OBJECTIVES: To observe the therapeutic effect of spermine in neonatal mouse models of severe hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection and explore its therapeutic mechanism in light of regulation of macrophage GBP5/NLRP3 inflammasome pathway. METHODS: Neonatal BALB/c mice (3-5 days old) were divided into control group, EV71 infection group and Spermine treatment group. The mice in the latter two groups received an intraperitoneal injection of 50 μL EV71 suspension (1×10⁶ TCID50 of EV71), followed 3 days later by intraperitoneal injection of 50 μL PBS or 100 μmol/L spermine. GBP5, NLRP3, CXCL10, and TNFSF10 expressions in heart, liver, lung and kidney tissues of the mice were detected using Western blotting and qPCR, and tissue pathologies and macrophage infiltration were assessed with HE staining and immunohistochemistry. In cultured THP-1 and RAW264.7 cells, the effects of EV71 infection, GBP5 siRNA transfection and treatment with spermine or eflornithine on GBP5, NLRP3, CXCL10, and TNFSF10 mRNA expressions were investigated using qPCR. RESULTS: In the neonatal mice, EV71 infection resulted in multiple organ damage, macrophage infiltration and activation of the GBP5/NLRP3 pathway, and spermine treatment significantly improved tissue injuries, reduced macrophage infiltration, and down-regulated the expressions of GBP5, NLRP3 and the inflammatory factors in the infected mice. In THP-1 and RAW264.7 cells, EV71 infection caused significant upregulation of GBP5, NLRP3, CXCL10, and TNFSF10 expressions, which were obviously lowered by spermine treatment. In THP-1 cells, treatment with eflornithine significantly suppressed the reduction of GBP5, NLRP3, CXCL10, and TNFSF10 expressions induced by GBP5 siRNA transfection. CONCLUSIONS Spermine suppressed EV71 infection-induced inflammatory responses by inhibiting GBP5-mediated NLRP3 inflammasome activation, suggesting a new strategy for treatment of severe HFMD.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice ; Macrophages/metabolism* ; Enterovirus A, Human ; Mice, Inbred BALB C ; Inflammasomes/metabolism* ; Spermine/therapeutic use* ; Animals, Newborn ; Humans ; Enterovirus Infections ; Hand, Foot and Mouth Disease/drug therapy* ; RAW 264.7 Cells ; Chemokine CXCL10/metabolism*

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Humans ; Bacteremia ; Cross Infection ; Methicillin-Resistant Staphylococcus aureus ; Retrospective Studies ; Sepsis ; Staphylococcal Infections/epidemiology* ; Staphylococcus aureus ; Tertiary Care Centers ; China

Objective:To explore the normal ranges of perfusion parameters between cerebral hemisphere, cerebellar hemisphere and brain anatomical subregions (56 pairs) in different gender and age groups with multiple post labeling delay time (Multi-PLD) arterial spin labeling (ASL) imaging.Methods:From November 2020 to December 2020, 42 healthy adult volunteers (Male 25, Female 17) were recruited to perform 7 PLD ASL imaging, including 21 young adults (15 males and 6 females, aged 23—35 years) and 21 seniors (10 males and 11 females, aged 36—74 years). The data was processed offline by Cereflow software to obtain arterial arrival time (ATT) and corrected cerebral blood flow (CBF) and cerebral blood volume (CBV) perfusion parameters. SimpleITK standardization function was used to standardize the calculated perfusion image according to the anatomical automatic labeling (AAL) template. Therefore, CBF, ATT, CBV perfusion values of brain subregions were obtained. Paired samples t test, Wilcoxon rank sum test, independent samples t test and Mann-Whitney U test were used to compare the differences of perfusion parameters in the cerebral hemisphere, the cerebellar hemisphere, brain subregions depending on side, gender and age. Pearson correlation analysis was used to compare the correlations of perfusion parameters with age. Results:CBF in 62.5% (35/56) subregions and CBV in 44.6% (25/56) subregions were higher in right side than those in left side. ATT in most brain anatomical subregions (16/56) were higher in left side. The CBF [(35.30±8.31) vs. (34.34±7.53) ml·100g -1·min -1, P=0.021], CBV [(0.47±0.11) vs. (0.45±0.09) ml/100g, P<0.001], ATT [(1.30±0.10) vs. (1.24±0.11) s, P<0.001] in left cerebellar hemisphere were higher than that of right side. The CBF (28/56) of cerebral hemisphere, cerebellar hemisphere and brain subregions was higher in females than that in males, while ATT in 83.9% (47/56) subregions was lower than that in males (all P<0.05). CBV in female subjects was higher only in 5 brain regions (superior occipital gyrus, middle occipital gyrus, inferior occipital gyrus, superior parietal gyrus and cerebelum_7b) (all P<0.05). In young subjects, CBF in 44.6% (25/56) subregions and CBV in 33.9% (19/56) subregions were higher than those in the senior group (all P<0.05). The ATT in most subregions in young group were lower than those in senior group, but the difference was statistically significant only in rectus gyrus ( P=0.026) and paracentral lobule ( P=0.006). The CBF ( r=-0.430, P=0.005) and CBV ( r=-0.327, P=0.035) of cerebral hemisphere were negatively correlated with age. The CBF (24/25, r range:-0.497 —-0.343, all P<0.05) and CBV (16/19, r range:-0.474 —-0.322, all P<0.05) in most subregions were negatively correlated with age, while ATT was positively correlated (gyrus rectus: r=0.311, P=0.045; paracentral lobule: r=0.392, P=0.010). Conclusions:Multi-PLD ASL imaging could be applied for quantitative analysis of brain perfusion. The perfusion parameters of anatomical subregions are different depending on side, gender, and age.

Key requirements of successful animal behavior research in the laboratory are robustness, objectivity, and high throughput, which apply to both the recording and analysis of behavior. Many automatic methods of monitoring animal behavior meet these requirements. However, they usually depend on high-performing hardware and sophisticated software, which may be expensive. Here, we describe an automatic infrared behavior-monitor (AIBM) system based on an infrared touchscreen frame. Using this, animal positions can be recorded and used for further behavioral analysis by any PC supporting touch events. This system detects animal behavior in real time and gives closed-loop feedback using relatively low computing resources and simple algorithms. The AIBM system automatically records and analyzes multiple types of animal behavior in a highly efficient, unbiased, and low-cost manner.

Objective:To analyze Helicobacter pylori ( Hp) resistance in Xiaoshan area from 2013 to 2020 and to provide reference for the selection of clinical antibiotics for the eradication of Hp in this area. Methods:Non-repetitive Hp strains isolated from patients treated in the First People′s Hospital of Xiaoshan District, Hangzhou from January 2013 to December 2020 and the drug susceptibility test results of these strains were collected. The patients were grouped by every 10 years of age to analyze the drug resistance of Hp in different groups and its changing trends. Results:A total of 54 912 Hp strains were isolated and cultured. The resistance rates of Hp isolates to amoxicillin, metronidazole, clarithromycin and levofloxacin were 0.42%, 92.94%, 22.41% and 29.83%, respectively. The drug resistance rates to clarithromycin and levofloxacin were increasing year by year. The resistance rates to levofloxacin, clarithromycin and metronidazole increased with age. The resistance rates to clarithromycin, levofloxacin and metronidazole in women were higher than those in men, especially in the 21-60 age group. The resistance rate to clarithromycin was significantly higher in people under 20 years old. In 2017 to 2019, the resistance rate to amoxicillin was higher in people under 20 years old than in other age groups. In 2020, the resistance rates to levofloxacin and clarithromycin in people over 70 years old both exceed 57% and increased rapidly. Conclusions:The resistance rates of Hp to levofloxacin, clarithromycin and metronidazole in Xiaoshan area were all at a high level. It was recommended to use individualized treatments for the eradication of Hp. In addition, attention should be paid to the young and older people.

BACKGROUND: China has the largest elderly population in the world; little attention has been paid to the mental health of elderly in areas of extreme poverty. This is the first study to investigate the mental health of the rural elderly in poverty state counties in Chongqing and was part of the Chongqing 2018 health literacy promotion project. METHODS: In 2019, a cross-sectional study was conducted to investigate the mental health status of the rural elderly in fourteen poverty state counties of Chongqing, in which a total of 1400 elderly aged ≥ 65 years were interviewed, where mental health status was measured by the ten-item Kessler10 (K10) scale. Ordered multivariate logistic regression was performed to evaluate the influencing factors related to mental health of the elderly in these areas. RESULTS: The average score of K10 in 14 poverty state counties was 17.40 ± 6.31, 47.6% was labeled as good, 30.2% was moderate, 17.0% was poor, and lastly 5.1% was bad, and the mental health status of the elderly in the northeastern wing of Chongqing was better than the one in the southeastern wing of Chongqing. A worse self-rated health was the risk factor for mental health both in the northeastern and southeastern wings of Chongqing (all P < 0.001). Lower education level (OR (95% CI) = 1.45 (1.12-1.87), P = 0.004) was a risk factor in the northeastern wing, whereas older age (OR (95% CI) = 1.33 (1.13-1.56), P = 0.001) was a risk factors in the southeastern wing. CONCLUSIONS The results showed that mental health of the elderly in poverty state counties was poor, especially in the southeastern wing of Chongqing. Particular attention needs to be paid to the males who were less educated, older, and single; female with lower annual per capital income; and especially the elderly with poor self-rated health.
Aged ; Aged, 80 and over ; China ; Cross-Sectional Studies ; Female ; Health Policy ; Humans ; Logistic Models ; Male ; Mental Health ; statistics & numerical data ; Multivariate Analysis ; Rural Population ; statistics & numerical data ; Socioeconomic Factors

Objective:To assess the translation activity of circ-PTPN22, and to investigate its relationship with systemic lupus erythematosus (SLE) .Methods:From May 10, 2019 to September 30, 2019, whole blood samples were collected from 6 female patients with SLE and 9 healthy female controls in the Department of Rheumatology and Immunology, Integrated Traditional Chinese and Western Medicine, and Physical Examination Center of Southwest Hospital, respectively. Peripheral blood mononuclear cells (PBMCs) were isolated from these blood samples, and PBMCs from 3 cases of SLE and 3 healthy controls were sorted into T, B and NK cells by using magnetic beads. The circ-PTPN22 internal ribosomal entry site (IRES) sequence and protein sequence translated from it were predicted in the circRNADb database, rabbit anti-circ-PTPN22pro polyclonal antibodies were prepared against the specific amino acid sequence at the circ-PTPN22 splice site, and Western blot analysis was performed to determine the protein expression of circ-PTPN22pro in PBMCs and T, B and NK cell subsets of the healthy controls and patients with SLE. Cultured Jurkat cells were divided into 4 groups to be transfected with recombinant lentiviral vectors carrying circ-PTPN22-FLAG, circ-PTPN22-NC-FLAG, circ-PTPN22-shRNA-FLAG, circ-PTPN22-shRNA-NC-FLAG respectively, with the normally cultured cells as the cell control group. Then, Western blot analysis was performed to determine the protein expression of circ-PTPN22pro in Jurkat cells, flow cytometry to evaluate the effect of circ-PTPN22 on cell activation and apoptosis. Statistical analysis was carried out by using two-way repeated measures analysis of variance and two-independent-sample t test. Results:Based on the circRNADb database, circ-PTPN22 was predicted to have a translation ability, and Western blot analysis showed that the relative molecular mass of circ-PTPN22pro was 20 000. Forty-eight hours after transfection, circ-PTPN22pro expression was significantly higher in the circ-PTPN22-FLAG group than in the circ-PTPN22-NC-FLAG group and cell control group. At 24, 48 and 72 hours after transfection, the interleukin 2 (IL-2) expression was significantly lower in the circ-PTPN22 group (22.20% ± 8.92%, 31.10% ± 5.88%, 53.20% ± 10.25%, respectively) than in the circ-PTPN22-NC Group (30.90% ± 11.00%, 51.23% ± 10.70%, 69.67% ± 9.00%, respectively; F = 284.881, P = 0.003) , but significantly higher in the circ-PTPN22-shRNA group (35.57% ± 8.79%, 78.10% ± 10.08%, 88.63% ± 3.89%, respectively) than in the circ-PTPN22-shRNA-NC group (26.73% ± 4.92%, 41.03% ± 10.45%, 41.33% ± 4.96%, respectively; F = 293.818, P = 0.003) . After 48, 72 and 96 hours after transfection, the apoptosis rate was significantly higher in the circ-PTPN22 group than in the circ-PTPN22-NC group ( F = 81.287, P = 0.012) , as well as in the circ-PTPN22-shRNA group than in the circ-PTPN22-shRNA-NC group ( F = 111.813, P = 0.009) . The SLE group showed decreased (almost no) circ-PTPN22pro expression in PBMCs compared with the healthy control group. The circ-PTPN22pro expression in T and B cells was significantly lower in the SLE group than in the healthy control group ( t = 3.047, 4.806, both P <0.05) , and there was no significant difference in the circ-PTPN22pro expression in NK cells between the two groups ( t = 0.582, P > 0.05) . Conclusions:Circ-PTPN22 can be translated into circ-PTPN22pro protein, and can inhibit the activation of Jurkat cells. The circ-PTPN22pro expression is lower in PBMCs of the SLE patients than in those of the healthy controls, suggesting that circ-PTPN22 may be related to the occurrence and development of SLE.

To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
 Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
 Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
 Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.
Amphetamine-Related Disorders ; Anisotropy ; Brain ; Diffusion Tensor Imaging ; Humans ; Methamphetamine

Quantitative susceptibility mapping (QSM) can provide tissue susceptibility information and has been adapted for clinical research and diagnosis. QSM of monkey brain at 9.4 T has not been demonstrated so far. In this study 9.4 T monkey brain QSM was performed with 200 μm isotropic high-resolution. It was found that the inherent singularity problem for QSM diverged significantly at ultra-high image resolution during regularization process and resulted in severe image artifacts. The K-space division (TKD) was applied to eliminate the artifacts, with an optimal threshold level between 0.2 and 0.3. High resolution QSM of monkey brain can thus provide a novel tool for brain research.
Algorithms ; Animals ; Brain ; diagnostic imaging ; Brain Mapping ; Haplorhini ; Magnetic Resonance Imaging