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

Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

Objective　To analyze the epidemic characteristics of dengue fever in Zhejiang Province from 2011 to 2023, and provide a scientific basis for formulating dengue prevention and control strategies in Zhejiang Province. Methods The data of dengue fever cases in Zhejiang Province from 2011 to 2023 were collected from the China Information System for Disease Control and Prevention. Descriptive and statistical analyses of the gender, age, occupation, seasonal distribution, regional distribution, and the time interval from onset to diagnosis of dengue fever imported cases and indigenous cases were conducted using SPSS26.0 software. Results A total of 3 021 cases of dengue fever were reported in Zhejiang Province from 2011 to 2023, including 1 421 imported cases and 1 600 indigenous cases. There were 1 692 males and 1 329 females, with a male-to-female ratio of 1.27∶1. The proportion of males among imported cases (62.28%) was higher than that of indigenous cases (50.44%) (χ2=42.838, P<0.001). The indigenous cases were mainly concentrated in 40 to <70 years old, while the imported cases were mainly concentrated in 20 to <50 years old, with the age of the indigenous cases being higher than that of the imported cases (Z=-18.435, P<0.001). The occupations of the cases were mainly business service, workers/migrant workers, retirees, domestic workers and unemployed people, and farmers. Among imported cases, the highest proportion was in business service workers (23.29%), while among local cases, the highest proportion was in retirees (24.38%). The occupational distribution difference between imported and indigenous cases was statistically significant (χ2=331.903, P<0.001). The indigenous cases predominantly occurred from August to October, while imported cases were reported throughout the year, mainly occurring from June to October, among which domestic imported cases mainly appeared from July to December, and imported cases from abroad could occur throughout the year. In addition to the period of COVID-19 prevention and control, the number of counties (cities and districts) reporting dengue cases in Zhejiang Province increased year by year from 2011 to 2023, with 96.67% of counties (cities and districts) reporting dengue cases, of which 51.11% counties reported indigenous cases. There was a statistically significant difference in the interval from onset to confirmation between imported cases and indigenous cases (Z=-3.269, P=0.001). Conclusions There are obvious seasonal, population, and regional distribution patterns of dengue fever in Zhejiang Province. Attention should be paid to the dynamics of dengue fever outbreaks in Yunnan border areas and Guangdong, and the control of imported cases, vector surveillance and control, and prevention and control work in key areas should be further strengthened. In 2023, the epidemic situation of dengue fever in Zhejiang Province is grim, with a substantial increase in imported cases and gradual expansion of epidemic coverage, which will remain the focus of infectious disease prevention and control in Zhejiang Province in the future.

Recently, small nucleolar RNAs (snoRNAs) have transcended the genomic "noise" to emerge as pivotal molecular markers due to their essential roles in tumor progression. Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance. Historically, snoRNA research has concentrated on two classical mechanisms: 2'-O-ribose methylation and pseudouridylation. This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors, encompassing transcriptional, post-transcriptional, and post-translational regulation. We further discuss the synergistic effect between snoRNA host genes (SNHGs) and snoRNAs in tumor progression. More importantly, snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes. Accordingly, we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.

Objective To investigate the expression of NMDAR1 in the hippocampus and cerebral cortex of old rats after 30-min -inhalation of 2% isoflurane, and to investigate the effects of isoflurane on the learning and memory functions of old rats and the underlying mechanism. Methods The healthy old male Sprague Dawley rats (n = 36) were randomly divided into the control group, the oxygen group, the 2-hour post-recovery group, the 1-day post-recovery group, the 3-day post-recovery group, and the 7-day post-recovery group. The morris water maze was used to detect the ethological effect of 30-min inhalation of isoflurane , and the immunohistochemistry assay was used to detect the expression of NMDAR1 in the hippocampus (CA1, CA3) and the cerebral cortex. Results The 30-min inhalation of 2% isoflurane inhibited the learning and memory abilities of old rats at 2 h post-recovery. On 1 d post-recovery, the inhibition of learning and memory began to reduce, then on 3 d and 7 d post-recovery, the learning and memory abilities continously recovered. The expression of NMDAR1 in the rat hippocampus and cerebral cortex decreased at 2 h post-recovery, and reversed on 1 d post-recovery and reached the normal level on 3 d and 7 d post-recovery. Conclusion 30-min inhalation of 2%isoflurane had an inhibitory effect on the learning and memory abilities of old rats, and the attenuation of NMDAR1 in the hippocampus and cerebral cortex may involve in this process.

OBJECTIVES: To expound the injury-disease relationship between spondylolysis and trauma for the points of forensic identification. METHODS: Total 26 cases of spondylolysis were collected and the characteristics of this disease such as age, accompanied symptoms, treatment and injury manner were discussed. RESULTS: The causal relationship existed between trauma and injury consequence in 2 appraised individuals and both of them aged less than 50 years old. The injury manners of both were high-energy injury with combined injury and these 2 patients were treated by operation. CONCLUSIONS The analysis of injury-disease relationship between spondylolysis and trauma should be paid attention in the middle-young age under 50 years old. More importantly, the injury-disease relationship should be analyzed in the patients who chose operative treatment.
Forensic Pathology ; Humans ; Middle Aged ; Spondylolysis/surgery* ; Wounds and Injuries/surgery*

OBJECTIVETo assess the effect of Shenmai Injection (SMI) on left ventricular diastolic function (LVDF) in patients with chronic heart failure (CHF) by tissue Doppler imaging (TDI).

METHODSSixty-four CHF patients were randomly assigned to two groups, the observation group and the control group. Basic treatment including polarized liquid therapy was given to all the patients. In addition, SMI was given to patients of the observation group. The treatment duration was 14 days. TDI was performed in all the patients 3 days prior to the initiation of the treatment and one week after the medication to measure the average movement velocity of the mitral ring of the left ventricle at the early systolic stage and late diastolic stage (Ea and Aa); the outcomes were compared with the corresponding parameters obtained from blood flow Doppler echocardiography, namely, the velocity of the E-wave (E) and A-wave (A).

RESULTSAfter treatment, Ea and Ea/Aa increased and Aa decreased significantly in the observation group (P<0.05). In the control group, although some improvement was seen, there was no statistically significant change (P>0.05). No statistical significance was shown between groups in these parameters after treatment.

CONCLUSIONTDI assessment shows that SMI could effectively improve the LVDF in CHF patients.

Adult ; Aged ; Cardiovascular Agents ; administration & dosage ; adverse effects ; pharmacology ; Chronic Disease ; Diastole ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; pharmacology ; Echocardiography, Doppler ; Female ; Heart Failure, Diastolic ; diagnostic imaging ; drug therapy ; physiopathology ; Humans ; Injections ; Male ; Middle Aged ; Treatment Outcome ; Ventricular Dysfunction, Left ; drug therapy ; Ventricular Function ; drug effects