Background Carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a critical threat in intensive care units (ICUs), with antibiotic exposure and colonization pressure identified as key associated factors. Prior studies have analyzed these two time-varying factors as static cumulative variables, obscuring heterogeneity in temporal patterns and their joint evolution. How distinct early trajectories of these factors jointly relate to CR-GNB acquisition risk remains unclear. Methods In this prospective cohort study conducted at four ICUs in a tertiary-care center in China from March 2024 to January 2025, we enrolled consecutive patients with systematic rectal surveillance cultures. We used group-based multi-trajectory modeling to identify distinct joint trajectories of daily antibiotic exposure (dose, duration, spectrum) and colonization pressure during the first five ICU days. Continuous-time Markov multi-state models with Day-5 landmark analysis were adopted to assess associations between trajectory groups and subsequent ICU-acquired CR-GNB, adjusting for baseline and cumulative covariates. Results Among 533 patients entering the Day-5 landmark analysis, three distinct trajectory groups were identified: Low exposure/low pressure (34.1%), escalating exposure/intermediate pressure (54.4%), and high exposure/high pressure (11.4%). CR-GNB acquisition occurred in 124 patients (23.3%), with rates of 9.3%, 26.2%, and 50.8% across trajectory groups, respectively. Compared with the low-exposure trajectory, adjusted hazard ratios were 1.68 (95% confidence interval [CI] 1.24–2.28) for escalating-exposure and 2.82 (95% CI, 1.53–5.19) for high-exposure trajectories (both P < 0.001). Conclusions This study identified distinct early trajectories of antibiotic exposure and colonization pressure that were associated with differential CR-GNB acquisition risk. This trajectory-based framework for early association-based risk stratification may inform targeted prevention strategies, but external validation is required before clinical implementation. Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR2400081352. Registered 28 February 2024.

OBJECTIVE:This study investigated the clinical characteristics of hospital-acquired Elizabethkingia meningoseptica (EM) colonization/infection and its antimicrobial resistance profiles, to provide evidence-based references for EM infection prevention, control, and treatment. METHODS:A retrospective analysis was performed on the clinical data and antimicrobial susceptibility results of 49 patients with hospital-acquired EM colonization/infection at the Hongqiao Campus of Huashan Hospital Affiliated to Fudan University between 2021 and 2024. Clinical characteristics, specimen sources, antimicrobial susceptibility, and outcomes were summarized, and clinical features were compared between the EM infection and colonization groups. RESULTS:Fifty hospital-acquired EM strains were included, mainly from the ICU (56.1%) and respiratory tract (88.0%). Patients were mostly male, with prolonged hospitalization, multiple comorbidities (pulmonary infection 91.8%, anemia 81.6%), combined antimicrobial use (91.8%) and invasive procedures (100% with indwelling urinary catheters). EM was highly susceptible to TMP-SMX, doxycycline, and minocycline, but resistant to most β-lactams, carbapenems, and aminoglycosides. Overall all-cause mortality was 20.4%. Forty-one percent of patients of patients were colonized without progression to infection. Only immunosuppressant use was an independent risk factor for EM infection (OR=5.571, 95%CI:1.42-21.86, P=0.014). CONCLUSION:Hospital-acquired EM mainly affects ICU patients with severe comorbidities, prolonged hospitalization, and invasive procedures, with profound intrinsic resistance. TMP-SMX, doxycycline, and minocycline are preferred therapeutic options. EM colonization does not always progress to infection but may facilitate nosocomial transmission. Immunosuppressant use may correlate with the clinical presentation of EM, with underlying mechanisms requiring further exploration. Early identification and isolation of colonized patients are critical for EM infection control.

Background While antibiotic exposure is a known key risk factor for acquiring Carbapenem-resistant Gram-negative bacteria (CR-GNB) in the ICU, the independent contributions and relative importance of its core dimensions—spectrum, dose, and duration—remain poorly understood. This study aimed to clarify these specific relationships to inform the optimization of antibiotic stewardship strategies. Methods We prospectively enrolled consecutive adult patients admitted to 4 ICUs at a university hospital between March 2024 and January 2025. Patients were screened for CR-GNB upon admission and weekly. Antibiotic exposure was quantified by spectrum (Antibiotic Spectrum Index per antibiotic day [ASI]), dose (Defined Daily Doses [DDDs]), and duration (Length of Therapy [LOT]). The primary outcome was ICU-acquired CR-GNB. We used interval-censored Cox regression to assess associations. Restricted cubic splines were used to explore potential non-linear relationships, and relative importance analysis was performed to compare the impact of the exposure metrics. Results Overall, 151 of 422 patients (35.8%) acquired CR-GNB during their ICU stay, with a median follow-up of 12.0 days (interquartile range, 8.0–17.0). ASI per antibiotic day was independently associated with an increased risk of ICU-acquired CR-GNB (adjusted Hazard Ratio [aHR] per 1-unit increase, 1.14; 95% Confidence Interval [CI] 1.09–1.19; P < 0.001), exhibiting a non-linear J-shaped relationship ( P for nonlinearity = 0.027). In contrast, after full adjustment, DDDs were not significantly associated with CR-GNB acquisition (aHR per 1-unit increase, 0.89; 95% CI 0.69–1.15; P = 0.374), despite displaying a non-linear inverted U-shaped relationship ( P for nonlinearity < 0.001). Similarly, LOT showed no significant independent association in the fully adjusted model (aHR per 1-day increase, 1.03; 95% CI 0.97–1.11; P = 0.214), although a non-linear trend suggested increasing risk with longer durations ( P for nonlinearity < 0.001). Relative importance analysis identified ASI per antibiotic day as the most critical factor ( P < 0.001), significantly outweighing both DDDs and LOT ( P > 0.05). Conclusions This study identifies ASI per antibiotic day as the principal independent risk factor for ICU-acquired CR-GNB, significantly outweighing the adjusted impact of DDDs or LOT. Therefore, prioritizing antibiotic spectrum optimization is crucial for stewardship strategies targeting CR-GNB prevention in the ICU. Trial registration Chinese Clinical Trial Registry Identifier ChiCTR2400081352. Registered 28 February 2024.

[Objective]To analyze the distribution,drug resistance characteristics,and changing trends of Acinetobacter baumannii(AB)isolated from environmental surfaces and healthcare workers'hands in a grade Ⅱ level A general hospital in Xuhui District of Shanghai from 2018 to 2023,and to provide reference for infection control in the hospital.[Methods]Environmental samples were collected quarterly from critical surfaces and healthcare workers'hands in the intensive care unit(ICU),geriatrics,and respiratory departments from 2018 to 2023.Clinical isolates were obtained from all patients with AB infections in ICU,geriatrics,respiratory department,rehabilitation department,infectious diseases department,emergency department,cardiology department,and orthopedics of the hospital from 2018 to 2023.Retrospective analyses were performed on AB detection rates,strain origins,resistance rates to commonly used antimicrobial agents,and resistance gene features,comparing the antimicrobial resistance between clinically isolated strains and environmentally isolated strains.[Results]From 2018 to 2023,a total of 1 416 samples were collected from the hospital and a total of 272 strains of AB were detected,with a positive detection rate of 19.21%.The detection rate gradually decreased year-on-year(χ2trend=45.290,P<0.001).The majority of samples originated from patient-contacted items(34.56%,94/272),followed by shared items(26.84%,73/272)and healthcare worker-contacted items(15.07%,41/272).From 2018 to 2023,the resistance rate of AB on environmental surfaces and healthcare workers'hands to commonly tested antibiotics in the hospital ranged from 10%to 40%.The resistance rates to cefotaxime(42.52%)and piperacillin(38.58%)were relative high,while the resistance to polymyxin E(1.57%),polymyxin B(2.36%),and doxycycline(3.94%)maintained low.The annual fluctuations in resistance to cefotaxime,piperacillin,ceftriaxone,tobramycin,doxycycline,minocycline and cotrimoxazole were statistically significant(all P<0.05).There were statistically significant differences in the resistance of clinical and environmental isolates to ampicillin/sulbactam,cefepime,ceftazidime,subamphetamine,meropenem,piperacillin,aztreonam,gentamicin,tobramycin,minocycline,ciprofloxacin,levofloxacin,and cotrimoxazole in the hospital from 2018 to 2023(all P<0.05).The resistance rate of clinical isolates was generally high,especially to β-lactam and quinolone drugs,which were mostly above 80%[such as cefepime(93.86%),cefotaxime(97.37%),imipenem(98.25%),and ciprofloxacin(99.12%)].The resistance rate of environmental isolated strains to similar antibiotics was relatively lower,mostly concentrated at 10%-30%.The whole-genome sequencing of 34 carbapenem-resistant Acinetobacter baumannii(CRAB)strains isolated from the hospital environment in 2023 revealed that the main resistance mechanism was overexpression of efflux pumps(51.97%),followed by changes in target sites(32.46%).Among the 34 CRAB strains,carbapenem resistance genes OXA-23 and OXA-51 were detected in 6 strains(17.65%),while genes such as KPC,IMP,VIM,and SIM were not detected.[Conclusion]From 2018 to 2023,AB in the hospital environment exhibited high resistance rates to certain antimicrobial agents and carried multiple resistance genes,indicating a potential transmission risk.It is necessary to further strengthen bacterial resistance monitoring and hospital infection control,and use antibiotics reasonably.

Background:Carbapenem-resistant infections are increasing, posing a serious public health threat. This study investigates the relationship between carbapenem-resistant Gram-negative (CRGN) organisms and antimicrobial consumption in a tertiary hospital from 2011 to 2023, particularly focusing on carbapenem consumption. Methods:A retrospective analysis was conducted on quarterly data from 2011 to 2023 at the First Affiliated Hospital of Xi'an Jiaotong University (FAHXJU), covering antibiotic consumption and the incidence rates of carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Enterobacter coli (CREC), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Antibiotics consumption was expressed as the number of defined daily doses/1000 patient-days (DDDs/1000 PDs). Trends and correlations assessed by regression and Spearman tests. Results:First, the total antibiotics consumption remained stable (β = 0.039, P ≥ 0.05). However, the consumption of carbapenems significantly increased (P < 0.05), from the lowest 7.91 to the highest 57.96 DDDs/1000 PDs. Second, the resistance rates of CRKP (β = 0.364) and CREC (β = 0.035) showed an upward trend (P < 0.05). While the resistance rates of CRAB (β = -0.096, P ≥ 0.05) and CRPA (β = -0.078, P ≥ 0.05) remained stable, a positive correlation was found between carbapenem use and resistance rates of CRKP and CREC (P < 0.05). Conclusion:Despite stable overall antibiotic use, carbapenem consumption has increased substantially and is significantly correlated with the rising resistance of CRKP and CREC. Targeted antimicrobial stewardship and empirical therapy optimization are urgently needed, with future multicenter studies are required to validate these findings.

BACKGROUND:Observational studies have previously shown a potential link between psycho-emotional disorders, such as mood swings, highly strung, anxious feelings, and gastroesophageal reflux disease (GERD). However, the credibility of these associations could be influenced by various confounding factors. Consequently, our study sought to employ a Mendelian randomization (MR) approach to elucidate a potential causal relationship between psycho-emotional disorders and GERD.METHOD:Information on independent genetic variants linked to mood swings, highly strung, and anxious feelings was gathered from European populations participating in the IEU Open GWAS research. The FinnGen Consortium provided the genome-wide association study (GWAS) summary statistics for GERD. Our analysis employed the inverse variance weighted (IVW) method under the random effects model as the main analytical method. To further bolster our findings, we employed the weighted median and MR Egger methods. In addition, we conducted a series of sensitivity analyses.RESULTS:Our study supports the existence of a causal relationship between psycho-emotional disorders and GERD. Mood swings, highly strung, and anxious feelings adversely affected GERD risk (mood swings: OR 2.21, 95% CI 1.19-5.59, p = 3.09 × 10-2; highly strung: OR 5.63, 95% CI 1.77-17.94, p = 3.42 × 10-3; anxious feelings: OR 2.48, 95% CI 1.08-4.33, p = 2.89 × 10-2).CONCLUSION:This Mendelian randomization study provides robust support for the notion that mood swings, highly strung and anxious feelings, are associated with an increased risk of developing GERD.

OBJECTIVES:Carbapenem-resistant Klebsiella pneumoniae (CRKP) pose an emerging clinical threat. We investigated its introduction and transmission in a new hospital, evaluating the effect of whole-genome sequencing (WGS) as an infection control measure. METHODS:Based on WGS of identified K. pneumoniae (Kpn) strains, a prospective molecular epidemiological study of nosocomial transmission of CRKP in a newly established Chinese hospital was conducted. RESULTS:Between September 2018 and August 2020, 206 Kpn strains were isolated, including 180 CRKP, from 152 patients. The first imported and nosocomial transmission cases were recorded in December 2018 and April 2019, respectively. Overall, 22 nosocomial transmission clusters involving 85 patients were identified, among which 5 were large-size clusters comprising 5-18 patients. Index cases of the large-size clusters were more likely associated with lower Glasgow Coma Scale scores than those of small-size clusters. Furthermore, results of multivariable logistic regression indicated that Kpn tended to transmit more among patients in the ICU [adjusted odds ratio (aOR) = 4.96, 95% confidence interval (CI) 1.97-13.47] and those infected with a ST11 strain (aOR = 8.04, 95% CI 2.51-29.53) or tetracycline-resistant strains (aOR = 17.63, 95% CI 6.32-57.32). However, transmission was less likely in strains bearing the rmpA gene (aOR = 0.12, 95% CI 0.03-0.37). The rate of nosocomial CRKP cases decreased by 2.25 with the intervention of WGS-based infection control. CONCLUSIONS:Kpn transmission in the newly established hospital originated from several imported cases. Rates of nosocomial CRKP infection were reduced considerably through precise infection control measures.

Background: Rapamycin has been recommended to treat Kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP), but the underlying mechanism of the clinical effect has not been established. Therefore, we determined rapamycin cytotoxicity on KHE cells in vitro and the underlying mechanism. Methods: KHE primary cells were derived from a tumor specimen and treated with rapamycin. Immunofluorescence was applied to identify the cells. Cell viability was measured using the Cell Counting Kit-8 (CCK-8) assay. Cell cycle and apoptosis were assessed using flow cytometry (FCM). Western blots (WB) were performed to determine phosphorylation of mammalian target of rapamycin (mTOR), p70 S6 kinase (S6K1), and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), as well light chain 3 (LC3) expression. Results: Rapamycin inhibited the growth of KHE primary cells in a dose- and time-dependent manner. Cell cycle progression was arrested in the G0/G1 phase and apoptosis was induced. WB results showed that LC3-II/I expression was significantly elevated in KHE primary cells treated with rapamycin, while the level of p-mTOR, p-S6K1, and p-4E-BP1 expression was reduced. LC3 fluorescent spots were increased in the rapamycin treatment group. Conclusions: Rapamycin inhibited KHE primary cell proliferation, induced apoptosis and autophagy, and blocked the mTOR signaling pathway. (C) 2022 Elsevier Inc. All rights reserved.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Long non-coding RNA LINC01296 has been shown to predict the invasiveness and poor outcomes of patients with NB. Our study validated its prognostic value and investigated the biological function and potential mechanism of LINC01296 regulating NB. Results illuminated that LINC01296 expression was significantly correlated with unfavorable prognosis and malignant clinical features according to the public NB database. We identified that silencing LINC01296 repressed NB cell proliferation and migration and promoted apoptosis. Moreover, LINC01296 knockdown inhibited tumor growth in vivo. The opposite results were observed through the dCas9 Synergistic Activation Mediator System (dCas9/SAM) activating LINC01296. Mechanistically, we revealed that LINC01296 could directly bind to nucleolin (NCL), forming a complex that activated SRY-box transcription factor 11 (SOX11) gene transcription and accelerated tumor progression. In conclusion, our findings uncover a crucial role of the LINC01296-NCL-SOX11 complex in NB tumorigenesis and may serve as a prognostic biomarker and effective therapeutic target for NB.

The aim of this paper is to explore the characteristics of the use of verbal collocations in English, to compare the use of verbal collocations in the English translation and the original English text, and then to compare and analyse the characteristics of the choice of verbal collocations in the English text. In this paper, we take bilateral marked causative complex sentences as the object of study and use deep learning methods to automatically explore the implied features of complex sentences while incorporating the significant knowledge of relational words in linguistic research. The experimental results achieved an F1 value of 92.13%, which is better than that of the existing comparison models, demonstrating the effectiveness of the method.

Purpose: Carbapenem-resistant organisms (CROs) have posed a great threat to antibiotic use and induce multi-drug resistance.Contamination of the hospital environment and infection of healthcare workers (HCWs) are reported as sources of nosocomial infections.Here, we performed a comprehensive environment sampling and timely epidemiological investigation during outbreaks to investigate the role of the environment and HCWs in CRO transmission.Patients and Methods: We enrolled carbapenem-resistant organism outbreaks in ICU-1 of Huashan Hospital from January 2019 to March 2019, and ICU-2 located at west branch of Huashan Hospital from October 2019 to November 2019.Carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates were collected from the patients.We performed a real-time comprehensive environmental and HCW sampling in the two ICUs.Isolated strains from patients and the positive colonies from the screening were sent for whole-genome sequencing.Finally, phylogenetic trees were constructed.Results: CRAB and CRKP outbreaks simultaneously occurred in ICU-1; the outbreak involved 13 patients.Meanwhile, the CRKP outbreak in ICU-2 included 11 patients.Twelve out of 146 environment and HCWs samples in ICU-1 were carbapenem-resistant bacteria, including six CRKP and six CRAB strains.For ICU-2, hospital surfaces and HCWs were negative for CRKP.Phylogenetic analyses showed that CRKP strains in ICU-1 were classified into two clades: Clade 1 and Clade 2, sharing a high similarity of isolates from the environment and HCWs.The same phenomenon was observed in CRAB. Conclusion:A timely comprehensive sampling combined with genome-based investigation may aid in tracking the transmission route of and controlling the infections.The environment and HCWs could be contaminated during CRO transmission, which calls for strengthened prevention and control measures.

With the accumulation of clinical practice, sirolimus is now widely viewed as an effective agent in kaposiform hemangioendothelioma (KHE) treatment using a dose based on experience. Therefore, this retrospective research aimed to provide evidence‐based suggestions on the most appropriate dose and trough level of sirolimus. All unresectable KHE cases diagnosed at our center from January 2016 to December 2019 were included. Sirolimus monotherapy was initiated when there was no sign of Kasabach–Merritt phenomenon (KMP) at a dose of 0.8 mg/m 2 twice a day in order to keep the trough level at 5–20 ng/mL. Patients’ clinical information, tumor volume change, trough level fluctuation, and complication occurrence were all recorded. Efficacy represented by tumor shrinkage speed and safety manifested by complication grades were compared between different trough level groups (5–10 vs. 10–15 vs. >15 ng/mL). Twenty‐one patients (10 girls and 11 boys) were enrolled. There were eight patients in the 5–10 ng/mL group, seven in the 10–15 ng/mL group, and six in the more than 15 ng/mL group. Trough level over 10 ng/mL manifested better efficacy in tumor shrinkage ( t ‐test, p = 0.011) while a level over 15 ng/mL had no further benefit in efficacy ( t ‐test, p = 0.65). In addition, tumors at a central location reacted better to sirolimus ( t ‐test, p = 0.022). No significant differences were observed in complication occurrence among different concentrations, although boys seemed to be at higher risk of more severe complications (>grade II, χ 2 ‐test, p = 0.009, odds ratio = 4.52, range = 1.20–17.24). It proved to be most efficacious in the management of KHE at a trough level between 10 and 15 ng/mL. Such concentration was safe and well tolerated.

Nonhuman primates (NHPs) are widely used for investigating retroviral pathogenesis.Before experiments are conducted and breeding programs established, the animals must be judged negative for endogenous retroviruses.We developed a multiplex high-throughput detection method using multiplexed Luminex fluorescent microbeads and the xTAG system (MMxTAG).We tested three retroviral DNA detection assays for use in a single tube reaction by taking advantage of the Luminex xTAG platform.The assay showed a high sensitivity that was comparable to qPCR methods.The detection limits approached 1-10 fg/μL of plasmid DNA.We compared the specificity, efficiency and accuracy with ELISA assays and found our assay was superior in all regards.The MMxTAG performed well with clinical specimens and could selectively detect a single virus in the presence of the other two.This MMxTAG procedure can be applied to pathogen monitoring in animals and is present in a high throughput format that has low operating and development costs for protecting monkey contacts against these infectious diseases.

Background The etiology of reflux esophagitis (RE) is multi-factorial. This study analyzed the relationship of depression, anxiety, lifestyle and eating habits with RE and its severity and further explored the impact of anxiety and depression on patients’ symptoms and quality of life. Methods From September 2016 to February 2018, a total of 689 subjects at Xuanwu Hospital Capital Medical University participated in this survey. They were divided into the RE group (patients diagnosed with RE on gastroscopy, n = 361) and the control group (healthy individuals without heartburn, regurgitation and other gastrointestinal symptoms, n = 328). The survey included general demographic information, lifestyle habits, eating habits, comorbidities, current medications, the gastroesophageal reflux disease (GERD) questionnaire (GerdQ), the Patient Health Questionnaire-9 depression scale and the General Anxiety Disorder-7 anxiety scale. Results The mean age and sex ratio of the two groups were similar. Multivariate logistic regression analysis identified the following factors as related to the onset of RE ( p < 0.05): low education level; drinking strong tea; preferences for sweets, noodles and acidic foods; sleeping on a low pillow; overeating; a short interval between dinner and sleep; anxiety; depression; constipation; history of hypertension; and use of oral calcium channel blockers. Ordinal logistic regression analysis revealed a positive correlation between sleeping on a low pillow and RE severity ( p = 0.025). Depression had a positive correlation with the severity of symptoms (r s = 0.375, p < 0.001) and patients’ quality of life (r s = 0.306, p < 0.001), whereas anxiety showed no such association. Conclusions Many lifestyle factors and eating habits were correlated with the onset of RE. Notably, sleeping on a low pillow was positively correlated with RE severity, and depression was positively related to the severity of symptoms and patients’ quality of life.

BACKGROUND:Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that occurs in children. Prox1 is a specific lymphatic marker for KHE. We intended to establish a Prox1 transgenic cell line resembling KHE and investigate the mechanism of sirolimus in treating KHE.METHODS:Prox1 was stably expressed in infantile hemangioma cell HemECs. RT-qPCR and Western blot were conducted to measure the expression of target genes. CCK-8, EdU assay, and cell cycle analysis were conducted to detect cell proliferation. Wound healing and transwell assay were used to evaluate cell migration and invasion.RESULTS:Both mRNA and protein levels of Prox1, LYVE-1, Podoplanin were upregulated in Prox1+ HemECs. An acceleration of cell growth and a rise in migration and invasion were observed with Prox1 overexpression. Sirolimus inhibited cell proliferation, promoted apoptosis and led to G1 phase arrest in Prox1+ HemECs. The expression of p-mTOR, p-4EBP1, and p-P70S6K decreased and the ratio of LC-3 II/LC-3 I elevated after treatment of sirolimus.CONCLUSIONS:Stable overexpression of Prox1 in HemECs induced a lymphatic endothelial reprogramming, and enhanced aggressive biological effects, partly resembled the invasion of KHE, and could serve as a novel model for KHE. Sirolimus may block mTOR-mediated pathways and induced autophagy in KHE.

Background: Lymphatic malformations are common congenital vascular lesions. Neither surgical resection nor other surgical treatments have been found to be effective for invasive cases. Recent research has suggested that sirolimus is effective in treating complex lymphatic malformations (LMs). We aimed to evaluate the effectiveness and safety of oral sirolimus for children living with LMs in our hospital. Methods: Fifty-six cases of complex LMs treated with sirolimus were collected from Shanghai Children's Medical Centre between June 2016 and March 2019. All cases were confirmed either by pathology (44) or enhanced MRI (12). Following informed consent, sirolimus 0.8 mg/m(2) bid was administered orally to participants and maintained at a trough concentration of 10-15 ng/ml. Children's ages at diagnosis were neonate to 16 years (mean 44.3 months). All children were followed up for 5 to 30 months, with a mean of 16.8 months. Results: During the follow-up period, blood, liver and kidney function as well as disseminated intravascular coagulation was regularly reviewed in all 56 children. Enhanced MRI was regularly performed to evaluate therapeutic effects. Total effective rate (complete response or partial response) of LMs was 89.3% (50/56). No serious adverse reactions were found. Conclusion: This study suggests that sirolimus is effective and tolerable for decreasing lesions in children with complex LMs, leading to fewer and more tolerable side effects. There is no need to pursue an excision rate to reduce unnecessary operative complications since adjuvant sirolimus therapy modifies the complex LMs clinical appearance and alleviates their symptoms. Type of study: Clinical research. Level of evidence: Level IV. (C) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Gorham-Stout disease (GSD) is a rare disease characterized by bone lesions and osteolysis. Therapy usually involves surgical resection. Sirolimus (Rapamycin) is used in some patients with GSD but the efficacy and safety of Sirolimus remains unclear. We propose that Sirolimus may be a novel therapeutic for GSD and present a case and review of literature that supports this. Case presentation We presented a 1-year-old boy with GSD involving osteolysis of the right humerus with fracture of the left femur complicated by an effusion in the right pleural cavity. X-rays showed osteolysis in the right clavicle. A large pleural effusion was observed on the right-side, and the left lung was significantly compressed. X-rays also showed a fracture of the left femur. A femoral biopsy was performed that showed necrotic tissue in the cortical bone and a large number of irregularly shaped capillaries that proliferated within the necrotic tissue. Dilated lymphatic vessels were seen adjacent to the cortex, with fibrous tissue hyperplasia. We prescribed sirolimus, which is an oral mTOR inhibitor, for two consecutive years. The boy recovered well without other progressive bone lesions and participates in normal daily activities. His growth and development are the same as that of his peers. Discussion and conclusion Gorham-Stout disease is a rare and enigmatic disease characterized by the presentation of an intraosseous lymphatic anomaly (LM), which results in progressive bone resorption. Based on this case report and a literature review, we conclude that sirolimus may be an effective alternative medication for GSD.

In this letter, we present a novel ship detection method for polarimetric synthetic aperture radar (PolSAR) images. Generalized polarization relative entropy (GPRE) is proposed to measure the differences between the target and clutter in scattering mechanism, randomness, and intensity. Since it is difficult to derive a theoretical closed-form of the GPRE, we employ the kernel density estimation to model the distribution of the GPRE in ocean regions. Then, a constant false alarm rate (CFAR) ship detection method is proposed based on the estimated distribution. Experiments performed on both synthetic and real scene images demonstrate the effectiveness of the proposed method.

Clinically occurring sulfonamide resistance in gram-negative bacteria is codified by several sul genes, mostly associated with the mobilized genetic elements named integrons, and integrons are frequently found in plasmids. There are four sul genes (sul1, sul2, sul3 and sul4) that encode resistance to sulfonamides. The aim of the present study was to develop a bead-based xTAG assay for the simultaneous detection of all four sul genes and related Class 1 integrons (int1) in Escherichia coli and Salmonella isolates. The limits of detection ranged from 10 to 1000 copies/μL of input purified plasmid DNA. Forty-one bacterial isolates from clinical samples were examined using the newly developed xTAG assay and also by conventional PCR to determine the relative performance of each. The results obtained by xTAG assay showed higher detection rates and accuracy for sul genes than conventional PCR. It indicated that the xTAG-multiplex PCR is a convenient method for rapid identification of sul genes.

This study was to establish a systemic C. parapsilosis infection model in immunosuppressed ICR mice induced by cyclophosphamide and evaluate the antifungal efficiency of fluconazole. Three experiments were set to confirm the optimal infectious dose of C. parapsilosis, outcomes of infectious model, and antifungal efficiency of fluconazole in vivo, respectively. In the first experiment, comparisons of survival proportions between different infectious doses treated groups showed that the optimal inoculum for C. parapsilosis was 0.9 × 105 CFU per mouse. The following experiment was set to observe the outcomes of infection at a dose of 0.9 × 105 CFU C. parapsilosis. Postmortem and histopathological examinations presented fugal-specific lesions in multiorgans, especially in kidneys, characterized by inflammation, numerous microabscesses, and fungal infiltration. The CFU counts were consistent with the histopathological changes in tissues. Th1/Th2 cytokine imbalance was observed with increases of proinflammatory cytokines and no responses of anti-inflammatory cytokines in sera and kidneys. In the last experiment, model based evaluation of fluconazole indicated that there were ideal antifungal activities for fluconazole at dosages of 10–50 mg/kg/d. Data demonstrates that the research team has established a systemic C. parapsilosis infection model in immunosuppressed ICR mice, affording opportunities for increasing our understanding of fungal pathogenesis and treatment.