Pleurotus eryngii root waste and soybean meal co-fermented protein improved the growth, immunity, liver and intestinal health of largemouth bass (Micropterus salmoides).

The present study aimed to evaluate the effect of king oyster mushroom (Pleurotus eryngii) root waste and soybean meal co-fermented protein (CFP) on growth performance, feed utilization, immune status, hepatic and intestinal health of largemouth bass (Micropterus salmoides). Largemouth bass (12.33 ± 0.18 g) were divided into five groups, fed with diets containing 0 %, 5 %, 10 %, 15 % and 20 % CFP respectively for 7 weeks. The growth performance and dietary utilization were slightly improved by the supplementation of CFP. In addition, improved immunoglobulin M (IgM) content and lysozyme activity in treatments confirm the enhancement of immunity in fish by the addition of CFP, especially in fish fed 20 % CFP (P < 0.05). Furthermore, CFP significantly improved liver GSH (glutathione) content in groups D10 and D15 (P < 0.05), and slightly improved total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity while slightly reduced malondialdehyde (MDA) content. Simultaneously, the upregulation of lipolysis-related genes (PPARα, CPT1 and ACO) expression and downregulation of lipid synthesis-related genes (ACC and DGAT1) expression was recorded in the group D20 compared with the control (P < 0.05), which were consistent with the decreased liver lipid contents, suggests that lipid metabolism was improved by CFP. In terms of intestinal structural integrity, ameliorated intestinal morphology in treatments were consistent with the upregulated Occludin, Claudin-1 and ZO-1 genes expression. The intestinal pro-inflammatory cytokines (TNF-α and IL-8) expression were suppressed while the anti-inflammatory cytokines (IL-10 and TGF-ß) were activated in treatments. The expression of antimicrobial peptides (Hepcidin-1, Piscidin-2 and Piscidin-3) and intestinal immune effectors (IgM and LYZ) were slightly up-regulated in treatments. Additionally, the relative abundance of intestinal beneficial bacteria (Firmicutes) increased while the relative abundance of potential pathogenic bacteria (Fusobacterium and Proteobacteria) decreased, which indicated that the intestinal microbial community was well-reorganized by CFP. In conclusion, dietary CFP improves growth, immunity, hepatic and intestinal health of largemouth bass, these data provided a theoretical basis for the application of this novel functional protein ingredient in fish.

A tuff interlayer in deep potash-bearing salt rocks and its implication for potash mineralization in the Simao Basin, southwestern China.

The lithology and genesis of a dark grey clastic interlayer first encountered within the deepest potassium-rich salt body in the Simao Basin, southwestern China, were analysed. Analyses of the petrography, mineralogy, and element geochemistry of the layer revealed that (1) the layer contains quartz crystals with gulf corrosion edges and explosion cracks and angular volcanic ash-sized glasses; (2) the main mineral components of the crystal fragments are chlorite, illite, biotite, quartz, anhydrite, gypsum, magnesite, pyrite, molybdenite, clinopyroxene, and zircon; (3) the rare earth element patterns, Zr/TiO2 and Nb/Y diagrams as well as boron content all indicate a volcanic origin for the layer. Based on these observations, the layer is suggested to be an altered tuff associated with various volcanic fragments dominated by chlorite and formed after alteration of a parent tuff in an alkaline, salty, and low-temperature water body. Discovery of the layer indicates that the potash-bearing salt rocks could have taken in volcanic materials during these volcanic activities and provides the possibility of reliable zircon U‒Pb dating to determine the absolute age of the host rock, which is fundamental in studying the genetic mechanism of this deeply buried salt body.

Sintilimab in Patients with Previously Treated Metastatic Neuroendocrine Neoplasms.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a group of diseases that show high heterogeneity but have limited treatment options. This phase I study evaluated the safety and efficacy of sintilimab, anti-PD-1 monoclonal antibody, in treating advanced NENs. METHODS: We prospectively enrolled patients pathologically diagnosed with NENs after standard treatment failure. Neuroendocrine neoplasms were classified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine cancers (NECs). Every patient received sintilimab, and response was assessed every 9 weeks. RESULTS: Twenty-four patients with a median age of 57.0 years were enrolled from November 2016 to 2017. The median Ki-67 index was 60%. Five patients had NET, 1 had NET G3, 17 had NEC, and 1 had mixed adenocarcinoma-neuroendocrine carcinoma. The most common primary tumor sites were the pancreas and gastrointestinal tract in 7 and 10 patients, respectively. In phase Ia trial, 2 patients received sintilimab 1 mg/kg every 2 weeks, one received 3 mg/kg every 2 weeks, and 21 patients enrolled in the phase Ib trial received 200 mg every 3 weeks. The objective response rate was 20.8% in all enrolled patients and 27.8% in NEC patients. The median progression-free survival was 2.2 and 2.1 months in patients with NET and NEC, respectively. The median OS was not applicable (NA) and 10.8 months (95% CI, 4.3, NA) with NET and NEC, respectively. The duration of response (DOR) was not reached, with a median follow-up time of 20.7 months. Treatment-related adverse events (TRAE) occurred in 17 (70.8%) patients. The most frequent TRAE was thyroid dysfunction (41.7%), and a grade 3 pulmonary infection occurred in 1 patient. The programmed cell death 1-ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) rate was 18.8% (3 out of 16) and the expression of PD-L1 did not correlate with response. CONCLUSION: Sintilimab was well-tolerated and showed encouraging response in NECs. CLINICALTRIALS.GOV IDENTIFIER: NCT02937116.

Negative air ion exposure ameliorates depression-like behaviors induced by chronic mild stress in mice.

The presence of negative air ions (NAI) is suggested to be a beneficial factor in improving psychological status and used in treating depression as an alternative approach. However, more biological evidence from animal models is needed to ensure the effects of NAI on the mood regulation, through which can facilitate identification of possible underlying mechanisms. In this study, the chronic mild stress (CMS) protocol was used to induce depressive-like behaviors in mice, and the effects of NAI exposure on CMS-induced depression-like behaviors were examined. Thirty-day NAI exposure prevented the CMS-induced depression-like behaviors as shown by the restoration of sucrose preference and reduced immobility time in the tail suspension test. In addition, the elevation of serous corticosterone was present in CMS-treated mice but not existed in those with the NAI exposure. Furthermore, we observed altered ratios of some cytokines secreted by type 1 T helper (Th1) cells and Th2 cells in CMS-treated mice, but it could be restored after NAI exposure. In conclusion, NAI intervention is able to ameliorate CMS-induced depression-like behaviors in mice, and this effect is associated with the alteration of corticosterone and functional rebalance between Th1 and Th2 cells.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

BACKGROUND: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. METHODS: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99). FINDINGS: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins. INTERPRETATION: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention. FUNDING: The funders are listed in the Acknowledgement.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms.

BACKGROUND: Poorly differentiated gastric neuroendocrine neoplasms (PDGNENs) include gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma, which are highly malignant and rare tumors, and their incidence has increased over the past few decades. However, the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated. AIM: To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs. METHODS: The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively. RESULTS: Among the 232 patients with PDGNENs, 191 (82.3%) were male, with an average age of 62.83 ± 9.11 years. One hundred and thirteen (49.34%) of 229 patients had a stage III disease and 86 (37.55%) had stage IV disease. Three (1.58%) of 190 patients had no clinical symptoms, while 187 (98.42%) patients presented clinical symptoms. The tumors were mainly (89.17%) solitary and located in the upper third of the stomach (cardia and fundus of stomach: 115/215, 53.49%). Most lesions were ulcers (157/232, 67.67%), with an average diameter of 4.66 ± 2.77 cm. In terms of tumor invasion, the majority of tumors invaded the serosa (116/198, 58.58%). The median survival time of the 232 patients was 13.50 mo (7, 31 mo), and the overall 1-year, 3-year, and 5-year survival rates were 49%, 19%, and 5%, respectively. According to univariate analysis, tumor number, tumor diameter, gastric invasion status, American Joint Committee on Cancer (AJCC) stage, and distant metastasis status were prognostic factors for patients with PDGNENs. Multivariate analysis showed that tumor number, tumor diameter, AJCC stage, and distant metastasis status were independent prognostic factors for patients with PDGNENs. CONCLUSION: The overall prognosis of patients with PDGNENs is poor. The outcomes of patients with a tumor diameter > 5 cm, multiple tumors, and stage IV tumors are worse than those of other patients.

Treatment Patterns and Outcomes in Chinese Patients with Gastric Cancer by HER2 Status: A Noninterventional Registry Study (EVIDENCE).

BACKGROUND: Real-world safety and effectiveness data for trastuzumab plus chemotherapy treatment of patients with HER2-positive metastatic gastric cancer (mGC) in China are lacking. PATIENTS AND METHODS: EVIDENCE was a prospective, multicenter, noninterventional registry study evaluating the safety and effectiveness of trastuzumab in five cohorts of Chinese patients with gastric cancer, stratified by HER2 status and trastuzumab treatment. Effectiveness was analyzed for cohorts I (HER2-positive, trastuzumab treated), II (HER2-positive, trastuzumab untreated), and IV (HER2-negative, trastuzumab untreated); trastuzumab-related adverse events (AEs) were analyzed for cohort I. RESULTS: Cohorts I, II, and IV included 174, 113, and 422 patients, respectively. Most patients received first-line chemotherapy (87.6%). Median overall survival (OS1) for first-line treatment was 22.3, 17.2, and 17.4 months in cohorts I, II, and IV, respectively. After excluding patients who had surgery, respective median OS1 was 19.9, 15.3, and 12.9 months. Respective first-line progression-free survival (PFS1) was 8.2, 6.9, and 6.2 months; and respective first-line response rates (RR) were 51.7%, 18.4%, and 32.8%. Cohort I was significantly favored over cohort II for propensity score-matched first-line median OS1 (hazard ratio [HR], 0.61), PFS1 (HR, 0.64), and RR (odds ratio, 4.93). Trastuzumab-related AEs, grade 3-5 AEs, serious AEs, and AEs with a fatal outcome occurred in 23.6%, 3.4%, 2.3%, and 0.6% of cohort I patients, respectively. CONCLUSION: Safety profiles were consistent with those known for trastuzumab and chemotherapy; trastuzumab treatment improved outcomes. Our study provides real-world data supporting first-line trastuzumab plus chemotherapy in Chinese patients with HER2-positive mGC. IMPLICATIONS FOR PRACTICE: This prospective, noninterventional registry study aimed to provide safety and effectiveness data for the use of trastuzumab in combination with chemotherapy in Chinese patients with HER2-positive metastatic gastric cancer (mGC) from the real-world clinical setting. Trastuzumab plus first-line chemotherapy was shown to be safe and to improve outcomes when compared with patients treated with chemotherapy alone. Trastuzumab was effective within a range of treatment regimens; subgroup analysis showed that trastuzumab paired most effectively with the XELOX regimen. This study provides real-world clinical safety and effectiveness data supporting the use of trastuzumab in the treatment of Chinese patients with HER2-positive mGC.

Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis.

BACKGROUND AND AIMS: Rifaximin has been recommended as a prophylactic drug for hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). This study aims to explore whether low-dose rifaximin can prevent overall complications and prolong survival in cirrhotic patients. METHODS: In this multi-centre randomized open-labelled prospective study, 200 patients with decompensated cirrhosis were randomly assigned at a ratio of 1:1. Patients in rifaximin group were administered 400 mg rifaximin twice daily for 6 months, and all other therapeutic strategies were kept unchanged in both groups as long as possible. The primary efficacy endpoints were the incidence of overall complications and liver transplantation-free survival. The secondary endspoints were the incidence of each major cirrhosis-related complication, as well as the Child-Pugh score and class. RESULTS: The major baseline characteristics were similar in the two groups except for HE. The cumulative incidence and frequency of overall complications were significantly lower in rifaximin group than in the control group (p < 0.001). Though liver transplantation-free survival was not significantly different between the two groups, subgroup analysis showed rifaximin markedly prolonged liver transplantation-free survival in patients with Child-Pugh score ≥ 9 (p = 0.007). Moreover, rifaximin markedly reduced the episodes of ascites exacerbation (p < 0.001), HE (p < 0.001) and gastric variceal bleeding (EGVB, p = 0.031). The incidence of adverse events was similar in the two groups. CONCLUSION: Low-dose rifaximin significantly decreases the occurrence of overall complications, leading to prolonged survival in patients with advanced stages of cirrhosis in this trail. Further study should be carried out to compare the effect of this low-dose rifaximin with normal dose (1200 mg/day) rifaximin in preventing cirrhosis-related complications. CLINICAL TRIAL NUMBER: NCT02190357.

Post-radiation circulating tumor DNA as a prognostic factor in locally advanced esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a highly malignant and deadly tumor. Radiation therapy is one of the primary treatments for locally advanced ESCC. However, the biomarkers for prognosis of definitive radiation remain undefined. Peripheral blood circulating tumor (ct)DNA provides information of tumor genetic alterations and has been confirmed as a potential non-invasive biomarker for several types of cancer. The present study investigated the clinical implications of ctDNA detection in patients with ESCC and receiving definitive radiation therapy. Patients with locally advanced ESCC were retrospectively recruited. Plasma samples were collected before, during and following radiation therapy. Next-generation sequencing was performed to identify somatic mutations in 180 genes. A total of 69 baseline and post-radiation plasma samples were collected from 25 patients. A total of 59 non-silent single nucleotide variants were present in 33 genes. All pre-radiation and 58.3% (14/24) of post-radiation samples had at least one mutation. Patients with lymph node metastases (LNM) exhibited a higher number of pre-radiation mutations compared with those without LNM. The variables, progression-free survival (PFS) and overall survival (OS) of the patients with one baseline mutation were not significantly different compared with that in patients with more than one baseline mutation. Patients with initial ctDNA-positive post-radiation samples exhibited significantly reduced PFS (P=0.047) and OS (P=0.005) compared with that in patients with ctDNA-negative samples. The post-radiation plasma ctDNA status was an independent prognostic factor from univariate and multivariate analyses. Dynamic monitoring of ctDNA during follow-up was examined. The results indicated that ctDNA was a predictive and prognostic marker in patients with ESCC and receiving definitive radiation therapy, which may guide subsequent treatment.

Clinicopathological characteristics and prognosis of 77 cases with type 3 gastric neuroendocrine tumours.

BACKGROUND: For the rarity of type 3 gastric neuroendocrine tumours (g-NETs), their clinicopathological characteristics and prognosis are not well illustrated. AIM: To describe the clinicopathological features and outcome of type 3 g-NETs in the Chinese population. METHODS: Based on the 2019 WHO pathological classification, the clinicopathological characteristics and prognosis of patients with type 3 g-NETs in China were retrospectively analysed. RESULTS: A total of 77 patients (55.8% of females) with type 3 g-NETs were analysed, with a median age of 48 years (range: 28-79 years). The tumours were mainly located in the gastric fundus/body (83.1%) and were mostly solitary (83.1%), with a median size of 1.5 cm (0.8-3.5 cm). Of these, there were 37 G1 tumours (48.1%), 31 G2 (40.3%), and 9 G3 (11.7%). Ten (13.0%) and 24 (31.2%) patients had lymph node and distant metastasis, respectively. In addition, type 3 g-NETs were heterogeneous. Compared with G1 NETs, G2 NETs had a higher lymph node metastasis rate, and G3 NETs had a higher distant metastasis rate. G1 and G2 NETs with stage I/II disease (33/68) received endoscopic treatment, and no tumour recurrence or tumour-related death was observed within a median follow-up time of 36 mo. Grade and distant metastasis were identified to be independent risk factors for prognosis in multivariable analysis. CONCLUSION: Type 3 g-NETs are obviously heterogeneous, and the updated WHO 2019 pathological classification may be used to effectively evaluate their biological behaviors and prognosis. Also, endoscopic treatment should be considered for small (< 2 cm), low grade, superficial tumours.

Trastuzumab plus docetaxel and capecitabine as a first-line treatment for HER2-positive advanced gastric or gastroesophageal junction cancer: a phase II, multicenter, open-label, single-arm study.

Gastric cancer (GC) is the second most common cancer in China. The ToGA study showed that trastuzumab in combination with fluoropyrimidine plus cisplatin prolonged overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced GC (AGC). However, some patients may not be able to receive this regimen. We conducted a clinical study to evaluate the efficacy and safety of trastuzumab in combination with docetaxel+capecitabine (DX) in patients with HER2-positive AGC. This phase II, multi-center, open-label, single arm study enrolled patients with HER2-positive AGC who had not received prior treatment for metastatic disease. Patients were treated with a regimen of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, day 1), capecitabine (1000 mg/m2 twice daily, days 1-14) and docetaxel (60 mg/m2, day 1 for 6 cycles) every 3 weeks. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), OS and safety profiles. Sixty-seven patients with AGC were enrolled from 14 centers. 64 were included in the full analysis set (FAS). The median PFS was 8.1 months (95% confidence interval [CI]: 5.6-12.8) and the median OS was 20.9 months (95% CI: 15.1-33.0). Response was evaluated in 59 patients. The ORR was 67.8%. The most common adverse events of Grade ≥3 were neutropenia, leukopenia, hand-foot syndrome, febrile neutropenia and anemia. We concluded that combination treatment with trastuzumab and DX was well-tolerated and highly effective in patients with HER2-positive AGC, and may offer an alternative to current treatments.

Lactulose improves cognition, quality of life, and gut microbiota in minimal hepatic encephalopathy: A multicenter, randomized controlled trial.

OBJECTIVE: Lactulose is effective in the treatment and prevention of overt hepatic encephalopathy (OHE), but there are limited data on its use on microbiota in relations to minimal hepatic encephalopathy (MHE) recovery. The present study aimed to assess the efficacy of lactulose in recovery of MHE in aspects of cognitive function, quality of life, and impact on intestinal microbiota. METHODS: This multicenter, open-label randomized controlled trial was conducted in 11 teaching hospitals in China. Participants were randomly allocated on a 2:1 basis to receive lactulose (Gp-L) or no therapy as control (Gp-NL) for 60 days. The primary endpoint was the MHE reversal rate. Gut microbiota were compared between MHE patients and healthy volunteers, as well as lactulose-responders and non-responders. RESULTS: A total of 98 cirrhotic patients were included in the study, with 31 patients in the Gp-NL group and 67 patients in the Gp-L group. At day 60, the MHE reversal rate in Gp-L (64.18%) was significantly higher than that in Gp-NL (22.58%) (P = .0002) with a relative risk of 0.46 (95% confidence interval 0.32-0.67). Number needed to treat was 2.4. Further, there was significantly more improvement in physical functioning in Gp-L (4.62 ± 6.16) than in Gp-NL (1.50 ± 5.34) (P = .0212). Proteobacteria was significantly higher in MHE patients compared with healthy volunteers (12.27% vs 4.65%, P < .05). Significant differences were found between lactulose responders and non-responders in Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. CONCLUSIONS: Treatment with lactulose significantly improves MHE recovery rate, and gut microbiota change in MHE patients can modulate the effectiveness of this therapy. Chinese Clinical Trial Register (ChiCTR) (ID: ChiCTR-TRC-12002342).

Computer-assisted diagnosis of early esophageal squamous cell carcinoma using narrow-band imaging magnifying endoscopy.

BACKGROUND: We developed a computer-assisted diagnosis model to evaluate the feasibility of automated classification of intrapapillary capillary loops (IPCLs) to improve the detection of esophageal squamous cell carcinoma (ESCC). METHODS: We recruited patients who underwent magnifying endoscopy with narrow-band imaging for evaluation of a suspicious esophageal condition. Case images were evaluated to establish a gold standard IPCL classification according to the endoscopic diagnosis and histological findings. A double-labeling fully convolutional network (FCN) was developed for image segmentation. Diagnostic performance of the model was compared with that of endoscopists grouped according to years of experience (senior > 15 years; mid level 10 - 15 years; junior 5 - 10 years). RESULTS: Of the 1383 lesions in the study, the mean accuracies of IPCL classification were 92.0 %, 82.0 %, and 73.3 %, for the senior, mid level, and junior groups, respectively. The mean diagnostic accuracy of the model was 89.2 % and 93.0 % at the lesion and pixel levels, respectively. The interobserver agreement between the model and the gold standard was substantial (kappa value, 0.719). The accuracy of the model for inflammatory lesions (92.5 %) was superior to that of the mid level (88.1 %) and junior (86.3 %) groups (P < 0.001). For malignant lesions, the accuracy of the model (B1, 87.6 %; B2, 93.9 %) was significantly higher than that of the mid level (B1, 79.1 %; B2, 90.0 %) and junior (B1, 69.2 %; B2, 79.3 %) groups (P < 0.001). CONCLUSIONS: Double-labeling FCN automated IPCL recognition was feasible and could facilitate early detection of ESCC.

Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition).

BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-ß1/Smad Signaling Pathway.

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect. Nevertheless, the mechanism is not completely identified. This study was conducted to investigate the effects of melatonin on TGF-ß1/Smad signaling pathway in liver fibrosis in rats. The liver fibrosis model was made by the subcutaneous injection of CCl4. The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer. Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry. Expression levels of TGF-ß1, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis. Results showed that melatonin suppressed CCl4-induced liver fibrosis, along with an improvement in histological changes, significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver. Melatonin improved liver function indicated by decreased serum ALT and AST activities. In addition, melatonin exerted its anti-oxidant effects, as supported by decreased MDA levels and increased GPx activities in liver. Furthermore, melatonin inhibited TGF-ß1/Smad pathway, as evidenced by decreased TGF-ß1, Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver. In conclusion, melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-ß1/Smad pathway. It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours.

BACKGROUND: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. METHODS: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). CONCLUSIONS: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.

What may cause fetus loss from acute pancreatitis in pregnancy: Analysis of 54 cases.

Acute pancreatitis in pregnancy (APIP) poses a serious threat to the mother and her fetus, and might lead to fetal loss including miscarriage and stillbirth in certain patients. We sought to identify possible factors that affect fetal distress and evaluated outcomes of patients with APIP.We retrospectively reviewed clinical records of 54 pregnant women with APIP, who were treated at 2 tertiary clinical centers over a 6-year period. Clinical characteristics including etiology and severity of APIP, fetal monitoring data, and maternofetal outcomes were analyzed.Etiology of APIP included acute biliary pancreatitis (ABP, n = 14), hyperlipidemic pancreatitis (HLP, n = 22), and other etiologies (n = 18). Severity was classified as mild acute pancreatitis (MAP, n = 23), moderately severe acute pancreatitis (MSAP, n = 24), and severe acute pancreatitis (SAP, n = 7). The incidence of preterm delivery, fetal distress, and fetal loss increased with the progression of severity of APIP (P < .05). The severity of HLP was significantly higher than that of ABP and APIP of other etiology (P < .01). HLP was more likely to lead to fetal distress than other APs (P < .01). Only 12 (22.2%) patients had fetal monitoring including non-stress test (NST); 1 case of SAP (14.3%) and 15 cases of MSAP (62.5%) were not transferred to intensive care unit for intensive monitoring.The incidence of fetal distress and fetal loss increased with worsening of APIP severity. HLP tends to result in worse fetal outcomes. The deficiencies of fetal state monitoring, lack of assessment, and management of pregnant women might increase the fetal loss in APIP.

Aspergillus niger bloodstream infection in gastric cancer after common hepatic artery embolization: A case report.

The present case study reported on a 62-year-old male patient with gastric cancer-associated Aspergillus (A.) niger bloodstream infection. The patient presented with massive hemorrhage in the gastrointestinal tract 3 months after total gastrectomy for gastric cancer. Conservative treatment consisting of blood transfusion to supplement blood volume loss was ineffective. Digital subtraction angiography indicated gastroduodenal artery bleeding. The first attempt of performing arterial embolization using gelatin sponges failed, while the second attempt of performing common hepatic artery embolization using gelatin sponges and micro-coil springs stopped the bleeding. Four weeks after angiography, the patient presented with the complication of A. niger bloodstream infection, which was cured using intravenous and oral voriconazole. Clinicians should be aware of the possibility of A. niger bloodstream infection after invasive operations in immunocompromised patients and apply timely antifungal treatment.

PIK3CA Mutations Contribute to Acquired Cetuximab Resistance in Patients with Metastatic Colorectal Cancer.

Purpose: Mutations in KRAS are considered to be the main drivers of acquired resistance to epidermal growth factor receptor (EGFR) blockade in patients with metastatic colorectal cancer (mCRC). However, the potential role of other genes downstream of the EGFR signaling pathway in conferring acquired resistance has not been extensively investigated.Experimental Design: Using circulating tumor DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we developed a targeted amplicon ultra-deep sequencing method to screen for low-abundance somatic mutations in a panel of genes that encode components of the EGFR signaling pathway. Mutations with significantly increased variant frequencies upon disease progression were selected by using quartile analysis. The functional consequences of the identified mutations were validated in cultured cells.Results: We analyzed 32 patients with acquired cetuximab resistance in a development cohort. Of them, seven (22%) carried five novel PIK3CA mutations, whereas eight (25%) carried previously reported KRAS mutations. Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N, p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of cetuximab. Only one novel PIK3CA mutation (p.K944N) was verified in one of the 27 patients with acquired resistance in a validation cohort, simultaneous KRAS and PIK3CA hotspot mutations were detected in two patients. Among the above 59 acquired resistance patients, those with PIK3CA or RAS mutations detected in ctDNA showed a pronounced decrease in progression-free survival than patients with no mutation.Conclusions: The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC. Clin Cancer Res; 23(16); 4602-16. ©2017 AACR.