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

Wandaitang, which is one of classical traditional Chinese medicine(TCM) prescriptions, is derived from Collected Exegesis of Recipes of Fu Qingzhu' s Obstetrics and Gynecology. It is commonly used in modern clinical practice, and included in the Catalogue of Ancient Classical Prescriptions (The First Batch). Collected Exegesis of Recipes of Fu Qingzhu' s Obstetrics and Gynecology and Chen Shi-duo' s Bianzhenglu have a complicated relationship. Both of them have another biography, named Nvke Xianfang and Bianzheng Qiwen. The composition of Wandaitang in the four books is slightly different, while the prescription's explanations and other records are almost the same. The research and development of Wandaitang should be based on the records of Collected Exegesis of Recipes of Fu Qingzhu's Obstetrics and Gynecology. Compared with other classical literatures, Collected Exegesis of Recipes of Fu Qingzhu's Obstetrics and Gynecology was published in a late period and less reproduced in other ancient books. To study the function of Wandaitang, we need to analyze the records in the original book. In addition, we need to make a multi-angle analysis by reference to the theory of TCM, the composition of drugs, the significance of compatibility, as well as the understanding of modern famous doctors, clinical reports and experimental studies in all aspects. The study found that the functions of Wandaitang were relatively concentrated, but with wide major functions involving internal medicine, surgery, gynecological, pediatric, andrological and other departments. According to the study, the authors believe that the functions of the classical TCM prescription of Wandaitang are invigorating spleen to eliminate dampness, dispersing the liver and rectifying Qi, and invigorating Yang. It can be used to treat leucorrhea, diarrhea, edema and stranguria with the syndromes of pale, languid, little food, loose stool and depression. Wandaitang can also be used to treat vaginitis, cervicitis, pelvic inflammatory disease, irritable bowel syndrome, chronic colitis, chronic nephritis, nephrotic syndrome and chronic prostatitis.

OBJECTIVE: To screen the key genes related to the prognosis of lung adenocarcinoma through big data analysis and explore their clinical value and potential mechanism. METHODS: We analyzed GSE18842, GSE27262, and GSE33532 gene expression profile data obtained from the Gene Expression Omnibus (GEO). Bioinformatics methods were used to screen the differentially expressed genes in lung adenocarcinoma tissues and KEGG and GO enrichment analysis was performed, followed by PPI interaction network analysis, module analysis, differential expression analysis, and prognosis analysis. The expressions of MAD2L1 and TTK by immunohistochemistry were verified in 35 non-small cell lung cancer specimens and paired adjacent tissues. RESULTS: We identified a total of 256 genes that showed significant differential expressions in lung adenocarcinoma, including 66 up-regulated and 190 down-regulated genes. Thirty-two up-regulated core genes were screened by functional analysis, and among them 29 were shown to significantly correlate with a poor prognosis of patients with lung adenocarcinoma. All the 29 genes were highly expressed in lung adenocarcinoma tissues compared with normal lung tissues and were mainly enriched in cell cycle pathways. Seven of these key genes were closely related to the spindle assembly checkpoint (SAC) complex and responsible for regulating cell behavior in G2/M phase. We selected SAC-related proteins TTK and MAD2L1 to test their expressions in clinical tumor samples, and detected their overexpression in lung adenocarcinoma tissues as compared with the adjacent tissues. CONCLUSIONS Seven SAC complex-related genes, including TTK and MAD2L1, are overexpressed in lung adenocarcinoma tissues with close correlation with the prognosis of the patients.
Adenocarcinoma of Lung/genetics* ; Big Data ; Cell Cycle Proteins/genetics* ; Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics* ; M Phase Cell Cycle Checkpoints ; Mad2 Proteins/genetics* ; Protein-Serine-Threonine Kinases/genetics* ; Protein-Tyrosine Kinases/genetics*

ObjectiveTo investigate the value of serum carbohydrate antigen 19-9 (CA19-9) combined with procalcitonin (PCT) in the diagnosis of acute cholangitis secondary to common bile duct stones. Methods A retrospective analysis was performed for the clinical data of 764 patients with common bile duct stones who were admitted to The Third Affiliated Hospital of Zunyi Medical University from June 2012 to June 2018, and according to the presence or absence of acute cholangitis, they were divided into cholangitis group with 173 patients and non-cholangitis group with 591 patients. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Receiver operating characteristic (ROC) curves were plotted for statistically different indices to calculate the cut-off value, sensitivity, and specificity of each index. ResultsCompared with the non-cholangitis group, the cholangitis group had significantly higher levels of C-reactive protein (CRP) (78.24±8.02 mg/L vs 30.14±4.25 mg/L, t=3.730, P=0.038), PCT (2.25±0.21 ng/ml vs 0.21±0.06 ng/ml,t= 9.297, P＜0.001), and CA19-9 (87.52±7.95 kU/L vs 2415±3.87 kU/L, t=26.35, P＜0.001). Serum PCT had an area under the ROC curve (AUC) of 0.907, a sensitivity of 82.4%, and a specificity of 86.1%, serum CA19-9 had an AUC of 0.825, a sensitivity of 85.2%, and a specificity of 80.5%, and serum CRP had an AUC of 0.643, a sensitivity of 69.2%, and a specificity of 54.3%; CRP had no diagnostic value due to an AUC of ＜0.7. Serum PCT combined with CA19-9 had a sensitivity of 97.11%, a specificity of 98.65%, a false negative rate of 2.89%, and a false positive rate of 1.35%. Conclusion Both serum CA19-9 and PCT have an important value in predicting acute cholangitis secondary to common bile duct stones, and combined measurement of serum CA19-9 and PCT has significant increases in specificity and sensitivity and can thus be used as a predictive indicator for acute cholangitis.

Being an important clinical fungal pathogen,Aspergillus (A.)fumigatus can cause fatal invasive fungal infections.Azoles are the first line drugs in treating various Aspergillus-caused diseases.Worldwidely,reports related to azole resistance in A.fumigatus have been increasing which posing a threat on the effectiveness of clinically used azole and agricultural fungicides.Currently,it has become an important public health issue.In this review,we summarize findings from literature regarding the following areas:the occurrence of azole resistance in A.fumigatus,the molecular mechanisms of resistance,contributing factors for the emergence of azole resistance,evolution of resistant strains and related control and prevention measures.

Objective To investigate the relationship between endoscopic diagnosis and pathological nature of gastric mucosal leukoplakia. Methods Analysis of gastric mucosal leukoplakia patients’ endoscopic features and pathological characteristics of last 3 years. Results Endoscopic diagnosis was made in 116 cases of gastric mucosal leukoplakia. Samples were gray white, round, round shaped or patchy in general observation. Diameter was 0.2 ~1.6 cm, foam cell aggregation appeared in the natural layer of mucous membrane in 88 cases (75.9 %), with varying degrees of inflammatory cells infiltration. The foam cells accumulation were observed in high rate among the gastric mucosal leukoplakia cases. Conclusion Pathological changes of gastric mucosal leukoplakia is gastric xanthoma with chronic inflammation of mucosa.

BACKGROUND:Hepatic fibrosis in chronic liver disease can be reversed. Studies have shown that Periplaneta americana extract has anti-fibrosis effect, and has protective effect on the experimental hepatic fibrosis rats.
OBJECTIVE:To observe the effect of Periplaneta americana extract sticky sugar amino acid on hepatic fibrosis, and to primarily explore the mechanism of sticky sugar amino acid against hepatic fibrosis.
METHODS:Rat models of immune hepatic fibrosis were induced by pig serum and intragastricaly administered 0.5, 0.25, 0.10 g/kg sticky sugar amino acid. Four indexes of hepatic fibrosis were detected by radioimmunoassay. Immunohistochemical staining wasused to measure transforming growth factor beta 1, tissue inhibitor of metaloproteinase protein expression intensity and positive cel rate, to determine the correlation of different concentrations of sticky sugar amino acid, transformation growth factorbeta 1 and tissue inhibitor of metaloproteinase.
RESULTS AND CONCLUSION:(1) The Periplaneta americana extract sticky sugar amino acid reduced the levels of laminin, type III procolagen, type IV colagen and hyaluronidase (P< 0.01) and reduced the expression of transformation growth factor beta 1 and tissue inhibitor of metaloproteinase 1 in liver tissue (P< 0.01). (2) Sticky sugar amino acid concentration and transformation growth factor beta 1 and tissue inhibitor of metaloproteinase 1 protein expression showed a significant negative correlation (|r| > 0.9). (3) Results confirmed that the Periplaneta americana extract sticky sugar amino acid can change the reversal of hepatic fibrosis. Its mechanism of action is associated with expression of transforming growth factor beta 1 and tissue inhibitor of metaloproteinase 1 inhibited by sticky sugar amino acids.

Objective To study the influencing factors of pediatric in-hospital cardiopulmonary resuscitation(CPR).Methods It was a retrospective observational study.We studied a total of 281 children who suffered in-hospital cardiopulmonary arrest(CPA).The outcome was defined as sustained return of spon-taneous circulation ﹥20 min.Results A total of 281 patients met study entry criteria.In 129 children (45.9%),return of spontaneous circulation sustained ﹥20 min and 20 cases(8.8%)survived to hospital discharge.In the univariate analysis,gender,age,weight,time of CPA happened,first cardiac rhythm,pH, blood lactate had no obvious influence on the outcome.Underlying disease,the place of CPA,personnel fac-tors,airway support,the duration of CPR,doses of adrenaline,use of bicarbonate and blood glucose level were associated with outcome.Conclusion At present,the rate of successful CPR and discharge of hospital is still low.Respiratory disease has a higher survival rate.CPR ﹥20 min,use of bicarbonate and using adrenaline≥3 doses are associated with poor outcome and an increase in mortality.

Animals ; Drosophila Proteins ; genetics ; metabolism ; Drosophila melanogaster ; Memory ; physiology ; Mushroom Bodies ; cytology ; metabolism ; Proteins ; genetics ; metabolism

China ; Critical Care ; trends ; Pediatrics ; trends