Nanotechnology-Based Drug Delivery Systems to Control Bacterial-Biofilm-Associated Lung Infections.

Airway mucus dysfunction and impaired immunological defenses are hallmarks of several lung diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary diseases, and are mostly causative factors in bacterial-biofilm-associated respiratory tract infections. Bacteria residing within the biofilm architecture pose a complex challenge in clinical settings due to their increased tolerance to currently available antibiotics and host immune responses, resulting in chronic infections with high recalcitrance and high rates of morbidity and mortality. To address these unmet clinical needs, potential anti-biofilm therapeutic strategies are being developed to effectively control bacterial biofilm. This review focuses on recent advances in the development and application of nanoparticulate drug delivery systems for the treatment of biofilm-associated respiratory tract infections, especially addressing the respiratory barriers of concern for biofilm accessibility and the various types of nanoparticles used to combat biofilms. Understanding the obstacles facing pulmonary drug delivery to bacterial biofilms and nanoparticle-based approaches to combatting biofilm may encourage researchers to explore promising treatment modalities for bacterial-biofilm-associated chronic lung infections.

Perforation of the superior vena cava by a tunnel-cuffed hemodialysis catheter via the right internal jugular vein in an elderly woman.

Oliguric patients with acute kidney injury (AKI) often requires an internal jugular vein or femoral venous catheter to establish vascular access for emergency hemodialysis. Puncture with catheterization (PC) of the right internal jugular vein (RIJV) is relatively simple and is often the first choice for hemodialysis catheters insertion. However, complications such as bleeding and hematoma at the puncture site can occur, and in rare cases, the hemodialysis catheter (HDC) can be misplaced into the internal carotid artery, subclavian artery, subclavian vein, or even the thoracic cavity and mediastinum, leading to intractability for processing next. In this study, we report a case of an elderly female patient with AKI who underwent RIJV puncture for long-term HDC because her renal function had not recovered in the short term, and the lower end of the catheter penetrated the superior vena cava (SVC) into the mediastinum due to operator's carelessness. We did not perform open surgery or endovascular interventions, and instead, the HDC was retained in that place for four weeks and then directly removed without surgery. The patient did not experience any problems, such as bleeding or hematoma, and has been receiving hemodialysis from femoral catheter subsequently since then.

Impact of cerebral microbleeds on cognitive functions and its risk factors in acute cerebral infarction patients.

BACKGROUND: Cerebral microbleeds (CMBs) are subclinical lesions of the brain parenchyma and an important marker for the clinical diagnosis of central nervous system vascular disease. However, the relationship between CMBs and cerebral infarction, cerebral hemorrhage, and cognitive impairment remains unclear. METHODS: In order to explore the cognitive function and risk factors of patients with acute cerebral infarction (ACI) complicated with cerebral microbleeds, 190 patients with ACI were collected. The patients were divided into groups with CMBs (n = 108) and groups without CMBs (n = 82) according to the presence or absence of CMBs. The general data, various examination indicators, Montreal Cognitive Assessment Scale (MoCA) scores of the two groups of patients were analyzed. Sixty healthy controls who underwent physical examination in our hospital during the same period were included as the healthy control group. RESULTS: ACI patients with CMBs had significantly higher rates of leukoaraiosis, hyperhomocysteinemia, hypercholesterolemia, and hypertension. Cognitive function was significantly lower in ACI patients with CMBs. Serum D-dimer, serum high-sensitivity C-reactive protein, serum neuron-specific enolase, and serum S100ß of ACI patients with CMBs were all negatively correlated with their MoCA scores. CONCLUSION: ACI patients with CMBs tended to have lower cognitive abilities than ACI patients without CMBs.

Paper Device Combining CRISPR/Cas12a and Reverse-Transcription Loop-Mediated Isothermal Amplification for SARS-CoV-2 Detection in Wastewater.

Wastewater-based surveillance of the COVID-19 pandemic holds great promise; however, a point-of-use detection method for SARS-CoV-2 in wastewater is lacking. Here, a portable paper device based on CRISPR/Cas12a and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with excellent sensitivity and specificity was developed for SARS-CoV-2 detection in wastewater. Three primer sets of RT-LAMP and guide RNAs (gRNAs) that could lead Cas12a to recognize target genes via base pairing were used to perform the high-fidelity RT-LAMP to detect the N, E, and S genes of SARS-CoV-2. Due to the trans-cleavage activity of CRISPR/Cas12a after high-fidelity amplicon recognition, carboxyfluorescein-ssDNA-Black Hole Quencher-1 and carboxyfluorescein-ssDNA-biotin probes were adopted to realize different visualization pathways via a fluorescence or lateral flow analysis, respectively. The reactions were integrated into a paper device for simultaneously detecting the N, E, and S genes with limits of detection (LODs) of 25, 310, and 10 copies/mL, respectively. The device achieved a semiquantitative analysis from 0 to 310 copies/mL due to the different LODs of the three genes. Blind experiments demonstrated that the device was suitable for wastewater analysis with 97.7% sensitivity and 82% semiquantitative accuracy. This is the first semiquantitative endpoint detection of SARS-CoV-2 in wastewater via different LODs, demonstrating a promising point-of-use method for wastewater-based surveillance.

Clinical features of children with colorectal polyps and the efficacy of endoscopic treatment: an analysis of 1 351 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with colorectal polyps and the efficacy of endoscopic treatment.@*METHODS@#A retrospective analysis was performed on the medical data of 1 351 children with colorectal polyps who were admitted and received colonoscopy and treatment in the past 8 years, including clinical features and the pattern and outcomes of endoscopic treatment.@*RESULTS@#Among the 1 351 children, 893 (66.10%) were boys and 981 (72.61%) had an age of 2-<7 years, and hematochezia (1 307, 96.74%) was the most common clinical manifestation. Of all the children, 89.27% (1 206/1 351) had solitary polyps, and 95.77% (1 290/1 347) had juvenile polyps. The polyps were removed by electric cauterization with hot biopsy forceps (6 cases) or high-frequency electrotomy and electrocoagulation after snare ligation (1 345 cases). A total of 1 758 polyps were resected, among which 1 593 (90.61%) were pedunculated and 1 349 (76.73%) had a diameter of <2 cm. Postoperative complications included bleeding in 51 children (3.77%), vomiting in 87 children (6.44%), abdominal pain in 14 children (1.04%), and fever in 39 children (2.89%), while no perforation was observed. The children aged <3 years had the highest incidence rates of postoperative bleeding and fever (P<0.0125), and the children with a polyp diameter of ≥2 cm had significantly higher incidence rates of postoperative bleeding, vomiting, and fever (P<0.05).@*CONCLUSIONS@#Solitary polyps, pedunculated polyps, and juvenile polyps are common types of pediatric colorectal polyps. Electric cauterization with hot biopsy forceps or high-frequency electrotomy and electrocoagulation after snare ligation can effectively remove colorectal polyps in children, with good efficacy and few complications. Younger age and larger polyp diameter are associated with a higher risk of postoperative bleeding.

Effect and safety evaluation of tacrolimus and tripterygium glycosides combined therapy in treatment of Henoch-Schönlein purpura nephritis.

OBJECTIVE: Henoch-Schönlein purpura nephritis has become a significant threat to children's health. Traditional combined therapy of glucocorticoids and cyclophosphamide leads to severe toxicity and complications. Therefore, identifying a feasible and effective strategy with low side-effects for the treatment of Henoch-Schönlein purpura nephritis is of great significance. METHODS: A randomized, controlled trial was carried out. A total of 279 children with Henoch-Schönlein purpura nephritis were recruited and randomly divided into three groups: control group (receiving the current standard therapy), TA group (receiving tacrolimus) and TA + tripterygium glycosides group (receiving tacrolimus + tripterygium treatment). The total duration of the trial was 6 months, and the duration of follow-up observation was 9 months. RESULTS: Various therapies showed similar therapeutic effects in the third and sixth months. The relief of Henoch-Schönlein purpura nephritis symptoms caused by TA + tripterygium glycosides was slower than the TA and control groups. The incidence of adverse reactions in the TA + tripterygium glycosides group was lower in the control and TA groups. The final treatment effect of the experimental groups was better than the control group. The recurrence rate in the TA + tripterygium glycosides group was also significantly lower. CONCLUSION: Tacrolimus and tripterygium glycosides combined therapy had better effects and safety for long-term treatment of Henoch-Schönlein purpura nephritis.

The significance of the hemalexin C1q, RBP, and urinary NAG levels in the diagnosis and prognosis of children with purpura nephritis.

PURPOSE: To investigate the significance of the hemalexin C1q, retinal-binding-protein (RBP), and urinary N-acety1-ß-D-glucosaminidase (NAG) levels in the diagnosis and prognosis of children with purpura nephritis. METHODS: A total of 130 children with purpura nephritis admitted to our hospital from January 2017 to December 2019 were recruited as the study cohort, including 43 children with purpura nephritis as the observation group, 51 children with purpura nephritis as the control group, and 36 healthy children undergoing physical examinations at the same time period as the healthy group. The basic data of the three groups of children were compared, and the hemalexin C1q, RBP, and urinary NAG levels were observed. The children were divided into a good prognosis group and a poor prognosis group according to the observation group's follow-up data. The significance of the hemalexin C1q, RBP, and urinary NAG levels for the diagnosis and prognosis of children with purpura nephritis was investigated by comparing the hemalexin C1q, RBP, and urinary NAG levels in these two groups. RESULTS: The hemalexin C1q, RBP, and urinary NAG levels in the observation group, the control group, and the healthy group were significantly reduced, and the differences were statistically significant (P < 0.05). The hemalexin C1q, RBP, and urinary NAG levels of the children in the good prognosis group were significantly lower than they were in the poor prognosis group (P < 0.05). CONCLUSION: The hemalexin C1q, RBP, and urinary NAG levels in the diagnosis and prognosis of children with purpura nephritis have a definite value and can be used as effective predictors for the prognosis of children with purpura nephritis.

miR-1224-3p Promotes Breast Cancer Cell Proliferation and Migration through PGM5-Mediated Aerobic Glycolysis.

Metabolic reprogramming of aerobic glycolysis is a hallmark of cancer cells. Regulators of aerobic glycolysis have become targets for cancer diagnosis and therapy. However, the regulators of aerobic glycolysis in breast cancer development have not been well elucidated. Here, we show that the phosphoglucomutase (PGM) family member PGM5 promotes conversion of glucose-1-phosphate (G1P) into glucose-6-phosphate (G6P) and inhibits breast cancer cell proliferation and migration through regulating aerobic glycolysis. In breast cancer patients, PGM5 is significantly downregulated, and its low expression is a predictor of poor prognosis. MicroRNA-1224-3p (miR-1224-3p) inhibits the PGM5 level through directly targeting its 3'-untranslated region and suppresses PGM5-mediated breast cancer cell proliferation, migration, and glycolytic function. Moreover, the miR-1224-3p/PGM5 axis regulates the expression of cell cycle- and apoptosis-related genes and the markers of epithelial-mesenchymal transition (EMT), a process involved in migration and metastasis of cancer cells. Taken together, our results indicate that miR-1224-3p/PGM5 axis plays important roles in breast cancer cell proliferation, migration, and aerobic glycolysis and may be a potential target for breast cancer therapy.

Serum Uric Acid and High-Sensitivity C-Reactive Protein as Predictors of Cognitive Impairment in Patients with Cerebral Infarction.

BACKGROUND: Cognitive impairment induced by cerebral infarction has become a devastating health problem. More efficient predictors are required to evaluate the potential cognitive decline after cerebral infarction in clinic. Serum uric acid (UA) and high-sensitivity C-reactive protein (hs-CRP) are two factors reported to correlate with cognitive impairment. However, the understanding on serum UA and hs-CRP with cognitive dysfunction remains unclear. METHODS: Serum UA and hs-CRP were evaluated in patients with cerebral infarction (n = 197) using single factor analysis and multivariate logistic regression analysis. Clinical and pathological characteristics were analyzed by logistic regression, respectively, and the results demonstrated the correlation between the pathological characteristics and the cognitive impairment post cerebral infarction. Montreal Cognitive Assessment (MoCA) was used to evaluate the patients' cognitive function, and patients with a MoCA score <26 were recognized as with cognitive impairment. RESULTS: Clinical characteristics related to cognitive impairment, including age, gender, blood pressure, serum UA, and hs-CRP were collected and analyzed. Serum UA and hs-CRP were identified to be potential predictors for post-stroke cognitive dysfunction, with higher serum UA levels correlated with better cognitive function and higher hs-CRP levels correlated with worse cognitive impairment. CONCLUSION: Serum UA and hs-CRP are two predictors for cognitive impairment post cerebral infarction.

Astragaloside IV Exerts Anti-tumor Effect on Murine Colorectal Cancer by Re-educating Tumor-Associated Macrophage.

Astragaloside IV (AS-IV) has shown anti-tumorigenic properties in certain cancers for its effect of boosting the body's immune system, but its role in colorectal cancer (CRC) remains unclear. In this study, we investigated the therapeutic effect of AS-IV in CRC and explored its underlying mechanism. CT26 colon cancer cells and mouse model by injection of CT26 cells subcutaneously were used as in vitro and in vivo model. M1 and M2 macrophage-associated markers, mRNA and protein expression levels were analyzed after AS-IV treatment. Inflammatory factors and cytokines in the tumors from mouse model were detected. Repolarization effect of AS-IV in vitro on bone-marrow-derived macrophages was also detected. In vitro, AS-IV inhibited the proliferation of CT26 cells and induced cell apoptosis dose-dependently, and significantly reduced M2 macrophages and increased M1 macrophages. In mouse model, it suppressed tumor growth and decreased the production of anti-inflammatory factors such as TGF-ß, IL-10 and VEGF-A, while increased the production of pro-inflammatory factors like IFN-γ, IL-12 and TNF-α in tumor. Combination of AS-IV and checkpoint inhibitor aPD-1 exhibited synergistic antitumor effect by inhibiting tumor growth and increasing T cell infiltration. AS-IV could induce M2 macrophages polarization to the M1 phenotype. Its combination with immune checkpoint inhibitors could be expected to become a potential new strategy for the treatment of CRC.

Let-7a-5p inhibits triple-negative breast tumor growth and metastasis through GLUT12-mediated warburg effect.

Triple-negative breast cancer (TNBC) is known for its aggressive phenotype with limited treatment modalities and poor prognosis. The Warburg effect (aerobic glycolysis) is a hallmark of cancer that serves as a promising target for diagnosis and therapy. However, how aerobic glycolysis regulates TNBC remains largely unknown. Here, we show that the glucose transporter (GLUT) family member GLUT12 promotes TNBC tumor growth and metastasis in vitro and in vivo through regulating aerobic glycolysis. MicroRNA let-7a-5p, a tumor suppressor, inhibited GLUT12 expression by targeting its 3'-untranslated region, and suppressed GLUT12-mediated TNBC tumor growth, metastasis, and glycolytic function, including alterations of glucose uptake, lactate production, ATP generation, extracellular acidification rate, and oxygen consumption rate. Inhibiting aerobic glycolysis abolished the ability of let-7a-5p and GLUT12 to regulate TNBC cell proliferation, migration and invasion. In TNBC patients, GLUT12 was significantly upregulated, and let-7a-5p expression was inversely correlated with GLUT12 expression. High expression of let-7a-5p and GLUT12 predicted better and worse clinical outcomes, respectively. Taken together, our results indicate that the let-7a-5p/GLUT12 axis plays key roles in TNBC tumor growth and metastasis, and aerobic glycolysis, and is a potential target for TNBC treatment.

Snail promotes the generation of vascular endothelium by breast cancer cells.

A further understanding of tumor angiogenesis is urgently needed due to the limited therapeutic efficacy of anti-angiogenesis agents. However, the origin of endothelial cells (EC) in tumors remains widely elusive and controversial. Snail has been thoroughly elucidated as a master regulator of the epithelial-mesenchymal transition (EMT), but its role in endothelium generation is not yet established. In this study, we reported a new and unexpected function of Snail in endothelium generation by breast cancer cells. We showed that high Snail-expressing breast cancer cells isolated from patients showed more endothelium generated from these cells. Expression of Snail was positively correlated with endothelial markers in breast cancer patients. The ectopic expression of Snail induced endothelial marker expression, tube formation and DiI-AcLDL uptake of breast cancer cells in vitro, and enhanced tumor growth and microvessel density in vivo. Snail-mediated endothelium generation depended on VEGF and Sox2. Mechanistically, Snail promoted the expression of VEGF and Sox2 through recruiting the p300 activator complex to these promoters. We showed the dual function of Snail in tumor initiation and angiogenesis in vivo and in vitro through activation of Sox2 and VEGF, suggesting Snail may be an ideal target for cancer therapy.

Study of wavefront aberration in DR patients with different degree of dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To compare the changes of wavefront aberrations in patients with diabetic retinopathy (DR) and with different degrees of dry eye and to explore the reasons of visual quality decline in them. METHODS: We randomly selected 40 eyes in our hospital for treatment with DR and varying degrees of dry eye, and 40 eyes of normal control group. Topcon KR-1W visual quality analyzer was used to record the mean square the total high order corneal aberration, spherical aberration, comatic aberration and trefoil aberration of cornea with pupil diameters of 4mm and 6mm. Analysis of variance were used to compare the wavefront aberrations and the aberration values in the control group and in patients with diabetic retinopathy and with different degrees of dry eye. RESULTS: For 4mm and 6mm pupil diameters, nondiabetic retinopathy (NDR) with dry eye group, the nonproliferative diabetic retinopathy (NPDR) with dry eye group and proliferative diabetic retinopathy (PDR) dry eye group had significantly increased tHOA, coma and trefoil compared with the contrast group (P<0.01),and PDR dry eye group were significantly higher than NDR with dry eye group and NPDR with dry eye group in tHOA,spherical aberration (SA), coma and trefoil (P<0.01). CONCLUSION: Dry eye of diabetic retinopathy with different degrees is closely related to the increase of wavefront aberration. lncreased wavefront aberration may be one of the reasons to reduced visual quality in patients with diabetic retinopathy and with dry eye, and provide the basis for the decline of visual function of diabetic patients with dry eye.

Research progress on exosomes in diagnosis and treatment of cardiovascular diseases / 浙江大学学报·医学版

Exosome is a specific subset of vesicles from intracellular origin vesicles containing varies of microRNAs, mRNAs, proteins and lipids. It has been demonstrated that contents of exosomes could be altered due to different physiological and pathological stress, which could be used as clinical biomarker to reveal the disease state. In addition, according to previous studies, exosomes could exert protective roles for cardiovascular diseases such as atherosclerosis, myocardial infarction and ischemia/reperfusion injury, etc. The aim of this review is to summarize current research progress on exosomes, related implications in diagnosis and treatment of cardiovascular diseases and corresponding mechanisms.

[Isolation, identification and characterization of a diethylstilbestrol-degrading bacterial strain Serratia sp].

Utilizing the diethylstilbestrol (DES)-degrading bacteria to biodegrade DES is a most reliable technique for cleanup of DES pollutants from the environment. However, little information is available heretofore on the isolation of DES-degrading bacteria and their DES removal performance in the environment. A novel bacterium capable of degrading DES was isolated from the activated sludge of a wastewater treatment plant. According to its morphology, physiochemical characteristics, and 16S rDNA sequence analysis, this strain was identified as Serratia sp.. The strain was an aerobic bacterium, and it could degrade 68.3% of DES (50 mg x L(-1)) after culturing for 7 days at 30 degrees C, 150 r x min(-1) in shaking flasks. The optimal conditions for DES biodegradation by the obtained strain were 30 degrees C, 40-60 mg x L(-1) DES, pH 7.0, 5% of inoculation volume, 0 g x L(-1) of added NaCl, and 10 mL of liquid medium volume in 100 mL flask.

Effects of temperature and hydraulic residence time (HRT) on treatment of dilute wastewater in a carrier anaerobic baffled reactor / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To examine the effect of hydraulic residence time (HRT) on the performance and stability, to treat dilute wastewater at different operational temperatures in a carrier anaerobic baffled reactor (CABR), and hence to gain a deeper insight into microbial responses to hydraulic shocks on the base of the relationships among macroscopic performance, catabolic intermediate, and microcosmic alternation.</p><p><b>METHODS</b>COD, VFAs, and microbial activity were detected with constant feed strength (300 mg/L) at different HRTs (9-18 h) and temperatures (10 degrees C-28 degrees C) in a CABR.</p><p><b>RESULTS</b>The removal efficiencies declined with the decreases of HRTs and temperatures. However, the COD removal load was still higher at short HRT than at long HRT. Devastating reactor performance happened at temperature of 10 degrees C and at HRT of 9 h. HRTs had effect on the VFAs in the reactor slightly both at high and low temperatures, but the reasons differed from each other. Microbial activity was sensitive to indicate changes of environmental and operational parameters in the reactor.</p><p><b>CONCLUSION</b>The CABR offers to certain extent an application to treat dilute wastewater under a hydraulic-shock at temperatures from 10 degrees C to 28 degrees C.</p>