FAT10 mediates the sorafenib-resistance of hepatocellular carcinoma cells by stabilizing E3 ligase NEDD4 to enhance PTEN/AKT pathway-induced autophagy.

Although sorafenib is the first-line therapeutic agent for advanced hepatocellular carcinoma (HCC), the development of drug resistance in HCC cells limits its clinical efficacy. However, the key factors involved in mediating the sorafenib resistance of HCC cells and the underlying mechanisms have not been elucidated. In this study, we generated sorafenib-resistant HCC cell lines, and our data demonstrate that HLA-F locus-adjacent transcript 10 (FAT10), a ubiquitin-like protein, is markedly upregulated in sorafenib-resistant HCC cells and that reducing the expression of FAT10 in sorafenib-resistant HCC cells increases sensitivity to sorafenib. Mechanistically, FAT10 stabilizes the expression of the PTEN-specific E3 ubiquitin ligase NEDD4 that causes downregulation of PTEN, thereby inducing AKT-mediated autophagy and promoting the resistance of HCC cells to sorafenib. Moreover, we screened the small molecule Compound 7695-0983, which increases the sensitivity of sorafenib-resistant HCC cells to sorafenib by inhibiting the expression of FAT10 to inhibit NEDD4-PTEN/AKT axis-mediated autophagy. Collectively, our preclinical findings identify FAT10 as a key factor in the sorafenib resistance of HCC cells and elucidate its underlying mechanism. This study provides new mechanistic insight for the exploitation of novel sorafenib-based tyrosine kinase inhibitor (TKI)-targeted drugs for treating advanced HCC.

Selective Laser Melting of the Porous Ta Scaffold with Mg-Doped Calcium Phosphate Coating for Orthopedic Applications.

Addressing the repair of large-scale bone defects has become a hot research topic within the field of orthopedics. This study assessed the feasibility and effectiveness of using porous tantalum scaffolds to treat such defects. These scaffolds, manufactured using the selective laser melting (SLM) technology, possessed biomechanical properties compatible with natural bone tissue. To enhance the osteogenesis bioactivity of these porous Ta scaffolds, we applied calcium phosphate (CaP) and magnesium-doped calcium phosphate (Mg-CaP) coatings to the surface of SLM Ta scaffolds through a hydrothermal method. These degradable coatings released calcium and magnesium ions, demonstrating osteogenic bioactivity. Experimental results indicated that the Mg-CaP group exhibited biocompatibility comparable to that of the Ta group in vivo and in vitro. In terms of osteogenesis, both the CaP group and the Mg-CaP group showed improved outcomes compared to the control group, with the Mg-CaP group demonstrating superior performance. Therefore, both CaP and magnesium-CaP coatings can significantly enhance the osseointegration of three-dimensional-printed porous Ta, thereby increasing the surface bioactivity. Overall, the present study introduces an innovative approach for the biofunctionalization of SLM porous Ta, aiming to enhance its suitability as a bone implant material.

Comparing triple scope-combined bile duct exploration lithotripsy with laparoscopic hepatectomy for hepatolithiasis (with video).

BACKGROUND: To compare the efficacy of Three-scope combined (laparoscopic, rigid choledochoscopy and electronic choledochoscopy, TS) with laparoscopic hepatectomy (LH) for patients with hepatolithiasis (HL). METHODS: Between January 2019 and January 2020, 118 consecutive patients with HL treated with TS (TS group, n = 57) or LH (LH group, n = 61) were analyzed in this study. Perioperative and long-term outcomes, including operative time, intraoperative blood loss, blood transfusion, postoperative bowel function recovery time, postoperative hospital stay, complication rate, stone removal rate, and stone recurrence rate, were compared and analyzed between the two groups. RESULTS: Compared with the LH group, the TS group had significantly lower intraoperative blood loss and transfusions, significantly shorter operative time and hospital stay, and fewer complications (P < 0.05 for all). There was no significant difference in the final stone removal rate, stone recurrence rate and postoperative bowel function recovery time (P > 0.05 for all). CONCLUSION: TS is a safe and effective treatment for HL and is superior to LH in terms of overall treatment outcome and complications.

Comparative analysis of postoperative curative effect of liver wedge resection and liver IVb + V segment resection in patients with T2b gallbladder cancer.

Objective: To compare the therapeutic effects of wedge resection and liver segment IVb + V resection on patients with T2b gallbladder cancer. Methods: The clinical and pathological data of 40 patients with gallbladder cancer admitted to the Second Affiliated Hospital of Nanchang University from January 2017 to November 2019 were retrospectively analyzed, and they were divided into two groups according to different surgical methods. The control group underwent liver wedge resection, while the experimental group underwent liver segment IVb + V resection. Preoperative age, bilirubin index, tumor markers, postoperative complications and survival were compared between the two groups. Log-rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. Kaplan-Meier survival curves were drawn. Results: Univariate analysis showed that tumor markers and degree of differentiation were the risk factors for the prognosis of patients with gallbladder carcinoma after radical cholecystectomy (P < 0.05). Multivariate analysis showed that the elevation of CA125 and CA199, poor differentiation, and Lymph node metastasis were independent risk factors for the prognosis of gallbladder carcinoma after radical resection (P < 0.05). According to the 3-year survival rate, the survival rate of patients with liver 4B + 5 segment resection + cholecystectomy was higher than that of patients with 2 cm liver wedge resection + cholecystectomy (41.6% vs. 72.7%). Conclusion: Patients with T2b gallbladder cancer should be treated with liver segment IVb + V resection, which is helpful to improve the prognosis of patients and should be widely promoted.

Research progress and clinical translation of three-dimensional printed porous tantalum in orthopaedics.

With continuous developments in additive manufacturing technology, tantalum (Ta) metal has been manufactured into orthopaedic implants with a variety of forms, properties and uses by three-dimensional printing. Based on extensive research in recent years, the design, processing and performance aspects of this new orthopaedic implant material have been greatly improved. Besides the bionic porous structure and mechanical characteristics that are similar to human bone tissue, porous tantalum is considered to be a viable bone repair material due to its outstanding corrosion resistance, biocompatibility, bone integration and bone conductivity. Numerous in vitro, in vivo, and clinical studies have been carried out in order to analyse the safety and efficacy of these implants in orthopaedic applications. This study reviews the most recent advances in manufacturing, characteristics and clinical application of porous tantalum materials.

Th22/IL-22 mediates the progression of HBV-related hepatocellular carcinoma via STAT3.

T helper cell 22 are abundant in Hepatitis B Virus-related hepatocellular carcinoma tissue, and the main cytokine interleukin 22 produced by Th22 cells is closely related to the initiation and development of HCC. Understanding the role of Th22/IL-22 in the progression of HBV-related HCC will facilitate new therapeutic development. Th22 cells were isolated from peripheral blood of healthy donors and co-cultured with HBV positive HepG2.2.15 cells. IL-22 secretion and HepG2.2.15 cell proliferation and apoptosis were monitored. Expressions of p-STAT3, Cyclin D1, Bcl-2, and cleaved caspase 3 were detected by Western blot analysis. Th22 cells significantly promoted the proliferation and inhibited the apoptosis of HepG2.2.15 cells; up-regulated expression of p-STAT3, Cyclin D1 and Bcl-2, and down-regulated cleaved caspase 3 in HepG2.2.15 cells. These effects were significantly attenuated when IL-22 and STAT3 was knockdown in Th22 and HepG2.2.15 cells, respectively. Our data suggests that HBV induces host Th22 cells to overexpress IL-22, which in turn triggers over-activation of STAT3 and its downstream signaling proteins to promote HCC progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-021-00517-9.

Safety and feasibility of laparoscopic left hepatectomy for the treatment of hepatolithiasis in patients with previous abdominal surgery.

BACKGROUND: The aim of the study was to compare the benefits and drawbacks of laparoscopic left hepatectomy (LLH) in patients with previous abdominal surgery (PAS) with those in patients without PAS and confirm the safety and feasibility of LLH as a treatment for patients with hepatolithiasis and PAS. MATERIALS AND METHODS: This retrospective comparative study included 111 patients who underwent LLH for hepatolithiasis (with PAS, n = 41; without PAS, n = 70) from August 2017 to August 2019. Patients' general information, surgical outcomes, hospital stay duration, hospitalisation cost, post-operative laboratory data and post-operative complications were evaluated. RESULTS: No statistically significant difference was noted in the post-operative laboratory data between patients with and without PAS (P > 0.05). Longer operative times were required for patients with PAS than for those without PAS (P = 0.025). Hospitalisation cost, hospital stay duration, blood loss, open conversion and post-operative complications were not significantly different between patients with and without PAS (P > 0.05). No cases of mortality were noted. CONCLUSIONS: LLH is a safe and feasible treatment for patients with hepatolithiasis and PAS.

Fabrication of 2D silicon nano-mold by side etch lift-off method.

Nano-imprint technology is a method of nano-pattern reproduction, has the characteristics of high resolution, high throughput, and low-cost. It can reduce the complexity and cost of the equipment while improving the resolution, which considered a promising industrial production technology. The key to nanoimprinting lies in the mold, and the quality of the mold directly determines the quality of the imprinted graphics. Here, a method for fabricating sub-100 nm concave 2D silicon nano-mold by side etch lift-off is proposed. The effects of different wet etching time and the metal deposition angle on the width of nanochannels were studied. The measurement result of dry etching shows that on the entire 4 inch silicon wafer, the width of the nanochannel varies by 4% and the depth by 2%. The width of the nanochannel between chips varies by 0.7%, and the depth variation is 1%. With this new method, high-precision and large-scale silicon nano-mold can be produced, which has great potential for realizing high-precision and low-cost manufacturing of nano devices.

Safety and feasibility for laparoscopic versus open caudate lobe resection: a meta-analysis.

BACKGROUND: Laparoscopic hepatectomy has been used widely due to its advantages as a minimally invasive surgery. However, multicenter, large-scale, population-based laparoscopic caudate lobe resection (LCLR) versus open caudate lobe resection (OCLR) has rarely been reported. We assessed the feasibility and safety of LCLR compared with OCLR using meta-analysis. METHODS: Relevant literature was retrieved using PubMed, Embase, Cochrane, Ovid Medline, Web of Science, CNKI, and WanFang Med databases up to July 30th, 2020. Multiple parameters of feasibility and safety were compared between the treatment groups. Quality of studies was assessed with the Newcastle-Ottawa Scale (NOS). The data were analyzed by Review Manager 5.3. Results are expressed as odds ratio (OD) or mean difference (MD) with 95% confidence interval (95% CI) for fixed- and random-effects models. RESULTS: Seven studies with 237 patients were included in this meta-analysis. Compared with OCLR, the LCLR group had a lower intraoperative blood loss (MD - 180.84; 95% CI - 225.61 to - 136.07; P < 0.0001), shorter postoperative hospital stays (MD - 4.38; 95% CI - 7.07 to - 1.7; P = 0.001), shorter operative time (MD - 50.24; 95% CI - 78.57 to - 21.92; P = 0.0005), and lower rates in intraoperative blood transfusion (OR 0.12; P = 0.01). However, there were no statistically significant differences between LCLR and OCLR regarding hospital expenses (MD 0.92; P = 0.12), pedicle clamping (OR 1.57; P = 0.32), postoperative complications (OR 0.58; P = 0.15), bile leak (P = 0.88), ascites (P = 0.34), and incisional infection (P = 0.36). CONCLUSIONS: LCLR has multiple advantages over OCLR, especially intraoperative blood loss and hospital stays. LCLR is a very useful technology and feasible choice in patients with caudate lobe lesions.

Comparative analysis of the safety and feasibility of laparoscopic versus open caudate lobe resection.

PURPOSE: Laparoscopic hepatectomy has been used widely in liver disease due to its advantages as a minimally invasive surgery. However, laparoscopic caudate lobe resection (LCLR) has been reported rarely. We aimed to investigate the safety and feasibility of LCLR by comparing it with open liver surgery. METHODS: A retrospective study was performed including all patients who underwent LCLR and open caudate lobe resection (OCLR) between January 2015 and August 2019. Twenty-two patients were involved in this study and divided into LCLR (n = 10) and OCLR (n = 12) groups based on preoperative imaging, tumor characteristics, and blood and liver function test. Patient demographic data and intraoperative and postoperative outcomes were compared between the two groups. RESULTS: There were no significant inter-group differences between gender, age, preoperative liver function, American Society of Anesthesiologists (ASA) grade, and comorbidities (P > 0.05). The LCLR showed significantly less blood loss (50 vs. 300 ml, respectively; P = 0.004), shorter length of hospital stay (15 vs. 16 days, respectively; P = 0.034), and shorter operative time (216.50 vs. 372.78 min, respectively; P = 0.012) than OCLR, but hospital expenses (5.02 vs. 6.50 WanRMB, respectively; P = 0.208) showed no statistical difference between groups. There was no statistical difference in postoperative bile leakage (P = 0.54) and wound infection (P = 0.54) between LCLR and OCLR. Neither LCLR nor OCLR resulted in bleeding or liver failure after operation. There were no deaths. CONCLUSION: LCLR is a very useful technology, and it is a feasible choice in selected patients with benign and malignant tumors in the caudate lobe.

Design, simulation and evaluation of improved air amplifier incorporating an ion funnel for nano-ESI MS.

An improved air amplifier design that takes advantage of the combined effects of aerodynamic and electrodynamic focusing was developed to couple a nanoelectrospray ionisation (nano-ESI) source and the heated mass spectrometer inlet to improve the sensitivity of a mass spectrometer. The new design comprises an electrodynamic ion funnel integrated into the main air pathway of the air amplifier to more effectively focus and transmit gas-phase ions from the nano-ESI source into the heated mass spectrometer inlet. Numerical computational fluid dynamics simulations were carried out using a commercial software package, ANSYS FLUENT, to provide more detailed information about the device's performance. The gas flow field as well as the electric field patterns and the Lagrangian ion motion were conveniently simulated using this single package and custom-written, user-defined functions. Experimental results show a nearly five-fold improvement in reserpine ion intensity with the air amplifier operated at a nitrogen gauge pressure of 40 kPa and no direct current (DC) or radiofrequency (RF) potentials applied to the ion funnel when the distance between the electrospray emitter and sampling inlet tube was 24 mm, as compared to direct sample infusion from the same distance without the air amplifier. More importantly, a nearly three-fold additional gain in ion intensity was measured when both DC and RF potentials were co-applied, resulting in more than a 13-fold overall ion intensity gain which could be attributed to the combined air amplifier aerodynamic and ion funnel electrodynamic focusing effect.