The N6-methyladenosine mRNA methylase METTL14 promotes renal ischemic reperfusion injury via suppressing YAP1.

Renal ischemia-reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI), which is closely related to high morbidity and mortality. However, the pathogenesis underlying renal IRI is complex and not fully defined. N6-methyladenosine (m6A) was recently found to be an abundant modification in mammalian messenger RNAs. It is implicated in various biological processes, while the role of m6A in IRI is not illustrated. Here we show that the m6A-methylated RNA level and its methyltransferase METTL14 are elevated in human AKI renal tissues and IRI HK-2 cells. Moreover, METTL14 knockdown protects the kidney against IRI in vitro and in vivo. Mechanistically, we identified that YAP1 is a direct target of METTL14 in AKI progression. Inhibition of YAP1-TEAD signaling by peptide 17 abrogates the protective effect of METTL14 against IRI in vitro and in vivo. Taken together, these results reveal that the N6-methyladenosine mRNA methylase METTL14 promotes the renal IRI via suppressing YAP1. The discovery of the METTL14-YAP1 pathway provides an important new perspective for understanding AKI and is conducive to revealing new therapeutic strategies and targets.

Combined use of murine double minute-2 promoter methylation and serum AFP improves diagnostic efficiency in hepatitis B virus-related hepatocellular carcinoma.

Objective: Hepatocellular carcinoma (HCC) accounts for approximately 85% of all cases of liver cancer. In China, chronic hepatitis B virus-related HCC (HBV-related HCC) is the most common type of HCC. However, the majority of HBV-related HCC patients are asymptomatic, and the best opportunities for treating these patients are missed. The precise diagnosis of HBV-related HCC is crucial. The main purpose of this study was to evaluate the diagnostic value of murine double minute-2 (MDM2) promoter methylation in HBV-related HCC patients. Methods: The methylation status of the MDM2 promoter was detected by methylation-specific PCR. The MDM2 expression levels were validated by quantitative real-time PCR. Enzyme-linked immunosorbent assay was used to determine the levels of interleukin-6 (IL-6) and tumor-necrosis factor-α (TNF-α) in plasma. Results: The methylation frequency of the MDM2 promoter was decreased in HBV-related HCC patients. The MDM2 mRNA levels of patients with HBV-related HCC were higher than those of patients with liver cirrhosis and chronic hepatitis B. The plasma levels of IL-6 and TNF-α were significantly higher in HBV-related HCC patients than that in liver cirrhosis and chronic hepatitis B patients. The TNF-α levels were higher in the unmethylated MDM2 promoter group than in the methylated MDM2 promoter group in HBV-related HCC patients. Moreover, the combination of MDM2 promoter methylation and alpha-fetoprotein (AFP) improved the diagnosis of HBV-related HCC. Conclusions: Our study indicates, for the first time, that MDM2 promoter hypomethylation is present in HBV-related HCC patients. The combination of MDM2 promoter methylation and AFP can greatly improve diagnostic efficiency in HBV-related HCC, which might provide a new method for HBV-related HCC diagnosis.

Measurement of Cyclin D2 (CCND2) Gene Promoter Methylation in Plasma and Peripheral Blood Mononuclear Cells and Alpha-Fetoprotein Levels in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma.

BACKGROUND Alpha-fetoprotein (AFP) is widely used to screen for hepatocellular carcinoma (HCC). However, the use of this biomarker has been challenged due to its low sensitivity and high rate of false negatives. In this study, we evaluated the diagnostic capability of cyclin D2 (CCND2) promoter methylation in patients with HCC related to hepatitis B virus (HBV). MATERIAL AND METHODS Using methylation-specific PCR and quantitative real-time PCR, we measured methylation status and mRNA levels of CCND2 in plasma and peripheral blood mononuclear cells (PBMCs) from 275 subjects: 75 patients with chronic hepatitis B (CHB), 47 with liver cirrhosis (LC), 118 with HCC, and 35 healthy controls (HCs). RESULTS The methylation rate of the CCND2 promoter was significantly higher in HCC patients than in patients without HCC (P<0.001). Furthermore, advanced HCC (TNM III/IV) was associated with a significantly higher frequency of CCND2 methylation and lower CCND2 mRNA levels than early-stage disease (TNM I/II; P<0.05). Combined measurement of CCND2 methylation and AFP yielded significantly higher sensitivity and area under the curve (AUC) than AFP alone in distinguishing patients with HCC from subjects with LC and CHB (P<0.001). CONCLUSIONS CCND2 methylation may be useful for predicting HCC progression. In addition, combined measurement of CCND2 methylation and AFP could serve as a non-invasive diagnostic marker for patients with HBV-related HCC.

Periodic surface structures on dielectrics upon femtosecond laser pulses irradiation.

The formation of laser-induced periodic surface structures (LIPSS) on two different dielectrics of K9 glass and fused silica upon irradiation in ambient conditions and in vacuum with multiple femtosecond (fs) laser pulse sequences at different pulse durations (35 fs, 260 fs, and 500 fs) was studied experimentally. Three types of LIPSS, so-called high-spatial-frequency LIPSS (HSFL), low-spatial-frequency LIPSS (LSFL), and supra-wavelength periodic surface structures (SWPSS) with different spatial periods and orientations were identified. The appearance was characterized with respect to the experimental parameters of laser fluence and number of laser pulses per spot. The crater morphologies - including nanoripples, periodic microgrooves, quasiperiodic microspikes, and central smooth zone - were observed by scanning electron microscope (SEM). The supra-wavelength structures exhibit periodicities, which are markedly, even multiple times, higher than the laser excitation wavelength. The SWPSS were formed with a broader range of laser fluences, upon the longer laser pulse durations (260 fs and 500 fs) and/or on the lower band-gap dielectrics (K9 glass), due to the deeper effective light penetration depths and thicker viscous surface layers formation. The HSFL were observed on the higher band-gap dielectrics (fused silica) and within a certain narrow laser parameter window. The formation mechanisms of LIPSS were also discussed.

Molecular cloning, expression and characterization of secreted ferritin in the silkworm, Bombyx mori.

Ferritin is a ubiquitous iron storage protein which plays key role in regulating iron homeostasis and metabolism. In this paper, the ferritin heavy chain homologs (HCH) and light chain homologs (LCH) from Bombyx mori (BmFerHCH and BmFerLCH) were amplified through PCR and cloned into the expression vector pET-30a(+). The recombinant BmFerHCH and BmFerLCH expressed in Escherichia coli were in the form of insoluble inclusion bodies, indicating that the two proteins were not in their natural structural conformation. In order to obtain refolded ferritin in vitro, the inclusion bodies (BmFerHCH and/or BmFerLCH) were dissolved in denaturing buffer (100 mM Tris, 50 mM Glycine, 8 M urea, 5 mM DTT, pH 8.0) and then refolded in refolding buffer (100 mM Tris, 400 mM L-arginine, 0.2 mM PMSF, 0.5 mM DTT). The result showed that it was only when both BmFerHCH and BmFerLCH were present together in the denaturing buffer that refolding was successful and resulted in the formation of heteropolymers (H-L chain dimers) over homopolymers (H-H chain or L-L chain dimers). Moreover, the molecules (NaCl, Triton and glycerol) were found to enhance protein refolding. The optimum temperature, pH and ratios of BmFerHCH/BmFerLCH required for refolding were found to be 10 °C, pH 7, 1:1 or 1:2, respectively. Finally, the refolded ferritin had the ability to store iron, exhibited ferroxidase activity, and could withstand high temperatures and pH treatment, which is consistent with ferritin in other species.

The Control of Conjugation Lengths and Steric Hindrance to Modulate Aggregation-Induced Emission with High Electroluminescence Properties and Interesting Optical Properties.

A series of novel AIE-active (aggregation-induced emission) molecules, named SAF-2-TriPE, SAF-3-TriPE, and SAF-4-TriPE, were designed and synthesized through facile reaction procedures. We found that incorporation of the spiro-acridine-fluorene (SAF) group, which is famous for its excellent hole-transporting ability and rigid structure, at different substitution positions on the phenyl ring affected the conjugation lengths of these compounds. Consequently, we have obtained molecules with different emission colors and properties without sacrificing good EL (electroluminescence) characteristics. Accordingly, a device that was based on compound SAF-2-TriPE displayed superior EL characteristics: it emitted green light with ηc, max =10.5 cd A(-1) and ηext, max =4.22 %, whereas a device that was based on compound SAF-3-TriPE emitted blue-green light with ηc, max =3.9 cd A(-1) and ηext, max = 1.71 %. These compounds also displayed different AIE performances: when the fraction of water in the THF solutions of these compounds was increased, we observed a significant improvement in the ΦF of compounds SAF-2-TriPE and SAF-3-TriPE; in contrast, compound SAF-4-TriPE showed an abnormal phenomenon, in that it emitted a strong fluorescence in both pure THF solution and in the aggregated state without a significant change in ΦF . Overall, this systematic study confirmed a relationship between the regioisomerism of the luminophore structure and its AIE activity and the resulting electroluminescent performance in non-doped devices.

[Efficacy Observation of Yiguanjian Decoction Combined Adefovir Dipivoxil Tablet in Treating HBeAg Negative Chronic Viral Hepatitis B Active Compensated Liver Cirrhosis Patients].

OBJECTIVE: To explore clinical efficacy of Yiguanjian Decoction (YD) combined Adefovir Dipivoxil Tablet (ADT) in treating HBeAg negative chronic viral hepatitis B (CVHB) active compensated liver cirrhosis (LC) patients. METHODS: Totally 68 HBeAg negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group using random digit table, 34 in each group. Patients in the control group took ADT alone, 10 mg each time, once per day. Those in the treatment group additionally took YD, one dose per day. The therapeutic course for all was 48 weeks. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) were detected once in every two weeks. Hepatitis B virus (HBV)-DNA and four items of serum liver fibrosis [procollagen type I (PCN), hyaluronidase (HA), procollagen III peptide (PCIII), laminin (LN)] were detected once per every 4 weeks. Abdominal ultrasound B was performed before and after treatment. The inner diameter of the portal vein and the size of spleen were recorded. The fibrosis degree of liver was evaluated using Fibroscan. Efficacy of Chinese medicine (CM) was evaluated between the two groups before and after treatment using CM syndrome integrals. Efficacy of Western medicine (WM) was also evaluated between the two groups using Child-Pugh grading. Results Compared with before treatment in the same group, ALT and AST levels restored to normal levels, HBV-DNA turned negative (HBV-DNA < or = 1 x 10(2)) in the two groups after 48-week treatment. Besides, levels of TBil, ALB, PCIV, HA, PCIII, and LN obviously decreased (P < 0.05, P < 0.01). Results of ultrasound B showed the inner diameter of the portal vein and the size of spleen decreased. Fibroscan results showed that the elasticity value of the liver obviously decreased (P < 0.05). Besides, post-treatment levels of PCIV, HA, PCEJ, and LN, and the elasticity value of the liver decreased more obviously in the treatment group than in the control group (P < 0.01). There was no statistical difference in post-treatment levels of ALT, AST, TBil, ALB, inner diameter of the portal vein, or the size of spleen between the two groups (P > 0.05). Compared with before treatment in the same group, scores of Chinese medical syndrome and Child-Pugh scores decreased in the two groups after treatment (P < 0.05, P < 0.01). Besides, scores of Chinese medical syndrome decreased more obviously in the treatment group than in the control group (P < 0.05). The effective rate was 8824% (30/34) in the treatment group, higher than that of the control group [67.65% (23/34)] with statistical difference (P <0.05). Conclusion Combined treatment of YD and ADT could significantly improve symptoms of CM and fibrosis degree of liver of HBeAg negative CVHB active compensated LC patients.

A solution-processed bathocuproine cathode interfacial layer for high-performance bromine-iodine perovskite solar cells.

Perovskite film generally has rough surface morphology due to the voids between the grain domains. Smoothed interface contact between the perovskite layer and the top electrode is critical for planar perovskite solar cells. We reported high efficiency bromine-iodine based perovskite solar cells with a flattening cathode interface by incorporating a solution-processed bathocuproine (sBCP) interfacial layer at the cathode side. Compared with vacuum evaporated bathocuproine (eBCP), sBCP demonstrated an excellent surface modification effect at the cathode side with very smaller charge transfer resistance. Accordingly, a high fill factor exceeding 85% and a power conversion efficiency exceeding 13% in CH3NH3PbI3-xBrx based perovskite solar cells were achieved. The largely improved fill factor was attributed to the smooth film morphology and full surface coverage of perovskite films modified by the solution-processed BCP layer.

A convenient and reproducible protocol for acquisition of the hepatocyte phase for liver function-impaired patients in gadoxetic acid disodium-enhanced magnetic resonance imaging.

Background: The hepatocyte phase (HCP) in gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) plays an important role in the detection and characterization of liver lesions, treatment planning, and liver function evaluation. However, the imaging protocol is complicated and time-consuming. This cross-sectional study aimed to develop a convenient and reproducible protocol for the HCP acquisition in Gd-EOB-DTPA-enhanced MRI. Methods: A total of 107 patients were prospectively included and assigned to three groups based on Child-Pugh (CP) classification, with 37, 40, and 30 in the non-cirrhosis, CP A, and CP B groups, respectively. Dynamic HCPs were acquired every 5 min after the Gd-EOB-DTPA administration and ended in 25 min in non-cirrhosis patients and 40 min in cirrhotic patients. The HCP acquired 5 min after the initial visualization of the intrahepatic bile duct (IBD) was selected from the dynamic HCPs as the adequate HCP (HCPproposed) and the corresponding acquisition time was recorded as Timeproposed. In addition, according to the 2016 Expert Consensus (EC) on the definition of the adequate HCP from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the adequate HCPEC and the corresponding TimeEC were also determined from the dynamic HCPs. The hepatic relative enhancement ratio (RER), the contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of hepatic focal lesions in the HCPEC and HCPproposed images, as well as the TimeEC and Timeproposed were compared by the paired t-test for the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed was compared by the χ2 test. Results: The RER, CNR, and SNR showed no significant difference between the HCPEC and HCPproposed in all three groups (all P>0.05). The paired differences between TimeEC and Timeproposed were 1.08±3.56 min (P=0.07), 2.88±4.22 min (P<0.001), and 5.83±5.27 min (P<0.001) in the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed were 0.804 (86/107) and 0.962 (103/107), respectively (χ²=13.09, P=0.001). Conclusions: The adequate HCP could be acquired 5 min after the initial visualization of the IBD, which could serve as a convenient and reproducible protocol for the HCP imaging.

Design of ultrathin plasmonic quarter-wave plate based on period coupling.

Based on an analysis of the surface admittance of a plasmonic film with a substrate, we propose an ultrathin quarter-wave plate consisting of a periodic plane array of symmetrical L-shaped plasmonic antennas. The period, which determines the coupling among L-shaped antennas, is an important parameter for optimizing the performance of the structure. Numerical simulation results show that an Au quarter-wave plate designed in this Letter can efficiently convert a linearly polarized light at normal incidence into circularly polarized light, whose ellipticity is 0.994 at an operating wavelength of 1550 nm. The thickness is only 30 nm, which is nearly 1/50 of the wavelength of incident light.

Optimization of hepatobiliary phase imaging in gadoxetic acid-enhanced magnetic resonance imaging: a narrative review.

Background and Objective: Gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) is widely used in clinical practice. Its unique hepatobiliary phase (HBP) has been used to improve the detection and identification of hepatic lesions and has also been used to evaluate hepatic function and fibrosis. At the early stage of its clinical practice, the HBP was typically collected empirically with a delay of 20 minutes after intravenous administration to image the liver with sufficient enhancement for diagnosis. However, numerous methods and consensus statements for optimizing HBP acquisition have been proposed. This review details the methods and consensus statements on optimizing HBP collection. Methods: The electronic literature search was performed using the databases PubMed, MEDLINE, Cochrane, and Embase without limit on publication period to identify published reports on optimizing HBP imaging in Gd-EOB-DTPA-enhanced MRI. Articles with low relevance to the topics were excluded. Key Content and Findings: Recently, an increasing number of investigations suggest that collecting HBP after 20 min is too drawn-out for patients with normal liver function but is too short for patients with cirrhosis. Previous studies demonstrated that liver enhancement is closely related to liver function in Gd-EOB-DTPA-enhanced MRI. Therefore several reports have proposed various HBP delay times at different liver function levels. These delay times could be evaluated by laboratory indicators, such as prothrombin (PT) activity, total bilirubin, direct bilirubin, and the model for end-stage liver disease. Other investigations have found that the initial visualization time of the intrahepatic bile duct (IHD) in Gd-EOB-DTPA-enhanced MRI to also be related to liver enhancement and function. Therefore, initial visualization of the IHD is considered necessary for adequate HBP and has been employed in HBP acquisition in recent reports. Conclusions: Optimizing HBP acquisition according to individual hepatic function is a good strategy and was followed in most of the investigations included in our review. Obtaining adequate HBP in the shortest possible time is the target condition in Gd-EOB-DTPA-enhanced MRI. However, a more concise and efficient HBP acquisition strategy is still expected to be developed in the future.

Identification of mercury species in coal combustion by-products from power plants using thermal desorption-atomic fluorescence spectrometry on-line coupling system.

Along with the environmental protection policies becoming strict in China, the air pollution control devices (especially selective catalytic reduction (SCR)) are widely equipped in coal-fired power plants. The installation and run of these devices will inevitably affect mercury (Hg) species distribution in coal fired by-products such like fly ash (FA) and gypsum. In this work, a new on-line coupling system based on atomic fluorescence spectrometry (AFS) with a home-made chromatographic workstation was successfully developed to identify Hg species through thermal programmed desorption (TPD). The influences of matrix, furnace temperature, and carrier gas flow on analytical performance were investigated and the parameters were optimized. The FA and gypsum samples from coal-fired power plants equipped with SCR were collected and the mercury species were analyzed by the developed coupling system. HgCl2 and HgO were the main species in FA, while Hg2Cl2 and HgO were the main species in gypsum. All of Hg species in the studied FA and gypsum samples were released below 400 °C. A sequential extraction procedure was applied to further verify the operational Hg species including mobile and non-mobile fractions in FA and gypsum samples. This study demonstrated that AFS coupled with TPD procedure was an effective method to analyze Hg species in coal combustion by-products from power plants.

Gene signature and prediction model of the mitophagy-associated immune microenvironment in renal ischemia-reperfusion injury.

Background: Renal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes. Method: The specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson's correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections. Results: The expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable. Conclusion: We clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI.

Wave propagation in deep-subwavelength mode waveguides.

This Letter proposes a dielectric waveguide with deep-subwavelength mode sizes. Results of both frequency domain and time domain analysis show that the effective mode area is below λ(0)(2)/400 and can even reach λ(0)(2)/1000 (λ(0) is the wavelength in vacuum). The effective electrical mode area can be comparable to that of a hybrid plasmonic subwavelength confinement waveguide, with reduced optical absorption. In contrast to slot waveguides, which guide light in low-index materials, the proposed structure guides light in high-index materials. Results obtained in this Letter show that the losses are sensitive to the surface roughness on the tens of nanometers scale. The structure can be used to design ring resonators with a quality factor comparable to that of a diffraction-limited dielectric ring resonator with the same standing wave numbers. The property can be applied in nonlinear effect enhancement or laser design with ultralow threshold.

Improving the room-temperature confinement of light by miniaturizing mode sizes into a deep subwavelength scale using dielectric spheres in metal cavities.

The confinement of light within nanometer-scale regions may result in the significant enhancement of light-matter interactions. However, light confinement to nanometers is hindered by the diffraction limit of a dielectric material. For a dielectric cavity, if the material loss is negligible, reducing the cavity size usually causes a significantly increase in radiation loss. Surface plasmons show great promise for potential subwavelength light confinement. However, in most circumstances, light confinement by dissipative metallic materials can cause ohmic losses at optical frequencies. In such cases, the realization of light confinement with deep subwavelength mode sizes results in great losses and thus has low quality factors. In the present study, a three-dimensional light confinement with deep subwavelength mode sizes is achieved using dielectric spheres in metal cavities. Contrary to other mechanisms for subwavelength light confinement that are based on the use of dielectric or metal cavities, the nanometer-scale regions ensure that most of the light energy is confined away from the metal-dielectric interfaces, thereby decreasing light absorption in the metal cavity. In turn, the metal cavity decreases the radiation loss of light. Thus, high quality factors ranging from 2×10(2) to 6×10(2) can be obtained at room temperature. An effective electrical mode volume ranging from 7×10(-5)λ(0)(3) to 2×10(-4)λ(0)(3) (where λ(0) is the resonant wavelength in a vacuum) can be achieved. Therefore, this method of three-dimensional light confinement with deep subwavelength mode sizes using dielectric spheres in metal cavities may have potential applications in the design of nanolasers, nanophoton detectors, nonlinear optical switches, and so on.

[Meta-analysis of clinical efficacy of TVT-S versus TVT-O/TOT in the treatment of stress urinary incontinence].

OBJECTIVE: To assess the current evidence of effectiveness and safety of Single-incision mini-slings (TVT-S) versus transobturator tension-free vaginal tapes (TVT-O/TOT) in the management of female stress urinary incontinence (SUI). METHODS: Literature searches were conducted for all randomized controlled trials (RCTs) comparing TVT-S and TVT-O/TOT from CNKI, CBM, VIP, MEDLINE, OVID, FMJS and Cochrane Library between November 1996 and November 2011. The Revman 5.1.0 software was used for Meta-analysis according to Cochrane system evaluation method. RESULTS: A total of 1545 females in 7 RCTs were included. Meta-analysis showed that no statistical differences existed in the rate of postoperative voiding dysfunction and dyspareunia between TVT-S and TVT-O/TOT (P > 0.05). But the rate of objective cure, re-operation, inner thigh and groin pain and de novo urgency were statistically significant (P < 0.05). CONCLUSION: As compared with TVT-O/TOT, TVT-S procedure is associated with less postoperative inner thigh and groin pain, but a lower objective cure rate and relatively higher rates of de novo urgency and re-operation.

The Risk Factors of Carbapenem-Resistant Klebsiella pneumoniae Infection: A Single-Center Chinese Retrospective Study.

Objective: The present study aims to explore potential infection and death risk factors in patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: A retrospective case-control study was performed at Beijing Shijitan Hospital, China. The clinical and microbiological data of patients infected with K. pneumoniae (K.pn) were collected; the clinical characteristics of patients infected with carbapenem-susceptible K.pn and CRKP were analyzed using logistic regression analysis. Results: CRKP infection was significantly associated with prior carbapenem use (odds ratio [OR] and 95% credibility interval [CI]: 5.161 [1.840-32.233], P < 0.001), the use of more than three types of antibiotics for seven or more days (OR and 95% CI: 9.681 [2.662-18.122], P < 0.001), tracheotomy (OR and 95% CI: 5.015 [2.343-11.724], P < 0.001), and intensive care unit (ICU) stay (OR and 95% CI: 6.322 [2.02-12.231], P < 0.001). The risk of death in patients with CRKP infection was significantly associated with older age (OR and 95% CI of 70-80 years: 8.894 [1.972-67.346], P < 0.001; ≥80 years: 15.234 [2.072-93.452], P < 0.001), renal dysfunction (OR and 95% CI: 1.672 [1.104-7.451], P = 0.016), tracheotomy (OR and 95% CI: 2.051 [1.217-11.235], P = 0.002), and ICU stay (OR and 95% CI: 3.043 [2.174-18.453], P < 0.001). Conclusion: Prior to carbapenem use, older age, renal dysfunction, tracheotomy, and ICU stay were independent risk factors for death in patients infected with CRKP.

Evaluation of the dual vascular supply patterns in ground-glass nodules with a dynamic volume computed tomography.

BACKGROUND: In recent years, the detection rate of ground-glass nodules (GGNs) has been improved dramatically due to the popularization of low-dose computed tomography (CT) screening with high-resolution CT technique. This presents challenges for the characterization and management of the GGNs, which depends on a thorough investigation and sufficient diagnostic knowledge of the GGNs. In most diagnostic studies of the GGNs, morphological manifestations are used to differentiate benignancy and malignancy. In contrast, few studies are dedicated to the assessment of the hemodynamics, i.e., perfusion parameters of the GGNs. AIM: To assess the dual vascular supply patterns of GGNs on different histopathology and opacities. METHODS: Forty-seven GGNs from 47 patients were prospectively included and underwent the dynamic volume CT. Histopathologic diagnoses were obtained within two weeks after the CT examination. Blood flow from the bronchial artery [bronchial flow (BF)] and pulmonary artery [pulmonary flow (PF)] as well as the perfusion index (PI) = [PF/(PF + BF)] were obtained using first-pass dual-input CT perfusion analysis and compared respectively between different histopathology and lesion types (pure or mixed GGNs) and correlated with the attenuation values of the lesions using one-way ANOVA, student's t test and Pearson correlation analysis. RESULTS: Of the 47 GGNs (mean diameter, 8.17 mm; range, 5.3-12.7 mm), 30 (64%) were carcinoma, 6 (13%) were atypical adenomatous hyperplasia and 11 (23%) were organizing pneumonia. All perfusion parameters (BF, PF and PI) demonstrated no significant difference among the three conditions (all P > 0.05). The PFs were higher than the BFs in all the three conditions (all P < 0.001). Of the 30 GGN carcinomas, 14 showed mixed GGNs and 16 pure GGNs with a higher PI in the latter (P < 0.01). Of the 17 benign GGNs, 4 showed mixed GGNs and 13 pure GGNs with no significant difference of the PI between the GGN types (P = 0.21). A negative correlation (r = -0.76, P < 0.001) was demonstrated between the CT attenuation values and the PIs in the 30 GGN carcinomas. CONCLUSION: The GGNs are perfused dominantly by the PF regardless of its histopathology while the weight of the BF in the GGN carcinomas increases gradually during the progress of its opacification.

A simple nomogram for predicting infectious diseases in adult kidney transplantation recipients.

Objective: To investigate the risk factors of infectious diseases in adult kidney transplantation recipients and to establish a simple and novel nomogram to guide the prophylactic antimicrobial therapy. Methods: Patients who received kidney transplantation between January 2018 and October 2021 were included in the study and were divided into a training and a testing set at a 1:1 ratio. Risk factors correlated to infectious diseases were selected using a Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The prediction model was built by incorporating the variables selected by the LASSO model into a logistic regression equation. Calibration curves and receiver operating characteristic (ROC) curves were also applied to assess the model calibration and discrimination. A nomogram consisting of the selected factors was established to provide individualized risks of developing infections. Decision curve analysis (DCA) was adopted to estimate the net benefit and reduction in interventions for a range of clinically reasonable risk thresholds. Results: In all, 863 adult kidney recipients were included in the study, and 407 (47.16%) of them developed infectious diseases during the 3-year follow-up period. A total of 8 variables were selected using LASSO regression and were retained for subsequent model construction and infection prediction. The area under the curve (AUC) was 0.83 and 0.81 in the training and testing sets, with high F scores of 0.76 and 0.77, sensitivity of 0.76 and 0.81, and specificity of 0.88 and 0.74, respectively. A novel nomogram was developed based on 8 selected predictors (requirement for albumin infusion, requirement for red blood cell infusion, triglyceride, uric acid, creatinine, globulin, neutrophil percentage, and white blood cells). The net benefit indicated that the nomogram would reduce unnecessary interventions at a wide range of threshold probabilities in both sets. Conclusions: Adult kidney transplantation recipients are high-risk hosts for infectious diseases. The novel nomogram consisting of 8 factors reveals good predictive performance and may promote the reasonable antimicrobial prescription. More external validations are required to confirm its effectiveness for further clinical application.

Prophylactic effect of low-dose trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia in adult recipients of kidney transplantation: a real-world data study.

OBJECTIVES: To evaluate the efficacy and safety of low-dose trimethoprim (TMP)-sulfamethoxazole (SMX) (TMP-SMX) as the primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in adult recipients of kidney transplantation. METHODS: Three kinds of prescriptions in kidney recipients were documented, including 20 mg TMP/100 mg SMX oral daily, 20 mg TMP/100 mg SMX oral every other day, and nonprophylaxis. The primary outcome was the incidence of PJP in the first 180 days of follow-up after kidney transplantation. The secondary outcomes were changes in renal and liver function. RESULTS: Among the 1469 recipients, 1066 (72.56%) received 20 mg TMP/100 mg SMX daily, 127 (8.65%) received 20 mg TMP/100 mg SMX every other day, and 276 (18.79%) did not have prophylaxis prescription. The 276 recipients in the nonprophylaxis group had 124.92 person-years of follow-up, during which PJP occurred in 29 patients, for an incidence rate of 23.21 (95% confidence interval 15.76-32.72) per 100 person-years. The TMP-SMX daily group and the TMP-SMX every other day group had 524.89 and 62.07 person-years of follow-up, respectively, with no occurrence of PJP. There was no significant difference among the three groups in changes in renal and liver function (P >0.05, respectively). A total of 111 recipients in each group were enrolled in the propensity score matching analysis. It was revealed that the 111 nonprophylaxis recipients had 51.27 person-years of follow-up and 10 PJP cases. Prophylaxis was considered effective because there was a significant difference between the three groups (P <0.001). CONCLUSION: Low-dose TMP-SMX prophylaxis significantly reduces the incidence of PJP within 6 months after kidney transplantation and has a favorable safety profile.