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Abstract The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

C32H44O6, monoclinic, P21 (no. 4), a = 12.2561 Å, b = 10.3674(4) Å, c = 23.3835(8) Å, β = 98.463°, V = 2938.85(19) Å3, Z = 2, Rgt(F) = 0.0602, wRref(F2) = 0.1537, T = 273(2) K.

Abstract Objective The exact mechanism and target molecules of liver fibrosis have remained largely elusive. Here, we investigated the role of long noncoding RNA Gm9866(lncRNA-Gm9866) on liver fibrosis. Methods The transcription of lncRNA-Gm9866 in activated cells and mouse fibrotic livers was determined by quantitative polymerase chain reaction (qRT-PCR). The effects of lentivirus-mediated knockdown or overexpression of lncRNA-Gm9866 in liver fibrosis were examined in vitro and in vivo. Furthermore, bioinformatics analysis, cell samples validation, fluorescence in situ hybridization (FISH) co-localization, RNA binding protein immunoprecipitation (RIP), actinomycin D test and Western blot (WB) were carried out to explore the potential mechanism of lncRNA-Gm9866. Results The expression of α-smooth muscle actin (α-SMA), Collagen I (COL-1) and lncRNA-Gm9866 were significantly increased in tissues and cells. Overexpressing lncRNA-Gm9866 promoted the activation of hepatic stellate cells (HSCs). Silencing lncRNA-Gm9866 inhibited the activation of HSCs and transforming growth factor-β1 (TGFβ1) induced fibrosis. Overexpressing lncRNA-Gm9866 promoted hepatocytes (HCs) apoptosis and the expression of pro-fibrogenic genes, inhibited the proliferation and migration of HCs. Knockdown of lncRNA-Gm9866 inhibited the apoptosis of HCs, the expression of pro-fibrogenic genes, TGFβ1 induced fibrosis and the occurrence of carbon tetrachloride (CCl4)-induced liver fibrosis, and promoted the proliferation and migration of HCs. Mechanistically, lncRNA-Gm9866 may directly bine with Fam98b. Silencing Fam98b in stably overexpressing lncRNA-Gm9866 cell lines reversed the increase of pro-fibrogenic genes and pro-apoptotic genes, fibrosis related pathway protein TGFβ1, Smad2/3, p-Smad2/3 and Notch3 induced by overexpressing lncRNA-Gm9866. Conclusions LncRNA-Gm9866 may regulate TGFβ/Smad and Notch pathways by targeting Fam98b to regulate liver fibrosis. LncRNA-Gm9866 may be a new target for diagnosis and treatment of liver fibrosis.

The heterogeneity of natural rocks complicates the study of carbon sequestration within these materials and raises concerns about the reproducibility of experimental results. Consequently, identifying appropriate rock-like materials has become critical. This research examined the impact of various factors—humidity, binder content, curing period, and cold pressure—on the bond strength of magnesium oxychloride cement (MOC) through orthogonal testing. The tests utilized a molar ratio of MgO to MgCl2-6H2O to H2O of 7:1:18. Both X-ray diffraction (XRD) and scanning electron microscopy (SEM) were employed to analyze the hydration reactions of MOC and to explore the correlation between the microstructure of the SiO2-MgO-MgCl2 system and its bonding characteristics. The findings indicated that a 5% relative humidity enhances the 7-day bond strength of MOC. Moreover, increasing the curing humidity to 60% relative humidity supports the ongoing hydration of the strength-contributing phases. A binder content ranging from 15% to 25% proved optimal, yielding samples with superior strength and stiffness. While cold pressing initially enhances the bonding properties of MOC, solution loss during the process adversely affects its long-term bonding characteristics. From a mechanical standpoint, the silica-magnesium oxide-magnesium chloride system demonstrates exceptional early strength and resilience, positioning it as a promising rock-like material system.

Quality makers (Q-markers) are pivotal for the standardization of quality control for traditional Chinese medicine (TCM) drugs. However, it’s a great challenge to identify the Q-markers of TCM drugs especially for TCM formulas. This study was designed to provide a method to discover Q-markers of TCM formulas and applied to identify the Q-markers responsible for the anti-cholestatic effect of Danning tablet (DNT), a TCM formulae consisting with seven herbal ingredients. In this study, the anti-cholestatic effect of DNT was evaluated in mice with cholestasis induced by α-naphthyl isothiocyanate (ANIT). An untargeted metabolomic profiling were performed using serum and liver samples of mice. Xenobiotics derived from DNT and endogenous compounds responsible for the anti-cholestatic effect of DNT were screened by statistical analysis and the Q-markers of DNT were illustrated, followed by predicting the potential targets and mechanisms via network pharmacology study. DNT exhibited a protective effect against liver injury in mice with ANIT-induced cholestasis. Three endogenous compounds, namely taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and glycocholic acid (GCA), were identified as the endogenous markers responsible for the anti-cholestatic effect of DNT. By setting a cutoff value of the correlation co-efficient at 0.8, 6 promising Q-markers, including luteolin, kaempferol, apigenin, emodin, luteolin-7-glucoside, and 5,4′-dihydroxy-3,6,7,8,3′-pentamethoxyflavone, were screened out. These Q-markers were stably existed in DNT and predicted to be highly active in treating cholestasis. This study established a pipeline to screen out the potential Q-markers of TCM formulas and 6 key Q-markers responsible for the anti-cholestatic effect of DNT were identified.

With the development of underground rail transit, the concept of intelligent tunnel construction has been proposed and promoted. High-quality networking during tunnel construction is a prerequisite for this, making it highly urgent to establish networking during tunnel construction. When studying intra-tunnel networking, it is necessary to consider the propagation characteristics of radio waves in the tunnel. In this paper, according to the actual needs of engineering in tunnel construction and the characteristics of tunnel scenes, an improved ray tracing method is proposed, which considers the type and installation position of antennas, transceiver frequency band and power in channel modeling, and proposes a field strength calculation method under different coordinate systems according to the characteristics of straight and curved segments during tunnel construction. In addition, the propagation characteristics of radio waves in dynamic tunnel construction scenarios are quantitatively analyzed. In this paper, by establishing antenna diagram, two-dimensional and three-dimensional models of tunnels, the computer simulation method is applied to compare with the improved algorithm, and the results have good consistency, in addition, the improved algorithm does not require a lot of modeling work in the early stage, and has high applicability and portability. Not only that, this paper also makes actual measurements of the subway under construction in Zhengzhou, China in different scenarios, and verifies the effectiveness of the method.

We aimed to determine the molecular characteristics of carbapenem-resistant Pseudomonas aeruginosa strains 18081308 and 18083286, which were isolated from the urine and the sputum of two Chinese patients, respectively. Additionally, we conducted a comparative analysis between Tn6411 carrying blaIMP-1 in strain 18083286 and transposons from the same family available in GenBank. Bacterial genome sequencing was carried out on strains 18081308 and 18083286 to obtain their whole genome sequence. Average nucleotide identity (ANI) was used for their precise species identification. Serotyping and multilocus sequence typing were performed. Furthermore, the acquired drug resistance genes of these strains were identified. The carbapenem-resistant P. aeruginosa strains isolated in the present study were of sequence type ST865 and serotype O6. They all carried the same resistance genes (aacC2, tmrB, and blaIMP-1). Tn6411, a Tn7-like transposon carrying blaIMP-1, was found in strain 18083286 by single molecule real time (SMRT) sequencing. We also identified the presence of this transposon sequence in other chromosomes of P. aeruginosa and plasmids carried by Acinetobacter spp. in GenBank, indicating the necessity for heightening attention to the potential transferability of this transposon.

This review discusses the application scenarios of the machine learning-supported performance prediction and the optimization efficiency of tunnel boring machines (TBMs). The rock mass quality ratings, which are based on the Chinese code for geological survey, were used to provide “labels” suitable for supervised learning. As a result, the generation of machine prediction for rock mass grades reasonably agreed with the ground truth documented in geological maps. In contrast, the main operational parameters, i.e., thrust and torque, can be reasonably predicted based on historical data. Consequently, 18 collapse sections of the Yinsong project have been successfully predicted by several researchers. Preliminary studies on the selection of the optimal penetration rate and cost were conducted. This review also presents a summary of the main achievements in response to the initiatives of the Lotus Pool Contest in China. For the first time, large and well-documented TBM performance data has been shared for joint scientific research. Moreover, the review discusses the technical problems that require further study and the perspectives in the future development of intelligent TBM construction based on big data and machine learning.

This review summarizes the research outcomes and findings documented in 45 journal papers using a shared tunnel boring machine (TBM) dataset for performance prediction and boring efficiency optimization using machine learning methods. The big dataset was collected during the Yinsong water diversion project construction in China, covering the tunnel excavation of a 20 km-section with 199 items of monitoring metrics taken with an interval of one second. The research papers were the result of a call for contributions during a TBM machine learning contest in 2019 and covered a variety of topics related to the intelligent construction of TBM. This review comprises two parts. Part I is concerned with the data processing, feature extraction, and machine learning methods applied by the contributors. The review finds that the data-driven and knowledge-driven approaches in extracting important features applied by various authors are diversified, requiring further studies to achieve commonly accepted criteria. The techniques for cleaning and amending the raw data adopted by the contributors were summarized, indicating some highlights such as the importance of sufficiently high frequency of data acquisition (higher than 1 second), classification and standardization for the data preprocessing process, and the appropriate selections of features in a boring cycle. The review finds that both supervised and unsupervised machine learning methods have been utilized by various researchers. The ensemble and deep learning methods have found wide applications. Part I highlights the important features of the individual methods applied by the contributors, including the structures of the algorithm, selection of hyperparameters, and model validation approaches.

Byline: Jiaying. Qiu, Jiajia. Gu, Shiyi. Chang, Zhenyu. Zhang, Haibo. Zhang, Tianqing. Liu, Jing. Jie, Jinhuan. Wei Background: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions [...]

Abstract In hadron spectrum physics, the partial wave analysis is a primary method used to extract properties of hadronic resonances. The covariant orbital-spin coupling scheme holds unique advantages over other partial wave methods due to its Lorentz covariant form and determined orbital-spin quantum numbers. This paper presents a general form of the covariant orbital-spin coupling scheme based on the irreducible tensor of the homogeneous proper Lorentz group and its little groups. A systematic procedure for constructing partial wave amplitude in a Lorentz covariant way is provided, which can be applied to both massive and massless particles. Specific examples are also included.

Abstract Aim The aim was to examine the effect of role overload, work addiction and leader‐member exchange on missed nursing care. Design A cross‐sectional study. Methods Chinese registered nurses from five Sichuan province public hospitals were studied from March 2022–May 2022. The measurements were derived from a questionnaire on role overload, work addiction, missed nursing care, leader‐member exchange and a sociodemographic datasheet. Descriptive statistics and inferential statistics were conducted (N = 403). Results Role overload was associated with missed nursing care, and work addiction played a mediation role. Leader‐member exchange negatively predicted work addiction and played a moderating role between role overload and work addiction. The effect of role overload on work addiction was attenuated when the level of leader‐member exchange was higher. Promoting leader‐member exchange could mitigate how role overload undermines missed nursing care.

Abstract Background Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients’ lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. Methods Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. Results Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Conclusion This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

ObjectiveCognitive dysfunction is common in insulinoma patients, but the underlying neural mechanisms are less well understood. This study aimed to explore the alterations of intra- and inter-network connectivity patterns associated with patients with insulinoma.MethodsResting-state fMRI were acquired from 13 insulinoma patients and 13 matched healthy controls (HCs). Group Independent component analysis (ICA) was employed to capture the resting-state networks (RSNs), then the intra- and inter-network connectivity patterns, were calculated and compared. Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function. The relationship between connectivity patterns and MoCA scores was also examined.ResultsInsulinoma patients performed significantly worse on MoCA compared to HCs. The intra-network connectivity analysis revealed that patients with insulinoma showed decreased connectivity in the left medial superior frontal gyrus within anterior default mode network (aDMN), and decreased connectivity in right lingual gyrus within the visual network (VN). The intra-network connectivity analysis showed that patients with insulinoma had an increased connectivity between the inferior-posterior default mode network (ipDMN) and right frontoparietal network (rFPN) and decreased connectivity between the ipDMN and auditory network (AUN). There was a significant negative correlation between the ipDMN-rFPN connectivity and MoCA score.ConclusionThis study demonstrated significant abnormalities in the intra- and inter-network connectivity in patients with insulinoma, which may represent the neural mechanisms underlying the cognitive impairment in insulinoma patients.

ABSTRACT Vibrio parahaemolyticus is a marine bacterium coming from estuarine environments, where the migratory birds can easily be colonized by V. parahaemolyticus. Migratory birds may be important reservoirs of V. parahaemolyticus by growth and re-entry into the environment. To further explore the spreading mechanism of V. parahaemolyticus among marine life, human beings, and migratory birds, we aimed to investigate the characteristics of the genetic diversity, antimicrobial resistance, virulence genes, and a potentially informative gene marker of V. parahaemolyticus isolated from migratory birds in China. This study recovered 124 (14.55%) V. parahaemolyticus isolates from 852 fecal and environmental (water) samples. All of the 124 strains were classified into 85 known sequence types (STs), of which ST-2738 was most frequently identified. Analysis of the population structure using whole-genome variation of the 124 isolates illustrated that they grouped into 27 different clonal groups (CGs) belonging to the previously defined geographical populations VppX and VppAsia. Even though these genomes have high diversity, an extra copy of tRNA-Gly was presented in all migratory bird-carried V. parahaemolyticus isolates, which could be used as a potentially informative marker of the V. parahaemolyticus strains derived from birds. Antibiotic sensitivity experiments revealed that 47 (37.10%) isolates were resistant to ampicillin. Five isolates harbored the plasmid-mediated quinolone resistance (PMQR) gene qnrD, which has not previously been identified in this species. The investigation of antibiotic resistance provides the basic knowledge to further evaluate the risk of enrichment and reintroduction of pathogenic V. parahaemolyticus strains in migratory birds. IMPORTANCE The presence of V. parahaemolyticus in migratory birds' fecal samples implies that the human pathogenic V. parahaemolyticus strains may also potentially infect birds and thus pose a risk for zoonotic infection and food safety associated with re-entry into the environment. Our study firstly highlights the extra copy of tRNA as a potentially informative marker for identifying the bird-carried V. parahaemolyticus strains. Also, we firstly identify the plasmid-mediated quinolone resistance (PMQR) gene qnrD in V. parahaemolyticus. To further evaluate the risk of enrichment and reintroduction of pathogenic strains carried by migratory birds, we suggest conducting estuarine environmental surveillance to monitor the antibiotic resistance and virulence factors of bird-carried V. parahaemolyticus isolates.

AIM: To demonstrate the feasibility of mesenchymal stem cell (MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxia-inducible factor-1α small interfering RNA (HIF-1α siRNA) between MSCs and retinal pigment epithelial cells (RPE) under hypoxia environment. METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α siRNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) through the water-in-oil-in-water (w/o/w) multiple emulsion technique. The effect of PLGA-NPs uptake on the expression of HIF-1α mRNA was tested in RPE cells by real-time quantitative polymerase chain reaction (qPCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α siRNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using qPCR at the time points 24h, 3d, and 7d. RESULTS: The average diameter of PLGA-NPs loaded with HIF siRNA was 314.1 nm and the zeta potential was -0.36 mV. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α siRNA can effectively reduce the expression of HIF-1α mRNA up to 7d in RPE (0.63±0.05 at 7d, P

Abstract Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar–Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1–2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL. Trial registration: chictr.org.cn number, ChiCTR1900023309.

This paper addresses the significance of preprocessing big data collected during a tunnel boring machine (TBM) excavation before it is used for machine learning on various TBM performance predictions. The research work is based on two water diversion tunneling projects that cover 29.52 km and 17 051 boring cycles. It has been found that the penetration rate calculated from the raw measured penetration distances exhibits more random behavior owing to their percussive and vibratory behavior of the cutterhead. A moving average method to process the negative instantaneous velocities and a noise reduction filter to deal with signals with abnormal frequencies have been recommended. An index called the drilling efficiency index is introduced to assess the relationships between the mechanical parameters in a boring cycle, whose linear regression coefficient R2 is taken for a preliminary investigation of possible problems requiring preprocessing. The research work defines the irrelevant data whose errors are caused by human or mechanical mistakes, and therefore should be cleaned or amended. These irrelevant data can be divided into five categories: (1) premature cycles, (2) sensor defects, (3) mechanical defects, (4) human interruption, and (5) missing files. A program TBM-Processing has been coded for the recognition and classification of these categories. PDF books generated by the program have been uploaded at GitHub to encourage discussions, collaboration, and upgrading of the data processing work with our peers.

The limitations of current medications for treating rheumatoid arthritis (RA) emphasize the urgent need for the development of new drugs. This study aimed to investigate the potential anti-RA mechanism of amygdalin using tandem mass tag (TMT)-based quantitative proteomics technology. First, the anti-RA activity of amygdalin was evaluated in a Complete Freund’s adjuvant (CFA)-induced rat model. Then, the roles and importance of proteins in the extracted rat joint tissue were evaluated using TMT-based quantitative proteomics technology. A bioinformatics analysis was used to analyze differentially abundant proteins (DAPs). A proteomics analysis identified 297 DAPs in the amygdalin group compared with the model group, of which 53 upregulated proteins and 51 downregulated proteins showed opposite regulatory trends to the DAPs produced after modeling. According to enrichment analyses of the DAPs, the signaling pathways with a high correlation degree were determined to be the complement and coagulation cascades. Furthermore, western blotting and molecular docking were used to further validate the key node proteins, e.g., complement C1s subcomponent (C1s), component C3 (C3) and kininogen 1 (Kng1). These results suggest that amygdalin may be a promising agent for treating RA by regulating the complement and coagulation cascades.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a serious problem in hospitals worldwide. We monitored a tertiary hospital in Changchun, Jilin Province, China, and found that CRKP was the major species among the carbapenem-resistant isolates in sewage. Subsequently, we evaluated the drug susceptibility, resistance genes, virulence genes, outer pore membrane protein-related genes (OmpK35 & OmpK 36), multi-locus sequence typing and replicons, biofilm formation capabilities, and resistance to chlorine-containing disinfectants among KP isolates. Identification of drug sensitivity, multiple resistance profiles were observed including 77 (82.80%) multidrug resistant (MDR), 16 (17.20%) extensive drug resistant (XDR). Some antibiotic resistance genes were detected, the most prevalent carbapenemase gene was blaKPC, and 16 resistance genes were associated with other antibiotics. In addition, 3 (3.23%) CRKP isolates demonstrated loss of OmpK-35 and 2 (2.15%) demonstrated loss of OmpK-36. In the detection of multi-locus sequence typing (MLST), 11 ST11 isolates carried virulence genes. The most common replicon type was IncFII. Biofilm-forming capabilities were demonstrated by 68.8% of the isolates, all of which were resistant to chlorine-containing disinfectants. The results of the study showed that antibiotic-resistant isolates, especially CRKP, could resist disinfectants in hospital wastewater, and improper treatment of hospital wastewater may lead to the spread of drug-resistant bacteria and their genes. Thus, these bacteria must be eliminated before being discharged into the municipal sewage system.

Objective: The dysregulation of ribosome biogenesis is associated with the progression of numerous tumors, including hepatocellular carcinoma (HCC). Small nucleolar RNAs (snoRNAs) regulate ribosome biogenesis by guiding the modification of ribosomal RNAs (rRNAs). However, the underlying mechanism of this process in HCC remains elusive. Methods: RNA immunoprecipitation and sequencing were used to analyze RNAs targeted by ribosome proteins. The biological functions of SNORA23 were examined in HCC cells and a xenograft mouse model. To elucidate the underlying mechanisms, the 2′-O-ribose methylation level of rRNAs was evaluated by qPCR, and the key proteins in the PI3K/Akt/mTOR pathway were detected using Western blot. Results: Twelve snoRNAs were found to co-exist in 4 cancer cell lines using RPS6 pull-down assays. SNORA23 was downregulated in HCC and correlated with the poor prognoses of HCC patients. SNORA23 inhibited the proliferation, migration, and invasion of HCC cells both in vitro and in vivo. We also found that SNORA23 regulated ribosome biogenesis by impairing 2′-O-ribose methylation of cytidine4506 of 28S rRNA. Furthermore, SNORA23, which is regulated by the PI3K/Akt/mTOR signaling pathway, significantly inhibited the phosphorylation of 4E binding protein 1. SNORA23 and rapamycin blocked the PI3K/AKT/mTOR signaling pathway and impaired HCC growth in vivo. Conclusions: SNORA23 exhibited antitumor effects in HCC and together with rapamycin, provided a promising therapeutic strategy for HCC treatment.

ObjectiveTo precisely determine the species of a carbapenem-resistant Pseudomonas strain 1809276 isolated from the urine of a Chinese patient and analyze its integrative and conjugative element (ICE) 1276 formation mechanism.MethodsSingle-molecule real-time (SMRT) sequencing was carried out on strain 18091276 to obtain the complete chromosome and plasmid (pCN1276) sequences, and average nucleotide identity (ANI) was used for precise species identification. The ICEs in GenBank with the same integrase structure as ICE 1276 were aligned. At the same time, the transfer ability of blaIMP−1 and the antibiotic sensitivity of Pseudomonas juntendi 18091276 were tested.ResultsThis bacterium was P. juntendi, and its drug resistance mechanism is the capture of the accA4' gene cassette by the Tn402-like type 1 integron (IntI1-blaIMP−1) to form In1886 before its capture by the ΔTn4662a-carrying ICE 1276. The acquisition of blaIMP−1 confers carbapenem resistance to P. juntendi 18091276.ConclusionThe formation of blaIMP−1-carrying ICE 1276, its further integration into the chromosomes, and transposition and recombination of other elements promote bacterial gene accumulation and transmission.

The synchronous reluctance motor (SynRM) has significant nonlinear characteristics due to the problems of magnetic saturation and cross-coupling and the poor adaptability of the general controller to parameter changes seriously affects the control performance of the motor. In order to solve the above problems, this paper proposed a control system for the SynRM with a brain emotion controller based on empirical information to solve the motor control problem of magnetic saturation. Firstly, the nonlinear mathematical model of the SynRM considering magnetic saturation is established by introducing the magnetic saturation parameter. Secondly, the sensory input function and emotional cue function based on systematic error are given and the vector control system of the SynRM considering magnetic saturation is designed. The influence of the parameters and the learning rate of the brain emotional learning based intelligent controller (EI-BELBIC) on the adjustment range of the controller parameters is studied. Then the SynRM is controlled under different working conditions and the control effect is observed. The results show that the designed vector control system of the SynRM based on EI-BELBIC has strong reliability, accurate control, rapid response, and strong anti-interference ability under magnetic saturation.

Laboratory medicine plays an important role in clinical diagnosis. However, no laboratory‐based artificial intelligence (AI) diagnostic system has been applied in current clinical practice due to the lack of robustness and interpretability. Although many attempts have been made, it is still difficult for doctors to adopt the existing machine learning (ML) patterns in interpreting laboratory (lab) big data. Here, a knowledge‐and‐data‐driven laboratory diagnostic system is developed, termed AI‐based Lab tEst tO diagNosis (AI LEON), by integrating an innovative knowledge graph analysis framework and “mixed XGboost and Genetic Algorithm (MiXG)” technique to simulate the doctor's laboratory‐based diagnosis. To establish AI LEON, we included 89 116 949 laboratory data and 10 423 581 diagnosis data points from 730 113 participants. Among them, 686 626 participants were recruited for training and validating purposes with the remaining for testing purposes. AI LEON automatically identified and analyzed 2071 lab indexes, resulting in multiple disease recommendations that involved 441 common diseases in ten organ systems. AI LEON exhibited outstanding transparency and interpretability in three universal clinical application scenarios and outperformed human physicians in interpreting lab reports. AI LEON is an advanced intelligent system that enables a comprehensive interpretation of lab big data, which substantially improves the clinical diagnosis.

Abstract Adult patients with relapsed or refractory T‐cell acute lymphoblastic leukemia (R/R‐T‐ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G‐CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R‐T‐ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T‐cell precursor (ETP) (n = 26) and non‐ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo‐HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non‐CR). With a median follow‐up time of 12 months, the estimated 2‐year overall survival and event‐free survival were 68.8% (95% CI, 47.3%‐83.0%) and 56.5% (95% CI, 37.1%‐71.9%), respectively. The CAG regimen was well‐tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R‐T‐ALL and providing a better bridge to transplantation.

Abstract Background Few empirical studies support a bio-psycho-social conceptualization of frailty. In addition to physical frailty (PF), we explored mental (MF) and social (SF) frailty and studied the associations between multidimensional frailty and various adverse health outcomes. Methods Cross-sectional and longitudinal analyses were conducted using data from a population-based cohort (SLAS-1) of 2387 community-dwelling Singaporean Chinese older adults. Outcomes examined were functional and severe disability, nursing home referral and mortality. PF was defined by shrinking, weakness, slowness, exhaustion and physical inactivity, 1–2 = pre-frail, 3–5 = frail; MF was defined by ≥1 of cognitive impairment, low mood and poor self-reported health; SF was defined by ≥2 of living alone, no education, no confidant, infrequent social contact or help, infrequent social activities, financial difficulty and living in low-end public housing. Results The prevalence of any frailty dimension was 63.0%, dominated by PF (26.2%) and multidimensional frailty (24.2%); 7.0% had all three frailty dimensions. With a few exceptions, frailty dimensions share similar associations with many socio-demographic, lifestyle, health and behavioral factors. Each frailty dimension varied in showing independent associations with functional (Odds Ratios [ORs] = 1.3–1.8) and severe disability prevalence at baseline (ORs = 2.2–7.3), incident functional disability (ORs = 1.1–1.5), nursing home referral (ORs = 1.5–3.4) and mortality (Hazard Ratios = 1.3–1.5) after adjusting for age, gender, medical comorbidity and the two other frailty dimensions. The addition of MF and SF to PF incrementally increased risk estimates by more than 2 folds. Conclusions This study highlights the relevance and utility of PF, MF and SF individually and together. Multidimensional frailty can better inform policies and promote the use of targeted multi-domain interventions tailored to older adults’ frailty statuses.

Migratory birds are recently recognized as Vibrio disease vectors, but may be widespread transporters of Vibrio strains. We isolated Vibrio cholerae (V. cholerae) and Vibrio metschnikovii (V. metschnikovii) strains from migratory bird epidemic samples from 2017 to 2018 and isolated V. metschnikovii from migratory bird feces in 2019 from bird samples taken from the Inner Mongolia autonomous region of China. To investigate the evolution of these two Vibrio species, we sequenced the genomes of 40 V. cholerae strains and 34 V. metschnikovii strains isolated from the bird samples and compared these genomes with reference strain genomes. The pan-genome of all V. cholerae and V. metschnikovii genomes was large, with strains exhibiting considerable individual differences. A total of 2,130 and 1,352 core genes were identified in the V. cholerae and V. metschnikovii genomes, respectively, while dispensable genes accounted for 16,180 and 9,178 of all genes for the two strains, respectively. All V. cholerae strains isolated from the migratory birds that encoded T6SS and hlyA were non-O1/O139 serotypes without the ability to produce CTX. These strains also lacked the ability to produce the TCP fimbriae nor the extracellular matrix protein RbmA and could not metabolize trimetlylamine oxide (TMAO). Thus, these characteristics render them unlikely to be pandemic-inducing strains. However, a V. metschnikovii isolate encoding the complete T6SS system was isolated for the first time. These data provide new molecular insights into the diversity of V. cholerae and V. metschnikovii isolates recovered from migratory birds.

C32H44O6, monoclinic, P21 (no. 4), a = 12.2561 Å, b = 10.3674(4) Å, c = 23.3835(8) Å, β = 98.463°, V = 2938.85(19) Å3, Z = 2, Rgt(F) = 0.0602, wRref(F2) = 0.1537, T = 273(2) K. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength. In the multimetal linear regression, Cu (β = −2.119), As (β = −1.318), Sr (β = −2.480), Ba (β = 0.781), Fe (β = 1.130) and Mn (β = −0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was −1.007 (95% confidence interval: −1.362, −0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (P interactions of 0.003 and 0.018, respectively). In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn. [ABSTRACT FROM AUTHOR]

Background: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy and significantly linked to poor outcomes. Early T-cell precursor (ETP) leukemia is a unique subtype of T-ALL. The aim of this study is to compare the differences between ETP and non-ETP ALLs in China.Methods: We retrospectively analyzed the records of 122 adult T-ALL patients diagnosed and treated at our center between January 2014 and June 2019. All the patients enrolled were categorized into ETP and non-ETP ALL by immunophenotype, and further statistical analyses about clinical data and prognostic factors were performed.Results: Among the 122 cases, the male-to-female ratio was 2.8:1, and the median age is 29 (range, 16–82) years. Except for 10 patients with insufficient immunophenotyping results, 47.3% (53/112) are ETP and 52.7% (59/112) are non-ETP. Compared with non-ETP patients, ETP-ALL patients had lower white blood cell counts and lactate dehydrogenase levels, while they were older and had higher platelet counts and fibrinogen levels (all p < 0.05). Complete remission (CR) was achieved in 68.0% (83/122) of patients, 64.2 and 76.3% in ETP and non-ETP, respectively (p = 0.160). In total, 44.6% (37/83) of patients relapsed. Allogeneic stem cell transplantation (allo-SCT) was successfully performed in 36.1% (44/122) of patients, of which 79.5% (35/44) were in CR1. With a median follow-up of 9.1 (range, 0.5–70.3) months, the estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates for the cohort were 38.0 ± 5.1 and 39.1 ± 6.3%, respectively. In the ETP group, the 2-year OS rate was 40.7 ± 8.2% and the RFS rate was 47.2 ± 10.7%, while in the non-ETP group, the 2-year OS rate was 37.9 ± 7.0% and the RFS rate was 39.2 ± 8.3% (both p > 0.05). In the landmark analysis of CR1 patients who had a survival of more than 6 months, the allo-SCT group had significantly better survival outcomes than the chemotherapy group, and the 2-year OS rates and RFS rates were 80.1 ± 7.3 vs. 28.4 ± 8.4% and 68.9 ± 8.8 vs. 12.8 ± 7.2%, respectively (both p < 0.0001). A multivariate analysis suggests that allo-SCT acts as an independent prognostic factor for both OS and RFS.Conclusions: Our results revealed that ETP accounted for a high proportion of T-ALL in Chinese. There are no CR rates and prognosis differences between ETP and non-ETP. Allo-SCT in CR1 can significantly improve patients' survival.