Objective To investigate the microbiota composition and diversity between autogenous and anautogenous Culex pipiens pallens, so as to provide insights into unraveling the pathogenesis of autogeny in Cx. pipiens pallens. Methods Autogenous and anautogenous adult Cx. pipiens pallens samples were collected at 25 ℃, and the hypervariable regions of the microbial 16S ribosomal RNA (16S rRNA) gene was sequenced on the Illumina NovaSeq 6000 sequencing platform. The microbiota abundance and diversity were evaluated using the alpha diversity index, and the difference in the microbiota structure was examined using the beta diversity index. The microbiota with significant differences in the abundance between autogenous and anautogenous adult Cx. pipiens pallens samples was identified using the linear discriminant analysis effect size (LEfSe). Results The microbiota in autogenous and anautogenous Cx. pipiens pallens samples belonged to 18 phyla, 28 classes, 70 orders, 113 families, and 170 genera, and the dominant phyla included Proteobacteria, Bacteroidetes, and so on. At the genus level, Wolbachia was a common dominant genus, and the relative abundance was (77.6 ± 11.3)% in autogenous Cx. pipiens pallens samples and (47.5 ± 8.5)% in anautogenous mosquito samples, while Faecalibaculum (0.4% ± 0.1%), Dubosiella (0.5% ± 0.0%) and Massilia (0.5% ± 0.1%) were specific species in autogenous Cx. pipiens pallens samples. Alpha diversity analysis showed that higher Chao1 index and ACE index in autogenous Cx. pipiens pallens samples than in anautogenous samples (both P values > 0.05), and lower Shannon index (P > 0.05) and Simpson index (P < 0.05) in autogenous Cx. pipiens pallens samples than in anautogenous samples. LEfSe analysis showed a total of 48 significantly different taxa between autogenous and anautogenous Cx. pipiens pallens samples (all P values < 0.05). Conclusion There is a significant difference in the microbiota diversity between autogenous and anautogenous Cx. pipiens pallens.

ObjectiveTo explore the possible mechanism of Chuanxiong （Rhizoma Chuanxiong） & Tianma （Rhizoma Gastrodiae） herbal pair in treating migraines based on AMP-activated protein kinase （AMPK）/transient receptor potential A1 channel （TRPA1） pathway. MethodsForty-eight healthy male SD rats were randomly divided into control group， model group， and Chuanxiong Tianma medication group， with 16 rats in each group. The control group and model group were given 10 ml/kg of normal saline by gavage， while the Chuanxiong Tianma medication group was given 0.675 g/kg of Chuanxiong Tianma herbal pair by gavage， once daily for 8 consecutive days in both groups. Migraime model was performed before the last administration， with subcutaneous injection of 10 ml/kg of normal saline in the control group， and subcutaneous injection of 10 ml/kg of nitroglycerin in the model group and Chuanxiong Tianma medication group. The Von Frey filament was used to measure the periorbital mechanical pain threshold of rats. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of calcitonin gene-related peptide （CGRP） in rat serum and cerebrospinal fluid. The nitric oxide （NO） assay kit was used to determine the NO level in serum and cerebrospinal fluid. RT-PCR was usedto detect the mRNA expression levels of immediate-early genes in the trigeminal ganglion of rats （c-Fos）， CGRP， transient receptor potential V1 channel （TRPV1）， AMPK alpha subunit （PRKAA）， and TRPA1. Immunofluorescence was used to detect the number of c-Fos-positive cells in the trigeminal cervical complex （TCC） and the protein expression levels of phosphorylated AMPK （pAMPK） and TRPA1 in the trigeminal ganglion. ResultsCompared to those in the control group， the mechanical stimulation threshold and pAMPK protein expression in the model group decreased， while the levels of CGRP and NO in serum， c-Fos， CGRP， TRPV1 and TRPA1 mRNA levels in the trigeminal ganglion， TRPA1 protein expression， and the number of c-Fos-positive cells in the TCC significantly increased （P＜0.05）. Compared to those in the model group， the mechanical stimulation threshold and pAMPK protein expression in the Chuanxiong Tianma medication group significantly increased， while the levels of CGRP and NO in serum， c-Fos， CGRP， TRPV1 and TRPA1 mRNA levels in the trigeminal ganglion， TRPA1 protein expression， and the number of c-Fos-positive cells in the TCC significantly decreased （P＜0.05）. ConclusionChuanxiong Tianma herbal pair may improve migraine symptoms by regulating the AMPK/TRPA1 pathway in the trigeminal ganglion and increasing the mechanical pain threshold.

Objective To explore the research status and trends in the field of post-stroke foot drop. Methods The literature on post-stroke foot drop was retrieved from the Web of Science Core Collection database from inception to January,2024.The data were analyzed using VOSviewer and CiteSpace. Results A total of 490 articles were included.The annul articles were published more and more year by year since 1992,peaking in 2020.The main institutions were located in USA.The literature focused on the fields of medicine,healthcare and clinical studies.There were as many as 230 papers on rehabilitation.The most frequency key-words were rehabilitation,hemiplegic gait,electrical stimulation,foot drop,and stroke,and so on.Keyword co-occurrence analysis showed ten major clusters as motor rehabilitation,neurorehabilitation technology,gait analy-sis,functional recovery technology,and assessment of rehabilitation treatment effects,and so on. Conclusion Researches on the rehabilitation of post-stroke foot drop are moving towards the integration of technology and therapeutic methods,emphasizing the assessment of motor function and evidence of treatment effects,and exploring personalized rehabilitation plans.

Objective:To analyze the distribution and drug resistance of pathogens of bacterial bloodstream infection in patients with hematological diseases in the Department of Hematology of Tianjin Medical University General Hospital, and to provide etiological data for clinical empirical anti-infection treatment.Methods:A retrospective analysis was conducted on the general clinical information, pathogenic bacteria and drug susceptibility test results of patients with hematological diseases diagnosed with bacterial bloodstream infection by menstrual blood culture in our center from January 2016 to December 2022.Results:Patients included 498 inpatients, with a total of 639 bacterial strains. Among the patients, 86.9% patients had malignancies, and 76.7% had agranulocytosis. Symptoms of concurrent infections, including those of the respiratory tract, oral mucosa, skin and soft tissues, and abdominal sources were observed in 68.3% patients. Gram-negative bacteria (G -) accounted for 79.0% of the isolated bacteria, and gram-positive bacteria (G +) accounted for 21.0%. The top five isolated pathogens were Klebsiella pneumoniae (22.5%), Escherichia coli (20.8%), Pseudomonas aeruginosa (15.0%), Enterococcus faecium (5.5%), and Stenotrophomonas maltophilum (5.0%). Escherichia coli exhibited a decreasing trend of resistance to quinolones, cephalosporins, and carbapenems. Klebsiella pneumoniae exhibited increasing rates of resistance to quinolones and cephalosporins between 2016 and 2018, but the rated decreased after 2019. The resistance rate to carbapenems exhibited by Pseudomonas aeruginosa was approximately 20%. Carbapenem-resistant strains of Pseudomonas aeruginosa strains were first detected in 2017, with a peak resistance rate of 35.7%, detected in 2019. A 60.0% resistance rate to methicillin was observed in methicillin-resistant coagulase-negative staphylococci (MRCNS), and one case of linezolid-resistant MRCNS was detected. Conclusions:Pathogenic bacteria of bacterial bloodstream infections were widely distributed in our center, and precautions are warranted against carbapenem resistant P. aeruginosa and Klebsiella pneumoniae.

Several mitochondrial dysfunctions in obesity and diabetes include impaired mitochondrial membrane potential, excessive mitochondrial reactive oxygen species generation, reduced mitochondrial DNA, increased mitochondrial Ca2+ flux, and mitochondrial dynamics disorders. Mitophagy, specialized autophagy, is responsible for clearing dysfunctional mitochondria in physiological and pathological conditions. As a paradox, inhibition and activation of mitophagy have been observed in obesity and diabetes-related heart disorders, with both exerting bidirectional effects. Suppressed mitophagy is beneficial to mitochondrial homeostasis, also known as benign mitophagy. On the contrary, in most cases, excessive mitophagy is harmful to dysfunctional mitochondria elimination and thus is defined as detrimental mitophagy. In obesity and diabetes, two classical pathways appear to regulate mitophagy, including PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent mitophagy and receptors/adapters-dependent mitophagy. After the pharmacologic interventions of mitophagy, mitochondrial morphology and function have been restored, and cell viability has been further improved. Herein, we summarize the mitochondrial dysfunction and mitophagy alterations in obesity and diabetes, as well as the underlying upstream mechanisms, in order to provide novel therapeutic strategies for the obesity and diabetes-related heart disorders.

Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.
Nanomedicine ; Nucleosides/chemistry* ; Nucleotides ; Nanoparticles/chemistry* ; Drug Delivery Systems ; Drug Carriers

Objective　To understand the infection status and typing of Wolbachia in Culex pipiens pallens population in coastal areas of Shandong Province, and to provide new research directions and theoretical basis for the prevention and control of mosquito-borne diseases. Methods　From June 2022 to August 2023, mosquito samples were collected from 8 sites in four coastal cities of Yantai, Qingdao, Rizhao, and Dongying in Shandong Province by light lure method. The collected samples were identified as Culex pipiens pallens by combining morphological and molecular methods. Then, using the PCR detection method established by the Wolbachia surface protein (wsp) gene sequence, the Wolbachia infection rate of Culex pipiens pallens collected in the field from 8 sites along the coast of Shandong Province was detected. In addition, the representative strain of Wolbachia was downloaded from the GenBank database, and the obtained gene sequences were subjected to phylogenetic analysis using Mega5.2 software for typing. Results　Wolbachia infection was found in all four coastal areas of Shandong Province, with an average infection rate of 80.8% (261/323). Among them, Yanti had the highest infection rate of 100% (46/46), while Wulian County, Rizhao City had the lowest infection rate of 60.6% (20/33). A total of 12 wsp haplotypes were identified, with 92.5% infection rates for Hap1, 70.0% for Hap2, and lower rates for Hap3 to Hap12. From the perspective of haplotype sources, Hap1 was detected in all 8 sampling sites, while other haplotypes were only detected in some geographical populations of sampling sites. Among them, Dongying District, Dongying City had the highest haplotype diversity, with six haplotypes detected. Phylogenetic tree analysis concluded that the Wolbachia strains found in all eight sampling points belonged to group B. Conclusions　Infection of Wolbachia group B is common in Culex pipiens pallens in coastal areas of Shandong Province. Still, there are certain differences in the haplotypes of Wolbachia infections in different regions. This provides a valuable theoretical basis for targeted prevention and control of specific mosquito-borne diseases in the region．

The finite element method is a new method to study the mechanism of brain injury caused by blunt instruments. But it is not easy to be applied because of its technology barrier of time-consuming and strong professionalism. In this study, a rapid and quantitative evaluation method was investigated to analyze the craniocerebral injury induced by blunt sticks based on convolutional neural network and finite element method. The velocity curve of stick struck and the maximum principal strain of brain tissue (cerebrum, corpus callosum, cerebellum and brainstem) from the finite element simulation were used as the input and output parameters of the convolutional neural network The convolutional neural network was trained and optimized by using the 10-fold cross-validation method. The Mean Absolute Error (MAE), Mean Square Error (MSE), and Goodness of Fit ( R ²) of the finally selected convolutional neural network model for the prediction of the maximum principal strain of the cerebrum were 0.084, 0.014, and 0.92, respectively. The predicted results of the maximum principal strain of the corpus callosum were 0.062, 0.007, 0.90, respectively. The predicted results of the maximum principal strain of the cerebellum and brainstem were 0.075, 0.011, and 0.94, respectively. These results show that the research and development of the deep convolutional neural network can quickly and accurately assess the local brain injury caused by the sticks blow, and have important application value for understanding the quantitative evaluation and the brain injury caused by the sticks struck. At the same time, this technology improves the computational efficiency and can provide a basis reference for transforming the current acceleration-based brain injury research into a focus on local brain injury research.
Brain ; Brain Injuries ; Computer Simulation ; Finite Element Analysis ; Humans ; Neural Networks, Computer

OBJECTIVE: The explore the genetic basis for a patient with microcytic hypochromic anemia and iron deficiency anemia. METHODS: Common deletions and variants of the globin genes were detected by Gap-PCR and next generation sequencing (NGS). Suspected mutations were verified by Sanger sequencing. RESULTS: Gap-PCR and NGS showed that the proband has carried a αα/-α CONCLUSION Patients with α HBA2 c.2T>A(p.Met1Lys) α/-α
Anemia, Hypochromic/genetics* ; Codon, Initiator/genetics* ; Female ; Genetic Counseling ; Genetic Variation ; Genotype ; Humans ; Male ; Mutation ; Pregnancy ; Prenatal Diagnosis ; alpha-Globins/genetics* ; alpha-Thalassemia/genetics*

OBJECTIVE: To assess the value of next generation sequencing (NGS) for the prevention and control of thalassemia. METHODS: NGS was used to sequence 3083 clinical blood samples suspected for thalassemia during initial screening. Retrospective analysis was conducted on blood samples detected with rare genotypes of thalassemia and abnormal hemoglobin. RESULTS: NGS analysis of the 3083 samples has found 1089 subjects with thalassemia genotypes (alpha-thelassemia genotype: 26.01%, beta-thalassemia genotype: 6.71%, and alpha-compound-beta genotype: 2.59%), which yielded a positive detection rate of 35.32%. Rare alpha-thalassemia genotypes including HBA2 c.123delG, HBA1 c.354_355insATC and Fusion gene, and rare beta-thalassemia genotypes including HBB c.-100G>A and HBB c.316-90A>G, were discovered. In addition, 19 patients were found to have abnormal hemoglobin, mainly including Hb Hamilton, Hb Hekinan II, Hb Shizuoka, Hb Owari, Hb New York, Hb J-Bangkok and Hb Port Phillip. CONCLUSION NGS can play a crucial role for improving of the prevention and control of thalassemia and formulating a screening system with better efficacy.