Sustained viral response and relapse after discontinuation of oral antiviral drugs in HBeAg-positive patients with chronic hepatitis B infection.

Objective: To investigate the sustained virological response and relapse in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) positive after stopping oral antiviral drugs, and to monitor the disease progression and the incidence of adverse events such as liver cirrhosis and hepatocellular carcinoma. Methods: This is a prospective observational study. Patients who continued nucleos(t)ide analogue (NA) treatment after achieving HBeAg seroconversion for more than 3 years were enrolled. After signing the informed consent form, patients stopped NA treatment and received follow-up. During the follow-up, the antiviral treatment information of the patients was collected, and the follow-up observation was carried out every 3 months since the enrollment. We monitored the virological indexes, liver and kidney function, serology and liver imaging during follow-up. The purpose of this study was to explore the sustained virological response rate, HBV DNA recurrence rate, clinical relapse rate and the related factors after drug withdrawal. Results: A total of 82 patients were enrolled, including 42 males (51.22%) and 40 females (48.78%), with a median age of 34.00 (31.00, 37.25) years. All enrolled patients were followed up for 1 year. At the end of the follow-up, 36.59% (30/82) of patients had sustained virological response, 63.41% (52/82) of patients had HBV DNA reactivation, 17.07% (14/82) of patients had clinical relapse, and 10.98% (9/82) of patients had HBeAg reversion. During the follow-up, there were no adverse events such as liver cirrhosis and hepatocellular carcinoma. The median level of hepatitis B surface antigen (HBsAg) in patients with sustained virological response was lower than that in patients with HBV DNA reactivation (2.92 vs.3.18 log10IU/ml, Z=-1.492/P=0.136), and the median level of baseline HBsAg in patients with HBV DNA reactivation was lower than that in patients with clinical relapse (3.01 vs.3.45 log10IU/mL, Z=-1.795/P=0.073), but the difference was not significant. There was no significant statistical difference between patients with sustained virological response and HBV DNA reactivation of the median total treatment time [69.50 (56.25, 86.00) vs.62.50 (44.00, 88.50) months, Z=-0.689/P=0.491], and the consolidation treatment time [41.50 (36.75, 54.75) vs.40.50 (36.00, 53.75) months, Z=-0.419/P=0.675]. Conclusion: The sustained virological response rate of HBeAg positive CHB patients after stopping oral antiviral treatment is lower, and it is more common in patients with lower HBsAg levels. Patients still need to be closely monitored after stopping NA therapy.

Dynamic changes of cytokine profiles and virological markers during 48 weeks of entecavir treatment for HBeAg-positive chronic hepatitis B.

Objective: The aims of this study were to investigate the kinetic changes of serum, virological, and immunological markers during entecavir (ETV) antiviral therapy and to explore whether these indicators can predict the antiviral efficacy of ETV in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. Methods: HBeAg-positive CHB patients were enrolled and treated with ETV 0.5 mg/day. Clinical biochemical, virological, and serological tests were performed at baseline and every 12 weeks during the 48-week treatment. Plasma levels of cytokines (Flt-3L, IFN-α2, IFN-γ, IL-10, IL-17A, IL-6, TGF-ß1, TGF-ß2, TGF-ß3, and TNF-α) were measured at baseline and at 12 and 24 weeks after treatment. Analysis of the trends of these clinical indicators in ETV antiviral therapy was performed. Results: A total of 105 HBeAg-positive CHB patients were enrolled, and 100 of them completed 48 weeks of ETV treatment and follow-up. After 48 weeks of treatment, hepatitis B s antigen (HBsAg) decline ≥ 1 log10 was found in seven patients, but no patient achieved HBsAg disappearance. serological HBeAg disappeared in 13 patients, and serological HBeAg transformed in 3 patients. The baseline HBsAg and HBeAg levels, HBV DNA load, IL-10, and TGF-ß1 levels in the complete virological response group were lower than those in the incomplete virological response group, while the ALT level in the complete virological response group was higher than that in the incomplete virological response group. Both univariate analysis and multivariate analysis showed that baseline biochemical indexes, virological indexes, and cytokine levels had no correlation with the complete virological response at 48 weeks. In multivariate analysis, low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment (HBeAg OR = 1.003, 95% CI 1.001-1.006, p = 0.007; HBV DNA OR = 0.184, 95% CI 0.046-0.739, p = 0.017; IL-10 OR = 0.040, 95% CI 0.972-0.999, p = 0.040). Conclusion: Cytokine levels changed dynamically during ETV antiviral therapy. Low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment.

Severe coagulopathy caused by cefminox sodium in a liver cirrhosis patient: a case report.

Cefminox sodium is an antimicrobial agent with broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. Cefminox sodium has high security in clinical practice for its few adverse effects such as coagulation dysfunction, which is rare in clinical treatment. Even in patients suffering from chronic liver disease with coagulation dysfunction, it rarely leads to further deterioration of coagulation function. Therefore, patients with chronic liver disease develop severe coagulation dysfunction during the application of cefminox sodium, which is often mistaken for worsening of liver disease other than considered to be the side effect of the drug. Therefore, we report a 55-year-old female patient with liver cirrhosis and hepatocellular carcinoma treated with cefminox sodium intravenously twice for peritonitis. During the treatments, severe coagulopathy occurred, and the coagulation function quickly recovered after drug withdrawal. The diagnosis and treatment of this patient provides us with ideas for dealing with similar problems in clinical practice in the future.

Cyy260, a novel small molecule inhibitor, suppresses non-small cell lung cancer cell growth via JAK2/STAT3 pathway.

Non-small cell lung cancer (NSCLC) is a malignant tumor that accounts for the most new cancer cases and cancer-related deaths worldwide, and the proliferation and metastasis of NSCLC are the main reasons for treatment failure and patient death. Traditional chemotherapeutic drugs have low selectivity, which can kill cancer cells and cause damage to normal cells at the same time. Therefore, it is particularly important to study therapies that target cancer cells and to find low-toxicity, high-efficiency anticancer drugs. Cyy260 is a novel small molecule inhibitor that we synthesized for the first time. Here, we investigated the in vitro and in vivo antitumor activities of Cyy260 and explored the underlying mechanisms in NSCLC. Cyy260 had a concentration- and time-dependent inhibitory effect on NSCLC cells, but it was less toxic to normal cells. Cyy260 regulated apoptosis through intracellular and extracellular apoptotic pathways. In addition, Cyy260 could also induce cell cycle arrest, thereby inhibiting cell proliferation. Further analysis of molecular mechanisms showed that the JAK2/STAT3 signaling pathway was involved in the antitumor effect mediated by Cyy260. Analysis of subcutaneously transplanted tumors in mice showed that Cyy260 suppressed tumor growth in vivo. Our results proved that Cyy260 is a novel inhibitor of the JAK2/STAT3 pathway thus may have potential in therapy of NSCLC and other cancers.

Effects of continuing nursing care under cognitive behavioral intervention on psychological state and living quality in patients with double J catheter after ureterolithiasis surgery.

OBJECTIVE: The effects of continuing nursing care under cognitive behavioral intervention on the psychological state and living quality of patients with double J catheter after ureterolithiasis surgery were analyzed in this research. METHODS: The research subjects in this study were 142 patients who were discharged from our hospital with a double J tube after ureterolithiasis surgeries from June 2019 to June 2020. According to the patient care plan, the subjects were divided into the control group (n=71) and the observation group (n=71) and respectively treated with routine basic nursing measures and continuing nursing care under cognitive-behavior intervention. Subsequently, the psychological state, living quality and the complications that occurred were compared between the two groups. RESULTS: The depression and anxiety scores of the two groups after 4 weeks of intervention, comparing to thoes before intervention, were seen with remarkably decreased significance (P<0.05). The scores of living quality and self-care quality of patients in the observation group were obviously higher than those in the control group (P<0.05). In addition, the incidence of complications in the observation group was critically lower than that in control group (P<0.05). CONCLUSION: Continuous nursing care under cognitive behavioral intervention can substantially improve the psychological state, living quality and self-care ability of patients with double J tube after ureterolithiasis surgery, and reduce the incidence of complications, which is worthy of clinic promotion.

Clinical Outcomes of Reresection in Patients with High-Risk Nonmuscle-Invasive Bladder Cancer Treated with En Bloc Transurethral Resection: A Retrospective Study with a 1-Year Follow-Up.

Purpose: To evaluate the impact of reresection on the clinical outcome in patients with primary high-risk nonmuscle-invasive bladder cancer (NMIBC) who initially received en bloc transurethral resection. Methods: A retrospective analysis of data on eligible high-risk NMIBC with en bloc resection from June 2015 to June 2019 was performed. Patients were divided into two groups based on the presence or absence of reresection after the initial en bloc resection. In the first group (reresection group), patients underwent en bloc reresection within 6 weeks. In the second group (non-reresection group), patients did not undergo en bloc reresection. Pathologic findings in patients with reresection and cystoscopic findings in all patients 3 months after initial resection were recorded. The primary study endpoint was recurrence-free survival (RFS). The secondary outcomes were the residual rate of the tumor after initial en bloc resection, tumor upstaging rate, and progression-free survival. Results: We identified 115 eligible patients, including 51 (44.3%) who underwent reresection within 6 weeks of the initial en bloc resection and 64 (55.7%) who did not undergo en bloc reresection after the initial en bloc resection. The clinicopathologic features were similar in patients with or without reresection. On finding tumor residues after the first en bloc resection, there were three cases (5.9%) in the reresection group compared with two cases (3.1%) in the non-reresection group (p = 0.473). Two patients (3.9%) in the reresection group had tumor progression to muscle-invasive bladder cancer, whereas one patient (1.6%) in the non-reresection group exhibited tumor progression (p = 0.430). The 1-year RFS rate was 94.1% in the reresection group and 90.6% in the non-reresection group (p = 0.269). In multivariate analysis, multifocality and T1 staging were independent prognostic factors for recurrence in patients with high-risk NMIBC who underwent en bloc resection. Conclusion: In patients with high-risk NMIBC not exceeding 4 cm in diameter with no more than four lesions and not in the anterior bladder wall, reresection after en bloc resection seems to have failed to improve the patient's prognosis. We predict that the future trend in the treatment of patients with high-risk NMIBC is from reresection to en bloc resection. However, a randomized controlled clinical study is required to confirm this hypothesis.

Dose-Independent Transfection of Hydrophobized Polyplexes.

Cationic polymers dynamically complex DNA into complexes (polyplexes). So, upon dilution, polyplexes easily dissociate and lose transfection ability, limiting their in vivo systemic gene delivery. Herein, it is found that polyplex's stability and endocytosis pathway determine its transfection dose-dependence. The polyplexes of hydrophilic polycations have dose-dependent integrity and lysosome-trafficking endocytosis; at low doses, most of these polyplexes dissociate, and the remaining few are internalized and trapped in lysosomes, abolishing their transfection ability. In contrast, the polyplexes of the polycations with optimal hydrophobicity remain integrated even at low concentrations and enter cells via macropinocytosis directly into the cytosol evading lysosomes, so each polyplex can accomplish its infection process, leading to dose-independent DNA transfection like viral vectors. Furthermore, the tuned hydrophobicity balancing the affinity of anionic poly(γ-glutamic acid) (γ-PGA) to the polyplex surface enables γ-PGA to stick on the polyplex surface as a shielding layer but peel off on the cell membrane to release the naked polyplexes for dose-independent transfection. These findings may provide guidelines for developing polyplexes that mimick a viral vector's dose-independent transfection for effective in vivo gene delivery.

Outcome of Chinese patients with hepatitis B at 96 weeks after functional cure with IFN versus combination regimens.

BACKGROUND & AIMS: Nucleotides with add-on interferon treatment (NUC-IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse. METHODS: Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC-IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse. RESULTS: 420 patients were included in intention-to-treat analysis with 290 and 130 in the IFN and NUC-IFN groups respectively. At week 96, the intention-to-treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per-protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC-IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC-IFN-treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero-reversion and recurrence of viremia in IFN treated group. CONCLUSION: NUC-IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).

The reduction in CD8+PD-1+ T cells in liver histological tissue is related to Pegylated IFN-α therapy outcomes in chronic hepatitis B patients.

BACKGROUND: Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy. METHODS: Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence. RESULTS: The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+ T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1- T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1- T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+ T cells had no significant difference. In addition, the levels of CD68+ mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05). CONCLUSIONS: The changes in the levels of CD8+PD-1+ T cells and CD68+ mononuclear cells may be related to the response to PEG-IFN-α therapy.

Evaluation of a logistic regression model for predicting liver necroinflammation in hepatitis B e antigen-negative chronic hepatitis B patients with normal and minimally increased alanine aminotransferase levels.

Liver necroinflammation is the indicator for treating patients with chronic hepatitis B (CHB) infection. However, there is no suitable non-invasive index for diagnosing liver necroinflammation. This study aimed to create a non-invasive index to predict liver necroinflammation in patients who lack clear-cut clinical inflammation parameters. Patients who were hepatitis B e antigen (HBeAg)-negative and underwent liver histological diagnosis, had a normal or minimally increased alanine aminotransferase (ALT) level were enrolled. Liver necroinflammation was defined as histological active index ≥4. A logistic regression model (LRM) was established based on the parameters independently associated with liver necroinflammation. Of all 550 patients, 36.73% had necroinflammation. In patients with an abnormal ALT level, the rate of necroinflammation was 52.49%. The area under the curve (AUC) of the ALT level for predicting necroinflammation was 0.655 (95% confidence interval [CI], 0.609-0.702), and that of the HBV DNA level ≥2000 IU/mL combined with an abnormal ALT level was 0.618. By using the LRM, the AUC improved to 0.769 (95% CI, 0.723-0.815) with a Youden index of 0.519 and diagnostic accuracy of 75.3%. The cutoff value ≥0.7 in the LRM had a specificity of 97.4% and positive predictive value of 85.0% for predicting necroinflammation. By using the cutoff value <0.15 in the LRM, the presence of necroinflammation could be excluded with a negative predictive value of 90.8%. This study indicated that the LRM can be used to effectively diagnose liver necroinflammation in HBeAg-negative patients with CHB who have normal or minimally elevated ALT levels.

Changes in APRI and FIB-4 in HBeAg-negative treatment-naive chronic hepatitis B patients with significant liver histological lesions receiving 5-year entecavir therapy.

According to guidelines, antiviral therapy for adults with immune-active chronic hepatitis B (CHB) should be adopted to decrease the risk of liver-related complications. Fibrosis assessment during antiviral treatment is a key step in antiviral therapy evaluation. Liver biopsy is the gold standard for assessing the degree of liver necroinflammation and fibrosis. However, because of its cost and the risk of life-threatening complications, performing a liver biopsy more than once after long-term effective treatment is difficult. In this study, we aimed to evaluate changes in liver fibrosis during 5 years of entecavir (ETV) treatment using noninvasive fibrosis markers in hepatitis B e-antigen (HBeAg)-negative treatment-naive CHB patients who require antiviral therapy. A total of 303 HBeAg-negative treatment-naive patients were enrolled in this study. Liver biopsy was performed before initiation of antiviral therapy. The diagnosis of CHB was made according to Chinese guidelines for the management of CHB. Patients requiring antiviral therapy (liver fibrosis stage ≥ F2, METAVIR scoring system) were treated with ETV for at least 5 years. These patients were followed up at 6-month intervals. A clinical and virological evaluation was performed at baseline and again at 12, 24, 36, 48, and 60 months during ETV treatment. Aspartate Aminotransferase to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) index were used to assess dynamic changes in liver fibrosis in HBeAg-negative CHB patients after 1, 2, 3, 4, and 5 years of ETV treatment. All enrolled patients underwent liver biopsy at baseline. Using the METAVIR fibrosis stages, there were 107, 125, 54, and 17 patients in F1, F2, F3, and F4 stages, respectively. The APRI and FIB-4 indexes enabled the correct identification of patients with severe fibrosis (METAVIR F3-F4), with an area under the receiver operating characteristic curve of 0.77 (95% confidence interval [CI] 0.72-0.83) and 0.76 (95% CI 0.70-0.82), respectively. The APRI values decreased significantly in F2 and F3 patients after 1 year of ETV therapy (P < 0.01). However, for F4 patients, APRI values decreased significantly at year 3 (P < 0.05). The FIB-4 values of F2, F3, and F4 patients who received ETV treatment were significantly decreased after 1, 3, and 5 years of ETV therapy, respectively (P < 0.05). APRI and FIB-4 values decreased significantly during 5-year ETV treatment in HBeAg-negative CHB patients, indicating that these noninvasive fibrosis tests might be useful for monitoring improvement in liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

Antioxidant Activity of Water Extract from Fermented Mycelia of Cordyceps sobolifera (Ascomycetes) in Caenorhabditis elegans.

This research aimed to evaluate the potential of Cordyceps sobolifera in mycelial biomass production via liquid culture and to assay the safety and determine the antioxidative and antiaging activities of Caenorhabditis elegans. A C. sobolifera isolate was cultured using the one-factor-at-a-time method to illustrate its carbon and nitrogen requirements. To assess safety, we determined the lethality, locomotion behavior, and reproduction of C. elegans cultured on a mycelial water extract (MWE) containing nematode growth medium (NGM). To investigate antiaging activity, C. elegans treated with MWE was incubated on NGM plates. The lethality was recorded throughout the whole life cycle. To identify antioxidant activity, C. elegans treated with MWE was exposed to paraquat, causing superoxide conditions. The results showed that C. sobolifera was favored by glucose and peptone as carbon and nitrogen sources, respectively. MWE was considered to be safe, as no abnormal behaviors were observed in C. elegans. Compared with nematodes pretreated with no MWE but with water instead, MWE at 1.0 mg/mL significantly prolonged the mean lifespan of C. elegans by 24%. We observed an obvious dose-effect relation between concentration and mean lifespan. The effective antioxidant activity was recorded at the high concentration of MWE. These findings demonstrate the potential antiaging and antioxidant properties of C. sobolifera as functional food and dietary supplement.

Negative Correlation of Serum Hepatitis B Surface Antigen and Hepatitis B e Antigen Levels with the Severity of Liver Inflammation in Treatment-naïve Patients with Chronic Hepatitis B Virus Infection.

BACKGROUND: Estimating the grades of liver inflammation is critical in the determination of antiviral therapy in patients chronically infected with hepatitis B virus (HBV). The aim of this study was to investigate the correlation of serum levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) with the liver inflammation grades in treatment-naïve patients with chronic HBV infection. METHODS: We retrospectively enrolled 584 treatment-naïve HBeAg-positive patients who underwent liver biopsy in Ditan Hospital from January 2008 to January 2016. Based on the severity of liver inflammation, the patients were divided into minimal, mild, and moderate groups. SPSS software was used for statistical analysis of all relevant data. RESULTS: The liver histological examinations showed that 324, 194, and 66 patients had minimal, mild, and moderate liver inflammation, respectively. The median age of the three groups was 30, 33, and 38 years, respectively (Χ2 = 26.00, P < 0.001). The median HBsAg levels in minimal, mild, and moderate inflammation groups were 4.40, 4.16, and 3.67 log U/ml, respectively, and the median HBeAg levels in the three groups were 3.12, 2.99, and 1.86 log sample/cutoff, respectively; both antigens tended to decrease as the grade of inflammation increased (Χ2 = 99.68 and Χ2 = 99.23, respectively; both P < 0.001). The cutoff values of receiver operating characteristic curve in the age, HBsAg and HBeAg levels were 36 years, 4.31 log U/ml, and 2.86 log S/CO, respectively, l to distinguish minimal grade and other grades of treatment-naïve HBeAg-positive patients with chronic HBV infection. CONCLUSIONS: Serum HBsAg and HBeAg quantitation might gradually decrease with aggravated liver inflammation and the corresponding cutoff values might help us to distinguish minimal grades and other grades and detect those who do not need antiviral therapy in treatment-naïve HBeAg-positive patients with chronic HBV infection.

Evaluation of different agricultural wastes for the production of fruiting bodies and bioactive compounds by medicinal mushroom Cordyceps militaris.

BACKGROUND: In commercial production of Cordyceps militaris (a famous Chinese medicine), cereal grains are usually utilized as cultivation substrates. This study aimed to evaluate the efficiency of agricultural wastes as substitute materials in the low-cost production of C. militaris. Cottonseed shells (CS), corn cob particles (CCP), Italian poplar sawdusts (IPS) and substrates spent by Flammulina velutipes (SS) were employed to cultivate C. militaris, using rice medium as control. RESULTS: CS and CCP were suitable for fruit body formation of C. militaris, with yields of 22 and 20 g per bottle respectively. Fruit bodies grown on CCP showed the highest levels of cordycepin and adenosine, up to 9.45 and 5.86 mg g-1 respectively. The content of d-mannitol in fruit bodies obtained on CS was 120 mg g-1 (80% of the control group), followed by that on CCP, 100 mg g-1 . Fruit bodies cultivated on CCP displayed a high crude polysaccharide level of 26.9 mg g-1 , which was the closest to that of the control group (34.5 mg g-1 ). CONCLUSION: CS and CCP are effective substrates for the production of fruit bodies and bioactive compounds by C. militaris. This study provides a new approach to decreasing the cost of C. militaris cultivation and dealing with these agricultural wastes. © 2016 Society of Chemical Industry.

Septic Pulmonary Embolism Requiring Critical Care: Clinicoradiological Spectrum, Causative Pathogens and Outcomes

OBJECTIVES: Septic pulmonary embolism is an uncommon but life-threatening disorder. However, data on patients with septic pulmonary embolism who require critical care have not been well reported. This study elucidated the clinicoradiological spectrum, causative pathogens and outcomes of septic pulmonary embolism in patients requiring critical care. METHODS: The electronic medical records of 20 patients with septic pulmonary embolism who required intensive care unit admission between January 2005 and December 2013 were reviewed. RESULTS: Multiple organ dysfunction syndrome developed in 85% of the patients, and acute respiratory failure was the most common organ failure (75%). The most common computed tomographic findings included a feeding vessel sign (90%), peripheral nodules without cavities (80%) or with cavities (65%), and peripheral wedge-shaped opacities (75%). The most common primary source of infection was liver abscess (40%), followed by pneumonia (25%). The two most frequent causative pathogens were Klebsiella pneumoniae (50%) and Staphylococcus aureus (35%). Compared with survivors, nonsurvivors had significantly higher serum creatinine, arterial partial pressure of carbon dioxide, and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, and they were significantly more likely to have acute kidney injury, disseminated intravascular coagulation and lung abscesses. The in-hospital mortality rate was 30%. Pneumonia was the most common cause of death, followed by liver abscess. CONCLUSIONS: Patients with septic pulmonary embolism who require critical care, especially those with pneumonia and liver abscess, are associated with high mortality. Early diagnosis, appropriate antibiotic therapy, surgical intervention and respiratory support are essential.

Septic pulmonary embolism caused by a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging findings, and clinical courses.

OBJECTIVES: Septic pulmonary embolism caused by a Klebsiella (K.) pneumoniae liver abscess is rare but can cause considerable morbidity and mortality. However, clinical information regarding this condition is limited. This study was conducted to elucidate the full disease spectrum to improve its diagnosis and treatment. METHOD: We reviewed the clinical characteristics, imaging findings, and clinical courses of 14 patients diagnosed with septic pulmonary embolism caused by a K. pneumoniae liver abscess over a period of 9 years. RESULTS: The two most prevalent symptoms were fever and shortness of breath. Computed tomography findings included a feeding vessel sign (79%), nodules with or without cavities (79%), pleural effusions (71%), peripheral wedge-shaped opacities (64%), patchy ground-glass opacities (50%), air bronchograms within a nodule (36%), consolidations (21%), halo signs (14%), and lung abscesses (14%). Nine (64%) of the patients developed severe complications and required intensive care. According to follow-up chest radiography, the infiltrates and consolidations were resolved within two weeks, and the nodular opacities were resolved within one month. Two (14%) patients died of septic shock; one patient had metastatic meningitis, and the other had metastatic pericarditis. CONCLUSION: The clinical presentations ranged from insidious illness with fever and respiratory symptoms to respiratory failure and septic shock. A broad spectrum of imaging findings, ranging from nodules to multiple consolidations, was detected. Septic pulmonary embolism caused by a K. pneumoniae liver abscess combined with the metastatic infection of other vital organs confers a poor prognosis.

Septic pulmonary embolism caused by a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging findings, and clinical courses

OBJECTIVES: Septic pulmonary embolism caused by a Klebsiella (K.) pneumoniae liver abscess is rare but can cause considerable morbidity and mortality. However, clinical information regarding this condition is limited. This study was conducted to elucidate the full disease spectrum to improve its diagnosis and treatment. METHOD: We reviewed the clinical characteristics, imaging findings, and clinical courses of 14 patients diagnosed with septic pulmonary embolism caused by a K. pneumoniae liver abscess over a period of 9 years. RESULTS: The two most prevalent symptoms were fever and shortness of breath. Computed tomography findings included a feeding vessel sign (79%), nodules with or without cavities (79%), pleural effusions (71%), peripheral wedge-shaped opacities (64%), patchy ground-glass opacities (50%), air bronchograms within a nodule (36%), consolidations (21%), halo signs (14%), and lung abscesses (14%). Nine (64%) of the patients developed severe complications and required intensive care. According to follow-up chest radiography, the infiltrates and consolidations were resolved within two weeks, and the nodular opacities were resolved within one month. Two (14%) patients died of septic shock; one patient had metastatic meningitis, and the other had metastatic pericarditis. CONCLUSION: The clinical presentations ranged from insidious illness with fever and respiratory symptoms to respiratory failure and septic shock. A broad spectrum of imaging findings, ranging from nodules to multiple consolidations, was detected. Septic pulmonary embolism caused by a K. pneumoniae liver abscess combined with the metastatic infection of other vital organs confers a poor prognosis. .

[The correlation study of the expression of VEGF with t-PA and PAI expression in plasma and intraocular tissue in proliferative diabetic retinopathy].

OBJECTIVE: To evaluate the correlation between the expression of VEGF with t-PA and PAI expression in plasma aqueous humor and vitreous of proliferative diabetic retinopathy (PDR). METHODS: It was an experimental study. The concentrations of VEGF t-PA and PAI in plasma, aqueous humor and vitreous body in PDR and normal group were detected by ELISA. RESULTS: The levels of VEGF (53.37 ng/L) and PAI (8.00 µg/L) in the plasma of PDR patients were higher than control group, and there was significant statistically difference between them (Z = -3.437, -5.816; P < 0.01). The levels of t-PA (24.32 µg/L) in plasma of PDR patients and control group was no statistically difference between them (Z = -1.715, P = 0.086). The levels of VEGF (335.00 ng/L) t-PA (5.70 µg/L) and PAI (0.63 µg/L) in the aqueous humor of PDR patients were higher than control group, and there was statistically difference between them (Z = -4.805, -1.967, -4.018; P < 0.05). The levels of VEGF (691.69 ng/L) t-PA (13.05 µg/L) and PAI (4.01 µg/L) in the vitreous of PDR patients were higher than control group , and there was statistically difference between them (Z = -2.807, -2.642, -2.230;P < 0.05). Compare the plasma aqueous humor and vitreous of PDR patients. The levels of VEGF is: vitreous>aqueous humor>plasma. The levels of t-PA is: plasma>vitreous>aqueous humor. The levels of PAI is: plasma and vitreous>aqueous humor. The expression of VEGF was highly correlated with t-PA and PAI in plasma aqueous humor and vitreous of PDR (P < 0.05). CONCLUSIONS: VEGF PAI in plasma, VEGF t-PA PAI in aqueous humor and vitreous were increases. The expression of VEGF was positive correlated with t-PA and PAI in plasma aqueous humor and vitreous of PDR.

SIRT1 promotes proliferation and inhibits apoptosis of human malignant glioma cell lines.

In mammalian cells, SIRT1 decreases PTEN acetylation and inactivates the AKT pathway in a SIRT1 deacetylase-dependent manner. However, the function of SIRT1 in glioma was unknown. SIRT1 reexpression or knockdown was induced in human glioma cell lines. The cell synchronization, BrdU labeling and mitotic index were detected. Subsequently, cell cycle, cell viability, apoptosis, cell growth and proliferation were analyzed. Our work identified that SIRT1-knockdown significantly delayed mitotic entry of glioma cells, inhibited its growth and proliferation, and promoted its apoptosis. The apoptosis was related to PTEN/PI3K/AKT signaling pathway. The results showed that SIRT1 might be a promoter factor on tumorigenesis of glioma through PTEN/PI3K/AKT signaling pathway.