New drug combination regimen based on pharmacokinetic characteristics-Erdafitinib combined with sertraline or duloxetine.

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

Safety evaluation of extracorporeal shockwave lithotripsy for pancreatic stones: Experience based on a large chronic pancreatitis cohort.

BACKGROUND: The safety of extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and adverse events were not evaluated and classified within large sample population. This study aimed to evaluate the safety and classify the adverse events of P-ESWL based on a large sample cohort. METHODS: This is an observational study based on the large prospective chronic pancreatitis (CP) cohort. Patients with painful pancreatic stones over 5 mm who underwent P-ESWL between March 2011 and June 2018 at Shanghai Changhai Hospital were included. Adverse events after P-ESWL including complications and transient adverse events (TAEs) were recorded. Risk factors of adverse events were analyzed through univariable and multivariable logistics regression analysis. Sensitivity analysis was conducted to test the stability of the study. RESULTS: Totally 2,071 patients underwent 5,002 sessions of P-ESWL were included. The overall complication rate and TAEs rate after all P-ESWL procedures were 5.2% and 20.9%. The complications and TAEs rate decreased obviously within the first 6 sessions. Several independent risk factors for adverse events after P-ESWL were identified. Sensitivity analysis suggested the stability of the results. CONCLUSIONS: P-ESWL is a safe treatment for pancreatic stones. Multiple P-ESWL sessions did not increase the complications and TAEs rate. ClincialTrials.gov number, NCT05916547.

Antifungal Activity of Phloroglucinol Derivatives against Botrytis cinerea and Monilinia fructicola.

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

In Vivo Interactions of Nucleic Acid Nanostructures With Cells.

Nucleic acid nanostructures, derived from the assembly of nucleic acid building blocks (e.g., plasmids and oligonucleotides), are important intracellular carriers of therapeutic cargoes widely utilized in preclinical nanomedicine applications, yet their clinical translation remains scarce. In the era of "translational nucleic acid nanotechnology", a deeper mechanistic understanding of the interactions of nucleic acid nanostructures with cells in vivo will guide the development of more efficacious nanomedicines. This review showcases the recent progress in dissecting the in vivo interactions of four key types of nucleic acid nanostructures (i.e., tile-based, origami, spherical nucleic acid, and nucleic acid nanogel) with cells in rodents over the past five years. Emphasis lies on the cellular-level distribution of nucleic acid nanostructures in various organs and tissues and the cellular responses induced by their cellular entry. Next, in the spirit of preclinical translation, this review features the latest interactions of nucleic acid nanostructures with cells in large animals and humans. Finally, the review offers directions for studying the interactions of nucleic acid nanostructures with cells from both materials and biology perspectives and concludes with some regulatory updates.

Management strategies and outcomes in pregnancy-related acute aortic dissection: a multicentre cohort study in China.

BACKGROUND: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD. METHODS: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed. RESULTS: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001). CONCLUSIONS: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability. TRIAL REGISTRATION NUMBER: NCT05501145.

[Separation/Conversion Disorders in Functional Coma With Pseudocataplexy: Report of One Case and Literature Review].

Separation/conversion disorders in functional coma with pseudocataplexy are rare.On December 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial magnetic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroencephalogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakefulness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocataplexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true coma and episodic sleep disorders.

Rongalite/iodine-mediated C(sp3)-H bond oximation and thiomethylation reaction of methyl ketones using copper nitrate as the [NO] reagent: synthesis of thiohydroximic acids.

In this work, a highly efficient rongalite/iodine-mediated oxime formation reaction for the preparation of thiohydroximic acids from methyl ketones by employing copper nitrate as the [NO] reagent has been developed. Notably, copper nitrate participated as both a catalyst and the mild oximation reagent in the transformation. This reaction is highly efficient and facile, with a broad substrate scope, especially for fused ring skeleton substrates, heterocyclic skeleton substrates, and acetyl-substituted natural products. Mechanistic studies revealed that copper nitrate might be converted into a NO2 radical or the NO2 radical dimeric forms as an ion-pair equivalent to participate in the transformation.

Tetraphenylborate enhanced enzymatic production of γ-cyclodextrin: System construction and its mechanism.

γ-Cyclodextrin (γ-CD) is an attractive material among the natural cyclodextrins owing to its excellent properties. γ-CD is primarily produced from starch by γ-cyclodextrin glycosyltransferase (γ-CGTase) in a controlled system. However, difficulty in separation and low conversion rate leads to high production costs for γ-CD. In this study, γ-CGTase from Bacillus sp. G-825-6 STB17 was used in γ-CD production from cassava starch. With the introduction of sodium tetraphenylborate (NaBPh4), the total conversion rate was promoted from an initial 18.07 % to 50.49 % and the γ-CD ratio reached 78.81 % with a yield of 39.79 g/L. Furthermore, the mechanism was conducted via the determination of binding constant, which indicated that γ-CD exhibited much stronger binding strength with NaBPh4 than ß-CD. The reformation of water molecules and the chaotropic effect might be the main driving forces for the interaction. Additionally, the conformations of CD complexes were depicted by NMR and molecular docking. The results further verified different binding patterns between CDs and tetraphenylborate ions, which might be the primary reason for the specific binding. This system not only guides γ-CD production with an efficient and easy-to-remove production aid but also offers a new perspective on the selection of complexing agents in CD production.

Late Bedtime and Altered Diurnal Axial Length Rhythms of the Eye.

PURPOSE: Affecting one-third of the population worldwide and increasing, the sight-threatening condition myopia is causing a significant socio-economic burden. To better understand its etiology, recent studies investigated the role of ocular and systemic rhythms, yet results are conflicting. Here we profiled 24-h variations of axial length of the eye and salivary melatonin concentration in young adults with and without myopia and explored the potential impacts of bedtime on these rhythms. METHODS: A total of 25 healthy young adults (age 25.0 ± 4.8 years, 13 females) completed this study, including 13 myopes (mean spherical equivalent refractive error -2.93 ± 1.46 diopters) and 12 non-myopes (0.14 ± 0.42 diopters). Saliva sample collection and axial length measurements were repeated for seven times over 24 h starting from 8 am. Information on sleep and chronotype was collected at first visit with the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire. RESULTS: Significant diurnal rhythms of axial length and salivary melatonin concentration were identified in both refractive groups (both p < 0.001), with no myopia-related rhythm difference (interaction of measurement time-point × myopia, p = 0.9). Late bedtime was associated with altered rhythms (p = 0.009) and smaller diurnal change (p = 0.01) in axial length. Elevated melatonin levels were observed in myopes (p = 0.006) and in late sleepers (p = 0.017). CONCLUSIONS: These findings suggest that sleep/wake cycles may be involved in the regulation of axial length rhythms. Further research is needed to determine if there exists a causal relationship between the two.

Unveiling Ionized Interfacial Water-Induced Localized H* Enrichment for Electrocatalytic Nitrate Reduction.

Electrocatalytic nitrate reduction reaction (NO3RR) is a process that requires the participation of eight electrons and nine protons. The regulation of active hydrogen (H*) supply and a deep understanding of related processes are necessary for improving the ammonia yield rate and Faradaic efficiency (FE). Herein, we synthesized a series of atomically precise copper-halide clusters Cu2X2(BINAP)2 (X = Cl, Br, I), among which the Cu2Cl2(BINAP)2 cluster shows the optimal ammonia FE of 94.0% and an ammonia yield rate of 373 µmol h-1 cm-2. In situ experiments and theoretical calculations reveal that halogen atoms, especially Cl in Cu2Cl2(BIANP)2, can significantly affect the distance of alkali metal-ionized water on the catalyst surface, which can promote the water dissociation to enhance the localized H* enrichment for the continues hydrogenation of nitrate to ammonia. This work explains the role of H* in the hydrogenation process of NO3RR and the importance of localized H* enrichment strategy for improving the FEs.

Phase angle is a predictor for postoperative complications in colorectal cancer.

Aim: The aim of this study was to develop a validated nomogram to predict the risk of postoperative complications in colorectal cancer (CRC) patients by analyzing the factors that contribute to these complications. Methods: We retrospectively collected clinical information on patients who underwent CRC surgery at a single clinical center from January 2021 to December 2021. Univariate and multivariate logistic regression analysis to identify independent risk factors for postoperative complications and to develop a predictive model. A receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) to assess the predicted probability. Calibration curve was drawn to compare the predicted probability of the nomogram with the actual probability, and decision curve analysis (DCA) was employed to evaluate the clinical utility of the nomogram. Results: A total of 190 CRC patients were included in this study. We retrospectively collected baseline information, clinical information, surgical information, and nutrition-related indicators for all patients. Through multivariate logistic regression analysis, preoperative albumin (p = 0.041, OR = 0.906, 95% CI = 0.824-0.996), surgical time (p = 0.009, OR = 1.006, 95% CI = 1.001-1.010), waistline (p = 0.049, OR = 1.011, 95% CI = 1.002-1.020) and phase angle (PA) (p = 0.022, OR = 0.615, 95% CI = 0.405-0.933) were identified as independent risk factors for postoperative complications in CRC, and a nomogram prediction model was established using the above four variables. The AUC of 0.706 for the ROC plot and the high agreement between predicted and actual probabilities in the calibration curves suggested that the prediction model has good predictive power. The DCA also confirmed the good clinical performance of the nomogram. Conclusion: This study developed a nomogram to predict the risk of postoperative complications in CRC patients, providing surgeons with a reliable reference to personalized patient management in the perioperative period and preoperative nutritional interventions.

Targeting DNA damage repair mechanism by using RAD50-silencing siRNA nanoparticles to enhance radiotherapy in triple negative breast cancer.

Radiotherapy (RT) is one of major therapeutic modalities in combating breast cancer. In RT, ionizing radiation is employed to induce DNA double-strand breaks (DSBs) as a primary mechanism that causes cancer cell death. However, the induced DNA damage can also trigger the activation of DNA repair mechanisms, reducing the efficacy of RT treatment. Given the pivotal role of RAD50 protein in the radiation-responsive DNA repair pathways involving DSBs, we developed a novel polymer-lipid based nanoparticle formulation containing RAD50-silencing RNA (RAD50-siRNA-NPs) and evaluated its effect on the RAD50 downregulation as well as cellular and tumoral responses to ionizing radiation using human triple-negative breast cancer as a model. The RAD50-siRNA-NPs successfully preserved the activity of the siRNA, facilitated its internalization by cancer cells via endocytosis, and enabled its lysosomal escape. The nanoparticles significantly reduced RAD50 expression, whereas RT alone strongly increased RAD50 levels at 24 h. Pretreatment with RAD50-siRNA-NPs sensitized the cancer cells to RT with ∼2-fold higher level of initial DNA DSBs as determined by a γH2AX biomarker and a 2.5-fold lower radiation dose to achieve 50 % colony reduction. Intratumoral administration of RAD50-siRNA-NPs led to a remarkable 53 % knockdown in RAD50. The pretreatment with RAD50-siRNA-NPs followed by RT resulted in approximately a 2-fold increase in DNA DSBs, a 4.5-fold increase in cancer cell apoptosis, and 2.5-fold increase in tumor growth inhibition compared to RT alone. The results of this work demonstrate that RAD50 silencing by RAD50-siRNA-NPs can disrupt RT-induced DNA damage repair mechanisms, thereby significantly enhancing the radiation sensitivity of TNBC MDA-MB-231 cells in vitro and in orthotopic tumors as measured by colony forming and tumor regrowth assays, respectively.

A new glycoprotein from pigeon egg: Study on its structure and digestive characteristics.

Pigeon egg white (PEW) is widely recognized as a promising source of bioactive proteins, with a high degree of glycosylation. This study focused on the characterization of a novel glycoprotein extracted from PEW, known as ovalbumin-related protein Y (OVAY). Our investigation included an analysis of the N-glycan and protein structures of OVAY, as well as an examination of simulated gastrointestinal digestive products and the transmembrane transport mechanism of OVAY-digested peptides. The results revealed that OVAY contains two glycosylation sites (Asn 62, 215) and consists of 30 N-linked glycoforms, with the top three glycans being N6H3, N6H7S1, and N6H5. Additionally, OVAY is rich in Gal and sialic acid and exhibits a rod-like molecular structure. Furthermore, it was found that OVAY demonstrates resistance to gastric digestion, with its digested peptides primarily transported via PepT1 and endocytosis. This study provides insight into the glycoprotein structure of OVAY and elucidates its physiological activity, providing a theoretical reference for the development of a novel sialate-rich protein.

Relationship between tree species diversity and water holding capacity of litter layer in subtropical region.

Litter layer, serving as the "skin" of forest soil, plays a crucial role in conserving water resources and maintaining soil and water conservation. We analyzed the relationship of tree species richness, community weighted mean traits, and functional diversity with the standing mass, maximum water holding rate, and effective water sto-rage capacity of litters from various tree species including Liquidambar formosana, Mytilaria laosensis, Castanopsis sclerophylla, Castanopsis hystrix, Cunninghamia lanceolata, Pinus massoniana, Fokienia hodginsii, Taxus wallichiana and their combinations of mixed forests in subtropical region. The results showed that across various tree species combinations, the ranges of maximum water holding rate, standing litter mass and effective water storage capacity of undecomposed layer were 0-419%, 0-0.58 t·hm-2, and 0-1.66 t·hm-2, respectively. For the semi-decomposition layer, these values spanned in 0-375%, 0-6.14 t·hm-2, and 0-16.03 t·hm-2, respectively. Tree species richness and community weighted mean specific leaf area had significantly positive effects on standing mass of litter and effective water storage capacity, while community weighted mean leaf N content had significantly negative effect on standing mass of litter. The maximum water holding rate increased with the increases of functional diversity of specific leaf area and community weighted mean specific leaf area, decreased with the increase of community weighted mean leaf thickness. Results of structural equation model showed that tree species richness increased litter water holding capacity by increasing functional diversity of specific leaf area. The community weighted mean specific leaf area increased the water holding capacity of litter layer by increasing standing mass of litter and the maximum water holding rate. It is necessary to consider planting mixed forest with higher community weighted mean specific leaf area in the management of subtropical artificial forest, so as to improve the water holding capacity of litter layer.

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The contribution of litterfall nutrient return to the maintenance of soil carbon pool and nutrient cycling is a crucial aspect of forest ecosystem functioning. Taking 21 tree species in subtropical young plantations as subjects, we investigated the correlation between litterfall nutrient return characteristics and functional traits of leaf and root and. The results showed notable variations in litterfall production, standing crop, and nutrient return across all the examined tree species. Mytilaria laosensis exhibited the highest litterfall production (689.2 g·m-2·a-1) and standing crop (605.1 g·m-2), while Cryptomeria fortunei demonstrated the lowest litterfall production (36.0 g·m-2·a-1) and standing crop (10.0 g·m-2). The nitrogen and phosphorus return amounts of 21 species ranged from 3.0 to 48.3 kg·hm-2 and from 0.1 to 2.0 kg·hm-2, respectively. Castanopsis fissa demonstrated the highest nitrogen return, while Liquidambar formosana exhibited the highest phosphorus return. C. fortunei had the lowest nitrogen and phosphorus return. Results of the stepwise regression analysis indicated that litterfall production exhibited a significant negative correlation with leaf nitrogen content and leaf dry matter content, and a significant positive correlation with fine root tissue density. Additionally, leaf nitrogen content, leaf dry matter content, and specific root length had a significant negative impact on standing crop. The structural equation modelling results indicated that leaf dry matter content had a direct or indirect negative effect on nitrogen return amount through the reduction of litterfall production. Conversely, fine root tissue density had a significant positive impact on nitrogen return amount by increasing litter leaf nitrogen content. Both leaf nitrogen content and leaf dry matter content had direct or indirect negative effects on phosphorus return amount through the reduction of litterfall production. In conclusion, the tree species with low leaf nitrogen content and dry matter content, as well as high fine root tissue density, was recommended for the establishment of plantations in the subtropical zone in order to enhance nutrient cycling through litter decomposition and improve soil fertility and forest productivity.

Platelet-Derived Growth Factor C Facilitates Malignant Behavior of Pancreatic Ductal Adenocarcinoma by Regulating SREBP1 Mediated Lipid Metabolism.

Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet-derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element-binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC-mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC-induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes.

CD36-mediated accumulation of MDSCs exerts abscopal immunosuppressive responses in hepatocellular carcinoma after insufficient microwave ablation.

The immune landscape of distant unablated tumors following insufficient microwave ablation (iMWA) in hepatocellular carcinoma (HCC) remains to be clarified. The objective of this study is to define the abscopal immune landscape in distant unablated tumor before and after iMWA for HCC. Two treatment-naive patients were recruited for tumor tissue sampling, of each with two HCC lesions. Tumor samples were obtained at before and after microwave ablation in distant unablated sites for single-cell RNA sequencing (scRNA-seq). Mouse model with bilateral hepatoma tumors were developed, and distant unablated tumors were analyzed using multicolor immunofluorescence, RNA sequencing and flow cytometry. The scRNA-seq revealed that a reduced proportion of CD8+ T cells and an increased proportion of myeloid-derived suppressor cells (MDSCs) were observed in the distant unablated tumor microenvironment (TME). A notable disruption was observed in the lipid metabolism of tumor-associated immune cells, accompanied by an upregulated expression of CD36 in tumor-infiltrating immune cells in distant unablated tumor. The administration of a CD36 inhibitor has been demonstrated to ameliorate the adverse effects induced by iMWA, primarily by reinstating the anti-tumor responses of T cells in distant unablated tumor. These findings explain the recurrence and progression of tumors after iMWA and provide a new target of immunotherapy for HCC.

Measuring and optimizing the spatial accessibility of primary health care in remote and rural areas: a case study of Liannan Yao Autonomous County in China.

The need for equitable access to primary healthcare services in the current global context has attracted widespread attention, prompting nations to continuously enhance their grassroots medical service levels. In response, China launched the "Healthy China" initiative, which prioritizes the enhancement of national health as a core goal of the healthcare system and uses this opportunity to deepen reforms aimed at strengthening primary care. However, in remote and rural areas, the optimization of medical resource allocation and the achievement of balanced service development remain critical challenges owing to limited resources. This study selected Liannan Yao Autonomous County, which is situated in the northwestern corner of Guangdong Province, as a case study due to its remote mountainous location, underdeveloped economy, and minority region characteristics. Through field research and interviews, this study thoroughly explored the needs of both supply and demand, factoring in elements such as the service capability of healthcare facilities and residents' travel thresholds to enhance the two-step floating catchment area model, thus making it more applicable to remote villages. By integrating electric bikes and cars, which are the primary means of transportation in rural areas, this study conducted a thorough analysis and comparison of the accessibility of medical services in Liannan Yao Autonomous County (Liannan County) . The results reveal significant disparities in healthcare accessibility, an uneven distribution of medical resources, and varying impacts of transportation conditions and facility service capabilities on accessibility. Notably, the study revealed that improving transportation conditions alone has limited effects in rural areas; the key lies in balancing medical service capabilities and the rationality of overall layouts. From the perspectives of equity and efficiency, this study employs the equitable coverage model and the efficiency-driven model to construct two scenarios, comparing accessibility changes in Liannan County under both conditions and proposing strategies to improve the spatial layout of local healthcare facilities. This research not only deepens the understanding of healthcare service accessibility in rural areas but also provides a scientific basis for optimizing resource allocation and enhancing primary medical services, offering valuable guidance and reference for Liannan County and other similar rural regions.

Application of MALDI-TOF mass spectrometry for identification of Nocardia species.

BACKGROUND: Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforward technique for identifying the pathogenic agent in clinical specimens is crucial to reduce fatality rates and facilitate timely antimicrobial treatment. In this study, we aimed to identify Nocardia spp. in clinical isolates, using MALDI-TOF MS as the primary method, with molecular methods as the gold standard. Clinical Nocardia isolates were identified using 16S rRNA/hsp65/gyrB/secA1/rpoB gene sequencing. Identification performance of the Bruker MALDI Biotyper 3.1 (V09.0.0.0_8468) and MBT Compass 4.1 (V11.0.0.0_10833) for Nocardia identification was evaluated. RESULTS: Seventy-six Nocardia isolates were classified into 12 species through gene sequencing. The MALDI Biotyper 3.1 (V09.0.0.0_8468) achieved 100% genus-level accuracy and 84.2% species accuracy (64/76). The MBT Compass 4.1 with the BDAL Database (V11.0.0.0_10833) improved species identification to 98.7% (75/76). The updated database enhanced species level identification with scores > 1.7, increasing from 77.6% (59/76) to 94.7% (72/76), a significant improvement (P = 0.001). The new and simplified extraction increased the proportion of strains identified to the species level with scores > 1.7 from 62.0% (18/29) to 86.2% (25/29) (P = 0.016). An in-house library construction ensured accurate species identification for all isolates. CONCLUSIONS: The Bruker mass spectrometer can accurately identify Nocardia species, albeit with some variations observed between different database versions. The MALDI Biotyper 3.1 (V09.0.0.0_8468) has limitations in identifying Nocardia brasiliensis, with some strains only identifiable to the genus level. MBT Compass 4.1 (V11.0.0.0_10833) effectively addresses this shortfall, improving species identification accuracy to 98.7%, and offering quick and reliable identification of Nocardia. Both database versions incorrectly identified the clinically less common Nocardia sputorum as Nocardia araoensis. For laboratories that have not upgraded their databases and are unable to achieve satisfactory identification results for Nocardia, employing the new and simplified extraction method can provide a degree of improvement in identification outcomes.