ObjectiveTo evaluate the effectiveness and safety of Sufei Pingchuan Formula （肃肺平喘方） in the treatment of bronchiectasis with airflow limitation， phlegm-heat obstructing the lung， and lung-spleen qi deficiency syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 72 patients with stable bronchiectasis with airflow limitation of phlegm-heat obstructing the lung and lung-spleen qi deficiency syndrome were randomly divided into treatment group and control group， with 36 cases in each group. On the basis of regular inhalation of tiotropium bromide inhalation spray， the treatment group was given Sufei Pingchuan Formula granules， and the control group was given Sufei Pingchuan Formula granule simulant. The course of treatment in both groups was 12 weeks. The pulmonary function of both groups before and after treatment was observed， specifically focusing on forced expiratory volume in one second （FEV1）； the modified British Medical Research Council （mMRC） dyspnea scale， 24-hour sputum volume， COPD assessment test （CAT）， and traditional Chinese medicine （TCM） syndrome scores were assessed before treatment and after 4， 8， and 12 weeks of treatment； acute exacerbations were recorded at weeks 4， 8， and 12； additionally， changes in routine blood tests， urinalysis， liver and kidney function， and adverse events were monitored before and after treatment. ResultsAfter treatment， 4 patients in the treatment group and 6 in the control group dropped out. After 12 weeks of treatment， FEV1 increased in both groups compared to pre-treatment levels （P＜0.05）， but the difference between groups was not statistically significant （P＞0.05）. Compared to before treatment， the treatment group showed a reduction in mMRC scores after 12 weeks （P＜0.05） and a decrease in 24-hour sputum volume， CAT scores， and TCM syndrome scores at weeks 4， 8， and 12 （P＜0.05）. In the control group， 24-hour sputum volume decreased after 12 weeks （P＜0.05）， and TCM syndrome scores decreased at weeks 8 and 12 （P＜0.05）. Compared to the control group， the treatment group showed a greater reduction in mMRC scores at week 12 （P＜0.05）， a decrease in 24-hour sputum volume and TCM syndrome scores at weeks 4， 8， and 12 （P＜0.05）， and lower CAT scores at weeks 8 and 12 （P＜0.05）. The frequency and number of acute exacerbations in the treatment group were significantly lower than those in the control group at week 12 （P＜0.05）. No severe adverse events occurred in either group. ConclusionSufei Pingchuan Formula can improve the pulmonary function FEV1， the severity of dyspnea， reduce 24-hour sputum volume and frequent acute exacerbations， and improve the quality of life in patients with bronchiectasis and airflow limitation， with good safety.

The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of Corynebacterium glutamicum, we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers. Next, temperature-sensitive L-glutamate fermentation with the CmpL1 and CmpL4 knockout strains were carried out in 5 L bioreactors, where the knockout strains showcased temperature-sensitive characteristics and enhanced capacities for L-glutamate production under high temperatures. Notably, the CmpL1 knockout strain outperformed the control strain in terms of L-glutamate production, showing production and yield increases of 69.2% and 55.3%, respectively. Finally, the intracellular and extracellular metabolites collected at the end of the fermentation process were analyzed. The modification of CmpLs greatly improved the L-glutamate excretion and metabolic flux for both L-glutamate production and transport. Additionally, the CmpL1 knockout strain showed decreased accumulation of downstream metabolites of L-glutamate and intermediate metabolites of tricarboxylic acid (TCA) cycle, which were consistent with its high L-glutamate biosynthesis capacity. In addition to offering an ideal target for improving the stability and performance of the industrial strains for L-glutamate production, the functional complementarity and redundancy of CmpLs provide a novel target and method for improving the transport of other metabolites by modification of the cell membrane and cell wall structures in C. glutamicum.
Corynebacterium glutamicum/genetics* ; Glutamic Acid/biosynthesis* ; Fermentation ; Metabolic Engineering ; Bacterial Proteins/metabolism* ; Bioreactors/microbiology* ; Gene Knockout Techniques

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Lymphoedema of lower extremities,chronic and progressive,will severely deteriorate the quality of life of patients as it progresses.Thus,early diagnosis and treatment to delay the progress of the disease is conducive to improving the prognosis of patients.At present,common techniques for the diagnosis of lower limb lymphedema,whose advantages and disadvantages vary,cannot be applied to individual case comprehensively.CEUS has the advantages of non-invasion,convenience,real-time,and good repeatability for this disease.CEUS can enhance the image of lymph in lymphatics,and has a high sensitivity to superficial lymphatics,gradually applied in lymphedema of lower limbs.This article reviews the application of CEUS in lower limb lymphedema.

Objective To investigate the risk factors for pulmonary infection in patients with acute-on-chronic liver failure(ACLF),and to establish a predictive model.Methods A retrospective analysis was performed for 585 ACLF patients who were admitted to Department of Infectious Diseases,The Second Affiliated Hospital of Air Force Medical University,from January 2009 to September 2022,and according to the condition of pulmonary infection after admission,they were divided into infection group with 213 patients and non-infection group with 372 patients.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between groups.The clinical data of these patients were collected.Univariate and multivariate Logistic regression analyses were used to investigate the risk factors for pulmonary infection in ACLF patients and establish a predictive model,and the receiver operating characteristic(ROC)curve was plotted to assess the predictive value of the model.The Hosmer-Lemeshow test was used to evaluate the degree of fitting of the model,and the ROC curve and the area under the ROC curve(AUC)were used to assess the predictive performance of the model.Results Among the 585 patients with ACLF,213 experienced pulmonary infection,with an infection rate of 36.41%.The multivariate logistic analysis showed that upper gastrointestinal bleeding(odds ratio[OR]=2.463,P=0.047),infection at other sites(OR=2.218,P=0.004),femoral vein catheterization(OR=2.520,P＜0.001),and combined use of two or more antibiotics(OR=2.969,P＜0.001)were risk factors for pulmonary infection in ACLF patients.These factors were included in the risk factor predictive model of Logit(P)=-1.869+0.901×upper gastrointestinal bleeding+0.755×infection at other sites+0.924×femoral vein catheterization+1.088×combined use of two or more antibiotics.The ROC curve analysis showed that the model had a good predictive value(Hosmer-Lemeshow χ2=3.839,P=0.698),with an AUC of 0.753(95%confidence interval:0.700-0.772).Conclusion There is a relatively high incidence rate of pulmonary infection in patients with ACLF,and upper gastrointestinal bleeding,spontaneous peritonitis,femoral vein catheterization,and combined use of two or more antibiotics are related risk factors.The model established based on these factors can effectively predict the onset of pulmonary infection in ACLF patients.

Objective:To investigate the effect of nuclear factor E2-related factor 2 (Nrf2) on the cellular tight junction protein Claudin-18 in endotoxin-induced acute lung injury (ALI).Methods:Eighteen healthy male C57BL/6 mice were divided into control group, endotoxin-induced ALI model group (ALI group) and Nrf2 activator tert-butylhydroquinone (tBHQ) pretreatment group (tBHQ+ALI group) according to random number table method, with 6 mice in each group. Mice endotoxin-induced ALI model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS, 15 mg/kg), and the mice in the control group was injected with an equal amount of phosphate buffer solution (PBS). The mice in the tBHQ+ALI group received three intraperitoneal injections of tBHQ (a total of 50 mg/kg) at an interval of 1 hour before molding. The last injection of tBHQ was accompanied by LPS of 15 mg/kg. The mice in the control group and model group were given equal amounts of PBS, and PBS or LPS was given at the last injection. The mice were sacrificed at 12 hours after LPS injection to take lung tissues. After the lung tissue was stained with hematoxylin-eosin (HE) staining, the pathological changes were observed under light microscopy, and the lung injury score was calculated. The lung wet/dry ratio (W/D) was determined. Nrf2 protein expression in the lung tissue was detected by Western blotting. Positive expression of Claudin-18 in the lung tissue was determined by immunohistochemistry.Results:The lung tissue showed normal structure, without significant pathological change in the control group. Compared with the control group, the alveolar septum widened accompanied by inflammatory cell infiltration, capillary hyperemia and tissue edema in the ALI group, the lung injury score and lung W/D ratio were significantly increased (lung injury score: 6.50±1.05 vs. 1.83±0.75, lung W/D ratio: 3.79±0.22 vs. 3.20±0.14, both P < 0.01), and the Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly lowered [Nrf2 protein (Nrf2/β-actin): 0.41±0.33 vs. 1.22±0.33, Claudin-18 ( A value): 0.28±0.07 vs. 0.44±0.10, both P < 0.05]. After tBHQ pretreatment, the degree of lung histopathological injury was significantly reduced compared with the ALI group, the alveolar space slightly abnormal, inflammatory cell infiltration and tissue edema reduced, the lung injury score and lung W/D ratio were significantly decreased (lung injury score: 3.00±0.89 vs. 6.50±1.05, lung W/D ratio: 3.28±0.19 vs. 3.79±0.22, both P < 0.01), and Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly increased [Nrf2 protein (Nrf2/β-actin): 1.26±0.09 vs. 0.41±0.33, Claudin-18 ( A valure): 0.45±0.04 vs. 0.28±0.07, both P < 0.05]. Conclusion:Nrf2 alleviated pulmonary edema and improved endotoxin-induced ALI by up-regulating Claudin-18 expression.

Objective To investigate the mechanism of copper ionophore elesclomol induced cuproptosis in endometrial cancer cells.Methods HEC-1-A cells were treated with different concentrations of copper ion carrier elesclomol and copper chloride.Cell proliferation was detected using a cell counting kit(CCK-8)assay.Enzyme-linked immunosorbent assay(ELISA)detected mitochondrial respiratory chain complexesⅠ,Ⅱ,Ⅲ,and IV.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expression.Western blotting and immunohistochemistry were used to detect protein expression.Results Adding elesclomol or copper chloride alone to HEC-1-A cells did not affect cell survival.However,the simultaneous addition of 50 nmol·L-1 elesclomol and 1 μmol·L-1 copper ions caused a significant decrease in cell survival(P＜0.01).Elesclomol-induced HEC-1-A cell death does not involve the apoptosis mechanism.After treatment with 50 nmol·L-1 elesclomol and 1 μmol·L-1 copper ions in HEC-1-A cells,the levels of mitochondrial respiratory chain complexes Ⅰ,Ⅱ,and Ⅲsignificantly increased.After knocking down ferredoxin 1(FDX1),the cuproptosis in HEC-1-A cells was significantly inhibited(P＜0.01).In addition,FDX1 was under-expressed in endometrial cancer tissues.Conclusion Elesclomol may promote cuproptosis in endometrial cancer cells through the FDX1/mitochondrial respiratory pathway.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Chronic aortic stenosis and regurgitation can cause left ventricular remodeling.Whether these changes are reversible and their reversibility after valve replacement are the main determinants affecting the timing and prognosis of surgery.Imaging techniques are commonly used to evaluate myocardial structure and function,in which echocardiography and enhanced CT are helpful to evaluate artificial flap function and monitor left ventricular deformation,while cardiac MR and PET/CT are helpful to identify the progression and regression of postoperative cardiac fibrosis.The combined application of these new techniques can improve clinical outcomes by early diagnosis and non-invasive detection of postoperative left ventricular reverse remodeling.This paper reviews the evaluation and application of multi-modal imaging techniques for left ventricular reverse remodeling after aortic valve replacement.

Objective:To construct a medical equipment management system based on improved evidence theory,and to analyze its application effect in the equipment management of geriatric gastroenterology department in hospitals.Methods:With the help of improved evidence theory,the risk of medical equipment management in geriatric gastroenterology department was identified,dynamic weights and static weights were introduced,and a medical equipment management system based on improved evidence theory was constructed by combining the game idea with the portfolio empowerment approach.A total of 60 medical devices in clinical use in the department of geriatric gastroentero1ogy of Xi'an No.1 Hospital from 2021 to 2023 were selected,and the medical devices used from 2021 to 2022 were managed by conventional methods,and the medical devices used from 2022 to 2023 were managed by using the improved evidence theory(improved evidence theory management).The equipment management quality,equipment data integrity score and comprehensive assessment score of equipment management team were compared between the two management methods.Results:The average failure rate and scrap rate of equipment managed by the improved evidence theory method were(12.36±3.65)％and(2.65±0.54)％,respectively,which were lower than those of the conventional management method(t=9.897,15.877,P＜0.05),the average self-maintenance rate and upgrade rate of faults were(90.69±6.25)％and(91.25±5.25)％,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=13.191,14.828,P＜0.05).The average scores of equipment data management,diagnosis and treatment data analysis and clinical application data integrity using the improved evidence theory method were(92.36±2.36)points,(93.69±2.36)points and(94.39±3.26)points,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=13.044,13.893,15.036,P＜0.05).The average comprehensive assessment scores of technical support team,technical development team,technical practice team and auxiliary management team members adopting the improved evidence theory method were(91.36±3.26)points,(94.26±3.59)points,(95.36±4.36)points and(96.36±3.26)points,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=8.224,14.796,14.129,19.005,P＜0.05).Conclusion:The medical equipment management system based on the improved evidence theory can evaluate the risks in the application of equipment,improve the quality of equipment management,enhance the level of equipment management team,and provide decision-making assistance for the equipment management in geriatric gastroenterology department.