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 investigate anxiety symptoms and associated factors in relocated elderly residents of new townships,and to provide evidence for prevention interventions.Methods:A cross-sectional study was conduc-ted in relocated elderly residents in new townships of three urban areas in Shandong Province from 2021 to 2023.The study instruments included Ascertain Dementia-8,Generalized Anxiety Disorder-7,self-administered de-mographic characteristics information questionnaire.Multivariate analysis of factors associated with anxiety symp-toms in elderly residents was performed using multivariate logistic regression.Results:The prevalence rate of mild anxiety symptoms was 5.8％,and the rate of moderate-to-severe anxiety symptoms was 1.3％in 3 313 resi-dents.Multivariate analysis found that self-assessed general psychological condition(OR=0.52),good family envi-ronment(OR=0.34),no self-perceived cognitive impairment(OR=0.31),no chronic diseases(OR=0.42),and only one chronic disease(OR=0.61)were protective factors for mild anxiety symptoms,and very good dietary structure(OR=2.15)and fair dietary structure(OR=2.39)were risk factors for those.Very good family environ-ment(OR=0.11)and average family environment(OR=0.16),and no self-perceived cognitive impairment(OR=0.14)were protective factors for moderate-to-severe anxiety symptoms,and 0-3 years(OR=3.24)and 4-6 years(OR=3.28)of relocation were risk factors for those.Conclusion:Family environment,dietary structure,and duration since relocation are key factors associated with anxiety symptoms among relocated elderly residents in new townships.Targeted interventions should be implemented to address their mental health needs.

Objective:To investigate anxiety symptoms and associated factors in relocated elderly residents of new townships,and to provide evidence for prevention interventions.Methods:A cross-sectional study was conduc-ted in relocated elderly residents in new townships of three urban areas in Shandong Province from 2021 to 2023.The study instruments included Ascertain Dementia-8,Generalized Anxiety Disorder-7,self-administered de-mographic characteristics information questionnaire.Multivariate analysis of factors associated with anxiety symp-toms in elderly residents was performed using multivariate logistic regression.Results:The prevalence rate of mild anxiety symptoms was 5.8％,and the rate of moderate-to-severe anxiety symptoms was 1.3％in 3 313 resi-dents.Multivariate analysis found that self-assessed general psychological condition(OR=0.52),good family envi-ronment(OR=0.34),no self-perceived cognitive impairment(OR=0.31),no chronic diseases(OR=0.42),and only one chronic disease(OR=0.61)were protective factors for mild anxiety symptoms,and very good dietary structure(OR=2.15)and fair dietary structure(OR=2.39)were risk factors for those.Very good family environ-ment(OR=0.11)and average family environment(OR=0.16),and no self-perceived cognitive impairment(OR=0.14)were protective factors for moderate-to-severe anxiety symptoms,and 0-3 years(OR=3.24)and 4-6 years(OR=3.28)of relocation were risk factors for those.Conclusion:Family environment,dietary structure,and duration since relocation are key factors associated with anxiety symptoms among relocated elderly residents in new townships.Targeted interventions should be implemented to address their mental health needs.

Objective To investigate the genetic characteristics and recombination of human-infected sapoviruses(SaVs)worldwide using bioinformatics.Methods The complete genome sequences of SaVs were downloaded from the National Center for Biotechnology Information(NCBI)while high-quality complete genomes were retained for analysis.Molecular phylogenetic trees of SaVs were constructed to analyze their genetic characteristics,followed by recombination analysis of human-infected SaV strains genetype Ⅰ,Ⅱ,Ⅳ,and V(G Ⅰ,G Ⅱ,GⅣ,and GⅤ)with recombination analysis software.Results SaVs exhibited substantial genetic diversity worldwide and infected a wide range of hosts.Human-associated SaVs included G Ⅰ,G Ⅱ,GⅣ,and GⅤ,with GⅤ shared between human and swine hosts.Genetype recombination analysis of SaVs revealed a high frequency of recombination in SaV G Ⅱ strains that involved diverse hosts in the field of SaV G V strains.Recombination breakpoints of the virus were concentrated in the major viral proteins 1(VP1)and minor viral proteins 2(VP2).Conclusion Based on systematic analysis of the genetic characteristics of human-infected SaVs,the genotype distribution and prevalence of SaVs are investigated,the recombination patterns of SaV revealed,and its genetic dynamics highlighted.These findings can offer insights into epidemiological trends of viruses and help devise effective prevention and control strategies.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective To comprehensively analyze the epidemiological characteristics and resistance mechanisms of New Delhi metallo-β-lactamase(NDM)-positive multidrug-resistant bacteria in China.Methods Relevant literatures on NDM-positive multidrug-resistant bacteria discovered in China were searched in the CNKI and PubMed databases(publications from January 1,2017 to December 31,2023).The epidemiological analysis was conducted on the types of NDM-positive bacterial strains,their regional distribution,infection sources,resistance profiles,and transfer mechanisms.Results A total of 118 eligible articles were collected,reporting 1627 NDM-positive bacterial strains.The number of reports increased annually from 2011 to 2019,but began to decline annually from 2020 onwards.NDM-1 and NDM-5 were the most commonly reported variants.The highest number of reports came from Eastern China,followed by Central China and North China.The primary pathogens were Klebsiella pneumoniae,Escherichia coli,and Enterobacter cloacae.The age distribution of patients with NDM-positive infections showed distinct patterns,with neonates and children accounting for 27.25％and patients over 50 years old accounting for 49.57％.The majority of positive bacterial infections came from sputum(38.28％),urine(28.94％),and blood(23.28％).The main departments reporting NDM-positive bacteria were the ICU(39.93％)and pediatrics(20.14％).These resistant bacteria exhibited resistance to more than 50.00％of antibiotics,with lower resistance to colistin and tigecycline(below 30.00％).The predominant plasmid type carrying the blaNDMwas IncX3,and the insertion sequences upstream and downstream of the blaNDM showed diversity.Conclusion NDM-positive multidrug-resistant bacteria are widely prevalent across regions in China,exhibiting multidrug-resistance.This poses significant challenges to clinical antibiotic selection and necessitates the development of effective countermeasures.

Objective:To investigate the MRI features of fibro-adipose vascular anomaly (FAVA).Methods:The clinical, pathological and MRI data of the FAVA patients confirmed clinically and pathologically in Henan Provincial People’s Hospital from January 2016 to June 2021 were retrospectively analyzed, including 17 females and 13 males, aged 4-53 (18.5±12.8) years.Through the analysis of the MRI images of FAVA performance, including the lesion area, shape, signal, the degree of reinforcement, inner structure, outer structure and other image characteristics, summarize the MRI features.Results:The lesions located at the lower leg (12 cases), thigh (12 cases), upper arm (4 cases), forearm (1 case) and trunk (1 case). Twenty-four case of lower limbs. All cases involved the muscular layer, including 21 cases of superficial muscle layer, 7 cases of deep muscle layer, and 2 cases of both. Twenty-three cases of superficial muscle layer. Most of the affected muscles were quadriceps femoris and gastrocnemius. Morphology: all lesions were intramuscular solid masses growing parallel to the long axis of the muscle. There were 11 cases of focal type, 11 cases of locally infiltrating type, and 8 cases of diffuse type. MRI findings: all lesions showed mixed signal. On T1WI, 28 cases showed cloud-like, band-like and patchy high signal on the background of medium and high signal. On T2WI-FS, all the 30 cases showed low to medium signal areas on the background of high signal, which were dendrimer, ribbon and cloud-like. The lesions showed moderate to obvious heterogeneous progressive enhancement. Twenty-seven lesions had different shapes of vascular shadow, and 28 lesions had drainage vein shadow adjacent to the lesions, 24 of which were located at the proximal end of the lesions. Fascial tail sign was found at the periphery of the lesions in 26 cases, of which 23 cases were located at the upper and lower ends of the lesions.Conclusion:FAVA is a complex vascular malformation with unclear pathological classification. MRI usually shows a solid mass in the superficial muscle layer of the lower limbs parallel to the long axis of the muscle, with cloud-like, band-like, and patchy hyperintensity on the background of high signal on T1WI, and dendritic, band-like, and cloud-like hypointensity on the background of high signal on T2WI-FS, which is helpful for the diagnosis of FAVA. Combined with the data of fascial tail sign, draining vein and clinical manifestations, the diagnosis of FAVA can be confirmed to a certain extent, which can provide reference and basis for clinical decision making.

Objective:To investigate the MRI features of fibro-adipose vascular anomaly (FAVA).Methods:The clinical, pathological and MRI data of the FAVA patients confirmed clinically and pathologically in Henan Provincial People’s Hospital from January 2016 to June 2021 were retrospectively analyzed, including 17 females and 13 males, aged 4-53 (18.5±12.8) years.Through the analysis of the MRI images of FAVA performance, including the lesion area, shape, signal, the degree of reinforcement, inner structure, outer structure and other image characteristics, summarize the MRI features.Results:The lesions located at the lower leg (12 cases), thigh (12 cases), upper arm (4 cases), forearm (1 case) and trunk (1 case). Twenty-four case of lower limbs. All cases involved the muscular layer, including 21 cases of superficial muscle layer, 7 cases of deep muscle layer, and 2 cases of both. Twenty-three cases of superficial muscle layer. Most of the affected muscles were quadriceps femoris and gastrocnemius. Morphology: all lesions were intramuscular solid masses growing parallel to the long axis of the muscle. There were 11 cases of focal type, 11 cases of locally infiltrating type, and 8 cases of diffuse type. MRI findings: all lesions showed mixed signal. On T1WI, 28 cases showed cloud-like, band-like and patchy high signal on the background of medium and high signal. On T2WI-FS, all the 30 cases showed low to medium signal areas on the background of high signal, which were dendrimer, ribbon and cloud-like. The lesions showed moderate to obvious heterogeneous progressive enhancement. Twenty-seven lesions had different shapes of vascular shadow, and 28 lesions had drainage vein shadow adjacent to the lesions, 24 of which were located at the proximal end of the lesions. Fascial tail sign was found at the periphery of the lesions in 26 cases, of which 23 cases were located at the upper and lower ends of the lesions.Conclusion:FAVA is a complex vascular malformation with unclear pathological classification. MRI usually shows a solid mass in the superficial muscle layer of the lower limbs parallel to the long axis of the muscle, with cloud-like, band-like, and patchy hyperintensity on the background of high signal on T1WI, and dendritic, band-like, and cloud-like hypointensity on the background of high signal on T2WI-FS, which is helpful for the diagnosis of FAVA. Combined with the data of fascial tail sign, draining vein and clinical manifestations, the diagnosis of FAVA can be confirmed to a certain extent, which can provide reference and basis for clinical decision making.

Objective:To explore the clinical effect of different flow rates of transnasal humidified rapid-insufflation ventilatory exchange (Thrive) on hypoxic events during painless gastroscopy.Methods:Patients who underwent painless gastroscopy in Nanjing First Hospital from April to July 2020 were randomly selected by random number table method and assigned to Thrive groups of 30 L/min ( n=52), 50 L/min ( n=55) and 70 L/min ( n=54). The incidences of different degree of hypoxic events (including subclinical respiratory depression, hypoxia and severe hypoxia) and adverse events related to Thrive were recorded. Results:The total incidence of hypoxic events in the 70 L/min group was 0 (0/54), which was significantly lower than that in the 30 L/min group (21.3%, 11/52, χ2=12.75, P<0.001) and 50 L/min group (12.7%, 7/55, P=0.007). There were no significant differences in subclinical respiratory depression [13.5% (7/52) VS 5.5% (3/55), χ2=1.19, P=0.194] or hypoxia [7.7% (4/52) VS 7.3% (4/55), P=0.610] between 30 L/min group and 50 L/min group. No severe hypoxia occurred in any group. The oxygenation of patients with hypoxemia in 30 L/min and 50 L/min groups was improved (SpO 2>95%) after opening the airway by mandibular support. In addition, there were no significant differences in the incidence of adverse events except hypoxemia among the three groups ( P>0.05). Conclusion:The flow rates of Thrive of 30 L/min, 50 L/min, and 70 L/min can prevent the occurrence of severe hypoxia during painless gastroscopy, and the flow rate of 70 L/min can further reduce the incidence of subclinical respiratory depression.

Objective:To investigate the long-term effects of porcine small intestinal submucosa (SIS) biologic mesh in open Lichtenstein tension-free hernia repair.Methods:The prospective randomized controlled study was conducted. The clinical data of 76 patients with unilateral inguinal hernia who underwent open Lichtenstein tension-free hernia repair in 2 medical centers (52 cases in Tianjin People′s Hospital and 24 cases in China-Japan Friendship Hospital) from August 2013 to March 2014 were selected. Based on random number method, patients were allocated into two groups. Patients undergoing Lichtenstein tension-free hernia repair using Biodesign Surgisis mesh were allocated into control group, and patients undergoing Lichtenstein tension-free hernia repair using SIS biologic mesh were allocated into experiment group. Observa-tion indicators: (1) grouping situations of the enrolled patients; (2) postoperative long-term effects. Follow-up was conducted using telephone interview, text message or mail to detect hernia recurrence or death due to other reasons as the end-point event of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented by M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Grouping situations of the enrolled patients: a total of 76 patients were selected for eligibility. There were 38 cases in the control group and the experiment group, respectively. The number of males and females, age, body mass index, cases with intraspinal anesthesia or local anesthesia (anesthesia method), cases with inguinal hernia on the left side or on the right side, cases classified as type Ⅰ, Ⅱ, Ⅲ, Ⅳ or Ⅴ of Gilbert classification, operation time of the control group were 35, 3, (56±15)years, (23.0±2.0)kg/m 2, 22, 16, 16, 22, 9, 16, 0, 11, 2 and (49±15)minutes, respectively. The above indicators of the experiment group were 34, 4, (54±13)years, (22.9±2.2)kg/m 2, 17, 21, 14, 24, 9, 21, 1, 7, 0, and (53±21)minutes, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.157, t=0.532, 0.367, χ2=1.317, 0.220, Z=-0.315, t=-0.765, P>0.05). (2) Post-operative long-term effects: 35 patients of the control group were followed up for (68.8±2.7)months, 4 cases of which died due to other reasons, 1 case had hernia recurrence, 1 case had chronic pain and no foreign body sensation and postoperative infection occurred. Thirty-one patients of the experiment group were followed up for (68.8±2.7)months, with no death or above complications. There was no significant difference in hernia recurrence or chronic pain between the two groups ( P>0.05). Conclusion:The long-term effects of biological mesh in open Lichtenstein tension-free hernia repair is satisfactory and there is no difference in the long-term effects between the domestic SIS biological mesh and Biodesign Surgisis mesh.