Jiawei Bai-Hu-Decoction ameliorated heat stroke-induced brain injury by inhibiting TLR4/NF-κB signal and mitophagy of glial cell.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Bai-Hu-Decoction (JWBHD), a prescription formulated with seven traditional Chinese medicinal material has demonstrated clinical efficacy in mitigating brain injury among heat stroke (HS) patients. AIM OF THE STUDY: This study aimed to evaluate the therapeutic efficacy of JWBHD on rat model of HS and to explore its therapeutic mechanisms by integrating network pharmacology and pharmacodynamic methodologies, which major components were analyzed by using UPLC-MS/MS. MATERIALS AND METHODS: The network pharmacology analysis was firstly conducted to predict the potential active ingredients and therapeutic targets of JWBHD. The anti-HS effectiveness of JWBHD was then evaluated on rats experienced HS. Rat brain tissues were harvested for a comprehensive array of experiments, including western blot, PCR, H&E staining, Nissl staining, ELISA, transmission electron microscope, flow cytometry and immunofluorescence to validate the protective effects of JWBHD against HS-induced brain damage. Furthermore, the inhibitory effects of JWBHD on TLR4/NF-κB signal and mitophagy of glial were further verified on HS-challenged F98 cell line. Finally, the chemical compositions of the water extract of JWBHD were analyzed by using UPLC-MS/MS. RESULTS: Network pharmacology has identified fifty core targets and numerous HS-related signaling pathways as potential therapeutic targets of JWBHD. Analysis of protein-protein interaction (PPI) and GO suggests that JWBHD may suppress HS-induced inflammatory signals. In experiments conducted on HS-rats, JWBHD significantly reduced the core temperature, restored blood pressure and alleviated neurological defect. Furthermore, JWBHD downregulated the counts of white blood cells and monocytes, decreased the levels of inflammatory cytokines such as IL-1ß, IL-6 and TNF-α in peripheral blood, and suppressed the expression of TLR4 and NF-κB in the cerebral cortex of HS-rats. Besides, JWBHD inhibited the apoptosis of cortical cells and mitigated the damage to the cerebral cortex in HS group. Conversely, overactive mitophagy was observed in the cerebral cortex of HS-rats. However, JWBHD restored the mitochondrial membrane potential and downregulated expressions of mitophagic proteins including Pink1, Parkin, LC3B and Tom20. JWBHD reduced the co-localization of Pink1 and GFAP, a specific marker of astrocytes in the cerebral cortex of HS-rats. In addition, the inhibitory effect of JWBHD on TLR4/NF-κB signaling and overactive mitophagy were further confirmed in F98 cells. Finally, UPLC-MS/MS analysis showed that the main components of JWBHD include isoliquiritigenin, liquiritin, dipotassium glycyrrhizinate, ginsenoside Rb1, ginsenoside Re, etc. CONCLUSIONS: JWBHD protected rats from HS and prevented HS-induced damage in the cerebral cortex by suppressing TLR4/NF-κB signaling and mitophagy of glial.

A causal relationship between particulate matter 2.5 and obesity and its related indicators: a Mendelian randomization study of European ancestry.

Background: In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM2.5) on obesity, but their relationship remains ambiguous. Methods: Utilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM2.5 exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings. Results: The UVMR analysis demonstrated a significant association between PM2.5 exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881-21.968; P FDR = 0.005). Additionally, PM2.5 concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244-2.776; P FDR = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092-5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106-2.841; P FDR = 0.019). Furthermore, PM2.5 exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269-3.022; P FDR = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34-4.649; P FDR = 0.007). Finally, a significant negative association was observed between PM2.5 concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025-0.89; P FDR = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM2.5 levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21. Conclusion: Our MR study demonstrates conclusively that higher PM2.5 concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

Hope experiences in parents of children with cancer: A qualitative meta-synthesis.

PURPOSE: To synthesise qualitative research on the parental hope experiences for children with cancer and identify the levels of parental hope experiences and psychosocial adjustment during cancer events. METHODS: Five electronic databases (Cochrane Library, PubMed, Embase, Web of Science, and CINAHL) and three Chinese databases (CNKI, Wanfang, and VIP) were used to retrieve qualitative studies on the hope experiences of parents of children with cancer from inception to February 2023. The Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) was used to assess the methodological quality of the included studies. Data were synthesised using a thematic analysis. RESULTS: Four analytical themes were identified: the process and way hope exists, sources of hope, positive effects of hope, and obstacles to hope maintenance. CONCLUSIONS: Maintaining hope is crucial for parents who are caring for their children with cancer. There are different sources of hope, and targeted interventions can enhance the experience of hope for parents of children with cancer. Families, healthcare providers, and society should pay more attention to the parents of children with cancer and provide them with psychological, social, and financial support to improve their level of hope and quality of care.

Identification of the Electrogenerated Hidden Nitrenium Ions by In Situ Mass Spectrometry.

The identification of the electrogenerated reactive intermediates is essential for an in-depth understanding of the electroredox processes. Although various short-lived intermediates are well characterized by coupling electrochemistry with mass spectrometry (EC/MS), many electrogenerated transient species (τ < 1 µs) are still rarely captured by the currently available EC/MS approaches. Here, we present a low-delay coupling device, which was constructed by decorating a microelectrode into the front tip of a microsized ion emitter. For the first time, the in situ detection of a previously hidden intermediate, i.e., the transient nitrenium ion of carbazole (τ = 333 ns), was achieved. The electrochemical generation of indole nitrenium ion, whose half-life is estimated to be shorter compared to the carbazole nitrenium ion due to less resonance stabilization, was also confirmed by direct observation. This clog-free microelectrode/ion emitter is cheap and easy to fabricate and offers a general and powerful approach to monitoring the fast reactions of electrogenerated reactive intermediates. We believe that our integrated EC/MS approach holds substantial potential for broad applicability, particularly in probing the intricate and ultrafast electroredox processes occurring at the electrode-solution interface.

Regeneration of Thyroid Glands in the Spleen Restores Homeostasis in Thyroidectomy Mice.

Surgical removal of the thyroid gland (TG) for treating thyroid disorders leaves the patients on lifelong hormone replacement that partially compensates the physiological needs, but regenerating TG is challenging. Here, an approach is reported to regenerate TG within the spleen for fully restoring the thyroid's functions in mice, by transplanting thyroid tissue blocks to the spleen. Within 48 h, the transplanted tissue efficiently revascularizes, forming thyroid follicles similar to the native gland after 4 weeks. Structurally, the ectopically generated thyroid integrates with the surrounding splenic tissue while maintaining its integrity, separate from the lymphatic tissue. Functionally, it fully restores the native functions of the TG in hormone regulation in response to physiological stimuli, outperforming the established method of oral levothyroxine therapy in maintaining systemic homeostasis. The study demonstrates the full restoration of thyroid functions post-thyroidectomy by intrasplenic TG regeneration, providing fresh insights for designing novel therapies for thyroid-related disorders.

Psychological distress and aggression among adolescents with internet gaming disorder symptoms.

The present study aimed to investigate the current situation of internet gaming disorder (IGD) in Chinese adolescents and explore the impact of IGD-related factors on adolescent aggression. We hypothesized that IGD symptoms in adolescents would be associated with aggressive behavior and that risk factors for IGD symptoms could increase the aggressive tendencies of adolescents. To verify the above hypothesis, a cross-sectional survey of junior and senior high school students from southern, southwestern, central, and eastern China was conducted. A total of 9306 valid questionnaires were collected. The results showed that the prevalence of IGD symptoms was 1.78 % among Chinese adolescents. The adolescents in the disordered gamer group had the most severe IGD symptoms, with the highest levels of psychological distress and aggression. Interestingly, adolescents in the casual gamer group had the lowest psychological distress and aggression scores. Linear regression analysis further showed that higher levels of aggression were significantly associated with male sex, younger age, more severe psychological distress and IGD symptoms, and more violent game exposure. Our results suggested that excessive online gaming not only contributes to psychological distress in adolescents but also increases their levels of aggressive behavior. Apart from male sex and younger age, severe IGD symptoms and psychological distress are the most important predictors of the development of aggressive behavior.

A Facile and General Oxidative Hydroxylation of Organoboron Compounds: Citric Acid as an Efficient Catalyst in Water to Access Phenolic and Alcoholic Motifs.

An efficient and convenient method for the synthesis of phenols and aliphatic alcohols is described in this paper. The oxidative hydroxylation reaction of various organoboron compounds proceeded smoothly by employing H2O2 as the oxidant and citric acid as the catalyst in water at room temperature to produce phenols and aliphatic alcohols in satisfactory to excellent yields (up to 99% yield). Various synthetically useful functional groups, such as halogen atom, cyano, and nitro groups, remain intact during the oxidative hydroxylation. The developed catalytic system also could accommodate phenylboronic pinacol ester and potassium phenyltrifluoroborate to give the target product good yields.

Exogenous Easily Extractable Glomalin-Related Soil Protein Stimulates Plant Growth by Regulating Tonoplast Intrinsic Protein Expression in Lemon.

Arbuscular mycorrhizal fungi (AMF) have the function of promoting water absorption for the host plant, whereas the role of easily extractable glomalin-related soil protein (GRSP), an N-linked glycoprotein secreted by AMF hyphae and spores, is unexplored for citrus plants. In this study, the effects on plant growth performance, root system characteristics, and leaf water status, along with the changes of mineral element content and relative expressions of tonoplast intrinsic protein (TIP) genes in lemon (Citrus limon L.) seedlings, were investigated under varying strengths of exogenous EE-GRSP application under potted conditions. The results showed that 1/2, 3/4, and full-strength exogenous EE-GRSP significantly promoted plant growth performance, as well as increased the biomass and root system architecture traits including root surface area, volume, taproot length, and lateral root numbers of lemon seedlings. The four different strengths of exogenous GRSP displayed differential effects on mineral element content: notably increased the content of phosphorus (P) and iron (Fe) in both leaves and roots, as well as magnesium (Mg) and zinc (Zn) content in the roots, but dramatically decreased the content of calcium (Ca) and manganese (Mn) in the roots, as well as Zn and Mn in the leaves. Exogenous EE-GRSP improved leaf water status, manifesting as decreases in leaf water potential, which was associated with the upregulated expressions of tonoplast intrinsic proteins (TIPs), including ClTIP1;1, ClTIP1;2, ClTIP1;3, ClTIP2;1, ClTIP2;2, ClTIP4;1, and ClTIP5;1 both in leaves and roots, and TIPs expressions exhibited diverse responses to EE-GRSP application. It was concluded that exogenous EE-GRSP exhibited differential responses on plant growth performance, which was related to its strength, and the effects were associated with nutrient concentration and root morphology, especially in the improvement in water status related to TIPs expressions. Therefore, EE-GRSP can be used as a biological promoter in plant cultivation, especially in citrus.

Univariable and multivariable Mendelian randomization investigating the effects of telomere length on the risk of adverse pregnancy outcomes.

Background: Numerous observational studies have revealed a correlation between telomere length (TL) and adverse pregnancy outcomes (APOs). However, the impacts of TL on APOs are still unclear. Methods: Mendelian randomization (MR) was carried out using summary data from genome-wide association studies (GWAS). Inverse variance weighted (IVW) was employed as the primary analysis to explore the causal relationship between TL and APOs. The exposure data came from a GWAS dataset of IEU analysis of the United Kingdom Biobank phenotypes consisting of 472,174 European participants. Summary-level data for five APOs were obtained from the GWAS datasets of the FinnGen consortium. We also performed multivariate MR (MVMR), adjusting for smoking, alcohol intake, body mass index (BMI), and number of live births. In addition, we conducted a series of rigorous analyses to further examine the validity of our MR findings. Results: After Bonferroni correction and rigorous quality control, univariable MR (UVMR) demonstrated that a shorter TL was significantly associated with an increased risk of spontaneous abortion (SA) (odds ratio [OR]: 0.815; 95% confidence interval [CI]: 0.714-0.930; P = 0.002) and preterm birth (PTB) (OR: 0.758; 95% CI: 0.632-0.908; P = 0.003) in the IVW model. There was a nominally significant relationship between TL and preeclampsia (PE) in the IVW model (OR: 0.799; 95% CI: 0.651-0.979; P = 0.031). However, no significant association was found between TL and gestational diabetes mellitus (GDM) (OR: 0.950; 95% CI: 0.804-1.122; P = 0.543) or fetal growth restriction (FGR) (OR: 1.187; 95% CI: 0.901-1.565; P = 0.223) among the five statistical models. Furthermore, we did not find a significant causal effect of APOs on TL in the reverse MR analysis. MVMR analysis showed that the causal effects of TL on SA remained significant after accounting for smoking, alcohol intake, BMI, and number of live births. Conclusion: Our MR study provides robust evidence that shorter telomeres were associated with an increased risk of SA. Further work is necessary to investigate the potential mechanisms. UVMR and MVMR findings showed limited evidence that TL affects the risk of PTB, PE, GDM, and FGR, illustrating that the outcomes of previous observational studies may have been confounded.

Enhanced Dielectric Properties of All-Cellulose Composite Film via Modulating Hydroxymethyl Conformation and Hydrogen Bonding Network.

Cellulose-based dielectrics with attractive dielectric performance are promising candidates to develop eco-friendly electrostatic energy storage devices. Herein, all-cellulose composite films with superior dielectric constant were fabricated by manipulating the dissolution temperature of native cellulose, where we revealed the relationship among the hierarchical microstructure of the crystalline structure, the hydrogen bonding network, the relaxation behavior at a molecular level, and the dielectric performance of the cellulose film. The coexistence of cellulose I and cellulose II led to a weakened hydrogen bonding network and unstable C6 conformations. The increased mobility of cellulose chains in the cellulose I-amorphous interphase enhanced the dielectric relaxation strength of side groups and localized main chains. As a result, the as-prepared all-cellulose composite films exhibited a fascinating dielectric constant of as high as 13.9 at 1000 Hz. This work proposed here provides a significant step toward fundamentally understanding the dielectric relaxation of cellulose, thus developing high-performance and eco-friendly cellulose-based film capacitors.

[Characteristics and Driving Mechanisms of Shallow Groundwater Chemistry in Xining City].

Groundwater is one of the major sources of water supply, especially in the western arid regions. However, with the deepening of the western development strategy, industrialization and urbanization have increased groundwater resource demands in Xining City. Overexploitation and utilization have led to a series of changes in the groundwater environment. Identifying the chemical evolution characteristics and formation mechanism of groundwater is crucial for preventing its deterioration and ensuring sustainable use. By combining hydrochemistry and multivariate statistical techniques, the chemical characteristics of groundwater in Xining City were analyzed, and the formation mechanism of groundwater and the influence of different factors were discussed. The results showed that there were as many as 36 chemical types of shallow groundwater in Xining City, mainly HCO3-Ca(Mg) (60.00%) and HCO3·SO4-Ca(Mg) (11.81%). There were 5-6 types of groundwater chemical types in bare land, grassland, and woodland. Groundwater chemical types in construction land and cultivated land were more complex, up to 21 types, indicating that they were strongly affected by human activities. The chemical evolution process of groundwater in the study area was mainly affected by rock weathering and leaching, evaporative crystallization, and cation exchange. The main controlling factors were water-rock interaction (contribution rate 27.56%) and industrial wastewater discharge (contribution rate 16.16%), acid-base environment (contribution rate 16.00%), excessive application of chemical fertilizers and pesticides (contribution rate 13.11%), and domestic sewage (contribution rate 8.82%). On account of the chemical characteristics of groundwater in Xining City and the influence of human activities, the management and control suggestions on the development and utilization of groundwater resources were put forward.

Advances in differential diagnosis of cerebrovascular diseases in magnetic resonance imaging: a narrative review.

Background and Objective: Cerebrovascular diseases (CVDs), particularly cerebral stroke, remain a primary cause of disability and death worldwide. Accurate diagnosis of CVDs is essential to guide therapeutic decisions and foresee the prognosis. Different CVDs have different pathological processes while they have many signs in common with some other brain diseases. Thus, differential diagnoses of strokes from other primary and secondary CVDs are especially important and challenging. Methods: This review is composed mainly based on searching PubMed articles between September, 2013 and December 26, 2022 in English. Key Content and Findings: Neuroimaging is a powerful tool for CVD diagnosis including cerebral angiography, ultrasound, computed tomography, and positron emission tomography as well as magnetic resonance imaging (MRI). MRI excels other imaging techniques by its features of non-invasive, diverse sequences and high spatiotemporal resolution. It can detect hemodynamic, structural alterations of intracranial arteries and metabolic status of their associated brain regions. In acute stroke, differential diagnosis of ischemic from hemorrhagic stroke and other intracranial vasculopathies is a common application of MRI. By providing information about the pathological characteristics of cerebral diseases exhibiting different degrees of behavioral alterations, cognitive impairment, motor dysfunction and other indications, MRI can differentiate strokes from other primary CVDs involving cerebral small vessels and identify vascular dementia from hyponatremia, brain tumors and other secondary or non-primary CVDs. Conclusions: Recent advances in MRI technology allow clinical neuroimaging to provide unique reference for differentiating many previously inconclusive CVDs. MRI technology is worthy of full exploration while breaking its limitations in clinical applications should be considered.

Post-traumatic growth among childhood cancer survivors: A qualitative meta-synthesis.

PURPOSE: To conduct a meta-synthesis of qualitative studies on the post-traumatic growth experiences of childhood cancer survivors. METHOD: Various databases, including PubMed, Cochrane Library, Web of Science, EMBASE, PsycInfo, ProQuest, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang Data, China Science and Technology Journal Database (CSTJ), and China Biology Medicine (CBM) were used to retrieve qualitative studies on childhood cancer survivors who experienced post-traumatic growth. RESULTS: Eight papers were included in this study, and similar fragments were combined to form eight categories, which were further combined into four synthesized findings: adjustment of cognitive system, enhancement of personal strength, improving relationships with others, resetting of life goals. CONCLUSIONS: Post-traumatic growth was observed in some childhood cancer survivors. The potential resources and positive forces contributing to this growth are of great significance in the fight against cancer, in tapping into individual and social resources to help survivors grow, and in improving their survival rates and quality of life. It also provides a new perspective for healthcare providers regarding the relevant psychological interventions.

Posttraumatic stress disorder symptoms among Chinese college students following the COVID-19 outbreak.

Objective: This study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms in college students 1 month after the lockdown of Wuhan to identify possible risk factors for PTSD symptoms in a cross-sectional study. Methods: Out of 10,502 who responded, 9,274 students impacted by the COVID-19 pandemic were included in our study. PTSD symptoms was evaluated by the Impact of Event Scale-revised (IES-R). Anxiety/depression symptoms were evaluated by the Kessler Psychological Distress Scale (K10). Personality traits, coping style, and social support were assessed by the Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). Logistic regression analysis was utilized to further explore risk factors for PTSD symptoms. Results: More than 1 month after the COVID-19 outbreak, 13.1% of college students developed PTSD symptoms, indicating that COVID-19 associated stressful experiences were connected with PTSD symptoms. After the COVID-19 outbreak, subjects with symptomatologic PTSD symptoms were more likely to experience strained relationships with their family, to have close contact with COVID-19 patients and to drop out of college. The logistic regression model demonstrated the association factors of PTSD symptoms. Neuroticism, psychoticism and an avoidant coping style were associated with increased risk for PTSD symptoms, while an active coping style was protective against PTSD symptoms during this pandemic. Conclusion: The results showed that PTSD symptoms was prevalent in Chinese college students 1 month after the COVID-19 outbreak. Effective psychological support work should be carried out accordingly.

mGluR5 in amygdala modulates fear memory generalization.

Introduction: Fear memory generalization is regarded as the core characteristic of posttraumatic stress disorder (PTSD) development. However, the mechanism that contributes to the generalization of conditioned fear memory is still unclear. The generalization is generally considered to be a mismatch that occurs during memory consolidation. Methods: Foot shocks and tones were given as unconditioned stress and conditioned stress, respectively for fear conditioning training. Immunofluorescence staining, western blotting and qPCR were performed to determine the expression of different genes in amygdala of mice after fear conditioning training. Cycloheximide was used as a protein synthesis inhibitor and 2-methyl-6-phenylethynyl-pyridine was injected for mGluR5 inhibition. Results: Fear conditioning using caused incremental generalization, which was clearly observed during training. The density of c-Fos+ cells or the synaptic p-NMDAR expression did not differ with stress intensities. Strong-shock fear conditioning could induce significant mGluR5 de novo synthesis in the amygdala, which was not observed in the weak-shock group. Inhibition of mGluR5 impaired fear memory generalization induced by strong-shock fear conditioning, but the generalization level induced by weak-shock training was enhanced. Discussion: These results indicated that mGluR5 in the amygdala is critical to the function of inappropriate fear memory generalization and suggested that this may be a potential target for the treatment of PTSD.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis.

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

[Detection of Fusion Gene and Prognosis Analysis in Children with Acute Lymphoblastic Leukemia of Different Immunophenotypes].

OBJECTIVE: To observe the detection of fusion gene in children with acute lymphoblastic leukemia (ALL) of different immunophenotypes, and analyze the relationship between fusion gene and prognosis. METHODS: The clinical data of 86 children with ALL treated in the hospital from May 2015 to May 2020 were retrospectively analyzed, the immunophenotypes and the prognosis of children were recorded, the detection of fusion gene in ALL children with different immunophenotypes was compared, the relationship between detection of fusion gene and prognosis was analyzed. RESULTS: The results of bone marrow immunophenotype showed that there were 13 cases of T cell type and 73 cases of B cell type in 86 children with ALL. The detection rate of fusion gene SIL-TAL1 in ALL children with T cell type was significantly higher than that in ALL children with B cell type (P<0.05). The detection rates of fusion genes BCR-ABL1, E2A-PBX1 and TEL-AML1 in ALL children with B cell type were higher than those in ALL children with T cell type, but the differences were not statistically significant (P>0.05). Followed up for 8-12 months, recurrence was taken as the end point, the average follow-up time was (10.14±1.75) months, in 86 children with ALL 15 cases recurred (17.44%). The recurrence curve drawn by Kaplan-Meier method showed that the median recurrence time of 15 children with recurrent ALL was 9 months. The proportions of positive minimal residual disease and extramedullary infiltration in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (P<0.05). The detection rates of fusion genes BCR-ABL and SIL-TAL1 in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (all P<0.05). Logistic regression analysis showed that positive minimal residual lesions, extramedullary infiltration, and detection of fusion genes BCR-ABL and SIL-TAL1 were risk factors for poor prognosis in children with ALL (OR>1, P<0.05). The ROC curve analysis showed that the area under the curve (AUC) of combined detection of fusion gene BCR-ABL and SIL-TAL1 for predicting the poor prognosis of ALL children was >0.707, which had a certain predictive value. CONCLUSION: There are differences in fusion genes among ALL children with different immunophenotypes, minimal residual disease, extramedullary infiltration, and fusion gene are associated with prognosis of ALL children. Fusion gene detection can be used as new method to predict the prognosis of children with ALL.

The neutrophil-to-lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90-day mortality in non-cirrhotic chronic severe hepatitis.

OBJECTIVES: To investigate the relationship between systemic inflammatory response and short-term mortality in patients with non-cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil-to-lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet-to lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). METHODS: Data were collected from two prospectively enrolled CATCH-LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90-day liver transplant (LT)-free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90-day LT-free mortality. Kaplan-Meier method was used to estimate the 90-year LT-free survival. RESULTS: The prevalence of CSH was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively, for patients with non-cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90-day LT-free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection. CONCLUSIONS: NLR may be an independent risk factor for 90-day LT-free mortality in patients with non-cirrhotic chronic liver disease. A NLR of 2.9 as the cut-off value can be used to predict disease aggravation in CSH patients without infection.