Objective To investigate the species of sandflies and the prevalence of Leishmania infections in sandflies from selected areas of northern and northwestern China, so as to provide insights into identification of leishmaniasis vectors and assessment of epidemiological trends of leishmaniasis in China. Methods Sandfly samples were collected from Mentougou District of Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County of Karamay District of Karamay City, Gaochang District of Turpan City in Xinjiang Uygur Autonomous Region from July 2023 to July 2024. Approximately 100 intact female sandfly samples were randomly selected from each site and the species of sandflies was identified according to morphological characteristics and molecular assays. Female sandflies originating from the same habitat were grouped into pools of 10 individuals. Leishmania infection was detected using polymerase chain reaction (PCR) assay targeting the internal transcribed spacer 1 (ITS-1) gene, and the prevalence of Leishmania infection was calculated in sandflies from different sampling sites using the minimum infection rate (MIR) method. In addition, positive amplicons were sequenced and subjected to phylogenetic analysis. Results A total of 6 155 sandflies were collected from different environments at sampling sites across the six aforementioned regions from July 2023 to July 2024. Phlebotomus chinensis (96.00%) was the dominant sandfly species in Mentougou District, Beijing Municipality, with a small proportion of Ph. sergenti (4.00%), and only Ph. chinensis was found in Xiangning County, Linfen City, Shanxi Province. Ph. wui was the only sandfly species detected in Ejin Banner, Alxa League, Inner Mongolia Autonomous Region, and Payzawat County, Kashgar City, Xinjiang Uygur Autonomous Region, and Ph. caucasicus (97.70%) was the dominant sandfly species in Karamay District, Karamay City, Xinjiang Uygur Autonomous Region, with a small proportion of Ph. wui (2.30%), while Ph. alexandri was the only species in Gaochang District, Turpan City, Xinjiang Uygur Autonomous Region. A total of 40, 60, 34, 18, 18, and 22 pools of sandfly samples were tested from Mentougou District in Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, Payzawat County in Kashgar City, Karamay District in Karamay City, and Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region, respectively. L. infantum was detected in Ph. chinensis samples from Mentougou District in Beijing Municipality, and Xiangning County of Linfen City in Shanxi Province, with MIR of 0.25% to 1.00%, and L. donovani was detected in Ph. wui from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region, with MIR of 0.56% to 0.88%; however, no Leishmania infection was detected in Ph. caucasicus from Karamay District in Karamay City or Ph. alexandri from Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region. Phylogenetic analysis showed that the Leishmania ITS-1 gene sequences obtained from Mentougou District in Beijing Municipality and Xiangning County in Linfen City of Shanxi Province were clustered into the same clade with the reference sequences of L. infantum ITS-1 gene, while the Leishmania ITS-1 gene sequences obtained from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region were clustered into the same clade with the reference sequences of L. donovani ITS-1 gene. Conclusions There are variations in sandfly species in selected areas of northern and northwestern China, and variations in the species of Leishmania infecting sandflies. Improved surveillance of sandfly vectors and targeted control strategies with adaptations to geographical features and leishmaniasis vectors are recommended.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

In analytical techniques such as ion mobility spectrometry(IMS)and mass spectrometry(MS),the ionization efficiency of target analytes is primarily constrained by the type of ionization source and factors such as the species and number density of the reactant ions.Systematic investigation into the reactivity differences of various reactant ions under varying conditions can not only significantly enhance the detection sensitivity of target compound product ions but also provide a theoretical foundation for establishing efficient detection methods based on ion-molecule reaction mechanisms.In this study,the pressure of a pressure-tunable photoionization tandem ion mobility spectrometry(PI-tandem-IMS)was reduced from ambient pressure(100 kPa)to low pressure(20 kPa)to systematically examine the reactivity differences between two negative reactant ions,CO3-and CO4-,and methyl salicylate(MeSA)under varying pressures.When the pressure decreased,the increased relative signal intensity of CO4-significantly influenced the detection sensitivity of the characteristic product ion[MeSA·O2]-.Based on differences in ion mobility(k0),the delay time for the opening of TPG2 was adjusted to selectively inject CO-3 and CO-4 in the drift region 2.Independent characterization of the reactivity of these reactant ions with MeSA in the reaction region confirmed that CO4-exhibited superior reactivity toward MeSA.The theoretical model revealed an Arrhenius plot for the ion-molecule reaction between CO4-and MeSA,showing a positive correlation between the reaction rate coefficient(k)and temperature,the activation energy Ea was 62.45 kJ/mol.Furthermore,controlling parameters such as pressure or temperature significantly influenced the progression of this ion-molecule reaction,demonstrating the technical advantages of PI-tandem-IMS in mechanistic studies and regulation of ion-molecule reactions.

The resolving power and sensitivity are critical for on-site detection of hazardous chemicals using stand-alone ion mobility spectrometry(IMS).However,improving the sensitivity and resolving power of IMS has long been a prominent research hot spot.In the commonly used IMS based on the Bradbury-Nielsen gate(BNG),the gating voltage difference(GVD)applied between the two sets of grid wires affects the electric field distribution in the ionization region and the drift region.This,in turn,influences the spatial distribution and temporal width of the injected ion swarm,and has an impact on the ion mobility discrimination,sensitivity,and resolving power of the instrument.This study showed that increasing the GVD could induce an ion converging effect,boosting the ion number density in front of the BNG by nearly 300％.To simultaneously utilize temporal compression and ion converging effects,a novel BNG controlling mode was proposed by adding a chopping state to the conventional controlling mode.This chopping state reduced the mobility discrimination effects between ions with mobility differences up to about 0.90 cm2/(V·s)to 1/22 of their original value.When analyzing hazardous chemical mixtures using the novel BNG controlling mode,compared with conventional mode,the signal intensity of low-mobility methyl salicylate ions(MS·O2)-increased by 18-fold while the resolving power maintained around 100,and the detection limit for MS was improved from 3.75 μg/L to 97 ng/L.This novel BNG controlling mode only added a potential wave to the low voltage wires,with no requirement of changing the structure of the drift tube,and was easy to apply to existing commercial instruments.

Time-of-flight secondary ion mass spectrometer(TOF-SIMS)is a highly sensitive surface analysis instrument with high spatial resolution.Traditional TOF-SIMS instruments for sample targets use high field extraction methods.Although the ion collection efficiency is high,it is prone to issues such as low-energy ion beam defocusing,sample morphology sensitivity,and organic molecule ion dissociation.This study aimed to develope an efficient low-field ion extraction system suitable for TOF-SIMS with a continuous beam source.The SIMION simulation software was used to construct a model of the secondary ion optical extraction system.The key factors affecting the extraction efficiency were studied,and the structural parameters of the extraction cone were optimized.Using an indium target as the sample,an experimental test of the performance of the ion extraction system was carried out on the TOF-SIMS instrument.The influences of the voltages of the ion extraction cone and the single lens on the ion extraction efficiency were consistent with the simulation results.By adopting the technology of deflection and coaxial dynamic compensation,the imaging field of view of the ion extraction system was increased to 500 μm×500 μm.The energy window of the ion extraction system reached 10 eV,and the large imaging depth of field of 400 μm was achieved.In the test of a 5 mg/L cholesterol thin film sample,the signal-to-noise ratio of the characteristic peak[M-OH]+reached 4453.The results showed that this low-field secondary ion extraction system effectively improved the performance of the continuous beam TOF-SIMS instrument.

OBJECTIVES: To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. METHODS: Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. RESULTS: At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU⁺PDGFR-α⁺ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU⁺Olig2⁺ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). CONCLUSIONS Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.
Animals ; Rats, Sprague-Dawley ; Magnetic Resonance Imaging/methods* ; Rats ; White Matter/injuries* ; Animals, Newborn ; Female ; Multimodal Imaging ; Male ; Hypoxia-Ischemia, Brain/pathology*