Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

Objective To explore the effect of nimodipine combined with minimally invasive puncture on neurological function,hemodynamics,and serum inflammatory factor levels in patients with hypertensive intracerebral hemorrhage(HICH).Methods A total of 108 patients with HICH treated at the Second Affiliated Hospital of Hebei North University from June 2019 to May 2022 were selected as the research subjects.They were divided into an observation group(n=55)and a control group(n=53)according to the treatment method.All patients in the two groups received minimally invasive puncture;on this basis,the patients in the observation group were treated with nimodipine for one month.The neurological deficit of patients in the two groups was evaluated by the National Institute of Health Stroke Scale(NIHSS)score before and after treatment.Before and after treatment,5 mL of fasting venous blood was taken from patients in the morning,and the serum was obtained by centrifugation.The serum levels of brain-derived neurotrophic factor(BDNF),neuron-specific enolase(NSE),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay.Ultrasonic transcranial Doppler blood flow analyzer was used to monitor the hemodynamic indexes such as mean blood flow velocity(Vm),resistance index(RI)and pulsitility index(PI)of patients in the two groups before and after treatment.The adverse reactions such as headache,dizziness,infection and rebleeding were recorded in the two groups after treatment.Results There was no statistically significant difference in the NIHSS score and serum NSE and BDNF levels between the two groups before treatment(P＞0.05).After treatment,the NIHSS score and serum NSE level of patients in the two groups were significantly lower than those before treatment,while the serum BDNF level was significantly higher than that before treatment(P＜0.05).After treatment,the NIHSS score and serum NSE level of patients in the observation group were significantly lower than those in the control group,while the serum BDNF level was significantly higher than that in the control group(P＜0.05).There was no statistically significant difference in the Vm,PI and RI between the two groups before treatment(P＞0.05).After treatment,the Vm and PI of patients in the two groups were significantly higher than those before treatment,while the RI was significantly lower than that before treatment(P＜0.05).After treatment,the Vm and PI of patients in the observa-tion group were significantly higher than those in the control group,while the RI was significantly lower than that in the control group(P＜0.05).There was no statistically significant difference in serum TNF-α,IL-6,and CRP levels between the two groups before treatment(P＞0.05).The levels of serum TNF-α,IL-6,and CRP of patients in the two groups after treatment were significantly lower than those before treatment(P＜0.05).After treatment,serum TNF-α,IL-6,and CRP levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of adverse reactions in patients in the control group and observation group was 7.55％(4/53)and 9.09％(5/55),respectively,and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Nimodipine combined with minimally invasive puncture can effectively improve the blood perfusion rate of HICH patients,reduce the degree of inflammatory response,and alleviate the patients'neurological function damage.

Background The Qingcaosha Reservoir is facing issues of algal blooms and eutrophication, and the resulting increase in the level of chlorination disinfection by-products in the water has been a major concern. Objective To evaluate the impact of "Algae Monitoring and Control Program in Qingcaosha Reservoir" (hereinafter referred to as the program) on the control of trihalomethanes (THMs) in conventional finished water. Methods From 2011 to 2019, water samples were collected from the Lujiazui Water Plant once per season, one sample each time, and the concentrations of four THMs (trichloromethane, dichlorobromomethane, monochlorodibromomethane, and tribromomethane) were measured in the samples. Using 2014 when the program was implemented as a cut-off point, the entire study period was divided into two phases: pre-implementation (2011–2013) and post-implementation(2014–2019). Segmented linear regression with interrupted time series analysis was applied to assess the concentrations and trends of THMs in the finished water before and after the program launch. Results The concentration of total THMs in finished water increased by 1.561 µg·L⁻¹ (P=0.010) for each season of time extension before launching the program. The change in the concentration of total THMs in finished water was not statistically significant after the program launch, but the THMs concentration showed a decreasing trend as the slope was −0.626 (P=0.001). From 2017 until the end of 2019, the average concentration of THMs in finished water of Lujiazui Water Plant dropped to 10 μg·L⁻¹ or less. Conclusions The algae and eutrophication control measures in Qingcaosha Reservoir have achieved good results, controlling THMs in finished water at a low level, and the trend of THMs has changed from a yearly increase pattern before the program to a yearly decrease pattern after the program.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.

Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi, of which cycloastragenol-type glycosides are the most typical and major bioactive compounds. This kind of compounds exhibit various biological functions including cardiovascular protective, neuroprotective, etc. Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis, re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides. However, the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps. Herein, guided by transcriptome and phylogenetic analyses, a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus. AmCAS1, the first reported cycloartenol synthase from Astragalus genus, is capable of catalyzing the formation of cycloartenol; AmUGT15, AmUGT14, AmUGT13, and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation, 3-O-glucosylation, 25-O-glucosylation/O-xylosylation and 2'-O-glucosylation of cycloastragenol glycosides, respectively. These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants, also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.

Objective:To investigate the effects of miRNA-30a-5p (miR-30a-5p) and metadherin (MTDH) on the proliferation, invasion and migration abilities of human breast cancer cells in vitro.Methods:The expression of MTDH in cancer and paracancerous tissues of 112 breast cancer patients in the database and miR-30a-5p in cancer and paracancerous tissues of 103 breast cancer patients in the database were analyzed using data from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to analyze the correlation between miR-30a-5p and MTDH in 1 222 breast cancer patients in the database; the data were updated to August 2022. Breast cancer MDA-MB-231 cells were divided into negative control group (transfected with negative control sequence), miR-30a-5p overexpression group (transfected with miR-30a-5p mimics), siMTDH group [transfected with small interfering RNA against MTDH (siMTDH)], siMTDH+miR-30a-5p overexpression group (transfected with both siMTDH and miR-30a-5p mimics); cell proliferation ability was detected by methyl thiazol tetrazolium (MTT) assay, cell migration ability was detected by cell scratch assay, cell invasion ability was detected by Transwell assay. The relative expressions of miR-30a-5p, MTDH, matrix metalloproteinase (MMP)-2, MMP-9, vimentin and β-catenin mRNA in cells were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR), and the expressions of MTDH, N-cadherin (N-cad), β-catenin, Snail and MMP-9 proteins were detected by Western blotting.Results:In the TCGA database, MTDH expression level was higher and miR-30a-5p expression level was lower in breast cancer tissues compared with paracancerous tissues, and the differences were statistically significant (both P < 0.001). There was a negative correlation between MTDH and miR-30a-5p expressions in 1 222 patients with breast cancer ( r=-0.134, P < 0.001). Compared with the negative control group, the cell proliferation ability was reduced in both siMTDH group and miR-30a-5p overexpression group at 24, 48 and 72 h (all P < 0.001). The cell scratch healing rate in miR-30a-5p overexpression group and siMTDH group was lower than that in negative control group [(61.6±1.6)%, (54.7±5.9)% vs. (80.3±3.0)%] (both P < 0.05). Compared with the negative control group, The number of migrated cells in miR-30a-5p overexpression group and siMTDH group was less than that in negative control group (881±50, 725±63 vs. 1 172±66) (both P < 0.05). Compared with the negative control group, the relative expressions of MMP-2, MMP-9, vimentin and β-catenin mRNA were all down-regulated in MDA-MB-231 cells of miR-30a-5p overexpression group and siMTDH group (all P < 0.05). Compared with the negative control group, the relative expressions of N-cad, β-catenin, Snail and MMP-9 proteins were down-regulated in MDA-MB-231 cells of miR-30a-5p overexpression group and siMTDH group (all P < 0.05). There was no statistical difference in the number of migrated MDA-MB-231 cells between siMTDH+miR-30a-5p overexpression group and siMTDH group (476±5 vs. 389±46, t = 3.37, P = 0.078). There was no statistical difference in the number of migrated cells between siMTDH+miR-30a-5p overexpression group and miR-30a-5p overexpression group (476±5 vs. 477±22, t = 0.02, P = 0.983). Conclusions:The expression of miR-30a-5p is negatively correlated with the expression of MTDH in breast cancer tissues, and either overexpression of miR-30a-5p or silence of MTDH in breast cancer MDA-MB-231 cells in vitro can inhibit cell proliferation, invasion and migration, but MTDH may not be a target gene of miR-30a-5p.

Objective: To construct an evaluation index system to assess the response capacity of universities to public health emergencies, so as to provide a basis for improvements the response capacity. Methods: In November 2019, in order to develop an evaluation system based on literature review and expert discussions, 15 experts were invited to conduct a subjective evaluation used hierarchical analysis. The objective evaluation was conducted in 120 universities in Jiangsu Province used the inverse entropy weighting method, and the final evaluation employed the joint subjective and objective weighting method. Results: The indicator system consisted of four primary indicators, nine secondary indicators, 32 tertiary indicators and 67 quaternary indicators. The analysis of the combined weighting method showed that the primary indicators, in descending order, included incident handling capability ( 0.666 ), incident detection capability (0.203), prior preparation capability (0.101) and post event recovery capability ( 0.031 ). The top three secondary indicator weights were emergency response (0.480), monitoring and reporting (0.203) and command and coordination (0.151). The results of the evaluation of the consistency indicators showed that the expert authority coefficient was 0.909 and the Kendall s W coordination coefficient was 0.836 ( P <0.01), with all consistency scale values < 0.1. Conclusion The evaluation system is highly scientific and credible, and provides basis for evaluating the response capability of universities to public health emergencies.

【Objective】 To compare the efficacy and safety between partial tubeless and standard percutaneous nephrolithotomy in the treatment of upper urinary tract calculi. 【Methods】 The clinical data of 802 patients with upper urinary tract calculi treated at our hospital during Jun.2018 and Dec.2021 were retrospectively analyzed. The patients were divided into the partial tubeless group and standard group, and 60 cases in either group were selected by a simple random method. Clinical data, complications and stone-free rate were compared between the two groups. 【Results】 All 120 patients completed the operation successfully. The postoperative hospital stay, pain score and postoperative recovery of the partial tubeless group were significantly superior to those of the standard group (P<0.05). There were no significant differences in operation time, blood loss, complications and stone clearance rate between the two groups (P>0.05). 【Conclusion】 In the treatment of upper urinary tract calculi, partial tubeless percutaneous nephrolithotomy can achieve satisfactory surgical results, and has obvious advantages in postoperative recovery and patients’ experience. It is worthy of clinical application.

The biofilms formed by pathogenic microorganisms seriously threaten human health and significantly enhance drug resistance, which urgently call for developing drugs specifically targeting on biofilms. Chitooligosaccharides extracted from shrimp and crab shells are natural alkaline oligosaccharides with excellent antibacterial effects. Nevertheless, their inhibition efficacy on biofilms still needs to be improved. Spirulina (SP) is a microalga with negatively charged surface, and its spiral structure facilitates colonization in the depth of the biofilm. Therefore, the complex of Spirulina and chitooligosaccharides may play a synergistic role in killing pathogens in the depth of biofilm. This research first screened chitooligosaccharides with significant bactericidal effects. Subsequently, Spirulina@Chitooligosaccharides (SP@COS complex was prepared by combining chitooligosaccharides with Spirulina through electrostatic adsorption. The binding of the complex was characterized by zeta potential, z-average size, and fluorescence labeling. Ultraviolet-visible spectroscopy (UV-Vis) showed the encapsulation efficiency and the drug loading efficiency reached up to 90% and 16%, respectively. The prepared SP@COS2 exhibited a profound synergistic inhibition effect on bacterial and fungal biofilms, which was mainly achieved by destroying the cell structure of the biofilm. These results demonstrate the potential of Spirulina-chitooligosaccharides complex as a biofilm inhibitor and provide a new idea for addressing the harm of pathogenic microorganisms.
Humans ; Spirulina ; Anti-Bacterial Agents/chemistry* ; Chitosan/pharmacology* ; Biofilms ; Chitin/pharmacology*