BACKGROUND:Molecular stability and biocompatibility of hemerythrin surpass those of human and mammalian hemoglobin,making it a potential candidate for a safer and more effective erythrocyte substitute after modification.OBJECTIVE:To prepare multi-modified hemerythrin nanoparticles,characterize them,and test their performance in vitro.METHODS:The hemerythrin of Sipunculus sphenodontus was separated and purified by tangential flow ultrafiltration.The intramolecular cross-linking was completed by genipin.The nanoparticles were encapsulated by dopamine,and passivated by polyethylene glycol to obtain multi-modified hemerythrin nanoparticles.The physicochemical properties of the nanoparticles were characterized.Hemerythrin nanoparticles,hemerythrin,and hemoglobin oxygen carrier HBOC-201 with different mass concentrations(0,0.25,0.5,1.0,and 2.0 mg/mL)were incubated with macrophages for 6 and 24 hours,and with endothelial cells for 24 hours.The cell survival rate was detected by CCK-8 assay.The levels of nitric oxide and vascular cell adhesion factor 1 in the culture medium of endothelial cells were detected by ELISA.RESULTS AND CONCLUSION:(1)Under electron microscopy,hemerythrin nanoparticles were ellipsoidal,with a dense outer membrane and a relatively uniform internal texture.The particle size was(150.12±1.67)nm;the dispersion index was 0.21±0.03;the Zeta potential was(-24.54±2.61)mV;the half-saturated oxygen partial pressure was(0.97±0.15)kPa,and the Hill coefficient was 1.49±0.16.(2)After incubation for 6 hours,within the mass concentration range of≤1.0 mg/mL,the survival rates of macrophages in the hemerythrin nanoparticle group,the hemerythrin group,and the HBOC-201 group were all above 85%.At a mass concentration of 2.0 mg/mL,only the survival rate of macrophages in the hemerythrin nanoparticle group was above 80%.After incubation for 24 hours,the survival rates of macrophages in the three groups were all lower than 80%,among which the survival rate of macrophages in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and the HBOC-201 group(P<0.05).(3)With the increase of drug concentration,the survival rate of vascular endothelial cells in the three groups decreased.At 1.0 mg/mL or 2.0 mg/mL mass concentration,the survival rate of cells in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).At the same mass concentration,the nitric oxide level in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).In the range of 0.25-2.0 mg/mL mass concentration,the vascular cell adhesion factor 1 level in the hemerythrin nanoparticle group was lower than that in the hemerythrin group and HBOC-201 group(P<0.05).(4)The results showed that the hemerythrin nanoparticles modified with intramolecular cross-linking and polydopamine/polyethylene glycol had good oxygen-carrying activity in vitro,better anti-phagocytic performance,and less cytotoxicity.

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide, highlighting the urgent need for novel preventive and therapeutic strategies. Emerging research highlights the crucial role of the gut microbiota, including bacteria, fungi, viruses, and their metabolites, in the pathogenesis of CRC. Dysbiosis, characterized by an imbalance in microbial composition, contributes to tumorigenesis through immune modulation, metabolic reprogramming, and genotoxicity. Specific bacterial species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis , along with fungal agents like Candida species, have been implicated in CRC progression. Moreover, viral factors, including Epstein-Barr virus and human cytomegalovirus, are increasingly recognized for their roles in promoting inflammation and immune evasion. This review synthesizes the latest evidence on host-microbiome interactions in CRC, emphasizing microbial metabolites, such as short-chain fatty acids and bile acids, which may act as both risk factors and therapeutic agents. We further discuss the latest advances in microbiota-targeted clinical applications, including biomarker-assisted diagnosis, next-generation probiotics, and microbiome-based interventions. A deeper understanding of the role of gut microbiome in CRC pathogenesis could pave the way for diagnostic, preventive, and personalized therapeutic strategies.
Humans ; Dysbiosis/microbiology* ; Colorectal Neoplasms/metabolism* ; Gastrointestinal Microbiome/physiology* ; Animals

Objective To investigate the characteristics of intestinal flora and its correlation with peripheral blood microinflammatory factors in patients with pulmonary tuberculosis complicated with diabetes mellitus(PTB-DM).Methods A total of 162 patients with PTB-DM admitted to the hospital from September 2022 to September 2024 were selected as the PTB-DM group,and another 150 healthy subjects who underwent physi-cal examinations during the same period in the hospital were selected as the control group.The clinical data of all research subjects was collected.The composition of intestinal flora of the research subjects was analyzed by using 16S rRNA gene sequencing technology.The levels of peripheral blood microinflammatory factors[inter-feron-γ(IFN-γ),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)]in all research subjects were detected.The clinical data,composition of intestinal flora and levels of microinflammatory factors of the PTB-DM group were compared with those of the control group.Spearman correlation analysis was used to analyze the correlation between the relative abundance of intestinal flora and the levels of peripheral blood microin-flammatory factors in patients with PTB-DM.Results The relative abundances of Bacteroidales and Clostridi-ales in the PTB-DM group were significantly lower than those in the control group,while the relative abun-dances of Enterobacterales and Actinobacteriales were significantly higher than those in the control group,and the differences were statistically significant(P<0.05).The levels of IFN-γ,IL-6 and TNF-α in the PTB-DM group were significantly higher than those in the control group,and the differences were statistically signifi-cant(P<0.05).The relative abundances of Bacteroidales and Clostridiales in the PTB-DM group were nega-tively correlated with the levels of IFN-γ,IL-6 and TNF-α.The relative abundances of Enterobacterales and Actinobacteriales were positively correlated with the levels of IFN-γ,IL-6 and TNF-α(all P<0.05).Conclu-sion There is a significant imbalance of intestinal flora in patients with PTB-DM,and the levels of microin-flammatory factors IFN-γ,IL-6 and TNF-α in peripheral blood are significantly increased,and are closely re-lated to the relative abundance of specific flora.

BACKGROUND:Molecular stability and biocompatibility of hemerythrin surpass those of human and mammalian hemoglobin,making it a potential candidate for a safer and more effective erythrocyte substitute after modification.OBJECTIVE:To prepare multi-modified hemerythrin nanoparticles,characterize them,and test their performance in vitro.METHODS:The hemerythrin of Sipunculus sphenodontus was separated and purified by tangential flow ultrafiltration.The intramolecular cross-linking was completed by genipin.The nanoparticles were encapsulated by dopamine,and passivated by polyethylene glycol to obtain multi-modified hemerythrin nanoparticles.The physicochemical properties of the nanoparticles were characterized.Hemerythrin nanoparticles,hemerythrin,and hemoglobin oxygen carrier HBOC-201 with different mass concentrations(0,0.25,0.5,1.0,and 2.0 mg/mL)were incubated with macrophages for 6 and 24 hours,and with endothelial cells for 24 hours.The cell survival rate was detected by CCK-8 assay.The levels of nitric oxide and vascular cell adhesion factor 1 in the culture medium of endothelial cells were detected by ELISA.RESULTS AND CONCLUSION:(1)Under electron microscopy,hemerythrin nanoparticles were ellipsoidal,with a dense outer membrane and a relatively uniform internal texture.The particle size was(150.12±1.67)nm;the dispersion index was 0.21±0.03;the Zeta potential was(-24.54±2.61)mV;the half-saturated oxygen partial pressure was(0.97±0.15)kPa,and the Hill coefficient was 1.49±0.16.(2)After incubation for 6 hours,within the mass concentration range of≤1.0 mg/mL,the survival rates of macrophages in the hemerythrin nanoparticle group,the hemerythrin group,and the HBOC-201 group were all above 85%.At a mass concentration of 2.0 mg/mL,only the survival rate of macrophages in the hemerythrin nanoparticle group was above 80%.After incubation for 24 hours,the survival rates of macrophages in the three groups were all lower than 80%,among which the survival rate of macrophages in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and the HBOC-201 group(P<0.05).(3)With the increase of drug concentration,the survival rate of vascular endothelial cells in the three groups decreased.At 1.0 mg/mL or 2.0 mg/mL mass concentration,the survival rate of cells in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).At the same mass concentration,the nitric oxide level in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).In the range of 0.25-2.0 mg/mL mass concentration,the vascular cell adhesion factor 1 level in the hemerythrin nanoparticle group was lower than that in the hemerythrin group and HBOC-201 group(P<0.05).(4)The results showed that the hemerythrin nanoparticles modified with intramolecular cross-linking and polydopamine/polyethylene glycol had good oxygen-carrying activity in vitro,better anti-phagocytic performance,and less cytotoxicity.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ 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) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had 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 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To explore the correlation between serum 1, 5-anhydroglucitol (1, 5-AG) and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes mellitus (T2DM).Methods:A total of 160 patients with T2DM aged 60-75 years old who visited the First Hospital of Hebei Medical University from May 2021 to July 2022 were selected. According to the Montreal cognitive assessment (MoCA), all patients were divided into T2DM with MCI group (T2DM+ MCI group, n=81) and T2DM without MCI group (T2DM group, n=79). All research subjects were tested for glycated hemoglobin A1c (HbA1c), serum 1, 5-AG, serum β-amyloid peptide 42 (Aβ42), and blood biochemical indicators.SPSS 25.0 statistical software was used for data analysis. The t test, Mann-Whitney U test and χ2 test were used to compare the two groups. Binary Logistic regression analysis was used to examine the relevant influencing factors. Results:(1) Compared with T2DM group, patients in T2DM+ MCI group had significantly higher age, systolic pressure and HbA1c(all P<0.05).The level of 1, 5-AG in T2DM+ MCI group was significantly lower than that in T2DM group( (15.65±2.56 )μg/mL, (18.17±3.72 )μg/mL, P<0.01), and the level of Aβ42 was higher than that of T2DM group (2.95 (3.36) pg/mL, 1.91 (2.48) pg/mL, P<0.05). (2) Binary Logistic regression analysis results showed that HbA1c( β=0.230, OR=1.259, 95% CI=1.010-1.568, P=0.040) and Aβ42( β=0.188, OR=1.206, 95% CI=1.033-1.409, P=0.018) were the independent risk factors for MCI in elderly patients with T2DM, while 1, 5-AG ( β=-0.240, OR=0.786, 95% CI=0.698-0.886, P<0.001) was the protective factor for MCI. Conclusion:There is a positive correlation between serum 1, 5-AG and cognitive function, and the decrease of 1, 5-AG level was associated with the increased risk of MCI in elderly patients with T2DM.

Objective:To summarize the clinical and EEG characteristics of children with self-limited epilepsy with centrotemporal spikes (SeLECTS), and explore the risk factors for comorbid attention-deficit hyperactivity disorder (ADHD).Methods:Demographic and medical history data, seizure characteristics, EEG data, and treatment information of 122 children with SeLECTS admitted to Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from July 2020 to March 2024 were collected. Based on Swanson, Nolan and Pelham-IV Rating Scale (SNAP-IV) results, these patients were divided into comorbid ADHD group ( n=64) and non-ADHD group ( n=58); the clinical data and EEG characteristics (location and lateralization of discharges, synchronicity of bilateral discharges, period of discharges, spike wave frequency and special waveforms) of the patients between the 2 groups were compared to analyze the risk factors for comorbid ADHD. Results:(1) In 122 SeLECTS children, 70 (57.38%) were males and 52 (42.62%) were females; onset age was (7.50±1.98) years (3-12 years); 72.95% (89/122) patients had seizures only within 1 h after falling asleep, 9.84% (12/122) had seizures only 1-2 h before awakening in the morning, 9.84% (12/122) had seizures both after falling asleep and before awakening in the morning; duration of a single episode was (116.60±89.68) seconds (10-600 seconds). (2) Background activity in EEG showed no obvious abnormalities; the discharges were located in the central temporal region in 93.20% (96/103) patients and in the central temporal region and other brain regions (including frontal region, anterior head, bilateral occipital midline and bilateral cerebral hemispheres) in 6.80% (7/103) patients; among 69 patients whose overnight EEG recording was obtained, the spike frequency was 35.00 (20.67, 55.00) times/min (0.33-86.33 times/min). (3) Among 120 patients who accepted drug treatment, 87 (72.50%) received monotherapy, including valproic acid ( n=30, 34.48%), oxcarbazepine ( n=21, 24.14%), lacosamide ( n=17, 19.54%), levetiracetam ( n=17, 19.54%), perampanel ( n=1, 1.15%), and lamotrigine ( n=1, 1.15%); 33 (27.50%) received combination therapy with two or more drugs. (4) The comorbid ADHD group had statistically younger age of onset, longer duration of a single episode, higher proportion of seizures both after falling asleep and before awakening, and higher spike wave frequency in EEG than the non-ADHD group ( P<0.05). Conclusions:SeLECTS patients generally have onset age of 3-12 years, seizures within 1 h after falling asleep or 1-2 h before awakening, normal EEG background activity, and epileptiform discharges mostly located in the centrotemporal area, which are different from other types of epilepsy. SeLECTS patients with young age of onset, long duration of a single episode, seizures both after falling asleep and before awakening and high spike wave frequency in EEG trend to develop ADHD comorbidity.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

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.

Background Silicosis is a diffuse fibrosis of the lungs caused by long-term inhalation of free silicon dioxide (SiO₂). It has a complex pathogenesis and lacks effective treatment. Brusatol (Bru) has a variety of biological activities, and its role in silicosis fibrosis is unclear yet. Objective To investigate the effects of different concentrations of Bru on SiO₂-induced silicosis fibrosis in mice. Methods Thirty male C57BL/6J mice were randomly divided into five groups: a control group, a silica group, and three Bru intervention groups with low, medium, and high doses (1, 2, and 4 mg·kg⁻¹), with 6 mice in each group. Except the control group, the remaining groups were established as SiO₂-induced silicosis mouse models by using a single tracheal infusion of 50 μL 60 mg·mL⁻¹ SiO₂ suspension. The control group was dosed with equal amount of saline. The Bru intervention groups were injected intraperitoneally with Bru for 5 consecutive days and then injected every other day. After 28 d of exposure, the mice were executed and lung tissues were collected. The lung coefficient of the mice was measured, and the pathological changes of the lung tissues were observed after hematoxylin-eosin (HE) and Masson staining. The levels of apoptotic protein Cleaved-caspase 3, fibrosis-related protein α-smooth muscle actin (α-SMA), type I collagen (Col-I), autophagy-associated protein Beclin1, microtubule-associated protein 1 light chain 3 (LC3), Sequestosome 1 (p62/SQSTM1), Kelch like ECH-associated protein-1 (Keap1), and nuclear factor erythroid 2 related factor 2 (Nrf2) were detected by Western blot. The mRNA levels of Caspase 3, α-SMA, and Col-I were measured by realtime fluorescence-based quantitative PCR. Results Compared with the control group, the lung coefficient of mice in the silica group was significantly increased (P < 0.01); the lung tissues of the silicosis mice showed damaged alveolar walls, along with infiltration of inflammatory cells, fibrous nodules, and collagen deposition; furthermore, the protein and mRNA levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly increased (P < 0.01); the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were increased, while that of Keap1 was decreased (P < 0.05). The interventions with low and medium doses of Bru reduced lung coefficient (P < 0.05) and protected against pathological damage and collagen deposition in the lung tissues of the silicosis mice; the protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly decreased in the low and medium dose groups (P < 0.05, P < 0.01), the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were also decreased (P < 0.05, P < 0.01), and the expression level of Keap1 was increased in the medium dose group (P < 0.05). However, compared with the silica group, the differences in lung coefficient, pathological damage, and protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I in the Bru high dose group were not statistically significant (P > 0.05). In addition, the high dose of Bru decreased Beclin1, LC3-II/I, and Nrf2 expression levels (P < 0.01), did not change p62 protein expression level (P > 0.05), while increased Keap1 protein level (P < 0.01). Conclusion Low and medium doses of Bru might regulate autophagy through the Keap1-Nrf2 pathway, ameliorate autophagic degradation impairment, reduce pulmonary coefficient, attenuate apoptosis, and delay the progression of fibrosis in SiO₂-induced silicosis mice.