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ObjectiveTo investigate the mechanism of Xuefu Zhuyu capsules against atherosclerosis via regulating polarization of macrophages based on Notch1/jagged canonical Notch ligand 1（Jagged1）/Hes family BHLH transcription factor 1（Hes1） signaling pathway. MethodThe mouse models with atherosclerosis were prepared by feeding the mice with an ApoE-/- high-fat diet for four weeks， and they were randomly divided into the model group， Xuefu Zhuyu capsule group， and atorvastatin group. C57BL/6 mice were fed as a normal group. The Xuefu Zhuyu capsule group was intragastrically given Xuefu Zhuyu capsules （0.728 g·kg-1·d-1）， and the atorvastatin group was intragastrically given atorvastatin tablet （6.07 mg·kg-1·d-1）. The normal group and the model group were given equal volume of the deionized water by intragastric administration， and the intervention lasted for 12 weeks. Aortic plaque morphology was observed by hematoxylin-eosin （HE） staining， and aortic plaque area and lipid deposition were observed by oil red O staining. The positive expression levels of CD86 and CD206 in aortic tissue were detected by immunohistochemistry， and serum levels of tumor necrosis factor （TNF）-α， interleukin（IL）-1β， transforming growth factor （TGF）-β1， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The relative mRNA expressions of inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， Notch1， Jagged1， and Hes1 in aortic tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The relative protein expression of iNOS， Arg-1， Notch1， Jagged1， and Hes1 in aortic tissue was detected by Western blot. ResultCompared with the normal group， the model group had significant aortic plaque and lipid deposition， and the expression levels of pro-inflammatory cytokines TNF-α and IL-1β were increased （P<0.01）. The expression level of anti-inflammatory cytokine TGF-β1 showed a downward trend， but the difference was not statistically significant. The mRNA and protein expressions of iNOS were increased （P<0.01）. The protein expression of Arg-1 was decreased （P<0.01）， and the mRNA expression of related pathway molecule Jagged1， as well as the protein expressions of Notch1， Jagged1， and Hes1 were increased in the model group （P<0.05， P<0.01）. Compared with those in the model group， the plaque area and lipid deposition had a decreasing trend in the Xuefu Zhuyu capsule group， and the expressions of TNF-α and IL-1β showed a downward trend. The expression of TGF-β1 was increased （P<0.05）， and the expression of macrophage marker CD86 was decreased. The mRNA and protein expressions of iNOS were decreased （P<0.01）. The mRNA and protein expressions of Arg-1 were increased （P<0.05， P<0.01）. Furthermore， the mRNA and protein expressions of Notch1， Jagged1， and Hes1 were decreased （P<0.01）. ConclusionXuefu Zhuyu capsules can reduce aortic plaque area and lipid deposition in mice with atherosclerosis， alleviate inflammation， inhibit M1 macrophages， and promote the expression of M2 macrophages， and the mechanism may be related to the regulation of Notch1/Jagged1/Hes1 signaling pathway.
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Tuberculosis (TB) remains one of the biggest infectious killers worldwide. Vaccine is the most satisfactory tool for prevention of TB; however, Bacillus Calmette-Guérin (BCG), the widely used vaccine in clinical for the prevention of TB, has limitations in protective effects. Development of novel TB vaccines is therefore of urgent need. Currently, there are 15 novel TB vaccine candidates in clinical trials, including live-attenuated vaccines, inactivated vaccines, subunit vaccines and viral-vectored vaccines, which open the door for the ultimate target of the End TB Strategy. This review summarizes the latest advances in the development of TB vaccines in global clinical trials, so as to provide insights into TB control.
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Objective @#To explore the candidate genes and potential molecular mechanisms of anti -neutrophil cyto- plasmic antibodies ( ANCA) -associated vasculitis by bioinformatics and experimental validation , and to provide a scientific theoretical basis for the treatment of potential inflammatory targets for ANCA-associated vasculitis .@*Methods@#The GSE108109 chip data was retrieved from the Gene Expression Omnibus (GEO) database , and the differential genes were processed , analyzed and screened using the R language related program package . Kyoto encyclo- pedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis was carried out using DAVID online network cable , and the interaction network of the protein encoded by the selected genes of inflammatory syn- drome was constructed through STRING web site . Further endogenous competitive RNA ( ceRNA) regulatory net- work was predicted and constructed through miRWalk and DIANA-LncBase databases , and key genes were screened from the network to draw ROC curve . The renal biopsy samples of patients with ANCA-associated vasculi- tis confirmed by our hospital were collected as the experimental group , and the renal biopsy samples of IgA ne- phropathy and micro-adaptive nephropathy were collected as the control group . Immunohistochemical staining was performed on the collected renal biopsy samples , and the average optical density was calculated by semi -quantita- tive analysis of immunohistochemical staining to further verify the expression of the key genes screened by the bioin- formatics analysis . Pearson linear correlation analysis was performed between the average optical density results and the clinical inflammatory data of patients . @*Results @#846 differential genes were screened , of which 444 genes were significantly up-regulated and 402 genes were significantly down-regulated . Through KEGG and GO analysis , im- portant differentially expressed genes related to inflammation regulation were obtained . Among them , CSF1R and TNFRSF1B , two differentially expressed genes never reported in ANCA-associated vasculitis , attracted our atten- tion . At the same time , we constructed multiple ceRNA regulatory axes including KCNQ1OT1 -hsa-miR-125 a-5p- TNFRSF1B . There were 15 samples of ANCA-associated vasculitis , 6 samples of IgA nephropathy , and 3 samples of micropathological kidney . Immunohistochemical results of renal biopsy specimens showed that the expression of CSF1R and TNFRSF1B in ANCA-associated vasculitis kidney tissue was higher than that in the control group . Pearson correlation analysis of clinical data of patients in ANCA group showed that the expression of CSF1R was positively correlated with the content of neutrophil count ( r = 0. 587) , and the expression of TNFRSF1B was posi- tively correlated with the content of serum C -reactive protein ( r = 0. 646) . @*Conclusion @#Key genes related to in- flammatory regulation such as CSF1R and TNFRSF1B were investigated by bioinformatics methods , and a rigorous ceRNA regulatory network was constructed . The expression of CSF1R and TNFRSF1B in ANCA vasculitis was high- er than that in the control group through immunohistochemistry . The results provides a scientific theoretical basis for the molecular mechanism of inflammation , and laid a good foundation for new therapeutic targets of ANCA-related vasculitis for inflammation .
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Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.
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Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
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[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].
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OBJECTIVE To explore the protective effect and possible mechanism of baicalein on hypoxia-induced cortical neuron injury in rats. METHODS The cortical neurons of rats （RN-C cells） were studied and cultured under hypoxic conditions （5%CO2， 94% N2， 1%O2） for 24 hours； the effects of different concentrations of baicalein （0.01， 0.1， 1， 10， 100 μmol/L） on the survival rate of hypoxic RN-C cells were investigated； the effects of baicalein （0.1 μmol/L） on the activities of lactate dehydrogenase （LDH） and superoxide dismutase （SOD）， the content of malondialdehyde （MDA）， migration rate， apoptotic rate， cell cycle and the expressions of cleaved caspase-3， B-cell lymphoma-2 （Bcl-2） and Bcl-2 X protein （Bax） were all detected. RESULTS Compared with control group， the survival rate of cells in the hypoxia group was significantly reduced （P＜0.01）； 0.01， 0.1 and 1 μmol/L baicalein could reverse survival rate of hypoxia-induced cortical neurons （P＜0.05 or P＜0.01）. Scratch experiments showed that baicalein significantly increased the migration rate of hypoxic RN-C cells （P＜0.01）. Compared with control group， the activity of LDH in the supernatant and the content of MDA in the cells， apoptotic rate and the proportion of cells in G1 phase， were significantly increased in the hypoxia group， while SOD activity and the proportion of cells in G2+S phase was decreased significantly （P＜0.01）. The protein expressions of cleaved caspase-3 were increased significantly， while the ratio of Bcl-2/Bax in cells was significantly reduced （P＜0.05 or P＜0.01）. Compared with hypoxia group， the above indexes were all reversed significantly in baicalein group （P＜0.01）. CONCLUSIONS Baicalein can promote the proliferation and migration of cortical neurons， improve hypoxia-induced cell apoptosis and cell cycle distribution， decrease the activity of LDH in supernatant and the level of cellular lipid peroxidation， and improve antioxidant levels. Its mechanism may be related to regulating the caspase- 3/Bax/Bcl-2 pathway.
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Background@#Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. @*Methods@#We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. @*Results@#In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing.Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. @*Conclusion@#This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.
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ObjectiveTo observe the effect of Banxia Xiexintang on the autophagy of interstitial cells of Cajal （ICCs） in the gastric antrum of rats with gastric electric dysrhythmia， and explore the protective effect and regulatory mechanism. MethodThirty-two SD rats were randomly assigned into a normal group， a model group， a Banxia Xiexintang （24.68 g·kg-1） group， and a positive drug （2.7 mg·kg-1） group. The rat model of gastric electric dysrhythmia was established by the method of dieting every other day and drinking dilute hydrochloric acid， and Banxia Xiexintang and the positive drug were administrated for intervention. The body weight of each rat was recorded weekly. The gastric electric activity was recorded by the biological function experimental system. The ultrastructural changes of the gastric antrum tissue were observed by a transmission electron microscope. The co-expression of receptor tyrosine kinase （c-kit）/mammalian homolog of yeast Atg6 （Beclin1） in the gastric antrum tissue was detected by double immunofluorescence labeling method. The expression of microtubule-associated protein 1 light chain 3B （LC3B） and p62 protein in the gastric antrum tissue was determined by Western blot， and the LC3BⅡ/Ⅰ ratio was calculated. ResultCompared with the normal group， the modeling reduced the body weight （P<0.01） and decreased the dominant frequency and dominant power of gastric electricity （P<0.01）. In addition， the modeling caused ultrastructural damage of ICCs in gastric antrum， degeneration and necrosis of organelles， and appearance of a small number of autophagic vesicles. The results of double immunofluorescence labeling showed that the modeling inhibited the positive expression of c-kit and promoted the positive expression of Beclin1 in gastric antrum tissue. Western blot results showed that the modeling increased the ratio of LC3BⅡ/Ⅰ （P<0.01） and down-regulated the expression of p62 protein （P<0.01） in the gastric antrum tissue. Compared with the model group， Banxia Xiexintang and the positive drug increased the body weight （P<0.01） and the dominant frequency and dominant power of gastric electricity （P<0.01）， repaired the ultrastructural damage of ICCs in gastric antrum tissue， promoted the positive expression of c-kit and inhibited the positive expression of Beclin1 in the gastric antrum tissue. Furthermore， Banxia Xiexintang up-regulated the expression of p62 （P<0.05） and inhibited the transformation of LC3BⅠ into LC3BⅡ in gastric antrum tissue （P<0.05）. ConclusionBy regulating the expression of autophagy-related proteins， Banxia Xiexintang can reduce the autophagy and regulate the number and structure of ICCs and thus improve the gastric electric rhythm of rats， which preliminarily explains the mechanism of Banxia Xiexintang in the treatment of epigastric stuffiness.
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OBJECTIVE To investigate the improvement effects and possible mechanism of 7-hydroxyethyl chrysin （7-HEC） on PC12 cell injury induced by hypobaric hypoxia. METHODS The rat adrenal pheochromocytoma cell line PC12 was cultured under low-pressure hypoxia （5%CO2， 94%N2， 1%O2， 54 004 Pa） to investigate the different concentrations of 7-HEC （100， 10， 1， 0.1， 0.01 μmol/L） on the survival rate of hypoxic cells； the effects of 7-HEC（1 μmol/L） on the contents of lactate dehydrogenase （LDH） and malondialdehyde （MDA）， superoxide dismutase （SOD） activity， apoptotic rate， cell cycle， and the expressions of cleaved caspase-3， Bcl-2 and Bax were detected. RESULTS Compared with control group， the survival rate of cells in hypobaric hypoxia group was decreased significantly （P＜0.01）； 10， 1， 0.1 μmol/L 7-HEC could reverse the decrease of cell survival rate caused by hypobaric hypoxia （P＜0.05 or P＜0.01）. Compared with control group， LDH content in supernatant， MDA content in cells， apoptotic rate， the proportion of cells at G1 stage and the protein expression of cleaved caspase-3 were increased significantly in hypobaric hypoxia group， while SOD activity in cells， the proportion of cells at S stage and G2 stage and Bcl-2/Bax ratio were decreased significantly （P＜0.05 or P＜0.01）. Compared with hypobaric hypoxia group， the contents of LDH and MDA， apoptotic rate， the proportion of cells at G1 stage and the expression of cleaved caspase-3 in 7-HEC group were decreased significantly， while SOD activity， the proportion of cells at G2 stage and Bcl-2/Bax ratio were increased significantly （P＜ 0.01）. CONCLUSIONS 7-HEC can significantly increase the survival rate of hypobaric hypoxia cells， reduce the LDH content in supernatant， improve cell cycle arrest， and reduce the rate of apoptosis. Its improvement effects on hypobaric hypoxia cell injury may be related to the inhibition of caspase-3/Bax/Bcl-2 pathway activation.
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Background Since the outbreak of COVID-19, primary health care workers have been facing unprecedented work pressure, and their occupational stress should be taken seriously. Objective To analyze the occupational stress situation and its influencing factors of primary health care workers in Guangdong Province, and to propose targeted interventions. Methods Using a multi-stage stratified random sampling method, each prefecture-level city in Guangdong Province was classified into "good", "medium", or "poor" category based on its gross domestic product (GDP) in 2019 released by the Guangdong Provincial Bureau of Statistics. In September 2021, four primary health care institutions were randomly selected from each stratum, and a total of 1327 staff members were selected for the study. The Core Occupational Stress Scale (COSS) and a basic information questionnaire designed by the authors were used. Mann-Whitney U test was used to compare the means between two groups, and Kruskal-Walis H test was used to compare the means among multiple groups. The comparison of categorical data was performed by trend χ2 test or Pearson χ2 test; the analysis of factors influencing occupational stress was performed by dichotomous multiple logistic regression analysis. Results There were 365 health care workers reporting occupational stress in this survey, and the positive rate of occupational stress was 27.5%. The total occupational stress score in M (P25, P75) and the scores of social support, organization and reward, demand and effort, and control were 45.0 (40.0, 50.0), 20.0 (17.0, 21.0), 14.0 (12.0, 17.0), 12.0 (10.0, 15.0), and 5.0 (4.0, 6.0), respectively. The results of dichotomous multiple logistic regression analysis showed that high education, low income, doctor positions, long working hours in a day, and shift work were associated with the occurrence of reporting occupational stress (P<0.05). Conclusion Education, average monthly income, job category, daily working hours, and shifts are factors influencing the occurrence of reporting occupational stress in primary health care workers; targeted interventions should be implemented to reduce their occupational stress levels.
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Stroke is one of the most common cerebrovascular diseases， including hemorrhagic stroke and ischemic stroke. From a modern medical perspective， stroke is caused by cerebrovascular damage or embolism leading to impaired blood circulation. From the traditional Chinese medicine （TCM） perspective， the pathogenesis of this disease is mainly due to the disorder of Qi and blood， which ascend to the brain， causing either blood extravasation or blockage of brain collaterals. Stasis is a pathological factor that runs throughout the entire course of stroke， and the method of promoting blood circulation and resolving stasis has been a core treatment for stroke for a long time. Hirudo， as a traditional insect drug， has shown good effects in promoting blood circulation and resolving stasis. Modern pharmacological research has confirmed that Hirudo contains anticoagulant components， which provide significant advantages in dissolving thrombi in ischemic stroke and facilitating hematoma absorption in hemorrhagic stroke. Hirudo and its related preparations have been proven to exert an anti-stroke effect through anticoagulation， anti-thrombosis， and protection of vascular endothelium. As a result， they have been widely used in the treatment of stroke. This article explored the theoretical basis and research status of using Hirudo for treating stroke based on its main active components and hemostatic properties and summarized the current research status of commonly used Hirudo-based formulations and preparations， aiming to provide references for the involvement of Hirudo in stroke treatment.
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Objective To standardize the selection of clinical research outcome indicators,which can objectively evaluate the clinical efficacy or effect of traditional Chinese medicine in the treatment of myasthenia gravis.This study aims to standardize the construction of the core outcome set of clinical research of traditional Chinese medicine in the treatment of myasthenia gravis.Methods We followed the core outcome set development specification(COS-STAD)to carry out research,established a research working group,which set up a Delphi-method advisory group.Two graduate students of working group conducted a document research and meetings of patients to establishe an outcome set item pool of myasthenia gravis in clinical trials of Chinese medicine under the instruction of other members.With the questionnaire based on the content of item pool,we then carried out Delphi-method expert consultations and a consensus meeting.Results The core outcome set of clinical research on myasthenia gravis treated with traditional Chinese medicine included five outcome domains:endpoint outcome,myasthenia gravis symptom evaluation,medication evaluation,quality of life evaluation and safety outcome;Nine outcome measures:recurrence rate,incidence of hormone complications,incidence of crisis,QMGS scale(MGFA quantitative myasthenia gravis score),daily activity scale of MG patients(ADL),analysis of immunosuppressant dosage,analysis of glucocorticoid dosage,analysis of cholinesterase inhibitor dosage,and incidence of adverse events.Conclusion The five outcome domains and nine outcome measures included in the core outcome set can be used as outcome options for the efficacy evaluation of myasthenia gravis clinical research.
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Objective:To determine the expression of Brahma-related gene 1 (BRG1) in cutaneous squamous cell carcinoma (cSCC) tissues and cells, and to investigate molecular mechanisms underlying the regulatory effect of its interaction with activating transcription factor 2 (ATF2) on the proliferation, migration and invasion of cSCC cells.Methods:From 2015 to 2021, 66 paraffin-embedded actinic keratosis (AK) tissue samples and 80 paraffin-embedded cSCC (including squamous cell carcinoma in situ) tissue samples were collected from the Department of Dermatology, Affiliated Hospital 2 of Nantong University, and the diagnoses of all the cases were confirmed histopathologically; at the same time, 35 paraffin-embedded normal skin tissue samples obtained by cosmetic surgery served as normal control group. Immunohistochemical staining was performed to determine the BRG1 expression in cSCC, AK, and normal skin tissues, and correlations between BRG1 expression and clinicopathological parameters of cSCC patients were analyzed. Fresh tissue samples were collected from 12 cSCC patients and 12 healthy controls, and cSCC cell lines A431 and Scl-1 and a human immortalized keratinocyte cell line HaCaT were routinely cultured; real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to determine the mRNA expression of BRG1 in tissues and cells, and co-immunoprecipitation assay and cellular immunofluorescence staining were conducted to analyze the interaction between BRG1 and ATF2. The expression of BRG1 (BRG1 siRNA1 - 5 groups) and ATF2 (ATF2-shRNA group) in A431 and Scl-1 cells was knocked down by RNA interference, and cells transfected with negative control siRNA or shNC served as controls (control siRNA group and shNC group, respectively), cell counting kit-8 (CCK8) assay, colony formation assay, cell scratch assay, and Transwell assay were conducted to evaluate effects of knocking down BRG1 and ATF2 on the proliferation, migration, and invasion of cSCC cells. Comparisons of measurement data among multiple groups were conducted using one-way analysis of variance, and multiple comparisons were conducted using Dunnett- t test. Results:Immunohistochemical staining showed that the expression intensity of BRG1 protein was significantly lower in the cSCC and AK tissues than in the normal skin tissues ( χ2 = 44.40, P < 0.001). qRT-PCR showed that the mRNA expression level of BRG1 was significantly lower in the cSCC tissues (1.345 ± 0.956) than in the normal skin tissues (2.499 ± 1.501, t = 2.25, P = 0.035), and also significantly lower in A431 and Scl-1 cells (0.041 ± 0.002, 0.026 ± 0.003, respectively) than in HaCaT cells (0.135 ± 0.033, t = 4.95, 5.73, P = 0.008, 0.005, respectively). The low expression of BRG1 was associated with tumors at sun-exposed sites ( P = 0.041), low tumor differentiation ( P = 0.001), and high Broder′s grade ( P < 0.001) in the cSCC patients. In both A431 cells and Scl-1 cells, the BRG1 siRNA1 group and BRG1 siRNA2 group showed significantly increased numbers of cell colonies, migratory cells and invasive cells, as well as cell migration rates compared with the control siRNA group (all P < 0.05). Co-immunoprecipitation assay showed that BRG1 protein could bind to ATF2 protein in A431 and Scl-1 cells, and immunofluorescence staining showed that the two proteins were co-localized; compared with the control siRNA group, the BRG1 siRNA1 group (both A431 and Scl-1 cells) and BRG1 siRNA2 group (A431 cells) both showed increased phosphorylation and activation of ATF2 (all P < 0.05) ; in both A431 cells and Scl-1 cells, the shATF2 group showed significantly decreased numbers of cell colonies (both P = 0.001), cellular proliferative activity at 24 - 96 hours (all P < 0.001), and numbers of migratory cells and invasive cells compared with the shNC group (all P ≤ 0.001) . Conclusion:BRG1 was lowly expressed in the cSCC and AK tissues, and could inhibit the proliferation, migration, and invasion of cSCC cells; ATF2 could promote the proliferation, migration, and invasion of cSCC cells; BRG1 may exert an anti-tumor effect by interacting with ATF2 protein and inhibiting phosphorylation-dependent activation of ATF2.
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Objective:To investigate the efficacy of metagenomic next generation sequencing (mNGS) in the etiological diagnosis of patients with spinal infection, so as to provide reference for timely diagnosis and treatment.Methods:A total of 40 patients with suspected spinal infection admitted to the Department of Infectious Diseases in Henan Provincial People′s Hospital from January 2020 to July 2022 were included. The results of tissue culture, histopathological examination and tissue mNGS detection were analyzed retrospectively. According to the clinical diagnose, the patients were divided into the spinal infection group (28 cases) and the non-spinal infection group (12 cases). The positive rate, sensitivity and specificity of mNGS and tissue culture in the pathogen detection of patients with spinal infection were compared. McNemar test was used for statistical analysis.Results:There were 23 males and 17 females in 40 patients. The positive rate of mNGS was higher than that of tissue culture (75.0%(30/40) vs 12.5%(5/40)), and the difference was statistically significant ( χ2=0.08, P<0.001). Based on clinical diagnostic criteria, the sensitivity of mNGS in the diagnosis of spinal infection was higher than that of tissue culture (82.1% vs 17.9%), with a statistically significant difference ( χ2=0.02, P<0.001), while the specificity compared to the tissue culture (33.3% vs 100.0%), the difference was not statistically significant ( P>0.05). Conclusions:mNGS has a high pathogen detection rate and sensitivity in the etiological diagnosis of patients with spinal infection, which could provide clinical guidance for the diagnosis and treatment of patients with spinal infection.
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Objective:To analyze the fetal ultrasonographic features of malformation of cortical development (MCD) during the second trimester, and explore and summarize the relevant diagnostic clues, so as to improve the ability of diagnosis and differential diagnosis of fetal MCD.Methods:A total of 313 fetuses with brain abnormalities suspected on ultrasound in Chengdu Women′s and Children′s Central Hospital from April 2018 to August 2022 were retrospectively analyzed. The fetuses were examined using MRI. The ultrasonographic characteristics of fetal MCD were summarized, and the fetal ultrasound and MRI imaging data were compared for fetal MCD.Results:Nineteen fetuses were diagnosed with MCD from 313 fetuses(6.07%, 19/313). Seventeen cases of MCD were identified by ultrasonography and subsequently validated by fetal MRI, including 6 cases of schizencephaly, 2 cases of hemimegalencephaly(HMEG), 3 cases of periventricular nodular heterotopia(PVNH), 3 cases of lissencephaly, 2 cases of microcephaly and 1 case of polymicrogyria(PMG). There were 3 cases with two concurrent MCD, 1 case of HMEG, and MRI increased the diagnosis of left parietal PMG; 1 case of lissencephaly, and MRI increased the diagnosis of PVNH. The other case was PMG, and MRI increased the diagnosis of lissencephaly. Two cases of fetal MCD were not indicated by ultrasonography, one of which was diagnosed as tuberous sclerosis and another one as schizencephaly by MRI, both due to ventriculomegaly.Conclusions:Various types of MCD in the second trimester have ultrasonographic characteristics. Abnormal lateral ventricles, intracranial structural changes such as sulci and gyrus can provide reliable ultrasound diagnostic clues for fetal MCD.
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Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties, a high incidence of pulmonary metastasis and a poor prognosis. Chemotherapy is the mainstay of treatment for osteosarcoma. Currently, there are no molecular targeted drugs approved for osteosarcoma treatment, particularly effective drugs for osteosarcoma with pulmonary metastases. It has been reported that fibroblast activation protein alpha (FAPα) is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis, demonstrating that FAPα-targeted agents might be a promising therapeutic strategy for osteosarcoma. In the present study, we reported that the FAPα-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPα-positive osteosarcoma cells in vitro and in vivo. Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells. Importantly, it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo. Mechanistically, Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway, leading to inhibition of the growth and metastatic spread of osteosarcoma cells. These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPα-positive osteosarcoma, particularly osteosarcoma with pulmonary metastases.
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Sodium glucose cotransporter 2 inhibitor (SGLT2i) emerged as a new hypoglycemic agent, which can inhibit glucose reabsorption and thus play a hypoglycemic role. Recent studies have shown that SGLT2i not only lowers blood glucose, but also has a protective effect on the cardiovascular system, which may benefit patients with heart failure.The specific mechanism of action is still not fully elucidated. This paper aims to summarize the latest research results of SGLT2i in the treatment of heart failure, and analyze the possible mechanisms for clinical guidance.
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Objective:To establish a scoring scale for trial of labor after cesarean section (TOLAC), to explore the evaluation ability of this scoring scale for vaginal delivery after cesarean section (VBAC), and to improve the success rate of TOLAC.Methods:The delivery information of 661 TOLAC pregnant women admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from 2014 to 2017 was retrospectively analyzed, and the TOLAC scoring scale was established by referring to relevant literatures. A prospective cohort study of pregnant women with TOLAC from January 2018 to December 2019 in Zhengzhou Central Hospital was conducted, including 440 pregnant women who were excluded from contraindications in trial labor. According to TOLAC scoring scale, pregnant women were divided into 3 groups, 0-6 group (94 cases), 7-9 group (234 cases) and 10-15 group (112 cases). The success rate of trial labor, failure reasons and incidence of maternal and neonatal complications were compared among the three groups.Results:(1) The overall success rate of TOLAC in 440 pregnant women was 75.0% (330/440). The success rates of 0-6, 7-9 and 10-15 groups were 53.2% (50/94), 76.9% (180/234) and 89.3% (100/112), respectively. The success rate of 10-15 group were significantly higher than those of 0-6 and 7-9 groups (all P<0.05). (2) Among the causes of trial labor failure, there were statistically significant differences between the three groups in terms of threatened uterine rupture and maternal abandonment (all P<0.05). Pairings showed that the incidences of threatened uterine rupture and maternal abandonment in 0-6 group was lower than those in 7-9 and 10-15 groups, and the differences were statistically significant (all P<0.05). (3) Maternal and neonatal complications mainly included postpartum hemorrhage and neonatal asphyxia, but there were no significant difference in the incidence of TOLAC success or failure among the three groups (all P>0.05). There was no uterine rupture in all groups. (4) The main factors affecting TOLAC score of pregnant women in the three groups included natural labor, estimated weight of the fetus at this time, Bishop score of the cervix at admission and gestational age, and the scores of the above indexes in 10-15 group were significantly higher than those in 0-6 group and 7-9 group (all P<0.05). Conclusions:TOLAC scoring scale has more accurate evaluation ability for VBAC, which could improve the success rate of TOLAC and maternal and child safety. The score of 0-6 is not recommended for vaginal trial labor, the score of 7-9 is recommended for vaginal trial labor, and the score of 10-15 is strongly recommended for vaginal trial labor.
ABSTRACT
Stroke is a common cerebrovascular disease， characterized by high incidence， mortality and disability rate. Neuronal cells， the basic unit of the central nervous system， can be injured to varying degrees when stroke occurs. Neuronal cell injury after stroke is also the key cause leading to neurological dysfunction， affecting the prognosis and quality of life of patients. Therefore， reducing the neuronal cell injury and delaying the process of cell death are effective to decrease the nerve function injury in stroke patients and improve their prognosis， thus lowering the death and disability rate of stroke. Ferroptosis is a new form of cell death that has been widely concerned in recent years. Several studies have confirmed that there is ferroptosis in neuronal cells after stroke. Since ferroptosis is an adjustable form， its intervention can help regulate the injury and death of neuronal cells. Studies have shown that inhibiting ferroptosis plays a role in protecting neuronal cells. Traditional Chinese medicine （TCM）， with the multi-channel and multi-target treatment advantages， has been widely used in the whole stroke and has achieved good clinical efficacy. It might be a new direction taking TCM regulation of ferroptosis as the entry point for stroke treatment in the future. This review revealed the mechanism of ferroptosis， discussed the research status of TCM in intervening in neuronal cell ferroptosis， and provided reference for further improving the efficacy of TCM in stroke.