Novel MIP gene mutation causes autosomal-dominant congenital cataract.

AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Molecular Prevalence, Genetic Diversity, and Tissue Tropism of Bartonella Species in Small Mammals from Yunnan Province, China.

Bartonella is an intracellular parasitic zoonotic pathogen that can infect animals and cause a variety of human diseases. This study investigates Bartonella prevalence in small mammals in Yunnan Province, China, focusing on tissue tropism. A total of 333 small mammals were sampled from thirteen species, three orders, four families, and four genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified thirty, ten, and five strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in Episoriculus leucops (GS136). Analysis of the different tissues naturally infected by Bartonella species revealed varied copy numbers across different tissues, with the highest load in spleen tissue. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting the presence of extensive tissue tropism in Bartonella species naturally infecting small mammalian tissues.

Constructing an Asymmetric Covalent Triazine Framework to Boost the Efficiency and Selectivity of Visible-Light-Driven CO2 Photoreduction.

The photocatalytic reduction of CO2 represents an environmentally friendly and sustainable approach for generating valuable chemicals. In this study, a thiophene-modified highly conjugated asymmetric covalent triazine framework (As-CTF-S) is developed for this purpose. Significantly, single-component intramolecular energy transfer can enhance the photogenerated charge separation, leading to the efficient conversion of CO2 to CO during photocatalysis. As a result, without the need for additional photosensitizers or organic sacrificial agents, As-CTF-S demonstrates the highest photocatalytic ability of 353.2 µmol g-1 and achieves a selectivity of ≈99.95% within a 4 h period under visible light irradiation. This study provides molecular insights into the rational control of charge transfer pathways for high-efficiency CO2 photoreduction using single-component organic semiconductor catalysts.

Camrelizumab plus famitinib in previously chemo-immunotherapy treated patients with advanced NSCLC: results from an open-label multicenter phase 2 basket study.

BACKGROUND: The combination of immune checkpoint inhibitors and antiangiogenic agents has been effective in treating multiple cancers. This was further explored in an open-label, multicenter phase 2 basket study (NCT04346381), which evaluated the antitumor activity and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) in patients with advanced solid tumors. We herein report the findings from the cohort of advanced NSCLC patients who progressed after treatment with platinum-doublet chemotherapy and immunotherapy. METHODS: Eligible patients were enrolled and treated with camrelizumab (200 mg once every 3 weeks via intravenous infusion) and oral famitinib (20 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled in this cohort, with a median follow-up duration of 11.5 months. Three patients (7.5%) achieved a partial response, and 29 patients (72.5%) achieved stable disease. The ORR and DCR with this combination regimen were 7.5% (95% CI, 1.6-20.4) and 80.0% (95% CI, 64.4-90.9), respectively. The median DoR was 12.1 months (95% CI, 10.3-not reached). The median PFS was 5.4 months (95% CI, 4.1-7.5), and the median OS was 12.1 months (95% CI, 9.1-16.7). The estimated 12-month OS rate was 51.5% (95% CI, 34.9-65.9). The most frequent grade 3 or higher treatment-related adverse events occurring in more than 5% of patients included hypertension (27.5%), palmar-plantar erythrodysesthesia syndrome (10%), decreased neutrophil count (10%), and proteinuria (7.5%). CONCLUSION: Camrelizumab plus famitinib demonstrated favorable benefits in PFS and OS, along with manageable safety profiles, in patients with advanced NSCLC who progressed after platinum-doublet chemotherapy and immunotherapy. This finding warrants further exploration.

Synergy of metallic Co and oxygen vacancy sites in Co/Ce-MOF catalysts for efficiently promoting lignin derived phenols and macromolecular lignin hydrodeoxygenation.

The enhanced utilization of biomass-derived chemicals for the generation of high value aromatics through an advanced catalytic strategy has captured considerable attention within the realm of eco-friendly manufacturing. This work presented four innovative three-dimensional rod-shaped mesoporous Ce-based MOF materials, which were coupled with a H-donor solvent to facilitate vanillin hydrodeoxygenation and macromolecular lignin. Under the optimized conditions (30 mg CoCe@C catalyst, 2 MPa N2 pressure, 15 mL isopropanol, 190 °C, and 5 h), the CoCe@C catalyst achieved nearly complete conversion of vanillin and demonstrated 87.8 % selectivity in the hydrogen-donor solvent. The characterization findings suggested that the synergy between metallic Co and oxygen vacancy sites enabled the effective activation of CHO group in vanillin, leading to formation of reactive product MMP. In addition, the optimal CoCe@C catalyst could also achieve macromolecular lignin hydrodeoxygenation to obtain high yield of lignin oil products with narrower molecular weight distribution. This study presented a viable approach for the concurrent utilization of lignin derivatives in the generation of high value fuels and chemicals.

Cancer associated fibroblast secreted miR-432-5p targets CHAC1 to inhibit ferroptosis and promote acquired chemoresistance in prostate cancer.

Prostate cancer (PCa) ranks as the sixth most serious male malignant disease globally. While docetaxel (DTX) chemotherapy is the standard treatment for advanced PCa patients with distant metastasis, some individuals exhibit insensitivity or resistance to DTX. Cancer-associated fibroblasts (CAFs) play a pivotal role as stromal cells within the tumor microenvironment, influencing tumor development, progression, and drug resistance through exosomes. Ferroptosis, a novel form of programmed cell death, is characterized by intracellular iron accumulation that triggers lipid peroxidation, ultimately leading to cell demise. To delve into the potential mechanisms of chemotherapy resistance in prostate cancer, our research delved into the impact of CAF-derived exosomes on ferroptosis. Our findings revealed that CAF exosomes hindered the buildup of lipid reactive oxygen species (ROS) in prostate cancer cells induced by erastin, as well as mitigated erastin-induced mitochondrial damage, thereby impeding iron-induced cell death in prostate cancer cells. Furthermore, miR-432-5p was identified to diminish glutathione (GSH) consumption by targeting CHAC1, consequently inhibiting ferroptosis in prostate cancer cells. Our study found that miR-432-5p, originating from cancer-associated fibroblast (CAF) exosomes, suppresses ferroptosis by targeting CHAC1, thereby increasing resistance to docetaxel (DTX) in PCa. This research introduces a novel approach to address resistance to DTX.

New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is responsible for a significant number of cancer-related deaths worldwide and its incidence is increasing. Locoregional treatments, which are precision procedures guided by imaging to specifically target liver tumors, play a critical role in the management of a substantial portion of HCC cases. These therapies have become an essential element of the HCC treatment landscape, with transarterial chemoembolization (TACE) being the treatment of choice for patients with intermediate to advanced stages of the disease. Other locoregional therapies, like radiofrequency ablation, are highly effective for small, early-stage HCC. Nevertheless, the advent of targeted immunotherapy has challenged these established treatments. Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in clinical settings. However, their specific uses and the development of resistance in subsequent treatments have led clinicians to reevaluate the future direction of HCC therapy. This review concentrates on the distinct features of both systemic and novel locoregional therapies. We investigate their effects on the tumor microenvironment at the molecular level and discuss how targeted immunotherapy can be effectively integrated with locoregional therapies. We also examine research findings from retrospective studies and randomized controlled trials on various combined treatment regimens, assessing their validity to determine the future evolution of locoregional therapies within the framework of personalized, comprehensive treatment.

Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study.

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. METHODS: We conducted a multicenter retrospective study to characterize ICI-associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer-Lemeshow test. RESULTS: Forty-four patients were identified, including thirty-five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin-I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme-MB (CK-MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty-one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N-terminal pro-B-type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK-MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non-severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK-MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055-2.984, p = 0.031) was the independent risk factor of the development of ICI-associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002-1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026-3.483, p = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK-MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016). CONCLUSIONS: Elevated CK-MB after ICI treatment is the independent risk factor for the incidence of ICI-associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI-associated severe myocarditis. CK-MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI-associated myocarditis and severe myocarditis.

Pulmonary Arterial Anatomical Patterns: a Classification Scheme Based on Lobectomy and 3D-CTBA.

PURPOSE: Preoperative evaluation of pulmonary vascular and tracheal routes and variations is of great importance to the surgeon. Three-dimensional computed tomography bronchography and angiography (3D-CTBA) has evolved in recent years with the optimization of 3D reconstruction techniques and artificial intelligence. We aim to apply CT angiography and Exoview 3D reconstruction technology to assess patients' pulmonary arterial tree and its anatomical variants and to try to summarize a set of anatomical typing of the pulmonary arterial tree that is relatively easy and conducive to promoting teaching based on surgical habits of lobectomy. METHODS: A total of 358 patients hospitalized in the Department of Thoracic Surgery of the First Affiliated Hospital of Soochow University between July 2020 and August 2021 were included in this study. We carefully analyzed the site of emanation, alignment, and number of branches of the pulmonary artery according to a uniform classification method in conjunction with the two-dimensional CT images and transformed them into 3D reconstruction models. RESULTS: Different types of pulmonary artery were observed in 358 cases. We evaluated the complete pulmonary artery tree and counted the number and frequency of major arteries of the pulmonary based on the surgical habits of anatomical lobectomy. CONCLUSION: The 3D-CTBA technique enables us to adequately assess the anatomy of the pulmonary arteries. Moreover, we provide a practical classification scheme of pulmonary arterial anatomical patterns based on lobectomy and 3D-CTBA. Our data can be used by clinicians in the teaching of pulmonary artery anatomy and the preoperative preparation for anatomical lobectomy.

A Stretchable and Tough Graphene Film Enabled by Mechanical Bond.

The pursuit of fabricating high-performance graphene films has aroused considerable attention due to their potential for practical applications. However, developing both stretchable and tough graphene films remains a formidable challenge. To address this issue, we herein introduce mechanical bond to comprehensively improve the mechanical properties of graphene films, utilizing [2]rotaxane as the bridging unit. Under external force, the [2]rotaxane cross-link undergoes intramolecular motion, releasing hidden chain and increasing the interlayer slip distance between graphene nanosheets. Compared with graphene films without [2]rotaxane cross-linking, the presence of mechanical bond not only boosted the strength of graphene films (247.3 vs 74.8 MPa) but also markedly promoted the tensile strain (23.6 vs 10.2%) and toughness (23.9 vs 4.0 MJ/m3). Notably, the achieved tensile strain sets a record high and the toughness surpasses most reported results, rendering the graphene films suitable for applications as flexible electrodes. Even when the films were stretched within a 20% strain and repeatedly bent vertically, the light-emitting diodes maintained an on-state with little changes in brightness. Additionally, the film electrodes effectively actuated mechanical joints, enabling uninterrupted grasping movements. Therefore, the study holds promise for expanding the application of graphene films and simultaneously inspiring the development of other high-performance two-dimensional films.

Reliable detection of malachite green by self-assembled SERS substrates based on gold-silicon heterogeneous nano pineapple structures.

Morphology regulation of heterodimer nanoparticles and the use of their asymmetric features for further practical applications are crucial because of the rich optical properties and various combinations of heterodimers. This work used silicon to asymmetrically wrap half of a gold sphere and grew gold branches on the bare gold surface to form heterogeneous nano pineapples (NPPs) which can effectively improve Surface-enhanced Raman scattering (SERS) properties through chemical enhancement and lightning-rod effect respectively. The asymmetric structures of NPPs enabled them to self-assemble into the monolayer membrane with consistent branch orientation. The prepared substrate had high homogeneity and better SERS ability than disorganized substrates, and achieved reliable detection of malachite green (MG) in clams with a detection limit of 7.8 × 10-11 M. This work provided a guide to further revise the morphology of heterodimers and a new idea for the use of asymmetric dimers for practically photochemical and biomedical sensing.

Platycodon grandiflorum saponins: Ionic liquid-ultrasound-assisted extraction, antioxidant, whitening, and antiaging activity.

This study explored the use of ionic liquid-ultrasound (ILU)-assisted extraction to enhance the extraction rate of Platycodon grandiflorum saponins (PGSs), and the content, extraction mechanism, antioxidant activity, whitening, and antiaging activity of PGSs prepared using ILU, ultrasound-water, thermal reflux-ethanol, and cellulase hydrolysis were compared. The ILU method particularly disrupted the cell wall, improved PGS extraction efficiency, and yielded a high total saponin content of 1.45 ± 0.02 mg/g. Five monomeric saponins were identified, with platycodin D being the most abundant at 1.357 mg/g. PGSs displayed excellent in vitro antioxidant activity and exhibited inhibitory effects on tyrosinase, elastase, and hyaluronidase. The results suggest that PGSs may have broad antioxidant, skin-whitening, and antiaging potential to a large extent. Overall, this study provided valuable insights into the extraction, identification, and bioactivities of PGSs, which could serve as a reference for future development and application of these compounds in the functional foods industry.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Anlotinib hydrochloride consolidation after concurrent chemoradiotherapy in stage III non-small-cell lung cancer: a truncated, randomized, multicenter, clinical study (ALTER-L029).

Anlotinib is an antiangiogenic drug that shows good efficacy and safety in patients with advanced non-small-cell lung cancer (NSCLC). This study aimed to explore the efficacy and safety of anlotinib for consolidation therapy in patients with stage III locally advanced, unresectable NSCLC after concurrent chemoradiotherapy (cCRT). This was a randomized, parallel-controlled, open-label, multicenter, phase II trial of patients with unresectable/nonoperated NSCLC treated with cCRT. The participants were randomized 2:1 to the anlotinib or control group. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the disease control rate (DCR) and overall survival. This study was terminated early due to poor recruitment. Nine and two participants were randomly assigned to the anlotinib and control groups, respectively. One participant in the control group was excluded due to taking prohibited medications before the first efficacy evaluation. In the anlotinib group, the median age was 63 (range, 37-74) years. Two participants achieved partial response, six stable disease, and one progressive disease as best response. The DCR was 88.9%. The median PFS was 11.5 months, and the 12-month PFS rate was 33.9%. All related adverse events were grade 1 or 2. Two participants had a dose adjustment during the study. The evaluable data suggest that anlotinib alone was effective and tolerable in consolidation therapy after cCRT in patients with stage III unresectable NSCLC. The results need to be confirmed by a large-sample trial. This clinical trial was registered on www.clinicaltrials.gov (NCT03743129). Registration date: 6 September 2018.

High-density, highly sensitive sensor array of spiky carbon nanospheres for strain field mapping.

While accurate mapping of strain distribution is crucial for assessing stress concentration and estimating fatigue life in engineering applications, conventional strain sensor arrays face a great challenge in balancing sensitivity and sensing density for effective strain mapping. In this study, we present a Fowler-Nordheim tunneling effect of monodispersed spiky carbon nanosphere array on polydimethylsiloxane as strain sensor arrays to achieve a sensitivity up to 70,000, a sensing density of 100 pixel cm-2, and logarithmic linearity over 99% within a wide strain range of 0% to 60%. The highly ordered assembly of spiky carbon nanospheres in each unit also ensures high inter-unit consistency (standard deviation ≤3.82%). Furthermore, this sensor array can conformally cover diverse surfaces, enabling accurate acquisition of strain distributions. The sensing array offers a convenient approach for mapping strain fields in various applications such as flexible electronics, soft robotics, biomechanics, and structure health monitoring.

Cystic adenomyoma of the uterus: Case report and literature review.

Cystic adenomyosis is a rare type of adenomyosis. The main clinical manifestation of uterine cystic adenomyoma is severe dysmenorrhoea, and the condition can be diagnosed by relevant clinical examination. The preferred treatment, with a good prognosis, is lesion resection. The clinical data of a patient with uterine cystic adenomyoma recorded at the Third Hospital of Hebei Medical University are reported herein. A 39-year-old female patient presented with tolerable menstrual pain and aggravated dysmenorrhoea, which she had experienced for 4 years, and menorrhagia, which she had had for approximately 1 year. Ultrasound and tumour marker tests suggested abnormalities, and magnetic resonance imaging confirmed a diagnosis of uterine cystic adenomyoma. A hysteroscopy and intrauterine lesion electrocision were performed, and the results of postoperative pathology tests suggested that the endometriosis cysts had returned to normal after the postoperative intervention. The analysis of the clinical manifestations and diagnosis and treatment of uterine cystic adenomyoma can improve the understanding of the disease and reduce the rates of misdiagnosis and missed diagnoses to ensure early detection with timely diagnosis and treatment.

Fabrication of SERS composite substrates using Ag nanotriangles-modified SiO2 photonic crystal and the application of malachite green detection.

A novel surface-enhanced Raman scattering (SERS) composite substrates on the basis of Ag triangular nanoplates(Ag TNPs)-modified SiO2 photonic crystals (PC) is fabricated and applied to the SERS detection of malachite green (MG). It consists of uniformly arranged Ag TNP@SiO2, a new PC. Notably, Ag TNP are uniformly aligned on the SiO2 surface, forming a three-dimensional high-density hotspot nanostructure. With the tip "hot spots" of Ag TNPs, Bragg diffraction of SiO2 and coupling enhancement between Ag TNPs and SiO2, the SERS enhancement of this composite substrates was multiplied. The effect on the SERS of Ag TNP@SiO2 composite substrate was systematically optimized by tuning Ag TNP size, size of SiO2 microspheres, coverage of Ag TNPs on SiO2 and fabrication method of Ag TNPs and PC. Moreover, the uniform of SERS composite substrates and Raman signal was dramatically increased by the method of vertical deposition. Eventually, the SERS composite substrates were employed in MG detection. Its broad detection range of 1 pM-1 µM and low limit of detection (LOD) of 0.49 pM indicated acceptable sensitivity and repeatability. This work illustrates the promising applicability in food safety analysis based on SERS composite substrates composed by Ag TNP@SiO2 with numerous SERS enhancements and excellent stability.

Efficient Glucose Isomerization to Fructose using Photoregenerable MgSnO3 Catalyst with Cooperative Acid-Base Sites.

The isomerization of glucose to fructose plays a crucial role in the food industry and the production biomass-derived chemicals in biorefineries. However, the catalyst used in this reaction suffers from low selectivity and catalyst deactivation due to carbon or by-product deposition. In this study, MgSnO3 catalyst, synthesized via a facile two-step process involving hydrothermal treatment and calcination, was used for glucose isomerization to fructose. The catalyst demonstrated outstanding catalytic performance, achieving a fructose equilibrium yield of 29.8% with a selectivity exceeding 90% under mild conditions owing to its acid-base interaction. Notably, spent catalysts can be regenerated by photoirradiation to remove surface carbon, thereby avoiding the changes in properties and subsequent loss of activity associated with conventional calcination regeneration method. This novel approach eliminates the energy consumption and potential structural aggregation associated with traditional calcination regeneration methods. The acid-base active sites of the catalyst, along with their corresponding catalytic reaction mechanism and photoregeneration mechanism were investigated. This study presents a demonstration of the comprehensive utilization of catalytic material properties, i.e., acid-base and photocatalytic functionalities, for the development of a green and sustainable biomass thermochemical conversion system.

Determination of vancomycin and meropenem in serum and synovial fluid of patients with prosthetic joint infections using UPLC-MS/MS.

Numerous studies have suggested that intra-articular administration of antibiotics following primary revision surgery may be one of the methods for treating prosthetic joint infection (PJI). Vancomycin and meropenem are the two most commonly used antibiotics for local application. Determining the concentrations of vancomycin and meropenem in the serum and synovial fluid of patients with PJI plays a significant role in further optimizing local medication schemes and effectively eradicating biofilm infections. This study aimed to establish a rapid, sensitive, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining the concentrations of vancomycin and meropenem in human serum and synovial fluid. Serum samples were processed using acetonitrile precipitation of proteins and dichloromethane extraction, while synovial fluid samples were diluted before analysis. Chromatographic separation was achieved in 6 min on a Waters Acquity UPLC BEH C18 column, with the mobile phase consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Quantification was carried out using a Waters XEVO TQD triple quadrupole mass spectrometer with an electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) mode was employed to detect the following quantifier ion transitions: 717.95-99.97 (norvancomycin), 725.90-100.04 (vancomycin), 384.16-67.99 (meropenem). The method validation conformed to the guidelines of the FDA and the Chinese Pharmacopoeia. The method demonstrated good linearity within the range of 0.5-50 µg/ml for serum and 0.5-100 µg/ml for synovial fluid. Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, matrix effect, and stability validation results all met the required standards. This method has been successfully applied in the pharmacokinetic/pharmacodynamic (PK/PD) studies of patients with PJI.