Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

Avian infectious bronchitis(IB),a rapidly spreading and acute disease in chickens,is caused by the infectious bronchitis virus(IBV).IB is characterized by its remarkable genetic varia-bility.IBV has a high degree of mutation,and the existing means of immunization often fail to a-chieve good results,seriously affecting the development of the domestic poultry industry.This ar-ticle offers a comprehensive review of the current understanding of the immune response to IBV,focusing on three key areas:non-specific immunity,mucosal immunity,and specific immunity.By dissecting these aspects,the aim is to provide a theoretical reference for the study of the immune mechanism of IBV.

Objective To establish the fingerprint of Xuemai Shutong granules by UPLC-ELSD and determine the contents of 9 components in the preparation simultaneously.Methods The UPLC-ELSD was used to establish the fingerprint of Xuemai Shutong granules,and determine the content of its 9 components.The similarity evaluation system,systematic,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used to evaluate the quality of different batches of preparation.Results The similarity degrees of UPLC-ELSD fingerprints of 11 batches of Xuemai Shutong granules were from 0.929 to 0.978,17 common peaks were calibrated,of which 11 peaks were identified:peak 3(notoginsenoside R1),peak 4[ginsenoside Rg,(Re)],peak 5(notoginsenoside R2),peak 6(ginsenoside Rb,),peak 9(astragaloside Ⅳ),peak 10(ginsenoside Rk3),peak 11(ginsenoside Rh4),peak 12[20(S)-ginsenoside Rg3],peak 13[20(R)-ginsenoside Rg3],peak 14(ginsenoside Rk1),peak 15(ginsenoside Rg5).The stoichiometric analysis divided 11 batches of samples into 2 classes,and the 2 principal components in PCA analysis reflected the information of 17common peaks,10 peaks which affected the quality difference are screened out.The linear relationship of the 9 components was good in their respective quality ranges in the content analysis(r＞0.999 2),the average recovery rate were between 95.02％-97.78％and the RSD were 0.69％-1.70％(n=6).The contents of notoginsenoside R1,notoginsenoside R2,ginsenoside Rb1,astragaloside Ⅳ,ginsenoside Rh4,20(S)-ginsenoside Rg3,20(R)-ginsenoside Rg3,ginsenoside Rk1 ginsenoside Rg5 in the 11 batches of Xuemai Shutong granules were 0.087 5-0.187 6,0.494 3-0.688 6,0.448 1-0.705 5,0.192 2-0.270 8,1.492 5-2.077 6,0.316 0-0.463 8,0.254 5-0.382 0,0.117 6-0.163 9,3.407 7-4.706 4 mg·g-1,respectively.Conclusions The established fingerprint and content determination method was accurate and reliable,which can improve the quality standard of Xuemai Shutong granules,and provide reference for its overall quality evaluation.

Objective To establish the fingerprint of Xuemai Shutong granules by UPLC-ELSD and determine the contents of 9 components in the preparation simultaneously.Methods The UPLC-ELSD was used to establish the fingerprint of Xuemai Shutong granules,and determine the content of its 9 components.The similarity evaluation system,systematic,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used to evaluate the quality of different batches of preparation.Results The similarity degrees of UPLC-ELSD fingerprints of 11 batches of Xuemai Shutong granules were from 0.929 to 0.978,17 common peaks were calibrated,of which 11 peaks were identified:peak 3(notoginsenoside R1),peak 4[ginsenoside Rg,(Re)],peak 5(notoginsenoside R2),peak 6(ginsenoside Rb,),peak 9(astragaloside Ⅳ),peak 10(ginsenoside Rk3),peak 11(ginsenoside Rh4),peak 12[20(S)-ginsenoside Rg3],peak 13[20(R)-ginsenoside Rg3],peak 14(ginsenoside Rk1),peak 15(ginsenoside Rg5).The stoichiometric analysis divided 11 batches of samples into 2 classes,and the 2 principal components in PCA analysis reflected the information of 17common peaks,10 peaks which affected the quality difference are screened out.The linear relationship of the 9 components was good in their respective quality ranges in the content analysis(r＞0.999 2),the average recovery rate were between 95.02％-97.78％and the RSD were 0.69％-1.70％(n=6).The contents of notoginsenoside R1,notoginsenoside R2,ginsenoside Rb1,astragaloside Ⅳ,ginsenoside Rh4,20(S)-ginsenoside Rg3,20(R)-ginsenoside Rg3,ginsenoside Rk1 ginsenoside Rg5 in the 11 batches of Xuemai Shutong granules were 0.087 5-0.187 6,0.494 3-0.688 6,0.448 1-0.705 5,0.192 2-0.270 8,1.492 5-2.077 6,0.316 0-0.463 8,0.254 5-0.382 0,0.117 6-0.163 9,3.407 7-4.706 4 mg·g-1,respectively.Conclusions The established fingerprint and content determination method was accurate and reliable,which can improve the quality standard of Xuemai Shutong granules,and provide reference for its overall quality evaluation.

Avian infectious bronchitis(IB),a rapidly spreading and acute disease in chickens,is caused by the infectious bronchitis virus(IBV).IB is characterized by its remarkable genetic varia-bility.IBV has a high degree of mutation,and the existing means of immunization often fail to a-chieve good results,seriously affecting the development of the domestic poultry industry.This ar-ticle offers a comprehensive review of the current understanding of the immune response to IBV,focusing on three key areas:non-specific immunity,mucosal immunity,and specific immunity.By dissecting these aspects,the aim is to provide a theoretical reference for the study of the immune mechanism of IBV.

Objective:To investigate the values of two-dimensional and three-dimensional echocardiographic parameters in predicting pulmonary vascular resistance (PVR) in chronic pulmonary thromboembolic pulmonary hypertension (CTEPH).Methods:A total of 141 patients diagnosed with CTEPH in China-Japan Friendship Hospital from November 2015 to December 2022 were included. Two-dimensional echocardiographic indicators reflecting PVR were constructed according to the calculation formula of PVR: echocardiographic estimated systolic pulmonary artery pressure (sPAP Echo)/left ventricular end-diastolic diameter (LVIDd), echocardiographic estimated mean pulmonary artery pressure (mPAP Echo)/LVIDd. sPAP Echo/left ventricular end-diastolic volume (LVEDV), sPAP Echo/left ventricular cardiac output (LVCO) were measured by three-dimensional echocardiography. The correlations between two-dimensional and three-dimensional echocardiographic ratios and invasive PVR were then analyzed using the Spearman correlation method. Using receiver operating characteristic curve analysis, cut-off values for the ratios were generated to identify patients with PVR>1 000 dyn·s -1·cm -5. Pre- and postoperative hemodynamics and echocardiographic data were analyzed, as well as the correlation between the reduction rate of the echocardiographic index and PVR in 54 patients who underwent pulmonary endarterectomy (PEA). Results:sPAP Echo/LVIDd, sPAP Echo/LVEDV and sPAP Echo/LVCO were moderately correlated with PVR( rs=0.62, 0.52, 0.63, both P<0.001). The ratio of sPAP Echo to LVEDV, when greater than or equal to 1.41, had a sensitivity of 0.800 and a specificity of 0.930 for determining PVR >1 000 dyn·s -1·cm -5 (AUC=0.860, P<0.001). Similarly, the ratio of sPAP Echo to LVIDd, when greater than or equal to 2.14, had a sensitivity of 0.647 and a specificity of 0.861 for determining PVR >1000 dyn·s -1·cm -5 (AUC=0.830, P<0.001). The sPAP Echo/LVIDd and mPAP Echo/LVIDd significantly decreased after PEA (both P<0.001). The sPAP Echo/LVIDd and mPAP Echo/LVIDd reduction rate (ΔsPAP Echo/LVIDd and ΔmPAP Echo/LVIDd) were significantly correlated with PVR reduction rate (ΔPVR), respectively ( rs=0.61, 0.63, both P<0.05). Conclusions:Two-dimensional ratio sPAP Echo/LVIDd and three-dimensional ratio sPAP Echo/LVEDV can be used to noninvasively estimate PVR in CTEPH patients. The conventional ratio sPAP Echo/LVIDd is convenient and reproducibly suitable for monitoring the improvement of PVR before and after treatment, and its ratio of 2.14 can predict the significant increase of PVR in CTEPH patients (>1 000 dyn·s -1·cm -5).

Objective:To understand the epidemiology of rubella and the genetic characteristics of the virus circulating during the period 2021-2022, providing basic scientific data for rubella prevention and control in China.Methods:National rubella incidence data for the period 2021-2022 were obtained from the Infectious Disease Surveillance System module and the Surveillance Report Management module of the China′s Disease Prevention and Control Information System. Positive rubella virus(RuV)isolates were obtained from the National Measles/Rubella Laboratory Network. Two nucleotide (nt) fragments [F1-480 (8 633-9 112 nt) and F2-633 (8 945-9 577 nt)] located in the E1 gene were amplified and determined by reverse transcription polymerase chain reaction (RT-PCR), and the target gene (E1-739) was obtained after collating and splicing. The sequences obtained in this study were used to construct a phylogenetic tree with the reported reference strains for genotype and lineage identification. Additionally, the phylogenetic analysis was performed to assess their genetic relatedness of RuV strains prevalent in China during 2018-2020 from GenBank database.Results:In 2021-2022, the rubella incidence in China was 0.06/100, 000 (2021: 840 cases; 2022: 784 cases), with cases primarily concentrated in the western and southern provinces. Age distribution analysis showed that rubella cases in 2021-2022 was mainly in children under 5 years of age (2021: 34.17%, 287/840; 2022: 42.09%, 330/784), with the highest proportion in children aged 0-2 years. Further analysis of the immunization history of cases revealed that in the 8-23 months age group, a significant proportion of cases had received only one dose of rubella containing vaccine (RCV); cases in the 2-14 years age group were mainly among children who had received two or more doses of RCV; however, cases over 15 years of age were primarily found in individuals who had not received RCV or had unknown immunization history. National virological surveillance data showed that totally 22 RuV virus isolates were obtained, from 6 provinces in China during 2021-2022, which belonged to lineage 1E-L2 (11 strains) and 2B-L2c (11 strains). And these viruses displayed high genetic homology with RuV prevalent from 2018 to 2020.Conclusions:The incidence of rubella in China was maintained at a low level during 2021-2022, and the prevalent RuV strains were lineage 1E-L2 and 2B-L2c.

BACKGROUND: Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. METHODS: Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. RESULTS: Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. CONCLUSION: Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. CLINICAL TRIAL REGISTRATION Chinese Clinical Trail Registry, No. ChiCTR2100044625.
Humans ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive/therapy* ; Cohort Studies ; Respiration, Artificial ; Inpatients ; Hospital Mortality

Objective:To study characteristics of changes in the demand for emergency medical services during epidemic prevention and control "10 new measures" in Zhejiang province.Methods:The data of 26 emergency centers connected to the provincial integration platform of Zhejiang Province (hereinafter referred to as "provincial platform" ) were retrospectively analyzed, and the data were collected from one week before the implementation of "10 new measures" to the sixth week after implementation (December 1, 2022 to January 18, 2023). The collected information included: the number of 120 calls and ambulance services, the types of disease, age composition of patients, performance of emergency medical services.Results:From the second week of the implementation of "10 new measures" (December 15 to 21, 2022), the number of 120 calls and ambulance services were increased rapidly, and the peak occurred in the third week of implementation (December 21 to 28, 2022). Among the types of diseases, the number and proportion of patients with abnormal symptoms and respiratory diseases increased significantly, reaching the highest peak in the third week (December 21 to 28, 2022) and the fourth week (December 29, 2022 to January 4, 2023) of implementation, respectively. After the second week of implementation, the number of elderly patients aged 71 to 100 increased significantly, reaching a peak in the fourth week (December 29, 2022 to January 4, 2023), accounting for 60.76% of the total. During the epidemic period, the quality control indicators such as emergency dispatch time, ambulance dispatch time and medical treatment all fluctuated, but the changes were not significant.Conclusions:During the implementation of epidemic prevention and control "10 new measures", there were obvious characteristic changes in the demand for pre-hospital emergency in Zhejiang Province, but the quality of pre-hospital emergency medical was basically stable.

Humans ; Blood Pressure/physiology* ; Cohort Studies ; Patient Discharge ; Ischemic Stroke ; Stroke ; Brain Ischemia ; Diabetes Mellitus ; Hypertension