Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

Objective:To explore the relationship between the ultrasound parameters of reproductive system and the expression of endocrine hormone in female pediatric patients with precocious puberty(PP),and to assess the treatment effect.Methods:A total of 160 female pediatric patients with PP who admitted to Beijing Jingmei Group General Hospital from January 2021 to December 2021 were selected,and they were divided into a positive group and a normal group based on the diagnostic criteria for precocious puberty,with 80 cases in each group.Ultrasound examination was performed on the uterus,ovaries and breasts of 160 female pediatric patients with PP,and the relevant parameters of them were measured,and the levels of endocrine hormone in the serums of them were detected.The pediatric patients of positive group underwent again the ultrasound examination and the detection of endocrine hormone after they completed treatment.The differences of ultrasound parameters and endocrine hormone between two groups were compared,and the correlation of ultrasound parameters and endocrine hormone between two groups were analyzed,as well as the influence factors of treatment effect.Results:The length and thickness of the uterus,the ratio of the length of the uterus to the length of cervix,the thickness of the endometrium,the size of the ovaries,the number of follicles,and the width and thickness of the hypoechoic area of the breast in the positive group were significantly larger than them in the normal group,and the differences of them were statistical significance(t=16.8,12.6,12.4,14.7,11.5,15.8,10.9,10.2,P<0.05),respectively.The resistance index(RI)of uterine artery of positive group was significantly smaller than that of normal group,and the difference was statistically significant(t=-7.9,P<0.05).The serum estradiol(E2),gonadotropin(GnRH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),progesterone(P)and growth hormone(GH)levels of positive group were significantly higher than those of normal group,and the differences of them were significant(t=20.6,19.8,15.4,17.6,15.2,8.9,P<0.05),respectively.After treatment,the above-mentioned ultrasound parameters and endocrine hormone levels of the pediatric patients in the positive group were significantly improved.The relevant analysis showed that ultrasound parameters were positively correlated with levels of endocrine hormone,and they were important influence factor on the levels of endocrine hormone.In addition,the treatment effect was related to ultrasound parameters(OR=0.78-1.28,P<0.05),the levels of endocrine hormone(OR=0.73-0.77,P<0.05),age,height,weight and BMI(OR=0.70-0.72,P<0.05).Conclusion:The ultrasound parameters of the reproductive system of female pediatric patients with PP are closely related to the expression of endocrine hormones.The levels of endocrine hormones can be used as important indicators of the disease condition and prognosis of female pediatric patients with PP.

The contents recorded in the rotation registration manual is not only the quantitative indicators for evaluating the quality of residency training, but also the important basis for training assessment and issuance of training certificates. In order to solve the problems of data authenticity, information delay, and repeated entry in the rotation registration manual for residency training, Shanghai East Hospital, Tongji University, launched a project to dock the electronic rotation registration manual with the hospital information system. Through the establishment of the project team, the development of working mechanisms, and the implementation of the project, data analysis was used for process reformation and system optimization, so as to continuously improve management efficiency and medical safety while solving problems and form a set of implementation system with reference significance in practice.

Metal working fluidis widely used as coolant, lubricant and rust remover in mechanical processing. Oil mist will be formed in the process of metal working fluid. The composition of oil mist is complex, which can produce many adverse effects on the environment and operators. This paper reviews the health hazards of metal working fluid oil mist on human skin, respiratory system, teratogenic and carcinogenic aspects, and discusses the establishment of occupational exposure limits in workplaces of oil mist in foreign countries, in order to provide reference for the prevention and control of occupational health risks of metal working fluid oil mist and the establishment of occupational exposure limits of oil mist in workplaces in China.

Metal working fluidis widely used as coolant, lubricant and rust remover in mechanical processing. Oil mist will be formed in the process of metal working fluid. The composition of oil mist is complex, which can produce many adverse effects on the environment and operators. This paper reviews the health hazards of metal working fluid oil mist on human skin, respiratory system, teratogenic and carcinogenic aspects, and discusses the establishment of occupational exposure limits in workplaces of oil mist in foreign countries, in order to provide reference for the prevention and control of occupational health risks of metal working fluid oil mist and the establishment of occupational exposure limits of oil mist in workplaces in China.

Objective:To explore the application effect of parent-child emotional regulation and resilience group training in adolescent depression patients.Methods:From August 2020 to September 2021, a total of 118 adolescent depression patients were enrolled and randomly divided into the intervention group(66 cases) and the control group(66 cases) by a random number table method.The intervention group received medication therapy and parent-child group emotional regulation and psychological resilience training, while the control group received medication therapy and commonly used individual, family or group therapy in clinical practice.The Hamilton Depression rating scale(HAMD-24 version), Herth hope scale(HHS), Connor-Davidson resilience scale(CD-RISC), and family adaptability and cohesion evaluation scale, second edition Chinese version(FACES-Ⅱ-CV) were adopted to investigate participants at baseline, 12-week, 24-week, and 36-week after intervention.SPSS 26.0 statistical software was used to perform repeated measurement analysis of variance on the data.Results:(1)The interaction effect between two groups of HAMD scores( F=54.0, P<0.001), group main effect( F=401.4, P<0.001), and time main effect( F=116.6, P<0.001) were all significant.Further simple effect analysis showed that there were statistically significant differences in HAMD scores at various time points after intervention between the intervention group(26.2±6.5, 19.3±5.9, 11.3±5.6) and the control group(33.1±9.1, 30.3±7.9, 25.0±8.4)(all P<0.05). Intragroup comparison showed the HAMD scores of the intervention group and control group at each time point after intervention were lower than those before intervention (all P<0.05). (2)The interaction effect of CD-RISC scores between two groups of patients( F=72.1, P<0.001), group main effect( F=48.9, P<0.001), and time main effect( F=174.9, P<0.001) were significant.Further simple effect analysis showed that the CD-RISC score of the intervention group at each time point after intervention were higher than those of the control group(all P<0.05). Intragroup comparison showed the scores of CD-RISC at each time point after intervention in the intervention group and the control group were higher than those before intervention(all P<0.05). (3)The interaction effect of HHS scores( F=121.6, P<0.001), group main effect( F=57.4, P<0.001), and time main effect( F=208.1, P<0.001) of the two groups of patients were significant.Further simple effect analysis showed that the HHS scores of the intervention group were higher than those of the control group at all time points after intervention(all P<0.05). Intragroup comparison showed the HHS scores of the intervention group and the control group at each time point after intervention were higher than those before intervention(all P<0.05). (4)The interaction effect of FACES-Ⅱ-CV scores( F=45.0, P<0.001), group main effect( F=20.3, P<0.001), and time main effect( F=154.5, P<0.001) of the two groups of patients were significant.Further simple effect analysis showed that the FACES-Ⅱ-CV scores of the intervention group were higher than those of the control group at all time points after intervention(all P<0.05). Intragroup comparison showed the FACES-Ⅱ-CV scores of the intervention group and the control group at each time point after intervention were higher than those before intervention(all P<0.05). (5)The total effective rate of the intervention group was higher than that of the control group(95.1%, 87.7%)( P<0.001). Conclusion:In adolescents with depression, parent-child group emotional regulation and resilience training can effectively reduce depression emotion, increase the level of hope and resilience of patients and enhance family intimacy and adaptability.

COVID-19 ; Humans ; Inflammation/genetics* ; Lung ; Pneumonia ; SARS-CoV-2 ; Serologic Tests

Objective:To illustrate a relatively complete knowledge system (e.g., research outputs, current hotspots, and future trends) in the sepsis field and to help scholars grasp the scientific research direction or clinical focus of treatment.Methods:The relevant literatures of sepsis during the time from 1985 to 2019 in Web of Science database were collected. Sepsis-related research contents were generated using softwares (CiteSpace 5.6.R2 and VOSviewer 1.6.13), which using data mining, information processing and knowledge map methods, to analyze the historical evolution and predict the development trend.Results:A total of 8 189 papers on sepsis were published. The volume of publications were increasing yearly from 1985 to 2019, and reached the top list of 1 276 in 2019. For research contents of sepsis, it has formed the basic characteristics of sepsis which focusing on epidemiological studies and animal experiments. Through cluster analysis, the researches mainly focused on six aspects: septic rat, necrotizingenterocolitis, sepsis-associated encephalopathy, acute kidney injury (AKI), gut-derived sepsis, and inflammatory mediator. And it presented the literature characteristics that related to the injury or dysfunction of intestines, brain, liver, kidney or other organs, but the heart and lung researches were more marginal. Additionally, based on the top key words with the strongest citation bursts, it reflected that the development trend of the continuous attention hotspots with "endotoxin" or "endotoxin shock", the significant attention hotspots with "inflammation", "immunity" and "multiple organ dysfunction syndrome" (MODS), and the novel burst attention hotspots with sepsis management including "diagnosis" and "chemotherapy".Conclusions:Through the hotspots and trends visualization of sepsis, the current researches are prefer to animal experiments, epidemiology, or other basic scientific aspects. Meanwhile, the researches are mostly focusing on inflammatory reaction, immune function or organ dysfunctions. Integrating the knowledge maps of hotspots and trends, based on researches of epidemiology, diagnosis, risk factors, pathogenesis, or treatment, we predict that the future scientific topics will concentrating on childhood sepsis, organ injury mechanism or intervention relating to MODS, and integrated management of sepsis by combining traditional Chinese medicine and Western medicine.

Objective To investigate the diagnostic value of Astograph methacholine provocation test in patients with chest tightness variant asthma ( CTVA)??Methods From January 2011 to February 2017,156 patients with CTVA in outpatient or inpatient department of respiratory medicine of Kailuan General Hospital affiliated to North China University of Science and Technology were selected as case group ( chest tightness variant asthma group )??The control group were 361 non?asthmatic patients including interstitial lung disease ( 23 cases), coronary disease ( 157 cases), hypertensive cardiopathy ( 22 cases), myocardiosis (16 cases),congenital heart disease ( 3 cases),rheumatic valvular heart disease (6 cases), central airway disease (3 cases),thyromegaly (10 cases),mediastinal tumor (5 cases),thoracic or spinal deformity (8 cases),phrenoparalysis (2 cases) and vegetative nerve functional disturbance (106 cases)??All participants received pulmonay ventilation test, average daily and nightly variation rate of PEF ( Peak expiratory flow) or PEF weekly variability, Astograph methacholine provocation test ( forced expirataory volume in one second≥70% expectation),and other relevant examinations??The diagnostic value of Astograph methacholine provocation test on CTVA was assessed by analyzing the sensitivity, specificity, positive predictive value,negative predictive value,and Yunden index of Astograph methacholine airway??Results Compared with the control group (( 1??18 ± 0??44)%), theforced expiratory flow from 75% of Forced vital capcacity ( FEF75 ) index of CTVA group (( 1??29 ± 0??50 )%) had significant difference (, t＝ 2??96, P＝0??006)??The sensitivity,specificity,positive predictive value,negative predictive value,Yunden index,and diagnostic accuracy of Astograph methacholine provocation test on CTVA were 0??814,0??695,0??536,0??305, 0??509 and 0??731, respectively??Conclusion The sensitivity, negative predictive value, Yunden index and diagnostic accuracy of Astograph methacholine provocation test on CTVA were higher,whereas the specificity and positive predictive value were relatively lower,suggesting that Astograph methacholine provocation test had a reliable diagnostic value on CTVA,with lower false negative and higher false positive??

Inulin has been used as a prebiotic to alleviate glucose and lipid metabolism disorders in mice and humans by modulating the gut microbiota. However, the mechanism underlying the alleviation of metabolic disorders by inulin through interactions between the gut microbiota and host cells is unclear. We use ob/ob mice as a model to study the effect of inulin on the cecal microbiota by 16S rRNA gene amplicon sequencing and its interaction with host cells by transcriptomics. The inulin-supplemented diet improved glucose and lipid metabolism disorder parameters in ob/ob mice, alleviating fat accumulation and glucose intolerance. The α diversity of gut microbial community of ob/ob mice was reduced after inulin treatment, while the β diversity tended to return to the level of wild type mice. Interestingly, Prevotellaceae UCG 001 (family Prevotellaceae) was obviously enriched after inulin treatment. A comparative analysis of the gene expression profile showed that the cecal transcriptome was changed in leptin gene deficiency mice, whereas the inulin-supplemented diet partially reversed the changes in leptin gene-related signaling pathways, especially AMPK signaling pathway, where the levels of gene expression became comparable to those in wild type mice. Further analysis indicated that Prevotellaceae UCG 001 was positively correlated with the AMPK signaling pathway, which was negatively correlated with markers of glycolipid metabolism disorders. Our results suggest that the inulin-supplemented diet alleviates glucose and lipid metabolism disorders by partially restoring leptin related pathways mediated by gut microbiota.
AMP-Activated Protein Kinases ; metabolism ; Animals ; Cecum ; enzymology ; metabolism ; microbiology ; Gastrointestinal Microbiome ; drug effects ; Inulin ; therapeutic use ; Leptin ; genetics ; Male ; Metabolic Diseases ; drug therapy ; enzymology ; metabolism ; microbiology ; Mice ; Mice, Obese ; Prebiotics ; Signal Transduction ; drug effects ; Transcriptome