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The underlying ischemic and bleeding risks of acute myocardial infarction (AMI) with active tuberculosis (TB) are unknown. The goal of this study was to explore the ischemic and bleeding risks, as well as treatment strategies during hospitalization, in patients with AMI with or without active TB.Patients were recruited from a tuberculosis hospital from 2014 to 2021. The primary outcomes were major cardiovascular and cerebrovascular events (MACE) and Bleeding Academic Research Consortium (BARC)-defined type 3 or 5 bleeding. Multivariate logistic regression and propensity score matching were performed for risk adjustment. Subgroups were defined according to AMI with active pulmonary TB and AMI with active TB undergoing percutaneous coronary intervention (PCI).A total of 242 patients were enrolled. Compared with AMI without active TB, AMI with active TB had a higher risk of MACE and BARC type 3 or 5 bleeding (P0.001 and P = 0.002, respectively). Multivariate logistic regression analysis showed that, compared with AMI without active TB, the odds ratio (OR) was 6.513 (95% CI, 2.195-19.331) for MACE in patients with AMI with active TB, and the OR was 16.074 (95% CI 3.337-77.436) for BARC type 3 or 5 bleeding in patients with AMI with active TB. After propensity score matching, AMI with active TB tended to increase the risk of MACE, although not statistically significantly (P = 0.189), and increased BARC type 3 or 5 bleeding (P0.001), compared with AMI without active TB. Results of subgroup analyses showed that active TB had outcomes consistent with those of the total cohort. AMI patients with active pulmonary TB who underwent PCI had a lower risk of MACE without an increase in the risk of bleeding compared with those not undergoing PCI.Patients with AMI with active TB have a higher risk of MACE (or severe MACE) and bleeding than patients with AMI without active TB. However, AMI patients with active TB are still advised to undergo PCI for a high net clinical benefit.

Background Mixed adenoneuroendocrine carcinoma is a rare clinical manifestation, especially in the gastric and ampullary. The purpose of this study was to investigate the clinicopathological features and prognosis of mixed adenoneuroendocrine carcinoma in the gastric and ampullary and summarize related treatment suggestions. Methods In all, 32 cases of mixed adenoneuroendocrine carcinoma in the gastric and ampullary that were diagnosed from resected specimens were analyzed from 2009 to 2015. The corresponding demographic, clinicopathological and survival data were retrospectively reviewed. Results The 1-year, 3-year and 5-year survival rates were 78.1%, 28.1 and 9.4%, respectively, and the median overall survival was 28.0 months. In all, 75.0% (24/32) had lymph node metastasis at the time of initial diagnosis. A multivariate analysis revealed that TNM stage (HR 6.444 95%CI 1.477–28.121 P = 0.013), lymph nodes metastasis (HR10.617 95%CI 1.409–79.997 P = 0.022), vascular invasion (HR 5.855 95%CI 1.719–19.940 P = 0.005), grade of the adenocarcinoma component (HR 3.876 95%CI 1.451–10.357 P = 0.007) and CD56 positivity (HR 0.265 95%CI 0.100–0.705 P = 0.008) were independent predictors of overall survival. Conclusions Mixed adenoneuroendocrine carcinoma is an aggressive clinical entity with a poor prognosis. Taking both the neuroendocrine component and the adenocarcinoma component into consideration of optimal treatment is strongly recommended.

Purpose The goal of this study was to evaluate the predictive ability of the inflammation-based Glasgow Prognostic Score (GPS), platelet-lymphocyte ratio (PLR), Global Registry of Acute Coronary Events (GRACE) score and combined diagnostic models for the occurrence of major adverse cardiovascular and cerebrovascular events (MACEs) in patients with acute myocardial infarction (AMI). Methods In this retrospective cohort study, eligible patients were required to meet the third global definition of myocardial infarction. The primary outcome of this study was the occurrence of MACEs during hospitalization. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive ability of the GPS, PLR, GRACE scores, and joint diagnostic models for primary outcomes; univariate and multivariate logistic regression analyses were performed. Findings A total of 175 patients were enrolled. The results of the univariate ROC curve analysis for the incidence of MACEs during hospitalization showed that the area under the curve (AUC) was 0.780 (95% confidence interval (CI) 0.696-0.864) for the GPS, 0.766 (95% CI 0.682-0.850) for the redefined GPS (RGPS), 0.561 (95% CI 0.458-0.664) for the PLR score (PLRS), and 0.793 (95% CI 0.706-0.880) for GRACE. Multivariate ROC curve analysis showed that the AUC value was 0.809 (95% CI 0.726-0.893) for the GPS combined with GRACE, 0.783 (95% CI 0.701-0.864) for the GPS combined with the PLRS, 0.794 (95% CI 0.707-0.880) for GRACE combined with the PLRS, and 0.841 (95% CI 0.761-0.921) for the GPS combined with GRACE and the PLRS. The combined diagnostic model including the GPS plus GRACE and the PLRS had a higher AUC value than the GPS, RGPS and GRACE models (P = 0.014, P = 0.004, and P = 0.038, respectively). The multivariate logistic regression model showed that the odds ratio for hospitalized MACEs was 5.573 (95% CI 1.588-19.554) for GPS scores of 2 versus 0, and the GRACE score was also an independent risk factor for MACEs, with an odds ratio of 1.023 (95% CI 1.009-1.036). Implications The diagnostic model combining the GPS plus GRACE and the PLRS has better predictive ability for the occurrence of MACEs during hospitalization than each single score. Thus, the use of a combined GPS plus GRACE and PLRS model will be of clinical benefit in a broad group of individuals with AMI.

Background The effect of postsurgical radiotherapy (PSRT) among T1-3 gallbladder cancer (GBC) patients with one to three lymph node metastases remains controversial. The aim of this study was to assess the impact of PSRT on gallbladder cancer-specific survival (GBCSS) in patients with stage IIIB. Methods The data of GBC patients were obtained from the American Surveillance, Epidemiology, and End Results (SEER) Data resources between 2004 and 2015. Then, a 1:1 propensity score matching (PSM) method was performed. GBCSS was compared among all patients. Subgroup analysis was conducted to identify patients who would benefit from PSRT. Results 726 AJCC (8th edition) stage IIIB GBC patients were included. PSRT failed to improve GBCSS (p = 0.168). Male sex, tumor size ≥ 4 cm and absence of chemotherapy were independent negative prognostic factors. No significant survival benefit from PSRT was found in any subgroup. Conclusions PSRT provides no survival benefit for IIIB GBC.

ObjectiveSystemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays a significant gender difference in terms of incidence and severity. However, the underlying mechanisms accounting for sexual dimorphism remain unclear. The aim of this work was to reveal the heterogeneity in the pathogenesis of SLE between male and female patients.MethodsPBMC were collected from 15 patients with SLE (7 males, 8 females) and 15 age-matched healthy controls (7 males, 8 females) for proteomic analysis. The proteins of interest were validated in independent samples (6 male SLE, 6 female SLE). Biomarkers for neutrophil activation (calprotectin), neutrophil extracellular traps (cell-free DNA and elastase), and reactive oxygen species (glutathione) were measured, using enzyme-linked immunosorbent assay, in plasma obtained from 52 individuals.ResultsEnrichment analysis of proteomic data revealed that type I interferon signaling and neutrophil activation networks mapped to both male and female SLE, while male SLE has a higher level of neutrophil activation compared with female SLE. Western blot validated that PGAM1, BST2, and SERPINB10 involved in neutrophil activation are more abundant in male SLE than in female SLE. Moreover, biomarkers of neutrophil activation and reactive oxygen species were increased in male SLE compared with female SLE.ConclusionType I interferon activation is a common signature in both male and female SLE, while neutrophil activation is more prominent in male SLE compared with female SLE. Our findings define gender heterogeneity in the pathogenesis of SLE and may facilitate the development of gender-specific treatments.

Fluid balance (FB) is associated with poor sepsis outcomes; however, it cannot accurately reflect the dynamic fluid accumulation status. Here, we explored a new index, the FB to fluid intake ratio (FB/FI), for evaluating dynamic fluid accumulation in sepsis. FB/FI values within 48 hours were recorded. Their association with in-hospital mortality was investigated using logistic regression and mediation analyses of data from 7,839 patients. In extended logistic models, a linear association was found between FB and mortality (odds ratio [OR]: 1.05-1.08, p < 0.001). However, this association became non-significant after the adjustment of FB/FI (OR: 1.00, 95% confidence interval [CI]: 0.98-1.02). For FB/FI and mortality, a cut-off value of 0.25 was defined. In the spline function logistic model, FB/FI > 0.25 was significantly associated with increased mortality (OR: 4.46, 95% CI: 2.92-6.80), whereas FB/FI ≤ 0.25 was not. For the FB/FI > 0.25 subgroup, mediation analysis was used to clarify the relationship between FB, FB/FI, and mortality. We observed that the direct effect of FB was non-significant (adjusted coefficient: −0.001, 95% CI: −0.005 to 0.002) while the indirect effect was significant (adjusted coefficient: 0.009, 95% CI: 0.006-0.011). In the FB/FI ≤ 0.25 subgroup, both the FB volume (0.9 ± 0.7 vs. −2.0 ± 1.9, p < 0.001) and the FB/FI ratio (0.14 ± 0.07 vs. −0.77 ± 1.60, p < 0.001) were significantly higher in patients with FB > 0 than those with FB ≤ 0. However, both the crude and adjusted comparisons of hospital mortality were non-significant. Similar associations were observed in septic shock patients. FB/FI > 0.25 is a significant risk factor for mortality in sepsis, while FB/FI ≤ 0.25 is not. The association between FB and mortality is completely mediated by this new fluid accumulation index. More comprehensive indices are required for evaluating dynamic fluid status in sepsis.

Hybridization of nitric oxide (NO) donors with known anti-cancer agents have been emerged as a strategy to achieve improved therapeutic effect and to overcome chemo-resistance in cancer therapy. In this study, furoxan moiety as an efficient NO donor was introduced to phenstatin, a microtubule-interfering agent (MIA), leading to the design and synthesis of a series of furoxan-based NO-releasing arylphenones derivatives. In biological evaluation, the synthesized compounds showed moderate to potent anti-tumor activities against several human cancer cell lines. Among them, compound 15h showed the most potent activities against both chemo-sensitive and resistant cancer cell lines with IC

Single cell biology has the potential to elucidate many critical biological processes and diseases, from development and regeneration to cancer. Single cell analyses are uncovering the molecular diversity of cells, revealing a clearer picture of the variation among and between different cell types. New techniques are beginning to unravel how differences in cell state-transcriptional, epigenetic, and other characteristics-can lead to different cell fates among genetically identical cells, which underlies complex processes such as embryonic development, drug resistance, response to injury, and cellular reprogramming. Single cell technologies also pose significant challenges relating to processing and analyzing vast amounts of data collected. To realize the potential of single cell technologies, new computational approaches are needed. On March 17-19, 2021, experts in single cell biology met virtually for the Keystone eSymposium "Single Cell Biology" to discuss advances both in single cell applications and technologies.

Molecular barcoding technologies that uniquely identify single cells are hampered by limitations in barcode measurement. Readout by sequencing does not preserve the spatial organization of cells in tissues, whereas imaging methods preserve spatial structure but are less sensitive to barcode sequence. Here we introduce a system for image-based readout of short (20bp) DNA barcodes. In this system, called Zombie, phage RNA polymerases transcribe engineered barcodes in fixed cells. The resulting RNA is subsequently detected by fluorescent in situ hybridization. Using competing match and mismatch probes, Zombie can accurately discriminate single-nucleotide differences in the barcodes. This method allows in situ readout of dense combinatorial barcode libraries and single-base mutations produced by CRISPR base editors without requiring barcode expression in live cells. Zombie functions across diverse contexts, including cell culture, chick embryos, and adult mouse brain tissue. The ability to sensitively read out compact and diverse DNA barcodes by imaging will facilitate a broad range of barcoding and genomic recording strategies., Editorial summary: The spatial location and sequence of DNA barcodes are detected with high sensitivity in fixed tissues.

Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions., HuBMAP supports technology development, data acquisition, and spatial analyses to generate comprehensive molecular and cellular three-dimensional tissue maps.

Mitochondrial trans-2-enoyl-CoA reductase (MECR) is a protein-coding gene, and the protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFASII). Numerous studies have shown disorder of lipid metabolism is closely related with malignance, especially in liver cancer. Through pre-experiment, we found that the expression of MECR gene was highly expressed in hepatocelluar carcinoma (HCC) cell lines in vitro. This suggests that the MECR gene may play a role of oncogene in HCC. Therefore, we conducted a preliminary experimental study on the role of MECR gene in HCC cells in vitro. Objective to explore whether the MECR gene can affect the malignant biological behavior of HCC. We selected HCC cell line BEL-7404 as experimental cell, which involves the highest expression of MECR in the pre-experiment. We constructed MECR knockdwon lentivirus vector, and then infected HCC cell lines to down-regulate MECR expression, and establish negative control group (NC). Through various experiments of cytology, our study showed that knockdown of MECR inhibited cell proliferation and colony formation, promoted apoptosis, and inhibited metastasis in HCC cell lines BEL-7404. MECR might serve as a novel gene therapeutic target for the treatment of HCC. Further study is needed to elucidate the signaling pathway through which MECR functions in HCC.

Axillary lymph node dissection is the standard surgical procedure for breast cancer patients with sentinel lymph node (SLN) positive. In clinical practice, axillary lymph node dissection may be an unnecessary treatment for some breast cancer patients with non-sentinel lymph node (NSLN) negative. The aim of this study was to analyze the risk factors of NSLN metastasis in breast cancer patients with SLN positive. Four hundred fifty-six clinical early stage breast cancer patients with SLN positive were collected and analyzed in the oncological surgery department of Fujian Provincial Hospital during 2013 to 2018. All these patients underwent surgical treatment. The average age and tumor size of 443 patients with SLN positive breast cancer were (49.8 ± 10.8) years and (2.42 ± 0.94) cm. Univariate analysis showed that the size of primary tumor, the number of positive SLN, the number of negative SLN, the ratio of positive SLNs, and the type of metastases in SLN were the influencing factors of NSLN metastasis. Multivariate regression analysis showed that primary tumor size T2 cm (P.001, OR = 2.609), the positive number of SLNs ≥3 (P = .002, OR = 5.435), the ratio of positive SLNs ≥ 50% (P = .017, OR = 1.770), and SLN macrometastases (P0.001, OR = 16.099) were independent risk factors for NSLN metastasis. Combined with the 4 independent risk factors, the area under the curve to predict NSLN metastasis was 0.7470.7. For clinical early breast cancer with positive SLN, primary tumor size T2 cm,the positive number of SLNs ≥ 3, the ratio of positive SLNs ≥ 50%, and SLN macrometastases could predict NSLN metastasis well, and guide surgery to avoid overtreatment.

Background Tuberculous pleural effusions (TBPEs) and malignant pleural effusions (MPEs) are two of the most common and severe forms of exudative effusions. Clinical differentiation is challenging; however, metabolomics is a collection of powerful tools currently being used to screen for disease‐specific biomarkers. Methods 17 TBPE and 17 MPE patients were enrolled according to the inclusion criteria. The normalization gas chromatography‐mass spectrometry (GC‐MS) data were imported into the SIMCA‐P + 14.1 software for multivariate analysis. The principal component analysis (PCA) and orthogonal partial least‐squares discriminant analysis (OPLS‐DA) were used to analyze the data, and the top 50 metabolites of variable importance projection (VIP) were obtained. Metabolites were qualitatively analyzed using the National Institute of Standards and Technology (NIST) databases. Pathway analysis was performed by MetaboAnalyst 4.0. The detection of biochemical indexes such as urea and free fatty acids in these pleural effusions was also verified, and significant differences were found between these two groups. Results 1319 metabolites were screened by non‐targeted metabonomics of GC‐MS. 9 small molecules (urea, L‐5‐oxoproline, L‐valine, DL‐ornithine, glycine, L‐cystine, citric acid, stearic acid, and oleamide) were found to be significantly different (p 0.8), with good sensitivity and specificity. Conclusion Stearic acid, L‐cystine, and citric acid may be potential biomarkers, which can be used to distinguish between the TBPE and the MPE., Two common exudative pleural effusions (tuberculous pleural effusion and malignant pleural effusion) were selected as the object of study. The sample derivatized was analyzed by gas chromatography combined with mass spectrometer. The differential metabolites were obtained by SIMCA14.1 analysis. The markers with differential diagnosis value were obtained by spss21 and MetaboAnalyst 4.0 analysis. Finally, some of the markers were verified by biochemical analysis.

Lipopolysaccharide (LPS) could induce apoptosis and dysfunction of endothelial cells. We aimed to reveal the effects of macrophages on cell proliferation and apoptosis in LPS induced human umbilical vein endothelial cells (HUVECs). THP-1 derived macrophages and HUVECs were co-cultured in the presence of LPS. Cell viability was measured by Cell Counting Kit-8 and apoptosis was analyzed by flow cytometry. Expression of Ang1, the NF-κB component p65 was evaluated by western blot and quantitative PCR. Small interfering RNAs (siRNAs) were used to knockdown the expression of proinflammatory cytokines and p65 in HUVECs. Plasmid transfection-mediated overexpression of Ang1 was employed to see its effects on cell proliferation and apoptosis in HUVECs. Macrophages enhanced LPS-induced proliferation impairments and apoptosis in HUVECs, which could be attenuated by siRNA-mediated knockdown of cytokines TNF-α, IL-1β, IL-6 and IL-12p70 in macrophages. The dysfunction of HUVECs was tightly associated with reduced Ang1 expression and increased phosphorylated p65 (p-65). Overexpression of Ang1 in HUVECs significantly decreased p-p65, suggesting negatively regulation of p-p65 by Ang1. Overexpression of Ang1, adding recombinant Ang1 or silencing of p65 substantially attenuated the dysfunction of HUVECs in terms of cell proliferation and apoptosis. In conclusions, THP-1-derived macrophages enhance LPS induced dysfunction of HUVECs via Ang1 and NF-κB pathways, suggesting new therapeutic targets for sepsis.

Chronic respiratory diseases’ (CRDs) impact on re-intubation rate remains unclear. We investigated the association between these factors in mechanically ventilated patients. Data were extracted from the freely available online Medical Information Mart for Intensive Care III database. CRDs were defined according to ICD-9 codes. Generalised linear regression and propensity score matching were performed. Of 13,132 patients, 7.9% required re-intubation. Patients with chronic obstructive pulmonary disease (COPD) had higher re-intubation (OR 2.48, 95% CI 1.83–3.33) and mortality rates (OR 1.64, 95% CI 1.15–2.34) than those without. Patients with asthma had a lower mortality rate (OR 0.63, 95% CI 0.43–0.92) but a similar re-intubation rate to those of patients without. These findings remained stable after propensity score matching and bootstrapping analysis. The association of COPD with re-intubation was significantly stronger in patients with high oxygen-partial pressure (PaO2) or mild disease severity but was independent of carbon dioxide partial pressure. Corticosteroid use was associated with increased re-intubation rates in subgroups without CRDs (OR 1.77–1.99, p 2 or mild disease severity should be carefully monitored as they have higher re-intubation and mortality rates.

Objective To investigate the surgical indication and tactics for liver hemangioma in the caudate lobe Methods From January 1994 to July 2019, 137 patients, including 51 males and 86 females with the average age of 49.2 years old were diagnosed with liver hemangioma in caudate lobe and received treatment at five tertiary referral hospitals. Clinical features, correlations between tumor size and clinical manifestations, treatments, and prognosis were analyzed. Results Of the 137 patients identified, 40 (29.20%) patients were asymptomatic, whereas other 94 patients had clinical symptoms mainly presented as upper abdominal discomfort, epigastric distention, upper abdominal dull pain, nausea, and vomiting. Fifteen (93.75%), 18 (39.13%), and 7 (10.45%) patients presented no clinical symptoms among those tumor size was less than 3 cm (D ≤ 3 cm, n = 16), 3 cm n = 46), and 6 cm n = 67), respectively, while all 8 patients with tumor larger than 9 cm were symptomatic. Tumor diameter was obviously associated with the presence of clinical symptoms. In follow-up period, 7 patients in the conservative group (n = 39) received surgery because of tumor growth or symptom appearance. Totally 105 patients received operation including partial resection or isolated complete resection of caudate lobe and caudate lobe resection combined with liver segment resection, right liver resection, or left liver resection. All operations went smoothly, and no severe complications appeared. Conclusion Tumor diameter was obviously associated with the presence of clinical symptoms in patients with hemangioma in caudate lobe. Surgical therapy is not recommended for asymptomatic patients and available for patient who has symptoms. Effective surgical strategies should be put into use to reduce operative bleeding.

Background: Gallbladder cancer (GBC) is the most common malignancy of the biliary system. Early T stage GBC patients with distant metastasis are proven to have a worse prognosis. In this study, our aim was to construct and validate a novel nomogram for predicting distant metastasis in T1 and T2 GBC. Methods: Between 2004 and 2014, patients with T1 and T2 GBC were identified in the Surveillance, Epidemiology, and End Results (SEER) database. All of the eligible patients were randomly divided into training and validation cohorts. Univariate and multivariate analyses were used to assess significant predictive factors associated with distant metastasis. A nomogram was developed and validated by a calibration curve and receptor operating characteristic curve (ROC) analysis. Results: According to the inclusion and exclusion criteria, 3013 patients with historically confirmed AJCC stage T1 and T2 GBC were enrolled. Younger age, high pathological grade, nonadenocarcinoma, T1, N1 and larger tumor size correlated positively with the risk of distant metastasis. A novel nomogram was established to predict distant metastasis in early T stage GBC patients. Internal validation with a calibration plot in the training cohort showed that this nomogram was well calibrated. Through ROC curve analysis, the areas under the ROC curves in the training and validation cohorts were 0.723 and 0.679, respectively. Conclusions: Although some limitations exist in this predictive model, the nomogram revealed the relationship between the clinicopathological characteristics of T1 and T2 GBC patients and the risk of distant metastasis. The novel nomogram will assist in patient counseling and guide treatment decision making for T1 and T2 GBC patients.

Background Acute respiratory distress syndrome (ARDS), a complex response to various insults, has a high mortality rate. As pulmonary edema resulting from increased vascular permeability is a hallmark of ARDS, management of the fluid status, including the urine output (UO) and fluid intake (FI), is essential. However, the relationships between UO, FI, and mortality in ARDS remain unclear. This retrospective study aimed to investigate the interactive associations among UO, FI, and mortality in ARDS. Methods This was a secondary analysis of a prospective randomized controlled trial performed at 10 centers within the ARDS Network of the National Heart, Lung, and Blood Institute research network. The total UO and FI volumes within the 24-h period preceding the trial, the UO to FI ratio (UO/FI), demographic data, biochemical measurements, and other variables from 835 patients with ARDS, 539 survivors, and 296 non-survivors, were analyzed. The associations among UO, FI, the UO/FI, and mortality were assessed using a multivariable logistic regression. Results In all 835 patients, an increased UO was significantly associated with decreased mortality when used as a continuous variable (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.98–0.99, P = 0.002) and as a quartile variable (OR of Q2 to Q4: 0.69–0.46, with Q1 as reference). To explore the interaction between UO and FI, the UO/FI was calculated, and a cut-off value of 0.5 was detected for the association with mortality. For patients with a UO/FI ≤0.5, an increased UO/FI was significantly associated with decreased mortality (OR: 0.09, 95% CI: 0.03–0.253, P 0.5 (OR: 1.04, 95% CI: 0.96–1.14, P = 0.281). A significant interaction was observed between UO and the UO/FI. The association between UO and mortality was significant in the subgroup with a UO/FI ≤0.5 (OR: 0.97, 95% CI: 0.96–0.99, P = 0.006), but not in the subgroup with a UO/FI > 0.5. Conclusions The association between UO and mortality was mediated by the UO/FI status, as only patients with low UO/FI ratios benefitted from a higher UO.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer-related mortality worldwide. In this review, we made a review on current guidelines published from January 2001 to June 2017 worldwide with a focus on the clinical management of HCC. The electronic databases MEDLINE, the Chinese SinoMed, and the Japanese CiNii were systematically searched. A total of 18 characteristic guidelines for HCC management were finally included, including 8 guidelines from Asia, 5 from Europe, and 5 from the United States of America (USA). If guidelines were published in multiple versions, the most recent update was included, and surveillance, diagnosis, and treatment were compared. The composition of and recommendations in current guidelines on HCC varied, so these guidelines were regrouped and diagnostic and treatment algorithms were summarized graphically to provide the latest information to clinicians. The diagnostic criteria were grouped into 2 categories of a "Size-based pathway" and a "Non-size-based pathway." The treatment criteria were divided into 4 categories: i) Criteria based on the Barcelona Clinic Liver Cancer staging system; ii) Criteria based on the modified Union of International Cancer Control staging system; iii) Criteria based on the Child-Pugh class of liver function; and iv) Criteria based on tumor resectability. Findings from comparison of current guidelines might help target and concentrate efforts to improve the clinical management of HCC. However, further studies are needed to improve the management and outcomes of HCC. More straightforward or refined guidelines would help guide doctors to make better decisions in the treatment of HCC in the future.

Perihilar cholangiocarcinoma (pCC, also known as a Klatskin tumor) is the most common type of cholangiocarcinoma (CC). Preoperative biliary drainage (PBD) is indicated for pCC patients with acute cholangitis or patients who need portal vein embolization (PVE). However, the routine performance of PBD in other patients with pCC is still controversial. The current study retrospectively examined patients with pCC who did not undergo PVE and who did not have cholangitis who were seen at this Hospital to assess the advantages and disadvantages of PBD. This study also sought to find an optimal value of total bilirubin (TB) to indicate performing PBD. Between 2009 and 2014, after excluding patients with acute cholangitis and PVE, patients who had undergone hepatectomy for pCC were enrolled in this study. First, the surgical outcomes and postoperative outcomes were compared between PBD group and direct surgery group. Second, ROC curve analysis of a subgroup of patients was performed to find the best cut off value of TB for indicating the PBD. Third, the costs for patients, including the total charges and the charges per day were compared between the two groups. Subjects were 218 patients in total. Fifty-five patients underwent PBD. This group had a longer operative time [390 (210-700) vs. 360 (105-730) min, p = 0.013], and a longer hospital stay [20 (9-48) vs. 17 (6-93) days, p = 0.007], but underwent vascular resection and reconstruction less often [8 (14.5%) vs. 50 (30.7%), p = 0.019]. Mortality and morbidity were comparable between the two groups. ROC curve analysis of a subgroup of patients indicated that the cut-off value for total bilirubin was 218.75 μmol/L (12.4 mg/dL). The total hospital charges and the charges per day did not differ significantly for the two groups. Disadvantages of PBD were a longer operating time and a longer duration of hospitalization, but the short-term surgical outcomes and hospital charges of PBD group were comparable to the direct surgery group. PBD should be considered for patients when the diagnosis is still suspicious of pCC. Based on the current data, the optimal cut-off value for preoperative TB was 218.75 μmol/L (12.4 mg/dL) to indicate PBD for patients with pCC.

Imaging the transcriptome in situ with high accuracy has been a major challenge in single-cell biology, which is particularly hindered by the limits of optical resolution and the density of transcripts in single cells1-5. Here we demonstrate an evolution of sequential fluorescence in situ hybridization (seqFISH+). We show that seqFISH+ can image mRNAs for 10,000 genes in single cells-with high accuracy and sub-diffraction-limit resolution-in the cortex, subventricular zone and olfactory bulb of mouse brain, using a standard confocal microscope. The transcriptome-level profiling of seqFISH+ allows unbiased identification of cell classes and their spatial organization in tissues. In addition, seqFISH+ reveals subcellular mRNA localization patterns in cells and ligand-receptor pairs across neighbouring cells. This technology demonstrates the ability to generate spatial cell atlases and to perform discovery-driven studies of biological processes in situ.

BACKGROUND Candida is a pathogenic fungus. In recent years, the increase in immunosuppressive diseases has led to an increase in Candida infections, with the lungs being the most common site. Therefore, the aim of this study was to compare the positive detection rates of Candida in sputum samples by Candida culture and fluorescent polymerase chain reaction (PCR), and to explore a new method for rapid, accurate, and effective detection of Candida in sputum, providing swift evidence of clinical fungal infection. MATERIAL AND METHODS From October 2016 to March 2017, 300 sputum samples were collected and detected by the conventional culture method and fluorescent PCR method. The positive rate of Candida detection was compared between the 2 methods. RESULTS In the 300 sputum samples, the positive detection rate of Candida was 50% by the culture method and 65.67% by the fluorescent PCR method (P

Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression, drug resistance and tumor recurrence. We have recently shown that the Notch pathway determines the tumor-regulatory role of experimentally created ‘CAFs’. Here, we examined the status of Notch signaling in human melanoma-associated fibroblasts (MAFs) versus their normal counterparts and tested whether manipulation of the Notch pathway activity in MAFs alters their tumor-regulatory function. Using tissue microarrays, we found that MAFs exhibit decreased Notch pathway activity compared with normal fibroblasts in adjacent and non-adjacent skin. Consistently, MAFs isolated from human metastatic melanoma exhibited lower Notch activity than did normal human fibroblasts, demonstrating that Notch pathway activity is low in MAFs. We then investigated the effect of increasing Notch pathway activity in MAF on melanoma growth in co-cultures and in a mouse co-graft model. We found that activation of the Notch pathway in MAFs significantly restricted melanoma cell growth in vitro and suppressed melanoma skin growth and tumor angiogenesis in vivo. Our study demonstrates that the Notch signaling is inhibited in MAFs. Increase of Notch pathway activity can confer tumor-suppressive function on MAFs. Thus, targeting melanoma by activating Notch signaling in MAF may represent a novel therapeutic approach.

Background: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC. Methods: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality. Results: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90° died compared to 31 of 193 patients with QRS-T angles ≤90° (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 ± 53.4° vs. 107.2 ± 54.4°, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class. Conclusions: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.

Phellinus rhabarbarinus soaked in wine has folk usages by local residents of Ailao mountain of Yunnan province, China, which were to daub the wound to prevent infection and to drink to enhance immunity and treat other diseases such as cough, gastritis, and cancer. Systemic investigation on the chemical constituents of fruiting bodies of P. rhabarbarinus resulted in the isolation of 11 lanostane triterpenoids (1-10) including three new ones, namely, phellibarins A-C (1-3), together with five ergosterols (11-15). This is the first time reporting secondary metabolites of P. rhabarbarinus. Compounds 2, 3, 7, and 8 showed inhibitory activities against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages, whereas compounds 2-4, 6, 7, and 10 exhibited cytotoxicities against human cancer cell lines. The results of this assessment suggested that the lanostane triterpenoids in fruiting bodies of P. rhabarbarinus played key roles in its folk usages.

Cholangiocarcinoma (CC) accounts for about 3% of all gastrointestinal tumors and is the second most common primary liver tumor. Quality guidelines on CC are needed to guide hepatobiliary surgeons. Here, current guidelines on CC were reviewed to provide useful information and suggestions to help institutes and organizations all around the world to draft better guidelines on CC. Literature databases were electronically searched to identify guidelines or consensus statements regarding CC published from 2002-2016. Nine guidelines were included in this review. Comparison of the current guidelines revealed several inconsistencies. Signs of conflicting views indicated a lack of high level evidence. More studies need to be conducted in areas of contention to help update the guidelines. Organizations and medical societies need to be encouraged to use standard evaluation measures, to restrict tumors to CC or iCC, pCC, or dCC specifically, to give recommendations in accordance with the equipment that is available for diagnosis and treatment in different counties, and to use an appropriate and consistent structure when establishing and drafting guidelines for CC.

The reassortment of two highly pathogenic avian influenza (HPAI) H5N1 and H7N9 viruses presents a potential challenge to human health. The hemagglutinins (HAs) and neuraminidases (NAs) of these simultaneously circulating avian influenza viruses were evaluated using the pseudoparticle (pp) system. Native and mismatched virus pps were generated to investigate their biological characteristics. The HAs and NAs of the two viruses reassorted successfully to generate infectious viral particles. H7 was demonstrated to have the ability to reassort with NA from the H5N1 viruses, resulting in the generation of virions that were highly infectious to bronchial epithelial cells. Although the Anhui H5+Anhui N9 combination showed an moderate infectivity to the four cell lines, it was most sensitive to oseltamivir. The H7 in the pps was found to be predominantly HA0. Further, H5 in the pps primarily presented as HA1, owing to the particular mechanisms underlying its maturation. All NAs predominantly existed in monomer form. In our study, HAs/NAs, in all combinations, were functional and able to perform their corresponding function in the viral life cycle. Our data suggest that HAs/NAs from the (HPAI) H5N1 and H7N9 viruses are capable of assembly into infectious virions, posing a threat topublic health.

Two new acetylenic compounds, asparoffins A (1) and B (2), together with two known compounds, nyasol (3) and 3″-methoxynyasol (4), were isolated from stems of Asparagus officinalis. The structures of two new compounds were elucidated on the basis of detailed spectroscopic analyses (UV, IR, MS, 1D, and 2D NMR). All compounds were evaluated for their cytotoxicities against three human cancer cell lines.

Hepatocellular carcinoma (HCC) with sarcomatous change (SC) is a rare malignancy associated with high aggressiveness and poor prognosis; however, its prognostic significance remains unclear. From January 1994 to April 2012, surgically resected HCCs with SC (n = 52) at West China Hospital were retrospectively reviewed. HCC with SC was defined as the concomitant presence of the sarcomatous component occupying at least 10 % (but not predominantly) of the HCC-bearing tissue. To validate its prognostic significance, we compared the clinicopathological features and survival rates of these patients with a cohort of 214 randomly selected ordinary HCC patients during the same period. The clinicopathological characteristics of HCC with SC were similar to those of ordinary HCC, with the exception of capsule formation, adjacent organ invasion, lymph node metastasis, and TNM staging. A total of 45 (86.5 %) HCC patients with SC experienced a recurrence, with a median time to recurrence of 6.0 months. Overall survival (OS) rates in the sarcomatous HCC group at 1, 2, and 3 years were 55.8, 25, and 17.3 %, respectively, which were significantly lower than those in the ordinary HCC group (p

Single-cell analysis is a rapidly evolving approach to characterize genome-scale molecular information at the individual cell level. Development of single-cell technologies and computational methods has enabled systematic investigation of cellular heterogeneity in a wide range of tissues and cell populations, yielding fresh insights into the composition, dynamics, and regulatory mechanisms of cell states in development and disease. Despite substantial advances, significant challenges remain in the analysis, integration, and interpretation of single-cell omics data. Here, we discuss the state of the field and recent advances and look to future opportunities., Genome Biology, 18, ISSN:1474-760X

Objective To study the differential expression of genes between Hirschsprung’s disease (HSCR) and normal tissue by using microarray for exploring the mechanism of HSCR development and establishing the gene expression profiles of HSCR. Methods Colon tissues (aganglionic and normal segments) of 4 patients with HSCR were detected by the Agilent SurePrint G3 Human GE 8x60K Microarrays. RT-PCR was used to verify the results of Microarray test. Then, immunohistochemistry was used to demonstrate the expression of HAND2 in the myenteric plexus of the colon from 46 patients with HSCR to further explore the relationship between HAND2 and development of HSCR. Results A total of 12,125 meaningful expressed genes were screened out. 4 pairs of specimens had 622 differentially expressed genes, 584 (93.89%) of which were up-regulated while 38(6.11%) were down-regulated. 6 of the 622 genes were tested by RT-PCR, which were consistent with the results detected by Microarray. The average optical density of positive expression of HAND2 in myenteric plexus was compared between the aganglionic, transitional, dilated, normal segments and control group. The average optical density in the aganglionic segments was obviously reduced. Statistical analyzed data showed that it has significant deviation (P Conclusion 1. A set of differentially expressed genes between aganglionic and normal segments of HSCR was obtained. Our data may provide significant information to research the pathogenesis of HSCR. 2. Reduced protein expression of HAND2 in the myenteric plexus of the aganglionic would suggest that HAND2 was involved in the pathogenesis of HSCR.

strongObjective/strongTo explore the effects of dermabrasion combined with ReCell

Objective To explore the risk factors of the progression of persistent pure ground-glass nodule (pGGN) and make the risk stratification for pGGN 10 mm or less in diameter. Methods From June 2008 to April 2015,100 patients (108 lesions) with persistent pGGN≤10 mm in diameter were included in this study. Patients were followed up at least 1 year using thin-section computed tomography (CT). Patients' baseline clinical data and CT characteristics of pGGN were compared between progression group (size increased or/and solid component appeared) and non-progression group. Cox regression analysis was used to assess the relationship between clinical data,CT characteristics of pGGN,and lesion progression. The risk indices of lesion progression were calculated according to the results of Cox regression analysis and the relative factors of lung adenocarcinoma in previous studies. Logistic regression analysis was used to assess the relationship between risk indices and lesion progression. The optimal cutoff value was decided on receiver operating characteristic curve of risk indices and verified for predicting lesion progression. Results Fifteen of 108 lesions showed progression. The mean follow-up duration was (1016.36±486.00) days. There were statistically significant differences of lesion size,air bronchogram,and vessel changes between progression group and non-progression group (P=0.040,P=0.003,P=0.030,respectively).Lesion density (CT value≥-542.5 HU) and air bronchogram were the risk factors of lesion progression (P=0.003,P=0.021,respectively). The optimal cutoff value of total risk indices on predicting lesion progression was 4.25,with the sensitivity of 46.7%,specificity of 89.2%,and consistency of 83.3%. Conclusions CT value ≥-542.5 HU of pGGN and air bronchogram within lesion may predict lesion progression in persistent pGGN 10 mm or less in diameter. A risk index of less than 4.25 often suggests small probability of disease progression and thus a longer follow-up interval is recommended.

Hepatocellular carcinoma (HCC) is a highly prevalent cancer with a high mortality rate and HCC is always accompanied with a hepatitis B virus (HBV) infection, unlike many other types of cancers. Over the past few years, cancer-related long non-coding RNAs (lncRNAs) and virus-related lncRNAs have attracted the attention of many researchers, and a number of previous studies have examined the relationship between lncRNAs and various cancers and viruses. The current study used The Cancer Genome Atlas database to screen for lncRNAs up-regulated in HCC in order to identify cancer biomarkers. Results revealed five lncRNAs that were the most up-regulated. This result was then verified in 10 HCC cell lines and two normal liver cell lines. Quantitative real-time PCR revealed that the five lncRNAs were substantially up-regulated in HCC cell lines. Several of the five lncRNAs were expressed at higher levels in a few HCC cell lines that were infected with HBV or that were positive for its protein or DNA than in HCC cell lines that were not infected with HBV or that were negative for its protein or DNA. These findings suggest that the five lncRNAs might play a role in the progression of HCC and/or HBV infection, and these findings need to be studied in further detail.

Regenerative medicine is an emerging discipline. Adipose tissue is a rich source of fat cells and mesenchymal stem cells, and autologous fat grafting has increasingly been applied in plastic surgeries and dermatological treatments. This paper reviews the latest advances in autologous fat grafting in scar revision.

In this review, we discuss a strategy to bring genomics and proteomics into single cells by super-resolution microscopy. The basis for this new approach are the following: given the 10 nm resolution of a super-resolution microscope and a typical cell with a size of (10 µm)^3, individual cells contain effectively 10^9 super-resolution pixels or bits of information. Most eukaryotic cells have 10^4 genes and cellular abundances of 10–100 copies per transcript. Thus, under a super-resolution microscope, an individual cell has 1000 times more pixel volume or information capacities than is needed to encode all transcripts within that cell. Individual species of mRNA can be uniquely identified by labeling them each with a distinct combination of fluorophores by fluorescence in situ hybridization. With at least 15 fluorophores available in super-resolution, hundreds of genes in can be barcoded with a three-color barcode (_3C_(15) = 455). These calculations suggest that by combining super-resolution microscopy and barcode labeling, single cells can be turned into informatics platforms denser than microarrays and that molecular species in individual cells can be profiled in a massively parallel fashion.

Objective: Using a block-designed BOLD-fMRI to explore the neural basis of spatial working memory impairment in patients with subclinical hypothyroidism (SCH) performing an n-back task. Methods: Sixteen patients with SCH before and after being treated with levothyroxine (LT4) for 6 months and 16 matched euthyroid subjects were scanned by fMRI under the n-back task. Results: The fMRI scan found that a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), supplementary motor area/anterior cingulate cortex, bilateral parietal lobe (PA) and right caudate nucleus/thalamus was activated, with right hemisphere dominance. In euthyroid subjects, all these regions of interest (ROIs) showed load effect; however, only left DLPFC, left PA, bilateral PreMA and right caudate nucleus/thalamus showed the same effect in Pre-SCH patients. Furthermore, activation intensities of most ROIs (especially DLPFC and right PA) for Pre-SCH patients were lower than those in the euthyroid subjects (F 0.062). Importantly, after a 6-month treatment with LT4, the load effect in SCH patients appeared the same as in the euthyroid subjects in all the ROIs (F >13.176, p < 0.0001). Conclusion: Our previous study shows that verbal working memory of SCH patients is impaired with abnormal activity in bilateral frontal areas. In this study, the results indicated that SCH patients may also have spatial working memory impairments, and the altered activities of right DLPFC and right posterior parietal lobe may be one of the underlying neural mechanisms. Most importantly, this study shows that LT4 replacement therapy can improve the memory impairment and reverse the altered neural activity network.

This study was designed to investigate the pathogenesis of gynaecomastia by measuring phosphatase and tensin homologue (PTEN), O6-methylguanine-DNA methyltransferase (MGMT) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) protein in breast tissue specimens from 68 patients with gynaecomastia and 24 normal male controls using immunohistochemical staining. The gynaecomastia cases were divided into three different histological types: florid, intermediate and fibrous. The PTEN, MGMT and DNA-PKcs proteins were detected in both gynaecomastia and normal breast tissue, but the levels of immunohistochemical staining of each protein were significantly lower in gynaecomastia breast tissue than in normal breast tissue. There were also significant differences in the levels of immunohistochemical staining for the three proteins according to gynaecomastia histological type. These results suggest that abnormally low levels of PTEN, MGMT and DNA-PKcs protein in gynaecomastia breast tissue may play a role in the development of gynaecomastia. Further research is required to elucidate fully their individual roles in the pathophysiology of gynaecomastia.

Heparin affects both dermal fibroblast proliferation and collagen and may mediate these effects by altering the levels of transforming growth factor-beta1 (TGF-beta1) production and TGF-beta1 mRNA expression as a wound healing modulator. The purpose of this study is to probe the effect of heparin on TGF-beta1 and TGF-beta1 mRNA production by human normal skin and hyperplastic scar fibroblasts. This research investigates the effect of heparin on TGF-beta1 and TGF-beta1 mRNA production by human normal skin and hyperplastic scar fibroblasts with exposure to 0 microg/mL, 100 microg/mL, 300 microg/mL, or 600 microg/mL heparin for 24, 48, 72, or 96 hours in a serum-free in vitro model. Levels of TGF-beta1 in the supernatants and TGF-beta1 mRNA expression of fibroblasts were determined by enzyme-linked immunosorbent assay (ELISA) and real time RT-PCR, respectively. Heparin (300 microg/mL and 600 microg/mL) stimulated TGF-beta1 production by normal skin (26% to 83%) and hyperplastic scar fibroblasts (63% to 85%), with statistical significance (P < 0.05) at various time points. Heparin (300 microg/mL and 600 microg/mL) also stimulated TGF-beta1 mRNA expression by normal skin (12% to 53%) and hyperplastic scar fibroblasts (33% to 52%), with statistical significance (P < 0.05) at various time points. These effects of heparin on normal skin and hyperplastic scar fibroblasts may have implications for hyperplastic scar formation and wound healing in vivo.

Background Choledochal cyst is rare in western countries.The relatively high incidence of coexistent hepatobiliary disease increases the difficulty of the surgical management of choledochal cyst.Here we analyze the diagnosis and treatment of congenital bile duct cyst in 122 Chinese adults. Methods The clinical data of 122 patients with congenital choledochal cysts admitted from 1981 to 2006 were analyzed. Results Clinical symptoms in most cases were nonspecific,resulting in delayed diagnosis.Sixty-one patients(50%) had coexistent pancreatobiliary disease.Among the 122 patients,119 patients underwent ultrasonic examination; ERCP/MRCP was performed in 63 cases and CT in 102 cases.Abnormal pancreatobiliary duct junction was found in 48 patients.Sixteen patients had malignant lesions in the bile duct,arising in 11 of them from incomplete choledochal cyst that underwent various operations including cystenterostomy or cystojejunostomy.There was significant difference between the patients who underwent incomplete cyst resection and complete cyst resection in malignancy rate of bile duct(Chi square test,P=0.000;odds ratio,7.800;95 % confidence interval,2.450 to 24.836). Conclusions ERCP,CT and MRCP had proved their great values in the classification of the disease.Cyst excision with Roux-en-Y hepaticojejunostomy is recommended as the treatment of choice for patients with type I or type Ⅳ cysts.For type Ⅴ cyst(Caroli's disease)with recurrent cholangitis,liver transplantation should be considered. Chin Med J 2007;120(16):1404-1407

To discuss the correlation of pathologic subtypes and immunohistochemical implication with CT features of lung adenocarcinoma 1 cm or less in diameter with focal ground-glass opacity (fGGO).CT appearances of 59 patients who underwent curative resection of lung adenocarcinoma ≤ 1 cm with fGGO were analyzed in terms of lesion location, size, density, shape (round, oval, polygonal, irregular), margin (smooth, lobular, spiculated, lobular and spiculated), bubble-like sign, air bronchogram, pleural tag, and tumor-lung interface. Histopathologic subtypes were classified according to International Association for the Study of Lung Cancer/ American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma. Common molecular markers in immunohistochemical study included human epidermal growth factor receptor (HER)-1,HER-2,Ki-67, vascular endothelial growth factor (VEGF) and DNA topoisomerase 2Α.Patients' age and lesions' size and density were compared with pathologic subtypes using analysis of variance or nonparametric Wilcoxon tests. Patients' gender, lesion location, shape and margin, bubble-like sign, air bronchogram, pleural tag, and tumor-lung interface were compared with histopathologic subtypes and immunohistochemical implication using ψ² test or Fisher's exact test.The patients' gender, age, lesion location, shape, air bronchogram, pleural tag, and tumor-lung interface were not significantly different among different histopathologic subtypes (P=0.194, 0.126, 0.609, 0.678, 0.091, 0.374, and 0.339, respectively), whereas the lesion size,density,bubble-like sign, and margin showed significant differences (P=0.028, 0.002, 0.003, 0.046, respectively). The expression of Ki-67 significantly differed among nodules with different shapes(P=0.015). Statistically significant difference also existed between tumor-lung interface and HER-1 expression (P=0.019) and between bubble sign and HER-2 expression (P=0.049).Of lung adenocarcinoma ≤ 1 cm with fGGO,bubble-like sign occurs more frequently in invasive pulmonary adenocarcinoma and less frequently in atypical adenomatous hyperplasia. In addition, preinvasive lesions (atypical adenomatous hyperplasia and adenocarcinoma in situ) more frequently demonstrates smooth margin,while invasive lesions (minimally invasive adenocarcinoma and invasive pulmonary adenocarcinoma) more frequently demonstrates lobular and spiculated margin. Some CT features are associated with immunohistochemical implication of lung adenocarcinoma ≤ 1 cm with fGGO.

Human augmenter of liver regeneration has been expressed in Escherichia coli, purified and crystallized. The crystals belong to space group C222, with unit-cell parameters a=51.7 A, b=78.8 A, c=63.7 A. Diffraction data were collected to 2.80 A with a completeness of 99.9% (99.9% for the last shell), a R(sym) value of 0.092(0.236) and an I/sigma(I) value of 6.2(2.7).

To investigate associations of single nucleotide polymorphisms (SNPs) rs2228314 of sterol regulatory element-binding protein-2 (SREBP-2) or rs11039155 of liver X receptor α (LXRα) with susceptibility to polycystic ovary syndrome (PCOS) in a Chinese Han population. SREBP-2 rs2228314 and LXRα rs11039155 polymorphisms were genotyped in patients with PCOS and age- and sex-matched PCOS-free controls from a Chinese Han population. A total of 605 patients with PCOS and 615 controls were recruited in this study. We found that GC and CC genotypes of rs2228314, and variant C, were associated with a significantly increased risk of PCOS. In addition, GA and AA genotypes of rs11039155, as well as variant A, were also associated with a significantly increased risk of PCOS. Our results showed that SREBP-2 rs2228314 G to C change and variant C genotype as well as LXRα rs11039155 G to A change and variant A may contribute to PCOS in Chinese Han population.

ObjectiveThe aim of this study was to compare the effectiveness of percutaneous needle aspiration (PNA) and percutaneous catheter drainage (PCD) in the management of liver abscess.MethodsElectronic searches (Cochrane Library, MEDLINE, EMBASE, SCIE) were conducted to identify randomized controlled trials (RCTs) comparing PNA and PCD. A meta-analysis was subsequently performed.ResultsA total of five RCTs covering 306 patients were included. The meta-analysis showed that outcomes in patients treated with PCD were superior to those in patients treated with PNA in terms of success rate [relative risk (RR): 0.81, 95% confidence interval (CI) 0.66–0.99; P = 0.04], clinical improvement [standardized mean difference (SMD): −0.73, 95% CI 0.36–1.11; P = 0.0001] and days to achieve a 50% reduction in abscess cavity size (SMD: −1.08, 95% CI 0.64–1.53; P < 0.00001). No significant differences were found in duration of hospitalization (mean difference: −0.17, 95% CI −2.10 to 1.75; P = 0.86) or procedure-related complications (RR: 0.50, 95% CI 0.10–2.63; P = 0.41). Days to achieve the total or near total resolution of the abscess cavity and mortality were not calculated because data in the RCTs in the meta-analysis were insufficient.ConclusionsBoth PNA and PCD are safe methods of draining liver abscesses. However, PCD is more effective than PNA because it facilitates a higher success rate, reduces the time required to achieve clinical relief and supports a 50% reduction in abscess cavity size. However, among successfully treated patients, the outcomes of PNA are comparable with those of PCD.

The cytochrome P450 2D6 (CYP2D6) is the most highly polymorphic isoenzyme of the cytochrome P-450-system, which affects the metabolism of one-fourth of all prescription drugs. Tramadol, a narcotic-like pain reliever used to treat moderate to severe pain, is primarily metabolized by CYP2D6. The CYP2D6*10 allele is the most common allele in the Chinese population. Therefore, we investigated the effects of CYP2D6*10 on tramadol pharmacokinetics in 45 post-operative patients who had undergone gastrointestinal tract surgery. Tramadol was administered to the patients after the operation, and the plasma concentrations of tramadol and O-desmethyltramadol were subsequently evaluated at 12 time points. Pharmacokinetic analyses were performed using non-compartmental methods. The area under the curve (AUC), plasma clearance (CL), elimination half-life (T1/2), mean residence time (MRT), peak concentration, and peak time of tramadol and O-desmethyltramadol were calculated. CYP2D6*10 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The frequency of CYP2D6*10 alleles was 51% in the 45 patients. The patients were divided into three groups according to their CYP2D6*10 genotype: wild-type, heterozygous, and homozygous mutant. Pharmacokinetic parameters were compared among the three groups. The analyses showed that T1/2, MRT, and AUC of tramadol were larger, and CL was lower in homozygous mutant patients compared to the wild-type group (P0.05). These results show that the CYP2D6*10 genetic polymorphism has a significant impact on the pharmacokinetics of tramadol in Chinese post-operative patients.

To explore the clinical classification method of keloids and providing a thread for the treatment of keloids.To summarize the 600 cases of keloid patients we accepted and diagnosed from November 2004 to October 2012, and filling in keloid patients information sheet, recording the keloids form by photographs, analyzing the treatment, putting forward the classification method of keloids in clinic.According to the position and quantity that keloids grow, the keloid patients are divided into four major categories:one in single site, one in each site, more than one in single site and more than one in each site; According to the area and thickness of keloids, the keloid single lesion is divided into four subclasses: type of small area and thin, type of small area and thick, type of large areas and thin,type of large areas and thick; According to the number of lesions, keloid multiple lesions is divided into two subgenera: isolated multiple and dispersion multiple, different kinds of keloids suit different methods of treatment.The clinical classification method of keloids can be used to provide thought for the treatment of keloids, and have a good application value.

What benefits and toxicities patients acquire from the use of bevacizumab combined with firstline chemotherapy remains controversial. This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer (mCRC).Several databases, including PubMed, Embase, and Cochrane Library, were searched up to April 30, 2013. Eligible studies were only randomized, controlled trials (RCTs) with a direct comparison between mCRC patients treated with and without bevacizumab. Overall risk ratio (RR), hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials.Six RCTs, including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group, were included. Overall, the addition of bevacizumab to first-line chemotherapy increased overall response rate (ORR) by 4.5%, prolonged both progression-free survival (PFS) and overall survival (OS), and increased the rate of total Grades 3 or 4 adverse events (G3/4AEs) by 6.9%. Significant differences were found in ORR (RR = 1.22 (95% CI 1.01-1.46), P = 0.03), PFS (HR = 0.60 (95% CI 0.47-0.77), P0.0001), OS (HR = 0.83 (95% CI 0.70-0.97), P = 0.02), and any G3/4AEs (OR = 1.56 (95% CI 1.29-1.89), P0.00001).Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC, because of conferring a significant improvement in ORR, PFS, and OS, even though it increased adverse events.

To explore the changes of sublingual microcirculation in elderly patients with severe sepsis/septic shock.Twenty-three patients with sepsis, 10 patients without sepsis and 10 healthy elderly patients were enrolled. Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. And the 28-day mortality rates of all septic patients were recorded.Compared with the healthy group, all elderly patients had significant sublingual microcirculation dysfunctions. Compared with the severe septic and nonseptic patients, perfused vessel density (PDV) , proportion of perfused vessels (PPV) and microvascular flow index (MFI) of septic shocks were significantly lower. Compared with the severe septic patients, PDV, PPV and MFI instead of lactate and MAP of septic shocks were significantly lower from Day 1 to Day 3. The values of PDV, PPV, MFI and lactate but not MAP of the surviving septic patients were significantly higher than those of the deceased ones.The elderly patients with septic shock have severe sublingual microcirculatory alterations. And these abnormalities are more marked in septic shock patients. Nonsurvivors showed more severe alterations than survivors. Microcirculatory alterations may be measured to guide the therapy.