Objective:Using T2-weighted imaging(T2WI),diffusion-weighted imaging(DWI),pulsed gradient spin echo(PGSE)multiparametric magnetic resonance imaging combined with various histopathological techniques to observe the effects of reperfusion after different times of cerebral ischemia(CIRI)on the cytotoxic edema of brain tis-sues in rats.This provides a solid foundation for the establishment of ischemic stroke models and clinical diagnosis and treatment.Methods:Healthy adult male Sprague Dawley rats were randomly allocated to four groups:the sham-opera-ted(Sham)group,the ischaemia 60 min reperfusion(IR-60 min)group,the IR-120 min group,and the IR-180 min group.CIRI rat model was prepared by modified Zea Longa method.Laser doppler flowmetry combined with hematoxy-lin-eosin(HE)staining was employed to identify the model.Multiparametric magnetic resonance imaging,combined with water content of brain,immunofluorescence staining of aquaporin-4(AQP4),and Western Blot were performed to observe cytotoxic edema of brain tissues and tumour necrosis factor alpha(TNF-α),interleukin 1β(IL-1β)in brain tissue of rats in each group.Results:HE staining and determination of brain tissue water content prove that as ischemia time prolongs,the degree of cerebral cortex edema on the ischemic side increases.The T2WI results showed that the injury in the IR-60 min group began to affect the cerebral cortex,the injury in the IR-120 min group had completely affected the cerebral cortex,and the injury in the IR-180 min group was the most severe(P＜0.05),with a significant shift of the midline of the brain towards the opposite side.The relative apparent diffusion coefficient and water exchange time of the cerebral cortex on the ischemic side of the rats were found to be significantly lower than those of the sham group,with an declining trend(P＜0.05).Additionally,the values of cell membrane permeability of the cerebral cor-tex on the ischemic side of the rats were observed to be significantly higher than those of the sham group in all groups(P＜0.05).The expression of AQP4,IL-1 β and TNF-α in the cerebral cortex of ischemic side was significantly higher than that in the sham group,and showed an upward trend(P＜0.05).Conclusion:Reperfusion following 60,120 and,180 minutes of middle cerebral artery ischemia in rats can result in brain damage.Prolongation of ischemia time has been shown to exacerbate the toxic edema of brain cells and brain damage.Ischemia of 120 minutes reperfusion has been identified as the optimal modeling time for ischemic stroke.Multiparametric MRI can be utilized to monitor the mi-crostructural changes of brain tissue in rats following CIRI in vivo,providing a foundation for the visualization of early clinical diagnosis and treatment.

Objective:Using T2-weighted imaging(T2WI),diffusion-weighted imaging(DWI),pulsed gradient spin echo(PGSE)multiparametric magnetic resonance imaging combined with various histopathological techniques to observe the effects of reperfusion after different times of cerebral ischemia(CIRI)on the cytotoxic edema of brain tis-sues in rats.This provides a solid foundation for the establishment of ischemic stroke models and clinical diagnosis and treatment.Methods:Healthy adult male Sprague Dawley rats were randomly allocated to four groups:the sham-opera-ted(Sham)group,the ischaemia 60 min reperfusion(IR-60 min)group,the IR-120 min group,and the IR-180 min group.CIRI rat model was prepared by modified Zea Longa method.Laser doppler flowmetry combined with hematoxy-lin-eosin(HE)staining was employed to identify the model.Multiparametric magnetic resonance imaging,combined with water content of brain,immunofluorescence staining of aquaporin-4(AQP4),and Western Blot were performed to observe cytotoxic edema of brain tissues and tumour necrosis factor alpha(TNF-α),interleukin 1β(IL-1β)in brain tissue of rats in each group.Results:HE staining and determination of brain tissue water content prove that as ischemia time prolongs,the degree of cerebral cortex edema on the ischemic side increases.The T2WI results showed that the injury in the IR-60 min group began to affect the cerebral cortex,the injury in the IR-120 min group had completely affected the cerebral cortex,and the injury in the IR-180 min group was the most severe(P＜0.05),with a significant shift of the midline of the brain towards the opposite side.The relative apparent diffusion coefficient and water exchange time of the cerebral cortex on the ischemic side of the rats were found to be significantly lower than those of the sham group,with an declining trend(P＜0.05).Additionally,the values of cell membrane permeability of the cerebral cor-tex on the ischemic side of the rats were observed to be significantly higher than those of the sham group in all groups(P＜0.05).The expression of AQP4,IL-1 β and TNF-α in the cerebral cortex of ischemic side was significantly higher than that in the sham group,and showed an upward trend(P＜0.05).Conclusion:Reperfusion following 60,120 and,180 minutes of middle cerebral artery ischemia in rats can result in brain damage.Prolongation of ischemia time has been shown to exacerbate the toxic edema of brain cells and brain damage.Ischemia of 120 minutes reperfusion has been identified as the optimal modeling time for ischemic stroke.Multiparametric MRI can be utilized to monitor the mi-crostructural changes of brain tissue in rats following CIRI in vivo,providing a foundation for the visualization of early clinical diagnosis and treatment.

Migraine is one of the most prevalent and disabling neurological disease, but the current pharmacotherapies show limited efficacy and often accompanied by adverse effects. Acupuncture is a promising complementary therapy, but further clinical evidence is needed. The influence of acupuncture on migraine is not an immediate effect, and its mechanism remains unclear. This study aims to provide further clinical evidence for the anti-migraine effects of acupuncture and explore the mechanism involved. A randomized controlled trial was performed among 10 normal controls and 38 migraineurs. The migraineurs were divided into blank control, sham acupuncture, and acupuncture groups. Patients were subjected to two courses of treatment, and each treatment lasted for 5 days, with an interval of 1 day between the two courses. The effectiveness of treatment was evaluated using pain questionnaire. The functional magnetic resonance imaging (fMRI) data were analyzed for investigating brain changes induced by treatments. Blood plasma was collected for metabolomics and proteomics studies. Correlation and mediation analyses were performed to investigate the interaction between clinical, fMRI and omics changes. Results showed that acupuncture effectively relieved migraine symptoms in a way different from sham acupuncture in terms of curative effect, affected brain regions, and signaling pathways. The anti-migraine mechanism involves a complex network related to the regulation of the response to hypoxic stress, reversal of brain energy imbalance, and regulation of inflammation. The brain regions of migraineurs affected by acupuncture include the lingual gyrus, default mode network, and cerebellum. The effect of acupuncture on patients' metabolites/proteins may precede that of the brain.
Humans ; Migraine Disorders/etiology* ; Brain/diagnostic imaging* ; Acupuncture Therapy/methods* ; Magnetic Resonance Imaging

Objective:To deeply explore the potential mechanism of Kangmin Zhisou Granules in the treatment of bronchial asthma through network pharmacology method; To verify it with animal experiments.Methods:The active components and corresponding target information of Kangmin Zhisou Granules were screened with the help of BATMAN-TCM database, and the related disease targets of bronchial asthma were obtained through GeneCards and OMIM databases. The drug targets and bronchial asthma targets were intersected and imported String database was used to establish PPI network. Cytoscape 3.9.1 software was used to draw the network diagram of "Chinese materia medica-active components-intersection targets" and the core targets were screened. GO and KEGG enrichment analysis was performed on the core targets using DAVID database. A mouse model of asthma induced by ovalbumin was prepared. After the intervention of Kangmin Zhisou Granules, the pathological changes of mouse lung tissue were observed, and the contents of serum TNF-α, IL-6, IL-1 β were detected by ELISA.Results:Totally 240 active components and 1 364 potential targets were obtained from Kangmin Zhisou Granules. Tumor necrosis factor (TNF), interleukin-6 (IL-6), protein kinase B (AKT1), albumin (ALB), interleukin 1-beta (IL-1β) and other 11 core targets were obtained after screening. The results of GO enrichment analysis showed that the treatment of bronchial asthma by Kangmin Zhisou Granules mainly involved the positive regulation of protein phosphorylation, the regulation of inflammatory response, lipopolysaccharide response and other biological processes, as well as TNF, activated protein kinase (MAPK), interleukin-17 (IL-17) and other signaling pathways. Animal experiments confirmed that Kangmin Zhisou Granules could reduce the expression levels of TNF-α, IL-6 and IL-1β in serum ( P<0.05), and reduce the infiltration of inflammatory cells in the lung tissue of mice, thereby relieving asthma symptoms. Conclusion:Kangmin Zhisou Granules may exert anti-inflammatory effects by acting on TNF-α, IL-6, IL-1β and other targets to alleviate asthma symptoms.

Background: Recent studies showed that the clinical outcome of moderately severe acute pancreatitis (MSAP) are different among different subgroups. Aims: To further subdivide MSAP, and explore the heterogeneity of MSAP subgroups. Methods: A retrospective analysis was performed on patients with acute pancreatitis (AP) from January 2016 to December 2020 at Northern Jiangsu People’s Hospital, including 538 patients with mild acute pancreatitis (MAP) and 461 patients with MSAP. MSAP patients were divided into four groups according to local complication and transient organ failure (TOF), including single acute peripancreatic fluid collection (APFC) without TOF group (group A), multiple APFC without TOF group (group B), other local complication without TOF group (group C) and TOF group (group D). The baseline data and the severity of AP among the four subgroups were compared. Meanwhile, the severity of disease between group A and MAP patients was also compared. Logistic regression analysis was used to evaluate the risk factors of MSAP. Results: Patients in group D were older than those in group A (P<0.05). There were statistically significant differences in different scoring systems among the four subgroups (P<0.05). The proportions of APACHE Ⅱ≥8, Glasgow≥3 and BISAP≥3 in group D were significantly higher than those in the other three groups (P<0.05). There were significant differences in levels of Ca

Objective:To assess if metagenomic next-generation sequencing (mNGS) of periprosthetic joint tissue can provide an alternative rapid and sensitive tool for the diagnosis of prosthetic joint infection (PJI), especially compared to microbiological culture.Methods:A total of 33 eligible patients who underwent revision arthroplasty from June 2019 to June 2020 in orthopedic surgery department of the first affiliated hospital of Zhengzhou University were retrospectively analyzed. Twenty-one patients were included in PJI group according to the American Academy of Musculoskeletal Infection diagnostic criteria, with 17 cases of knee and 4 cases of hip, including 9 cases of male and 12 cases of female, with an average age of 59.14±14.55 years old (range from 28 to 84), and an average BMI of 23.7±2.8 kg/m 2 (range from 17.7 to 29.4 kg/m 2). Twelve patients were included in aseptic loosening group (control group), with 4 cases of knee and 8 cases of hip, including 4 cases of male and 8 cases of female, with an average age of 53.08±10.05 years old (range from 39 to 70), and an average BMI of 25.2±2.9 kg/m 2 (range from 18.3 to 31.2 kg/m 2 ). Microbiological culture results of synovial fluid and periprosthetic joint tissue and mNGS results of periprosthetic joint tissue were collected. The sensitivity and specificity of mNGS and microbiological culture were calculated and compared. The species of pathogenic microorganismsdetected by the two techniques were summarized. In addition, the impact of antibiotic use on the efficacy of both techniques were compared. Results:mNGS detected 13 positive cases and microbiological culture detected 6 positive cases in the PJI group. In the aseptic loosening group, 1 case was determined positive by mNGS, and all the microbiological culture results were negative. In the diagnosis of PJI, mNGS showed significantly higher sensitivity than that of culture (61.9% vs 28.6%, χ2=4.71, P=0.03), while no statistical difference was observed in terms of specificity (91.7% vs 100%, χ2=1.04, P=0.31). In the PJI cases with prior exposure to antibiotics within two weeks, the sensitivity of mNGS was significantly higher than that of culture (53.8% vs 15.4%, χ2=4.25, P=0.04). However, there was no significant difference in the sensitivity between mNGS and culture in patients without antibioticsexposure (66.7% vs 44.4%, χ2=0.90, P=0.34). In the detection of pathogenic microorganism, mNGS detected 9 kinds of bacteria (Staphylococcus aureus, Staphylococcus family, Moraxella Oslo, Propionibacterium acnes, Streptococcus acnes, Staphylococcus epidermidis, Mycobacterium tuberculosis, Staphylococcus Lyons, Bacteroides fragilis) and 2 kinds of fungi (Aspergillus fumigatus, Candida parapsilosis), while microbiological culture detected 3 kinds of bacteria (Staphylococcus aureus, Moraxella catarrhalis, Mycobacterium tuberculosis) and one kind of fungi (Candida parapsilosis). mNGS and microbiological culture were both positive in 5 cases, among which 3 cases had completely matched results (Staphylococcus aureus, Mycobacterium tuberculosis, Candida parapsilosis), one case had partly matched results (mNGS detected more bacteria than culture) and one case had totally mismatched results. Additionally, in the diagnosis of the 3 included tuberculous PJI, mNGS showed 100% specificity and sensitivity. Conclusion:mNGS of periprosthetic joint tissue is a more powerful tool for diagnosis and pathogen detection of PJI compared to microbiological culture, especially in the diagnosis of tuberculosis PJI. Besides, mNGS is more resistant to antibiotic exposure than culture.

Objective:To develop rapid screening tools for assessing the risk of mild cognitive impairment(MCI)based on neuropsychological scales and cognitive paradigms.Methods:Two baseline datasets from the Beijing Ageing Brain Rejuvenation Initiative(BABRI)cohort were studied: dataset 1 contained 5 593 subjects, with 1 500 cases with MCI and 4 093 cases with normal cognitive function(the control group); dataset 2 consisted of 588 subjects, with 92 cases with MCI and 496 cases with normal cognitive function(the control group). Dataset 1 was used to simplify the Mini-Mental State Examination(MMSE), and the sub-item combination with the strongest MCI discriminative ability was selected to integrate into the cognitive rapid assessment(BABRI-mini MMSE). Dataset 2 with scores of encoding-recognition episodic memory task was used for further MCI discriminant analysis and was adapted into an episodic memory test(BABRI-EMT). We applied the receiver operating characteristic curve(ROC)for those analyses.Results:The control group and the MCI group showed significant differences in multi-domain cognitive ability and episodic memory task performance( P<0.01). Among sub-items of MMSE measured using dataset 1, MMSE12 and MMSE19 had the highest discriminative accuracy for MCI, and the area under the ROC(AUC)was 0.699 and 0.631, respectively.Dataset 2 was used to investigate the discriminative ability of the episodic memory score in combination with the above two MMSE sub-items for MCI, and the AUC value was 0.732, the sensitivity was 0.731, and the specificity was 0.656. Conclusions:The BABRI-mini MMSE and BABRI-EMT are suitable for the large-scale universal screening of MCI risk.

Brucellosis is a common global zoonotic disease caused by Brucella, which has a variety of clinical manifestations. Fever, sweating and musculoskeletal pains appear in partial brucellosis patients. The most common complication of brucellosis is osteoarthritis, including spondylitis, sacroiliitis, and peripheral arthritis such as osteomyelitis, bursitis, and tenosynovitis. The spine and sacroiliac are the most frequent affected sites of brucellosis osteoarthritis; however, the reports of peripheral arthritis such as osteomyelitis, bursitis, and tenosynovitis are low. Early and proper treatment is vital for patients with brucellosis osteoarthritis. The therapy of drugs and surgery are two current options for treatment of brucellosis osteoarthritis. In this review, clinical manifestations and treatments of brucellosis osteoarthritis are discussed in detail, which are helpful to deepen clinicians' knowledge in brucellosis.

The clinical characteristics of the pneumonia includes hyperthermia, cough and pectoralgia, etc with simultaneous mixed signs of inflammatory infiltration, consolidation, cavity/air sac and abscess in pulmonary CT scan, and these signs change rapidly. Respiratory failure and septic shock frequently occur in severe such patients, resulting in refractory management and relatively long therapeutic course. The timely diagnosis, use of sensitive antibiotics, respiratory and nutritional support, etc comprehensive effective measures can elevate the rescue success rate with severe hematogenous staphylococcus aureus pneumonia.

Brucellosis is a common bacterial zoonotic disease that affects a variety of organs and tissues and causes a variety of clinical manifestations. Bone and joint are the most frequently involved parts, among which sacroiliac arthritis, spondylitis and peripheral arthritis are the most common osteoarticular disease. Brucella induces bone damage by affecting various cells of the skeletal system and the immune system, Brucella increases the expression of nuclear factor kappa B receptor activating factor ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-17 in osteoclasts and osteocytes, enhances the activity of osteoclasts. Brucella can proliferate in osteoblasts and osteocytes, induce apoptosis of osteoblasts and osteocytes, and inhibit the deposition of mineral and organic matrix in osteoblasts. After Brucella infection, inflammatory cells such as monocyte macrophages, neutrophils, T cells and B cells also participate in the inflammatory response, these inflammatory cells and bone system secrete more pro-inflammatory cytokines, chemokines and matrix metalloproteinases (MMPs), which enhance the inflammatory response and promote the degradation of extracellular matrix. Finally, the bone homeostasis is broken and the bone injury is aggravated. With the development of research on the molecular mechanism of Brucella osteoarthropathy, more and more people will understand the pathogenesis of chronic osteoarthropathy caused by Brucella.