OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective:To evaluate the clinical utility of machine learning model based radiomics in predicting high-risk molecular subtypes of lower-grade gliomas(LrGGs).Methods:This was a cross-sectional study. A total of 287 patients diagnosed with LrGGs in the First Hospital of Shanxi Medical University, Shanxi Provincial People′s Hospital, and the Third Hospital of Shanxi Medical University from January 2011 to September 2023 were retrospectively collected, including 166 males and 121 females; 114 cases of high-risk molecular subtypes and 173 cases of non-high-risk molecular subtypes. All patients were divided into 201 cases in the training set and 86 cases in the test set according to 7∶3 in simple randomized grouping method. All patients underwent contrast-enhanced T 1WI (CE-T 1WI) and T 2-weighted fluid-attenuated inversion recovery sequence imaging (T 2-FLAIR), and the imaging features of high-risk and non-high-risk molecular subtypes were analyzed. Analysis of variance, recursive feature elimination, and Kruskal-Wallis were used for radiomics feature screening, and a support vector machine (SVM) classifier was used to construct a radiomics-based classifier model. Univariate and multivariate logistic regression were used to analyze clinical variables independently influencing high-risk molecular subtypes of LrGGs to construct a clinical model; a combined model was developed by integrating radiomics labels and clinical variables. Receiver operating characteristic curve and area under the curve (AUC), calibration curve, and decision curve were used to compare the predictive performance of different models. Results:The patient′s age ( OR=1.042, 95% CI 1.018-1.068, P=0.001), pathological grade ( OR=2.270, 95% CI 1.212-4.311, P=0.011), MGMT methylation status ( OR=0.456, 95% CI 0.238-0.866, P=0.017), and ependymal involvement ( OR=7.335, 95% CI 2.929-18.370, P<0.001) were independent influencing factors for the high-risk molecular subtype of LrGGs, and a clinical model was developed based on these factors. An SVM model was constructed based on 12 radiomics features (3 radiomics features based on CE-T 1WI and 9 radiomics features based on T 2-FLAIR). The radiomics score of the probability output by the SVM model was combined with age, pathological grade, MGMT methylation status, and ependymal involvement to develop a combined model. The AUC values of the SVM model for predicting the high-risk molecular subtype of LrGGs were 0.824 and 0.859 in the training set and test set, respectively; the AUC values of the clinical model in the training set and test set were 0.759 and 0.721, respectively; and the AUC values of the combined model in the training set and test set were 0.823 and 0.815, respectively. The combined model had a high clinical net benefit. Conclusion:The machine learning MRI radiomics model can preoperatively predict high risk molecular subtypes of LGGrs, assist in individualized treatment decisions.

Objective:To construct a stable oral squamous cell carinoma(OSCC)cell line overexpressing miR-181a-5p,and to ob-serve the effects of miR-181a-5p on the biological behavior of the cells.Methods:miR-181a-5p lentivirus and the control virus vec-tor were respectively constructed and respectively transfected into OSCC CAL-27 cells.The stablely transfected cells(OE)and con-trol cells(NC)were screened out by purinomycin.The fluorescence of the cells was observed by laser confocal microscopy.The ex-pression of miR-181a-5p and Bcl-2 was detected by qRT-PCR and the expression of target protein Bcl-2 was detected by Western blot.The invasion,migration and proliferation ability of the cells were detected by cell scratch,Transwell assay and clonal formation assay.qRT-PCR was used to detect the expression of the related genes of cell invasion and migration.Results:It was found that the expression level of miR-181a-5p in OE cells was significantly higher than that in NC and untransfected control cells(P＜0.01).The expression of Bcl-2 in OE cells was significantly decreased.The invasion,migration and proliferation of OE cells were decreased.In ad-dition,the expression levels of MMP2,MMP9,Vimentin and Ki67 in OE cells were decreased,while E-cadherin was increased(P＜0.01).Conclusion:Overexpression of miR-181a-5p can significantly inhibit the proliferation,invasion and migration OSCC cells.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Objective:To construct a stable oral squamous cell carinoma(OSCC)cell line overexpressing miR-181a-5p,and to ob-serve the effects of miR-181a-5p on the biological behavior of the cells.Methods:miR-181a-5p lentivirus and the control virus vec-tor were respectively constructed and respectively transfected into OSCC CAL-27 cells.The stablely transfected cells(OE)and con-trol cells(NC)were screened out by purinomycin.The fluorescence of the cells was observed by laser confocal microscopy.The ex-pression of miR-181a-5p and Bcl-2 was detected by qRT-PCR and the expression of target protein Bcl-2 was detected by Western blot.The invasion,migration and proliferation ability of the cells were detected by cell scratch,Transwell assay and clonal formation assay.qRT-PCR was used to detect the expression of the related genes of cell invasion and migration.Results:It was found that the expression level of miR-181a-5p in OE cells was significantly higher than that in NC and untransfected control cells(P＜0.01).The expression of Bcl-2 in OE cells was significantly decreased.The invasion,migration and proliferation of OE cells were decreased.In ad-dition,the expression levels of MMP2,MMP9,Vimentin and Ki67 in OE cells were decreased,while E-cadherin was increased(P＜0.01).Conclusion:Overexpression of miR-181a-5p can significantly inhibit the proliferation,invasion and migration OSCC cells.

BACKGROUND:The timing of tourniquet application in traditional total knee arthroplasty has been clearly reported.With the continuous refinement of joint-related techniques,the timing of tourniquet application in total knee arthroplasty under navigation system has rarely been reported.OBJECTIVE:To evaluate the effect of total knee arthroplasty with Brainlab navigation system using full-course and half-course tourniquets.METHODS:From January to December 2022,data of 145 eligible patients who underwent total knee arthroplasty under navigation system in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province were retrospectively analyzed and they were divided into the full course group(n=71)and the half course group(n=74)according to the timing of tourniquet release.General data,perioperative conditions,postoperative swelling around the knee joint,postoperative lower extremity deep venous thrombosis,visual analog scale score,Hospital for Special Surgery knee score,and forgotten joint score were collected to assess knee joint function and statistically compared.RESULTS AND CONCLUSION:(1)The operation time of the full course group was shorter than that of the half course group,the incidence of lower extremity deep venous thrombosis was higher,and the postoperative knee joint swelling was more severe(P＜0.001,P=0.027,P＜0.001).The intraoperative blood loss of the full course group was less than that of the half course group(P＜0.001),and the occult blood loss of the full course group was more than that of the half course group(P＜0.001),with statistically significant differences.(2)At 1 week after surgery,the visual analog scale score in the full course group was significantly higher than that in the half course group(P＜0.001).(3)There was no significant difference in forgotten joint score between the two groups at 3,6 months and 1 year after surgery(P＞0.05).(4)It is indicated that in patients undergoing total knee arthroplasty using a navigation system,the half-course group has less occult blood loss,lower postoperative swelling and incidence of postoperative lower extremity deep venous thrombosis,and faster recovery of knee joint function.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.

BACKGROUND:The timing of tourniquet application in traditional total knee arthroplasty has been clearly reported.With the continuous refinement of joint-related techniques,the timing of tourniquet application in total knee arthroplasty under navigation system has rarely been reported.OBJECTIVE:To evaluate the effect of total knee arthroplasty with Brainlab navigation system using full-course and half-course tourniquets.METHODS:From January to December 2022,data of 145 eligible patients who underwent total knee arthroplasty under navigation system in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province were retrospectively analyzed and they were divided into the full course group(n=71)and the half course group(n=74)according to the timing of tourniquet release.General data,perioperative conditions,postoperative swelling around the knee joint,postoperative lower extremity deep venous thrombosis,visual analog scale score,Hospital for Special Surgery knee score,and forgotten joint score were collected to assess knee joint function and statistically compared.RESULTS AND CONCLUSION:(1)The operation time of the full course group was shorter than that of the half course group,the incidence of lower extremity deep venous thrombosis was higher,and the postoperative knee joint swelling was more severe(P＜0.001,P=0.027,P＜0.001).The intraoperative blood loss of the full course group was less than that of the half course group(P＜0.001),and the occult blood loss of the full course group was more than that of the half course group(P＜0.001),with statistically significant differences.(2)At 1 week after surgery,the visual analog scale score in the full course group was significantly higher than that in the half course group(P＜0.001).(3)There was no significant difference in forgotten joint score between the two groups at 3,6 months and 1 year after surgery(P＞0.05).(4)It is indicated that in patients undergoing total knee arthroplasty using a navigation system,the half-course group has less occult blood loss,lower postoperative swelling and incidence of postoperative lower extremity deep venous thrombosis,and faster recovery of knee joint function.