Case Report: Persistent response to combination therapy of pemigatinib, chemotherapy, and immune checkpoint inhibitor in a patient with advanced intrahepatic cholangiocarcinoma.

Patients with advanced intrahepatic cholangiocarcinoma (iCCA) often have a poor prognosis. Recent advancements in targeted molecular therapy and immunotherapy have been made. Herein, we report a case of advanced iCCA treated with a combination of pemigatinib (a selective FGFR inhibitor), chemotherapy, and an immune checkpoint inhibitor. A 34-year-old female was diagnosed with advanced iCCA with multiple liver masses and metastases in the peritoneum and lymph nodes. Next-generation sequencing (NGS) identified the genetic mutations. An FGFR2-BICC1 gene fusion was found in this patient. The patient was treated with pemigatinib in combination with pembrolizumab plus systemic gemcitabine and oxaliplatin. After 9 cycles of the combination therapy, the patient achieved a partial response, complete metabolic response, and normalization of tumor markers. Sequentially, the patient received pemigatinib and pembrolizumab for 3 months. Due to the elevated tumor biomarker, she is currently receiving chemotherapy, pemigatinib, and pembrolizumab treatment again. She regained an excellent physical status after 16 months of treatment. To the best of our knowledge, this was the first reported case of advanced iCCA successfully treated with a combination of pemigatinib, chemotherapy, and ICIs as a first-line regimen. This treatment combination may be effective and safe in the advanced iCCA.

Preparation and characterization of starch-based composite films reinforced by quinoa (Chenopodium quinoa Willd.) straw cellulose nanocrystals.

The development of green and biodegradable nanomaterials is significant for the sustainable utilization of renewable lignocellulosic biomass. This work aimed to obtain the cellulose nanocrystals from quinoa straws (QCNCs) by acid hydrolysis. The optimal extraction conditions were investigated by response surface methodology, and the physicochemical properties of QCNCs were evaluated. The maximum yield of QCNCs (36.58 ± 1.42 %) was obtained under the optimal extraction conditions of 60 % (w/w) sulfuric acid concentration, 50 °C reaction temperature, and 130 min reaction time. The characterization results of QCNCs showed that it is a rod-like material with an average length of 190.29 ± 125.25 nm, an average width of 20.34 ± 4.69 nm, excellent crystallinity (83.47 %), good water dispersibility (Zeta potential = -31.34 mV) and thermal stability (over 200 °C). The addition of 4-6 wt% QCNCs could significantly improve the elongation at break and water resistance of high-amylose corn starch films. This study will pave the route for improving the economic value of quinoa straw, and provide relevant proof of QCNCs for the preliminary application in starch-based composite films with the best performance.

Trichoderma asperellum as a novel source to prepare chitooligosaccharides by enzymatic hydrolysis and its antimicrobial activity.

Chitooligosaccharides (COS), an important biological functional component, are mainly extracted from marine products, but its raw materials are currently facing challenges such as marine resources pollution and demineralization. This study aimed to explore Trichoderma asperellum as a novel source to prepare COS. The COS were prepared by the enzymatic degradation of chitosan from T. asperellum, and single factor experiment and orthogonal designs were used to optimize the enzymatic conditions for the preparation of COS. The composition of COS was performed by thin-layer chromatography, high-performance liquid chromatography, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results showed that the degree of deacetylation of T. asperellum chitosan was 87.59%, and its enzymatic hydrolysis yield was 89.37 % under optimized extraction conditions. Moreover, the composition of COS in T. asperellum included chitotriose, chitopentaose, and chitohexaose. Compared with shrimp shells, COS prepared from T. asperellum showed stronger antibacterial properties against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Salmonella bacilli.

Preparation of microcrystalline cellulose from agricultural residues and their application as polylactic acid/microcrystalline cellulose composite films for the preservation of Lanzhou lily.

Microcrystalline celluloses were isolated from four agricultural residues, including sweet sorghum stalk, Jerusalem artichoke stalk, grains stillage, and Chinese herb residue, and characterized in terms of physicochemical and structural properties. The obtained microcrystalline celluloses were composited with polylactic acid as a packing film for the preservation of Lanzhou lily. All the agricultural residues-derived microcrystalline celluloses were in cellulose Iß structure with high purity and good thermal stability. Microcrystalline celluloses from sweet sorghum stalk had a higher degree of polymerization (327) and crystallinity (70.52 %) than others. The preservation effect of lily bulbs packaged by films were significantly improved indicated by the lessened weight loss rate and the meliorative hardness and whiteness, which ascribe to the repressed oxidation reactions. Polylactic acid/microcrystalline cellulose composite films prepared from sweet sorghum straw have been proved the most effective. This work could offer a value-added outlet for agricultural residues to produce microcrystalline celluloses-based biocompatible films for preservation of Lanzhou lily.

Structural characterization of a polysaccharide from Abelmoschus esculentus L. Moench (okra) and its hypoglycemic effect and mechanism on type 2 diabetes mellitus.

A novel acidic polysaccharide named AeP-P-1 was prepared from Abelmoschus esculentus L. Moench (okra). AeP-P-1 is a heteropolysaccharide with a molecular weight of 3.02 × 103 kDa and is composed of L-rhamnose, D-galactose, and D-galacturonic acid in the ratio 1.87 : 3.58 : 1.00. Structural characterization based on methylation and 1D/2D NMR analyses indicated that AeP-P-1 is composed of T-linked-Rhap, T-linked-Galp, 1,2,4-linked-Rhap, 1,4-linked-Galp, 1,6-linked-Galp, and 1,3,4-linked-Galp in a molar ratio of 2.42 : 3.36 : 6.46 : 13.31 : 3.12 : 1, respectively. The hypoglycemic effect and mechanism of AeP-P-1 on type 2 diabetes mellitus were also explored. Firstly, AeP-P-1 can reduce blood lipids and liver and kidney damage caused by T2DM. Finally, AeP-P-1 induces the phosphorylation of GSK3ß, maintains the activity of glycogen synthase (GCS), and promotes glycogen synthesis by regulating the expression of insulin/PI3K/Akt pathway proteins. These results indicated that AeP-P-1 could be developed as a potential ingredient in immunostimulatory agents.

Sirolimus increases the anti-cancer effect of Huai Er by regulating hypoxia inducible factor-1α-mediated glycolysis in hepatocellular carcinoma.

BACKGROUND: Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α (HIF-1α) in the immune microenvironment promotes the progression of hepatocellular carcinoma (HCC), leading to enhanced drug resistance in cancer cells. Therefore, altering the immunosuppressive microenvironment by imp-roving the hypoxic state is a new goal in improving cancer treatment. AIM: To analyse the role of HIF-1α, which is closely related to tumour proliferation, invasion, metastasis, and angiogenesis, in the proliferation and invasion of liver cancer, and to explore the HIF-1α pathway-mediated anti-cancer mechanism of sirolimus (SRL) combined with Huai Er. METHODS: Previous studies on HCC tissues identified the importance of HIF-1α, glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA) expression. In this study, HepG2 and Huh7 cell lines were treated, under hypoxic and normoxic conditions, with a combination of SRL and Huai Er. The effects on proliferation, invasion, cell cycle, and apoptosis were analysed. Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells. RESULTS: High levels of HIF-1α, LDHA, and GLUT-1 were found in poorly differentiated HCC, with lower patient survival rates. Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment. This was achieved by activation of HIF-1α and glycolysis in HCC, leading to the upregulation of LDHA, GLUT-1, Akt/mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p27. The hypoxia-induced activation of HIF-1α showed the greatest attenuation in the SRL/Huai Er (S50 + H8) group compared to the drug treatments alone (P < 0.001). The S50 + H8 treatment significantly downregulated the expression of mTOR and HIF-1α, and significantly reduced the expression of VEGF mRNA. Meanwhile, the combined blocking of mTOR and HIF-1α enhanced the downregulation of Akt/mTOR, HIF-1α, LDHA, and GLUT-1 mRNA and resulted in the downregulation of PTEN, p27, and VEGF mRNA (P < 0.001). CONCLUSION: SRL increases the anti-cancer effect of Huai Er, which reduces the promotion of hypoxia-induced HIF-1α on the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1α and HIF-1α-PTEN signalling pathways in HCC.

Influence of leaf morphological characteristics on the dynamic changes of particulate matter retention and grain size distributions.

ABSTRACTPlant leaves can retain atmospheric particulate matter (PM) and thus alleviate air pollution. Herein, four plant species (Cerasus. serrulata, H. syriacus, H. tuberosus, and E. japonicus) from the central part of Shanxi Province, China, were investigated to analyse the dynamic changes in their PM retention capacity and grain size over five periods. The relationship between leaf morphological characteristics (leaf size and leaf surface microstructure) and dynamic changes were discussed in PM retention, revealing the influence of leaf morphological characteristics on the amount of PM retention and its composition. The results showed that amount and grain sizes of the retained PM differed significantly among the various studied species; however, the trends in PM retention of different species in the time series were the same. The grain size distributions of PM from the four species displayed a bimodal distribution, in which the main peak distribution range was 5-60 µm and the secondary peak distribution range was 0.4-1 µm. Leaves of smaller sizes and those with rough surfaces had a high PM retention capacity. Leaves with deep grooves are conductive to retaining PM2.5 and PM2.5-10, while leaves with hair are conductive to retaining PM>10. Therefore, the morphological characteristics of leaves should be considered when selecting the use of plant species to alleviate air pollution.Highlights Dynamics of PM retention capacity and grain size distributions of four plant species were analysed.Grain size distributions of PM retained on leaves had a bimodal distribution.Small leaves with grooves or hair are conductive to PM retention.Grooves are conductive to fine PM retention while hairs are conductive to coarse PM retention.

Structure, antioxidant property and protection on PC12 of a polysaccharide isolated and screened from Abelmoschus esculentus L.Moench (okra).

AeP-P-2, a pectic polysaccharide, was extracted from the fruit pod of okra. It composed of rhamnose (Rha), arabinose (Ara), glucose (Glc), galactose (Gal) and galacturonic acid (GalA) with the ratio of 4.75:2.01:1.00:4.91:7.24. The main structural feature of AeP-P-2 are 1,4-linked galacturonan units (homogalacturonan backbone) and (1 → 2) and (1 → 2,4) linked Rha (rhamnogalacturonan I region). And the other side chains contained →1)-linked Ara, (1 → 5)-linked Ara, (1 → 4)-linked Glc, (1 → 6)-linked Gal, (1 → 4)-linked Rha, (1 → 2,4)-linked Rha, →1)-linked Ara and →1)-linked Gal. When the concentration of AeP-P-2 was 3.2 mg/mL, the scavenging rates on DPPH·, ABTS, O2-· and ·OH reached to 61.88%, 87.10%, 52.17% and 60.32%, respectively. AeP-P-2 also could protect PC12 cells from the damage of H2O2 and reduce apoptosis caused by oxidative damage by decreasing the level of ROS. The findings indicated that okra was a functional vegetable and AeP-P-2 was worth studying and developing into antioxidant component.

Prognostic Value of Preoperative NLR and Vascular Reconstructive Technology in Patients With Pancreatic Cancer of Portal System Invasion: A Real World Study.

The purpose was aimed to establish a simple computational model to predict tumor prognosis by combining neutrophil to lymphocyte Ratio (NLR) and biomarkers of oncological characteristics in patients undergoing vascular reconstructive radical resection of PDAC. The enrolled patients was divided into high or low NLR group with the cutoff value determined by the receiver operator characteristic (ROC) curve. Different vascular anastomoses were selected according to the Chaoyang classification of PDAC. Survival rates were calculated using the Kaplan-Meier and evaluated with the log-rank test. Cox risk regression model was used to analyze the independent risk factors for prognostic survival. The optimal cut-off value of NRL was correlated with the differentiation, tumor size, TNM stage and distant metastasis of advanced PDAC. A curative resection with vascular reconstructive of advanced PDAC according to Chaoyang classification can obviously improve the survival benefits. Cox proportional hazards demonstrated higher evaluated NLR, incisal margin R1 and lymphatic metastasis were the independent risk predictor for prognosis with the HR > 2, meanwhile, age beyond 55, TNM stage of III-IV or Tumor size > 4cm were also the obvious independent risk predictor for prognosis with the HR ≤ 2. The advanced PADC patients marked of RS group (3 < RS ≤ 6) showed no more than 24 months of survival time according to RS model based on the six independent risk predictors. Vascular reconstruction in radical resection of advanced PDAC improved survival, higher elevated NLR (>2.90) was a negative predictor of DFS and OS in those patients accompanying portal system invasion.

PD-L1+NEUT, Foxp3+Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma.

Background: This presented study was aimed to evaluate the diagnostic and prognostic value of PD-L1+Neutrophils (PD-L1+NEUT) and neutrophil to lymphocyte ratio (NLR) based on our previous experience of Foxp3+Treg in transplantation. Methods: the NLR cutoff value of 1.79 was used to include 136 cases from the 204 patients with hepatocellular carcinoma (HCC) confirmed by clinical pathology, which were divided into highly-moderately and poorly differentiated HCC groups. The expressions of PD-L1+NEUT and Foxp3+Treg in peripheral blood and cancer tissue were detected with flow cytometry, meanwhile, PD-L1 and Foxp3 expressed in carcinoma and para-carcinoma tissues were marked by immunohistochemistry. Survival rates, including overall survival and disease-free survival, were calculated by the Kaplan-Meier curve and evaluated with the log-rank test. Finally, Cox risk regression model was used to analyze the independent risk factors for prognostic survival. Results: The level of PD-L1+NEUT, Foxp3+Treg, and NLR in peripheral blood of patients with poorly differentiated HCC were significantly increased (all P < .001). Both PD-L1+NEUT and NLR were positively correlated with Foxp3+Treg (r = 0.479, P = .0017; r = 0.58, P < .0001). The level of PD-L1+NEUT and Foxp3+Treg as well as PD-L1 and Foxp3 in cancer tissue and patients with poorly differentiated HCC were obviously increased (all P < .01), respectively. Cox regression analysis indicated that PD-L1+NEUT, NLR, and Foxp3+Treg were independent risk factors for the prognosis (P = .000, .000, .006) with a RR and 95%CI of 2.704-(2.155-3.393), 3.139-(2.361-4.173), 1.409-(1.105-1.798), respectively. Conclusion: PD-L1+NEUT, NLR, and Foxp3+Treg are independent risk factors for prognosis which maybe new marker of lower survival benefits.

Rapamycin treated tol-dendritic cells derived from BM-MSCs reversed graft rejection in a rat liver transplantation model by inducing CD8+CD45RC-Treg.

OBJECTIVE: To investigate the influence of tolerance dendritic cells (tolDCs), generated from Bone marrow mesenchymal stem cells (BM-MSCs) treated with rapamycin (Rapa) on liver allograft survival in a rat acute liver transplantation model. METHODS: Different GM-CSF induction project was used to obtain immature DCs (imDCs), mature DCs (matDCs) or tolDCs from BM-MSCs. First, MLR was performed to analyze the activity of tolDCs on polyclonaly stimulated total T cells. Then, co-cultured imDCs, matDCs and tolDCs with CD8+T cells isolated by magnetic activated cell sorting to analyze the influence on its regulatory characteristic. Last, the established rat acute liver transplantation model were adoptive transfused with imDCs, matDCs or tolDCs isolated by anti-CD11c immunomagnetic beads. The phenotype of DC cells and level of CD8+Treg in the culture system and in vivo, the expression of CD8 and CD45RC in the tissues were analyzed by flow cytometry and immunohistochemistry, respectively. RESULTS: The loGM-CSF plus IL-4 decreased the costimulatory molecules of CD80/86 and MHC class II of DCs comparison with hiGM-CSF from BM-MSCs no matter whether stimulation by LPS (P<0.05). Rapa treated not only reduced the expression of CD80/86 and MHC class II but also down-regulated the expression of CD11c after LPS stimulation which was more obviously in tolDCs by loGM-CSF project (P<0.05). Moreover, tolDCs displayed a rather higher level of IL-10 and low level of IL-12p70 than others (P<0.01), which shown a rather lower stimulative effect on the proliferation of T cells comparison with matDCs and imDCs. Co-cultured with CD8+Treg showed an improvement on induction of CD8+TCR+CD45RC-T cells (CD8+Treg) in ex vivo. The rats transfused with tolDCs has a delayed survival benefits with high level of CD8+Tregs (P<0.01) and high expression of CD45RC in liver tissue (P<0.01) and spleen when comparison with other groups. The infused tolDCs improved a mean survival time (MST) of 32 days comparison with a MTS of 9.5 days and 15.75 days displayed by rat that per-infused with matDCs and imDCs, respectively. CONCLUSION: Rapa modified tolDCs derived from BM-MSCs reversed graft rejection by improve tolerance characteristics of CD8+CD45RC-Treg in acute liver rat transplantation.

Effect of steam explosion pretreatment on the structure and bioactivity of Ampelopsis grossedentata polysaccharides.

Steam explosion (SE) was a friendly environmentally pretreatment method. In this study, the effect of steam explosion (SE) pretreatment on structure and α-glucosidase inhibitory activity of Ampelopsis grossedentata polysaccharides was evaluated. Two novel polysaccharides (AGP and AGP-SE) were extracted, isolated, purified and analyzed by NMR, FT-IR and methylation. The results indicated that AGP mainly consisted of Rha, Xyl, Glc, and Ara with a molecular weight of 2.74 × 103 kDa and AGP-SE mainly consisted of Man, Ara, and Gal with a molecular weight of 2.14 × 103 kDa. Furthermore, the backbone of AGP and AGP-SE were mainly composed of 5)-Araf-(1→, -Glcp-(1→, 6)-Glcp-(1→, 6)-Galp-(1→, 3,6)-Manp-(1→, and 2,3,6)-Glcp-(1→. Finally, we demonstrated that all polysaccharides exhibited obviously α-glucosidase inhibition activity and mixed type inhibition. AGP-SE had better α-glucosidase inhibition activity and the binding affinity KD on α-glucosidase by using Surface Plasmon Resonance (SPR) than AGP. Overall, SE pretreatment is an effective method for extracting polysaccharide and provides a new idea into the improvement of biological activity.

Structure analysis and antioxidant activity of polysaccharide-iron (III) from Cordyceps militaris mycelia.

Iron-enriched Cordyceps militaris was obtained by adding FeSO4 solution to the mycelia for biotransformation. The polysaccharide-iron (III) was extracted by water extraction and alcohol precipitation. High performance liquid chromatography showed that the crude polysaccharide-iron (III) had three components. The second component was purified by Sephadex G-150 and named as CPS-iron-II. The average molecular weight of CPS-iron-II was 44.136 kDa. The content of iron was 2.73%. The monosaccharide composition analysis indicated that the CPS-iron-II was composed of rhamnose, arabinose, galactose, glucose, mannose, galacturonic acid with percentage ratio of 0.94:3.12:27.01:36.62:30.20:2.12. The results of methylation analysis revealed that the CPS-iron-II was made of →2)-ß-D-Glcp-(1→, with →2, 4)-α-D-Glcp-(1→ highly branched. Congo-red test showed that CPS-iron-II can cause flocculation of Congo red solution. The anti-oxidative analysis showed that antioxidant activity of CPS-iron-II was almost equal to that of Vc. The manuscript provided a new way for the preparation of polysaccharide-iron(III) from Cordyceps militaris.

Robotic hepatic resection in postero-superior region of liver.

OBJECTIVE: Laparoscopic hepatectomy in the posterosuperior hepatic region is technically challenging and demanding. However, minimally invasive procedures carried out using the Da Vinci robot provide potential advantages in complex hepatectomy. This study reported the experience of a single center on robotic hepatectomy in the posterosuperior hepatic region. METHODS: This retrospective study evaluated the general characteristics and perioperative outcomes of consecutive patients who underwent robotic hepatectomy in the posterosuperior hepatic region at our center from March 2015 to January 2020. RESULTS: For 100 patients who were included into this study, 53 underwent anatomical segmentectomy or subsegmentectomy and 47 non-anatomical partial hepatectomy. There was no conversion to laparotomy. The R0 resection rate was 100%. The following perioperative outcomes were compared between patients who underwent anatomical segmentectomy/subsegmentectomy versus those who underwent non-anatomical partial hepatectomy: operation times of 160 versus 126 min, intraoperative blood losses of 100 versus 50 ml, intraoperative blood transfusion rates of 7.54% versus 4.26%, postoperative lengths of hospital stay of 5 versus 4 days, Clavien-Dindo Grade I-II complications rates of 15.09% versus 19.15%, Grade III-V complications rates of 3.77% versus 0%, bile leakage rates of 4% versus 7% and pleural effusion rates of also 4% versus 7%, respectively. CONCLUSION: The results indicated the safety and feasibility of robotic anatomical and non-anatomical liver resections in the posterosuperior hepatic region. The robotic transabdominal approach is an option for hepatectomy in the posterosuperior hepatic region.

Structural characterization and inhibitions on α-glucosidase and α-amylase of alkali-extracted water-soluble polysaccharide from Annona squamosa residue.

A novel acidic polysaccharide, named as AWPA, was extracted form Annona squamosa residue by 0.1 M NaOH alkaline solution and purified by DEAE-cellulose and Sephadex G-150. HPLC analysis indicated that AWPA was a homogeneous polysaccharide with molecular weight of 3.08 × 103 kDa. The monosaccharide composition of AWPA, determined by ion chromatography, was consisted of L-arabinose, D-galactose, d-glucose, D-mannose, D-galacturonic acid in a percentage of 15.58:13.48:60.14:9.02:1.78, respectively. The results of FT-IR, methylation and NMR showed that the sugar residue of AWPA were mainly composed of α-L-Araf-(1→, →4)-α-D-Glcp-(1→, →4)-ß-D-Galp-(1→, →6)-ß-D-Glcp-(1→, →4,6)-ß-D-Galp(1→, →3,6)-α-D-Manp-(1→, respectively. The Congo red experiment on AWPA showed that there was helix conformation. The microstructure of AWPA was detected by scanning electron microscopy, showing that the shape of AWPA was reticular and its structure was irregular. AWPA had effectively α-glucosidase inhibitory activity and α-amylase inhibitory activity with IC50 of 0.667 mg/mL and 1.360 mg/mL, respectively. The inhibitory effects of AWPA on α-glucosidase and α-amylase were both reversible with mixed type and competitive type competition, respectively. The significance of manuscript was not only to avoid the waste of Annona squamosa residue, but provided alternative in the developments of inhibitors of α-glucosidase and α-amylase.

Robotic anatomic isolated complete caudate lobectomy: Left-side approach and techniques.

BACKGROUND: To demonstrate the surgical procedures and techniques of the robotic anatomical isolated complete caudate lobectomy. METHODS: A retrospective analysis was performed on the demographic, operative, postoperative outcomes of seven patients who underwent robotic anatomical isolated complete caudate lobectomy at our department from January 2018 to November 2019. Mobilization of the left lateral and Spiegel lobe, dissection of the short hepatic veins and liver parenchyma transection from the dorsal plane of middle and right hepatic vein were crucial procedures for the robotic left-side approach. Anatomic complete caudate lobectomy was defined as total removal of the caudate lobe, in which the dorsal middle and right hepatic vein, the inferior vena cava and its right side were fully exposed on the raw surface. RESULTS: All patients successfully underwent the robotic anatomical isolated caudate lobectomy with a left-side approach without conversion to laparotomy, and without Clavien-Dindo Grade III or higher complications. The average tumor diameter was 65.00 ± 10.61 mm, the average operation time was 212.00 ± 74.53 min, the median bleeding loss was 100 mL, and the average postoperative hospital stay was 8.71 ± 4.89 d, respectively. There were four patients with primary hepatocellular carcinoma, one with tumor recurrence five months after surgery and three patients were free of recurrence. All patients survived at the last follow-up. CONCLUSION: Robotic anatomical isolated complete caudate lobectomy with a left-sided approach is safe and feasible for selected patients.

Chemical structure and antioxidant activity of a polysaccharide from Siraitia grosvenorii.

A novel polysaccharide from Siraitia grosvenorii residues (SGP, molecular weight 1.93 × 103 KDa) was isolated and purified. SGP was composed of α-L-Arabinose, α-D-Mannose, α-d-Glucose, α-D-Galactose, Glucuronic acid, and Galacturonic acid with the ratio of 1: 1.92: 3.98: 7.63: 1.85: 7.34. The backbone of SGP was consist of galactoses and linked by α-(1,4)-glycosidic bond. The branch chains including α-1,6 linked glucose branch, α-1,6 linked mannose branch, α-1,3 linked galactose branch and arabinose branched (α-L-Ara(1→). The results of bioactivity experiments suggested that SGP had antioxidant in vitro, especially on scavenging DPPH radicals. Besides, SGP resulted in the decrease of ROS and the percentage of apoptotic and necrotic cells in a dose-dependent manner in H2O2 oxide injury PC12 cells. This research could help to develop the potential value and utilization of Siraitia grosvenorii.

Robotic isolated partial and complete hepatic caudate lobectomy: A single institution experience.

BACKGROUND: Current reports on robotic hepatic caudate lobectomy are limited to Spiegel lobectomy. This study aimed to compare the safety and feasibility of robotic isolated partial and complete hepatic caudate lobectomy. METHODS: Clinical data of 32 patients who underwent robotic resection of the hepatic caudate lobe in our department from May 2016 to January 2020 were retrospectively analyzed. The patients were divided into three groups according to the lobectomy location: left dorsal segment lobectomy (Spiegel lobectomy), right dorsal segment lobectomy (caudate process or paracaval portion lobectomy), and complete caudate lobectomy. General information and perioperative results of the three groups were compared and analyzed. RESULTS: Among the 32 patients, none had conversion to laparotomy, three received intraoperative blood transfusion (9.38%), and none had complications of Clavien-Dindo grade III or higher or died in the perioperative period. Among them, 17 patients (53.13%) underwent Spiegel lobectomy, 7 (21.88%) underwent caudate process or paracaval portion lobectomy, and 8 (25.00%) underwent complete caudate lobectomy. The operative time and blood loss in the left dorsal segment lobectomy group were significantly better than those in the right dorsal segment lobectomy and complete caudate lobectomy groups (operative time: P = 0.010 and P = 0.005; blood loss: P = 0.005 and P = 0.017, respectively). The postoperative hospital stay in the left dorsal segment lobectomy group was significantly shorter than that in the complete caudate lobectomy group (P = 0.003); however, there was no difference in the postoperative hospital stay between the left dorsal segment lobectomy group and right dorsal segment lobectomy group (P = 0.240). CONCLUSIONS: Robotic isolated partial and complete caudate lobectomy is safe and feasible. Spiegel lobectomy is relatively straightforward and suitable for beginners.

Successful robotic radical resection of hepatic echinococcosis located in posterosuperior liver segments.

BACKGROUND: Radical resection is an important treatment method for hepatic echinococcosis. The posterosuperior segments of the liver remain the most challenging region for laparoscopic or robotic hepatectomy. AIM: To demonstrate the safety and preliminary experience of robotic radical resection of cystic and alveolar echinococcosis in posterosuperior liver segments. METHODS: A retrospective analysis was conducted on the clinical data of 5 patients with a median age of 37 years (21-56 years) with cystic and alveolar echinococcosis in difficult liver lesions admitted to two centers from September to December 2019. The surgical methods included total pericystectomy, segmental hepatectomy, or hemihepatectomy. RESULTS: Among the 5 patients, 4 presented with cystic echinococcosis and 1 presented with alveolar echinococcosis, all of whom underwent robotic radical operation successfully without conversion to laparotomy. Total caudate lobectomy was performed in 2 cases, hepatectomy of segment VII in 1 case, total pericystectomy of segment VIII in 1 case, and right hemihepatectomy in 1 case. Operation time was 225 min (175-300 min); blood loss was 100 mL (50-600 mL); and postoperative hospital stay duration was 10 d (5-19 d). The Clavien-Dindo complication grade was I in 4 cases and II in 1 case. No recurrence of echinococcosis was found in any patient at the 3 mo of follow-up. CONCLUSION: Robotic radical surgery for cystic and selected alveolar echinococcosis in posterosuperior liver segments is safe and feasible.

Reduction of FoxP3+ Tregs by an immunosuppressive protocol of rapamycin plus Thymalfasin and Huaier extract predicts positive survival benefits in a rat model of hepatocellular carcinoma.

BACKGROUND: Investigate immunoregulation and anti-tumor immunity of FoxP3+Tregs after treatment with rapamycin (RAPA/SRL) plus thymalfasin (Zadaxin) and Huaier extract (PS-T) in a hepatocellular carcinoma (HCC) rat model simulating HCC relapse after liver transplant (LT). METHODS: We successfully established a rat model simulating HCC relapse after LT using an optimized chemical induction method with TACROLIMUS, methylprednisolone, and diethylnitrosamine as identified by visible liver nodules and hematoxylin-eosin staining. The model rats were then treated with RAPA, Zadaxin, and PS-T. Immune status changes were analyzed by flow cytometry, and protein expression of Akt and mTOR was determined by western blotting. Cytokines were measured by ELISAs. RESULTS: Combined therapy by RAPA plus Zadaxin and PS-T obviously alleviated hepatic pathological changes and significantly decreased the levels of FoxP3+Tregs in peripheral blood, the spleen, and the liver (P<0.05) and expression of mTOR protein (P<0.01) in the liver, obviously improved survival time (P=0.02). Moreover, the levels of CD8+T cells were increased significantly to almost normal levels (P<0.05) in comparison with no SRL monotherapy protocols. Inhibitory cytokines were also decreased in accordance with FoxP3+Tregs. Significant decreases of IL-10 and TGF-ß were observed after SRL-based therapy (P<0.01) in comparison with the other groups. Serum alpha fetoprotein (AFP) and vascular endothelial growth factor (VEGF) levels were also decreased significantly (P<0.05). FoxP3+Tregs showed a negative correlation with CD8+ and CD4+/CD8+T cells and a positive correlation with AFP, and VEGF (P<0.05). CONCLUSIONS: SRL-based therapy reduces FoxP3+Tregs to decrease secreted inhibitory cytokines which may enhancement the viability and number of CD8+T cells to exert anti-tumor effects that are mainly mediated through the AKT-mTOR signaling pathway.