DeepFundus: A flow-cytometry-like image quality classifier for boosting the whole life cycle of medical artificial intelligence.

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.

Cystohepatic duct can be the bridge of calculous cholecystitis complicating cholangitis and obstructive jaundice.

Cholestasis and obstructive jaundice can be extrahepatic or intrahepatic. Here we present one case with calculous cholecystitis who presenting with repeated obstructive jaundice and without bile duct dilation. The patient received laparoscopic cholecystectomy, and cystohepatic duct was identified intraoperatively, there was no cholestasis or obstructive jaundice postoperatively. Cystohepatic duct is a rare biliary anomaly observed in 0.7% of all surgical cases and in 1.5% of all cadaveric dissections. The cystohepatic duct can be the bridge of calculous cholecystitis complicating cholangitis and obstructive jaundice, here we for the first time presented this entity.

Inhibiting Th1/2 cells influences hepatic capillarization by adjusting sinusoidal endothelial fenestrae through Rho-ROCK-myosin pathway.

CD4+ T cells are considered to be vital in chronic liver diseases, but their exact roles in hepatic capillarization, the typical characteristic of liver fibrosis, are poorly understood. This study aimed to assess the roles of typical subtype of CD4+ T cells, named T helper 1 (Th1) and Th2 cells in liver fibrosis. Taking advantage of well established fibrotic rat model, we conducted in vitro and in vivo experiments to explore the interactions between liver sinusoidal endothelial cells (LSECs) and Th1/2 cells; meanwhile we evaluated the degree of hepatic capillarization when inhibiting these interactions with inhibitory antibodies. Our results showed that prohibiting interactions between Th2 cells and LSECs caused the restoration of fenestrae, increased cytokine level of Th1 cells and reduction of hepatic capillarization; inhibiting the interaction between Th1 cells and LSECs produced the opposite effects. Moreover, increased Rho and myosin light chain phosphorylation were observed when Th1 cells were inhibited with the corresponding inhibitory antibody; Th2 cell inhibition yielded the opposite results. This study indicated that Th1/2 cells steer the capillarization process in different directions and this effect is probably mediated by the Rho-Rho kinase (ROCK)-myosin signaling pathway.

Application of near-infrared fluorescent cholangiography using indocyanine green in laparoscopic cholecystectomy.

OBJECTIVE: Near-infrared fluorescence cholangiography (NIRF-C) can help to identify the bile duct during laparoscopic cholecystectomy. This retrospective study was performed to investigate the effect of NIRF-C in laparoscopic cholecystectomy. METHODS: Consecutive patients who underwent NIRF-C-assisted laparoscopic cholecystectomy (n = 34) or conventional laparoscopic cholecystectomy (n = 36) were enrolled in this study. Identification of biliary structures, the operation time, intraoperative blood loss, and postoperative complications were analyzed. RESULTS: Laparoscopic cholecystectomy was completed in all patients without conversion to laparotomy. The median operation time and intraoperative blood loss were not significantly different between the two groups. No intraoperative injuries or postoperative complications occurred in either group. In the NIRF-C group, the visualization rate of the cystic duct, common bile duct, and common hepatic duct prior to dissection was 91%, 79%, and 53%, respectively. The success rate of cholangiography was 100% in the NIRF-C group. NIRF-C was more effective for visualizing biliary structures in patients with a BMI of <25 than >25 kg/m2. CONCLUSIONS: NIRF-C is a safe and effective technique that enables real-time identification of the biliary anatomy during laparoscopic cholecystectomy. NIRF-C helps to improve the efficiency of dissection.

Decreased expression of ApoF associates with poor prognosis in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is frequently associated with metabolism dysfunction. Increasing evidence has demonstrated the crucial role of lipid metabolism in HCC progression. The function of apolipoprotein F (ApoF), a lipid transfer inhibitor protein, in HCC is incompletely understood. We aimed to evaluate the functional role of ApoF in HCC in this study. METHODS: We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines (SMMC-7721, HepG2, and Huh7). Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues. The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed. The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo. RESULTS: ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues. In SMMC-7721 and Huh7 HCC cells, ApoF overexpression inhibited cell proliferation and migration. In a xenograft nude mouse model, ApoF overexpression effectively controlled HCC growth. Kaplan-Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients. Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage. CONCLUSIONS: ApoF expression was down-regulated in HCC, which was associated with low recurrence-free survival rate. ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.

Antiviral therapy predicts the outcomes following resection of hepatocellular carcinoma in patients negative for HBV DNA: a propensity score matching analysis.

BACKGROUND: The effect of antiviral therapy (AVT) on clinical outcomes in patients with hepatocellular carcinoma (HCC) who are seronegative for hepatitis B virus (HBV), defined as HBV DNA < 100 IU/ml prior to surgical resection, is unknown. The main purpose of this study was to evaluate the possible value of AVT in this cohort of patients. METHODS: From January 2006 to January 2013, 161 HCC patients with positive serum tests for HBV surface antigen (HBsAg) but negative tests for HBV DNA who had undergone hepatectomy were included and analyzed. Propensity score matching (PSM) was used to balance the heterogeneity in baseline characteristics. RESULTS: All patients were divided into the following two groups: the AVT group (n = 73, 45.34%) and the non-AVT group (n = 88, 54.66%). HBV reactivation occurred in 20 patients in the non-AVT group (22.73%) but in only 2 patients in the AVT group (2.74%, p < 0.001). After PSM, the 1-, 2-, and 3-year recurrence-free survival (RFS) rates in the AVT group and the non-AVT group were 78.38%, 72.97%, and 62.16% and 81.08%, 72.97%, and 72.97%, respectively (p = 0.564); the 1-, 2-, and 3-year overall survival (OS) rates were 97.30%, 97.3%, and 91.89% and 94.59%, 94.59%, and 86.49% in the AVT group and non-AVT group, respectively (p = 0.447). CONCLUSIONS: Antiviral therapy can reduce HBV reactivation but is not correlated with a significant increase in postoperative RFS and OS in HCC patients with HBV DNA levels < 100 IU/ml.

TRIM29 prevents hepatocellular carcinoma progression by inhibiting Wnt/ß-catenin signaling pathway.

TRIM29 plays an important role in many neoplasms. In this study, we aimed to elucidate its role in hepatocellular carcinoma (HCC) and explore the corresponding potential mechanism. The expression level of TRIM29 in HCC samples and hepatoma cell lines was detected. We found that TRIM29 was down-regulated in clinical HCC samples and cultured hepatoma cell lines by western blot analysis and quantitative polymerase chain reaction. In addition, we demonstrated that higher TRIM29 expression was associated with higher differentiation grade of HCC. To explore the effect of TRIM29 on hepatoma cells and its possible mechanisms, TRIM29-knockdown and overexpression cell models were constructed. The results showed that the depletion of TRIM29 promoted liver cancer cell proliferation, clone formation, migration and invasion in vitro probably through the Wnt/ß-catenin signaling pathway. This study revealed the inhibitory roles of TRIM29 in HCC and the possible mechanisms.

RNAi-mediated human Nestin silence inhibits proliferation and migration of malignant melanoma cells by G1/S arrest via Akt-GSK3ß-Rb pathway.

Human Nestin (hNestin) has been found to express in melanoma, and its expression is positively correlated with the advanced stage of melanoma. However, the precise role of hNestin in the development of melanoma has not been fully understood. The present study aimed to explore the role of hNestin in the proliferation and invasion of melanoma cells. The lentivirus vector carrying a short hairpin RNAs (shRNAs) targeting hNestin (hNestin-shRNA-LV) was stably infected into human melanoma cells UACC903, which expressed high levels of hNestin. The effects of hNestin knockdown on the proliferation, apoptosis, migration of melanoma cells and the related signaling pathways were investigated by immunofluorence, Western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. The results showed that hNestin was expressed in most melanoma specimens and the melanoma cells studied. Knockdown of hNestin expression significantly inhibited the proliferation of melanoma cells, blocked the formation of cell colony, arrested cell cycle at G1/S stage and suppressed the activation of Akt and GSK3ß. hNestin-silent cells also showed a sheet-like appearance with tight cell-cell adhesion, decreased membrane expression of N-cadherin and ß-catenin, and attenuated migration. Furthermore, hNestin silence resulted in the inhibition of tumor growth in vivo. Our study indicates that hNestin knockdown suppresses the proliferation of melanoma cells, which might be through affecting Akt-GSK3ß-Rb pathway-mediated G1/S arrest, and hNestin silence inhibits the migration by selectively modulating the expression of cell adhesion molecules in the process of epithelial-mesenchymal transition.

Associating liver partition and portal vein ligation for staged hepatectomy versus conventional two-stage hepatectomy: a systematic review and meta-analysis.

BACKGROUND: It is generally accepted that an insufficient future liver remnant is a major limitation of large-scale hepatectomy for patients with primary hepatocellular carcinoma. Conventional two-stage hepatectomy (TSH) is commonly considered to accelerate future liver regeneration despite its low regeneration rate. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which is characterized by a rapid regeneration, has brought new opportunities. METHODS: Relevant studies were identified by searching the selected databases up to September 2017. Then, a meta-analysis of regeneration efficiency, complication rate, R0 resection ratio, and short-term outcomes was performed. RESULTS: Ten studies, comprising 719 patients, were included. The overall analysis showed that ALPPS was associated with a larger hyperplastic volume and a shorter time interval (P < 0.00001) than TSH. ALPPS also exhibited a higher completion rate for second-stage operations (odds ratio, OR 9.50; P < 0.0001) and a slightly higher rate of R0 resection (OR 1.90; P = 0.11). Interestingly, there was no significant difference in 90-day mortality between the two treatments (OR 1.44; P = 0.35). CONCLUSIONS: These results indicate that compared with TSH, ALPPS possesses a stronger regenerative ability and better facilitates second-stage operations. However, the safety, patient outcomes, and patient selection for ALPPS require further study.

Surgical treatments for patients with recurrent bile duct stones and Oddis sphincter laxity.

Recurrent bile duct stones is the most common complication after gallstone surgery and the incidence is about 4-24%. Sphincter of Oddi laxity will lead to duodenal content flow into the bile or pancreatic duct. Patients with recurrent bile duct stones and Oddis sphincter laxity were intractable. Here we sought to present the possible and helpful surgical treatments for such patients. Prospective randomized clinical trial are needed for evaluating the outcome of surgical treatments.

Key role of liver sinusoidal endothelial cells in liver fibrosis.

Because of the prevalence of viral hepatitis and nonalcoholic fatty liver disease (NAFLD), liver fibrosis has become a very common disease in Asia and elsewhere in the world, constantly increasing the burden of care borne by society. Hepatic sinusoidal capillarization, characterized by gradually shrinking fenestrae on the surface of liver sinusoidal endothelial cells (LSECs) and the formation of an organized basement membrane, is an initial pathologic change associated with liver fibrosis. Basic and clinical studies have indicated that LSECs play a key role in hepatic sinusoidal capillarization by affecting various aspects of the development and progression of liver fibrosis. Reviewing studies on the effect of LSECs on liver fibrosis is essential to better understanding the pathogenesis of liver fibrosis and its mechanism of progression. Moreover, such a review will provide a theoretical basis for identifying new methods to promote the regression or even inhibition of fibrosis. This review will focus on structural and functional changes in LSECs during hepatic sinusoidal capillarization and the interaction between the micro-environment of the liver and the body's immune system.

Hepatitis B Virus Core Promoter A1762T/G1764A (TA)/T1753A/T1768A Mutations Contribute to Hepatocarcinogenesis by Deregulating Skp2 and P53.

BACKGROUND AND AIM: Hepatitis B virus core promoter (CP) mutations can increase risk of hepatocellular carcinoma. The CP region overlaps with the HBV X (HBx) gene, which has been associated with hepatocarcinogenesis. The cyclin kinase inhibitor P53 is an important regulator of cell cycle progression. We determined whether HBx mutants that result from mutations in the CP deregulate P53. METHODS: A HBx combination (combo) mutant with changes in the CP region that corresponded to A1762T/G1764A (TA), T1753A, and T1768A was constructed and expressed in L-02 and Hep3B cells. The effects of CP mutations on expression and degradation of P53, and the effects on cell cycle progression and proliferation were analyzed. RESULTS: The combo mutant decreased levels of P53 and increased cyclin D1 expression, accelerated P53 degradation in L-02 cells, accelerated cell cycle progression, and increased expression of S-phase kinase-associated protein 2 (Skp2) in L-02 and Hep3B cells. Silencing of Skp2 abrogated the effects of CP mutations on P53 expression. The kinetics of P53 expression correlated with changes in cell cycle distribution. CONCLUSIONS: The HBx mutant with a combination of CP mutations can up-regulate Skp2, which then down-regulates P53 via ubiquitin-mediated proteasomal degradation, increasing the risk of hepatocellular carcinoma.

Reappraisal of evidence of microscopic portal vein involvement by hepatocellular carcinoma cells with stratification of tumor size.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death internationally, it is necessary to reappraise evidences of HCC cells involving the portal vein, especially considering tumor size. MATERIALS AND METHODS: Histopathological evidence and dynamic evidences of radiology and cytology from publication were collected and analyzed. RESULTS: Frequencies of microscopic portal vein involvement (MPVI) and microscopic intrahepatic metastasis (MIM) in resected specimens with single nodule HCC were lower than that of multi nodule HCC, although not significantly. Early HCC (≤1.5 cm) was with extremely low to 0 frequencies of MPVI and MIM. HCC >5 cm showed a tendency of flowing HCC cells into portal vein, which was coincident with significantly high frequency (64.1 %) of MPVI for HCC >5 cm. There were no significant difference of frequencies of MPVI and MIM between groups of tumor ≤2, ≤3, and ≤5 cm. CONCLUSIONS: Single nodule HCC >5 cm needs anatomic resection and the root of portal vein should be firstly ligated because of tendency of flowing HCC cells into portal vein. For single nodule HCC ≤2 cm, there was a risk of about 16.2 % of MPVI, and a risk of about 16.2-26.4 % of MPVI for those single nodule HCC ≤5 cm, however, there was a risk of extremely low to 0 of MPVI for early HCC (≤1.5 cm). Surgeons have to balance liver reserve and risk of MPVI for HCC ≤5 cm before deciding anatomic or nonanatomic resection.

Delayed bronchobiliary fistula and cholangiolithiasis following percutaneous radio frequency ablation for hepatocellular carcinoma.

Although percutaneous radio frequency ablation for hepatocellular carcinoma is a minimally invasive therapy, there are some complications reported; major complications include hemorrhage (0.477%), hepatic injuries (1.690%), and extrahepatic organ injuries (0.691%). We, for the first time, described a rare complication of delayed bronchobiliary fistula and cholangiolithiasis in common bile duct following radio frequency ablation and the salvage treatment in a patient with chronic hepatitis B virus infection. Surgeons should be aware of severe and rare complications before deciding the ablation area and when performing radio frequency ablation, and should be aware of the relevant salvage treatment.

Primary hepatic mucosa-associated lymphoid tissue lymphoma and hemangioma with chronic hepatitis B virus infection as an underlying condition.

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma has a low incidence and is a rare subtype of hepatic malignant lymphoma. Described here is a rare case of primary hepatic MALT lymphoma and hepatic hemangioma with chronic HBV infection as an underlying condition. Possible treatment modalities, which should be selected in accordance with tumor size, tumor location, tumor number, and underlying liver disease, are discussed in conjunction with a review of the literature. In addition, the potential use of hepatic resection, radio frequency ablation (RFA), or radiotherapy followed by chemotherapy via the R-CHOP regimen is also discussed.

Effect of transplantation route on stem cell migration to fibrotic liver of rats via cellular magnetic resonance imaging.

BACKGROUND AIMS: Assessing mesenchymal stromal cells (MSCs) after grafting is essential for understanding their migration and differentiation processes. The present study sought to evaluate via cellular magnetic resonance imaging (MRI) if transplantation route may have an effect on MSCs engrafting to fibrotic liver of rats. METHODS: Rat MSCs were prepared, labeled with superparamagnetic iron oxide and scanned with MRI. Labeled MSCs were transplanted via the portal vein or vena caudalis to rats with hepatic fibrosis. MRI was performed in vitro before and after transplantation. Histologic examination was performed. MRI scan and imaging parameter optimization in vitro and migration under in vivo conditions were demonstrated. RESULTS: Strong MRI susceptibility effects could be found on gradient echo-weighted, or T2∗-weighted, imaging sequences from 24 h after labeling to passage 4 of labeled MSCs in vitro. In vivo, MRI findings of the portal vein group indicated lower signal in liver on single shot fast spin echo-weighted, or T2-weighted, imaging and T2∗-weighted imaging sequences. The low liver MRI signal increased gradually from 0-3 h and decreased gradually from 3 h to 14 days post-transplantation. The distribution pattern of labeled MSCs in liver histologic sections was identical to that of MRI signal. It was difficult to find MSCs in tissues near the portal area on day 14 after transplantation; labeled MSCs appeared in fibrous tuberculum at the edge of the liver. No MRI signal change and a positive histologic examination were observed in the vena caudalis group. CONCLUSIONS: The portal vein route seemed to be more beneficial than the vena caudalis on MSC migration to fibrotic liver of rats via MRI.

Adjuvant systemic drug therapy and recurrence of hepatocellular carcinoma following curative resection.

Postoperative recurrence of hepatocellular carcinoma (HCC) has a negative impact on long-term survival. According to available evidence, many systemic untargeted agents are ineffective as adjuvant therapy to prevent the recurrence of HCC following curative resection. Interferon α has potential effectiveness as adjuvant therapy for HCC in the presence of underlying conditions such as HBV or HCV infection. Oral polyprenoic acid has also proven its effectiveness according to a prospective study; however, no other studies have reported polyprenoicacid (acyclic retinoid) to be effective. Sorafenib is the only systemic molecular targeted agent that has proven effectiveness as adjuvant therapy according to a pilot study. To date, 11 randomized clinical trials are underway with different agents as adjuvant systemic drug therapy to prevent the recurrence of HCC following curative resection according to Clinicaltrial.gov. Adjuvant systemic drugs may be the most promising of all adjuvant modalities in the near future since HCC may be a systemic disease rather than a local disease.

Impaired phosphate and tension homologue deleted on chromosome 10 expression and its prognostic role in radical surgery for hepatocellular carcinoma with family aggregation resulting from hepatitis B and liver cirrhosis.

This study aimed to retrospectively investigate the expression of the phosphate and tension homologue deleted on chromosome 10 (PTEN) protein and its prognostic role in hepatocellular carcinoma (HCC) with family aggregation resulting from hepatitis B and liver cirrhosis, which have not been established. Immunohistochemical analysis was performed to evaluate the PTEN protein expression in HCC and paired para-cancerous tissues from 79 patients with HCC caused by hepatitis B and liver cirrhosis. Of these cases, 34 represented HCC with family aggregation (HCCF group), and 45 represented HCC with no family aggregation (HCCN group). Follow-up data were collected for 3 months to 10 years and analysed for HCC recurrence, survival time and prognostic risk factors. The expression of the PTEN protein in the HCC tissue was dramatically lower in the HCCF group than in the HCCN group. The six-month, one-year and two-year overall recurrence (OR) rates of the HCCF group were significantly higher than those of the HCCN group. The one-year, two-year and five-year overall survival (OS) rates of the HCCF group were lower than those of the HCCN group. Impaired PTEN protein expression was an independent prognostic risk factor that was significantly correlated with OR and OS in HCC patients. Dramatically impaired PTEN protein expression in HCC patients with family aggregation resulting from hepatitis B and liver cirrhosis was correlated with OR and OS, and impaired PTEN expression was an independent risk factor for prognosis after radical surgery.

Strategies to prevent hepatitis B virus infection in China: immunization, screening, and standard medical practices.

China has one of the world's highest rates of hepatitis B infection. Over the past 20 years, a series of strategies have been implemented to prevent infection with the hepatitis B virus (HBV) in China. These strategies include hepatitis B (hepB) immunization for susceptible populations such as infants and young children and for high-risk populations such as health care workers and patients, premarital health care for couples of childbearing age, and standard medical practices. A series of measures implemented by the Chinese government caused the HBV infection rate in China to decrease from 9.75% in 1992 to 7.2% in 2006. However, a report on infectious diseases indicated that more than 1 million people in China were infected with hepB in 2011. There is room for improvement. The current work analyzed the current status of and challenges for strategies to prevent HBV infection in China. This work also recommends clear guidance regarding hepB immunization for parents in rural areas, more flexible premarital health care, health education for both patients and health care workers, and routine HBV screening for high-risk health care workers.

Generation of a human bone marrow-derived mesenchymal stem cell line expressing and secreting high levels of bioactive α-melanocyte-stimulating hormone.

α-Melanocyte-stimulating hormone (α-MSH) functions as a mediator of inflammation and immunity; however, the short half-life and high dose needed limit the comprehensive clinical application of α-MSH. The aim of this study was to generate human bone marrow-derived mesenchymal stem cells (MSCs) that express and secrete high levels of bioactive α-MSH. MSCs were obtained from a normal donor and assessed for proliferation, surface markers, and adipogenic and osteogenic differentiation. A lentivirus-encoding α-MSH was constructed. MSCs were infected with this lentivirus-encoding α-MSH and assessed for stability and the expression and secretion of bioactive α-MSH. The cumulative MSC expansion rates pre- and post-lentivirus infection were not significantly different (P > 0.05). The MSCs remained stable after infection with the lentivirus-encoding α-MSH. The concentration of α-MSH in the supernatants of MSCs infected with the lentivirus-encoding α-MSH was 17.55 ng/ml (P < 0.001), and a melanin assay indicated that bioactive α-MSH was secreted from MSCs infected with the lentivirus-encoding α-MSH, with an optical absorbance at OD(405) of 0.886 (P < 0.001). These results suggested that MSCs were promising cell carriers for the expression and secretion of high levels of bioactive α-MSH.