Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

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

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.

Objective To analyze the diversity and composition changes of gut fungal communities between mouse model of total parental nutrition(TPN)and normal control mice.Methods After mouse model of TPN was constructed,fresh feces were collected from TPN mice(n=5)and normal control mice(n=5).Internal transcribed spacer(ITS)DNA sequencing was applied to determine intestinal fungi,and then bioinformatics analysis was conducted to identify the differences in fungal diversity,structure,and functional properties between the 2 groups of mice.Results There were significant differences in Alpha diversity(P＜0.05)and Beta diversity(P＜0.01)of intestinal fungi between the 2 groups.In the TPN model group,the relative abundances of Candida,Penicillium,Aspergillus and Talaromyces were obviously reduced(all P＜0.01).LEfSe analysis indicated that the above 4 strains were notably enriched in the normal control mice.Conclusion TPN mice exhibit characteristic changes in the composition of gut fungal flora compared to normal control mice.Dysfunction of gut fungal community may promote the occurrence of TPN related complications,and regulating the balance of gut fungal community may become a new strategy for preventing TPN related complications.

OBJECTIVE: To retrospectively analyze the results of chromosomal microarray analysis (CMA) and parental origins of unbalanced translocations among 17 patients, so as to provide reference for their genetic counseling. METHODS: The results of CMA for 7 001 samples tested in Chengdu Women and Children's Central Hospital from January 2019 to January 2022 were retrospectively reviewed. Unbalanced reciprocal translocation was defined as two non-homologous chromosomes with lost and gained segments respectively or both with gained segments, and their parental origins were identified by parental chromosomal karyotyping and/or fluorescence in situ hybridization (FISH). RESULTS: In total 17 unbalanced translocations were identified. In three cases, two non-homologous chromosomes both had gained segments, which constituted a derivative chromosome, with the total number of chromosomes being 47. In the remaining 14 cases, there was a terminal deletion on one chromosome and a terminal duplication on the other, 10 of which were confirmed by karyotyping, with the total number of chromosomes being 46. In the derivative chromosome, the lost segment was replaced by a gained segment from another chromosome. Among 15 cases undergoing parental origin analysis, 12 had paternal or maternal chromosomal abnormalities, including 11 balanced translocations and 1 unbalanced translocation. The unbalanced gametes therefore may form through meiosis. In 3 cases, the parental chromosomes were normal, indicating a de novo origin. CONCLUSION Discovery of terminal duplication and deletion or gained segments on two non-homologous chromosomes by CMA is suggestive of parental balanced translocation, which can facilitate genetic counseling and assessment the recurrence risk for subsequent pregnancies.
Child ; Pregnancy ; Humans ; Female ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Translocation, Genetic ; Microarray Analysis ; Chromosomes

In order to explore a suitable pathway for the scientific and technological achievement transformation at prefecture-level public hospitals, in October 2020, a prefecture-level tertiary hospital carried out the " 3+ 3+ 3" mode for scientific and technological innovation and achievement transformation. A three-level management structure was established, consisting of the ministry of science and education, the working group on the transformation of scientific and technological achievements, and the leading group. Three management systems were improved and formulated, including the " measures for reimbursement and rewards of scientific and technological achievements ", the " measures for intellectual property management", and the " implementation plan for promoting the transfer and transformation of scientific and technological achievements". The management measures for the three stages of intellectual property protection, incubation of scientific and technological achievements, and transfer and transformation of achievements were improved. These measures provided organizational support, institutional support, and feasible paths for this practice. After nearly three years of practice, hospitals had reduced the number of low-quality patent applications, and the number and amount of scientific and technological achievements transformed increased from 1 achievement and 10 000 yuan in 2020 to 9 achievements and 320 000 yuan in 2022. This exploration could provide a reference for the transfer and transformation of professional scientific and technological achievements in prefecture-level public hospitals in China.

WHO Guideline on Country Pharmaceutical Pricing Policies,published in 2020,outlines 10 commonly used pricing methods internationally.However,due to the unique composition of costs for traditional Chinese medicine(TCM),directly applying pricing methods designed for chemical and biological drugs may lead to discrepancies.Currently,in China,drug pricing primarily in-volves internal reference pricing,tender negotiation pricing,promoting the use of quality-assured generic and biosimilar drugs,and centralized procurement.It systematically analyzes various pricing methods and identifies their applicability and underlying reasons concerning the pricing of TCMwithin the medical insurance system.The method of value-based pricing and increasing price transparency has advantages for the pricing regulation of traditional Chinese medicine under medical insurance.

Objective:To clarify the infection and epidemic characteristics of the human metapneumovirus (HMPV) in Chinese patients with febrile respiratory syndrome (FRS), and to provide important baseline data for clinical diagnosis, treatment, prevention and control of HMPV-induced respiratory tract diseases in China.Methods:FRS cases from January 2009 to June 2021 in 9 provinces in China, including Beijing, Hebei, Jilin, Shandong, Shaanxi, Xinjiang, Anhui, Guangdong, Hunan were retrospectively analyzed for their respiratory samples, clinical and epidemic data.The respiratory samples were detected for HMPV by quantitative real-time PCR.Results:A total of 11 660 cases were tested for HMPV, involving 296 (2.54%) HMPV-positive cases.Among 296 HMPV-positive cases, 218 were single HMPV infection, and 78/296 (26.35%) were co-infected with one or more respiratory viruses.HMPV mainly affected children under 5 years of age (3.10%), and in this population, the proportion of pneumonia in HMPV co-infection cases was significantly higher than that of single HMPV infection.HMPV could be detected all year round, which was more popular in winter and spring, with the peak of HMPV epidemic in March.Conclusions:HMPV is one of the important pathogens causing acute respiratory infection in children, showing a clear seasonal epidemic.HMPV can be infected alone or in combination with other respiratory viruses, which may increase the risk of pneumonia in children.

At present, total hip arthroplasty (THA) is the primary treatment for hip diseases such as femoral head necrosis and developmental dysplasia of the hip. It has good effects in reducing pain and improving joint function. The appearance of modular hip prosthesis facilitates adjustment of limb length and femoral offset. However, the wear between the interface of hip prosthesis can lead to inflammatory pseudotumor, osteolysis and other adverse reactions. To explore the risk factors of wear between hip prosthesis interface is helpful to improve the design and manufacturing concept of the product, improve the product performance, help surgeons optimize the operation technology and reduce the impact of human factors on the wear of the prosthesis. Many literatures have reported the mechanism of wear between the head-acetabula interface of prosthesis. The mechanism of wear between the interfaces has been described relatively clearly. In addition to the head-acetabula interface, the wear between the head-neck interface is another major cause of unexplained pain around the joint and prosthesis loosening after hip replacement. Many factors affect head-neck wear. The design of prosthesis (such as prosthesis material and prosthesis taper), surgical technology (such as impact strength and prosthesis mismatch) and patient factors (such as age, gender and activity) have important impact on head-neck wear. Adverse reactions caused by head-neck wear have also been widely concerned. However, there is no considerable solution for wear prevention. Thus, we should optimize the design of prosthesis, improve the surgical technology, and guide the rehabilitation of patients to prevent wear. In order to improve the attention of joint surgeons, the present paper reviews the literatures and analyzes the risk factors of head-neck interface wear and the clinical manifestations caused by head-neck wear.