To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention.

Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM_2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM_2.5 (IQR=64.9 μg·m⁻³) at prior 18 h and NO (IQR=40.5 μg·m⁻³) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

BACKGROUND:Most rotator cuff injuries occur in the supraspinatus tendon.Clinical treatment of rotator cuff injuries is very limited due to the lack of blood vessels and the complex anatomical structure of the rotator cuff.The rapid development of tissue engineering technology and stem cell biology has brought new hope for improving the quality of tendon repair.OBJECTIVE:To prepare human umbilical cord mesenchymal stem cells/gelatin methacrylate composite scaffolds by bio-3D printing technology to observe the effect of this scaffold on repairing rotator cuff injury.METHODS:(1)In vitro cell assay:The gelatin microcarrier was prepared.The tissue engineered stem cells were constructed by inoculating human umbilical cord mesenchymal stem cells on the surface of gelatin microcarrier.Gelatin methacrylate hydrogel printing ink was prepared.Tissue engineered stem cells were re-suspended with gelatin methacrylate hydrogel printing ink and put into the bio-ink container of 3D printer for printing.Human umbilical cord mesenchymal stem cells/gelatin methacrylate composite scaffold was obtained after 5 minutes of blue light irradiation and curing.The activity of human umbilical cord mesenchymal stem cells in scaffolds was detected by dead/alive staining and CCK-8 assay.(2)In vivo animal experiments:A random block design method was used to randomly assign 24 SD rats to 4 groups with 6 rats in each group.No treatment was given in the normal group.The rotator cuff injury model of supratinatus tendon tear was established in the rotator cuff injury group,the simple scaffold group,and the cellular scaffold group.The gelatin methacrylate scaffold and human umbilical cord mesenchymal stem cell/gelatin methacrylatecomposite scaffold were implanted into the tendon injury after the model was made in the simple scaffold group and the cellular scaffold group,respectively.Four weeks after operation,behavioral tests and histopathological morphology observation of supraspinatus tendon of rotator cuff were performed.RESULTS AND CONCLUSION:(1)In vitro cellular assay:The dead/alive staining showed that gelatin microcarrier could reduce the damage of human umbilical cord mesenchymal stem cells caused by 3D printing process.With the extension of culture time,the survival rate of human umbilical cord mesenchymal stem cells increased in the scaffold.The results of CCK-8 assay showed that with the extension of culture time,the activity of human umbilical cord mesenchymal stem cells in the scaffold did not change significantly.(2)In vivo animal experiments:Behavioral test results showed that compared with rotator cuff injury group and simple scaffold group,cellular scaffold group significantly improved limb motor function.The results of hematoxylin-eosin and Masson staining of rotator cuff supraspinatus tendon showed that compared with rotator cuff injury group and simple scaffold group,the muscle fiber arrangement in the cellular scaffold group was more regular;there was no obvious inflammatory cell infiltration,and the percentage of collagen volume decreased.The results of immunofluorescence staining showed that the expression levels of interleukin 6 and tumor necrosis factor α in the rotator cuff supraspinatus tendon were significantly decreased in the cellular scaffold group compared with the rotator cuff injury group and the simple scaffold group.(3)The results showed that bio-3D-printed cell scaffolds encapsulating human umbilical cord mesenchymal stem cells/gelatin methacrylate could promote tissue repair and regeneration of rotator cuff injuries.

Objective: This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction (XFBD) in a mouse model of dampness-heat toxin pneumonia. By exploring how XFBD exerts its effects, we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action, thereby supporting its clinical application. Methods: Ultra-high-performance liquid chromatography and high-resolution mass spectrometry (HRMS) were employed to analyze the chemical constituents of XFBD. The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model, established through dampness-heat exposure and HCoV-229E infection. XFBD was administered orally, followed by assessments including lung index measurement, micro-CT imaging, viral load quantification, cytokine analysis, and histological evaluation via hematoxylin-eosin staining. Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects. A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway. Molecular docking and surface plasmon resonance (SPR) experiments confirmed the strong binding affinity between key XFBD components and PKA. Finally, PKA activators and inhibitors were applied in vitro to validate these mechanistic findings. Results: In vivo studies demonstrated that XFBD significantly reduced the lung index, improved the structural integrity of lung and tongue tissues, and decreased levels of proinflammatory mediators, including IL-6, IL-8, and TNF-α. Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation. The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects. Notably, Western blot, ELISA, molecular docking, and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression, thereby activating the cAMP/PKA signaling pathway in vitro. Conclusion: This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia. Its therapeutic effects are mediated, at least in part, through activation of the cAMP/PKA signaling pathway. These findings provide compelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Objective To observe the effect of Shaoyao Gancao decoction combined with electroacupuncture on poststroke spasticity in rats.Methods Healthy male Sprague-Dawley(SD)rats were randomly divided into blank group,model group,electroacupuncture group,baclofen group,electroacupuncture combined with high dose of Chinese medicine group,electroacupuncture combined with middle dose of Chinese medicine group,electroacupuncture combined with low dose of Chinese medicine group,high dose of Chinese medicine group,middle dose of Chinese medicine group and low dose of Chinese medicine group,with 10 rats in each group.Open field test and integrated electromyography of quadriceps femoris were tested before modeling and on the 1st,3rd and 6th day after modeling.The samples were taken on day 6.The expression of inflammatory factors in M1 cortex were detected by liquid phase factor technique.The expression of brain-derived neurotrophic factor(BDNF),synaptophysin(SYP),postsynaptic density 95(PSD95),Nestin and β-catenin in M1 cortex was detected by ELISA and Western blot.Results Compared with model group and other intervention groups,the electroacupuncture combined with middle dose of Chinese medicine group make best total distance(P=0.021)and average speed(P=0.021)in open field test on 6th day.make better in integrated electromyography of quadriceps femoris test(P=0.006)on day 3,have higher Ⅱ type fiber ratio,promote IL-10(P=0.006),GMcsf(P=0.045)secretion.ELISA and Western blot also showed that this group behave better in the test of BDNF,SYP,PSD95,Nestin and β-catenin.Conclusion Electroacupuncture combined with Shaoyao-Gancao decoction groups were effective in the treatment of poststroke spasticity in rats,and its mechanism may be to improve the inflammatory environment of the injured site,promote the proliferation of neural stem cells and synaptic regeneration.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.