ObjectiveTo understand the epidemiological distribution and gene evolutionary variation of influenza A (H3N2) viruses in Fengxian District, Shanghai, in the surveillance year of 2023, and to provide a reference basis for influenza prevention and control. MethodsThe prevalence of influenza virus in Fengxian District in the 2023 influenza surveillance year (April 2023‒March 2024) was analyzed. The hemagglutinin (HA) gene, neuraminidase (NA) gene, and amino acid sequences of 75 strains of H3N2 influenza viruses were compared with the vaccine reference strain for similarity matching and phylogenetic evolutionary analysis, in addition to an analysis of gene characterization and variation. ResultsIn Fengxian District, there was a mixed epidemic of H3N2 and H1N1 in the spring of 2023, with H3N2 being the predominant subtype in the second half of the year, and Victoria B becoming the predominant subtype in the spring of 2024. A total of 75 influenza strains of H3N2 with HA and NA genes were distributed in the 3C.2a1b.2a.2a.2a.3a.1 and B.4 branches, with overall similarity to the reference strain of the 2024 vaccine higher than that of the reference strain of the 2022 and 2023 vaccine. Compared with the 2023 vaccine reference strain, three antigenic sites and one receptor binding site were changed in HA, with three glycosylation sites reduced and two glycosylation sites added; where as in NA seven antigenic sites and the 222nd resistance site changed with two glycosylation sites reduced. ConclusionThe risk of antigenic variation and drug resistance of H3N2 in this region is high, and it is necessary to strengthen the publicity and education on the 2024 influenza vaccine and long-term monitoring of influenza virus prevalence and variation levels.

To report 3 cases of acute generalized exanthematous pustulosis (AGEP) caused by hydroxychloroquine. All the 3 patients were females, aged 23, 30, and 28 years respectively. In cases 1 and 3, the rashes appeared 4 days and 12 days respectively after the treatment with hydroxychloroquine for systemic lupus erythematosus; case 2, who was 8 weeks pregnant, developed rashes 10 days after starting hydroxychloroquine treatment for antiphospholipid syndrome. All the 3 patients had high fever, and clinically presented with generalized round or oval-shaped edematous erythema on the face, neck, trunk and limbs, covered with a large number of pinhead-sized pustules, and with multiple erythema multiforme-like lesions on the trunk and both upper limbs, including targetoid lesions. Mutations in the IL36RN gene were identified in all the 3 patients: a homozygous mutation c.115+6T>C in the IL36RN gene was found in case 1, and her parents were heterozygous carriers; case 2 inherited the heterozygous mutation c.115+6T>C in the IL36RN gene from her mother; the heterozygous mutation c.115+6T>C found in case 3 was a de novo mutation. A diagnosis of AGEP was made in all the 3 cases. Cases 1 and 2 received subcutaneous injections of adalimumab in addition to the treatment of their underlying diseases, and skin lesions markedly regressed after 1 week of treatment; case 3 was treated with high-dose glucocorticoids, and lesions subsided after 4 weeks; no significant adverse reactions were observed in cases 1 and 2, however, femoral head necrosis was noted in case 3. During a follow-up period of 42 months, none of the patients experienced recurrence, and case 2 gave birth to a healthy baby boy after 8-month treatment.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To investigate the clinical characteristics of sepsis-induced myocardial injury and microbial distribution.Methods:It was a retrospective observational study conducted from Jan 2023 to Dec 2023 in the Department of Emergency Intensive Care Medicine, Changshu Hospital Affiliated to Soochow University. Patients meeting the sepsis 3.0 criteria were included, excluding those with underlying cardiovascular diseases or incomplete data. Patients were categorized into myocardial injury (SIMI) and non-myocardial injury (Non-SIMI) groups based on troponin levels. General patient information, laboratory results, microbial findings, and prognostic indicators were collected. Differences in clinical parameters between the two groups were compared. Factors showing statistical differences in univariate analysis were further analyzed using multivariable logistic regression to identify risk factors for SIMI. Conduct propensity score matching among Pulmonary infection patients who underwent bronchoalveolar lavage high-throughput sequencing to compare microbial distribution between groups. Bracken was used to estimate species-level abundance from Kraken2 results, and α and β diversity analyses were conducted on the metagenomic samples.Results:A total of 179 patients were included in the study, with 98 (54.4%) in the Non-SIMI group and 81 (45.5%) in the SIMI group. There were 69 deaths overall (38.5%), with 23 (23.7%) in the Non-SIMI group and 46 (56.8%) in the SIMI group (χ 2=20.347, P<0.01). The 28-day survival curve indicated survival rates in the SIMI group were significantly lower compared to the Non-SIMI group (Log Rank χ 2=21.270, P<0.01). Univariate analysis revealed that fungal infection rate ( P=0.007), C-reactive protein ( P=0.021), procalcitonin, blood urea nitrogen, creatinine, alanine transaminase, and lactate levels were higher in the SIMI group compared to the Non-SIMI group (all P<0.01), prothrombin time was prolonger ( P<0.01) and APACHEⅡ scores were higher ( P<0.01), while serum albumin, base excess, and platelet levels were lower (all P<0.01). Multivariable logistic regression analysis indicated that fungal infection ( OR=3.441, P=0.015) was a risk factor for SIMI, whereas base excess and platelets were protective factors ( OR=0.845, 0.988, both P<0.01). Comparison of bronchoalveolar lavage high-throughput sequencing results in the pulmonary infection subgroup showed the relative abundance of Haemophilus paraininfluenzae in Non-SIMI group was higher than SIMI group among the top 20 species ( P=0.013). There were no statistically significant differences in microbial αand β-diversity between the two groups. Conclusions:The incidence of SIMI is relatively highamong sepsis patients and it affects their prognosis. Risk factors for SIMI include fungal infection, decreased platelet count, and reduced base excess levels. Among patients with pulmonary infections, there is a lower risk of SIMI associated with Haemophilus influenzae infection.

Ischemic stroke is a disease resulting from the cerebral ischemia and hypoxia caused by the blockage of brain vessels in the brain,and is characterized by the focal neurological signs.Pathologically,neuronal necrosis in the infarcted area and the neuronal degeneration or delayed death of neurons in the ischemic penumbra,contribute to the morphological basis of the disease.Ischemic stroke is regulated by multiple processes,including ferroptosis,apoptosis,and autophagy.Ferroptosis,a type of iron-dependent cell death,is closely associated with ischemic stroke.Nuclear factor erythroid 2-related factor 2(Nrf2),a key transcription factor,plays a critical role in maintaining cellular redox balance and regulating inflammatory responses.Nrf2 promotes the expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),thereby activating the Nrf2 signaling pathway to counteract ferroptosis and protect cells from damage.This article reviews and analyzes recent experimental studies on traditional Chinese medicine(TCM)therapy targeting the Nrf2/SLC7A11/GPX4 pathway to suppress ferroptosis.The studies have found that TCM therapy with herbal compounds,Chinese patent medicines,single herbal components and their active ingredients,and acupuncture and moxibustion can inhibit ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway,which will provide novel strategies for the TCM intervention of ischemic stroke.

Objective:To investigate alterations in static regional homogeneity(ReHo) and dynamic regional homogeneity (dReHo) and glucose metabolism in MRI-negative refractory temporal lobe epilepsy (TLE) patients using resting-state PET-MRI, and to evaluate their efficacy in predicting surgical outcomes.Methods:This study was a cross-sectional design. A retrospective analysis was conducted on the clinical and imaging data of 30 patients with MRI-negative refractory TLE (patient group) treated at Xuanwu Hospital, Capital Medical University, between 2016 and 2020, and data from 30 healthy controls (control group). All MRI-negative refractory TLE patients underwent surgical treatment and were further divided into a good prognosis subgroup (Engel Class I, 16 cases) and a poor prognosis subgroup (Engel Class Ⅱ-Ⅳ, 14 cases) based on postoperative Engel classification. Analysis of variance was used to compare differences in static ReHo, dReHo, and glucose metabolism(SUVR) among the three groups. The correlation of static ReHo, dReHo, and SUVR values of differential brain regions with Engel grading was analyzed using Spearman. A support vector machine (SVM) model was constructed using the static ReHo, dReHo, and SUVR values from these differential regions to classify and predict patient prognosis. The predictive performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC).Results:Differential dReHo regions among the good prognosis subgroup, poor prognosis subgroup, and control group were located in the right lateral middle temporal gyrus temporal pole, the right fusiform gyrus, the right insula subfrontal gyrus, the left cuneate lobe, the right medial and paracortical cingulate gyrus, and the right supraparietal gyrus; the differential static ReHo regions were primarily found in the bilateral inferior temporal gyrus, the supraparietal gyrus, and the right subfrontal gyrus, the left medial supraparietal gyrus, the left median frontal gyrus, and the right marginal supraparietal gyrus; SUVR differences were in the affected superior, middle and inferior temporal lobes, the internal olfactory cortex and the temporal pole region. dReHo of right middle temporal gyrus temporal pole in patients with MRI-negative TLE showed a positive correlation with Engel classification ( r=0.421, P=0.020). The SVM model based on dReHo combined with SUVR values classified patients with good and poor prognosis with an AUC of 0.825 and an accuracy of 73.3%. Conclusions:In MRI-negative refractory TLE patients, abnormal dReHo regions are predominantly located in the contralateral default mode network areas and are associated with Engel classification. Combined with glucose metabolism values, dReHo can predict postoperative outcomes in MRI-negative TLE patients.

AIM:This study aims to investigate the regulatory effect of the endocannabinoid 2-arachidonoyl glycerol(2-AG)on voltage-gated calcium channels(VGCCs)in caudate nucleus(CN)neurons subjected to kainic acid(KA)-induced damage,and to elucidate the underlying mechanisms involved.METHODS:Primary cultured CN neu-rons from neonatal Sprague-Dawley(SD)rats were treated with KA to establish an excitotoxic cellular model.The whole-cell patch-clamp technique was utilized to assess the effects of 2-AG on KA-induced excitotoxicity,along with the changes in the electrical properties of VGCCs.This included evaluations of current density,current-voltage relationships,and the kinetics of channel activation and inactivation.RESULTS:Treatment with KA significantly increased the current density and altered the electrical properties of VGCCs,as indicated by a reduction in the half-inactivation voltage and a shift of the inactivation curve towards depolarized potentials.Notably,KA did not affect the activation characteristics of VGCCs.Ad-ministration of exogenous 2-AG or the application of the monoacylglycerol lipase inhibitor URB602,which inhibits 2-AG degradation and elevates intracellular levels of 2-AG,effectively inhibited the KA-induced increase in VGCC current den-sity and the depolarization shift of the inactivation curve,highlighting the involvement of cannabinoid receptor 1(CB1R).CONCLUSION:The endocannabinoid 2-AG can modulate the function of VGCCs in CN neurons via the CB1R pathway,offering protective effects against excitotoxic damage induced by KA.

Objective:To investigate the effect of triglyceride-glucose(TyG) index and alkaline phosphatase(ALP) on brachial-ankle pulse wave conduction velocity(baPWV) in postmenopausal women.Methods:A cross-sectional study was conducted, enrolling 3 483 postmenopausal women who underwent health checkup at Taihu Sanatorium in Jiangsu Province from March 2020 to June 2021. The physical activity, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, triglycerides, high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDL-C), ALP, and baPWV were collected.Results:Age, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, and LDL-C levels were significantly lower in the normal baPWV group( n=1 971) than those in the elevated baPWV group( n=1 512; P<0.001). Logistic regression identified the TyG index( OR=1.75) and ALP level( OR=1.20) as independent risk factors for elevated baPWV( P<0.001), besides with age, body mass index, systolic blood pressure, diastolic blood pressure, and regular exercise. Individuals with both high TyG index and elevated ALP had a 2.51-fold higher risk of elevated baPWV(95% CI 2.01-3.14). Adjusted interaction measures(including age, body mass index, systolic blood pressure, diastolic blood pressure, and regular exercise) showed RERI=2.825(95% CI 1.255-3.905), AP=0.348(95% CI 0.180-0.875), and SI=1.657(95% CI 0.628-3.374). Conclusions:The TyG index and ALP levels are independent risk factors for elevated baPWV in postmenopausal women and exhibit an additive interaction effect on arterial stiffness in this population.

Objective:To evaluate whether the reconstructed image on the basis of deep learning(DL)can improve the success rate and display quality of automatic segmentation of computed tomography(CT)with ultralow dose for chest of children on airway.Methods:The clinical data of 41 consecutive cases who adopted ultralow dose CT to underwent reexamination on chest at Beijing Children's Hospital,Capital Medical University from February 2020 to September 2020 were selected,whose average age was(4.43±1.61 years).The scan protocol of ultralow dose CT was(0.05 mGy).The reconstructed images included 6 groups,which were respectively filtered reflection projection(FBP)image with 0.625 mm thickness,50%adaptive iterative recombination(ASIR-V)images,100%ASIR-V images,low energy DL(DL-L),medium energy DL(DL-M),and high energy DL(DL-H).The automatically segmentation software was used to conduct automatically segmentation for airway,and the success rate of automatic segmentation was recorded.For images that were successful segmented,a 5-point scale was adopted to subjectively evaluate the displayed quality for airway(5 point is the best).In addition,the CT values and noise values of the images of 6 groups for airway were objectively measured.Results:The success rate of automatic segmentation of DL-H image was the highest(60.98%),and that of the 100%ASIR-V was the lowest(39.02%).The subjective score of DL-H image of the automatic segmentation was the highest(4.06±0.55)point,and that of 100%ASIR-V was the lowest(2.44±0.76)point.DL-H can display more fine and small airways.The noise values of objective measurement showed that both of DL-H and 100%ASIR-V had the lowest noise value,and there was no statistical difference in that between them.Conclusion:The use of high energy deep learning iterative reconstruction(DLIR)algorithm can improve the success rate and display effect of automatic segmentation of ultralow dose CT for chest of children on airway,and DLIR is contribute to improve the accuracy of automatic segmentation algorithm of artificial intelligence.

Objective:To evaluate the outcomes of minimally invasive therapy for aortic arch pathology after ascending aortic replacement.Methods:A retrospective analysis was conducted at the Department of Cardiovascular Surgery, West China Hospital of Sichuan University from 2016 to 2024. After multidisciplinary discussion, these included patients were evaluated to be at high risk for traditional open surgery. Various minimally invasive repair techniques were employed, including Ⅳb hybrid technique, physician-modified endograft and novel unibody endograft. The study outcomes were technical success, in-hospital and follow-up mortality, stroke, endoleak, and the patency of the supra-aortic vessels.Results:A total of 40 patients(32 males and 8 females) with a median age of 60 years old were included in this study. The technique success rate was 100%, with no deaths or strokes reported. The patency of the supra-aortic vessels was 100%. 10 patients underwent Type Ⅳb hybrid surgery without any endoleaks occurring. Among the 22 patients who received physician-modified endograft, endoleaks were observed in 2 cases. One of these type Ⅰc endoleaks persisted and underwent reintervention. One patient underwent femoral artery replacement due to vascular injury. For the 8 patients who received novel unibody endograft, one case required reintervention due to persistent type Ⅰc endoleaks.Conclusion:With the development of different endovascular techniques and novel branched endograft, patients with aortic arch pathology who are at high risk for redo open surgery can achieve favorable outcomes with various minimal invasive techniques. However, long-term and large-sample follow-up studies are needed for further evaluation.