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BackgroundStroke is a devastating disease, including intracerebral haemorrhage (ICH) and ischaemic stroke. Emerging evidences indicate that systemic inflammatory cascades after stroke contribute to brain damage. However, the direct effects and features of systemic inflammation on brain injury, especially comparing between ischaemic and haemorrhagic stroke, are still obscure.MethodsPertussis toxin (PT) was used to build a pro-inflammatory milieu after ICH and ischaemic stroke in mouse model. The neurodeficits, stroke lesion, immune response and blood–brain barrier (BBB) destruction were assessed.ResultsIn ICH mouse model, PT-induced systemic inflammation exacerbated neurological deficits, and enlarged haemorrhage lesion and perihaematomal oedema. We also found promoted leucocyte infiltration and inflammatory cytokine release into the brain after PT treatment. Moreover, the integrity of the BBB was further disrupted after receiving PT. Furthermore, we demonstrated that PT enhanced brain inflammation and aggravated stroke severity in middle cerebral artery occlusion mouse model.ConclusionsOur results suggest that PT increases inflammatory response that exacerbates brain injury after ICH or ischaemic stroke in mouse model.

MicroRNA-491-5p (miR-491-5p) plays an important role in regulating cell proliferation and migration; however, the effect of miR-491-5p on neovascularization after traumatic brain injury remains poorly understood. In this study, a controlled cortical injury model in C57BL/6 mice and an oxygen-glucose deprivation model in microvascular endothelial cells derived from mouse brain were established to simulate traumatic brain injury in vivo and in vitro, respectively. In the in vivo model, quantitative real-time-polymerase chain reaction results showed that the expression of miR-491-5p increased or decreased following the intracerebroventricular injection of an miR-491-5p agomir or antagomir, respectively, and the expression of miR-491-5p decreased slightly after traumatic brain injury. To detect the neuroprotective effects of miR-491-p, neurological severity scores, Morris water maze test, laser speckle techniques, and immunofluorescence staining were assessed, and the results revealed that miR-491-5p downregulation alleviated neurological dysfunction, promoted the recovery of regional cerebral blood flow, increased the number of lectin-stained microvessels, and increased the survival of neurons after traumatic brain injury. During the in vitro experiments, the potential mechanism of miR-491-5p on neovascularization was explored through quantitative real-time-polymerase chain reaction, which showed that miR-491-5p expression increased or decreased in brain microvascular endothelial cells after transfection with an miR-491-5p mimic or inhibitor, respectively. Dual-luciferase reporter and western blot assays verified that metallothionein-2 was a target gene for miR-491-5p. Cell counting kit 8 (CCK-8) assay, flow cytometry, and 2?,7?-dichlorofluorescein diacetate (DCFH-DA) assay results confirmed that the downregulation of miR-491-5p increased brain microvascular endothelial cell viability, reduced cell apoptosis, and alleviated oxidative stress under oxygen-glucose deprivation conditions. Cell scratch assay, Transwell assay, tube formation assay, and western blot assay results demonstrated that miR-491-5p downregulation promoted the migration, proliferation, and tube formation of brain microvascular endothelial cells through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor pathway. These findings confirmed that miR-491-5p downregulation promotes neovascularization, restores cerebral blood flow, and improves the recovery of neurological function after traumatic brain injury. The mechanism may be mediated through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway and the alleviation of oxidative stress. All procedures were approved by Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China (approval No. 2020-304) on June 22, 2020.

BackgroundBrain ischemia compromises natural killer (NK) cell-mediated immune defenses by acting on neurogenic and intracellular pathways. Less is known about the posttranscriptional mechanisms that regulate NK cell activation and cytotoxicity after ischemic stroke.MethodsUsing a NanoString nCounter® miRNA array panel, we explored the microRNA (miRNA) profile of splenic NK cells in mice subjected to middle cerebral artery occlusion. Differential gene expression and function/pathway analysis were applied to investigate the main functions of predicted miRNA target genes. miR-1224 inhibitor/mimics transfection and passive transfer of NK cells were performed to confirm the impact of miR-1224 in NK cells after brain ischemia.ResultsWe observed striking dysregulation of several miRNAs in response to ischemia. Among those miRNAs, miR-1224 markedly increased 3 days after ischemic stroke. Transfection of miR-1224 mimics into NK cells resulted in suppression of NK cell activity, while an miR-1224 inhibitor enhanced NK cell activity and cytotoxicity, especially in the periphery. Passive transfer of NK cells treated with an miR-1224 inhibitor prevented the accumulation of a bacterial burden in the lungs after ischemic stroke, suggesting an enhanced immune defense of NK cells. The transcription factor Sp1, which controls cytokine/chemokine release by NK cells at the transcriptional level, is a predicted target of miR-1224. The inhibitory effect of miR-1224 on NK cell activity was blocked in Sp1 knockout mice.ConclusionsThese findings indicate that miR-1224 may serve as a negative regulator of NK cell activation in an Sp1-dependent manner; this mechanism may be a novel target to prevent poststroke infection specifically in the periphery and preserve immune defense in the brain.

Studies have shown that downregulation of nuclear-enriched autosomal transcript 1 (Neat1) may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice. Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear. Therefore, the effects of Neat1 on neuronal apoptosis were observed. C57BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro, and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro. The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons, and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed. The experiment was divided into four groups: the control group, without any treatment, received normal culture; the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol; the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol. The protein expression levels of neurons p53-induced death domain protein 1 (PIDD1, a pro-apoptotic protein), caspase-2 (an apoptotic priming protein), cytochrome C (a pro-apoptotic protein), and cleaved caspase-3 (an apoptotic executive protein) were measured in each group using the western blot assay. To observe changes in the intracellular distribution of cytochrome C, the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay. Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. The results showed that the apoptosis rate, PIDD1, caspase-2, and cleaved caspase-3 expression levels significantly decreased, and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group; however, Neat1 downregulation reversed these changes. Compared with the Neat1 downregulation group, the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased, and the mitochondrial cytochrome C level significantly increased. These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway, reducing the activation of caspase-3, and preventing neuronal apoptosis after oxygen and glucose deprivation, which might reduce secondary brain injury after traumatic brain injury. All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China, on December 19, 2020 (approval No. 2020-895).

Introduction Recurrent cystitis, defined as at least two episodes within six months or three episodes within one year, presented among about one fifth to one-third of women with history of cystitis or urinary tract infection (UTI) according to previous studies. However, the use of antibiotics can only resolve the urinary symptoms but not reduce the frequency of urinary symptoms recurrence, and meanwhile increasing rates of adverse effect of repetitive antimicrobial therapy and bacterial antimicrobial resistance became clinical concerns. This case report aims to present a case of recurrent cystitis treated by electroacupuncture (EA) in reducing recurrent frequency, amount of antibiotics used and urinary symptoms. Case presentation A 42-year-old woman diagnosed with recurrent cystitis for five years presented mainly with recurrent dysuria, urine frequency and urgency. She received EA treatment 3 to 5 sessions a week and 30 min per session from August 2019 to August 2020 with 3-month suspension due to Coronavirus Disease 2019 (COVID-19). During the treatment, both the frequency of recurrent urinary episode and symptoms were reduced. Although there was some fluctuation, the mean frequencies of daytime voiding reduced dramatically from 17.7 to 8.3, and night-time voiding from 4 to 1, and the number of voiding with moderate urgency was reduced from 17.7 to 2.3, and severe urgency dropped from 2.7 to 0. The patient's scores of overactive bladder symptom score (OABSS) and overactive bladder questionnaire short form (OAB-q SF) were also improved. The postvoid residual urine volume (PVR) reduced from 42 mL to less than 10 mL. Conclusion This case of individual effect of EA for a woman with frequent recurrent cystitis suggested a plausible benefit of EA on reducing frequency, amount of antibiotics used and symptoms of recurrent cystitis, but further research is necessary to proof the efficacy and effectiveness among a wider population.

Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-020-01302-6.

Normal aging is accompanied by escalating systemic inflammation. Yet the potential impact of immune homeostasis on neurogenesis and cognitive decline during brain aging have not been previously addressed. Here we report that natural killer (NK) cells of the innate immune system reside in the dentate gyrus neurogenic niche of aged brains in humans and mice. In situ expansion of these cells contributes to their abundance, which dramatically exceeds that of other immune subsets. Neuroblasts within the aged dentate gyrus display a senescence-associated secretory phenotype and reinforce NK cell activities and surveillance functions, which result in NK cell elimination of aged neuroblasts. Genetic or antibody-mediated depletion of NK cells leads to sustained improvements in neurogenesis and cognitive function during normal aging. These results demonstrate that NK cell accumulation in the aging brain impairs neurogenesis, which may serve as a therapeutic target to improve cognition in the aged population.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221116048 for Brain-derived programmed death-ligand 1 mediates immunosuppression post intracerebral hemorrhage by Nuo Cheng, Hong Wang, Ming Zou, Wei-Na Jin, Fu-Dong Shi and Kaibin Shi in Journal of Cerebral Blood Flow & Metabolism

Background The tumor microenvironment (TME) has received an increasing amount of attention. CXC chemokines can regulate immune cell transport and tumor cell activity to exert anti-tumor immunity. However, studies on the expression and prognosis of CXC chemokines in cervical cancer (CC) are more limited. Methods The study investigated the role of CXC chemokines in TME of CC by using public databases. Moreover, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) of CXC chemokines were performed to further verify. Results The transcriptional levels of CXCL1/3/5/6/8/9/10/11/13/16/17 in CC tissues were significantly elevated while the transcriptional levels of CXCL12/14 were significantly reduced. We reached a consistent conclusion that the expression of CXCL9/10/11/13 was verified by quantitative real-time PCR and immunohistochemistry. Moreover, CC patients with low transcriptional levels of CXCL1/2/3/4/5/8 were significantly associated with longer overall survival (OS). The CCL family was related to CXC chemokines neighboring alteration. RELA, NFKB1, LCK and PAK2 were the key transcription factors and kinase targets of CXC chemokines, respectively. We also found there were significant correlations between the expression of CXCL9/10/11 and the infiltration of immune cells (CD8+ T cell, CD4+ T cell, neutrophils and dendritic cells). Conclusions In brief, we conducted a comprehensive analysis of CXC chemokines via clinical data and some online public databases. Our results may provide a new idea for the selection of immunotherapeutic targets and prognostic biomarkers for cervical cancer.

Background Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them. Methods Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients. Results The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (r=0.8550, p

Chromosomal translocations and generating fusion genes are closely associated with disease initiation and progression in acute myeloid leukemia (AML). In this study, we identified a novel t(X;17)(q28;q21) chromosomal rearrangement in a patient with acute monocytic leukemia. Using RNA-sequencing, we identified a KANSL1-MTCP1 and a KANSL1-CMC4 fusion gene. 5'-UTR sequences of the KANSL1 gene were found to become fused upstream of the coding sequence region of the MTCP1 and CMC4 genes, respectively, resulting in an aberrantly high expression of these genes. Functional studies revealed that overexpression of the MTCP1 gene induced an increased cell proliferation and partial blockage of cell differentiation, suggesting that the aberrant expression of MTCP1 is of critical importance in leukemogenesis.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, with acute respiratory failure as the most significant symptom, has led to a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is considered as the most important receptor of SARS-CoV-2 and wildly expressed in human tissues. Whereas, the extremely low expression of ACE2 in lung could hardly interpret the severe symptom of pneumonia in COVID-19 patients. Here we profiled two SARS-CoV-2 infection related genes, the transmembrane serine protease 2 (TMPRSS2) and the interferon-inducible transmembrane protein 3 (IFITM3), in human tissues and organs. Consistent with the expression and distribution of ACE2, TMPRSS2 was also highly expressed in digestive, urinary and reproductive systems, but low expressed in lung. Notably, the anti-virus protein IFITM3 also expressed much lower in lung than other tissues, which might be related to the severe lung symptoms of COVID-19. In addition, the low expression of IFITM3 in immune cells suggested that SARS-CoV-2 might attack lymphocytes and induce the cytokine release syndrome (CRS). Furthermore, cancer patients were considered as more susceptible to SARS-CoV-2 infection. Our data supposed that fourteen types of tumors might have different susceptibility to the virus according to ACE2, TMPRSS2 and IFITM3 expression patterns. Interestingly the prognosis of six types of cancers including breast carcinoma (BRCA), lung adenocarcinoma (LUAD), uterine corpus endometrial carcinoma (UCEC), renal clear cell carcinoma (KIRC), prostate adenocarcinoma (PRAD), and hepatocellular carcinoma (LIHC) were closely related to these gene expressions. Our study explored the expression and distribution profiles of two potential novel molecules that might participate in SARS-CoV-2 infection and involved in immunity, which may provide a functional basis for preventing infection of SARS-CoV-2.

The power of inhibin B to predict competent spermatogenesis is not fully understood. The aims of this study were to identify the reliable reference range of inhibin B among normozoospermic men in China and to evaluate the diagnostic accuracy of serum inhibin B level as a complementary predictor of successful sperm retrieval in patients with azoospermia.This was a cross-sectional study. The male partners of 30 613 infertile couples who visited our hospital were investigated between March 2017 and March 2019. We analysed semen parameters, serum levels of reproductive hormones (inhibin B, FSH and testosterone) and sperm retrieval results from PESA/TESE in Chinese men.The normal reference range of inhibin B was 87.42-299.93 pg/mL among men with normozoospermia in China. Inhibin B levels were negatively correlated with age (r = -.111; P .001) but positively correlated with total sperm counts in the overall population, reference group and case group (r = .311, r = .208 and r = .444, respectively; P .001). Stepwise multiple regression analyses revealed that compared with the FSH and testosterone levels, the inhibin B level had the closest relationship with the total sperm count. The best cutoff value of inhibin B for predicting the retrieval outcome of testicular/epididymal sperm was77.72 pg/mL (sensitivity = 59.14%, specificity = 92.00% and AUC = 0.801). The inhibin B:FSH ratio (cutoff value 6.98, sensitivity = 56.99%, specificity = 96.00% and AUC = 0.814) performed better than either the inhibin B level or the FSH level alone.A new reference range for serum inhibin B was established in China. However, neither serum inhibin B, FSH nor their ratio is adequate for men to decide whether to undergo PESA/TESE to determine the adequacy of spermatogenesis.

Background Primary malignant melanoma of the esophagus accounts for 0.1%-0.2% of all esophageal malignancies, including melanotic and amelanotic melanomas. Primary amelanotic malignant melanoma of the esophagus is extremely rare, and only about 20 cases have been published in the literature to date. Most primary malignant melanomas of the esophagus are diagnosed following development of metastatic lesions and thus have a very poor prognosis. The median survival duration of patients with metastatic melanoma has been reported to be 6.2 mo. Case summary A 49-year-old woman was referred to our hospital with a diagnosis of esophageal cancer. Endoscopy, biopsy, imaging evaluation, and physical examination at our hospital indicated a diagnosis of advanced primary amelanotic malignant melanoma of the esophagus. Immunohistochemical staining confirmed melanoma. Nuclear medicine examination revealed a left iliac bone metastatic lesion. After discharge, the patient self-administered apatinib for 3 mo, followed by oral treatment with Chinese medicines (also self-administered) for 2 mo. No treatments had been taken since then. The patient has survived with no growth out to the most recent follow-up (24 mo post diagnosis), and she always presented with a positive attitude about her condition during this period. Conclusion Survival following metastatic melanoma might be related to the pharmaceutical and Chinese medicine treatment and the patient's positive attitude.

A fluorescence-enhanced and lysosome-targeted Al3+ probe (1) based on a pyrazole-containing hydrazone was developed in this work. The fluorescent probe 1 displays an OFF–ON fluorescence response to Al3+ in the lysosome pH environment. In addition, the resultant 1–Al3+ complex could act as an ON–OFF fluorescence sensor for F−. Fluorescence imaging shows that 1 is suitable for visualization of Al3+ in lysosomes of HeLa cells.

Background: Lung cancer is one of the most common malignances with an ever-increasing incidence and high mortality. The insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as RNA-binding proteins play an important role in messenger RNA (mRNA) regulation during tumor development. Even so, the expression and prognostic values of IGF2BPs in lung cancer have not been clarified.Main methods: To address this issue, the study investigated the roles of IGF2BPs in the prognosis of lung cancer by using public databases and quantitative real-time PCR (Q-PCR).Results: The transcriptional levels of IGF2BP1/2/3 in lung cancer tissues were significantly elevated, associating with pathological stages and poor prognosis of overall survival (OS) and progression-free survival (FP) in lung cancer patients. A high mutation rate of IGF2BPs (24%) was also observed of patients with lung cancer. The functions of differentially expressed IGF2BPs are primarily related to the spliceosome, hippo signaling pathway and transcriptional misregulation in cancer. Finally, we found significant correlations among the expression of IGF2BPs and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells).Conclusions: The results indicated that high mRNA expression of IGF2BP1/2/3 was found in lung cancer tissues, significantly associating with tumor grades and poor prognosis of OS and FP. Our results may provide insights for the selection of therapeutic targets and prognostic biomarkers for lung cancer patients.

Objective EAF2 plays an important role in transcription elongation and the regulation of gene expression in mammalian cells. EAF2’s depletion has been demonstrated to enhance cell proliferation and greatly increase the risk of cancer. Even so, its expression and prognostic role in cervical cancer (CC) remains controversial. Methods To solve this issue, we comprehensively investigated the role of EAF2 in CC through various databases including ONCOMINE, UALCAN, Kaplan-Meier Plotter and TIMER. Results In all, we found that the EAF2 was highly expressed in CC tissue and was significantly correlated with better patient survival. Among the CNAs, amplification was the dominant alteration. Then the co-expression profile and enrichment analysis of EAF2 were related to the potential signaling pathways. The function of genes such as Kinase LYN, mi-RNA133A-133B and transcription factor OCT1 were also enriched in CC. The positively relation EAF2 expression to 6 immune cells revealed that EAF2 expression may affect development of patients with CC partially due to immune infiltration. Conclusions Taken together, our data suggest that EAF2 might be a potential prognostic marker and therapeutic target for CC patients.

Supplemental Digital Content is available in the text., Background and Purpose— Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. Methods— Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients. Results— By coupling transfer of labeled MOG35-55-specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG91-108 and MOG103-125 in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke. Conclusions— Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury.

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for effective control and prevention. Chinese medicine (CM) has developed systematic theories and approaches for infectious disease prevention over 2000 years. Here, we review and analyze Chinese herbal medicines (CHM) used in infectious disease prevention from ancient pestilences to modern epidemics and pandemics to share cumulative preventive medical experience. A total of 829 formulas, including 329 herbs from 189 ancient books, 131 formulas with 152 herbs, and 13 Chinese patent medicines (CPM) from 30 official Chinese prevention programs used in ancient epidemics, SARS, influenza and COVID-19 prevention, were reviewed and analyzed. Preventive CHM mainly has four functions and can be taken orally or applied externally. CHM that kill pathogens (Realgar [Xionghuang], Cyrtomium Fortunei J. Sm[Guanzhong]) were commonly used externally for disinfection in ancient prevention while CHM tonifying Qi (Astragali Radix [Huangq], Glycyrrhizae Radix et Rhizoma [Gancao]) are used for modern prevention. Taking CHM that expel pathogens (Realgar [Xionghuang], Lonicerae Japonicae Flos[Jinyinhua]) and CHM eliminating dampness (Atractylodis Rhizoma [Cangzhu], Pogostemonis Herba[Guanghuoxiang]) have been commonly used from ancient times to COVID-19. Damp toxins are a common characteristic of infectious diseases such as SARS and COVID-19. Thus, taking CHM expelling damp toxins and tonifying Qi are the main methods for SARS and COVID-19 prevention. CHM with different approaches have been widely used in infectious disease prevention from ancient times to the present. Multiple CM prevention methods may provide new perspectives for future pandemics.

Background Thymosin β4 (Tβ4) is the most abundant member of the β-thymosins and plays an important role in the control of actin polymerization in eukaryotic cells. While its effects in multiple organs and diseases are being widely investigated, the safety profile has been established in animals and humans, currently, little is known about its influence on Alzheimer’s disease (AD) and the possible mechanisms. Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice. Methods Behavior tests were conducted to assess the learning and memory, anxiety and depression in APP/PS1 mice. Thioflavin S staining, Nissl staining, immunohistochemistry/immunofluorescence, ELISA, qRT-PCR, and immunoblotting were performed to explore Aβ accumulation, phenotypic polarization of glial cells, neuronal loss and function, and TLR4/NF-κB axis in APP/PS1 mice. Results We demonstrated that Tβ4 protein level elevated in all APP/PS1 mice. Over-expression of Tβ4 alone alleviated AD-like phenotypes of APP/PS1 mice, showed less brain Aβ accumulation and more Insulin-degrading enzyme (IDE), reversed phenotypic polarization of microglia and astrocyte to a healthy state, improved neuronal function and cognitive behavior performance, and accidentally displayed antidepressant-like effect. Besides, Tβ4 could downregulate both TLR4/MyD88/NF-κB p65 and p52-dependent inflammatory pathways in the APP/PS1 mice. While combination drug of TLR4 antagonist TAK242 or NF-κB p65 inhibitor PDTC exerted no further effects. Conclusions These results suggest that Tβ4 may exert its function by regulating both classical and non-canonical NF-κB signaling and is restoring its function as a potential therapeutic target against AD.

Tumor microenvironment (TME) plays a particularly important role in the progression, invasion and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of the tumor microenvironment in CC. However, the results of studies on the correlation between TAMs and progression in CC are still controversial. This research aimed to investigate the relationship between TAMs infiltration and progression in CC. A total of 100 patients with CC were included in the study. The correlation between TAMs and clinicopathologic features was studied. Besides, a systematic literature search was conducted from legitimate electronic databases to specifically evaluate the role of TAMs in TME of cervical carcinoma. In the meta-analysis, high stromal CD68+ TAMs density was relevant to lymph node metastasis (WMD = 11.89, 95% CI: 5.30–18.47). At the same time, CD163+ M2 TAM density was associated with lymph node metastasis (OR = 2.42, 95% CI: 1.09–5.37; WMD = 39.37, 95% CI: 28.25–50.49) and FIGO stage (WMD = -33.60, 95% CI: -45.04 to -22.16). This was further confirmed in the experimental study of 100 tissues of cervical cancer. It supported a critical role of TAMs as a prospective predictor of cervical cancer. In conclusion, CD68+ TAM and CD163+ M2 TAM infiltration in CC were associated with tumor progression. And CD163+ M2 TAM infiltration was associated with more advanced FIGO stage and lymph node metastasis in CC.

Liquid chromatography (LC) is a common and straight forward approach used in the evaluation of the quality of Traditional Chinese Medicines (TCMs). Quality control is a critical step when systematically assessing the efficacy of TCMs. In the present study, the spectrum-effect correlation method was used to identify pharmacologically active substances. The aim of the present study was to investigate the underlying correlations between common chemical compounds with antipyretic effects and the anti-endotoxin activity of Lonicera japonica. The common chemical constituents of Lonicera japonica were analyzed using LC, and the antipyretic effects and anti-endotoxin activity were determined using ELISAs. Combining the results of bivariate and principal component analysis methods, eight active constituents were qualitatively and quantitatively analyzed. The results of these analyses indicated that neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and isochlorogenic acids A, B and C served a synergistic role with respect to antipyretic effects and anti-endotoxin activity. The present study lays a foundation for the future clinical use of Lonicera japonica.

1. The objective of this study was to reveal the role of chicken RB1 (Gallus gallus RB1, gRB1) in the proliferation of preadipocytes.2. To measure gene expression of gRB1 in the proliferati...

Objective: To compare osseous outcomes of block and cancellous iliac bone grafting in older unilateral alveolar cleft patients. Design: Retrospective and observational follow-up study. Setting: Cleft Lip and Palate Centre, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China. Patients: Forty-five nonsyndromic patients with unilateral complete alveolar cleft were enrolled in this study (25 patients in block bone graft group and 20 patients in cancellous bone graft group). Interventions: In cancellous bone graft group, the alveolar cleft was filled with iliac cancellous bone particulate. In group of block bone graft, the harvested bone block was trimmed and fixed in alveolar defect. Main Outcome Measures: A novel method was proposed to investigate the volume and density of residual bone graft at 1-week, 3- and 6-month, 1- and 2-year postoperatively based on cone beam computed tomography scans. Results: No difference in bone graft volume was found between 2 groups at 1-week and 3-month postoperatively; however, the residual volume of block bone graft group was significantly larger than that of cancellous bone graft group at 6-month, 1- and 2-year postoperatively. The bone density of block bone graft group was lower at 1-week and 3-month postoperatively but was comparable at 6-month, 1- and 2-year postoperatively. Our method was reliable and accurate to identify the range of residual bone graft when the boundary of grafted bone could not be identified clearly. Conclusion: Block bone graft could achieve comparable bone density and retain a greater amount of residual bone comparing to cancellous bone graft.

To analyse the impact of dezocine-remifentanil intravenous anaesthesia on perioperative signs, serum tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in liver cancer patients undergoing radiofrequency ablation (RFA).An experimental study.Renmin Hospital of Wuhan University, Wuhan, China, from January 2017 to February 2018.Eighty patients with small hepatocellular carcinoma (SHCC) were selected as the research object. They were divided into Group A and Group B with the random number table method, with 40 cases in each group. Group A were given dezocine-remifentanil intravenous anaesthesia and Group B were given midazolam-remifentanil intravenous anaesthesia. Patients' situations in the surgery were compared between the two groups. Changes in heart rate (HR), mean arterial pressure (MAP) and blood oxygen saturation (SpOsub2/sub) were recorded before the surgery (Tsub0/sub), at 5 minutes after the RFA (Tsub1/sub) and at the end of the RFA (Tsub2/sub). Levels of tumour necrosis factor-alpha; (TNF-alpha;) and interleukin-6 (IL-6) on the 1sup2/supday after the RFA were compared between the two groups.The wake-up time in Group A was shorter than Group B (p0.001), and the VAS pain score in Group A was lower than Group B (p0.001). At Tsub1/sub, the MAP in Group A was higher than Group B (p0.001). There was no significant difference in MAP between the two groups at Tsub0/suband Tsub2/sub(p=0.881, 0.696, respectively). At Tsub1/suband Tsub2/sub, the HR in Group A was lower than Group B (all p0.001). There was no significant difference in HR between the two groups at Tsub0/sub(p=0.684). There was no significant difference in SpOsub2/subbetween the two groups at Tsub0/sub, Tsub1/suband Tsub2/sub(p=0.654, 0.884 and 0.798, respectively). On the 1st day after the RFA, the level of TNF-alpha;, IL-6 in Group A were lower than those of Group B (all p0.001). There was no significant difference in the incidence of intraoperative complications between the two groups (p=0.644).Compared with midazolam-remifentanil intravenous anaesthesia, the dezocine-remifentanil method has a better analgesic effect, shorter wake-up time, and can effectively regulate the expression of inflammatory cytokines TNF-alpha; and IL-6. However, the effect of remifentanil on the respiratory function is dose-dependent. Therefore, respiratory cycle monitoring and management should be strengthened during the surgery.

Introduction The efficacy of the most commonly used interventions for clavicle fractures remains controversial. These interventions are: open reduction and plate fixation (ORPF), non-surgical intervention (NSI), and use of an intramedullary nail (IMN). In adult patients with clavicle fractures, choosing which intervention might be best is challenging. Materials and methods PubMed, Journals@Ovid Full Text, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and Embase were performed to search English-language studies from the inception to February 2020. Randomized controlled trials (RCTs) comparing any of these three interventions were included. Patient and baseline characteristics, nonunion, major complications, Constant-Murley score (CMS), and Disabilities of the Arm, Shoulder and Hand score (DASH) were extracted. Then, we evaluated the functional outcomes and adverse effects after use of these three interventions for the management of displaced midshaft clavicle fractures in a Bayesian network meta-analysis. Results A Bayesian random-effects model was conducted, and nonunion and major complications were evaluated with: risk ratio (RR) and 95% confidential interval (CI); while CMS and DASH were evaluated with mean differences (MD) and the corresponding 95% confidential interval CI. The rank probability of each endpoint was assessed on the basis of the surface area under the cumulative ranking curve (SUCRA). Discussion ORPF is most likely to be successful in achieving objective functional outcomes as captured by the CMS, and IMN demonstrates significant efficacy for subjective functional outcomes, as captured by DASH scores. Compared with the other interventions examined, IMN was associated with decreased risk for adverse effects. Levels of evidence I; meta-analysis.

Amyloid β peptide 1-42 (Aβ1-42) could induce cognitive deficits through oxidative stress, inflammation, and neuron death in Alzheimer's disease (AD). MAPK pathways have been thought to mediate Aβ1-42-induced neuroinflammation responses, neuron death and cognitive decline in AD. The α7 nicotinic acetylcholine receptor (α7nAChR) exerts a neuroprotective effect. However, whether α7nAChR alleviates Aβ1-42-induced neurotoxicity through MAPKs (p38, ERK, JNK) in vivo remains unclear. In our study, memory was assessed in C57BL/6 mice using a Y-maze test. Cell death was assessed by Nissl and Hoechst staining and Bax, Bcl-2, Caspase 3, and Cytochrome C levels using Western blotting. Oxidative stress was assayed by superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. Inflammation was examined with GFAP and Iba1 using immunohistochemistry. The Aβ degrading enzymes insulin degrading enzyme (IDE) and neprilysin (NEP) were tested using Western blotting. We found that activating α7nAChR or inhibiting p38 or JNK pathway alleviated Aβ1-42-induced cognitive deficits and neuron loss and death by reducing oxidative stress. In addition, activating α7nAChR or inhibiting p38 or JNK pathway also reduced inflammation, which was observed as reduced GFAP and Iba1 levels with different effects on Aβ degrading enzymes. Finally, we found that the activation of α7nAChR led to the downregulation of pp38 and pJNK levels. Conversely, the inhibition of p38 or JNK resulted in the upregulation of α7nAChR levels in the hippocampus and cortex. Our data indicate that the activation of α7nAChR alleviates Aβ1-42-induced neurotoxicity, and this protective effect might act through the downregulation of p38 and JNK MAPKs.

Objective To detect cerebral autoregulation (CA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) by near-infrared spectroscopy and to assess its association with delayed cerebral ischemia (DCI). Methods From January to August 2017, 81 patients (average age 53.25 ± 10.27 years) were studied. Near-infrared spectroscopy was used to monitor CA, and associated factors were evaluated. Monitoring of CA was carried out at 5 time points (preoperative day 1 and postoperative days 1, 2, 3, and 7). Patients were sorted into 2 groups according to whether DCI occurred (DCI group and non-DCI group). The relationship between CA and DCI in patients with aSAH was analyzed. Results Among 81 patients, CA trended toward being impaired in patients with aSAH with a poorer grade. DCI occurred in 39 of 51 (48.15%) patients with impaired CA. DCI occurred in 6 of 30 (7.4%) patients with intact CA. Conclusions Impaired CA monitored by near-infrared spectroscopy was shown in patients with aSAH before and after surgical intervention. Older age, smoking, hypertension, and especially impaired CA are independent risk factors for patients with DCI.

Clofibric acid (CFA), a drug and personal care product, has been identified as ubiquitous in the aquatic system and surface water, causing pollution to the environment. In this study, after environmental (4 µg/L) levels of CFA challenge, the LvFABP, LvACS gene expressions, total haemocyte count (THC), relative enzymes (SOD1 and GST) activities in Litopenaeus vannamei were observed to decrease. In the meantime LvFATP, LvRXR expression and the level of NEFA were upregulated in L. vannamei body. LvFABP expression in vivo was knocked down by dsRNA-mediated RNA interference (RNAi), which led to significantly decreased levels of PPARα (including LvFATP, LvRXR and LvACS). When exposed to environmental CFA after 4 days, LvFABP knocked down group had a sharp upregulation of LvFATP, LvRXR, LvACS expression, GST activity and NEFA amount, following decreased THC and SOD1 activity. These results suggested that environmental concentration CFA may have some toxicological effect on L. vannamei, following fatty acids metabolism and oxidative stress responses by LvFABP via the PPARα/RXR signaling pathway, including LvFATP, LvRXR and LvACS.

Hypochlorite plays a significant role in physiological processes, particularly regulation of lysosomal functions, and is involved in various diseases. Thus, it is crucial to develop highly sensitive and selective molecule tools to detect HClO in lysosomes. Herein, a novel 2H-benzo[h]chromene-pyridine derivative (1) was synthesized through condensation reaction, which exhibited a notable deep-red emission at 640 nm in pure water. This deep-red emission was specifically quenched by adding ClO−. The response of probe 1 toward ClO− was rapid (within 10 s), sensitive (detection limit of 0.012 μM), and effective over a wide range of pH (1.0–12.0). Due to the existence of morpholine as the lysosome-targeting unit, the probe was successfully utilized to monitor lysosomal ClO−. Moreover, the probe 1 was also applied to detecting ClO− in zebrafish.

The fibrinogen-to-albumin ratio index (FAR) is a valuable tool reflecting the systemic inflammation level and associated with the severity of coronary artery disease. However, the utility of the FAR in predicting the long-term prognosis of patients with ST-elevation myocardial infarction (STEMI) and multivessel disease has remained to be determined. A total of 424 patients diagnosed with STEMI and multivessel disease were recruited for the present study. They were given emergent percutaneous coronary intervention treatment and then completed a follow-up for primary (all-cause mortality) and secondary endpoints (major adverse cardiac events, including MI, stroke, emergent revascularization and rehospitalization due to heart failure). The association between FAR and the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score was investigated, while receiver operating characteristic curve analysis was adopted to assess the ability of the FAR to predict long-term outcomes. The long-term survival of high and low FAR groups was compared by drawing Kaplan-Meier survival curves. Multivariate Cox regression analysis was adopted to evaluate the risk factors of primary and secondary endpoints. The FAR was revealed to have a linear correlation with the SYNTAX score (y=0.022x+17.737; P=0.015). Furthermore, the FAR was a significant predictor of all-cause death with a cut-off value of 128.4 (area under the curve, 0.832; P

Background and Objective: Computed tomography guided percutaneous lung biopsy is a commonly used method for clarifying the nature of pulmonary nodules. However, due to the existence of breathing movement, the lungs have greater mobility, and biopsy of small pulmonary nodules is difficult. In recent years, 3D-printed coplanar templates are gradually used in percutaneous biopsy of small pulmonary nodules. Therefore, this study aimed to evaluate the application value of 3D-printed coplanar puncture template assisted computed tomography guided percutaneous core needle biopsy of small (≤20mm) pulmonary nodules. Method: From January 2018 to January 2021 in Taihe Hospital, 210 hospitalized patients with pulmonary nodules underwent percutaneous core needle biopsy for histopathology/cytopathology diagnosis and were included in the study. All patients were randomly allocated into two groups, patients in Free-hand group underwent percutaneous core needle biopsy without 3D-printed coplanar templates, and patients in 3D-PCT group underwent percutaneous core needle biopsy with 3D-printed coplanar templates. The number of needle adjustments, number of CT scans, surgical time-consuming, diagnostic accuracy, and incidence of complications were recorded and compared between the two groups. Rapid on site evaluation was routinely used for guiding specimens’ triage. Approval for this trial was obtained from the Ethics Committee of the Taihe hospital. Result: The number of needle adjustments (1.41±0.63 vs. 2.23±0.85), the number of CT scans (3.63±0.73 vs. 4.25±0.81) and the incidence of pneumothorax (9.6% vs. 21.1%) during the procedure were significantly lower in the observation group than the control group (P< 0.05), whereas there were no significant differences in the diagnostic accuracy (95.2% vs. 94.3%) and incidence of pulmonary hemorrhage (65.4% vs. 62.3%) between the two groups (P> 0.05), however, the surgical time-consuming in 3D-PCT group is significantly more than Free-hand group.Conclusions: These findings indicated that the 3D-printed coplanar puncture template combined with CT guided percutaneous biopsy can relatively fix the target lesion, reduce the number of needle adjustments and number of CT scans, reduce iatrogenic radiation, and reduce the incidence of complications, especially pneumothorax.

Objective The ongoing pandemic of COVID‐19 caused by the novel coronavirus Syndrome‐Coronavirus‐2 (SARS‐CoV‐2) is an emerging, rapidly evolving situation. Excluded typical manifestation of pneumonia and acute respiratory symptoms, COVID‐19 patients also have abnormal D‐dimer concentration in the serum, but the results are controversial. Method A meta‐analysis first aims to explored the connection between D‐dimer concentration and COVID‐19 patients. Results Our results found a significant relationship between D‐dimer and COVID‐19, with a pooled OR of 1.90 (95% CI: 1.32‐2.48; P

Premature ovarian failure (POF) is a clinical term used to describe a condition in which women present with amenorrhoea, hypergonadotropic hypogonadism, and infertility under 40 years old, which are mainly characterized by ovarian granulosa cell inflammation and death. Pyroptosis is a proinflammatory form of programmed cell death. However, the roles of pyroptosis in POF and moxibustion (Mox) on pyroptosis in POF have not been elucidated. The aim of the present study was to investigate the protective effect of moxibustion against cyclophosphamide- (CP-) induced POF and to determine the underlying mechanisms. The results indicated that Mox could decrease the follicle-stimulating hormone (FSH) and luteotropic hormone (LH) and increase estradiol (E2) in serum, which indicated that it could improve ovarian reserve capacity. Mox also ameliorated CP-induced ovarian injury accompanied by decreased levels of interleukin-1β (IL-1β), IL-18, and gasdermin D (GSDMD), which are key features of pyroptosis. Further investigation showed that Mox alleviated POF through NLRP3-mediated pyroptosis. On the one hand, Mox directly inhibited TXNIP/NLRP3/caspase-1 signaling-induced pyroptosis, and on the other hand, it indirectly decreased NLRP3, pro-IL-1β, and pro-IL-18 through inhibiting TLR4/MyD88/NF-κB signaling. Our results show that Mox might be a new therapeutic strategy for the treatment of POF.

The proteins related to the biosynthesis of salvianolic acids and lignins were regulated by smoke–water and karrikinolide in Salvia miltiorrhiza hairy roots. The effects of smoke–water (SW) and karrikinolide (KAR1) on the biosynthesis of salvianolic acids and lignins in Salvia miltiorrhiza hairy roots have been studied using proteomic technology. The results showed that a total of 1290 and 1678 differentially expressed proteins were respectively obtained in SW and KAR1 comparing to the control. Bioinformatics analysis indicated the differentially expressed proteins responding to SW and KAR1 treatments mainly involved in macromolecule metabolic process, cell part, binding, etc., and most of the proteins were located at the cytoplasm and cell membrane, followed by nuclear. In addition, the proteins involved in salvianolic acids biosynthesis were up-regulated, including 4-coumarate-CoA ligase (EC 6.2.1.12) and shikimate O-hydroxycinnamoyl-transferase (EC 2.3.1.133). Enzymes involved in lignins biosynthesis were also identified, e.g. cinnamyl-alcohol dehydrogenase (EC 1.1.1.195) and peroxidase (EC 1.11.1.7). The results indicated that proteins related to the biosynthesis of salvianolic acids and lignins were regulated by SW and KAR1 in S. miltiorrhiza hairy roots. This study will enhance our understanding of the mechanism by which SW and KAR1 on the biosynthesis of salvianolic acids and lignins in S. miltiorrhiza hairy roots.

Urinary tract infections (UTI) are common infections that can be mild to life threatening. However, increased bacterial resistance and poor patient compliance rates have limited the effectiveness of conventional antibiotic therapies. Here, we investigated the relationship between nitrofurantoin and amikacin against 12 clinical MDR uropathogenic Escherichia coli (UPEC) strains both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in all 12 test strains by standard checkerboard and time-kill assays. Importantly, amikacin or nitrofurantoin at half of the clinical doses were not effective in the treatment of UPEC infections in the G. mellonella model but the combination therapy significantly increased G. mellonella survival from infections caused by all 12 study UPEC strains. Taken together, these results demonstrated synergy effects between nitrofurantoin and amikacin against MDR UPEC.

Purposes: Minichromosome maintenance (MCM) proteins play an important role in replication and cell cycle progression. Even so, their expression and prognostic roles in cancer remain controversial. Methods: To address this issue, the study investigated the roles of MCMs in the prognosis of GC by using ONCOMINE, GEPIA2, UALCAN, Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, and DAVID databases. Results: Over expressions of mRNA and cell lines were found in all members of the MCM family, and MCMs were found to be significantly associated with pathological tumor grades in GC patients. Besides, higher mRNA expressions of MCM1/5/7 were found to be significantly associated with shorter overall survival (OS) and progression-free survival (FP) in GC patients, while higher mRNA expression of MCM4/6/9 were connected with favorable OS and FP. Moreover, a high mutation rate of MCMs (68%) was also observed in GC patients. Conclusions: The results indicated that MCM1/5/7 were potential targets of precision therapy for patients with GC. And MCM4/6/9 were new biomarkers for the prognosis of GC. The results of the study will contribute to supplement the existing knowledge, and help to explore therapeutic targets and enhance the accuracy of prognosis for patients with GC.