Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

BACKGROUND:Studies have shown that short-chain fatty acids(SCFAs)are a potential regulator of skeletal muscle energy metabolism,but the exact mechanism is unclear. OBJECTIVE:To observe the effect of SCFAs on aged rats with sarcopenia and to explore the underlying mechanism. METHODS:Sprague-Dawley rats were randomly divided into control group,sarcopenia group,and sarcopenia+SCFAs group(SCFAs group).In the latter two groups,rat models of sarcopenia were established using ovariectomized rats injected with 5 mg/kg dexamethasone for 7 days.In the control group,the abdominal cavity was only exposed but not removed,and then sutured.Rats in the SCFAs group were administered drinking water containing 150 mmol/L short-chain fatty acids,600 mg/kg sodium acetate,200 mg/kg sodium propionate,and 200 mg/kg sodium butyrate for 4 weeks.Rats in the control and sarcopenia groups were given the same volume of normal saline.Successful modeling was assessed by measuring the bilateral gastrocnemius muscle mass and body mass to calculate the gastrocnemius index after modeling.Food intake,body mass and grip strength of rats were measured at 0,1,2 and 4 weeks after successful modeling;morphological changes of gastrocnemius muscle were observed by hematoxylin-eosin staining;and the expression of p-AMPK and p-ULK1 proteins in gastrocnemius muscle was detected by western blot. RESULTS AND CONCLUSION:Compared with the control group,the sarcopenia group showed significantly decreased body mass,food intake,forelimb grip strength(P<0.05),wet mass of gastrocnemius muscle(P<0.05),and protein levels of p-AMPK and p-ULK1(P<0.05).Compared with the sarcopenia group,the SCFAs group showed a significant increase in food intake,body mass,grip strength,wet mass of gastrocnemius muscle,and protein levels of p-AMPK and p-ULK1 in gastrocnemius muscle(P<0.05).All these findings indicate that SCFAs improve symptoms of sarcopenia in the elderly and may be associated with the upregulation of AMPK and ULK1 proteins in skeletal muscle.

Objective:To establish a rapid quantitative PCR (qPCR) technique for Mycobacterium marinum skin infections, and to analyze its clinical diagnostic efficiency. Methods:DNA was extracted from Mycobacterium marinum colonies and serially diluted (10 -1 to 10 -8). Twelve pairs of previously reported primers and probes, as well as 6 pairs of newly designed primers and probes in this study, were used for qPCR amplification to identify the most sensitive primers and probes for the detection of Mycobacterium marinum. Skin lesion tissues were collected from 72 patients with confirmed Mycobacterium marinum infections (experimental group) and 68 with other mycobacterial infections (control group) at Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences in 2021. These skin tissues were subjected to qPCR amplification, interferon-gamma release assay (IGRA), acid-fast staining, and tissue culture to evaluate the diagnostic efficacy. Results:The newly designed primers and probes targeting the mycobacterial enhanced infection locus 2 (Mel2) demonstrated the highest sensitivity, with a detection limit of 0.86 copies/μl (cycle threshold value = 37) ; the qPCR amplification with the Mel2 primers/probes did not yield positive results when used for the detection of other mycobacteria (including Mycobacterium leprae and Staphylococcus spp) . Among the 72 patients in the experimental group, 44 were positive for qPCR with a sensitivity of 61.1% (95% CI: 49.6% - 71.5%), and 47 were positive for culture with a sensitivity of 65.2% (95% CI: 53.8% - 75.3%) ; all the 68 controls were negative for both qPCR and culture, with their specificities both being 100%. Among 65 patients subjected to IGRA, 31 were positive with a sensitivity of 47.7% (95% CI: 36.0% - 59.6%), while 16 out of 25 controls were negative for IGRA with a specificity of 64.0% (95% CI: 44.5% - 79.8%). Among 58 patients subjected to acid-fast staining, 37 were positive with a sensitivity of 63.8% (95% CI: 50.9% - 74.9%), and 52 out of 66 controls were negative for acid-fast staining with a specificity of 78.8% (95% CI: 67.5% - 86.9%). The combination of qPCR and culture resulted in a sensitivity of 93% and a specificity of 100% for the detection of Mycobacterium marinum. Conclusion:In this study, a highly sensitive qPCR assay was developed for the detection of Mycobacterium marinum, and its combination with culture could further improve the detection sensitivity.

Background: and Purpose The eye-movement examination can be applied as a noninvasive method to identify multiple-system atrophy (MSA). Few studies have investigated eye movements during the early stage of MSA with predominant parkinsonism (MSA-P). We aimed to determine the characteristic oculomotor changes in the early stage of MSA-P. Methods: We retrospectively selected 17 patients with MSA-P and 40 with Parkinson’s disease (PD) with disease durations of less than 2 years, and 40 age-matched healthy controls (HCs).Oculomotor performance in the horizontal direction was measured in detail using videonystagmography. Results: We found that the proportions of patients with MSA-P and PD exhibiting abnormal eye movements were 82.4% and 77.5%, respectively, which were significantly higher than that in the HCs (47.5%, p<0.05). Compared with HCs, patients with MSA-P presented significantly higher abnormal proportions of fixation and gaze-holding (17.6% vs. 0%), without-fixation (47.1% vs. 0%), prolonged latency in reflexive saccades (29.4% vs. 5.0%), memory-guided saccades (93.3% vs. 10.0%), and catch-up saccades in smooth-pursuit movement (SPM, 41.2% vs. 0) (all p<0.05). Compared with those with PD, patients with MSA-P presented a significantly higher proportion of catch-up saccades in SPM (41.2% vs. 2.5%, p<0.001). Conclusions MSA-P presented the characteristic of catch-up saccades in SPM in the early stage, which may provide some value in differentiating MSA-P from PD.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

ACC oxidase (ACO) is one of the key enzymes that catalyze the synthesis of ethylene. Ethylene is involved in salt stress response in plants, and salt stress seriously affects the yield of peanut. In this study, AhACO genes were cloned and their functions were investigated with the aim to explore the biological function of AhACOs in salt stress response, and to provide genetic resources for the breeding of salt-tolerant varieties of peanut. AhACO1 and AhACO2 were amplified from the cDNA of salt-tolerant peanut mutant M29, respectively, and cloned into the plant expression vector pCAMBIA super1300. The recombinant plasmid was transformed into Huayu22 by pollen tube injection mediated by Agrobacterium tumefaciens. After harvest, the small slice cotyledon was separated from the kernel, and the positive seeds were screened by PCR. The expression of AhACO genes was analyzed by qRT-PCR, and the ethylene release was detected by capillary column gas chromatography. Transgenic seeds were sowed and then irrigated with NaCl solution, and the phenotypic changes of 21-day-seedings were recorded. The results showed that the growth of transgenic plants were better than that of the control group Huayu 22 upon salt stress, and the relative content of chlorophyll SPAD value and net photosynthetic rate (Pn) of transgenic peanuts were higher than those of the control group. In addition, the ethylene production of AhACO1 and AhACO2 transgenic plants were 2.79 and 1.87 times higher than that of control peanut, respectively. These results showed that AhACO1 and AhACO2 could significantly improve the salt stress tolerance of transgenic peanut.
Salt Tolerance/genetics* ; Arachis/genetics* ; Plant Breeding ; Ethylenes/metabolism* ; Plants, Genetically Modified/genetics* ; Gene Expression Regulation, Plant ; Plant Proteins/genetics*

OBJECTIVE To screen the potential drug targets and signaling pathways of Acanthopanax senticosus for the treatment of Alzheimer’s disease(AD) by bioinformatics and network pharmacology-based approach, and to preliminarily validate its efficacy. METHODS The ingredients of Acanthopanax senticosus were obtained through literature, the ingredients were screened by Swiss ADME, and potential targets were predicted by Swiss Target Prediction. AD’s differentially expressed genes were screened from the GSE28146 dataset. The target of Acanthopanax senticosus and AD target were mapped to construct a “drug-ingredients-potential target-disease” network and protein-protein interaction network. The DAVID database was used for GO and KEGG enrichment analysis. Autodock software was used to verify the molecular docking between key active ingredients and core targets. AD mice model was induced by D-galactose combined with aluminum chloride. Morris water maze test was performed to examine the learning memory ability of each group of mice and to observe the pathological changes in the hippocampus of mice. RESULTS Screened to obtain 24 active components and 74 potential targets of Acanthopanax senticosus for the treatment of AD. “Drug-ingredients-potential target-disease” network indicated that quercetin and kaempferol were the main components of Acanthopanax senticosus for the treatment of AD, and the protein-protein interaction network indicated that STAT3, MAPK1 and PIK3CA were the key targets. Obtained 366 GO enrichment entries(P<0.01) and 109 KEGG enrichment pathways(P<0.01). It mainly involved PI3K-AKT, AGE-RAGE, TNF and other pathways. The molecular docking results showed that the main active ingredients of Acanthopanax senticosus were able to bind well to the main targets. The in vivo pharmacological results showed that Acanthopanax senticosus could significantly improve the learning and memory ability of mice, reduce hippocampal tissue damage, and decrease the content of TNF-α, IL-6, and IL-1β in hippocampal tissue. CONCLUSION Acanthopanax senticosus may exert anti-AD effects by inhibiting the expression of inflammatory factors and reducing inflammatory damage.

Objective To construct an intervention program for diabetic retinopathy(DR)patients undergoing surgery based on the theory of'Timing It Right'.Methods Guided by the theory of'Timing It Right',based on literature review and semi-structured interview,the first draft of the intervention program was formulated.From December 2022 to February 2023,15 medical and nursing experts in ophthalmology and endocrinology from 5 provinces(cities)in Zhejiang,Sichuan,Shanxi,Chongqing and Shanghai were interviewed by Delphi expert for 2 rounds to seek their advice and revision,and the final draft was formed.Results The effective recovery rate of 2 rounds of expert consultations was 93.75％and 100％.The authority coefficients were 0.87.The importance and feasibility of Kendall'W coordination coefficients were 0.325,0.138 and 0.193,0.141 in 2 rounds,respectively(P＜0.001).The finalized intervention program consisted of 6 months,which included 5 first-level items,18 second-level items and 43 third-level items.Conclusion The intervention program for DR patients undergoing surgery based on the theory of'Timing It Right'is reliable,scientific,feasible and practical,and it can meet the needs of such patients,providing a reference for improving their self-management ability,improving their negative emotions and delaying disease progression.

Objective:To evaluate the effects of exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation on ventricular electrical conduction during hypothermic cardiac ischemia-reperfusion (I/R) in rats.Methods:SPF neonatal Sprague-Dawley rats of either sex, aged 1-2 days, were used, and primary cardiac fibroblasts were extracted by differential adhesion method. The cells were passaged for 2-4 generations. When the cell density reached 60%-70%, the cells were transferred and exposed to 95% N 2 + 5% CO 2 for 1 h at 4 ℃, and then exposed to 95% air + 5% CO 2 for 24-48 h at 37 ℃, and then exosomes were extracted. Twenty-four SPF healthy adult male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were divided into 3 groups ( n=8 each) according to the random number table method: control group (group C), hypothermic cardiac IR group (I/R group) and exosome + hypothermic cardiac IR group (Exo-IR group). At 48 h before equilibrium perfusion, 1.5 ml (200 μg) of exosomes secreted by cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation was injected into the tail vein in Exo-IR group, and PBS 1.5 ml was injected into the tail vein in C group and IR group each. Group C received 110 min equilibration perfusion. After 20 min of equilibration, the perfusion was suspended for 60 min (global ischemia) followed by 30 min of reperfusion in IR and Exo-IR groups. Microelectrode arrays were applied at 20 min of equilibrium perfusion and 15 and 30 min of reperfusion to obtain myocardial conduction velocity (CV), absolute conduction inhomogeneity (P 5-95) and inhomogeneity index (P 5-95/P 50) on the left ventricular surface of isolated rat hearts. Results:Compared with group C, the CV was significantly decreased at 15 and 30 min of reperfusion, and P 5-95 and P 5-95/P 50 were increased in IR and Exo-IR groups ( P<0.05). Compared with IR group, CV was significantly increased at 15 and 30 min of reperfusion, and P 5-95 and P 5-95/P 50 were decreased in Exo-IR group ( P<0.05). Conclusions:Exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation can improve ventricular electrical conduction during hypothermic cardiac I/R in rats.