Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

This study was designed to explore the immune reconstitution efficacy of human thymic slices transplanted into renal capsule,subcutaneous or muscle of nude mice,and further explore the optimal location of heterotopic transplantation.The thymus tissue discarded from congenital heart disease patients was made into 0.5-1 mm thick tissue sections and cultured in vitro to remove immune cells.H&E staining and immunohistochemical staining were used to assess the residual tissue structure and cell types in thymic slices,while quantitative PCR methods were used to assess the function of residual cells in thymic slices.Then thymic slices were transplanted into the renal capsule,subcutaneous or muscle of nude mice,and the immune reconstitution efficacy was compared by flow cytometry and histology.Data showed that after 14 days of culture in vitro,the clearance rate of T lymphocytes in the thymic slices was more than 90%,and the epithelial cell network structure of the tissue was intact,while a large number of macrophages,dendritic cells and endothelial cells remained.Quantitative PCR results showed that the gene expression levels of epithelial cell markers and secreted cytokines in cultured thymic slices could be effectively maintained.Flow cytometry showed that at 16 weeks after transplantation,the proportion of T cells in peripheral blood of mice in different transplantation groups were significantly increased,whereas the proportion of T cells in muscle group was the highest.In situ histological examination showed that the regeneration of thymus tissue was detected at all three transplant sites.In addition,the graft detection rate was 40%in the renal capsule group,60%in the subcutaneous group and 100%in the musclegroup.In conclusion,the human thymic slices cultured in vitro for 14 days retain a complete thymic matrix microenvironment.Transplantation of human thymic slices can effectively reconstruct the ratio of T cells in nude mice,and the muscle is the most effective transplantation site.

Atrial functional mitral regurgitation (AFMR) is mitral regurgitation in patients with atrial fibrillation (AF), whose left atrium (LA) is enlarged, the left ventricle is not enlarged or only slightly enlarged, the left ventricular ejection fraction is preserved, and the mitral valve itself has no apparent lesion. At present, the etiology, pathophysiology and mechanism of this disease have not been completely clear yet. Existing studies have found that the causes of AFMR mainly include AF, enlargement of LA and mitral annulus, destruction of mitral annular shape, inability of mitral valve remodeling to compensate for mitral annular expansion, and hamstringing of the posterior mitral leaflet by atriogenic tethering. AFMR is demonstrated to be associated with an increased risk of mortality and readmission due to heart failure. Therefore, it serves as a primary therapeutic target for patients with heart failure and AF. However, the optimal treatment of AFMR still remains controversial. Therefore, this article will mainly expound the current definition, etiology, pathophysiological mechanism, treatment, and prognosis of AFMR.

Objective:To compare the correlation and consistency of central corneal thickness (CCT) measured by four different instruments, specular microscope SP-1P, IOLMaster 700, Pentacam HR and RTVue XR-OCT.Methods:A diagnostic test study was performed.A total of 50 right eyes of 50 consecutive outpatients who planned to undergo corneal refractive surgery at Hanyang Aier Eye Hospital from January to May 2022 were included.CCT was measured with the specular microscope SP-1P, IOLMaster 700, Pentacam HR and RTVue XR-OCT, respectively.The differences of CCT measurements by the four instruments were compared.The correlation and consistency between the CCT values was analyzed by Pearson linear analysis and Bland-Altman test, respectively.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Hanyang Aier Eye Hospital (No.HYEYE20221229JM).Written informed consent was obtained from each subject.Results:The mean CCT values measured by SP-1P, IOLMaster 700, Pentacam HR and RTVue XR-OCT were (522.68±30.08), (544.06±32.85), (541.00±31.75) and (528.86±31.60)μm, respectively, with a statistically significant overall difference ( F=5.09, P=0.002).CCT measurements obtained with SP-1P were lower than those obtained with IOLMaster 700 and Pentacam HR, while the IOLMaster 700 measurements were higher than those of RTVue XR-OCT, showing statistically significant differences (all at P<0.05).Pearson correlation analysis revealed significant positive correlations of CCT measurements between SP-1P and IOLMaster 700, SP-1P and Pentacam HR, SP-1P and RTVue XR-OCT, IOLMaster 700 and Pentacam HR, IOLMaster 700 and RTVue XR-OCT, Pentacam HR and RTVue XR-OCT ( r=0.988, 0.980, 0.988, 0.981, 0.982, 0.973; all at P<0.01).Bland-Altman consistency analysis showed that the 95% limits of agreement (95% LoA) for CCT measurements between SP-1P and RTVue XR-OCT, IOLMaster 700 and Pentacam HR were -16.46-6.14 and -10.56-14.48 μm, respectively, with 3(6%) and 2(4%) data points outside the 95% LoA, respectively.The mean difference lines for the CCT measurements were close to 0, indicating good consistency and clinically acceptable differences without statistical significance. Conclusions:CCT values measured with specular microscope SP-1P and RTVue XR-OCT, as well as those measured with IOLMaster and Pentacam HR, are relatively close in patients with low to moderate myopia, show good consistency and can therefore be considered interchangeable.

Objective:To study the role of myocardial work parameters in early identification of myocardial injury in neonatal asphyxia.Methods:From July 2020 to December 2021, neonates diagnosed with mild neonatal asphyxia admitted to the Department of Neonatology of our hospital within 24 h after birth were prospectively enrolled into the asphyxia group. Neonates without asphyxia during the same period were selected as the control group and matched with the asphyxia group for gender, gestational age and birth weight at a ratio of 1:1~1:2. The asphyxia group was subgrouped into preterm asphyxia group and term asphyxia group. All neonates received echocardiography within 24 h after birth. Multiple parameters were measured including M-mode, two-dimensional image, Doppler image, global longitudinal strain (GLS) and myocardial work parameters [global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE)]. The level of serum N-terminal pro brain natriuretic peptide (NT-proBNP) was recorded in the asphyxia group. The data were compared between the asphyxia group and the control group. Correlations between myocardial work parameters and other parameters were analyzed.Results:A total of 33 cases were in the asphyxia group and 43 cases were in the control group. The preterm asphyxia group (18 cases) showed significantly lower GWI and GCW than the preterm control group (18 cases) [GWI: (702±153) mmHg vs. (879±205) mmHg, GCW: (1 016±221) mmHg vs. (1 200±271) mmHg] ( P<0.05). No differences existed in GLS, GWW and GWE. The term asphyxia group (15 cases) showed significantly lower GWW than the term control group (25 cases) [45.0 (30.0, 65.0) mmHg vs. 71.0 (35.5,85.5) mmHg] ( P<0.05). No differences existed in GLS, GWI, GCW and GWE. GWI was negatively correlated with serum NT-proBNP level ( r=-0.327, P<0.05). Conclusions:GWI and GCW may indicate myocardial injury in preterm neonates with mild asphyxia.

Objective To explore the clinical characteristics and risk factors of occult pneumonia in advanced elderly patients.Methods A total of 170 advanced elderly patients with community-acquired pulmonary infection in geriatric department of Xijing hospital from January 2014 to October 2017 were enrolled.Patients were divided into two groups:the observation group (with occult pneumonia,n=80)and the control group(without occult pneumonia,n =90).Clinical data of patients were collected,and clinical characteristics and related risk factors of occult pneumonia in elderly patients were analyzed.Results There was no statistically significant difference in the positive rate of sputum culture and the distribution of pathogenic bacteria between the two groups (P ＞ 0.05).Gram-negative bacteria predominated in pathogenic bacteria.The hospitalization time was longer in the observation group than in the control group[(17.3 ± 3.0) d vs.(10.3 ± 3.9) d,P ＜ 0.05].The mortality rate was higher in the observation group than in the control group(10.0 ％ vs.3.3 ％,P ＜ 0.05).The age was older in the observation group than in the control group[(87.0± 1.7) years vs.(82.0± 2.4) years,P ＜ 0.05].The incidences of diabetes,Alzheimer's disease,hypothyroidism and long-term bed rest were higher in the observation group than in the control group (P ＜ 0.05).Multivariate logistic regression analysis showed that age (OR =6.93),dementia (OR =4.32),hypothyroidism(OR =4.89) were independent risk factors for occult pneumonia (P ＜ 0.05).Conclusions The pathogenic bacteria in advanced elderly patients with occult pneumonia are mainly gram-negative bacteria.The positive rate of CT scan confirmed-occult pneumonia is much higher than that by chest X-ray.The advanced elderly patients with occult pneumonia have longer hospitalization time and higher mortality rates.Old age,senile dementia and hypothyroidism are independent risk factors for occult pneumonia in advanced elderly patients.

Objective To explore the regional changes of cerebral function in patients with liver cirrhosis before and 1 month after liver transplantation (LT). Methods A total of 11 patients with liver cirrhosis who underwent LT in Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University between September 2012 and September 2013 were enrolled in this prospective study (liver cirrhosis group), and at the same period 11 healthy subjects were enrolled in control group. The informed consents of all patients were obtained and the local ethical committee approval was received. Subjects in liver cirrhosis group and control group were all males, with an average age of (49±9) and (48±8) years old, respectively. Changes of regional homogeneity (ReHo) of the cerebral function in patients of liver cirrhosis group before and 1 month after LT was studied by using resting-state functional MRI (rs-fMRI). ReHo values were compared between both groups by t test. Results Compared with control group, ReHo values of right middle occipital gyrus, left middle temporal gyrus, right precuneus/posterior cingulate gyrus, left inferior parietal lobule/postcentral gyrus in liver cirrhosis group significantly decreased before LT (t=-4.65, -4.56,-4.41, -5.87; P<0.05), and those of left middle temporal gyrus, posterior cingulate gyrus, right superior parietal lobule/precuneus also significantly decreased 1 month after LT (t=-4.42, -5.23, -4.41; P<0.05). The ReHo value of middle cingulate gyrus 1 month after LT was significantly higher than that before LT (t=5.24, P<0.05).Conclusions Cerebral dysfunction is observed in patients with liver cirrhosis before LT,and it can change within 1 month after LT, but cannot get a full recovery, which may be related to some irreversible injuries of patients with liver cirrhosis.

Objective To investigate regional activity abnormalities of patients with liver cirrhosis before and after liver transplantation using resting-state fMRI and amplitude of low frequency fluctuations (ALFF)method.Methods Totally 11 patients preparing to accept liver transplantation were adopted into liver cirrhosis group and 11 healthy volunteers in the health examination were adopted into the control group. The liver cirrhosis group was investigated at a week before operation and repeatedly a month after liver trans-plantation.Healthy volunteers were investigated at the same time.MR imaging data were obtained from a Phil-ips Achieva 1.5-T MR imager.The imaging data were mainly preprocessed with a MATLAB toolbox called DPARSF.REST software was used to calculate the ALFF value of each subject.A second-level random-effect two-sample t-test was performed on the individual ALFF.Significant differences were set at the standard of a corrected cluster level of P<0.05,and software Xjview 8.1 was adopted to express the outcome.Results (1)Compared with control group,decreased ALFF were found in bilateral middle occipital gyrus(MOG) (MNI:x=36,y=-72,z=9),bilateral precuneus/cuneus(PCu/Cu)/posterior cingulated(PCC)(MNI:x=15,y=-66,z=24),left inferior parietal lobule(LIPL)(MNI:x=-39,y=-54,z=42),and bilateral para-central lobule/cingulate gyrus(MNI:x=3,y=-36,z=45)of cirrhosis patients,no increased ALFF were found.(2)Compared with cirrhosis patients,no increased or decreased ALFF were found in postoperative group.After relaxing standards of statistics,increased ALFF were found in left inferior parietal lobule(IPL) (MNI:x=-39,y=-51,z=42),cingulate gyrus(MNI:x=3,y=-33,z=42),and right middle frontal gyrus (MNI:x=35,y=57,z=0)of postoperative group,no decreased ALFF were found.(3)Compared with control group,decreased ALFF were found in bilateral precuneus/posterior cingulated(PCC),and left middle occipi-tal gyrus(MOG)of postoperative group,no increased ALFF were found.Conclusions Significant decreased ALFF is found in visual cortex(PCu),DMN((PCu/Cu/PCC),and LIPL of cirrrhosis patients,and those ab-normalities reflect the weakness of local neurons spontaneous low-frequency.Compared with beforeoperative group,ALFF of LIPL,in cingulate gyrus,and right middle frontal gyrus have a tendency of rising.One month after liver transplantation,decreased ALFF is found in BA7 and BA 31,suggesting that the spontaneous low-frequency of local neurons haven't recoverd to normal level.

Objective To investigate the CT features of hepatic echinococcosis in children.Methods Clinical and CT data of 27 cases with hepatic echinococcosis confirmed by pathology and/or serology were retrospectively analyzed.Results Totally there were 26 cases of cystic echinococcosis and 1 case of alveolar echinococcosis.Ten cases were with simple hepatic echinococcosis and 17 cases with other organic echinococcosis,18 cases of intrahepatic single hydatid and 9 cases of intrahepatic multiple hydatid.A total of 1 alveolar lesion and 47 cystic lesions were found,including unilocular cyst accounted for 51.06％ (24/47),cysts with collapse of the internal capsule accounted for 42.55％ (20/47),cysts with wall calcification accounted for 4.26％ (2/47) and multiple cysts accounted for 2.13％ (1/47).There was no solid lesions.The cyst diameters which were larger than 5 cm accounted for 74.47％ (35/47).Conclusion The CT can qualitatively diagnose hepatic echinococcosis in children.It is a reliable method of examination.

With the rapid development of new technologies and global trade and increasing collaboration among countries worldwide,public health has become a global issue.Global health,as a new discipline,has been drawing more attention from both academia and governments.The Belt and Road (B&R) Initiative,proposed by China in 2013,aims to promote trade and resource exchange,including education,research,and health issues,with over 60 countries in Asia,Africa,and Europe.The B&R Initiative provides good opportunities for involved countries to address health problems jointly as well.In response to the B&R Initiative and to promote international collaboration on global health issues,"The 2017 Belt and Road Initiative Global Health International Congress & 2017 Chinese Preventive Medicine Association-Chinese Society on Global Health Annual Meeting" was held on September 24-27,2017 in Xi'an,China.Thus far,this is the largest high-quality international conference held in China that focused on the B&R Initiative global health issues.This article summarizes the background,key sessions and topics covered during the congress,important events and highlights different perspectives of the B&R Initiative and global health by invited experts from China and abroad.The conference included 17 sessions (3 keynote speech forums and 10 scientific sessions,3 young scholar forums,and a research poster session) and about 100 speakers,around 40 of which were leading experts outside of China.All the major sessions were held in English.More than 40 leaders and experts of health sectors from 13 countries presented their work in the congress.Approximately 400 delegates from 29 countries attended the congress.Delegates had extensive discussions about global health related issues,future cooperation and development in global health.The congress fostered international exchange and collaboration.