Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy

Advanced hepatocellular carcinoma(HCC)is a severe malignancy that poses a serious threat to human health.Owing to challenges in early diagnosis,most patients lose the opportunity for radical treatment when diagnosed.Nonetheless,recent advancements in cancer immunotherapy provide new directions for the treatment of HCC.For instance,monoclonal antibodies against immune check-point inhibitors(ICIs)such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC.However,tumor cells can evade the immune system through various mechanisms.With the rapid development of genetic engineering and molecular biology,various new immunotherapies have been used to treat HCC,including ICIs,chimeric antigen receptor T cells,engineered cytokines,and certain cancer vaccines.This review summarizes the current status,research progress,and future directions of different immunotherapy strategies in the treatment of HCC.

Fracture geometry and breakdown pressure of radial borehole fracturing in multiple layers

Radial borehole fracturing that combines radial boreholes with hydraulic fracturing is anticipated to improve the output of tight oil and gas reservoirs.This paper aims to investigate fracture propagation and pressure characteristics of radial borehole fracturing in multiple layers.A series of laboratory experiments with artificial rock samples(395 mm×395 mm×395 mm)was conducted using a true triaxial fracturing device.Three crucial factors corresponding to the vertical distance of adjacent radial borehole layers(vertical distance),the azimuth and diameter of the radial borehole are examined.Experimental results show that radial borehole fracturing in multiple layers generates diverse fracture geometries.Four types of fractures are identified based on the connectivity between hydraulic fractures and radial boreholes.The vertical distance significantly influences fracture propagation perpendicular to the radial borehole axis.An increase in the vertical distance impedes fracture connection across multiple radial borehole layers and reduces the fracture propagation distance along the radial borehole axis.The azimuth also influences fracture propagation along the radial borehole axis.Increasing the azimuth reduces the guiding ability of radial boreholes,which makes the fracture quickly curve to the maximum horizontal stress direction.The breakdown pressure correlates with diverse fracture geometries observed.When the fractures connect multi-layer radial boreholes,increasing the vertical distance decreases the breakdown pressure.Decreasing the azimuth and increasing the diameter also decrease the breakdown pressure.The extrusion force exists between the adjacent fractures generated in radial boreholes in multiple rows,which plays a crucial role in enhancing the guiding ability of radial boreholes and results in higher breakdown pressure.The research provides valuable theoretical insights for the field application of radial borehole fracturing technology in tight oil and gas reservoirs.

Clinicopathological features,psychological status,and prognosis of 33 patients with occult breast cancer

BACKGROUND Occult breast cancer(OBC)has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast cancer.Due to the small number of cases and limited clinical experience,treatments vary greatly around the world and no standardized treatment has yet been established.AIM To investigate the clinicopathological features,psychological status and prognostic features of patients with OBC.METHODS The clinicopathological data of 33 OBC patients diagnosed and treated in the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from November 2015 to November 2022 were retrospectively analyzed.The psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression Scale.Patients’emotions,stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule,the Chinese Perceived Stress Scale,and the Connor-Davidson Resilience Scale(CD-RISC),respectively.Patient survival was calculated using the Kaplan-Meier method,and survival curves were plotted for analysis with the log-rank test.Univariate and multivariate survival analyses were performed using the Cox regression model.RESULTS The 33 OBC patients included 32 females and 1 male.Of the 33 patients,30(91%)had axillary tumors,3(9%)had a neck mass as the primary symptom;18(54.5%)had estrogen receptor-positive tumors,17(51.5%)had progesterone receptor-positive tumors,and 18(54.5%)had Her-2-positive tumors;24(72.7%)received surgical treatment,including 18 patients who underwent modified radical mastectomy,1 patient who underwent breast-conserving surgery plus axillary lymph node dissection(ALND),and 5 patients who underwent ALND alone;12 patients received preoperative neoadjuvant therapy.All 30 patients developed anxiety and depression,with low positive affect scores and high negative affect scores,accompanied by a high stress level and poor psychological resilience.There were no differences in the psychological status of patients according to age,body mass index,or menopausal status.The overall survival and disease-free survival(DFS)of all the patients were 83.3%and 55.7%,respectively.Univariate analysis demonstrated that the initial tumor site(P=0.021)and node stage(P=0.020)were factors that may affect patient prognosis.The 5-year DFS rate of OBC patients who received radiotherapy was greater(P<0.001),while the use of different surgical methods(P=0.687)had no statistically significant effect on patient outcomes.Multivariate analysis revealed that radiotherapy(P=0.031)was an independent prognostic factor.Receiving radiotherapy had a significant effect on the CD-RISC score(P=0.02).CONCLUSION OBC is a rare breast disease whose diagnosis and treatment are currently controversial.There was no significant difference in the efficacy of other less invasive surgical procedures compared to those of modified radical mastectomy.In addition,radiotherapy can significantly improve patient outcomes.We should pay attention to the psychological state of patients while they receive antitumor therapy.

An Innovative Three-Dimensional Method for Identifying a Proper Femoral Intramedullary Entry Point in Total Knee Arthroplasty

Background： Identification of the proper femoral intramedullary （IM） access point is an important determinant of final implant position in IM-guided total knee arthroplasty （TKA）. The aim of this study was to identify the optimal entry point in Chinese participants using a new three-dimensional method. Methods： A series of computed tomography scans of 44 femurs in Chinese participants from October 2014 to October 2015 were imported into Mimics 17.0 software to identify the optimal entry point. The apex of the intercondylar notch （AIN） was used as the reference bony anatomical landmark to identify the proper entry point to insert the IM rod. The statistical significance was calculated on the basis of a 5% level （P 〈 0.05） using the Student＇s t-test. Results： For the males, the average ideal entry point was 1.49 mm medial and 13.39 mm anterior to the AIN. The values were 1.77 mm medial and 15.29 mm anterior to the AIN in females. A significant difference was present between males and females （13.39 ±2.46 mm vs. 15.29 ± 3.44 mm, t = 2.124, P = 0.040）. When using the recommended location as the entry point for the IM rod, the mean potential error differed significantly from the femoral trochlear groove （the potential error of IM in males in coronal plane： 0.93~ ±0.24~ vs. 1.27~ ± 0.32~, t = -4.166, P 〈 0.001; the potential error of 1M in males in sagittal plane： 1.40° ± 0.42° vs. 2.79° ± 0.70°, t = -7.155, P 〈 0.001; the potential error oflM in females in coronal plane： 0.73° ± 0.28° vs. 1.15° ± 0.35°, t = -3.940, P 〈 0.001 ： and the potential error of 1M in females in sagittal plane： 1.48° ±0.47° vs. 2.76° ± 0.83°, t = -5.574, P 〈 0.001 ）. A significant difference was present between the recommended point and the point 10 mm anterior to the origin of the posterior cruciate ligament （the potential error of IM in males in coronal plane： 0.93° ± 0.24° vs. 1.53° ±0.43°, t = -5.948, P 〈 0.001 ; the potential error of IM in males in sagittal plane： 1.40° ± 0.42° vs. 2.15°± 0.75°, t = -3.152, P = 0.003; the potential error of IM in females in coronal plane： 0.73° ± 0.28° vs. 1.28° ±0.42°, t = -4.632, P 〈 0.001; and the potential error oflM in females in sagittal plane： 1.48°± 0.47° vs. 2.40°± 0.93°, t = -3.763, P = 0.001）. Conclusions： The technique described here is an innovative method for swift, easy, and accurate access to the medullary canal during TKA, and it can optimize the position and orientation of the prosthetic components in knee arthroplasty.

Glycosaminoglycan Content of the Lateral Compartment Cartilage in Knees Conforming to the Indications for Oxford Medial Unicompartmental Knee Arthroplasty

Background： The quality of the lateral compartment cartilage is important to preoperative evaluation and prognostic prediction of unicompartmental knee arthroplasty （UKA）. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage （dGEMRIC） enables noninvasive assessment of glycosaminoglycan （GAG） content in cartilage. This study aimed to determine the GAG content of the lateral compartment cartilage in knees scheduled to undergo Oxford medial UKA. Methods： From December 2016 to May 2017, twenty patients （20 osteoarthritic knees） conforming to the indications fbr Oxford medial UKA were included as the osteoarthritis （OA） group, and 20 healthy volunteers （20 knees） paired by sex, knee side, age （±3 years）, and body mass index （BMI） （i3 kg/m2） were included as the control group. The GAG contents of the weight-bearing femoral cartilage （wbFC）, the posterior non-weight-bearing femoral cartilage （pFC）, the lateral femoral cartilage （FC）, and tibial cartilage （TC） were detected using dGEMRIC. The dGEMRIC indices （T1Gd） were calculated in the middle three consecutive slices of the lateral compartment. Paired t-tests were used to compare the T1Gd in each region of interest between the OA group and control group. Results： The average age and BMI in the two groups were similar. In the OA group, TIGd of FC and TC was 386.7 ± 50.7 ms and 429.6 ± 59.9 ins, respectively. In the control group, T1Gd of FC and TC was 397.5 ± 52.3 ms and 448.6 ±62.5 ms, respectively. The respective T 1Gd ofwbFC and pFC was 380.0 ± 47.8 ms and 391.0 ± 66.3 ms in the OA group and 400.3 ± 51.5 ms and 393.6 ± 57.9 ms in the control group. Although the T 1Gd ofwbFC and TC tended to be lower in the OA group than the control group, there was no significant difference between groups in the TIGd in any of the analyzed cartilage regions （P value ofwbFC, pFC, FC, and TC was 0.236, 0.857, 0.465, and 0.324, respectively）. Conclusions： The GAG content of the lateral compartment cartilage in knees confonning to indications for Oxford medial UKA is similar with those of age- and BMl-matched participants without OA.