The aim of this study was to establish a laboratory research model for the desiccation tolerance of Coxiella bur-netii(C.burnetii),based on an axenic culture system.The conditions for osmotic pressure in the axenic culture system of C.burnetii were set via a gradient.Quantitative PCR was used to determine the C.burnetii genome equivalents during the culture cycle under different osmotic pressures,and the growth curves were recorded.In addition,the bacterial manifestations of C.burnetii obtained from eukaryotic cell cultures or cell-free cultures were analyzed with phase contrast microscopy and transmis-sion electron microscopy(TEM).The bacterial infection levels and vacuole forming units(VFU)were measured by infection of BGMK cells.C.burnetii showed as many as 7 days of adaptive survival in osmotic axenic medium under high osmotic condi-tions.The bacteria shrank by dehydration under extremely high osmotic pressure and appeared primarily as hypo-hydrated small cell variants(SCVs).The VFUs were significantly diminished 24 hours after infection,as compared with the parallel contrasts.The method for researching desiccation tolerance was thus successfully established.This method provides a basis for further investigation of the genetic mechanisms of the anti-desiccation properties of C.burnetii in the natural environment,through proteomics and other methods.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Objective To study and verify the function of de novo interferon regulatory factor(IRF8)frameshift mutation detected in an etiology screening of the cohort of children with recurrent pneumonia at the molecular level.Methods The recombinant overexpression plasmids with wildtype or mutated IRF8 genes were constructed to transiently transfect HEK293T cells,or packed into lentivirus to infect two kinds of immune cell lines.Q-PCR,Western blot,immunofluorescence and other experimental assays were performed to explore the differences of expression and the regulatory effect on downstream genes associated with inflammation.Results The recombinant vectors with wildtype or mutated IRF8 genes were constructed successfully,and the efficiency of transfection by plasmids and infection by packed lentivirus was remarkable as well.Compared with wildtype,the molecular weight of IRF8 variant was slightly increased,while the expression level presents in opposition,even if on transcription level.Moreover,the localization of IRF8 variant was detected in abundance in nucleus rather than cytoplasm,and its inhibition effect was enhanced on the downstream ISRE element in comparison with the wildtype IRF8 protein.Conclusion The de novo frameshift mutation was presumed as gain-of-function(GOF)mutation.

Objective:To systematically review the current status of research on risk prediction models for feeding intolerance (FI) in patients receiving enteral nutrition (EN), and to provide a reference for medical workers to select, apply, and calibrate models, or to construct related prediction models. Methods:A literature search was conducted in the China National Knowledge Infrastructure (CNKI), VIP, WanFang, Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Embase, Web of Science, and CINAHL databases published on risk prediction models for FI in patients receiving EN. The search time was limited from the database establishment to February 28, 2023. Two researchers independently reviewed the literature, extracted relevant information, and evaluated the bias and applicability of the included studies. Results:A total of 10 studies were included, involving 14 models. The area under the receiver operating characteristic curve (AUC) of the included models ranged from 0.70 to 0.889. The top three predictors in the included models were age, mechanical ventilation, and albumin level, with albumin level being a protective factor. Conclusion:The occurrence of FI in patients receiving EN is related to advanced age, mechanical ventilation, and low albumin level. The existing risk prediction models have a high risk of bias. In the future, appropriate machine learning algorithms should be selected, and large-sample, multicenter studies should be conducted to construct FI risk prediction models with universal applicability. Targeted preventive measures should be implemented to reduce the risk of FI.

Human Respiratory Syncytial Virus (HRSV) is a serious threat to the population health. The elderly are one of the susceptible populations. The prevalence of HRSV in the elderly is generally higher than that in other age groups except children, which has gradually attracted attention in recent years. This paper reviewed the prevalence, common complications and major complications of HRSV in the elderly, briefly expounded the economic burden of HRSV infection, and proposed that attention should be paid to the disease burden of the elderly after HRSV infection, timely treat common complications, so as to reduce the occurrence of adverse survival outcomes and provide scientific evidence for the prevention and control of HRSV infection in the elderly.
Child ; Humans ; Aged ; Respiratory Syncytial Virus Infections/epidemiology* ; Respiratory Syncytial Virus, Human

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Objective: To explore the impact of health management measures for entry personnel (entry management measures) against COVID-19 on the epidemiological characteristics of imported Dengue fever in Guangdong Province from 2020 to 2022. Methods: Data of imported Dengue fever from January 1, 2016 to August 31, 2022, mosquito density surveillance from 2016 to 2021, and international airline passengers and Dengue fever annual reported cases from 2011 to 2021 in Guangdong were collected. Comparative analysis was conducted to explore changes in the epidemic characteristics of imported Dengue fever before the implementation of entry management measures (from January 1, 2016 to March 20, 2020) and after the implementation (from March 21, 2020 to August 31, 2022). Results: From March 21, 2020, to August 31, 2022, a total of 52 cases of imported Dengue fever cases were reported, with an imported risk intensity of 0.12, which were lower than those before implementation of entry management measures (1 828, 5.29). No significant differences were found in the characteristics of imported cases before and after implementation of entry management measures, including seasonality, sex, age, career, and imported countries (all P>0.05). 59.62% (31/52) of cases were found at the centralized isolation sites and 38.46% (20/52) at the entry ports. However, before implementation of entry management measures, 95.08% (1 738/1 828) of cases were found in hospitals. Among 51 cases who had provided entry dates, 82.35% (42/51) and 98.04% (50/51) of cases were found within seven days and fourteen days after entry, slightly higher than before implementation [(72.69%(362/498) and 97.59% (486/498)]. There was significant difference between the monthly mean values of Aedes mosquito larval density (Bretto index) from 2020 to 2021 and those from 2016 to 2019 (Z=2.83, P=0.005). There is a strong positive correlation between the annual international airline passengers volume in Guangdong from 2011 to 2021 and the annual imported Dengue fever cases (r=0.94, P<0.001), and a positive correlation also existed between the international passenger volume and the annual indigenous Dengue fever cases (r=0.72, P=0.013). Conclusions: In Guangdong, the entry management measures of centralized isolation for fourteen days after entry from abroad had been implemented, and most imported Dengue fever cases were found within fourteen days after entry. The risk of local transmission caused by imported cases has reduced significantly.
Animals ; Humans ; COVID-19 ; Aedes ; Epidemics ; China/epidemiology* ; Dengue/epidemiology*

[Abstract] Objective To study the effects of pranlinide on cognitive behavior, β amyloid(Aβ) protein 6E10, inflammatory factors and neuronal cell morphology in brain and retina of 5×FAD mice and WT mice. Methods Thirty two 5×FAD mice and 16 WT mice were selected. All were female. 5×FAD mice were randomly divided into blank group and treatment group; No treatment was given in WT group. Blank group was intraperitoneally injected with PBS; treatment group was received intraperitoneal injection of pranlinide once a day for 8 weeks. The changes of cognitive ability were measured by Morris water maze test. The expression of Aβ6E10 protein in mice hippocampal cells and retina was detected by immunohistochemistry. Tumor necrosis factor α(NF-α) was determined by enzyme-linked immunosorbent assay. The same method was also used for interleukin-1β(IL-1β) detection (The content of inflammatory factors). The arrangement and morphology of nerve cells in mouse hippocampal tissue were determined by hematoxylin-eosin (HE) staining. Results The latency time of treatment group was shorter than that of 5×FAD group,and the times of crossing the platform and the percentage of target quadrant stay in the treatment group were higher than those in the 5×FAD group, and the differences were statistically significant (P<0. 05). Compared with the retinal area and the brain area of Aβ6E10 in the 5×FAD group and in the treatment group, the content was halved (P<0. 05). There was positive correlation between Aβ6E10 in retina and brain (P<0. 05).There was no significant difference in TNF-α and IL-1β in brain and retina between treatment group and 5×FAD group (P>0. 05). Compared with the 5×FAD group, the nerve cells in the treatment group were arramged in order and clear relatively. The distribution of glial cells was concentrated; The surrounding clearance was small. Conclusion Pranlinide can improve the cognitive ability of mice. The arrangement of nerve cells is regular, the shape is regular and the boundary is clear; The distribution of glial cells is concentrated; surrounding of clearance decrease. Aβ6E10 is synchronized in brain and retina.