This article reports a first case of combined infection with severe fever with thrombocytopenia syndrome(SFTS)and scrub typhus in Dalian City.The patient was admitted to the hospital due to recurrent fever for 7 days and loss of consciousness for 1 day.Pathogen metagenomic sequencing(mNGS),SFTSV quantitative PCR,and enzyme-linked immunosorbent assay(ELISA)IgM tests were performed,showing positive results for Orientia tsutsugamushi and SFTSV nucleic acids.Based on clinical manifestations and epidemiological history,the patient was diagnosed with combined infections.

Objective:To explore the role and possible mechanism of ACOT11 in renal fibrosis model mice.Methods:A mouse model of renal fibrosis was established by unilateral ureteral obstruction(UUO)(Sham group and UUO7 group),and the expression of ACOT11 in the kidneys of UUO induced fibrosis mouse models was detected by protein immunoblotting and real-time fluorescence quantitative PCR(qRT-PCR).Subsequently,immunohistochemistry,Masson staining,H&E staining,PAS staining,and other experimental methods were used to detect the expression levels of fibrosis biomarkers fibronectin,α-SMA,and COL-1 in the kidneys of control and experimental group mice.In addition,by constructing ACOT11 gene knockout model mice and using the gene knockout model mice to construct a renal fibrosis model,the expression levels of fibrosis biomarkers such as fibronectin,α-SMA,COL-1,as well as fibrosis mechanism pathway related indicators TGF-β and Smad2 in the kidneys of each group of mice were further detected.Results:The results of WB and qRT-PCR experiments showed that the expression of ACOT11 in the kidney tissue of UUO model mice was significantly reduced compared to the Sham group.After knocking out the ACOT11 gene,H&E staining,PAS staining,and Masson staining showed that pathological inflammatory reactions such as abnormal glomerular and tubular structures,inflammatory cell infiltration and interstitial fibrous tissue proliferation in mice were significantly aggravated compared to the control group,and the expression of fibrosis markers Fibronectin,α-SMA,and COL-1 was significantly higher than that of the control group.Conclusion:ACOT11 plays a protective role in mice with unilateral ureteral obstruction model.After ACOT11 gene knockout,the fibrosis biomarkers of the mouse kidney increases and the degree of fibrosis worsens.

Objective:To characterize the epidemiology, antimicrobial susceptibility, and molecular mechanisms of carbapenem-resistant Enterobacterales (CRE) carrying multiple carbapenemase genes in China, and to provide evidence for infection control and antibiotic stewardship.Methods:From 2016 to 2023, 115 CRE isolates harboring at least two carbapenemase genes were collected from 41 hospitals in 18 provinces across China. Species identification, antimicrobial susceptibility testing, and whole-genome sequencing were performed. Multilocus sequence typing (MLST) and capsular typing were conducted using Kleborate, plasmid replicon types were identified with PlasmidFinder, and a core genome phylogenetic tree was constructed.Results:The majority of isolates belonged to Klebsiella spp. (80.0%, 92/115), followed by E. cloacae (8.7%, 10/115) and E. coli (6.1%, 7/115). The isolates were mainly from Hebei, Beijing, Shandong, and Hunan (60.9%, 70/115), and sputum was the predominant specimen (43.5%, 50/115). The most common genotype was bla KPC+bla NDM (73.0%, 84/115), primarily in Klebsiella spp. (79.8%, 67/84), followed by bla NDM+bla IMP (15.7%, 18/115). The prevalent plasmid replicon types were IncFII (77.5%, 86/111), IncFIB (68.5%, 76/111), IncR (51.4%, 57/111), and IncX3 (20.7%, 23/111). Notably, 88.6% (31/35) of ST11-KL64 K. pneumoniae strains co-harbored IncFII, IncFIB, and IncR plasmids simultaneously. Between 2016 and 2022, the dominant subtype among Klebsiella spp. isolates was bla KPC-2+bla NDM-1 (56.2%, 36/64). In 2023, the bla KPC-2+bla NDM-13 subtype (29.5%, 19/64) emerged and exhibited clonal transmission (single nucleotide polymorphism 2?74 bp) in Hebei, Beijing, and Jilin. Susceptibility testing showed widespread resistance to β-lactams (90.2%-100%). Aztreonam-avibactam, tigecycline, and colistin retained high activity, with susceptibility rates of 90.16%-98.36%. Conclusions:In China, the majority of clinical Enterobacteriaceae strains that harbor multiple carbapenemases are Klebsiella spp. co-producing KPC and NDM enzymes. Dissemination is driven by both clonal expansion of ST11-KL64 and horizontal transfer of IncFII, IncFIB, and IncR plasmids. The recent emergence and regional clonal spread of the bla KPC-2+bla NDM-13 genotype underscore the urgent need for strengthened surveillance and containment measures.

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To assess the viability of reducing radiation dose, contrast media volume, injection flow rate and contrast medium concentration (quadruple low-dose protocol) by utilizing virtual monoenergetic images (VMI) in photon-counting detector CT (PCD-CT) for aortic CT angiography (CTA), while maintaining image quality in comparison to images obtained from energy-integrating detector CT (EID-CT).Methods:From April 2024 to June 2024, a total of 40 participants who underwent aortic CTA on PCD-CT were prospectively enrolled in the experimental group (PCD-CT group), while 40 patients with similar baseline characteristics who had previously undergone aortic CTA using EID-CT were retrospectively selected for the conventional group (EID-CT group). The EID-CT group used a tube voltage of 90 kVp, a contrast media volume of 60 ml of contrast, an injection flow rate of 3 ml/s, and a contrast concentration of 350 mgI/ml; the PCD-CT group used the QuantumPlus mode, with a tube voltage of 140 kVp, a total amount of iodine in the contrast media of 140 mgI/kg, and an injection flow rate=contrast media volume/(delay time+scan time), and a contrast media concentration of 320 mgI/ml. VMIs in PCD-CT group were reconstructed in 5-keV intervals ranging from 45 to 65 keV. The effective radiation dose and contrast injection protocols were recorded and compared between two groups. Objective image quality assessment was performed for each group. CT attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured at five anatomical locations (ascending aorta, aortic arch, descending aorta, abdominal aorta, and right common iliac artery), and image noise was recorded. Subjective image quality was independently evaluated by two readers using a 5-point Likert scale in a blinded manner. Based on data normality, the one-way ANOVA or Kruskal-Wallis test was used for image quality assessment, with Bonferroni-corrected post-hoc analysis for multiple comparisons.Results:There were no significant differences in the baseline characteristics between two groups (all P0.05). The PCD-CT group demonstrated significantly lower effective radiation dose [(3.88±0.65) mSv vs. (5.97±1.15)mSv], contrast media volume [(29.25±4.56) ml vs. 60 ml], and injection rate [(2.65±0.42) ml/s vs. 3 ml/s] than the EID-CT group, with reductions of 35%, 51%, and 12%, respectively (all P0.001). For objective image quality, except for the ascending aortic CT attenuation, the CT attenuation, SNR, and CNR of other vessels in the 55 keV PCD-CT group were comparable to those in the EID-CT group. Additionally, the difference in image noise between these two groups was not statistically significant ( P0.05). Concerning subjective image quality, at 55 keV, the PCD-CT group had similar image noise scores and vessel attenuation scores (both P0.05) and better visualization of renal artery branching ( P=0.001) compared to the EID-CT group. Conclusion:In comparison to EID-CT, the use of a 55 keV image in PCD-CT for aortic CTA has demonstrated reductions in radiation dose, contrast media volume, injection flow rate and contrast medium concentration, while maintaining image quality.

Objective:To evaluate the feasibility of head and neck vascular imaging using photon-counting detector computed tomography (PCD-CT) combined with a “quadruple lows” protocol—characterized by low contrast media volume, low iodine concentration, low injection rate, and low radiation dose—and to compare the image quality with that obtained by energy-integrating detector CT (EID-CT).Methods:A total of 105 patients with suspected cerebrovascular disease were prospectively enrolled at the First Affiliated Hospital of Zhengzhou University between April and June 2024. Patients were randomly assigned to three groups ( n=35). Group A underwent conventional head and neck CTA using EID-CT. Group B underwent PCD-CT with a protocol involving ultra-low contrast media volume, low iodine concentration, and low injection rate. Group C underwent PCD-CT with the full “quadruple low” protocol. Objective image quality parameters—including CT attenuation, image noise (standard deviation, SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)—were measured at the ascending aorta, common carotid artery, internal carotid artery, vertebral artery, basilar artery, posterior cerebral artery, and middle cerebral artery. Two radiologists independently rated subjective image quality using a 5-point Likert scale. Differences among groups were analyzed using one-way ANOVA and the Kruskal-Wallis test. Results:Compared to Group A [contrast volume: (42.78±6.64)ml], contrast agent volume was significantly reduced in Groups B and C[ (26.26±4.45) ml and (26.54±3.83)ml, respectively], demonstrating reductions of 39% and 38% (both P<0.01). The iodine concentration was 320 mg/ml in Groups B and C, lower than 350 mg/ml in Group A (8.5%). The injection rate was also reduced in Groups B and C [(3.39±0.61) and (3.55±0.51)ml/s, respectively] compared to Group A [(4.28±0.66) ml/s], with reductions of 21% and 17% (both P<0.01). The effective dose (ED) was similar between Groups A and B [(1.40±0.15) vs. (1.40±0.19)mSv, P>0.05], while Group C demonstrated a significantly lower ED [(0.99±0.09) mSv], with a reduction of 30% compared to Group A and 29% compared to Group B (both P<0.01).In terms of objective image quality, significant differences in image noise (SD) were observed among the three groups at the vertebral artery, internal carotid artery, posterior cerebral artery, and middle cerebral artery (all P<0.05). Groups B and C showed significantly lower SD compared to Group A ( P<0.05), with no significant difference between B and C ( P>0.05). SNR was significantly higher in Groups B and C than in Group A at multiple vascular segments (all P<0.05). CNR differed only at the internal carotid artery, where Groups B and C demonstrated superior performance compared to Group A ( P<0.05).Subjective image quality scores showed no significant difference between Groups A and C ( P>0.05), while Group B had significantly higher scores than both A and C ( P<0.05). All images were deemed diagnostically acceptable. Conclusion:Compared with conventional EID-CT, PCD-CT combined with a “quadruple lows” protocol enables substantial reductions in contrast media and radiation dose while further improving image quality in head and neck CTA.

Objective To observe the feasibility of photon-counting detector(PCD)-CT combined with"four-lows"protocol(low contrast agent concentration,low contrast dose,low contrast agent flow rate,low radiation dose)for coronary CT angiography(CCTA).Methods Totally 106 patients with suspected coronary artery disease were prospectively enrolled and randomized into energy-integrating detector(EID)-CCTA(group A,using conventional scanning protocol,n=52)or PCD-CCTA(group B,using"four-lows"scanning protocol,n=54)groups and underwent relative examinations.The radiation dose,subjective and objective evaluation results of imaging quality were compared between groups.Results The contrast agent dose and flow rate,volume CT dose index,dose length product and effective dose in group B were all lower than those in group A(all P＜0.001).The subjective scores in group B were higher than in group A(5[4,5]vs.4[4,5],Z=-2.310,P=0.021).Compared with group A,CT value,signal-to-noise ratio and contrast-to-noise ratio of aortic root and most of the main branches of coronary arteries increased in group B,while standard deviation of CT value decreased(all P＜0.05).Conclusion PCD-CT combined with"four-lows"protocol could be used for CCTA,which could improve imaging quality and reduce contrast agent usage and radiation dose.

AIM To investigate the effects of rice wine type and wine processing method on chemical constituents and anti-coagulation effect of Angelicae sinensis Radix.METHODS Wine-washed products and wine-stir-fried products were prepared by different types and ages of rice wine,respectively,after which HPLC was adopted in the content determination of tryptophan,chlorogenic acid,vanillic acid,phthalic acid,ferulic acid,senkyunolide I,senkyunolide H,coniferyl ferulate and ligustilide,and PT,APTT,TT were detected in rabbit plasma.RESULTS Phenolic acids and volatile constituents demonstrated lower contents in the wine-stir-fried products than those in the raw product(P＜0.05),while those in the wine-washed products displayed no obvious changes(except for senkyunolide I)(P＞0.05).The contents of volatile constituents in the wine-washed products were higher than those in the wine-stir-fried products(P＜0.05).After being processed with dry rice wine,various constituents exhibited increased contents as compared with those after being processed with sweet rice wine(P＜0.05).Compared with the raw product,prolonged PT,APTT and TT were observable in the processed products prepared by 3-year semi-dry rice wine(P＜0.05).CONCLUSION The optimal rice wine type is determined to be 3-year semi-dry.Wine-washed Angelicae sinensis Radix shows high contents of ferulic acid and volatile constituents,whose activating blood and resolving stasis effect may be stronger.