"No-Touch" Left Approach for Recipient Hepatectomy: A Promising Strategy to Minimize Hepatocellular Carcinoma Recurrence in Liver Transplantation.

Background: Managing hepatocellular carcinoma (HCC) presents significant clinical challenges, often necessitating orthotopic liver transplantation (OLT). To mitigate the risk of iatrogenic metastasis during OLT and reduce posttransplantation recurrence (PTR), we introduced the "no-touch" left (NTL) approach for recipient hepatectomy in OLT. Methods: In this retrospective cohort study, our aim was to compare the safety and PTR rates in patients undergoing OLT via either the NTL technique or the conventional approach for recipient hepatectomy. We included 106 patients who met the Hangzhou criteria and exhibited a high tumor burden in the right lobe, with 50 patients assigned to the NTL group and 56 to the conventional group. The primary endpoint was the 1-y PTR rate, whereas secondary endpoints encompassed the safety of the NTL approach, PTR rates at 2 and 5 y, and overall survival. Results: Baseline demographics and clinical characteristics showed no significant differences between the groups. The NTL approach exhibited major surgical outcomes similar to those of the conventional approach. The cumulative PTR rates at 1, 2, and 5 y were 14.0% in the NTL group, compared with 24.5%, 35.8%, and 35.8% in the conventional group (P = 0.013). Cumulative overall survival rates at 1, 2, and 5 y were 94.0%, 91.9%, and 89.7% in the NTL group and 88.7%, 75.5%, and 72.5% in the conventional group (P = 0.03). Conclusions: This innovative surgical technique enhances safety and significantly reduces the risk of PTR, leading to improved long-term survival. Further prospective studies with larger cohorts and longer follow-up periods are needed to validate our findings and establish the NTL approach as a standard practice in OLT.

The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China.

BACKGROUND: Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms. METHODS: This single-centre, cross-sectional cohort study was done at China-Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18-33 days), 2 months (55-84 days), or 4 months (115-134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms. FINDINGS: Between Jan 3 and April 28, 2023, 317 tissue samples were collected from 225 patients, including 201 residual surgical specimens, 59 gastroscopy samples, and 57 blood component samples. Viral RNA was detected in 16 (30%) of 53 solid tissue samples collected at 1 month, 38 (27%) of 141 collected at 2 months, and seven (11%) of 66 collected at 4 months. Viral RNA was distributed across ten different types of solid tissues, including liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid. Additionally, subgenomic RNA was detected in 26 (43%) of 61 solid tissue samples tested for subgenomic RNA that also tested positive for viral RNA. At 2 months after infection, viral RNA was detected in the plasma of three (33%), granulocytes of one (11%), and peripheral blood mononuclear cells of two (22%) of nine patients who were immunocompromised, but in none of these blood compartments in ten patients who were immunocompetent. Among 213 patients who completed the telephone questionnaire, 72 (34%) reported at least one long COVID symptom, with fatigue (21%, 44 of 213) being the most frequent symptom. Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64-10·13, p<0·0001). Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms. INTERPRETATION: Our findings suggest that residual SARS-CoV-2 can persist in patients who have recovered from mild COVID-19 and that there is a significant association between viral persistence and long COVID symptoms. Further research is needed to verify a mechanistic link and identify potential targets to improve long COVID symptoms. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and New Cornerstone Science Foundation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Short-term outcomes of combined therapy with sirolimus and interferon-alpha 2b for advanced hepatic epithelioid hemangioendothelioma.

Background: Hepatic epithelioid hemangioendothelioma (EHE) is an extremely rare tumor, and no standard therapy has been established yet. Objectives: The aim of this study was to investigate the short-term results of combined therapy with sirolimus and interferon-alpha 2b (IFN-a 2b) (SI therapy). Methods: From January 2022 to April 2023, 40 patients histologically diagnosed with hepatic EHE and progressive disease received SI therapy. All patients were regularly evaluated for the safety and efficacy of the SI therapy. Patients who received SI therapy for <3 months without a tumor status evaluation after treatment were excluded. Results: Twenty-nine patients with hepatic EHE were included in this study. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 19 (65.5%) patients and 1 in 10 (34.5%) patients. The median duration of the SI therapy was 8 months (range, 3-15 months). Twenty-three (79.3%) patients showed a decrease in tumor size, including 11 (37.9%) patients who achieved a partial response and one (3.4%) who achieved a complete response; the objective response rate was 41.4%. Stable disease was observed in 13 (44.8%) patients, with a disease control rate of 86.2%. Adverse events (AES) were observed in 18 patients, including leukopenia (31.0%), oral ulcers (13.8%), and liver injury (10.3%). No severe (grade ⩾ 3) AEs were recorded, and SI therapy was not interrupted for any patient due to AEs. Conclusion: Sirolimus and IFN-a 2b may have synergistic effects in the treatment of hepatic EHE. SI therapy is a safe and effective treatment for hepatic EHE patients with good ECOG performance status.

Highly sensitive magnetic field sensors based on Fe2O3 nanorods grown on the surface of a tapered few mode fiber.

A magnetic field (MF) sensor with a stable structure and high sensitivity has been proposed and experimentally verified. We used the water bath method to produce a layer of Fe2O3 nanorods on a tapered few mode fiber (FMF) surface to form a Mach-Zehnder interferometer (MZI). The experiment found that the nanostructure produced on the surface of FMF were particularly stable and firm. Under the action of an external MF, the magnetic permeability of a Fe2O3 nanorod will change, leading to a change in its refractive index, resulting in a linear shift in the resonance wavelength of MZI. The experimental results showed that the MF sensitivity of MZI reached -0.5348 nm/mT in 10 mT∼80 mT. In addition, MZI has a certain sensitivity to environmental humidity and temperature. A long-period fiber grating and a fiber Bragg grating are cascaded with MZI to achieve a simultaneous measurement of three quantities and eliminate their cross-sensitivity.

CT appearances and classification of hepatic epithelioid hemangioendothelioma.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare, and CT features have never been analyzed in a large group of patients. METHODS: A retrospective study was designed to review the contrast-enhanced CT images of HEH patients. Intrahepatic lesions were categorized into three types: nodular, locally coalescent (coalescent lesion contained in one segment) or diffusely coalescent (coalescent lesion occupied more than one segment). CT features were compared among lesions of different sizes and patients with different lesion types. RESULTS: A total of 93 HEH patients were included in this study, and 740 lesions were analyzed. The results of per-lesion analysis showed that medium lesions (2-5 cm) had the highest rate of lollipop sign (16.8%) and target-like enhancement (43.1%), while lesions in large group (> 5 cm) had the highest rate of capsular retraction (38.8%) and vascular invasion (38.8%). The differences on enhancement pattern and the rates of lollipop sign and capsular retraction were significant among lesions of different sizes (p < 0.001, respectively). The results of per-patient analysis showed that patients in locally coalescent group had the highest rates of lollipop sign (74.3%) and target sign (94.3%). All patients in diffusely coalescent group had capsular retraction and vascular invasion. CT appearances of capsular retraction, lollipop sign, target sign and vascular invasion differed significantly among patients with different lesion types (p < 0.001, p = 0.005, p = 0.006 and p < 0.001, respectively). CONCLUSION: CT features variated among HEH patients with different lesion types, and radiological appearances of HEH should be classified into nodular type, locally coalescent type and diffusely coalescent type.

Pathogenic genomic alterations in Chinese pancreatic cancer patients and their therapeutical implications.

BACKGROUND: Approximately 90% of pancreatic ductal adenocarcinoma (PDAC) cases are driven by the untargetable non-G12C KRAS mutations, and only a small subset of patients are eligible for FDA-approved precision therapies. The practice of precision therapy in pancreatic cancer was limited by the paucity of targetable genetic alterations, especially in the Asian population. METHODS: To explore therapeutic targets in 499 Chinese PDAC patients, a deep sequencing panel (OncoPanscan™, Genetron health) was used to characterize somatic alterations including point mutations, indels, copy number alterations, gene fusions as well as pathogenic germline variants. RESULTS: We performed genomic profiling in 499 Chinese PDAC patients, which revealed somatic driver mutations in KRAS, TP53, CDKN2A, SMAD4, ARID1A, RNF43, and pathogenic germline variants (PGVs) in cancer predisposition genes including BRCA2, PALB2, and ATM. Overall, 20.4% of patients had targetable genomic alterations. About 8.4% of patients carried inactivating germline and somatic variants in BRCA1/2 and PALB2, which were susceptible to platinum and PARP inhibitors therapy. Patients with KRAS wild-type disease and early-onset pancreatic cancer (EOPC) harbored actionable mutations including BRAF, EGFR, ERBB2, and MAP2K1/2. Compared to PGV-negative patients, PGV-positive patients were younger and more likely to have a family history of cancer. Furthermore, PGVs in PALB2, BRCA2, and ATM were associated with high PDAC risk in the Chinese population. CONCLUSIONS: Our results demonstrated that a genetic screen of actionable genomic variants could facilitate precision therapy and cancer risk reduction in pancreatic cancer patients of Asian ethnicity.

Case report: Successful treatment with the combined therapy of interferon-alpha 2b and anlotinib in a patient with advanced hepatic epithelioid hemangioendothelioma.

Hepatic epithelioid hemangioendothelioma (HEH) is a very rare tumor originating from vascular endothelial cells, with unpredictable malignancy. At present, there is no standard treatment protocol yet established. Both surgical resection and liver transplantation have been reported to be effective treatments for HEH; however, multiple intrahepatic lesions or extrahepatic metastasis make these procedures unsuitable to most patients. Systematic therapy has also been investigated, but the results are undetermined due to the limited cases. Interferon-alpha 2b (IFN-a 2b) has also been used for the treatment of HEH. Based on our previous study, the rate of tumor regression with IFN-a 2b monotherapy was more than 50%. Here, we reported a patient with advanced HEH, who achieved a partial response with the combined therapy of anlotinib and IFN-a 2b. The tumor stayed stable for 2 years with anlotinib monotherapy and regressed 3 months after the combined therapy of anlotinib and IFN-a 2b. The synergistic effect of combined therapy with anlotinib and IFN-a 2b provided promising guidance for future clinical study.

The efficacy of oxaliplatin, surufatinib, and camrelizumab on neuroendocrine carcinoma: a case report and literature review.

Background: Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are rare, accounting for ~1/100,000 of NECs, aggressive neoplasms and poor prognosis. Sometimes, a non-neuroendocrine component is also accompanying these EP-NECs. Curative surgery is suggested for early stage patients while system chemotherapy and locoregional radiotherapy are considered for advanced inoperable disease. Nonetheless, there was lack of standard second-line treatment strategy. Herein, we report a case of NEC involving a large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma of the gallbladder treated with a surufatinib-containing regimen in the second-line treatment setting and establish the efficacy of this regimen in the treatment of EP-NECs. Case Description: A 58-year-old male presented with symptoms such as distension in the upper right abdomen and a palpable mass. The abdominal magnetic resonance imaging (MRI) scan showed a giant soft tissue mass in the left lobe of the liver, and liver biopsy suggested LCNEC with a non-neuroendocrine (NNE) component. Based on the available literature, a first-line therapy of oxaliplatin + gemcitabine + camrelizumab + apatinib was started initially; however, there was rapid tumor progression. Thus, a second line of treatment was started, where apatinib was replaced with surufatinib, which was given along with oxaliplatin and camrelizumab and continued for seven complete cycles. The patient was re-examined with MRI, which showed a significant decrease in tumor size. And a partial response was achieved. Main adverse events included hand and foot numbness, hypertension, proteinuria, hematuria, and hyperthyroidism. The patient underwent surgery after the second line of treatment and the post-operative pathology report revealed the presence of LCNEC and adenocarcinoma of the gallbladder. Two months later, re-examination result showed no tumor recurrence. Conclusions: As yet, the criteria strategy for unresectable EP-NECs to improve survival outcomes is scarce. EP-NECs are badly in need of effective second-line therapy to carry out survival benefits after resistance to first-line regimen. The case report demonstrated that a surufatinib-containing regimen including oxaliplatin and camrelizumab could be an effective treatment strategy for the second-line treatment of EP-NECs. Furthermore, this strategy is well tolerated and treatment-related toxicity are manageable. More clinical trials are warranted to further confirm the efficacy.

Sirolimus combined with interferon-alpha 2b therapy for giant hepatic epithelioid hemangioendothelioma: a case report.

Hepatic epithelioid hemangioendothelioma (HEH) is a very rare tumor originated from vascular endothelial cells, with unpredictable malignancy. No standard treatment has been established yet. Although surgical resection and liver transplantation have been reported to be effective treatments with favorable long-term outcomes, the multiple intrahepatic lesions or extrahepatic metastasis makes these procedures unsuitable to most patients. Sirolimus was reported to be an effective drug for epithelioid hemangioendothelioma but only about 10% achieved partial response. Interferon-alpha 2b (IFN-a 2b) has also been used for the treatment of HEH, and the rate of tumor regression was more than 50%. Here, we report a HEH patient with giant intrahepatic tumor (>15cm), who achieved partial response after the combined therapy of sirolimus and IFN-a 2b. The giant intrahepatic lesion (>15 cm) regressed obviously after 8 months treatment and no severe adverse event was reported. The good response and safety of combined therapy with sirolimus and IFN-a 2b provide a promising guidance for future clinical study.

Comparison of efficacy and safety of laparoscopic and open enucleation for liver hemangioma in the right hemi liver: a retrospective cohort study.

Background: Open enucleation (OE) is often performed for giant liver hemangioma (LH) because of its advantage in maximum preservation of functional liver parenchyma. Laparoscopic enucleation (LE) has been applied to LHs more frequently for its potential advantages in postoperative recovery and blood loss. However, to date, LE is still a difficult and complex surgical technique especially when the hemangioma is located in the right hemi liver. The aim of this study was to analyze whether LE is superior to OE for LH in the right hemi liver. Methods: Demographics and perioperative data of patients who underwent LE or OE for LH in the right hemi liver between May 2013 and July 2020 were collected. To decrease the selection bias, patients who underwent OE in first 2 years and those underwent LE in next 5 years by a same operation team were included. The data of sex, age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, largest tumor size, and removed tumor number were enrolled in the propensity score matching (PSM) method to compensate for differences in the baseline characteristics between LE and OE groups. The perioperative outcomes were compared between 2 matched groups after PSM method. Results: A total of 110 patients (36 LE vs. 74 OE) were matched by age, sex, BMI, ASA grade score, largest tumor size, removed tumor number and tumor location. Finally, 34 patients in each group were retained after PSM. There were no significant differences in operative time, estimated blood loss, amount of autologous transfusion, morbidity grade and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) on postoperative day 1 or 3 or 5. LE was associated with a significantly higher rate of use of the Pringle maneuver (P<0.001), shorter time to oral feeding (P<0.001) and shorter postoperative length of stay (P<0.001). Conclusions: For LHs in the right hemi liver, the perioperative safety of LE is not inferior to OE, and LE seems to achieves a faster recovery from surgery compared with OE.

Humanization of Yeasts for Glycan-Type End-Products.

Yeasts are often considered microorganisms for producing human therapeutic glycosylated end-products at an industrial scale. However, the products with non-humanized glycans limited their usage. Therefore, various methods to develop humanized glycosylated end-products have been widely reported in yeasts. To make full use of these methods, it is necessary to summarize the present research to find effective approaches to producing humanized products. The present research focuses on yeast species selection, glycosyltransferase deletion, expression of endoglycosidase, and expression of proteins with galactosylated and or sialylated glycans. Nevertheless, the yeasts will have growth defects with low bioactivity when the key enzymes are deleted. It is necessary to express the corresponding repairing protein. Compared with N-glycosylation, the function of yeast protein O-glycosylation is not well-understood. Yeast proteins have a wide variety of O-glycans in different species, and it is difficult to predict glycosylation sites, which limits the humanization of O-glycosylated yeast proteins. The future challenges include the following points: there are still many important potential yeasts that have never been tried to produce glycosylated therapeutic products. Their glycosylation pathway and related mechanisms for producing humanized glycosylated proteins have rarely been reported. On the other hand, the amounts of key enzymes on glycan pathways in human beings are significantly more than those in yeasts. Therefore, there is still a challenge to produce a large body of humanized therapeutic end-products in suitable yeast species, especially the protein with complex glycans. CRISPR-Cas9 system may provide a potential approach to address the important issue.

Knockdown of TANK-Binding Kinase 1 Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular-Targeted Drugs.

The protein kinase, TANK-binding kinase 1 (TBK1), not only regulates various biological processes but also functions as an important regulator of human oncogenesis. However, the detailed function and molecular mechanisms of TBK1 in hepatocellular carcinoma (HCC), especially the resistance of HCC cells to molecular-targeted drugs, are almost unknown. In the present work, the role of TBK1 in regulating the sensitivity of HCC cells to molecular-targeted drugs was measured by multiple assays. The high expression of TBK1 was identified in HCC clinical specimens compared with paired non-tumor tissues. The high level of TBK1 in advanced HCC was associated with a poor prognosis in patients with advanced HCC who received the molecular-targeted drug, sorafenib, compared to patients with advanced HCC patients and a low level of TBK1. Overexpression of TBK1 in HCC cells induced their resistance to molecular-targeted drugs, whereas knockdown of TBK1 enhanced the cells' sensitivity to molecular-targeted dugs. Regarding the mechanism, although overexpression of TBK1 enhanced expression levels of drug-resistance and pro-survival-/anti-apoptosis-related factors, knockdown of TBK1 repressed the expression of these factors in HCC cells. Therefore, TBK1 is a promising therapeutic target for HCC treatment and knockdown of TBK1 enhanced sensitivity of HCC cells to molecular-targeted drugs.

MRI appearances of hepatic epithelioid hemangioendothelioma: a retrospective study of 57 patients.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare and the MRI features have never been investigated in a large group of patients. METHODS: A retrospective study was designed to review the MRI images of HEH patients. Two radiologists separately evaluated signal intensity (SI) on unenhanced imaging, morphological features, contrast-enhancement pattern at dynamic study. The MRI features were compared between patients with HEH and hepatic metastatic tumor (HMT). RESULTS: Fifty-seven HEH patients were included in this study and a total of 412 lesions were evaluated. On per-lesion analysis, the rate of coalescent lesion and subcapsular lesion were 18.2% and 39.8%, respectively. Capsular retraction and lollipop sign were observed in 47 lesions (11.4%) and 60 lesions (14.6%), respectively. Large lesions (> 5 cm) had the highest rate of coalescent lesion, subcapsular lesion, capsular retraction and lollipop sign. Target sign appeared in 196 lesions (47.6%) on T2 weighted (T2W) and 146 lesions (35.4%) on portal phase. Medium lesions (2-5 cm) had the highest rate of target sign on both T2W (72.9%) and portal phase (55.2%). On per-patient analysis, compare with HEH patients, HMT patients seldom had the appearance of lollipop sign (66.7% versus 6.4%, p < 0.01), capsular retraction (59.6% versus 3.2%, p < 0.01) and target appearance on both T2Wand portal phase (64.9% versus 12.7%, p < 0.01). CONCLUSION: MRI features of HEH correlated with the lesion size. Capsular retraction, lollipop sign and coexistence of target sign on both T2W and portal phase were relatively specific MRI features of HEH, which could be helpful in suggesting the diagnosis.

Systematic characterization of the tumor microenvironment in Chinese patients with hepatocellular carcinoma highlights intratumoral B cells as a potential immunotherapy target.

Hepatocellular carcinoma (HCC) is an immunogenic malignancy, which exhibits low responsiveness to programmed cell death protein­1 (PD­1)/programmed death ligand­1 (PD­L1) antibodies. Therefore, the identification of novel immunotherapeutic targets to treat HCC is imperative. Systematic characterization of the HCC tumor microenvironment (TME) can provide novel insight into additional therapeutic approaches. In the present study, the RNA­sequencing (RNA­seq) data of 360 patients with HCC were integrated from The Cancer Genome Atlas to assess the expression of membrane spanning 4­domains A1 (MS4A1; encoding CD20) in tumors and normal liver tissues. Immunofluorescence and multiplex tissue fluorescence analyses were performed and combined with flow cytometry staining to measure CD20/CD19 expression at the protein level. In addition, published single cell RNA­seq data of CD45+ cells were derived from 16 treatment­naïve patients from Beijing Shijitan Hospital with HCC to illustrate the characteristics of CD19+ B cells. The results indicated that the HCC TME included nuclear receptor subfamily 4 group A member 2+ (NR4A2) B cells. Patients with HCC and high density of intratumoral B cells demonstrated compromised antitumor immunity manifested by low percentages of cytotoxic CD8+ T cells and high density of regulatory T cells. Furthermore, PD­L1 expression was significantly correlated with the B cell signature marker CD20. The present study indicated that tumor­infiltrating B cells may play a negative role in antitumor immunity and serve as a promising target for HCC immunotherapy, alone or in combination with anti­PD­L1/PD­1 antibodies.

Location of Hemangioma is an Individual Risk Factor for Massive Bleeding in Laparoscopic Hepatectomy.

BACKGROUND AND OBJECTIVES: The scope of laparoscopic surgery has expanded to encompass hepatic resections, specifically hepatic hemangioma. The most serious intraoperative complication is bleeding, often requiring laparotomy. Because risk factors associated with such massive blood loss have not been well evaluated, the intent of this retrospective study was to analyze these risk factors associated with laparoscopic resection of hepatic hemangiomas. METHODS: From June 1, 2011 to January 31, 2021, 140 consecutive patients underwent laparoscopic surgery for hepatic hemangioma in our hospital. According to quantity of intraoperative blood loss, they were divided into massive (≥ 800 ml) and minor blood loss (< 800 ml) groups. Perioperative data were analyzed by univariate and multivariate analyses with logistic regression to identify the risk factors for potential massive blood loss during laparoscopic resection. RESULTS: There were 24 and 116 patients in the massive and minor blood loss groups, respectively. Of four risk factors significantly associated with massive blood loss by univariate logistic regression analysis (location of hemangioma in the liver, postcaval or hepatic venous compression, hilar compression, and body mass index exceeding 28) the multifactorial logistic model identified only location in the liver of the hemangioma as statistically (P = 0.012) associated with intraoperative massive blood loss. CONCLUSIONS: Location of the hepatic hemangioma was the single statistically significant risk factor for massive blood loss during laparoscopic surgery for hepatic hemangioma. Of particular importance, location in Couinaud liver segments I, IVa, VII, and VIII necessitates precautions to mitigate the risk of massive blood loss.

Efficacy and Safety of Interferon-Alpha 2b for Patients with Hepatic Epithelioid Hemangioendothelioma: Outcomes of a Case-Series Analysis.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor type. No effective medicine or standard treatment for HEH has been established. PATIENTS AND METHODS: From March 2014 to April 2021, 62 patients with pathologically diagnosed HEH were observed regularly, and interferon-alpha 2b (IFN-a 2b) was administered to patients with progressive disease or reoccurrence. Adverse events (AEs) were assessed and recorded, and a tumor assessment scan was performed every 3 months. RESULTS: A total of 42 patients with HEH received IFN-a 2b treatment in this study. No severe (grade ≥3) AEs were reported in the group overall. The most common treatment-related AEs in patients receiving IFN-a 2b were fever (50.0%) and fatigue (21.4%). Partial response and complete response were achieved in 20 patients (47.6%) and 2 patients (4.8%), respectively, and the objective response rate was 52.4%. Stable disease was observed in 12 patients (28.6%), and the disease control rate was 81.0%. Progressive disease was observed in 8 patients (19.0%). The 1-, 3-, and 5-year progression-free survival rates were 81.0%, 69.2%, and 62.3%, respectively. Only 1 patient died as a result of disease progression during the study. The 1-, 3-, and 5-year overall survival rates were 100%, 97.2%, and 97.2%, respectively. CONCLUSION: IFN-a 2b is a safe and effective treatment for patients with HEH. The encouraging results with IFN-a 2b use make it a promising option for patients who have other types of epithelioid hemangioendothelioma; additional clinical trials are needed.

Ki-67 index of 5% could better predict the clinical prognosis of well-differentiated pancreatic neuroendocrine tumours.

BACKGROUND: The pathological classification of well-differentiated pancreatic neuroendocrine tumour (pNET) is based largely upon Ki-67 index. However, current controversies abound about the classification of pNETG1/pNETG2. PATIENTS AND METHODS: Clinicopathological data were retrospectively analysed for 153 pNETG1/pNETG2 patients hospitalized at China-Japan Friendship Hospital. The critical values of pNETG1/pNETG2 were examined by using the area under the receiver operating characteristic curve and survival analysis was used to compare the clinical prognosis of pNETG1/G2. RESULTS: Among them, 52.3% were males. The median age was 49 (18-81) years and the clinical types were pNETG1 (n = 38) and pNETG2 (n = 115). According to the receiver operating characteristic curve, the optimal cut-off value was 5.5% for classifying pNETG1/pNETG2. Significant differences between pNETG1 (n = 101) and pNETG2 (n = 52) existed in overall survival (P = 0.001) and disease-free survival (P = 0.013) when Ki-67 index was 5%. Yet no significant differences existed in overall survival (P = 0.378) or disease-free survival (P = 0.091) between pNETG1 and pNETG2 when Ki-67 index was 3%. Furthermore, multivariate analysis indicated that the revised pathological grade was an independent risk factor for mortality and post-operative recurrence of pNET patients (P = 0.003 and 0.014; hazard ratio (HR) = 4.005 and 2.553). CONCLUSION: Thus, differentiating pNETG1/pNETG2 with Ki-67 index (5%) is proposed as the cut-off value and a new Ki-67 index (5%) is a better predictor of pNET mortality and post-operative recurrence than Ki-67 index (3%).

Characterization of recombinant E. coli expressing a novel fucosidase from Bacillus cereus 2-8 belonging to GH95 family.

Fucoidan oligosaccharides possesses diverse physicochemical and biological activities. Specific glycoside hydrolases are valuable tools for degrading polysaccharides to produce oligosaccharides. In this study, BcFucA, a novel fucosidase belonging to GH95 family from Bacillus cereus 2-8, was cloned into pET21a vector, expressed in E. coli BL21 (DE3) and characterized. The protein consists of 1136 amino acid residues encoded by 3411 bases and has a molecular weight of 125.35 kDa. The optimal temperature and pH of this enzyme are 50 °C and pH 4.0. In addition, this study showed that the unknown function domain (encoding Lys261-Thr681) defined as a linker is quite important for its activity. The obtained novel enzyme BcFucA will contribute to the effective degradation of fucoidan and future industrial applications.

Identification and characterization of a novel glucomannanase from Paenibacillus polymyxa.

Konjac glucomannan oligosaccharide has attracted much attention due to its broad biological activities. Specific glucomannan degrading enzymes are effective tools for the production of oligosaccharides from konjac glucomannan. However, there are still few reports of commercial enzymes that can specifically degrade konjac glucomannan. The gene ppgluB encoding a glucomannanase consisting of 553 amino acids (61.5 kDa) from Paenibacillus polymyxa 3-3 was cloned and heterologous expressed in Escherichia coli BL21 (DE3). The recombinant PpGluB showed high specificity for the degradation of konjac glucomannan. Moreover, the hydrolytic products of PpGluB degrade konjac glucomannan were a series of oligosaccharides with degrees of polymerisation of 2-12. Furthermore, the biochemical properties indicated that PpGluB is the optimal active at 45 to 55 °C and pH 5.0-6.0, and shows highly pH stability over a very broad pH range. The present characteristics indicated that PpGluB is a potential tool to be used to produce oligosaccharides from konjac glucomannan.