BackgroundUnresectable hepatocellular carcinoma (u-HCC) still accounts for the majority of newly diagnosed HCC which with poor prognosis. In the era of systemic therapy, combination therapy with programmed cell death protein-1 (PD-1) inhibitors and tyrosine kinase inhibitors (TKIs) has become mainstream. Hepatic arterial infusion chemotherapy (HAIC) as a local treatment has also shown a strong anti-tumor effect. This study aimed to investigate the efficacy and safety of HAIC, PD-1 inhibitors plus TKIs for u-HCC.MethodsThis retrospective study included patients with initially u-HCC between October 2020 to April 2022 who had received at least one cycle of therapy with HAIC, PD-1 inhibitors plus TKIs. The primary outcome included overall response rate (ORR), the disease control rate (DCR), surgical conversion rate, progression-free survival (PFS) and treatment-related adverse events.ResultsA total of 145 patients were included in the study. The median treatment cycle of HAIC and PD-1 inhibitors were 3 and 4, respectively. According to the modified RECIST criteria, the best ORR was 57.2% (83/145), 9 had achieved complete response (CR), DCR was 89.7% (130/145). Median time to achieve CR or PR was 65 days. Surgical conversion rate was 18.6% (27/145), seven patients (7/27,25.9%) achieved pathological complete response (pCR). The median follow-up was 12.5 months (4.5-20 months), and the median PFS was 9.7 months. Subgroup analysis showed that Child-pugh A patients had higher DCR (92.2% vs 79.3%, p=0.041) than Child-pugh B patients, as well as increased successful conversion rate (22.4% vs 3.4%, p=0.019). Patients without vascular invasion and extrahepatic metastases showed higher PR (63.4% vs 43.3%, p<0.05) and ORR (73.2% vs 50.0%, p<0.05) than those with vascular invasion. The ORR (73.2% vs 45.5%, p<0.05) and DCR (95.1% vs 78.8%, p<0.05) were also significantly better than those of patients with extrahepatic metastases. HAIC regimen was not related to efficacy (All p>0.05). The incidence rate of grade 3/4 treatment-related AEs was 17.7% without fatal events.ConclusionThe triple combination therapy of HAIC and PD-1 inhibitors plus TKIs for patients with initially unresectable HCC exhibited satisfactory efficacy with tolerable toxicity.

Conversion therapy gives some patients with initially unresectable hepatocellular carcinoma (HCC) access to surgery. The purpose of this study was to evaluate the safety and efficacy of hepatectomy after conversion therapy and how it differed from those who undergoing direct hepatectomy. Patients and Methods: From January 2018 to April 2022, 745 patients underwent hepatectomy for HCC were enrolled. Among them, 41 patients of unresectable HCC underwent hepatectomy after conversion therapy. A demographically and clinically comparable cohort was created from the remaining patients in a 1:1 ratio using propensity score matching. Results:The median duration of conversion therapy was 108 (42-298) days, 8 patients achieved complete response (CR) and 33 achieved partial response (PR). Conversion therapy resulted in some degree of myelosuppression, but liver function index remained good. Compared with the direct hepatectomy group, the conversion group had more blood loss (600 mL vs 400 mL, p=0.015), longer operative time (270 min vs 240 min, p=0.02), higher blood transfusion rates, and longer hospital stay (8 days vs 11 days, p<0.001). Patients in the conversion group had significantly more complications of any grade (82.9% vs 51.2%, p=0.002) and grade 3/4 (26.8% vs 4.9%, p=0.013), and 6 patients developed post-hepatectomy liver failure (PHLF). There were no deaths in either group. All patients achieved R0 resection, 6 (6/41, 14.6%) achieved pathological complete response (pCR), 14 achieved major pathologic responses (MPR). During a median follow-up of 12.8 months, 14 patients in the conversion group experienced recurrence or metastasis, no deaths. Conclusion: Hepatectomy after conversion therapy was more difficult than direct hepatectomy, but accurate preoperative assessment could ensure the safety of the surgery. The damage of liver function after conversion therapy was more severe than expected, PHLF should be prevented and treated. Hepatectomy was effective and necessary, postoperative pathological examination could provide guidance for adjuvant therapy.

Background A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects that can significantly improve the recovery of motor function after spinal cord injury (SCI). Here, we explore the role and molecular mechanisms of Alpinetin on activating microglia‐mediated neuroinflammation and neuronal apoptosis after SCI. Methods Stimulation of microglia with lipopolysaccharide (LPS) to simulate neuroinflammation models in vitro, the effect of Alpinetin on the release of pro‐inflammatory mediators in LPS‐induced microglia and its mechanism were detected. In addition, a co‐culture system of microglia and neuronal cells was constructed to assess the effect of Alpinetin on activating microglia‐mediated neuronal apoptosis. Finally, rat spinal cord injury models were used to study the effects on inflammation, neuronal apoptosis, axonal regeneration, and motor function recovery in Alpinetin. Results Alpinetin inhibits microglia‐mediated neuroinflammation and activity of the JAK2/STAT3 pathway. Alpinetin can also reverse activated microglia‐mediated reactive oxygen species (ROS) production and decrease of mitochondrial membrane potential (MMP) in PC12 neuronal cells. In addition, in vivo Alpinetin significantly inhibits the inflammatory response and neuronal apoptosis, improves axonal regeneration, and recovery of motor function. Conclusion Alpinetin can be used to treat neurodegenerative diseases and is a novel drug candidate for the treatment of microglia‐mediated neuroinflammation.

Background There is still no standardized policy regarding how to identify patients who are not benefiting from transarterial chemoembolization (TACE). We aimed to establish and validate a nomogram model to predict the survival rate of hepatocellular carcinoma (HCC) patients after TACE. Methods A total of 578 HCC patients undergoing initial TACE at the First Affiliated Hospital of Wenzhou Medical University were retrospectively recruited to the study. The patients were randomly divided into 2 cohorts: a training cohort (n=405) and a validation cohort (n=173). To develop the nomogram, Cox regression analyses were used to identify independent risk factors. The performances of the nomogram were assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA), and were compared to 4 developed prognostic models. Results We used 5 independent risk factors including postoperative albumin-bilirubin (ALBI) grade, tumor diameter, number of tumors, portal vein invasion, and tumor response to develop the nomogram. Calibration curves showed consistency between the nomogram and the actual observation. The C-index of the nomogram was 0.753 [95% confidence interval (CI): 0.722, 0.784], which was higher than the other prognostic models (P<0.001). The DCA showed that the nomogram had the highest net benefit among the models. According to predicted survival risk, the nomogram could divide patients into 3 groups (P<0.001). All the results were verified in the validation cohort. Conclusions This study developed and validated a nomogram model for HCC patients undergoing TACE, which could predict the survival rate and provide support for further treatment strategies.

Background/Aim: Recently, an increase in the number of asymptomatic rare benign liver tumors (BLTs) has been reported during health checkups. It is di cult to determine the nature of partial rare BLTs and not easy to distinguish from malignant liver tumors. This study aimed to analysis clinical features, diagnosis, and treatment of rare BLTs to reduce misdiagnosis and provide reference for clinical practice.Methods: From January 2012 to January 2021, we treated 112 rare BLTs by hepatectomy, including 54 focal nodular hyperplasia, 14 hepatocellular adenoma, 28 hepatic angiomyolipoma, 3 hepatic granuloma, 2 in ammatory pseudotumor of the liver, 2 nodular regenerative hyperplasia, 2 hepatic lipoma, 1 solitary brous tumor of the liver, 1 hepatic schwannoma and 1 hepatic myelolipoma.Results: The majority of patients were middle-aged female and asymptomatic. Single tumors were dominant. The diagnostic accuracies of computed tomography (CT) and magnetic resonance imaging (MRI) were 32.5% and 44.2%, respectively. The majority of tumors were likely to be misdiagnosed as hepatocellular carcinoma (HCC) or di cult to distinguish from HCC. All patients underwent surgical treatment.Postoperative pathological and immunohistochemical examination can con rm the diagnosis. No patients without tumor recurrence or metastasis during follow up period.Conclusion: Altogether, the clinical symptoms of rare BLTs lack speci city, and their preoperative diagnosis largely depends on imaging examination, with a low diagnostic accuracy rate and high chances of misdiagnosis as HCC. Diagnosis is con rmed by pathological and immunohistochemical examination. Surgical resection for rare BLT is safe and effective, regular postoperative follow-up is necessary. 14), HAML (n = 28, including 12 epithelioid angiomyolipomas), hepatic granuloma (n = 3), in ammatory pseudotumor of the liver (IPL) (n = 2), nodular regenerative hyperplasia (NRH) (n = 2), hepatic lipoma (n = 2), solitary brous tumor of the liver (SFTL) (n = 1), hepatic schwannoma (n = 1), and hepatic myelolipoma (n = 1).Clinical data included age, sex, oral contraceptive use, chronic diseases, clinical symptoms, liver function, blood routine, coagulation function, tumor markers (alpha-fetoprotein [AFP], carbohydrate antigen [CA] 19 − 9, carbohydrate antigen 125, and carcinoembryonic antigen), imaging ndings, tumor number, size and location, preoperative diagnosis, operation method, results of operation, postoperative pathologic and immunohistochemical results, and postoperative follow-up.Excised tumoral specimens were xed in formalin and embedded in para n. Next, the specimens were stained with hematoxylin-eosin and histologically examined, and immunohistochemical examination was performed on other sections.