Relationships Among Serological Indicators and In Vitro High-Throughput Drug Sensitivity Screening Results in Patients with Hepatocellular Carcinoma.

AIM: The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC). METHODS: This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman's correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50. RESULTS: In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman's correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators. CONCLUSIONS: NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.

Comparison of different adjuvant therapy regimen efficacies in patients with high risk of recurrence after radical resection of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical surgery. Postoperative adjuvant transhepatic arterial chemoembolization (PA-TACE), postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC), postoperative adjuvant radiotherapy (PA-RT), and postoperative adjuvant molecular targeted therapy have been demonstrated to be effective in reducing the postoperative recurrence rate. The present network meta-analysis was conducted to compare the effects of PA-TACE, PA-HAIC, PA-RT and postoperative adjuvant molecular targeted therapy on the overall survival (OS) and disease-free survival (DFS) in HCC patients after radical resection and to determine the optimal treatment strategy. METHODS: Network meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Library, and Web of Science were used to collect eligible studies up to December 25, 2022. Studies related to PA-TACE, PA-HAIC, and postoperative adjuvant molecular targeted therapy after radical HCC resection was included. The endpoints were OS and DFS, and the effect size was determined using hazard ratio with a 95% confidence interval. R software and "gemtc" package were employed to analyze the results. RESULTS: A total of 38 studies involving 7079 patients with HCC after radical resection were ultimately enrolled to be analyzed. Four postoperative adjuvant therapy measures and two oncology indicators were evaluated. In this study, OS-related investigations validated that PA-Sorafenib and PA-RT markedly enhanced the OS rates in patients after radical resection when compared to PA-TACE and PA-HAIC. However, statistical analysis revealed no significant difference between PA-Sorafenib and PA-RT, as well as PA-TACE and PA-HAIC. In the DFS-related investigations, PA-RT demonstrated superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC. Additionally, PA-Sorafenib displayed better efficacy than PA-TACE. Nevertheless, there was no statistical significance between PA-Sorafenib and PA-HAIC, as well as PA-TACE and PA-HAIC. We also performed a subgroup analysis of studies focusing on HCC complicated by microvascular invasion after radical resection. In terms of OS, both PA-RT and PA-Sorafenib demonstrated a noteworthy improvement over PA-TACE, whereas no statistical significance was detected between PA-RT and PA-Sorafenib. Likewise, for DFS, both PA-Sorafenib and PA-RT exhibited superior efficacy compared to PA-TACE. CONCLUSION: In patients with HCC after radical resection and a high risk of recurrence, both PA-Sorafenib and PA-RT significantly improved OS and DFS when compared to PA-TACE and PA-HAIC. Notably, PA-RT exhibited superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC in terms of DFS. Similarly, PA-Sorafenib appeared to be more effective than PA-TACE for DFS.

Correlation between Immunohistochemical Markers in Hepatocellular Carcinoma Cells and In Vitro High-Throughput Drug Sensitivity Screening.

AIM: This study analyzed the correlation between immunohistochemical markers in hepatocellular carcinoma cells and the results of in vitro high-throughput drug sensitivity screening, to provide a reference for individualized drug treatment in patients with liver cancer. METHODS: Seventy-four patients with hepatocellular carcinoma were included in this study from December 2019 to June 2021, and their liver cancer cells were used for in vitro high-throughput drug sensitivity screening. According to the screening results, the patients were divided into relatively sensitive and insensitive groups, and the correlations between sensitivity and immunohistochemistry results were analyzed statistically. RESULTS: Alpha-fetoprotein (AFP)-positive liver cancer cells were significantly more sensitive to gemcitabine than AFP-negative cells (χ 2 = 6.102, P=0.014). AFP was also positively correlated with sensitivity of liver cancer cells to three combined regimens containing oxaliplatin (L-OHP) and epirubicin (EPI) : L-OHP + EPI + irinotecan + 5-fluorouracil (5-FU), L-OHP + irinotecan + EPI, and L-OHP + EPI (χ 2 = 8.168, P=0.004, χ 2 = 5.705, P=0.017, and χ 2 = 8.275, P=0.004, respectively). CONCLUSION: Gemcitabine and L-OHP + EPI + irinotecan + 5-FU, L-OHP + EPI, and L-OHP + irinotecan + EPI were more effective against AFP-positive compared with AFP-negative liver cancer cells according to in vitro high-throughput drug sensitivity screening. These results may guide the selection of personalized drug treatments for patients with advanced liver cancer in the future but still need further clinical studies to confirm.

Therapeutic effect of postoperative adjuvant transcatheter arterial chemoembolization based on the neutrophil-to-lymphocyte ratio.

Aim: To evaluate the feasibility of the preoperative neutrophil-to-lymphocyte ratio (NLR) as an index to guide postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in patients with liver cancer. Methods: We recruited a total of 166 patients with liver cancer who underwent surgery alone or surgery plus PA-TACE between January 2013 and June 2017 and compared the 1, 2, and 3-year recurrence-free survival (RFS) and overall survival (OS) between patients with high and low NLRs, surgery and surgery plus PA-TACE groups, and relevant subgroups using the Kaplan-Meier method. We also evaluated the independent factors affecting the prognosis of liver cancer after surgery using a Cox risk ratio model and correlation between NLR levels and high-risk recurrence factors of liver cancer with logistic regression analysis. Results: The 1, 2, and 3-year RFS rates were all significantly higher in the low-NLR group compared to the high-NLR group (P < 0.05). However, the 1, 2, and 3-year OS rates were similar in the low- and high-NLR groups (P > 0.05). After propensity score matching, the 1, 2, and 3-year RFS and OS rates were significantly better in patients treated with surgery plus PA-TACE compared with surgery alone (P < 0.05). The 1, 2, and 3-year RFS and OS rates were also significantly better in the surgery plus PA-TACE subgroup compared with the surgery-alone subgroup in the high-NLR group (P < 0.05), but there was no significant difference in RFS or OS between the surgery plus PA-TACE and surgery-alone subgroups at 1, 2, and 3 years in the low-NLR group (P > 0.05). Multivariate analysis in the high-NLR group showed that a poorly differentiated or undifferentiated tumor was an independent risk factor for postoperative RFS. Multiple tumors were an independent risk factor for postoperative OS (P < 0.05), while PA-TACE was an independent protective factor for postoperative RFS and OS (P < 0.05). In the low-NLR group, AFP > 400 µg/L was an independent risk factor for postoperative OS (P < 0.05). Multivariate logistic regression indicated that patients with a maximum tumor diameter of >5 cm were at increased risk of having high NLR levels compared to patients with a maximum tumor diameter of <5 cm (P < 0.05). Conclusion: PA-TACE can improve the prognosis of patients with a high preoperative NLR (≥2.5), but has no obvious benefit in patients with low preoperative NLR (<2.5). This may provide a reference for clinical selection of PA-TACE.

Conversion therapy of hepatic artery ligation combined with transcatheter arterial chemoembolization for treating liver cancer: A case report.

BACKGROUND: Hepatocellular carcinoma is an aggressive tumor, and its latency and lack of clinical symptoms mean that most patients are already in the late stage when diagnosed. Large tumor volume and metastasis are the main reasons for not attempting surgery. Portal vein embolization and associated liver partition and portal vein ligation for staged hepatectomy are commonly used in clinical practice to increase the volume of remnant liver to allow surgical resection; however, research in this area is currently lacking. CASE SUMMARY: A 48-year-old male patient with a history of viral hepatitis B for at least 30 years attended our center with a hepatic space-occupying lesion detected 3 d previously. Enhanced computed tomography scanning of the upper abdomen revealed a large mass in the right lobe of the liver, centered on the right posterior lobe, with the larger section measuring about 14 cm × 10 cm × 14 cm. He successfully underwent conversion therapy for a large right liver tumor after combined hepatic artery ligation and transcatheter arterial chemoembolization, and finally had an opportunity to undergo right hemi-hepatectomy and cholecystectomy. He remained asymptomatic with no obvious abnormalities on computed tomography scanning review at 2 mo after surgery. CONCLUSION: This case highlights new ideas and provides a reference for conversion therapy of large liver tumors.

Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats.

Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of α-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, but also significantly enhanced neurons' survival, and attenuated neuronal apoptosis, as well as promoted motor and sensory function recovery in hind limbs. While, overexpression SNCA exhibited the opposite effects. In vitro, cortical neurons transfected with SNCA-shRNA lentivirus gave rise to an optimal neuronal survival and neurite outgrowth, while it was accompanied by reverse efficiency in SNCA-ORF group. In molecular level, SNCA silence induced the upregulation of Bcl-2 and the downregulation of Bax, and the expression of NGF, BDNF and NT3 was substantially upregulated in cortical neurons. Together, endogenous SNCA play a crucial role in motor and sensory function regulation, in which, the underlying mechanism may be linked to the regulation of apoptosis associated with apoptotic gene (Bax, Bcl2) and neurotrophic factors expression (NGF, BDNF and NT3). These finds provide novel insights to understand the role of SNCA in cerebral cortex after SCT, and it may be as a novel treatment target for SCI repair in future clinic trials.

[Research on cells ablation characters by laser plasma].

The study on the mechanism of laser ablated cells is of importance to laser surgery and killing harmful cells. Three radiation modes were researched on the ablation characteristics of onion epidermal cells under: laser direct irradiation, focused irradiation and the laser plasma radiation. Based on the thermodynamic properties of the laser irradiation, the cell temperature rise and phase change have been analyzed. The experiments show that the cells damage under direct irradiation is not obvious at all, but the focused irradiation can cause cells to split and moisture removal. The removal shape is circular with larger area and rough fracture edges. The theoretical analysis found out that the laser plasma effects play a key role in the laser ablation. The thermal effects, radiation ionization and shock waves can increase the deposition of laser pulses energy and impact peeling of the cells, which will greatly increase the scope and efficiency of cell killing and is suitable for the cell destruction.

Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats.

With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5 × 10(5) NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.