Purpose For patients with advanced or unresectable hepatocellular carcinoma (HCC), safe and effective therapies are urgently needed to improve their long-term prognosis. Although the guidelines recommend first-line treatments such as sorafenib, lenvatinib, and atezolizumab in combination with bevacizumab (T+A) and second-line treatments such as regorafenib, the efficacy comparison between drugs is lacking, that is, a treatment is not recommended as the optimal or alternative choice for a specific patient population. Therefore, we will conduct a high-quality network meta-analysis based on Phase III randomized controlled trials (RCTs) to systematically evaluate and compare overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and serious adverse events (SAE) of different treatment protocols in the context of first-line and second-line therapies, which are critical for clinical decision making and prognostic improvement in advanced HCC patients. Methods The studies of interest were Phase III RCTs evaluating the efficacy or safety of first- or second-line therapies in patients with unresectable or advanced HCC. Literature published in English from the four databases of PubMed, Embase, Cochrane Library, and Web of Science was comprehensively searched from the inception to May 23, 2022. Outcomes of interest included OS, PFS, ORR, and SAE. A league table was developed to show the results of the comparison between different treatments. A histogram of cumulative probability was drawn to discuss the ranking probability of treatments based on different outcomes. The effectiveness and safety of various treatments were comprehensively considered and the two-dimensional diagram was plotted to guide clinical practice. The Gemtc package in R Studio was used for network meta-analysis in a Bayesian framework. Results The results showed that HAIC-FO was superior to T+A regimen, regardless of OS, PFS or ORR. TACE combined with lenvatinib performed better than T+A in PFS, and ORR. In addition to the T+A regimen, Sintilimab combined with IBI305 and camrelizumab combined with apatinib were also associated with longer OS, PFS, and ORR, and their SAE incidence was not higher than that of T+A, especially for camrelizumab combined with apatinib, its safety was better than that of T+A regimen. There were no new treatments or combinations that were more effective than regorafenib. It was important to note that for PFS, the efficacy of apatinib and cabozantinib was not statistically different from that of regorafenib, so these two treatments could be used as alternative treatment options in cases where regorafenib was not tolerated or treatment failed. Conclusions We conducted a network meta-analysis to evaluate the efficacy and safety of multiple treatment modalities by integrating the results of direct and indirect comparisons. This study included high-quality multicenter Phase III RCTs, collated and summarized all treatments involved in advanced or unresectable HCC in first-line and second-line settings, and compared with T+A and regorafenib, respectively, and ranked based on efficacy and safety to support clinical decision making.

Introduction and Objectives: With rising prevalence of pre-sarcopenia in metabolic dysfunction-associated steatotic liver disease (MASLD), this study aimed to develop and validate machine learning-based model to identify pre-sarcopenia in MASLD population. Materials and Methods: A total of 571 MASLD subjects were screened from the National Health and Nutrition Examination Survey 2017–2018. This cohort was randomly divided into training set and internal testing set with a ratio of 7:3. Sixty-six MASLD subjects were collected from our institution as external validation set. Four binary classifiers, including Random Forest (RF), support vector machine, and extreme gradient boosting and logistic regression, were fitted to identify pre-sarcopenia. The best-performing model was further validated in external validation set. Model performance was assessed in terms of discrimination and calibration. Shapley Additive explanations were used for model interpretability. Results: The pre-sarcopenia rate was 17.51 % and 15.16 % in NHANES cohort and external validation set, respectively. RF outperformed other models with area under receiver operating characteristic curve (AUROC) of 0.819 (95 %CI: 0.749, 0.889). When six top-ranking features were retained as per variable importance, including weight-adjusted waist, sex, race, creatinine, education and alkaline phosphatase, a final RF model reached an AUROC being 0.824 (0.737, 0.910) and 0.732 (95 %CI: 0.529, 0.936) in internal and external validation sets, respectively. The model robustness was proved in sensitivity analysis. The calibration curve and decision curve analysis confirmed a good calibration capacity and good clinical usage. Conclusions: This study proposed a user-friendly model using explainable machine learning algorithm to predict pre-sarcopenia in MASLD population. A web-based tool was provided to screening pre-sarcopenia in community and hospitalization settings.

Background To evaluate the prognostic value of skeletal muscle index (SMI) and its change in patients with hepatocellular carcinoma (HCC) experiencing curative hepatectomy plus adjuvant transarterial chemoembolization (TACE). Materials and methods A total of 62 patients with HCC who underwent adjuvant TACE after curative hepatectomy were analysed retrospectively. Skeletal muscle area at the third lumbar level was quantitated using computed tomography images and was normalized for height squared to obtain skeletal muscle index (SMI). Skeletal muscle loss (SML) over 6 months was computed with two SMIs before and after hepatectomy plus adjuvant TACE. Correlation analyses were preformed to investigate factors associated with SML. The curves of cause-specific survival (CSS) were analysed using the Kaplan-Meier method. A Cox proportional hazards model was used to assess prognostic factors. Results Low SMI was diagnosed in 23(37.1%) patients preoperatively. The median SML standardized by 6 months was - 1.6% in the entire cohort. Liver cirrhosis and microvascular invasion correlated negatively with SML, respectively (r = - 0.320, P = 0.002; r = - 0.243, P = 0.021). Higher SML (< - 2.42%) predicted a significant reduction in CSS (P = 0.001), whereas low SMI did not(P = 0.687). Following the multivariate analysis for CSS, AFP > 400 ng/ml (HR, 5.643; 95%CI, 3.608-17.833; P < 0.001) and SML < - 2.42%(HR, 6.586; 95%CI, 3.610-22.210; P < 0.001) were independent predictors for poor CSS. Conclusions Skeletal muscle loss during hepatectomy plus adjuvant TACE was remarkable. Higher SML was an independent risk factor for CSS in patients with HCC, especially those with liver cirrhosis.

Aims: To investigate the predictive value of hepatic venous pressure gradient (HVPG) and the efficacy and significance of early percutaneous transhepatic varices embolization (PTVE) for gastrointestinal bleeding after transcatheter arterial chemoembolization (TACE) for liver cancer. Methods and Materials: This retrospective study enrolled 60 patients diagnosed with stage B or stage C liver cancer, according to the Barcelona Clinic Liver Cancer (BCLC) staging system, between December 2019 and October 2021. TACE and HVPG measurement (>16 mmHg or >20 mmHg) were performed on all 60 patients, who were randomized into control and experimental (PTVE) groups. All patients were followed up for 12 months. Statistical Analysis Used: SPSS 20.0 software was used for data analysis. The two groups were compared with respect to the initial occurrence time of hemorrhage after TACE, recurrence time of hemorrhage, liver function, TACE frequency, TACE type, and tumor control. Results: The initial hemorrhage rates at one, three, six, and 12 months after TACE were 3.2%, 12.9%, 22.6%, and 48.4%, respectively, in the control group (n = 31) and 0%, 0%, 3.4%, and 10.3%, respectively, in the PTVE group (n = 29). Differences between the groups in terms of initial hemorrhage rate at six and 12 months postoperatively were significant (P < 0.05). The recurrence rates of hemorrhage at one, three, six, and 12 months after TACE were 11.1%, 22.2%, 22.2%, and 33.3%, respectively, in 27 patients in the control group. In eight patients in the PTVE group, the corresponding rates were 0%, 0%, 0%, and 25.0%. The differences between the groups in the recurrence rate of hemorrhage at the four time points were significant (P < 0.05). At six months postoperatively, liver function recovery and remission were noted in eight (25.8%) and 18 (66.7%) patients, respectively, in the control group; these events were noted in 10 (34.5%) and 19 patients (65.5%), respectively, in the PTVE group, and the difference between the groups was not significant (P > 0.05). In the control group, TACE was performed for a total of 94 times on 31 patients within 12 months, including conventional transcatheter arterial chemoembolization (C-TACE, 75.5%) and the drug-eluting bead TACE (DEB-TACE, 24.5%); the objective response rate (ORR) was 39.3%. In the PTVE group, TACE was performed for a total of 151 times on 29 patients within 12 months, with an average of 5.21 times on each patient, including the C-TACE (57.6%) and DEB-TACE (42.4%); the ORR was 60.1%. Differences in TACE frequency, proportion of C-TACE/DEB-TACE, and ORR were significant between the two groups (P < 0.05). Conclusion: HVPG can accurately evaluate gastrointestinal bleeding after TACE in patients with liver cancer. Early PTVE can significantly lower the risk of gastrointestinal bleeding and help TACE control tumor progression in patients with an HVPG >16 mmHg or >20 mmHg.

Arterioportal fistulas (APFs) are defined as vascular communications between the systemic arteries and portal circulation. APFs are classified as congenital or acquired, large or small, intrahepatic or extrahepatic, and traumatic or spontaneous. The consistent abnormal connection may result in severe presinusoidal portal hypertension, leading to gastrointestinal bleeding (GIB), ascites, elevated liver function enzymes, heart failure, diarrhea, and even pancreatitis or hematobilia in some unusual cases. Indeed, less than half reported cases have GIB, predominately caused by variceal rupture. Peptic ulcer bleeding has rarely been reported in the setting of APFs. Herein, we describe a case in which intrahepatic APF manifested as gastric ulcer bleeding, progressive portal thrombosis, and massive ascites, with these symptoms successfully relieved by endovascular treatment.

目的 观察电针对帕金森病(Parkinson's disease,PD)模型小鼠纹状体内原癌基因蛋白(c-Fos)表达的选择性调控作用,以探究电针治疗PD的潜在机制.方法 制备6-羟基多巴胺(6-hydroxydopamine,6-OHDA)右侧损伤的PD模型小鼠,实验分为对照组、对照+电针组、模型组和模型+电针组.电针施加于小鼠下肢双侧的"足三里"和"三阴交"穴位,采用100 Hz电针刺激持续30 min,继而用免疫组化检测纹状体背侧、腹侧和扣带回皮质的c-Fos蛋白表达.结果 模型组小鼠右侧背部纹状体c-Fos表达较对照组显著降低(P<0.001),而电针刺激显著增加了模型组右侧背部和腹部纹状体的c-Fos的表达(P<0.05).检测扣带回皮质的c-Fos表达,各组之间差异无统计学意义,电针未产生明显的调控作用.结论 电针可区域特异性地激活PD小鼠损伤侧纹状体背部神经元的活性.

Purpose: To evaluate the efficacy and safety of placement of a modified microcoil for precise preoperative localization of solitary pulmonary nodules (SPNs) before video-assisted thoracoscopic surgery (VATS). Materials and Methods: This prospective, single-arm, multicenter study included patients who underwent computed tomography (CT)-guided modified microcoil insertion prior to SPN resection by VATS between January 2018 and June 2018. The patient demographics, nodule characteristics, and histopathologic findings were recorded. The primary endpoints included efficacy and safety. Results: A total of 96 patients (41 men and 55 women; mean age, 59.3 years +/- 8.9) with 96 SPNs were eligible for enrolment in the study. The mean maximal transverse diameter of the nodules was 10.3 mm +/- 5.2 (range, 8-20 mm). The mean time between CT-guided microcoil insertion and the start of the surgical procedure was 14.6 hours (range, 12-24 hours). The duration of the preoperative CT-guided microcoil localization procedure was 29 minutes +/- 9 (range, 10-35 minutes), and the intraoperative fluoroscopy time was 0.7 minutes +/- 0.7 (range, 0.5-3 minutes). The clinical success rate was 96.9% (93/96), and all nodules were successfully resected using VATS. One patient experienced asymptomatic pneumothorax, but there were no cases of pulmonary hemorrhage. Conclusions: SPN localization with the modified microcoil is feasible and safe. The modified microcoil can facilitate the thoracoscopic resection of SPNs.

Background Parkinson's disease is characterized by abnormal synaptic transmission in the corticostriatal circuit that leads to deficits in motor abilities. Electro-acupuncture has shown to improve the motor behaviors in parkinsonian models. However, the potential mechanisms underlying the electro-acupuncture treatment, specifically in the partial-lesioned model, remain unclear. Methods By utilizing multiple approaches, including electrophysiological, immunohistochemistrical, molecular and behavioral methods, we assessed the effect of electro-acupuncture on the motor dysfunction and striatal synaptic plasticity in a partial-lesioned mouse model induced by intrastriatal injection of 6-hydroxydopamine. Results Electro-acupuncture ameliorated the disrupted gross and fine motor skills in 6-hydroxydopamine-lesioned mice. Notably, electro-acupuncture not only restored the injured corticostriatal long-term potentiation, but also reversed the loss of GluN1-containing NMDA receptors and GluA1-containing AMPA receptors in the striatum. Furthermore, the antagonists selective for AMPA receptors and NMDA receptors blocked the effect of electro-acupuncture on the corticostriatal long-term potentiation in 6-hydroxydopamine-treated mice. Conclusions These data suggest that the postsynaptic glutamate receptors in the striatum undergo the maladaptive changes in the early stage of Parkinson's disease. Electro-acupuncture improves the motor skills via a mechanism involving the modulation of corticostriatal synaptic plasticity and specific glutamate receptors in a partial-lesioned rodent model.

As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), apatinib has a certain anti-tumor effect for a variety of solid tumors. The present study evaluates its efficacy and safety in advanced hepatocellular carcinoma (HCC). In this study, 47 patients with advanced HCC were included. TACE monotherapy group included 22 patients that responded to TACE, while the group that received TACE and apatinib included 25 patients that progressed on TACE and were able to receive apatinib off label. Median overall survival (OS) was significantly improved in the apatinib plus TACE group compared with the TACE group. Similarly, apatinib in combination with TACE significantly prolonged median progression-free survival (PFS) compared with TACE monotherapy. Furthermore, there was a significant difference between combination therapy and monotherapy in both Barcelona clinic liver cancer (BCLC) B and BCLC C group. The combination therapy had a dramatic effect on OS and PFS for patients at both BCLC B and BCLC C level. The most common clinically adverse events of apatinib plus TACE group were fatigue, weight loss, hypertension, hand-foot syndrome and anorexia, which were manageable and tolerable. The efficacy analysis showed that there was no significant association of survival benefit with age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, hypertension and hand-foot syndrome. Patients with macrovascular invasion and extrahepatic invasion showed worse survival benefits. In conclusion, apatinib combined with TACE revealed certain survival benefits for HCC patients who experienced progression following TACE, which can provide a promising strategy for HCC treatment.

Bone metastases are the most common sites for malignant tumors. Patients who failed to respond to initial first-line treatment with bisphosphonates usually suffer from extreme pain. The aim of this study was to observe the efficacy of arterial chemoembolization combined with Iodine-125 seed implantation in the treatment of bone metastatic cancer pain. All 14 patients with metastatic bone tumor wo failed first-line treatment underwent arterial chemoembolization the day before the implantation of the particles. A computer stereoscopic TPS was used to design the treatment plans, the number and dose of particles required for implantation. Pain relief was evaluated using several parameters such as Visual Analog Scale (VAS) and Verbal Rating Scales (VRS). Pain intensity was measured pre-operation and 1-week, 1-month, 3-month after the treatment. Meanwhile, we also assessed tumor size using computer tomography (CT). Pain palliation was observed in 35.7% (5/14), 57.1% (8/14), and 78.6% (11/14) of all patients at 1-week, 1-month and 3-month post treatment. Likewise, our analysis showed that the combination therapy resulted in a significant decrease of VAS score (6.71 ± 0.49 before treatment vs 3.36 ± 0.40 at 3 month post treatment) and overall responding rate of 92.0% using VRS pain assessment. Consistently, tumor size was reduced from 42.16 ± 10.32 before treatment to 29.11 ± 8.73 at 3 months post treatment. No serious complications were detected. Our study demonstrate that the combination of arterial chemoembolization and 125I particles resulted in evident pain relief and reduction of tumor burden, suggesting that the combination treatment could be a feasible and promising therapy for bone tumor management.

OBJECTIVE: To investigate the relationships between upstream venous sinus stenosis and pulsatile tinnitus (PT), and to assess the correlation with diverticulum growth and the effectiveness of stent implantation. METHODS: Patient-specific geometric models were constructed using computed tomography venography images from a patient with PT, with sigmoid sinus diverticulum, and with upstream transverse sinus stenosis, in whom stenting of the upstream sinus stenosis alone achieved complete remission of PT. Computational fluid dynamics simulation based on this patient-specific geometry was performed using commercially available finite element software (ANSYS-14) to qualitatively and quantitatively compare the flow velocity, flow rate, velocity vector, pressure, vorticity, and wall shear stress on the affected side transverse and sigmoid sinuses, before and after stent implantation. RESULTS: Stenting improved the flow direction and magnitude. After stenting, the flow pattern became smoother and more regular. High-speed blood flow at the level of the diverticulum neck was confined to a smaller area, and its direction changed from approximately perpendicular to the diverticular dome to the distal side of the diverticular neck. The diverticulum showed obvious flow reduction, with decreases of 80.7%, 68.7%, 96.1%, and 91.3% in peak velocity, inflow rate, pressure gradient, and peak vorticity, respectively. The abnormally low wall shear stress at the dome of diverticulum was eliminated. CONCLUSIONS: Our findings strongly support a major role of diverticulum stenosis before in PT development and suggest that such stenosis is a causative factor of diverticulum growth. They also confirm the effectiveness of stent implantation for the treatment of PT.

Background and ObjectivesTo evaluate efficacy and aesthetic outcome for combined endoscopic subcutaneous mastectomy (E‐SM) and endoscopic sentinel lymph node biopsy (E‐SLNB) in early stage breast cancer patients.MethodsCombined E‐SM+E‐SLNB was compared to modified radical resection in a cohort of Chinese patients (n = 49) with stages I and II breast cancer. Patient satisfaction with the aesthetic results was assessed 1 year after surgery with a 5‐item‐by‐4‐step scoring system for evaluating cosmetic outcomes.ResultsAll patients were alive 1 year following surgery with no locoregional recurrence or distant metastases and without any critical complications. The average length of incision was less in patients receiving E‐SM+E‐SLNB (4.4 vs. 19.4 cm; P < 0.001), but time in surgery was longer (131.6 vs. 99.2 min; P = 0.024). After 1 year, nearly all E‐SM+E‐SLNB patients rated satisfaction with their appearance as excellent or good (23/24; 95.8% vs. 19/25; 76.0%; P < 0.001), and exhibited less disturbance of sensory (P < 0.001) and motor function (P = 0.014) relative to modified radical resection.ConclusionsE‐SM+E‐SLNB provides significant aesthetic and functional advantages for patients with early stage breast cancer without compromising medical efficacy as assessed at 16 months postsurgery. J. Surg. Oncol. 2016;113:616–620. © 2016 Wiley Periodicals, Inc.

Liver kinase B1 (LKB1) functions as a tumor suppressor gene, and loss in the expression of LKB1 contributes to human carcinogenesis and tumor progression. The present study investigated the association between LKB1 and gastric cancer. SGC‑7901 gastric cancer cell lines and 63 patients with gastric cancer were examined in the present study, and lentivirus transfection, reverse transription‑quantitative polymerase chain reaction and flow cytometric analyses were performed. By examining the expression of LKB1 using immunohistochemical analyses, the present study found that the expression of LKB1 was reduced in the gastric cancer tissues, and restoration of the expression of LKB1 reduced tumor cell viability, migration rate and the expression of CD44, induced cell cycle arrest at the G2 phase of the cell cycle, and increased the sensitivity of the gastric cancer cells to anticancer drugs. LKB1 protein is a tumor‑suppressor in gastric cancer and may be potentially be developed as a novel gene therapy target in the treatment of gastric cancer.

Background Long life of memory T cell (Tm) determines its crucial role in the carcinogenesis and carcinogenic progression which usually take long time. The Tm compartment contains two populations, central memory T cells (Tcm) and effector memory T cells (Tem), based on their phenotypic markers, functional attributes, and migratory properties. Methods We investigated the subsets of the Tm in peripheral blood and tumor microenvironments in patients with gastric cancer by flow cytometry, and aimed to explore the correlation between the Tm and clinicopathologic features of gastric cancer. Results The percentages of CD4 + /CD8 + Tm and CD4 + /CD8 + Tcm in peripheral blood from gastric cancer patients were statistically lower, whereas the percentages of CD4 + /CD8 + Tem were significantly higher than healthy controls. The proportion of CD4 + /CD8 + Tcm increased after tumor resection, while the percentage of the CD4 + /CD8 + Tem decreased significantly. Significant associations were detected between the peripheral CD4 + /CD8 + Tm and clinical stage, as well as the CD8 + Tcm and clinical stage and nodal involvement. Tumor infiltrating CD8 + Tm expressed both central and effector memory phenotypes, whereas CD4 + Tm displayed predominantly an effector memory phenotype. Higher percentages of tumor infiltrating CD4 + /CD8 + Tm were significantly associated with the early disease stage. Conclusions Tm and its subsets were good immune indicators for the disease stage of gastric cancer. The proportion of Tm subsets may reflect the immune suppressive and immune response to the tumor associated antigen.