Molecular Epidemiology and Risk Factors of Carbapenem-Resistant Klebsiella Pneumoniae Bloodstream Infections in Wuhan, China.

OBJECTIVE: The clinical characteristics and microbiological data of patients with K. pneumoniae bloodstream infections (BSI) from January 2018 to December 2020 were retrospectively analyzed to study the molecular epidemiology of Carbapenem-resistant Klebsiella pneumoniae (CRKP). We also aimed to identify the risk factors for the development of CRKP BSI. METHODS: This retrospective study was conducted at Renmin Hospital of Wuhan University from January 2018 to December 2020. The date of non-duplicate K. pneumoniae isolates isolated from blood samples was identified using the microbiology laboratory database. The data from patients diagnosed with K. pneumoniae BSI were collected and analyzed. RESULTS: From 2018 to 2020, there were 510 non-duplicated K. pneumoniae blood isolates, mainly distributed in the intensive care unit (ICU) (28.4%), that were identified in our research. These cases included 77 strains of CRKP and 433 strains of carbapenem-susceptible K. pneumoniae (CSKP). The resistance rate of K. pneumoniae to meropenem and imipenem increased from 11.2% in 2018 to 27.1% in 2020. Moreover, Compared with CSKP, all CRKP isolates showed multi-resistance to tested antibiotics. The phylogenetic analysis showed that the CRKP isolates could be grouped into four major clades, and multilocus sequence typing revealed that the isolates had considerable clonality. Overall, 8 sequence types (STs) of CRKP were detected, of which ST11 comprised the majority and clustered into clade 3. The most prevalent carbapenemase gene was blaKPC (87%) among the CRKP isolates, followed by blaNDM (9.1%) and blaIMP (1.3%). A total of 74 (16.6%) patients with CRKP BSI and 373 (83.4%) patients with CSKP BSI were categorized as the case and control groups. The mortality in the CRKP group was 44.6%, and 11.5% in CSKP group (P<0.001). A multivariate analysis that a long hospital stay before BSI (OR=1.42, 95% CI 1.02-4.31, P=0.011), ICU hospitalization history (OR=3.30, 95% CI 1.35-8.05, P=0.002), and prior use of carbapenems (OR=3.33, 95% CI 1.29-7.27, P=0.001) and antifungals (OR=2.81, 95% CI 1.24-6.04, P<0.001) were independent risk factors for CRKP BSI. CONCLUSION: ST11 is the predominant type of CRKP mediating inter-hospital transmission, and blaKPC is the main carbapenemase gene harboured by CRKP blood isolates. ICU stay, prolonged hospitalization before BSI, and prior use of carbapenems and antifungals were independent risk factors for acquiring CRKP BSI. Our study may provide insights into early infection control practices.

[Development of preparation process of icaritin-coix seed oil microemulsion based on quality by design concept].

To optimize the formulation and preparation process of icaritin-coix seed oil microemulsion(IC-MEs) based on quality by design(QbD) concept. IC-MEs were prepared by water titration. Firstly, the risk factors that may affect the quality of IC-MEs were evaluated. Then Plackett-Burman design was used to screen out prescription factors and process parameters that had a significant effect on the indicators. Finally, Box-Behnken design was used to optimize the prescription ratio of IC-MEs. Through the risk assessment and Plackett-Burman design, three formulation factors [drug loading efficiency, the ratio of mixed-oil(coix seed oil-Glycerol tributyrate) to mixed-surfactant(HS15-RH40) and water addition] were determined as the key factors affecting IC-MEs. The regression model established by Box-Behnken design had a good predictability. The optimal formula was as following: the drug loading efficiency of 0.92%, the ratio of mixed-oil(coix seed oil-glycerol tributyrate) to mixed-surfactant(HS15-RH40) of 4∶6, and the water addition of 5.7 mL. According to this prescription, IC-MEs were prepared, and its encapsulation efficiency after 1 week was 92.45%±1.00%. Therefore, the stability of IC-MEs could be improved by optimizing prescription and process parameters of IC-MEs based on the QbD concept, which can provide certain reference value for the future development of IC-MEs.

The Clinical Role of Changes of Maximum Expiratory Flow at 25% and 50% of Vital Capacity before and after Bronchodilator Reversibility Test in Diagnosing Asthma.

Changes of maximum expiratory flow at 25% and 50% of vital capacity (MEF25 and MEF50, respectively), and predominant parameters indicating small airways function in asthmatics before and after bronchodilator (BD) reversibility test have been less interpreted. Our study aimed to investigate the clinical role of changes of MEF25 and MEF50 before and after BD reversibility test in diagnosing asthma. Forced expiratory volume in the first second (FEV1), MEF25, and MEF50 were measured before and after BD reversibility test in 207 asthmatic patients using standard process. Forty healthy individuals were enrolled as controls. Receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of reversibility of MEF25 and MEF50 before and after BD reversibility test (ΔMEF25% and ΔMEF50%, respectively) in diagnosing asthma. Among these functional criteria, ΔMEF25% and ΔMEF50% ≥ 25% performed the best diagnostic performance. The sensitivity, specificity, and accuracy of ΔMEF25% ≥ 25% as an objective diagnostic test for asthma were 63.29%, 87.50%, and 67.21%, and of ΔMEF50% ≥ 25% were 79.23%, 85.00%, and 80.16%, respectively. The area under the ROC curve of the indicators was 0.8203 and 0.9104, respectively. By contrast, an increase in FEV1 ≥ 12% and 200 mL demonstrated a sensitivity of 62.32%, specificity of 82.50%, and accuracy of 65.59% in diagnosing asthma. The changes of MEF25 and MEF50 before and after BD reversibility test may be of additional value in the clinical diagnosis of asthma, with cutoff values of 25% being the most.

Impact of Anxiety or Depression Symptoms on Propofol Requirements for Sedation in Females: A Prospective Cohort Study.

Mental disorders are thought to affect various clinical outcomes during the perioperative period. Among them, anxiety and depression are 2 of the most common types. However, the impacts of anxiety or depression on propofol requirements remain unclear. This study aimed to investigate the effects of anxiety or depression symptoms on the propofol requirements for sedation in females. This study recruited female patients aged 18 to 65 years, with American Society of Anesthesiologists physical status classification of 1 to 2, who were scheduled for hysteroscopic surgery under propofol-based intravenous anesthesia. The day before surgery, the Hospital Anxiety and Depression Scale (HADS) was used to assess the symptoms of anxiety and depression within the past 6 months. Target-controlled propofol was gradually titrated to achieve 3 desired levels of sedation: Modified Observer's Assessment of Alertness/Sedation scale (MOAA/S) score 3, MOAA/S score 1, and MOAA/S score 1 and Narcotrend Index <65. The effect-site concentration of propofol correlated with HADS-Anxiety scores for the sedation levels of MOAA/S 3 and 1 (r = .249, P = .008; and r = .190, P = .045, respectively). However, the propofol requirements did not correlate with HADS-Depression scores at any sedation level. In conclusion, female patients with anxiety symptoms, but not depression symptoms, required a higher dose of propofol for sedation in hysteroscopy.

Activation of PD-1 Protects Intestinal Immune Defense Through IL-10/miR-155 Pathway After Intestinal Ischemia Reperfusion.

BACKGROUND: To date, mechanisms of intestinal immunoglobulin (Ig) dysfunction following intestinal ischemia/reperfusion (I/R) remain unclear. Programmed death 1 (PD-1) is associated with immune responses of lymphocytes. AIM: We aimed to verify the hypothesis that activation of PD-1 may improve intestinal immune dysfunction by regulating IL-10/miR-155 production after intestinal IR injury. METHODS: Intestinal I/R injury was induced in mice by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-L1 fusion Ig, anti-interleukin (IL)-10 monoclonal antibody (mAb), and microRNA (miR)-155 agomir were administered. PD-1 expression, IL-10 mRNA, and protein expression in Peyer's patches (PP) CD4+ cells were measured. MiR-155 levels, tumor necrosis factor (TNF)-α and IL-1ß concentration, and activation-induced cytidine deaminase (AID), a key enzyme for intestinal immune antibodies, in PP tissues were measured, respectively. Importantly, the production and cecal bacteria-binding capacity of IgA and IgM were detected. RESULTS: Intestinal I/R led to decreased PD-1 expression, imbalanced production, and impaired bacteria-binding capacity of IgA and IgM. Activating PD-1 by PD-L1 Ig facilitated IL-10 synthesis, then decreased miR-155 levels, and subsequently promoted AID expression and reduced TNF-α, IL-1ß concentration. Upregulation of AID improved the disruptions of intestinal immune barrier caused by IgA and IgM dysfunction. Anti-IL-10 mAb and miR-155 agomir abolished the protective effects of PD-L1 Ig on the intestinal immune defense. CONCLUSION: Activation of PD-1 with PD-L1 Ig relieves intestinal immune defensive injury through IL-10/miR-155 pathway following intestinal I/R attack. PD-1, IL-10, and miR-155 may be potential targets for the damages of intestinal barrier and immunity.

Bakuchiol inhibits cell proliferation and induces apoptosis and cell cycle arrest in SGC-7901 human gastric cancer cells.

PURPOSE: The main purpose of the present study was to evaluate the antiproliferative activity of bakuchiol in human gastric tumor cell line (SGC-7901) along with an effort to demonstrate its mode of action. METHODS: he effect of the compound on cell viability was evaluated by MTT assay. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Flow cytometry was used to assess the effect on cell cycle phase distribution. RESULTS: The results revealed that bakuchiol exerted potent, dose-dependent as well as time-dependent growth inhibitory effects in SGC-7901 cell proliferation with IC50 values of 58.4, 42.3 and 32.5 µM at 12, 24 and 48 hrs time intervals, respectively. On treatment with 10, 50 and 100 µM dose of bakuchiol for 48 hrs, phase contrast microscope revealed that the cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 µM of bakuchiol, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Bakuchiol also induced sub-G1 cell cycle arrest in a dose-dependent manner. CONCLUSION: The current findings reveal that bakuchiol is a potent cytotoxic agent against gastric cancer cells and its cytotoxicity is mediated through induction of apoptosis and sub-G1 cell cycle arrest.

Evaluation of biocompatibility and toxicity of biodegradable poly (DL-lactic acid) films.

Regeneration and functional recovery of nerves after peripheral nerve injury is the key to peripheral nerve repair. One of the putative therapeutic strategies is to use anti-adhesion polymer films, made of polymeric biomaterials. Recently, a novel biodegradable poly (DL-lactic acid) (PDLLA) film has been prepared using a method of phase transformation with biodegradable polylactic acid polymer as the substrate. This novel, anti-adhesion film has a porous structure, which provides better mechanical properties, better flexibility, more complete diffusion through the polymer of tissue biologic factors like growth factors, and more controllable degradation compared to traditional non-porous films. Little is known, however, about the in vitro and in vivo biocompatibility and cytotoxicity of this type of PDLLA film. Therefore, our aim was to evaluate the biocompatibility and cytotoxicity of this novel PDLLA film using various experimental methods, including a skin irritation test, MTT analysis, and the mouse bone marrow cell micronucleus test, as well as hematology or clinical chemistry measurements in rats after receiving sciatic nerve transection and anastomosis with wrapping of the anastomosis with DLLA films. We demonstrated that exposure to PDLLA film extracts did not generate apparent erythema or edema in rabbit skin and had no effect on the proliferation of Vero cells. Additionally, treatment with PDLLA film extracts did not alter the incidence of micronucleated polychromatic erythrocytes as compared with saline Treated group. Furthermore, implantation of PDLLA film did not alter liver or renal function as measured by serum levels of ALT, AST, TP, A/G, Cr, and BUN, and pathologic examinations showed that implantation of PDLLA film did not cause pathologic changes to the rat liver, kidney, pancreas, or spleen. Taken together, these results suggest that PDLLA films have excellent biocompatibility and no obvious toxicity in vivo, and may be used to prevent nerve adhesion, thereby promoting nerve regeneration.

Highly effective permeability and antifouling performances of polypropylene non-woven fabric membranes modified with graphene oxide by inkjet printing and immersion coating methods.

In the current study, graphene oxide (GO)-modified polypropylene non-woven fabric (PP-NWF) membranes were prepared via inkjet printing and immersion coating methods. Scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle measurements, pure water permeation (JPWP) and protein adsorption were tested to evaluate the impact of the GO nanosheet on the characteristics and performance of modified PP-NWF membranes. The results showed that the exfoliated GO nanosheets uniformly deposited on the membrane surface and firmly embedded into the interlaced fibers, resulting in the improvement of membrane hydrophilicity, permeability and antifouling properties comparing with original PP-NWF membranes. The GO-printed and GO-coated membranes had 113 and 188% higher fluxes, and 70.95 and 75.74% lower protein adsorptions than the original PP-NWF membranes, respectively. After cross-linked treatment, ultrasound processing was conducted to evaluate the stability of the modified PP-NWF membranes. The results demonstrated that there was almost no decrease in permeation after ultrasonic treatment indicating that the cross-linking treatment could enhance the immobilization of the GO nanosheets on and into the modified membranes.

[Detection of anxiety and depression status of BALB/c asthmatic mice model].

OBJECTIVE: To detect the anxiety and depression status of BALB/c asthmatic model in mice. METHODS: A total of 20 mice were randomly divided into asthma and control groups (n = 10 each). The animals were sensitized and challenged with ovalbumin for asthmatic model. Phosphate buffer solution was used in the control group. The mice were challenged with increasing concentrations of methacholine aerosol and the airway resistance was measuring non-invasively by enhanced pause (Penh). And elevated plus maze test system and forced swim were employed to evaluate their anxiety and depression status. Then bronchoalveolar lavage cytology was detected for evaluating the airway inflammation. RESULTS: In both groups, Penh value increased with the rising concentration of methacholine. The Penh values of asthmatic mice exciting with normal saline and methacholine concentration of 0, 5 g/L were 0.43 ± 0.04, 0.41 ± 0.05 and 0.44 ± 0.04 versus 0.42 ± 0.03, 0.39 ± 0.03,0.43 ± 0.04 in control group. The difference had no statistical significance (P = 0.290,0.652,0.723). At the concentration of methacholine 10, 15, 20 g/L, the Penh values of asthmatic mice were 0.57 ± 0.03,0.85 ± 0.04, 1.57 ± 0.08 and they were significantly higher than those of control group (0.45 ± 0.08,0.57 ± 0.06,0.82 ± 0.09) (P = 0.001,0.000,0.000). Asthmatic mice in the elevated plus maze on a behavioral test and found that asthmatic mice open arm entries sum closed arm entries (OE+CE), percent of open arm/total entries (OE%) and percent of open arm/total time (OT%) was (18.3 ± 3.6) times, (22.2 ± 3.1)%, (16.7 ± 4.2)%. They were significantly lower than those of control group ((24.0 ± 2.9) times,(28.0 ± 3.4)%, (21.8 ± 4.6)%) (P = 0.001,0.001,0.019). Asthmatic mice swimming time was significantly higher than that of control group (147 ± 12) vs (133 ± 10) s (P = 0.010). The total number of cells and eosinophil ratio in asthma group was (10.0 ± 4.0)×10(5)/ml and (68.18 ± 3.76)%. And they were significantly larger than those of control group ((1.7 ± 0.4)× 10(5)/ml, (0.12 ± 0.07)%) (both P = 0.000). CONCLUSION: Asthmatic mice with concurrent anxiety and depression may be a model for elucidating the molecular mechanisms of asthma with anxiety and depression.

[Estimation and remote sensing inversion of diffuse attenuation coefficient Kd(490) in Lake Taihu in spring based on semi-analytical model].

Diffuse attenuation coefficient is not only an important optical parameter, but also an important factor of water ecological system. Two datasets measured in April 2009 and May 2010 were firstly used to calculate absorption coefficient [a (490)] and backscattering coefficient [b(b) (490)] at 490 nm, and then, the relationship between b(b) (490) and simulated remote sensing reflectance at different bands of HJ-1 was studied. The semi-analytical model of Kd (490) in Lake Taihu in spring was constructed based on this basis, and it was used to estimate Kd (490) of Lake Taihu via an image of HJ-1 finally. The results show that: 1) The values of a(490) and b(b)(490) can be calculated accurately based on optical closure principle, and the mean absolute percent error (MAPE) of a(490) between calculated and measured is 17.1%. In addition, the backscattering coefficient at 490 nm [b(b) (490)] exponentially relate with the simulated remote sensing reflectance at the fourth band of HJ-1; 2) The semi-analytical model constructed in this study has good accuracy and stability. The MAPE is 21.6% and RMSE is 1.68 m(-1) by comparing inversion result and quasi-synchronous measured data; 3) Kd (490) of Lake Taihu in spring differs a lot in space distribution. The values are relatively smaller in north and east part of Lake Taihu, but larger in west and south part.