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Acute liver injury can result from a number of different diseases. Inflammatory cytokines are known to be involved in the development of this condition; however, their precise roles and effects on liver function remain unclear. The goal of this study was to determine the relationship between serum cytokine levels and both the severity of liver damage and recovery in acute liver injury. We enrolled 100 patients with acute liver injury caused by drug application who were hospitalized from September 2012 to September 2017 and measured serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the cytokines, interleukin (IL)-2 and IL-6, before and after clinical therapy. Our results indicate that IL-2 and IL-6 levels are altered significantly following clinical therapy. However, with the exception of an association between IL-2 and ALT, we found no correlation between the differences in cytokine levels pre- and post-therapy and recovery of liver function. In contrast, we observed that pre- vs post-treatment difference in the IL-2/IL-6 ratio negatively correlates with the pre- vs post-treatment difference in ALT and AST values, and positively correlates with ALT and AST at 1-month post-discharge. Thus, our data suggest that IL-2/IL-6 ratio may represent a novel predictor for the prognosis of liver injury.

Serotonin and its receptors have been shown to play critical regulatory roles in cancer biology. Nevertheless, the contributions of 5-hydroxytryptamine 1D (5-HT1D), an indispensable member of the serotonergic system, to hepatocellular carcinoma (HCC) remain unknown. The present study demonstrated that the 5-HT1D expression level was significantly up-regulated in HCC tissues and cell lines. The 5-HT1D expression level was closely correlated with unfavorable clinicopathological characteristics. Survival analyses show that elevated 5-HT1D expression level predicts poor overall survival and high recurrence probability in HCC patients. Functional studies revealed that 5-HT1D significantly promoted HCC proliferation, epithelial-mesenchymal transition, and metastasis in vitro and in vivo. Mechanistically, 5-HT1D could stabilize PIK3R1 by inhibiting its ubiquitin-mediated degradation. The interaction between 5-HT1D and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) enhanced the expression of FoxO6 through the PI3K/Akt signaling pathway; FoxO6 could also be directly transcriptionally activated by 5-HT1D in an Akt-independent manner. MicroRNA-599 was found to be an upstream suppressive modulator of 5-HT1D. Additionally, 5-HT1D could attenuate tryptophan hydroxylase 1 expression through the PI3K/Akt/cut-like homeobox 1 axis in HCC. Conclusion: Herein, we uncovered the potent oncogenic effect of 5-HT1D on HCC by interacting with PIK3R1 to activate the PI3K/Akt/FoxO6 pathway, and provided a potential therapeutic target for HCC.

Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future.

Purpose To explore the role of indocyanine green (ICG) fluorescence navigation in laparoscopic hepatectomy and investigate if the timing of its administration influences the intraoperative observation. Methods The subjects of this retrospective study were 120 patients who underwent laparoscopic hepatectomy; divided into an ICG-FN group (n = 57) and a non-ICG-FN group (n = 63). We analyzed the baseline data and operative data. Results There were no remarkable differences in baseline data such as demographic characteristics, lesion-related characteristics, and liver function parameters between the groups. Operative time and intraoperative blood loss were significantly lower in the ICG-FN group. The rate of R0 resection of malignant tumors was comparable in the ICG-FN and non-ICG-FN groups, but the wide surgical margin rate was significantly higher in the ICG-FN group. The administration of ICG 0–3 or 4–7 days preoperatively did not affect the intraoperative fluorescence imaging. Operative time, intraoperative blood loss, and a wide surgical margin correlated with ICG fluorescence navigation. ICG fluorescence navigation helped to minimize intraoperative blood loss and achieve a wide surgical margin. Conclusion ICG fluorescence navigation is safe and efficient in laparoscopic hepatectomy. It helps to achieve a wide surgical margin, which could result in a better prognosis. The administration of ICG 0–3 days preoperatively is acceptable.

BACKGROUND: Autoimmune liver diseases (AILD) is a type of autoimmune disease which may cause end-stage liver failure and require liver transplantation. Regulatory T cells (Tregs) play an irreplaceable role in maintaining immunological homeostasis. METHODS: In this study, we made a comparative analysis of the immune balance and graft function between AILD patients’ post-transplantation and the patients who have had liver failure with hepatitis B virus (HBV) infection post-transplantation. Immune cell phenotype of two groups were analyzed. We sorted CD4+CD25+CD127-Tregs both in vitro and vivo and did TSDR methylation status assay to explore further possible mechanisms. RESULTS: Our data showed that there is a worse prognosis with severe graft function in liver transplant patients with AILD compared to patients with HBV-induced liver failure. Immune cell phenotype analysis showed that more Tregs could be detected in AILD patients compared with HBV patients’ post-transplantation. We sorted CD4+CD25+CD127-Tregs in vivo and showed that Tregs presented decreased function both in vitro and vivo. Mechanism study also proved that modulation of the phosphorylation level of STAT1 and STAT3 as well as the methylation level of TSDR in Foxp3 might partially result in the function loss of Tregs. CONCLUSIONS: These results suggest that loss of Foxp3 expression and suppressive function of Tregs may be the critical factor that causes graft loss for liver transplant patients after AILD.

Object To investigate N-acetyl-cysteine (NAC) would able to alleviate liver injury and systemic inflammatory response caused by microwave ablation (MWA) in rats. Materials and methods Male Sprague-Dawley rats weighing 150–200 g were randomly divided into sham group (only anesthesia and laparotomy except MWA but with intraperitoneal PBS or NAC solution injection according to different situations), control group (intraperitoneal PBS injection for comparation 2 h prior to MWA), and NAC-treated group (intraperitoneal N-acetyl-cysteine (300 mg/kg) injection 2 h prior to MWA). Experimental rats were sacrificed at 4 h following operation in line with the liver injury severity curve. Liver tissue and serum samples were collected for determination of pathology, apoptosis, macrophages contents and protein expression. Results The elevated serum level of liver enzymes, Myeloperoxidase (MPO) and inflammatory factors (TNF-α and CXCL1) in MWA-treated rats revealed injurious and pro- inflammatory effect of MVA. Macrophages aggregation was detected in MWA exposure rats similarly. and NAC pre-conditioning mitigate liver damage and hepatocyte apoptosis, besides macrophages accumulation and following inflammatory response in liver tissue. Conclusion Our results demonstrated that N-acetyl-cysteine application alleviate macrophages aggregation and inflammatory response in liver suffering microwave ablation, and mitigating liver injury and cell apoptosis.

Purpose: To evaluate the feasibility of precoagulation with microwave ablation (MWA) for hepatic parenchymal transection during liver partial resection. Methods: A total of 66 eligible patients were enrolled in this double-blind, randomized, controlled study. Patients were randomized to receive either the traditional clamp-crushing method (Control group) or the MWA precoagulation method (MWA group) for hepatic parenchymal transection during liver partial resection. The operative time, hepatic portal occlusion time, intraoperative blood loss and transfusion, postoperative complications and recovery outcomes were compared. Results: Compared to the Control group, the MWA group had significantly less intraoperative blood loss. Fewer red blood cell transfusions were observed in the MWA group but without statistical significance. The MWA group showed significantly higher serum alanine aminotransferase and aspartate aminotransferase levels at day 1 postoperatively, but no differences between the MWA and Control groups were found at days 3 and 7. There were no significant differences in terms of operative time, hepatic portal occlusion time, postoperative total bilirubin levels, human albumin solution consumption or length of hospital stay. Postoperative complications such as impaired renal function, pyrexia, admission to ICU, abscess, biliary leakage, intrahepatic and distant tumor recurrence and in-hospital mortality were comparable between the two groups. Conclusion: Precoagulation with MWA reduced intraoperative blood loss with similar postoperative complications, providing a safe, effective, novel alternative for hepatic parenchymal transection during liver partial resection. Additional results from larger series are recommended to confirm these findings.

Rationale: Gallbladder carcinoma is a malignant biliary tract tumor which is characterized by poor prognosis. Recent advances in genomic medicine have identified a few novel germline mutations that contribute to the increased risk of gallbladder carcinoma. RAD52 is a crucial human deoxyribonucleic acid (DNA) repair gene involved in maintaining genomic stability and preventing tumor occurrence. Patient concerns: A 57-year-old man was hospitalized for space-occupying lesions in the gallbladder. Diagnosis: A diagnosis of gallbladder adenocarcinoma was made based on computed tomography, B-ultrasound, blood tests, and postoperative pathology. Interventions: Next-generation sequencing using a 599-gene panel and Sanger sequencing were performed to validate the mutation in the proband and his family members, respectively. Outcomes: A novel potentially pathogenic heterozygous germline RAD52 missense mutation (c.276T > A: p.N92K) was identified in the patient. Sanger sequencing revealed that this variation was not observed in unaffected family members. Lessons: We identified a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma. Our results added to the current body of knowledge. It also provides new insights into genetic counseling and targeted therapeutic strategies for patients with gallbladder carcinoma.

Background Acute liver injury (ALI) is a severe liver disease. Chitinase 3-like-1 (CHI3L1), a protein belonging to the glycosyl hydrolase family 18, is involved in many diseases, such as inflammatory diseases, bacterial infections, and various malignant tumors; however, the function of CHI3L1 in ALI remains unclear. The objective of this study was to evaluate the protective functions of CHI3L1 against thioacetamide (TAA)-induced ALI in mice and explore its potential mechanisms. Methods Data from 20 patients with ALI and 10 healthy subjects was collected. Serum CHI3L1, serum aspartate transaminase (AST), and serum alanine aminotransferase (ALT) were measured. To establish ALI mouse models, thioacetamide was intraperitoneally injected into groups of the CHI3L1-knockout (CHI3L1-KO) and wild-type (WT) mice (80 and 150 mg/kg). Recombinant CHI3L1 protein (rCHI3L1) (5 µg/kg), IFN-γ (500 ng), and WP1033 (an inhibitor of P-STAT3, 0.2 mL) were injected before TAA treatment, after which the effects were estimated. Splenic CD4+CD62L+ naive T cells were isolated from CHI3L1-KO mice and stimulated to differentiate into regulatory T (Treg) cells, T-helper 1 (Th1) cells, T-helper 2 (Th2) cells, and T-helper 17 (Th17) cells. Results Increased serum CHI3L1 levels were seen both in healthy subjects and post-therapy patients compared with ALI patients. CHI3L1 levels were negatively correlated with serum ALT and AST levels in ALI patients. CHI3L1-KO group showed higher serum ALT and AST levels than the WT group following TAA treatment, while tail vein injection of rCHI3L1 reduced liver tissue injury and improved Treg cell differentiation in vivo. In vitro experiment showed that knockout of CHI3L1 improved IFN-γ+ Th1 cell differentiation. Furthermore, intraperitoneal administration of IFN-γ produced more severe hepatocellular necrosis compared with rCHI3L1 injection alone. Mechanism study showed that T-box expressed in T cells (T-bet), and signal transducer and activator of transcription 3 (STAT3), play a critical role in adversely mediating the effect of CHI3L1, which is consistent with the finding that treatment with WP1033 down-regulated the differentiation of the Th1 cells in vitro and reduced severity of liver injury in vivo. Conclusions CHI3L1 reduced the production of IFN-γ and inhibited Th1 cell differentiation through the STAT3 signaling pathway, which could be a potential therapeutic strategy for treating ALI.

Our previous study demonstrated that preoperative short-term fasting attenuates mice hepatic ischemia/reperfusion injury (IRI), which greatly piqued our interest in verifying if fasting produces similar protective effects in patients undergoing hepatectomy.Eighty patients with liver tumors were randomized into control (Ctrl, n=40, preoperative fasting for 6 h) or fasting group (Fasting, n=40, preoperative fasting for 24 h). Serum was collected at pre-operation (Pre-Op), post-operation 1 day (POD-1), post-operation 3 days (POD-3), and post-operation 7 days (POD-7). Liver tissue was removed from the resected specimen.Sixty-three patients were eventually enrolled, with 33 in Ctrl and 30 in Fasting group. Our data showed that 24 h fasting effectively attenuated elevated sALT and sAST levels after operation (P0.05), but serum total bilirubin was significantly lower at only POD-3 (P0.05); and serum albumin was not markedly different in either of the groups. Interestingly, 24 h fasting partially attenuates expression of pro-inflammatory cytokine (TNF-α) and improves oxidative stress (MDA and SOD). Our data further showed short-term fasting triggered Nrf2 signaling pathway.This study demonstrates preoperative short-term fasting effectively improves clinical outcomes and markedly attenuates inflammatory responses and oxidative stress in patients undergoing hepatectomy, and Nrf2 signaling pathway may play a key role in fasting against inflammatory responses and oxidant stress.

Background: This study aimed to investigate the mechanism of galectin (Gal)-1 of regulating Treg/Th17 in pathogenesis of acute rejection after liver transplantation in rat. Methods: Mononuclear cells were induced to immature dendritic cells (imDCs), which were transfected with or without NF-κB/RelB. Western Blot was performed to detect the expression of NF-κB/RelB. the expression of CD11c, CD45RB, CD80 and MHC II were detected by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokines IL-27 and TGF-β. Lewis and dark agouti (DA) rats were generally anaesthetized by isoflurane inhalation to establish liver transplant models. Results: We demonstrate that Gal-1 disturbs maturation of imDCs by downregulating NF-κB/RelB expression, and Gal-1 negatively controls CD4 + proliferation though IL-27 pathway. Conclusions: In aggregate, Gal-1 promotes Treg differentiation in CD4 + T cells though NF-κB/RelB- IL-27 pathway. These findings suggest a new therapeutic target to mediate Treg population.

Objectives Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1) is a cancer/testis antigen reactivated in several human malignancies. So far, the major focus of studies on KK‐LC‐1 has been on its potential as diagnostic biomarker and immunotherapy target. However, its biological functions and molecular mechanisms in cancer progression remain unknown. Materials and Methods Expression of KK‐LC‐1 in HCC was analysed using RT‐qPCR, Western blot and immunohistochemistry. The roles of KK‐LC‐1 on HCC progression were examined by loss‐of‐function and gain‐of‐function approaches. Pathway inhibitor DAPT was employed to confirm the regulatory effect of KK‐LC‐1 on the downstream Notch signalling. The interaction of KK‐LC‐1 with presenilin‐1 was determined by co‐immunoprecipitation. The association of CpG island methylation status with KK‐LC‐1 reactivation was evaluated by methylation‐specific PCR, bisulphite sequencing PCR and 5‐Aza‐dC treatment. Results We identified that HCC tissues exhibited increased levels of KK‐LC‐1. High KK‐LC‐1 level independently predicted poor survival outcome. KK‐LC‐1 promoted cell growth, migration, invasion and epithelial‐mesenchymal transition in vitro and in vivo. KK‐LC‐1 modulated the Notch1/Hes1 pathway to exacerbate HCC progression through physically interacting with presenilin‐1. Upregulation of KK‐LC‐1 in HCC was attributed to hypomethylated CpG islands. Conclusions This study identified that hypomethylation‐induced KK‐LC‐1 overexpression played an important role in HCC progression and independently predicted poor survival. We defined the KK‐LC‐1/presenilin‐1/Notch1/Hes1 as a novel signalling pathway that was involved in the growth and metastasis of HCC.

It has been demonstrated that ursolic acid (UA) could effectively induces apoptosis of cancer cells by inhibiting the expression of cyclooxygenase 2 (COX-2), which constitutively expresses in gastric cancer. However, the hydrophobicity of UA increases the difficulty in its potential clinical application, which raises the possibility for its application as a novel model drug in nanoparticle-based delivery system. UA-loaded nanoparticles (UA-NPs) were prepared by a nano-precipitation method using amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers as drug carriers. UA was effectively transported into SGC7901 cells by nanoparticles and localized around the nuclei in the cytoplasms. The in vitro cytotoxicity and apoptosis test indicated that UA-NPs significantly elicited more cell death at almost equivalent dose and corresponding incubation time. Moreover, UA-NPs led to more cell apoptosis through stronger inhibition of COX-2 and activation of caspase 3. The most powerful evidence from this report is that the significant differences between the cytotoxicity of free UA and UA-NPs are closely related to the expression levels of COX-2 and caspase-3, which demonstrates the superiority of UA-NPs over free UA through penetrating cell membrane. Therefore, the study offer an effective way to improve the anticancer efficiency of UA through nano-drug delivery system.

Perivascular epithelioid cell tumor (PEComa) is a rare, soft tissue tumor that can occur in various locations. The present report included three patients (one male and two females; age range, 25-51 years) with hepatic PEComas. The collected data included the clinical manifestations, diagnosis, management, treatment, and prognosis. Since it is difficult to diagnose hepatic PEComas by imaging, the patients were diagnosed by tumor tissue examination such as immunohistochemistry, which was positive for HMB-45, Melan-A, and SMA on all slides. The tumor was composed of diverse tissues including smooth muscle, adipose tissue, and thick-walled blood vessels. During the follow-up period, one of the tumors was malignant (double-positive for CD34 and Ki-67) and recurred 3 months after surgery. In addition, malignant hepatic PEComas were reviewed in the literature, indicating that the majority of hepatic PEComas are benign, but few hepatic PEComas exhibit malignant behaviors in older female patients (>50 years of age) with abdominal discomfort and pain, larger tumor size (>10 cm), or positive staining for CD34 and Ki-67. In conclusion, there is no effective method to diagnose PEComas. Currently, the diagnosis of PEComas depends on immunohistochemical staining. Tumor resection and close follow-up are the principal methods for the management of PEComas.

Calorie restriction or starvation (fasting) has some beneficial effects in terms of prolonging life and increasing resistance to stress. It has also been shown that calorie restriction has a protective role during ischemia-reperfusion injury (IRI) in several organs, but the underlying mechanism has not been elucidated. In this study we investigated the effects and molecular mechanisms of short-term starvation (STS) on liver IRI in a mouse liver IRI model. We found that STS significantly attenuated liver IRI in this model, as evidenced by inhibition of serum aminotransferase levels, and decreased pathological damage and hepatocellular apoptosis, especially after 2- or 3-day starvation. Furthermore, we found that 2- or 3-day starvation induced expression of hepatocellular autophagy in vivo and in vitro. Further experiments provided support for the notion that STS-induced autophagy played a key role during starvation-regulated protection against liver IRI via autophagy inhibition with 3-methyladenine. Interestingly, the longevity gene Sirt1 was also significantly up-regulated in liver after STS. Importantly, inhibition of Sirt1 by sirtinol abolished STS-induced autophagy and further abrogated STS-mediated protection against liver IRI. In conclusion, our results indicate that STS attenuates liver IRI via the Sirt1-autophagy pathway. Our findings provide a rationale for a novel therapeutic strategy for managing liver IRI.

Recent studies have shown that microRNA-146a (miR-146a) is associated with cancer metastasis. However, the mechanisms underlying this process remain poorly understood. In this study, we aimed to investigate the potential role of miR-146a in gastric cancer metastasis. A wound-healing assay and a Transwell assay were used to investigate the impact of miR-146a on the migratory and invasive abilities of MKN-45 cells in vitro. MKN-45 cells stably expressing miR-146a or the negative control were transplanted into nude mice through the lateral tail vein to explore the effect of miR-146a on tumor metastasis in vivo. A luciferase reporter assay and western blot analysis were used to identify the potential target genes. Our results show that the overexpression of miR-146a inhibits the invasion and metastasis of MKN-45 cells in vitro and in vivo. Furthermore, the L1 cell adhesion molecule (L1CAM) was identified as a novel target of miR‑146a in gastric cancer. Taken together, our results provide evidence that miR-146a suppresses gastric cancer cell invasion and metastasis in vitro and in vivo, which may be in part due to the downregulation of L1CAM. miR-146a may have the therapeutic potential to suppress gastric cancer metastasis.

Fast-track surgery and enhanced recovery after surgery have been applied to many surgical procedures; however, data on fast-track surgery and enhanced recovery after surgery following liver transplantation is limited. This study aimed to conduct a prospective study to determine the effects of fast-track surgery on prognosis after liver transplantation.This was a prospective, single-blinded, randomized study. One hundred twenty-eight patients undergoing liver transplantation were selected for the fast-track (FT group, n=54) or conventional process (NFT group, n=74). The primary endpoints were intensive care unit (ICU) stay and hospital stay. The secondary endpoints were as follows: operative time, anhepatic phase time, intraoperative blood loss, intraoperative blood transfusion volume, postoperative complications, readmission rate, and postoperative mortality.There was no significant difference in preoperative demographics between the two groups. The median ICU stay was 2 days (range 1-7 days) in the FT group and 5 days (range 3-12 days) in the NFT group (P0.01). Furthermore, the hospital stay was also significantly reduced in the FT group (P0.01). The operative time, anhepatic phase time, intraoperative blood loss, and intraoperative blood transfusion volume were decreased in the FT group compared with the NFT group (P0.05). Based on Spearman correlation analysis, the ICU stay and hospital stay may be positively correlated with operative time, anhepatic phase time and intraoperative blood loss. There were no differences in the incidence of postoperative complications, readmissions, and postoperative mortality between the two groups.Fast-track procedures effectively reduce the ICU stay and hospital stay without adversely affecting prognosis. This study demonstrated that fast-track protocols are safe and feasible in liver transplantation.

Background and aims Recently, a couple of the long noncoding RNAs (lncRNAs) have been proved to participate in hepatocellular carcinoma development and progression. However, their associations with liver cirrhosis have not been reported. In this study, we aimed to identify the affection of HULC on regulatory T cells (Tregs) differentiation in HBV-related liver cirrhosis. Methods Seven lncRNAs were chosen as candidate lncRNAs based on the association with liver disease. The candidate lncRNAs were validated by RT-qPCR. Additional flow cytometry of Tregs was performed in 34 HBV-related liver cirrhosis patients and 34 healthy volunteers. To investigate the function of HULC, HULC expression was modified by gene overexpression via lentivirus vector. RIP assay was performed further to validate the association between HULC and p18. Results Circulation Tregs and HULC were significantly up-regulated in plasma samples of HBV-related cirrhosis patients. In addition, overexpression of HULC by lentivirus vector elevated Treg frequency in vitro. Furthermore, RIP assay showed that HULC down-regulated the level of p18 directly. Conclusions We confirmed the effects of HULC on Tregs differentiation in HBV-related liver cirrhosis. In addition, it was proved that HULC regulates the function of Tregs through down-regulated the level of p18 directly.

Xiaolin Li,1,* Hua’e Xu,2,* Xinzheng Dai,3,4,* Zhenshu Zhu,5 Baorui Liu,6 Xiaowei Lu11Department of Geriatrics, 2Department of Pharmacy, the First Affiliated Hospital to Nanjing Medical University, Nanjing; 3Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, 4Liver Transplantation Center, the First Affiliated Hospital to Nanjing Medical University, Nanjing; 5Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing; 6The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China*These authors contributed equally to this workAbstract: Paclitaxel (Ptx), one of the most widely used anticancer agents, has demonstrated extraordinary activities against a variety of solid tumors. However, the therapeutic response of Ptx is often associated with severe side effects caused by its nonspecific cytotoxic effects and special solvents (Cremophor EL®). The current study reports the stable controlled release of Ptx/tetrandrine (Tet)-coloaded nanoparticles by amphilic methoxy poly(ethylene glycol)–poly(caprolactone) block copolymers. There were three significant findings. Firstly, Tet could effectively stabilize Ptx-loaded nanoparticles with the coencapsulation of Tet and Ptx. The influence of different Ptx/Tet feeding ratios on the size and loading efficiency of the nanoparticles was also explored. Secondly, the encapsulation of Tet and Ptx into nanoparticles retains the synergistic anticancer efficiency of Tet and Ptx against mice hepatoma H22 cells. Thirdly, in the in vivo evaluation, intratumoral administration was adopted to increase the site-specific delivery. Ptx/Tet nanoparticles, when delivered intratumorally, exhibited significantly improved antitumor efficacy; moreover, they substantially increased the overall survival in an established H22-transplanted mice model. Further investigation into the anticancer mechanisms of this nanodelivery system is under active consideration as a part of this ongoing research. The results suggest that Ptx/Tet-coloaded nanoparticles could be a potential useful chemotherapeutic formulation for liver cancer therapy.Keywords: tetrandrine, paclitaxel, nanoparticle, liver cancer