The alteration of serum bile acid profile among traumatic brain injury patients: a small-scale prospective study.

Traumatic brain injury is one of the major causes of morbidity and mortality worldwide. With the development of bile acids as a potential treatment, to identify the influence of traumatic brain injury on bile acid metabolism shows growing importance. This present study did a preliminary exploration of the bile acid profile alteration among traumatic brain injury patients. In total, 14 patients and 7 healthy volunteers were enrolled. The bile acid profile of the blood samples were detected by an Ultra-performance Liquid Chromatography Mass Spectrometer/Mass Spectrometer system. It was found that 6 bile acids were statistically decreased in traumatic brain injury patients comparing with healthy volunteers: glycocholic acid (median level 44.4 ng/ml vs 98.7 ng/ml, p = 0.003), taurocholic acid (median level 10.9 ng/ml vs 19.5 ng/ml, p = 0.006), glycoursodeoxycholic acid (median level 17.4 ng/ml vs 71.4 ng/ml, p = 0.001), ursodeoxycholic acid (median level <1 ng/ml vs 32.4 ng/ml, p = 0.002), taurochenodeoxycholic acid (median level <1 ng/ml vs 53.6 ng/ml, p = 0.003) and glycochenodeoxycholic acid (GCDCA, median level 160 ng/ml vs 364 ng/ml, p<0.001). In conclusion, traumatic brain injury events are able to induce bile acid metabolism alteration in plasma and might cause reduction in glycocholic, taurocholic, glycoursodeoxycholic, ursodeoxycholic, taurochenodeoxycholic and glycochenodeoxycholic acid levels.

A rapid preliminary prediction model for intestinal necrosis in acute mesenteric ischemia: a retrospective study.

BACKGROUND: Acute mesenteric ischemia (AMI) is a life-threatening condition. However, there is no accurate method to predict intestinal necrosis in AMI patients that may facilitate early surgical intervention. This study thus aimed to explore a simple and accurate model to predict intestinal necrosis in patients with AMI. METHODS: A single-center retrospective study was performed on the data of 132 AMI patients treated between October 2011 and June 2020. The patients were divided into the intestinal necrosis and non-intestinal necrosis groups. The clinical characteristics and laboratory data were analyzed by univariate analysis, and the variables with statistical significance were further analyzed by multivariate logistic regression analysis. The independent predictors of intestinal necrosis were determined and a logistic prediction model was established. Finally, the accuracy, sensitivity, and specificity of the model in predicting intestinal necrosis were evaluated. RESULTS: Univariate analysis showed that white blood cell (WBC) count, blood urea nitrogen (BUN) level, neutrophil ratio, prothrombin time (PT), and LnD-dimer were associated with intestinal necrosis. According to logistic regression multivariate analysis, WBC count, BUN level and LnD-dimer were independent predictors of intestinal necrosis. These parameters were used to establish a clinical prediction model of intestinal necrosis (CPMIN) as follows: model score = 0.349 × BUN (mmol/L) + 0.109 × WBC × 109 (109/L) + 0.394 × LnD - Dimer (ug/L) - 7.883. The area under the receiver operating characteristics (ROC) curve of the model was 0.889 (95% confidence interval: 0.833-0.944). Model scores greater than - 0.1992 predicted the onset of intestinal necrosis. The accuracy, specificity, and sensitivity of the model were 82.6%, 78.2%, and 88.3%, respectively. The proportion of intestinal necrosis in the high-risk patient group (CPMIN score ≥ - 0.1992) was much greater than that in the low-risk patient group (CPMIN score < - 0.1992; 82.7% vs. 15.0%, p < 0.001). CONCLUSION: The CPMIN can effectively predict intestinal necrosis and guide early surgical intervention to improve patient prognosis. Patients with AMI who are classified as high-risk should be promptly treated with surgery to avoid the potential complications caused by delayed operation. Patients classified as low-risk group can receive non-surgical treatment. This model may help to lower the morbidity and mortality from AMI. However, this model's accuracy should be validated by larger sample size studies in the future.

Microglia: A Potential Drug Target for Traumatic Axonal Injury.

Traumatic axonal injury (TAI) is a major cause of death and disability among patients with severe traumatic brain injury (TBI); however, no effective therapies have been developed to treat this disorder. Neuroinflammation accompanying microglial activation after TBI is likely to be an important factor in TAI. In this review, we summarize the current research in this field, and recent studies suggest that microglial activation plays an important role in TAI development. We discuss several drugs and therapies that may aid TAI recovery by modulating the microglial phenotype following TBI. Based on the findings of recent studies, we conclude that the promotion of active microglia to the M2 phenotype is a potential drug target for the treatment of TAI.

Predicting the outcomes of shunt implantation in patients with post-traumatic hydrocephalus and severe conscious disturbance: a scoring system based on clinical characteristics.

Post-traumatic hydrocephalus is a common complication secondary to traumatic brain injury. It can cause cerebral metabolic impairment and dysfunction. Therefore, timely treatment with shunt implantation is necessary. However, the outcomes of shunt surgery in patients with post-traumatic hydrocephalus combined with disturbance of consciousness are doubtful. The objective was to develop a predictive model that uses the information available before surgery to predict the outcome of shunt implantation in such patients. Retrospectively collected data were used to develop a clinical prediction model. The model was derived from 59 patients using logistic regression analysis, and then it was evaluated by the area under the receiver operating characteristic curve and Hosmer-Lemshow test. A validation cohort verified the model. Four independent predictors were identified: age < 50 years, mild hydrocephalus, Glasgow Coma Scale scores 9-12 at the time of injury, and time interval from trauma to shunting < 3 months. We calculated the total score and defined the patients into three groups: low-probability (0-10 points), medium-probability (11-16 points), and high-probability (17-30 points). The rates of improved outcomes in the three groups were 14.3%, 52.6%, and 94.7%, respectively (P < 0.0001). The correlative rates of the validation cohort were 21.4%, 54.5%, and 85.7%. The prognostic model showed good discrimination (area under the receiver operating characteristic curve = 0.869) and calibration (Hosmer-Lemshow test, P = 0.391). The developed predictive model can identify patients with post-traumatic hydrocephalus combined with disturbance of consciousness who can benefit from shunt implantation. Therefore, our prognostic model can predict the outcomes of patients with post-traumatic hydrocephalus and disturbance of consciousness after shunt surgery.

Risk Factors for Anterior Hypopituitarism in Patients With Traumatic Brain Injury.

BACKGROUND: Hypopituitarism is a common but potentially undiagnosed complication in patients who suffer traumatic brain injury (TBI). The identification of risk factors of hypopituitarism after TBI is vital to establish a rational testing approach for these patients. METHODS: The authors retrospectively reviewed the case records of patients with TBI, who underwent pituitary function evaluation in our department between January 2014 and December 2016. RESULTS: In all, 193 patients (66.3% male) hospitalized with TBI were included in this study. Anterior hypopituitarism was observed in 33 (17.1%) patients, with 4.7% of the patients having multiple pituitary axes dysfunction. Patients with hypopituitarism had a longer length of ICU stay (8.7 ±â€Š5.5 versus 3.3 ±â€Š4.6, P < 0.001), longer length of total hospital stay (28.7 ±â€Š20.1 versus 21.0 ±â€Š15.8, P = 0.011), and lower Glasgow coma scale (GCS) on admission (9.1 ±â€Š3.5 versus 11.8 ±â€Š3.6, P < 0.001) than those without the condition. Length of ICU stay (P = 0.004, OR = 1.253) and intracranial hypertension (P = 0.027, OR = 3.206) were independent risk factors for posttraumatic hypopituitarism. CONCLUSIONS: The prevalence of anterior hypopituitarism was estimated to be 17.1%. Patients with intracranial hypertension and longer length of ICU stay are at risk of hypopituitarism. Routine pituitary function evaluation is indicated for this group of patients.

Hyperbaric Oxygen Therapy in Liver Diseases.

Hyperbaric oxygen therapy (HBOT) is an efficient therapeutic option to improve progress of lots of diseases especially hypoxia-related injuries, and has been clinically established as a wide-used therapy for patients with carbon monoxide poisoning, decompression sickness, arterial gas embolism, problematic wound, and so on. In the liver, most studies positively evaluated HBOT as a potential therapeutic option for liver transplantation, acute liver injury, nonalcoholic steatohepatitis, fibrosis and cancer, especially for hepatic artery thrombosis. This might mainly attribute to the anti-oxidation and anti-inflammation of HBOT. However, some controversies are existed, possibly due to hyperbaric oxygen toxicity. This review summarizes the current understandings of the role of HBOT in liver diseases and hepatic regeneration. Future understanding of HBOT in clinical trials and its in-depth mechanisms may contribute to the development of this novel adjuvant strategy for clinical therapy of liver diseases.

Prevalence of and risk factors for recurrence of chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease in neurosurgical practice with substantial recurrence rate. We aimed to estimate recurrence rate of CSDH and to identify risk factors for CSDH recurrence. METHODS: We retrospectively studied consecutive cases with CSDH and performed surgical therapy in our hospital. Univariate and multivariate logistic regression analyses were performed to identify factors associated with recurrence of CSDH. RESULTS: A total of 226 patients with CSDH were included; 34 patients recurred after surgery with a recurrence rate of 15.0%. Univariate analysis showed that the recurrence group had more patients with homogenous hyper-dense hematoma (20.6 vs 6.3%, p = 0.035) and shorter duration of subdural drainage post-surgery (1.2 ± 1.4 vs 1.5 ± 0.9, p = 0.022) than the non-recurrence group. Logistic regression analysis revealed that duration of subdural drainage (OR = 0.66, p = 0.05) and hyper-dense of hematoma (OR = 4.94, p = 0.012) were independent predictors for CSDH recurrence. CONCLUSIONS: Homogenous hyper-dense of hematoma and duration of subdural drainage post-surgery were independent predictors for CSDH recurrence; longer duration of postoperative subdural drainage was associated with lower risk of recurrence.

Dasatinib synergises with irinotecan to suppress hepatocellular carcinoma via inhibiting the protein synthesis of PLK1.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumour and has poor prognosis. Currently, systematic chemotherapy is the only approach to prolong survival. Thus the development of new treatment regimens is urgently needed to improve the therapeutic efficacy. Our study intended to assess the combination of dasatinib and irinotecan against HCC and made an effort to develop a potential medical choice for advanced HCC patients. METHODS: We used SRB colorimetric assay and clonogenic assay to assess antitumour effect in vitro and HCC xenograft model to assess antitumour effect in vivo. We applied flow cytometry and western blotting to explore the mechanism of the combined therapy. Knockdown and overexpression of PLK1 are also applied for validation. RESULTS: We confirmed that dasatinib has synergistic effect with irinotecan (or SN38) on HCC both in vitro and in vivo. The effect is due to arisen apoptosis rate of HCC cells that is accompanied by mitochondria dysfunction. The enhanced antitumour efficacy of SN38 could be explained by additional inhibition of PLK1, which is triggered by dasatinib. Unlike existed PLK1 inhibitors, dasatinib does not inhibit PLK1 activity in a direct way. Instead, we found that dasatinib reduces PLK1 level by interfering with its protein synthesis progress. We validated that this kind of downregulation of PLK1 level has a key role in the synergistic effect of the two agents. CONCLUSIONS: Dasatinib is able to reinforce the anti-HCC efficacy of irinotecan/SN38 by downregulation of PLK1 synthesis. The combination of the two agents might be a potential medical choice for HCC therapy.

Traumatic Brain Injury Induces Gastrointestinal Dysfunction and Dysbiosis of Gut Microbiota Accompanied by Alterations of Bile Acid Profile.

Gastrointestinal dysfunction is a common peripheral organ complication after traumatic brain injury (TBI), yet the underlying mechanism remains unknown. TBI has been demonstrated to cause gut microbiota dysbiosis in animal models, although the impacts of gut microbiota dysbiosis on gastrointestinal dysfunction were not examined. Bile acids are key metabolites between gut microbiota and host interactions. Therefore, the aim of this study was to investigate the mechanistic links between them by detecting the alterations of gut microbiota and bile acid profile after TBI. For that, we established TBI in mice using a lateral fluid percussion injury model. Gut microbiota was examined by 16S rRNA sequencing, and bile acids were profiled by ultra-performance liquid chromatography-tandem mass spectrometry. Our results showed that TBI caused intestinal inflammation and gut barrier impairment. Alterations of gut microbiota and bile acid profile were observed. The diversity of gut microbiota experienced a time dependent change from 1 h to 7 days post-injury. Levels of bile acids in feces and plasma were decreased after TBI, and the decrease was more significant in secondary bile acids, which may contribute to intestinal inflammation. Specific bacterial taxa such as Staphylococcus and Lachnospiraceae that may contribute to the bile acid metabolic changes were identifed. In conclusion, our study suggested that TBI-induced gut microbiota dysbiosis may contribute to gastrointestinal dysfunction via altering bile acid profile. Gut microbiota may be a potential treatment target for TBI-induced gastrointestinal dysfunction.

Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury.

Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.

Contribution of Patient Care Technicians to the Prevention of External Ventricular Drain Infection: A Retrospective Study.

ABSTRACT: BACKGROUND: External ventricular drains (EVDs) are commonly used in neurosurgery. Preventing EVD-related infections is important, and nursing plays a significant role in infection control. However, because of the limited number of neurosurgical nurses and heavy workload in developing countries, well-trained patient care technicians (PCTs) might be able to assist nurses under this circumstance. METHODS: This study retrospectively screened patients who underwent EVD procedures in our medical center from January 2012 to June 2018. Clinical characteristics including EVD-related infection rates of patients with or without PCTs were compared. RESULTS: We analyzed 234 patients in total. There were 26 EVD infection cases, and the overall infection rate was 11.1%. There were 122 patients who were given additional care by PCTs. They were elder (58.1 ± 13.1 vs 49.9 ± 17.0 years old, P < .001) and had lower level preoperational Glasgow Coma Scale (7.04 ± 3.66 vs 13.5 ± 2.53, P < .001) and higher intubation rate (28.7% vs 3.6%, P < .001) than those without PCTs. They also had a longer drainage duration (10.3 ± 4.97 vs 8.01 ± 4.35, P < .001) as well as more cerebrospinal fluid sampling times (2.45 ± 2.00 vs 1.75 ± 1.83, P = .006) and were kept at artificial airway status for a longer duration (10.1 ± 18.7 vs 1.93 ± 7.86, P < .001). External ventricular drain-related infection rates were similar between 2 groups (11.5% vs 10.7%, P = .853). CONCLUSION: Patient care technicians with proper training are beneficial to the prevention of EVD-related infection as a measure of improving staffing adequacy.

Influence of Ward Environments on External Ventricular Drain Infections: A Retrospective Risk Factor Analysis.

Background: Ventriculostomy-related infection (VRI) is one of the most severe and common complications of external ventricular drains (EVD). Ward environment is closely related to hospital-acquired infection, but its role in EVD infection is unclear. For some other recognized risk factors, clinical evidence also remains complicated and undetermined. We aimed to evaluate ward environment including multi-bed accommodation and intensive care unit (ICU) stay as potential risk factors for VRI, as well as to confirm those already known factors. Methods: We reviewed EVDs retrospectively in our center between January 2012 and January 2017. Univariable and logistic regression analysis were performed to identify risk factors for EVD-related infection. Results: A total of 284 patients who underwent EVD procedure were included. Thirty-six (12.7%) developed EVD-related infection. Univariable analysis revealed that the infection group had longer intensive care unit (ICU) stay (6.81 vs. 3.65 days, p = 0.045) but multi-bed accommodation showed no statistical difference between the two groups (p = 0.404). Univariable analysis also showed VRI patients had lower pre-operational Glasgow Coma Scale (6.89 vs. 9.32, p = 0.001), longer drainage placement duration (11.4 vs. 8.30 days, p < 0.001), greater numbers of cerebrospinal fluid (CSF) sampling (3.89 vs. 1.73, p < 0.001), higher percentage of pre-operational artificial airway status (50.0% vs. 18.1%, p < 0.001), and higher percentage of intracranial hemorrhage diagnosis (88.9% vs. 73.8%, p = 0.048). Logistic regression analysis demonstrated longer post-operational ICU stay (>5 days, odds ratio [OR] = 3.21, p = 0.026) as independent risk factor for EVD-related infection. Other independent risk factors included CSF sampling counts (>3, OR = 5.14, p <0.001), EVD duration (>7 days, OR = 3.85, p = 0.028), and pre-operational artificial airway status (OR = 2.85, p = 0.038). Conclusions: Longer post-operational ICU stay, frequent CSF sampling, longer duration of EVD placement, and pre-operational intubation are independent risk factors for EVD infection. Multi-bed accommodation and bilateral EVD placement have no substantial influence on VRI risk.

A Retrospective Clinical Analysis of the Serum Bile Acid Alteration Caused by Traumatic Brain Injury.

Traumatic brain injury (TBI) can cause damage to peripheral organ systems, such as digestive organ system, and alterations of gut microbiota in addition to brain injury. Our previous study found that TBI induced gastrointestinal dysfunction accompanied by alterations of bile acid metabolism. Bile acid and its receptors have been reported to play important roles in various neurological diseases. To further examine the changes of bile acid metabolism in TBI patients, we performed a retrospective clinical analysis. In this study, 177 patients were included, and the results showed that TBI patients had more frequent antibiotic use compared with a control group. Regression analysis identified TBI as an independent factor for reduction of serum bile acid level (B = -1.762, p = 0.006), even with antibiotic use taken into a regression model. Sub-group regression analysis of TBI patients showed that antibiotic use was negatively associated with bile acid level, while creatinine and triglyceride were positively associated with bile acid level. In conclusion, these data indicated that TBI could greatly reduce serum bile acid. This study provided preliminary but novel clinical evidence of TBI interfering with bile acid metabolism, and further studies with large sample sizes are needed to validate these findings in the future.

Cranioplasty as the treatment for contralateral subdural effusion secondary to decompressive craniectomy: a case report and review of the relevant literature.

Subdural effusion (SDE) is a common complication secondary to decompressive craniectomy (DC). This current case report describes a patient with contralateral SDE with a typical clinical course. Initially, he made a good recovery following a head trauma that caused a loss of consciousness and was treated with decompressive craniectomy. However, he only achieved temporary relief after each percutaneous fluid aspiration from an Ommaya reservoir implanted into the cavity of the SDE. He was eventually transferred to the authors' hospital where he underwent cranioplasty, which finally lead to the reduction and disappearance of his contralateral SDE. Unexpectedly, his clinical condition deteriorated again 2 weeks after the cranioplasty with symptoms of an uncontrolled bladder. A subsequent CT scan found the apparent expansion of the whole cerebral ventricular system, indicating symptomatic communicating hydrocephalus. He then underwent a ventriculoperitoneal shunt procedure, which resulted in a favourable outcome and he was discharged 2 weeks later. A review of the current literature identified only 14 cases of contralateral SDE that were cured by cranioplasty alone. The mechanism of contralateral SDE has been widely discussed. Although the exact mechanism of contralateral SDE and why cranioplasty is effective remain unclear, cranioplasty could be an alternative treatment option for contralateral SDE.

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice.

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also demonstrate that traumatic brain injuries cause changes to the gut microbiota. However, mechanisms underlying the bidirectional regulation of the brain-gut axis remain unknown. Currently, few models exist for studying the changes in gut microbiota after traumatic brain injury. Therefore, the presented study combines protocols for inducing traumatic brain injury using a lateral fluid percussion device and analysis of caecum samples following injury for investigating alterations in the gut microbiome. Alterations of the gut microbiota composition after traumatic brain injury are determined using 16S-rDNA sequencing. This protocol provides an effective method for studying the relationships between enteric microorganisms and traumatic brain injury.

The contribution of keratinocytes in capecitabine-stimulated hand-foot-syndrome.

Capecitabine, as the first-line treatment for multiple tumor types, has a serious drawback of hand-foot-syndrome (HFS) that limits its clinical use. However, the pathophysiology and mechanism of capecitabine-induced HFS is rarely known. Here we built the experimental mouse model of HFS induced by capecitabine at first and it was shown that 3 of 6 mice appeared HFS in the 5th day and 5 mice occurred HFS in the 30th day. The corneous layer was reduced in capecitabine-induced HFS in vivo. Moreover, we found that capecitabine could significantly induce keratinocytes cells death in vitro through activated apoptosis pathway and decreased mitochondrial membrane potential. In conclusion, these results suggested that HFS of capecitabine may be developed from reduction of corneous layer through stimulation of intracellular mitochondrial dysfunction following activation of caspase-dependent apoptosis pathway.

Gefitinib Synergizes with Irinotecan to Suppress Hepatocellular Carcinoma via Antagonizing Rad51-Mediated DNA-Repair.

Chemotherapy is the only choice for most of the advanced hepatocellular carcinoma (HCC) patients, while few agents were available, making it an urgent need to develop new chemotherapy strategies. A phase II clinical trial suggested that the efficacy of irinotecan in HCC was limited due to dose-dependent toxicities. Here, we found that gefitinib exhibited synergistic activity in combination with SN-38, an active metabolite of irinotecan, in HCC cell lines. And the enhanced apoptosis induced by gefitinib plus SN-38 was a result from caspase pathway activation. Mechanistically, gefitinib dramatically promoted the ubiquitin-proteasome-dependent degradation of Rad51 protein, suppressed the DNA repair, gave rise to more DNA damages, and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of gefitinib combined with irinotecan was further validated in a HepG2 xenograft mice model. Taken together, our data demonstrated for the first time that the combination of irinotecan and gefitinib showed potential benefit in HCC, which suggests that Rad51 is a promising target and provides a rationale for clinical trials investigating the efficacy of the combination of topoisomerase I inhibitors and gefitinib in HCC.

Anticancer effect of SN-38 combined with sorafenib on hepatocellular carcinoma in vitro and its mechanism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the anticancer effect and its mechanism of SN-38 combined with sorafenib on hepatocellular cancer cell lines HepG-2 and BEL-7402.</p><p><b>METHODS</b>SRB colorimetry was employed to measure the viability of HepG-2 and BEL-7402 cells after the treatment of SN-38 with sorafenib. Propidium iodide flow cytometric assay and DAPI staining were used to evaluate the apoptosis of HCC cells. Western blotting was conducted to detect the expression level of apoptosis-related and DNA damage-related proteins.</p><p><b>RESULTS</b>SRB colorimetry showed the synergistic anticancer activities of SN-38 combined with sorafenib, with a combination index of <0.9. The apoptotic rates of HepG-2 cells in control, 60 nmol/L SN-38, 2.5μmol/L sorafenib and combination groups were 4.25%±2.45%, 28.95%±10.75%, 3.49%±2.49% and 53.19%±11.21%, respectively(P<0.05). Western blotting showed that the combination of these two drugs increased the enzymolysis of PARP, Caspase-8 and Caspase-3, and promoted the expression levels of p53, p21 and γ-H2AX significantly.</p><p><b>CONCLUSION</b>SN-38 and sorafenib have synergistic anticancer activity on hepatocellular carcinoma cells in vitro with the augmentation of apoptosis.</p>