Characterization of tumor microbiome and associations with prognosis in intrahepatic cholangiocarcinoma.

BACKGROUND: The tumor microbiome has been characterized in several malignancies; however, no previous studies have investigated its role in intrahepatic cholangiocarcinoma (ICC). Hence, we explored the tumor microbiome and its association with prognosis in ICC. METHODS: One hundred and twenty-one ICC tumor samples and 89 adjacent normal tissues were profiled by 16S rRNA sequencing. Microbial differences between tumor and adjacent nontumoral liver tissues were assessed. Tumor microbial composition was then evaluated to detect its association with prognosis. Finally, a risk score calculated by the tumor microbiota was accessed by the least absolute shrinkage and selector operator method (Lasso) to predict prognosis of ICC. RESULTS: The tumor microbiome displayed a greater diversity than that in adjacent nontumoral liver tissues. Tumor samples were characterized by a higher abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteriota. Higher tumor microbial α diversity was associated with lymph node metastasis and predicted shortened overall survival (OS) and recurrence-free survival (RFS). A total of 11 bacteria were selected to generate the risk score by Lasso. This score showed potential in predicting OS, and was an independent risk factor for OS. CONCLUSION: In conclusion, our study characterized the tumor microbiome and revealed its role in predicting prognosis in ICC.

Qishen Yiqi Dripping Pills for Cardiovascular Diseases: Effects and Mechanisms / 中国结合医学杂志

Qishen Yiqi Dripping Pills (QSYQ) is a compound of Chinese medicine, which has been used to treat coronary heart disease and cardiac dysfunction. Its natural components include astragaloside IV, flavonoids, danshensu, protocatechualdehyde, salvianolic acid B, salvianolic acid A, ginsenosides Rg1, ginsenosides Rb1, and essential oils, etc. It exerts effects of nourishing qi and promoting blood circulation to relieve pain. In this review, the bioactive components of QSYQ and its effects for treating cardiovascular diseases and possible mechanism were summarized, providing references for further study and clinical application of QSYQ.

CircRPN2 Inhibits Aerobic Glycolysis and Metastasis in Hepatocellular Carcinoma.

Although circular RNAs (circRNA) are known to modulate tumor initiation and progression, their role in hepatocellular carcinoma (HCC) metastasis remains poorly understood. Here, three metastasis-associated circRNAs identified in a previous circRNA-sequencing study were screened and validated in two HCC cohorts. CircRPN2 was downregulated in highly metastatic HCC cell lines and HCC tissues with metastasis. Patients with HCC with lower circRPN2 levels displayed shorter overall survival and higher rates of cumulative recurrence. Mechanistic studies in vitro and in vivo revealed that circRPN2 binds to enolase 1 (ENO1) and accelerates its degradation to promote glycolytic reprogramming through the AKT/mTOR pathway, thereby inhibiting HCC metastasis. CircRPN2 also acted as a competing endogenous RNA for miR-183-5p, which increases forkhead box protein O1 (FOXO1) expression to suppress glucose metabolism and tumor progression. In clinical samples, circRPN2 expression negatively correlated with ENO1 and positively correlated with FOXO1, and expression of circRPN2, either alone or in combination with ENO1 and FOXO1, was a novel indicator of HCC prognosis. These data support a model wherein circRPN2 inhibits HCC aerobic glycolysis and metastasis via acceleration of ENO1 degradation and regulation of the miR-183-5p/FOXO1 axis, suggesting that circRPN2 represents a possible therapeutic target in HCC. SIGNIFICANCE: The circRNA circRPN2 is a potential prognostic biomarker and therapeutic target in hepatocellular carcinoma that suppresses aerobic glycolysis and metastasis.

The spatial distribution of immune cell subpopulations in hepatocellular carcinoma.

Infiltrating immune cells in the tumor microenvironment (TME) influence tumor progression and patient prognosis, making them attractive therapeutic targets for immunotherapy research. A deeper understanding of immune cell distributions in the TME in hepatocellular carcinoma (HCC) is needed to identify interactions among different immune cell types that might impact the effectiveness of potential immunotherapies. We performed multiplex immunohistochemistry using a tissue microarray of samples from 302 patients with HCC to elucidate the spatial distributions of immune cell subpopulations (CD3+ , CD4+ , CD8+ , CD66b+ , and CD68+ ) in HCC and normal liver tissues. We analyzed the associations between different immune subpopulations using Pearson's correlation. G(r) functions, K(r) functions and Euclidean distance were applied to characterize the bivariate distribution patterns among the immune cell types. Cox regression and Kaplan-Meier analysis were used to evaluate the associations between tumor infiltration by different immune cells and patient outcomes after curative surgery. We also analyzed the relationship between the spatial distribution of different immune cell subpopulations with HCC patient prognosis. We found that the immune cell spatial distribution in the HCC TME is heterogeneous. Our study provides a theoretical basis for HCC immunotherapy.

Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. METHODS: To evaluate pDCs' distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. RESULTS: Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. CONCLUSIONS: Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

Circular RNA Sequencing Identifies CircASAP1 as a Key Regulator in Hepatocellular Carcinoma Metastasis.

BACKGROUND AND AIMS: There is growing evidence that single-stranded, circular RNA (circRNA) plays a key role in the development of certain cancers, including hepatocellular carcinoma (HCC). It is less clear, however, what role circRNA plays in HCC metastasis. APPROACH AND RESULTS: In this study, through circRNA sequencing, we identified a circRNA: circASAP1 (a circRNA derived from exons 2 and 3 of the ASAP1 gene, hsa_circ_0085616), which is associated with pulmonary metastasis after curative resection in patients with HCC. CircASAP1 was overexpressed in HCC cell lines with high metastatic potential and in metastatic HCCs. In vitro, circASAP1 promoted cell proliferation, colony formation, migration, and invasion, and in vivo, it enhanced tumor growth and pulmonary metastasis. Mechanism studies showed that circASAP1 acts as a competing endogenous RNA for microRNA 326 (miR-326) and microRNA 532-5p (miR-532-5p), both of which are tumor suppressors in HCC. We found that mitogen-activated protein kinase (MAPK) 1 and colony stimulating factor (CSF)-1 were direct common targets for microRNA 326 (miR-326) and microRNA 532-5p (miR-532-5p), which were regulated by circASAP1. CircASAP1 promotes HCC cell proliferation and invasion by regulating miR-326/miR-532-5p-MAPK1 signaling and, furthermore, mediates tumor-associated macrophage infiltration by regulating the miR-326/miR-532-5p-CSF-1 pathway. Clinical HCC samples exhibited a positive correlation between circASAP1 expression and levels of CSF-1, MAPK1, and CD68+ tumor-associated macrophages, all of which were predictive of patient outcomes. CONCLUSION: We identified circASAP1 as a key regulator of HCC metastasis that acts on miR-326/miR-532-5p-MAPK1/CSF-1 signaling and serves as a prognostic predictor in patients with HCC.

Lyme Borreliosis-associated Risk Factors in Residents of Beijing Suburbs: a Preliminary Case-control Study / 生物医学与环境科学（英文）

A population-based case-control study was conducted to evaluate the relative factors in the environments, agricultural works, outdoor activities, and the effectiveness of Lyme borreliosis (LB)- associated personal protective measures in Beijing. Thirty-four cases and 272 controls were personally interviewed by well-trained interviewers. Venous blood samples were taken from each subject. Sowing or harvesting in summer (OR=2.571, 95% CI: 1.109-5.962), living in house with weeding in the yard (OR=2.247, 95% CI: 1.062-4.755), and residence at the plain area (OR=2.630, 95% CI: 1.050-6.588) were the independent relative factors for seropositive LB. Wearing long pants and clothes with cuffs was the only protective behavior against tick bite (OR=0.186, 95% CI: 0.041-0.846). The findings showed that local farmers were easily infected with LB and almost no protective measure was taken against LB infection. Infection with LB was easier in residents of plain regions. Pets raising and outdoor activities were not the risk factors for infection with LB. Further studies are needed to fully understand the risk of infection with LB in China.

Endoscopic ultrasonography in tandem with endoscopic retrograde cholangiopancreatography in the management of suspected distal obstructive jaundice.

GOALS: To examine the benefits and feasibility of endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in tandem for distal obstructive jaundice. MATERIALS AND METHODS: From September 2007 to August 2012, patients with suspected distal obstructive jaundice were randomized to single-session EUS-ERCP (group A), EUS, and ERCP in different sessions (group B), and an ERCP-only procedure (group C). Data were prospectively collected on the following parameters: ERCP-avoided, duration of procedure, the dose of propofol, complications, and diagnostic yield. RESULTS: A total of 180 patients were divided randomly into 60 patients in group A, 60 in group B, and 60 in group C. A total of four therapeutic ERCP were canceled after EUS. The ERCP procedural time in group A was shorter, although not significantly different from that in group B (group A vs. group B: 41.24±7.57 vs. 43.38±6.57 min; P>0.05), but both were significantly less than that in group C (group C: 49.12±7.46 min; P<0.05). The total procedural time did not differ significantly between group A and group B (70.05±15.35 vs. 73.70±15.12 min; P>0.05), nor were there significant differences in the dose of propofol between them (group A vs. group B: 357.11±115.86 vs. 369.55±133.86 mg; P>0.05). In all, 22 anesthetic complications and 21 endoscopic complications occurred without significant differences among the three groups (P>0.05). CONCLUSION: As a triaging or a screening tool, diagnostic EUS gives added benefit to therapeutic ERCP. EUS and ERCP in a tandem approach are safe and feasible in patients with suspected distal obstructive jaundice.

Investigation on Ehrlichia chaffeensis and Anaplasma phagocytophilum infection among farmers and domestic animals in rural areas of Beijing, China / 中华流行病学杂志

Objective To investigate the status of Ehrlichia (E.)chaffeensis and A naplasma (A.) phagocytophilum infection among farming populations and domestic animals in the rural area of Beijing,China.Methods Blood samples from 562 farmers and 163 blood samples including 90 goats,71 ox and 2 dogs,were collected.Specificity of IgG antibodies against E.chaffeensis and A.phagocytophilum were tested by micro-indirect immunofluorescent assay (mIFA).16S rRNA genes of A.phagocytophilum were amplified from the domestic animal blood samples and products were sequenced and analyzed by nested PCR.Results The positive rates of E.chaffeensis and A.phagocytophilum antibody were 16.5％ and 14.0％ respectively for farmers.The total positive rates of A.phagocytophilum were 2.3％ and 0 for both goats and oxen respectively.No antibody was found for the 2 tested dogs.The PCR positive rates were 48.9％ and 23.9％ for goats and oxen respectively.Three dominant varieties of A.phagocytophilum were demonstrated in goats and oxen.Conclusion The prevalence rates of E.chaffeensis and A.phagocytophilum were identified in the rural areas of Beijing.

Exposure to avian influenza virus and the infection status of virus among people breeding or butchering ducks in the suburb of Beijing / 中华流行病学杂志

Objective To understand the exposure and the infection status of virus among people engaging in breeding or butchering ducks in the suburb of Beijing.Methods People from six districts (Daxing,Fangshan,Huairou,Miyun,Shunyi,Tongzhou) who engaged in breeding or butchering ducks were studied and the status of infecting avian influenza virus was obtained by testing antibody level in serum.Information on demographic characteristics,status of regular exposure and exposure to sick or dead poultry were collected through a self-designed questionnaire.Results 1741people were involved in this study in which 313 (18.0％ ) were workers in duck-breeding enterprise,562 (32.3％) were workers in duck slaughterhouse,261 (15.0％) farmers were in individualsmall-scale duck farms,605 (34.7％) were farmers raising duck in backyard.Among farmers raising duck in backyard,the percentage of people whose ducks ever contacted with wild birds was higher than the other three groups (66.8％)(P＜0.05).Among farmers who bred their ducks in the backyard (35.2％) and those abattoir workers (31.3％ ),the percentage of people who had contacted ducks but not been vaccinated with avian influenza vaccine was higher than the other two groups (P＜0.05).Regarding the status on cleaning and disinfection among the studied farmers who had bred their ducks in the backyard,the percentage of people who had closer contact with ducks would clean the settings more than 4 times per month (8.8％) and disinfected those places more than 12 times per year (27.3％) but still lower than the other three groups (P＜0.05).Among those farmers who bred ducks in the backyard,the percentage of people who had ever touched duck with their hands was high (34.4％) (P＜ 0.05).Regarding exposure to sick or dead poultry,higher proportion was found among those who had ever closely contacted sick or dead poultry commercial duck raisers (36.1％) and individuals who raise large amount of ducks (36.0％).70.8％ of the individual duck raisers had never taken any protective measures when closely contacting the sick or dead poultry.Among 1741 samples,0 were positive to avian influenza virus H5 and H7 subtypes.12 were positive to H9 subtype (positive rate was 0.7％ ),in which 10 were farmers raising ducks in backyard (the positive rate of 1.7％ ).Differences between H9 subtype antibody positive rates difference in 4 population groups were statistically significant (x2=13.699,P＜0.05).Conclusion Farmers who bred their ducks in the backyard had greater risk of contracting the avian influenza.Individual duckers who raise ducks in large scale and the farmers who bred their ducks in the backyard were in lack of protective measures when contacting the sick or dead poultry.Our findings suggested that some intervention measures should be taken to reduce the risk of avian influenza infection.