with the incidence of severe complications for 0 and 13％(4/31)(P<0. 05), respectively. According to Burwell-Charnley imaging evaluation criteria, 18 patients obtained anatomical reduction in the study group, one had unsatisfactory reduction and one had poor reduction, with satisfaction rate of 90％. In the control group, 29 patients obtained anatomical reduction and two had unsatisfactory reduction, with satisfaction rate of 94％ (P>0. 05). At the last follow-up, AOFAS ankle-hind foot function scores were excellent in 12 patients, good in five patients, fair in two patients and poor in one patient in the study group with excellence rate of 85％, while the scores were excellent in 20 patients, good in six patients, fair in three patients and poor in two patients in the control group, with excellence rate of 84％ (P>0. 05). Conclusion For pilon fracture of distal tibia, both minimally invasive single locking plate combined with multi-plate screw internal fixation and open reduction combined with multi-plate internal fixation have good reduction effect and satisfactory recovery of ankle function, but the former can significantly shorten the operation time and reduce the incidence of serious complications after operation.

Objective: To explore the clinical effect of minimally invasive treatment of C type pilon fracture with single main plate combined with multiple planar screws for supporting fixation. Methods: From January 2013 to March 2017, data of 22 patients treated by minimally invasive treatment with single main plate combined with multiple planar screws for supporting fixa-tion were retrospectively analyzed. There were 17 males and 5 females, aged from 23 to 69 years (average, 51.2 years). All cases were closed fractures involving fibula including weight hitting (5 cases), traffic accident (7 cases) and fall injury (10 cases). There were 3 cases of 43-C1 type, 11 cases of 43-C2 type and 8 cases of 43-C3 type according to AO/OTA classification. According to the Rüedi-Allgöwer classification, there were 5 cases of type Ⅱ and 17 cases of type Ⅲ. Complications were recorded postopera-tively and the articular surface reduction was evaluated using the Burwell-Charnley score. At the last follow-up, Tornetta’s pilon fracture clinical treatment outcome criteria was used to evaluate ankle joint function. Results: All the patients were followed up for 13 to 25 months (average, 17.3 months). There were 20 cases of anatomical reduction, 1 case of fair reduction and 1 case of poor reduction according to the Burwell-Charnley score. All the 22 patients were healed with healing time of 3 to 6 months (aver-age, 4.8 months). The efficacy was evaluated according to the evaluation criteria of the clinical treatment results of pilon fracture by Tornetta: excellent in 8 cases, good in 10 cases, fair in 3 cases, and poor in 1 case. The excellent and good rate was 81.8% (18/22) . All patients had no complications such as wound edge blistering, skin necrosis and infection. Among them, 1 case of internal fixa-tion rejection occurred, and the incision was well healed after removal of the internal fixation after 3 months. Conclusion Mini-mally invasive treatment of C type pilon fracture with single main plate combined with multiple planar screws for supporting fixa-tion not only provides a better anatomical reduction of the articular surface, but also effectively reduces or even avoids incision complications. The long-term clinical results are satisfactory.

Objective To explore the efficacy of temporary titanium plate screwing for positional maintenance in reduction and internal fixation for displaced acetabular fractures.Methods A retrospective study was conducted of the 28 patients (28 hips) with displaced acetabular fracture who had been treated by open reduction and internal fixation from October 2013 to March 2016.They were 20 males and 8 females,aged from 24 to 68 years (average,42.3 years).The time from injury to surgery ranged from 7 to 21 days(average,14.5 days).According to the Letournel-Judet classification,there were 2 posterior column fractures,4 transverse fractures,5 posterior column plus posterior wall fractures,6 transverse plus posterior wall fractures,2 T-shaped fractures,3 anterior and posterior transverse fractures and 6 double column fractures.The posterior acetabular approach or combined anterior and posterior approach was used.In all the patients temporary titanium plate screwing was conducted to fix one side of the fracture so as to facilitate accomplishment of open reduction and internal fixation without losing the indirect anatomic reduction of the intraarticular fracture.After the open reduction and internal fixation was accomplished,the temporary screw fixation was removed in 26 patients but retained in 2 patients as needed.The reduction quality,complications and outcomes at the final follow-ups were recorded.Results All the 28 patients were followed up for 10 to 36 months (mean,15.6 months).By the Matta criteria,anatomical reduction was achieved in 26 cases,unsatisfactory reduction in one and poor reduction in one,yielding an anatomic reduction rate of 92.9％.By the improved Mere d'Aubigne & Postel criteria,the clinical outcomes at the final follow-up were excellent in 27 cases and good in one,yielding a good to excellent rate of 100％.Postoperatively,heterotopic ossification of different severities occurred in 11 cases but did not affect their joint function;transient paralysis of the sciatic nerve was reported in 6 cases but recovered 3 months after surgery.No complications like avascular necrosis of the femoral head or walking pain were observed during follow-ups.Conclusion Temporary fixation with titanium plate screws during open reduction and internal fixation for displaced acetabular fractures can effectively improve the reduction and fixation of the articular surface,leading to satisfactory short-term clinical outcomes.

Objective To analyse the safety and effectiveness of microvascular decompression completely under endoscopy-assisted or microscope-assisted (EVD or MYD) for trigeminal neuralgia.Methods A retrospective analysis was conducted for patients who underwent completely EVD or MVD from January,2014 to September,2016.The clinical data,operative data and results were analyzed.The patients were divided into two groups according to the techniques.The all procedure of distinguishing the responsible vessels and decompressing which was done completely under endoscope were EVD group (n=141).Those being done completely under microscope were MVD group (n=125).All operations were done by same operator and same approach.Results The intracranial nerve symptoms disappeared in 137 cases(97.2％) in EVD group and 120 cases(96.0％) in MVD group.There were no severe operative complications such as intracranial infection,facial paralysis,intracranial hematoma and death.Mild hearing loss was happened in 2 cases (1.42％) in EVD group and 5 cases (4.00％) in MVD group;facial hypoesthesia,5 cases (3.54％) in EVD group,8 cases(6.40％) in MVD group;Transient ataxia,3 cases (2.13％) in EVD group,5 cases(4.00％) in MVD group;cerebrospinal fluid leakage,3 cases(2.13％) in EVD group,3 cases(2.40％) in MVD group;Oral herpes,23 cases (22.5％) in EVD group,27 cases(24.3％) in MVD group.There was no statistically significant differences in curative effect and complications between two groups (P＞ 0.05).Conclusion There is no difference in curative effect and complications between the two methods of completely EVD and MVD.