Safety and effectiveness of laparoscopic renal biopsy: a single-center review and meta-analysis.

BACKGROUND: While renal biopsy remains the preferred diagnostic method for assessing proteinuria, hematuria, or renal failure, laparoscopic renal biopsy (LRB) can serve as an alternative for high-risk patients when percutaneous kidney biopsy (PKB) is not recommended. This study was aimed to evaluate the safety of LRB. METHODS: In study 1, Fourteen patients from January 2021 to January 2023 had a LRB taken for various indications, such as morbid obesity, abnormal kidney construction, uncontrolled hypertension, and coagulopathy. We also conducted a Meta-analysis of the success rate and complication rate of previous LRB in study 2. RESULTS: All the patients completed biopsies and adequate renal tissues were obtained. The success rate was 100%. The median number of glomeruli obtained was 22.5 (range:12.0, 45.0). The complication rate was 7.1% (urinary tract infection). There were no significant differences between levels of hemoglobin, serum creatinine, and urinary NAGL before and after surgery. In the meta-analysis, the success rate of operation, satisfactory rate of sample, and complication rate of surgery were 99.9%, 99.1%, and 2.6% respectively. CONCLUSION: LRB can achieve a good success rate and specimen retrieval and does not increase the risk of complications for high-risk patients. It can present as one of the alternative methods for patients with glomerular diseases.

[Diagnostic value of early bedside ultrasound measurement of quadriceps femoris on in-hospital mortality of septic patients].

OBJECTIVE: To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality. METHODS: A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. RESULTS: A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95%CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. CONCLUSIONS: For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.

An Indoor Navigation Algorithm Using Multi-Dimensional Euclidean Distance and an Adaptive Particle Filter.

The inertial navigation system has high short-term positioning accuracy but features cumulative error. Although no cumulative error occurs in WiFi fingerprint localization, mismatching is common. A popular technique thus involves integrating an inertial navigation system with WiFi fingerprint matching. The particle filter uses dead reckoning as the state transfer equation and the difference between inertial navigation and WiFi fingerprint matching as the observation equation. Floor map information is introduced to detect whether particles cross the wall; if so, the weight is set to zero. For particles that do not cross the wall, considering the distance between current and historical particles, an adaptive particle filter is proposed. The adaptive factor increases the weight of highly trusted particles and reduces the weight of less trusted particles. This paper also proposes a multidimensional Euclidean distance algorithm to reduce WiFi fingerprint mismatching. Experimental results indicate that the proposed algorithm achieves high positioning accuracy.

Association between admission serum procalcitonin and the occurrence of acute kidney injury in patients with septic shock: A retrospective cohort study.

BACKGROUND: Procalcitonin (PCT) is an effective and sensitive diagnostic biomarker that can facilitate the early detection of infection and septicemia, but whether it can similarly be utilized to predict the development of acute kidney injury (AKI) in patients suffering from septic shock remains to be established. Herein, the relationship between serum PCT at admission and the onset of AKI in septic shock patients was thus evaluated following adjustment for other potential covariates. METHODS: This was a retrospective cohort study of 303 septic shock patients treated in a Chinese hospital between May 2015 and May 2019. All patients in whom PCT levels were measured on admission and who did not exhibit AKI or chronic kidney disease at the time of admission were assessed for AKI development within one week following intensive care unit (ICU) admission as per the KDIGO criteria. The relationship between serum PCT at admission and AKI incidence was then assessed for these patients. RESULTS: These 303 patients were an average of 64 years old, and were 59.7% male. Of these patients, 50.5% developed AKI within the first 7 days following ICU admission. A dully-adjusted binary logistic regression analysis revealed PCT levels at admission to be associated with AKI following adjustment for potential confounding factors (odds ratio (OR) = 1.01, 95%CI (1.01,1.02), p = 0.0007). Receiver operating characteristic curve analysis further indicated that a PCT cutoff level of 52.59 ng/ml at admission was able to predict the incidence of AKI with respective sensitivity and specificity values of 50% and 84%. Interaction analysis revealed no significant interactive relationship between PCT and AKI, suggesting that serum PCT levels represent an early predictor of AKI incidence in septic shock patients. CONCLUSIONS: Serum PCT at the time of admission can be used as a predictor of AKI in patients suffering from septic shock.

[Combined prognostic value of serum lactic acid, procalcitonin and severity score for short-term prognosis of septic shock patients].

OBJECTIVE: To explore the value of lactic acid (Lac), procalcitonin (PCT), sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation II (APACHE II) score in assessing the severity and predicting the prognosis in sepsis shock. METHODS: A retrospectively study was conducted. Patients with septic shock hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University from April 2015 to June 2019 were enrrolled. The patient's gender, age, body mass index (BMI), infection site, organ dysfunction status; Lac, PCT, C-reactive protein (CRP), heart rate and body temperature immediately after admission to the intensive care unit (ICU); APACHE II and SOFA scores within 24 hours, and 28-day prognosis were collected. According to the 28-day prognosis, the patients with septic shock were divided into the survival group and the death group, and the differences in the indicators between the groups were compared. Multivariate Logistic regression analysis was used to screen the risk factors of 28-day death in patients with septic shock; receiver operating characteristic curve (ROC curve) was used to analyze the value of Lac, PCT, SOFA, APACHE II, and age in predicting the 28-day prognosis of patients with septic shock. RESULTS: A total of 303 septic shock patients were enrolled, of which 124 cases survived and 179 died on the 28th day, and the 28-day mortality was 59.08%. (1) Compared with the survival group, patients in the death group were older (years old: 66.58±15.22 vs. 61.15±15.68), APACHE II, SOFA, proportion of lung infections, Lac increased [APACHE II score: 22.79±7.62 vs. 17.98±6.88, SOFA score: 9.42±3.51 vs. 5.65±1.59, proportion of lung infections: 53.63% (96/179) vs. 39.52% (49/124), Lac (mmol/L): 5.10±3.72 vs. 3.71±2.56], oxygenation index (PaO2/FiO2) and ICU body temperature decreased [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 198.94±80.15 vs. 220.68±72.06, ICU body temperature (centigrade): 37.47±1.08 vs. 37.80±1.14], and the differences were statistically significant (all P < 0.05). (2) Multivariate Logistic regression analysis results: after adjusted for potential confounding factors, APACHE II, PCT, Lac, age and SOFA were independent risk factors for death in patients with septic shock [APACHE II: odds ratio (OR) =1.05, 95% confidence interval (95%CI) was 1.01-1.10, P = 0.039; PCT: OR = 0.99, 95%CI was 0.98-1.00, P =0.012; Lac: OR = 1.23, 95%CI was 1.08-1.40, P = 0.002; age: OR = 1.03, 95%CI was 1.01-1.05, P = 0.009; SOFA score: OR =1.88, 95%CI was 1.59-2.22, P < 0.001]. (3) ROC curve analysis showed that APACHE II, Lac, age and SOFA could predict the prognosis of patients with septic shock [APACHE II: the area under the ROC curve (AUC) = 0.682 4, 95%CI was 0.621 7-0.743 1, P = 0.000; when the best cut-off value was 18.500, its sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 72.63%, 54.84%, 69.89%, 58.12%, 1.608 1 and 0.499 2, respectively. Lac: AUC = 0.604 5, 95%CI was 0.540 8-0.668 2, P = 0.002; when the best cut-off value was 3.550 mmol/L, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 50.84%, 73.39%, 73.39%, 50.94%, 1.910 3 and 0.669 9, respectively. Age: AUC = 0.599 1, 95%CI was 0.535 4-0.662 7, P = 0.003; when the best cut-off value was 72.500 years old, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 42.46%, 75.00%, 71.03%, 47.45%, 1.698 3 and 0.767 2, respectively. SOFA: AUC = 0.822 3, 95%CI was 0.776 7-0.867 9, P = 0.000; when the best cut-off value was 7.500, its sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 68.72%, 87.90%, 89.13%, 66.06%, 5.680 4, 0.355 9 respectively]. The combined prediction had a good sensitivity (72.63%) and specificity (84.86%), and AUC (0.876 5) was higher than that of a single variable, suggested that the multivariate combination was more accurate in predicting the short-term outcome of septic shock. CONCLUSIONS: Lac, PCT, SOFA score, APACHE II score and age were independent risk factors for death in patients with septic shock, and the accuracy of Lac, SOFA score, APACHE II score and age in predicting short-term prognosis of septic shock was better than that of single variable, and the diagnostic value was higher.

Long non­coding RNA NEAT1 modifies cell proliferation, colony formation, apoptosis, migration and invasion via the miR­4500/BZW1 axis in ovarian cancer.

Ovarian cancer (OC) is a frequently occurring malignant tumor in women. Increasing evidence has indicated that long non­coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) participates in OC pathogenesis. Thus, the aim of the present study was to explore the function of NEAT1 during OC progression. The expression levels of NEAT1, microRNA (miR)­4500 and basic leucine zipper and W2 domain­containing protein 1 (BZW1) were assessed via reverse transcription­quantitative PCR and western blotting. Furthermore, cell proliferation, colony formation, apoptosis, migration and invasion were assessed using Cell­Counting Kit 8, colony formation, flow cytometry and Transwell assays, respectively. Cell glycolysis was analyzed using an XF96 metabolic flux analyzer, and the relationship between miR­4500 and NEAT1 or BZW1 was verified via dual­luciferase reporter and RNA binding protein immunoprecipitation assays. miR­4500 expression levels were low, whereas NEAT1 expression levels were high in OC tissues and cell lines compared with control tissues and cell lines. Moreover, the results indicated that NEAT1 was a sponge of miR­4500, which directly targeted BZW1. NEAT1 knockdown induced OC cell apoptosis, and inhibited OC cell proliferation, colony formation, migration, invasion and glycolysis. miR­4500 inhibitor reversed NEAT1 knockdown­mediated effects. Similarly, miR­4500 mimic­mediated effects on cell functions were reversed by BZW1 overexpression. In addition, the results indicated that BZW1 expression was regulated by NEAT1 and miR­4500. Collectively, the present study suggested that NEAT1 modulated cell proliferation, colony formation, apoptosis, migration, invasion and glycolysis via the miR­4500/BZW1 axis in OC; therefore, NEAT1 may serve as a therapeutic target for OC.

Tumor suppressive BTB/POZ zinc-finger protein ZBTB28 inhibits oncogenic BCL6/ZBTB27 signaling to maintain p53 transcription in multiple carcinogenesis.

Zinc-finger and BTB/POZ domain-containing family proteins (ZBTB) are important transcription factors functioning as tumor suppressors or oncogenes, such as BCL6/ZBTB27 as a key oncoprotein for anti-cancer therapy. Through epigenome study, we identified ZBTB28/BCL6B/BAZF, a BTB/POZ domain protein highly homologous to BCL6, as a methylated target in multiple tumors. However, the functions and mechanism of ZBTB28 in carcinogenesis remain unclear. Methods: ZBTB28 expression and methylation were examined by reverse-transcription PCR and methylation-specific PCR. The effects and mechanisms of ectopic ZBTB28 expression on tumor cells were assessed with molecular biological and cellular approaches in vitro and in vivo. Results: Albeit broadly expressed in multiple normal tissues, ZBTB28 is frequently downregulated in aero- and digestive carcinoma cell lines and primary tumors, and correlated with its promoter CpG methylation status. Further gain-of-function study showed that ZBTB28 functions as a tumor suppressor inhibiting carcinoma cell growth in vitro and in vivo, through inducing cell cycle arrest and apoptosis of tumor cells. ZBTB28 suppresses cell migration and invasion by reversing EMT and cell stemness. ZBTB28 transactivates TP53 expression, through binding to the p53 promoter in competition with BCL6, while BCL6 itself was also found to be a direct target repressed by ZBTB28. Conclusion: Our results demonstrate that ZBTB28 functions as a tumor suppressor through competing with BCL6 for targeting p53 regulation. This newly identified ZBTB28/BCL6/p53 regulatory axis provides further molecular insight into carcinogenesis mechanisms and has implications in further improving BCL6-based anticancer therapy.

Protective effects of ghrelin on brain mitochondria after cardiac arrest and resuscitation.

Mitochondrial dysfunction plays a critical role in brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Our recent study demonstrated that ghrelin protected against post-resuscitation brain injury with an elevated expression of mitochondrial uncoupling protein 2 (UCP2). However, the effects of ghrelin on mitochondrial dysfunction after CA are not clear. In the present study, the protective role of ghrelin was evaluated on mitochondrial dysfunction and the subsequent damage induced by CA in rats. In addition, mitochondrial unfolded protein response (UPRmt), an intrinsic cytoprotective pathway, was observed at the same time. Either vehicle (saline) or ghrelin (80 µg/kg) was injected blindly immediately after 6 min of CA and successful resuscitation. Neurological deficit was evaluated 6 h after CA and then cortex was collected for assessments. As a result, we found that ghrelin significantly improved the neurological deficit score in rats after CA. The functional analysis of isolated mitochondria revealed that ghrelin improved the mitochondrial ATP synthesis capacity and significantly reduced the reactive oxygen species (ROS) leakage after 6 h of CA. Concomitantly, we observed an increased ATP level and an attenuated oxidative stress in ghrelin treated animals. Moreover, ghrelin markedly improved the mitochondrial morphology compared with the vehicle animals. Further research revealed that ghrelin treatment significantly activated the UPRmt as demonstrated by the increased expression of heat shock protein 60 (HSP60), heat shock protein 10 (HSP10), caseinolytic protease 1 (CLPP1), and high-temperature requirement protein A2 (HTRA2). Our results suggest that ghrelin protected against cerebral mitochondria dysfunction after CA and the mechanism may involve a UPRmt pathway.

Trace Elements in the Feathers of Waterfowl from Nanhaizi Wetland, Baotou, China.

The trace element concentrations (Cr, Ni, Pb, Hg, Cu, Zn, Mn, and Fe) of feathers from Ferruginous duck (Aythya nyroca), Gadwall (Anas strepera), and Green-winged Teal (Anas crecca) from Nanhaizi Wetland, China were measured. (1) There were significant differences in the concentrations of the Cr, Ni, and Pb among the waterfowl species. The concentrations of Cr and Ni in Gadwall feathers and Pb in Green-winged Teal feathers were higher than the concentrations of Cr, Ni and Pb in Ferruginous duck. (2) The Pb concentrations in the feathers of four Green-winged Teals and one Ferruginous duck, Cr concentrations in the feathers of Gadwalls (geomean 5.33 µg g-1 dry weight) and Green-winged Teals (geomean 4.55 µg g-1 dry weight) exceeded the thresholds at which they pose a threat to bird health (i.e., Pb > 4 µg g-1, Cr > 2.8 µg g-1). (3) The Cu, Zn, Fe, and Mn concentrations of feathers were within the normal ranges reported for most waterfowl.

Efficacy of different doses of alteplase thrombolysis on acute ischemic stroke in patients.

Atyplase is a kind of thrombolytic drug with strong fibrin specificity. It can promote the synthesis of fibrinolytic enzymes by combining fibrin and plasminogen in thrombus, and then dissolve thrombus. Ateplase intravenous thrombolysis is the only effective method for stroke treatment proved by evidence-based medicine. The aim of this study was to observe the effect of different doses of ateplase on acute ischemic stroke. They were randomly divided into control group (n=43) and observation group (n=43). The patients in the control group were treated with low-dose alteplase, while those in the observation group were treated with standard-dose alteplase. The control group was treated with 0.6 mg/kg ateplase intravenous thrombolysis, and the observation group was treated with 0.9mg/kg ateplase. The GCS scores on the 1 day was 14.06±1.57 in the control group after treatment, and 13.84±2.48 in the observation group. The NIHSS score was 4.59±1.12 in the control group, and 7.13±1.05 in the observation group. Intravenous thrombolytic therapy with intravenous thrombolytic therapy is effective and safe in the treatment of acute ischemic stroke. At the same time, there were no persistent adverse reactions after treatment, mainly in gingival bleeding, epistaxis, intracranial hemorrhage, gastrointestinal bleeding, and hematuria and so on. The results showed that different doses of alteplase could improve neurological function and living ability of patients. Future studies need to broaden the sample size to study the safety of low and standard doses of alteplase in patients with acute cerebral infarction.

Inactivation of ADAMTS18 by aberrant promoter hypermethylation contribute to lung cancer progression.

Lung cancer is the most frequently diagnosed cancer worldwide. Epigenetic regulation contributes to lung cancer pathogenesis. The ADAMTS18 tumor suppressor gene is inactivated in some cancers, but its involvement in lung cancer has not been shown. Immunohistochemistry, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and methylation-specific PCR were used to assay ADAMTS18 expression and promoter methylation in lung tumor tissues and adjacent tissues. Cell viability, transwell, and wound-healing assays, as well as flow cytometry were used to characterize the biological activity of ADAMTS18. The influence of ADAMTS18 on protein expression was assayed using western blots analysis, and its effect on chemosensitivity was assayed by the response to cisplatin. We found that ADAMTS18 was silenced in lung cancer cells by promoter methylation. Demethylation by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, with or without the histone deacetylase inhibitor trichostatin A, restored ADAMTS18 expression. Compared with normal lung tissue, ADAMTS18 in lung tumors was frequently methylated. Overexpression of ADAMTS18 in lung cancer cells inhibited cell proliferation, migration, and invasiveness and induced G0/G1 cell cycle arrest. Furthermore, ADAMTS18 suppressed epidermal growth factor receptor/protein kinase B (EGFR/AKT) signaling, which sensitized lung cancer cells to cisplatin. Thus, our results demonstrated that the tumor suppressor gene ADAMTS18 was downregulated in lung cancer by promoter CpG methylation, and it promoted sensitivity to cisplatin via EGFR/AKT signaling. Our study suggests that ADAMTS18 promoter methylation is a potential epigenetic biomarker for early detection of lung cancer and warrants investigation as a therapeutic target for early-stage lung cancer.

Effect of baicalein with different concentrations on myocardial ischemia reperfusion injury in rats.

Baicalein is a kind of flavonoids. Long term use of flavonoids can reduce blood pressure by releasing physiological NO to keep the vascular endothelial function of hypertensive animals and reduce myocardial ischemia injury. The purpose of this study is to explore the effect of baicalein on myocardial I/R damage and explore its mechanism of action, so as to provide experimental evidence for treatment. The results show that baicalein has a significant improvement in I/R damage, mainly in reducing myocardial infarction rate, reducing the release of myocardial isozyme LDH and CK, reducing the level of oxidative stress and reducing the apoptosis of cardiac myocytes. In the baicalein group, the myocardial ischemia state of isolated rat hearts was improved. Among them, myocardial infarction rate in low and middle concentration group was significantly decreased (P<0.05 or P<0.01), and there was no significant change in high concentration group (P>0.05). The apoptosis rate of cardiac myocytes in the isolated group of baicalein was significantly decreased (P<0.01). The role of baicalein in the cardiovascular system needs further test and clinical research.

Levels of persistent toxic substances in different biochars and their potential ecological risk assessment.

This study investigated the levels of persistent toxic substances, such as 16 polycyclic aromatic hydrocarbons (Σ16PAHs) and heavy metals (Cu, As, Cd, Zn, Pb, Ni, Mo, and Cr) in biochars produced from crop residues (walnut shell, corn cob, corn straw, rice straw, and rice husk) at different heat treatment temperatures (HTTs, 250, 400, and 600 °C). The levels of Σ16PAHs in different biochars were 0.47-7.11 mg kg-1, with naphthalene and phenanthrene contributing the most. The Σ16PAHs had the positive correlations with H/C and (O + N)/C, but had negative correlations with biochar surface areas. This finding indicates the increasing hydrophobic π-π interactions between the PAHs and the aromatic sheets of biochars and even the trapping of PAHs within the micropores with the increase of HTTs. The levels of heavy metals in rice residue-derived biochars were significantly higher than those in other biochars. The heavy metals had positive correlations with ash contents in the biochars, indicating the enrichment of heavy metals in the ash. The potential ecological risks of PAHs and heavy metals (dosage: 1%, w/w; frequency: 1) were minimal according to the risk quotient of negligible concentrations (RQNCs: 2.50-47.40, << 800) and maximum permissible concentrations (RQMPCs: 0.02-0.48, << 1) for PAHs and the potential ecological risk indexes (PERI: 0.01-0.28, << 150) for heavy metals.

Investigation of an antitumor drug-delivery system based on anti-HER2 antibody-conjugated BSA nanoparticles.

Conjugation of a monoclonal antibody with a nanoparticle often improves its specificity and drug loading in cancer therapy. In this study, we prepared a novel targeting nanodrug-delivery system using 2-methoxy-estradiol (2-ME) based on anti-human epidermal growth factor receptor 2 (HER2) antibody-modified BSA to improve the clinical application and antitumor effect of 2-ME. 2-ME-loaded albumin nanoparticles (2-ME-BSANPs) were prepared using a desolvation method and the anti-HER2 antibodies were conjugated to 2-ME-BSANPs (HER2-2-ME-BSANPs) using the coupling agent, succinimidyl 3-(2-pyridyldithio)propionate. HER2-2-ME-BSANPs were characterized using SDS-polyacrylamide gel electrophoresis, an agglutination test, and an immunofluorescence assay. We found that mouse anti-human anti-HER2 monoclonal antibody was successfully conjugated to the 2-ME-BSANPs. Thereafter, the in-vitro and in-vivo toxicities were evaluated using two cancer cell lines, SK-BR-3 (HER2-overexpressing) and MCF-7 (HER2-underexpressing), using classic pharmacological methods and in-vivo imaging technology. We found that the HER2-2-ME-BSANPs retained the immunospecificity of the anti-HER2 monoclonal antibody, rapidly localized to HER2 receptors, and could be used for targeted cancer therapy.

The 3p14.2 tumour suppressor ADAMTS9 is inactivated by promoter CpG methylation and inhibits tumour cell growth in breast cancer.

Chromosome region 3p12-14 is an important tumour suppressor gene (TSG) locus for multiple cancers. ADAMTS9, a member of the metalloprotease large family, has been identified as a candidate 3p14.2 TSG inactivated by aberrant promoter CpG methylation in several carcinomas, but little known about its expression and function in breast cancer. In this report, ADAMTS9 expression and methylation was analysed in breast cancer cell lines and tissue samples. ADAMTS9 RNA was significantly down-regulated in breast cancer cell lines (6/8). After treating the cells with demethylation agent Aza and TSA, ADAMTS9 expression was dramatically increased. Bisulphite genomic sequencing and methylation-specific PCR detected promoter methylation, which was associated with decreased ADAMTS9 expression. Hypermethylation was also detected in 130/219 (59.4%) of primary tumours but only in 4.5% (2/44) of paired surgical margin tissues. Ectopic expression of ADAMTS9 in tumor cells induced significant growth suppression, cell cycle arrest at the G0/G1 phase, enhanced apoptosis and reduced cell migration and invasion. Conditioned culture medium from ADAMTS9-transfected BT549 cells markedly disrupted tube formation ability of human umbilical vein endothelial cell (HUVEC) in Matrigel. Furthermore, ADAMTS9 inhibited AKT signaling and its downstream targets (MDM2, p53, p21, p27, E-cadherin, VIM, SNAIL, VEGFA, NFκB-p65 and MMP2). In addition, we demonstrated, for the first time, that ADAMTS9 inhibits AKT signaling, through suppressing its upstream activators EGFR and TGFß1/TßR(I/II) in breast cancer cells. Our results suggest that ADAMTS9 is a TSG epigenetically inactivated in breast cancer, which functions through blocking EGFR- and TGFß1/TßR(I/II)-activated AKT signaling.

Isolation and identification of an aerobic denitrifying phosphorus removing bacteria and analysis of the factors influencing denitrification and phosphorus removal.

Excessive emission of plant nutrients (such as nitrogen and phosphorus) into the water body can induce eutrophication. Therefore, how to control eutrophic water efficiently and economically is very important. In the paper, highly efficient aerobic denitrifying phosphorus removing J16 bacteria was isolated from the activated sludge of an aerobic bioreactor in Taiyuan municipal wastewater treatment plant by using the blue-white spot screening method, an aerobic phosphorus absorption test, nitrate reduction test, nitrogen removal experiments, and plate coating and streaking methods. Through 16S rDNA gene homology comparison and physiological and biochemical identification, the J16 strain was preliminarily identified as Escherichia coli, with a sequence similarity of 99%. The 16S rDNA sequence of strain J16 was submitted to GenBank (accession number: MF667015). The effect of temperature, pH, percentage of inoculum and phosphate-P (PO4 3--P) concentration on denitrification and phosphorus removal efficiency was investigated through a single-factor experiment. The optimum conditions of the J16 strain for denitrification and phosphorus removal were as follows: 30°C, neutral or weak alkaline (pH: 7.2-8), and 3% of inoculum, respectively. The denitrification and phosphorus removal efficiency of strain J16 was the highest when PO4 3--P and nitrate-N(NO3 --N) concentrations were 8.9 and 69.31 mg/L, and the removal were 96.03% and 94.55%, respectively. In addition, strain J16 could reduce phosphoric acid to phosphine (PH3) and remove some phosphorus under hypoxia conditions. This is the first study to report the involvement of Escherichia coli in nitrogen and phosphorus removal under aerobic and hypoxia conditions. Based on the above results, the strain J16 can effectively remove nitrogen and phosphorus, and will be utilized in enhancing treatment of nitrogen and phosphorus-containing industrial wastewater and phosphorus reclamation.

[Usefulness of procalcitonin for the diagnosis of infection in cardiac surgical patients].

OBJECTIVE: To determine the value of procalcitonin (PCT) as an early marker of postoperative infection after cardiac surgery with cardiopulmonary bypass (CPB). METHODS: A retrospective study was conducted. Patients with systemic inflammatory response syndrome (SIRS) after cardiac surgery with CPB admitted to intensive care unit (ICU) of Peking Union Medical College Hospital from November 2014 to January 2017 were enrolled. The cardiac surgery types and intraoperative conditions, the treatments in ICU, postoperative 28-day mortality and hospital mortality of the patients; the levels of plasma PCT measured at ICU admission, postoperative 1, 3, and 5 days were collected. According to whether patients with postoperative infection or not, they were divided into infection group and non-infection group. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of plasma PCT levels at different time points in patients with infection. RESULTS: Eighty-two patients were included in this study, 25 (30.5%) had microbiological evidence of pneumonia. The levels of plasma PCT were increased with a peak 1 day after cardiac surgery in all patients, then significantly decreased 5 days after operation. Compared with patients without infection, the levels of plasma PCT were significantly increased in patients with infection at immediate and 1, 3, 5 days post operation in ICU [µg/L: 10.0 (6.0, 64.5) vs. 5.0 (1.0, 10.0), 31.0 (10.0, 116.2) vs. 5.0 (1.0, 10.0), 34.7 (10.0, 60.4) vs. 2.9 (0.7, 9.3), 15.8 (7.7, 29.4) vs. 0.7 (0.5, 2.6), all P < 0.01]. The area under the ROC curve (AUC) of the plasma PCT levels at ICU admission, and 1, 3, 5 days thereafter to predict infection for critically ill patients with SIRS after CPB was 0.77, 0.82, 0.86, and 0.91, respectively (all P < 0.01), cut-off values were 6.8, 9.4, 9.2 and 3.9 µg/L, with the sensitivities of 76.0%, 84.0%, 79.2%, and 88.0%, and the specificities of 66.7%, 68.4%, 75.4%, and 78.9%, respectively. CONCLUSIONS: In the presence of SIRS, elevated plasma PCT levels correlated with evidence of infection in early stage post operation in the ICU patients after cardiac surgery with use of CPB. The level of plasma PCT exceeded the cut-off value in different time points, suggesting infection, and it is helpful to predict the occurrence of infection early after operation.

Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast cancer through AKT and NF-κB signaling.

ADAMTS18 dysregulation plays an important role in many disease processes including cancer. We previously found ADAMTS18 as frequently methylated tumor suppressor gene (TSG) for multiple carcinomas, however, its biological functions and underlying molecular mechanisms in breast carcinogenesis remain unknown. Here, we found that ADAMTS18 was silenced or downregulated in breast cancer cell lines. ADAMTS18 was reduced in primary breast tumor tissues as compared with their adjacent noncancer tissues. ADAMTS18 promoter methylation was detected in 70.8% of tumor tissues by methylation-specific PCR, but none of the normal tissues. Demethylation treatment restored ADAMTS18 expression in silenced breast cell lines. Ectopic expression of ADAMTS18 in breast tumor cells resulted in inhibition of cell migration and invasion. Nude mouse model further confirmed that ADAMTS18 suppressed breast cancer metastasis in vivo. Further mechanistic studies showed that ADAMTS18 suppressed epithelial-mesenchymal transition (EMT), further inhibited migration and invasion of breast cancer cells. ADAMT18 deregulated AKT and NF-κB signaling, through inhibiting phosphorylation levels of AKT and p65. Thus, ADAMTS18 as an antimetastatic tumor suppressor antagonizes AKT and NF-κB signaling in breast tumorigenesis. Its methylation could be a potential tumor biomarker for breast cancer.

Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway.

The KRAB-zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.

Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay.

CONTEXT: Doxorubicin (DOX)-loaded folate-targeted poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) [P(HB-HO)] nanoparticles [DOX/FA-PEG-P(HB-HO) NPs] were prepared by the W1/O/W2 solvent extraction/evaporation method for applications in cancer treatment. However, the biodistribution, pharmacokinetics, and targeting of the nanoparticles (NPs) have not yet been studied. OBJECTIVE: The biodistribution, pharmacokinetics, and targeting of DOX/FA-PEG-P(HB-HO) NPs were evaluated in female BALB/c nude mice bearing HeLa tumors. MATERIALS AND METHODS: Three DOX formulations were injected into the tail vein of the mice at a dosage of 5 mg/kg. At each time point, blood and various tissues were collected. All samples were then processed and analyzed by a validated high performance liquid chromatographic (HPLC) method. RESULTS: The t1/2 values of DOX/P(HB-HO) NPs and DOX/FA-PEG-P(HB-HO) NPs were 2.7- and 3.5-times higher than that of free DOX. No significant difference (p > 0.05) was found in Cmax between the NPs and free DOX. The Tmax values of the two NPs were prolonged from 0.25 to 1 h. The AUC0-t values were 1.55- and 3.05-folds higher than that of free DOX, and MRT increased to 15.99 h for DOX/P(HB-HO) NPs and 25.14 h for DOX/FA-PEG-P(HB-HO) NPs. For DOX/FA-PEG-P(HB-HO) NPs, the DOX content in the tumors were 10.81- and 3.33-times higher than those for free DOX and DOX/P(HB-HO) NPs at 48 h, respectively. DISCUSSION AND CONCLUSIONS: DOX/FA-PEG-P(HB-HO) NPs displayed reduced cardiac toxicity and improved bioavailability. Moreover, the NPs exhibited a significant extent of DOX accumulation in the tumors, thus suggesting that folate-targeted NPs could effectively transport into HeLa tumors with satisfying targeting.