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To determine a rapid and accurate method for locating the keypoint and "keyhole" in the suboccipital retrosigmoid keyhole approach. (1) Twelve adult skull specimens were selected to locate the anatomical landmarks on the external surface of the skull.The line between the infraorbital margin and superior margin of the external acoustic meatus was named the baseline. A coordinate system was established using the baseline and its perpendicular line through the top point of diagastric groove.The perpendicular distance (x), and the horizontal distance (y) between the central point of the "keyhole" and the top point of the digastric groove in that coordinate system were measured. The method was applied to fresh cadaveric specimens and 53 clinical cases to evaluate its application value. (1) x and y were 14.20 ± 2.63 mm and 6.54 ± 1.83 mm, respectively (left) and 14.95 ± 2.53 mm and 6.65 ± 1.61 mm, respectively (right). There was no significant difference between the left and right sides of the skull (P > 0.05). (2) The operative area was satisfactorily exposed in the fresh cadaveric specimens, and no venous sinus injury was observed. (3) In clinical practice, drilling did not cause injury to venous sinuses, the mean diameter of the bone windows was 2.0-2.5 cm, the mean craniotomy time was 26.01 ± 3.46 min, and the transverse and sigmoid sinuses of 47 patients were well-exposed. We propose a "one point, two lines, and two distances" for "keyhole" localization theory, that is we use the baseline between the infraorbital margin and superior margin of the external acoustic meatus and the perpendicular line to the baseline through the top point of the digastric groove to establish a coordinate system. And the drilling point was 14.0 mm above and 6.5 mm behind the top point of the digastric groove in the coordinate system.
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Cadáver , Senos Craneales , Craneotomía , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Senos Craneales/anatomía & histología , Senos Craneales/cirugía , Craneotomía/métodos , Procedimientos Neuroquirúrgicos/métodos , Anciano , Adulto Joven , Senos Transversos/anatomía & histología , Senos Transversos/cirugía , Cráneo/anatomía & histología , Cráneo/cirugíaRESUMEN
BACKGROUND: In recent years, immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy across diverse malignancies. Notably, in patients with advanced gastric cancer, the use of programmed death 1 (PD-1) blockade has significantly prolonged overall survival, marking a pivotal advancement comparable to the impact of Herceptin over the past two decades. While the therapeutic benefits of ICIs are evident, the increasing use of immunotherapy has led to an increase in immune-related adverse events. CASE SUMMARY: This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis. Following sintilimab therapy, the patient developed severe rashes accompanied by cytokine release syndrome (CRS). Fortunately, effective management was achieved through the administration of glucocorticoid, tocilizumab, and acitretin, which resulted in favorable outcomes. CONCLUSION: Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
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Since its emergence, SARS-CoV-2 has been continuously evolving, hampering the effectiveness of current vaccines against COVID-19. mAbs can be used to treat patients at risk of severe COVID-19. Thus, the development of broadly protective mAbs and an understanding of the underlying protective mechanisms are of great importance. Here, we isolated mAbs from donors with breakthrough infection with Omicron subvariants using a single-B cell screening platform. We identified a mAb, O5C2, which possesses broad-spectrum neutralization and antibody-dependent cell-mediated cytotoxic activities against SARS-CoV-2 variants, including EG.5.1. Single-particle analysis by cryo-electron microscopy revealed that O5C2 targeted an unusually large epitope within the receptor-binding domain of spike protein that overlapped with the angiotensin-converting enzyme 2 binding interface. Furthermore, O5C2 effectively protected against BA.5 Omicron infection in vivo by mediating changes in transcriptomes enriched in genes involved in apoptosis and interferon responses. Our findings provide insights into the development of pan-protective mAbs against SARS-CoV-2.
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Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , SARS-CoV-2/inmunología , Humanos , COVID-19/inmunología , COVID-19/virología , Anticuerpos Antivirales/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Animales , Ratones , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Microscopía por Crioelectrón , Epítopos/inmunología , Anticuerpos ampliamente neutralizantes/inmunología , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , FemeninoRESUMEN
OBJECTIVES: To evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000-December 2010. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All healthcare facilities in Taiwan. PARTICIPANTS: A total of 28 772 individuals were enrolled. INTERVENTIONS: 26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted. PRIMARY OUTCOME MEASURE: To identify risk differences in developing osteoporosis among patients with a medical history of NS. RESULTS: After adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis. CONCLUSION: NS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.
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Síndrome Nefrótico , Osteoporosis , Humanos , Taiwán/epidemiología , Osteoporosis/epidemiología , Osteoporosis/complicaciones , Femenino , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Síndrome Nefrótico/epidemiología , Síndrome Nefrótico/complicaciones , Adulto , Anciano , Factores de Riesgo , Comorbilidad , Adulto Joven , Adolescente , Corticoesteroides/efectos adversosRESUMEN
Most membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use. Here, we describe GlycoSHIELD, a reductionist method that can be implemented on personal computers to graft realistic ensembles of glycan conformers onto static protein structures in minutes. Using molecular dynamics simulation, small-angle X-ray scattering, cryoelectron microscopy, and mass spectrometry, we show that this open-access toolkit provides enhanced models of glycoprotein structures. Focusing on N-cadherin, human coronavirus spike proteins, and gamma-aminobutyric acid receptors, we show that GlycoSHIELD can shed light on the impact of glycans on the conformation and activity of complex glycoproteins.
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Glicoproteínas , Simulación de Dinámica Molecular , Humanos , Microscopía por Crioelectrón , Glicoproteínas/química , Glicosilación , Polisacáridos/químicaRESUMEN
AIMS: Prenatal stress (PS) has an important impact on the brain development of offspring, which can lead to attention deficits, anxiety and depression in offspring. Geniposide (GE) is a kind of iridoid glycoside extracted from Gardenia jasminoides Ellis. It has various pharmacological effects and has been proved that have antidepressant effects. The aim of this study was to investigate the effect of GE on depression-like behavior in PS-induced male offspring mice and explore the possible molecular mechanisms. METHODS: We used a prenatal restraint stress model, focusing on male PS-induced offspring mice to study the effects of GE. KEY FINDINGS: The results showed that GE administration for 4 weeks significantly improved the depression-like behavior in PS offspring mice, which was manifested by markedly increasing the sucrose preference of PS offspring and the activity in the open field test, and reducing the immobility time in the forced swimming test. In addition, GE significantly reduced the levels of hypothalamic-pituitary-adrenal (HPA) axis-related hormones and exceedingly increased the protein expression of MAP2 and GAP43 in PS offspring. Furthermore, GE increased Glucocorticoid receptors (GR) nuclear translocation in the hippocampus of PS offspring, and enhanced the expression of synaptic plasticity-related proteins. CONCLUSION: The results of this study showed that GE exerts antidepressant effects in male PS offspring mice by regulating the HPA axis, GR function and proteins related to synaptic plasticity.
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Depresión , Iridoides , Efectos Tardíos de la Exposición Prenatal , Femenino , Embarazo , Masculino , Ratones , Animales , Humanos , Depresión/tratamiento farmacológico , Depresión/etiología , Depresión/metabolismo , Receptores de Glucocorticoides/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Estrés Psicológico/complicaciones , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Hipocampo/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Corticosterona/metabolismoRESUMEN
BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage â cohort (510 HCCs and 2074 LCs) and Stage â ¡ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage â cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage â ¡ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.
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Carcinoma Hepatocelular , Ácidos Nucleicos Libres de Células , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/epidemiología , alfa-Fetoproteínas , Estudios Transversales , Detección Precoz del Cáncer/métodos , Ultrasonografía/métodos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/complicaciones , Biomarcadores de TumorRESUMEN
Proteins can spontaneously tie a variety of intricate topological knots through twisting and threading of the polypeptide chains. Recently developed artificial intelligence algorithms have predicted several new classes of topological knotted proteins, but the predictions remain to be authenticated experimentally. Here, we showed by X-ray crystallography and solution-state NMR spectroscopy that Q9PR55, an 89-residue protein from Ureaplasma urealyticum, possesses a novel 71 knotted topology that is accurately predicted by AlphaFold 2, except for the flexible N terminus. Q9PR55 is monomeric in solution, making it the smallest and most complex knotted protein known to date. In addition to its exceptional chemical stability against urea-induced unfolding, Q9PR55 is remarkably robust to resist the mechanical unfolding-coupled proteolysis by a bacterial proteasome, ClpXP. Our results suggest that the mechanical resistance against pulling-induced unfolding is determined by the complexity of the knotted topology rather than the size of the molecule.
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Inteligencia Artificial , Proteínas Bacterianas , Pliegue de Proteína , Ureaplasma urealyticum , Modelos Moleculares , Péptidos , Proteínas Bacterianas/química , Estructura Terciaria de ProteínaRESUMEN
The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.
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Anticuerpos Monoclonales , Anticuerpos ampliamente neutralizantes , COVID-19 , Animales , Humanos , Ratones , Enzima Convertidora de Angiotensina 2/genética , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales , COVID-19/terapia , Dependovirus/genética , ARN Viral , SARS-CoV-2/genética , Anticuerpos ampliamente neutralizantes/farmacología , Anticuerpos ampliamente neutralizantes/uso terapéuticoRESUMEN
BACKGROUND: Cranionasal communicating tumors often originate from the extra-axial intracranial tissue, nasal cavity, and sinuses, and mostly invade the anterior skull base, leading to communication between the cranial and nasal cavities. Cranionasal communicating tumors are clinically rare and thus have been rarely reported in the literature. OBJECTIVE: To investigate the clinical outcomes of combined transcranial and endoscopic transnasal approaches in the surgical management of cranionasal communicating tumors. METHODS: We retrospectively analyzed patients with cranionasal communicating tumors treated at the Department of Neurosurgery, Jinhua Hospital, affiliated with Zhejiang University, from July 2017 to March 2020. All patients were surgically treated using combined transcranial and endoscopic transnasal approaches or the cranionasal dual approach, and skull base reconstruction was performed simultaneously. The postoperative gross tumor resection rate, perioperative complications, and postoperative efficacy were evaluated. RESULTS: Eleven patients with 14-37 months of follow-up were included. Eight patients underwent total resection, two patients underwent subtotal resection, and one patient was treated with partial resection. Postoperative pathological diagnoses revealed four olfactory neuroblastomas, three atypical meningiomas, two recurrent papilloma malignancies, one recurrent invasive pituitary tumor, and one recurrent invasive pituitary adenocarcinoma. Among the 11 patients, severe cerebral edema was observed postoperatively in one patient, and decompression craniectomy was performed. Intracranial infection was observed in two patients, including one with transient cerebrospinal fluid leakage, which was cured after symptomatic treatment. Moreover, postoperative ocular dysmotility and worse olfactory sensation were observed in one and two patients, respectively. The mean follow-up time of the 11 patients was (24.4 ± 5.7) months. The one-year survival rate of the patients was 100%; 10 patients (90.9%) had a favorable outcome (Glasgow Outcome Scale score of 4-5), and only one patient (9.1%) had a Glasgow Outcome Scale score of 3. Furthermore, during the last follow-up, tumor recurrence occurred in two patients (18.2%). CONCLUSION: Surgical treatment of cranionasal communicating tumors using the cranionasal dual approach and simultaneous skull base reconstruction improves the gross tumor resection rate with fewer postoperative complications and good short-term efficacy.
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Adenocarcinoma , Neoplasias Nasales , Neoplasias de la Base del Cráneo , Humanos , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Endoscopía , Base del Cráneo/patología , Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/cirugía , Neoplasias Nasales/cirugía , Resultado del TratamientoRESUMEN
Gypsophila huashanensis Y. W. Tsui & D. Q. Lu (Caryophyllaceae) is an endemic herb species to the Qinling Mountains in China. In this study, we characterized its whole plastid genome using the Illumina sequencing platform. The complete plastid genome of G. huashanensis is 152,457 bp in length, including a large single-copy DNA region of 83,476 bp, a small single-copy DNA region of 17,345 bp, and a pair of inverted repeat DNA sequences of 25,818 bp. The genome contains 130 genes comprising 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Evolutionary analysis showed that the non-coding regions of Caryophyllaceae exhibit a higher level of divergence than the exon regions. Gene site selection analysis suggested that 11 coding protein genes (accD, atpF, ndhA, ndhB, petB, petD, rpoCl, rpoC2, rps16, ycfl, and ycf2) have some sites under protein sequence evolution. Phylogenetic analysis showed that G. huashanensis is most closely related to the congeneric species G. oldhamiana. These results are very useful for studying phylogenetic evolution and species divergence in the family Caryophyllaceae.
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OBJECTIVE: To observe and explore the effect of Fuling () in alleviating the spleen deficiency symptom pattern (SDSP). METHODS: We established an animal model of SDS in Sprague-Dawley () rats by treating them with deficiency-inducing factors, including irregular feeding and tail clamping. Mice were administered Fuling () and its extracts (raw/cooked powder, aqueous/alcohol extract) by gavage once a day for 21 d. The body weight, rectal temperature, and spleen and thymus organ coefficients were calculated. The levels of motilin (MTL), gastrin (GAS), aquaporin 2 (AQP2), interleukin 2 (IL-2), IL-4, and 5-hydroxytryptamine (5-HT) in the serum and the level of AQP2 in the kidneys were evaluated by enzyme-linked immunosorbent assay. RESULTS: Fuling () and its extracts did not change the body weight, rectal temperature, and organ coefficients of the spleen and thymus. However, it reduced the levels of MTL and GAS and increased the levels of IL-2 and AQP2. In addition, the levels of IL-4 and 5-HT showed no significant alteration. CONCLUSIONS: These results suggested the crucial function of () in SDSP, especially promoting digestive function and water metabolism.
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Bazo , Wolfiporia , Ratas , Ratones , Animales , Ratas Sprague-Dawley , Interleucina-2/genética , Interleucina-4 , Serotonina , Acuaporina 2 , Peso Corporal , Gastrinas/farmacologíaRESUMEN
Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Approximately 40% of CRC patients are KRAS sequence variation, including KRAS G13D mutation (KRASG13D) CRC patients, accounting for approximately 8% of all KRAS mutations in CRC patients and showing little benefit from anti-EGFR therapy. Therefore, there is an urgent need for new and effective anticancer agents in patients with KRASG13D CRC. Here, we identified a natural product, erianin, that directly interacted with purified recombinant human KRASG13D with a Kd of 1.1163 µM, which also significantly improve the thermal stability of KRASG13D. The cell viability assay showed that KRASG13D cells were more sensitive to erianin than KRASWT or KRASG12V cells. In vitro, results showed that erianin suppressed the migration, invasion and epithelial-mesenchymal transition (EMT) of KRASG13D CRC cells. Furthermore, erianin induced ferroptosis, as evidenced by the accumulation of Fe2+ and reactive oxygen species (ROS), lipid peroxidation, and changes in the mitochondrial morphology of KRASG13D CRC cells. Interestingly, we also found that erianin-induced ferroptosis was accompanied by autophagy. Moreover, the occurrence of erianin-induced ferroptosis is reversed by autophagy inhibitors (NH4Cl and Bafilomycin A1) and ATG5 knockdown, suggesting that erianin-induced ferroptosis is autophagy-dependent. In addition, we evaluated the inhibition of tumor growth and metastasis by erianin in vivo using a subcutaneous tumor model and a spleen-liver metastasis model, respectively. Collectively, these data provide novel insights into the anticancer activity of erianin, which is valuable for the further discussion and investigation of the use of erianin in clinical anticancer chemotherapy for KRASG13D CRC.
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Neoplasias Colorrectales , Ferroptosis , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Ferroptosis/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Mutación , AutofagiaRESUMEN
AIMS: We aimed to evaluate the effect of periplocin on inhibiting hepatocellular carcinoma (HCC) and further determine its mechanisms. MAIN METHODS: Cytotoxic activity of periplocin against HCC cells was tested by CCK-8 and colony formation assays. The antitumor effects of periplocin were evaluated in human HCC SK-HEP-1 xenograft and murine HCC Hepa 1-6 allograft mouse models. Flow cytometry was used to measure cell cycle distribution, apopotosis, and the number of myeloid-derived suppressor cells (MDSCs). Hoechst 33258 dye was applied to observe the nuclear morphology. Network pharmacology was performed to predict possible signaling pathways. Drug affinity responsive target stability assay (DARTS) was used to evaluate AKT binding of periplocin. Western blotting, immunohistochemistry, and immunofluorescence were used to examine the protein expression levels. KEY FINDING: Periplocin inhibited cell viability with IC50 values from 50 nM to 300 nM in human HCC cells. Periplocin disrupted cell cycle distribution and promoted cell apoptosis. Moreover, AKT was predicted as the target of periplocin by network pharmacology, which was confirmed by that AKT/NF-κB signaling was inhibited in periplocin-treated HCC cells. Periplocin also inhibited the expression of CXCL1 and CXCL3, leading to decreased accumulation of MDSCs in HCC tumors. SIGNIFICANCE: These findings reveal the function of periplocin in inhibiting HCC progression by G2/M arrest, apoptosis and suppression of MDSCs accumulation through blockade of the AKT/NF-κB pathway. Our study further suggests that periplocin has the potential to be developed as an effective therapeutic agent for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Supresoras de Origen Mieloide , Humanos , Ratones , Animales , Carcinoma Hepatocelular/patología , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Hepáticas/patología , Células Supresoras de Origen Mieloide/metabolismo , Proliferación Celular , Apoptosis , Línea Celular TumoralRESUMEN
Central nervous system (CNS) disorders exhibit complex neurophysiological and pathological mechanisms, which seriously affect the quality of life in patients. Acupuncture, widely accepted as complementary and alternative medicine, has been proven to exert significant therapeutic effects on CNS diseases. As a part of the innate immune system, NLRP3 inflammasome contributes to the pathogenesis of CNS diseases via regulating neuroinflammation. To further explore the mechanisms of acupuncture regulating NLRP3 inflammasome in CNS diseases, our study focused on the effects of acupuncture on neuroinflammation and the NLRP3 inflammasome in vascular dementia, Alzheimer's disease, stroke, depression, and spinal cord injury. This study confirmed that the activation of NLRP3 inflammasome promotes the development of CNS diseases, and inhibiting the activation of NLRP3 inflammasome is a potential key target for the treatment of CNS diseases. In addition, it is concluded that acupuncture alleviates neuroinflammation by inhibiting the activation of the NLRP3 inflammasome pathway, thereby improving the progression of CNS diseases, which provides a theoretical basis for acupuncture to attenuate neuroinflammation and improve CNS diseases.
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BACKGROUND: Diabetic ulcer is a common complication of diabetes. It is characterized by a long-term disease course and high recurrence rate. Shengji Huayu Formula (SHF) is an effective formula for treating diabetic ulcers. However, the specific effective parts of SHF remain unclear. Clarifying the active polar site of SHF would be helpful to refine research on the components in SHF that promote wound healing. This research aims to focus on evaluating the activity of polar fractions. METHODS: A diabetic rat model was established by intraperitoneally injecting streptozotocin (STZ) and was adopted to confirm the therapeutic effect of SHF. Four different polarity parts were extracted from SHF and prepared into a cream to evaluate the activity. High-performance liquid chromatography (HPLC) was used to detect chemical constituents in chloroform extracts. RESULTS: It was discovered that dracorhodin, aloe-emodin, rhein, imperatorin, emodin, isoimperatorin, chrysophanol, physcion, and tanshinone IIA were the main components of the chloroform extract from SHF. The results revealed that chloroform extract could effectively accelerate diabetic wound healing by promoting collagen regeneration and epidermal repair. Chloroform extract of SHF could stimulate the generation of vascular endothelial growth factor (VEGF). The results are also indicated that the effective active fraction was the chloroform part, and the method of detecting the main chemical constituents in the active part was successfully established. CONCLUSION: SHF could improve diabetic ulcers by promoting granulation tissue synthesis. In this study, four polar parts (petroleum ether, chloroform, ethylacetate, n-butanol) were extracted from a 95% ethanol extract. In contrast, chloroform polar parts showed a higher wound closure rate, stimulated more collagen regeneration and promoted more production of vascular endothelial cells. In conclusion, the chloroform extract of SHF was the effective polar part in ameliorating diabetic wound healing.
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Diabetes Mellitus , Emodina , Animales , Ratas , Etanol , Estreptozocina , Úlcera , Cloroformo , Células Endoteliales , Factor A de Crecimiento Endotelial Vascular , Cicatrización de HeridasRESUMEN
BACKGROUND/AIM: Infection is a common cause of morbidity and mortality in patients treated for diffuse large B-cell lymphoma (DLBCL). However, there is limited information on the impact and risk factors for infection among patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone (R-CHOP). PATIENTS AND METHODS: A retrospective study evaluating patients with DLBCL receiving R-CHOP and R-COP between 2004 and 2021 was conducted at a medical center. Hospital patients' records for the five-item modified frailty index (mFI-5), sarcopenia, blood-based inflammatory markers, and clinical outcomes were statistically analyzed. RESULTS: Patients with frailty, sarcopenia, and high neutrophil-to-lymphocyte ratio (NLR) were associated with a higher risk of infections. The revised International Prognostic Index poor-risk group, high NLR, infections, and treatment modality were risk factors for shorter progression-free and overall survival. CONCLUSION: Pre-treatment high NLR was a predictor of infection and survival outcome in DLBCL patients.
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Fragilidad , Linfoma de Células B Grandes Difuso , Sarcopenia , Humanos , Neutrófilos , Estudios Retrospectivos , Linfocitos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Ciclofosfamida/efectos adversos , Doxorrubicina , Rituximab/uso terapéutico , Vincristina/efectos adversosRESUMEN
OBJECTIVE: To observe the therapeutic effect of electroacupuncture(EA) on obese mice, and to explore the underlying mechanism of EA in treating obesity by focusing on the balance of regulatory T cells (Treg) and T helper 17 cells (Th17) and related inflammatory factors. METHODS: C57BL/6J male mice were randomly divided into normal group, model group and EA group, with 10 mice in each group. The obesity model was established by feeding the mice with high-fat diet. Mice in the EA group was treated with EA at "Zhongwan"(CV12), "Guanyuan"(CV4), "Zusanli"(ST36) and "Fenglong"(ST40) for 20 min every time, 3 times every week, for a total of 8 weeks. The food intake and body weight of mice were observed and recorded, and Lee's index was calculated; the contents of interleukin 2(IL-2), IL-4, IL-6, IL-10, IL-17A, gamma interferon (IFN-γ) and tumor necrosis factor(TNF)-α in serum were detected by multiplex liquid chip quantitative technique; the levels of Treg and Th17 cells in mice spleen tissues were detected by flow cytometry; and the expression levels of foxhead box p3(Foxp3) and retinoic acid related orphan receptor γt(ROR-γt) mRNA in spleen were detected by real-time quantitative PCR. RESULTS: Compared with the normal group, the food intake, body weight, Lee's index, the contents of IL-2, IL-6, IL-17A, IFN-γ and TNF-α in the serum, and the percentage of Th17 and expression of ROR-γt mRNA in the spleen tissues were significantly increased (P<0.01, P<0.001), while the contents of IL-4 and IL-10 in the serum, the percentage of Treg and expression of Foxp3 mRNA in the spleen tissues were significantly decreased (P<0.001, P<0.01) in the model group. Compared with the model group, the food intake, body weight, Lee's index, the contents of IL-2, IL-6, IL-17A, IFN-γ, and TNF-α in the serum, the percentage of Th17 and expression of ROR-γt mRNA in the spleen tissues were significantly decreased (P<0.01), while the contents of IL-4 and IL-10 in serum, the percentage of Treg and expression of Foxp3 mRNA in the spleen tissues were significantly increased(P<0.01, P<0.05) in the EA group. CONCLUSION: EA may improve the obese state of mice by regulating the balance of Treg/Th17 in spleen and the expression of inflammatory factors in serum.
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Electroacupuntura , Bazo , Ratas , Ratones , Masculino , Animales , Ratas Wistar , Bazo/metabolismo , Células Th17/metabolismo , Interleucina-2 , Ratones Obesos , Interleucina-10 , Interleucina-17/genética , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Factor de Necrosis Tumoral alfa/metabolismo , Linfocitos T Reguladores/metabolismo , Interleucina-6 , Interleucina-4 , Ratones Endogámicos C57BL , Inflamación , Obesidad/genética , Obesidad/terapia , Factores de Transcripción Forkhead/genéticaRESUMEN
Fungi-derived ß-glucan, a type of glucopolysaccharide, has been shown to possess immune-modulatory properties in clinical settings. Studies have indicated that ß-glucan derived from Ganoderma lucidum (commonly known as Reishi) holds particular promise in this regard, both in laboratory and in vivo settings. To further investigate the efficacy and safety of Reishi ß-glucan in human subjects, a randomized, double-blinded, placebo-controlled clinical trial was conducted among healthy adult volunteers aged 18 to 55. Participants were instructed to self-administer the interventions or placebos on a daily basis for 84 days, with bloodwork assessments conducted at the beginning and end of the study. The results of the trial showed that subjects in the intervention group, who received Reishi ß-glucan, exhibited a significant enhancement in various immune cell populations, including CD3+, CD4+, CD8+ T-lymphocytes, as well as an improvement in the CD4/CD8 ratio and natural killer cell counts when compared to the placebo group. Additionally, a statistically significant difference was observed in serum immunoglobulin A levels and natural killer cell cytotoxicity between the intervention and placebo groups. Notably, the intervention was found to be safe and well tolerated, with no statistically significant changes observed in markers of kidney or liver function in either group. Overall, the study provides evidence for the ability of Reishi ß-glucan to modulate immune responses in healthy adults, thereby potentially bolstering their defense against opportunistic infections.
RESUMEN
Introduction: Cystitis glandularis (CG) is a rare chronic bladder hyperplastic disease that mainly manifests by recurrent frequent urination, dysuria and gross hematuria. The current lack of unified diagnosis and treatment criteria makes it essential to comprehensively describe the inflammatory immune environment in CG research. Methods: Here, we performed scRNA-sequencing in CG patients for the first time, in which four inflamed tissues as well as three surrounding normal bladder mucosa tissues were included. Specifically, we isolated 18,869 cells to conduct bioinformatic analysis and performed immunofluorescence experiments. Results: Our genetic results demonstrate that CG does not have the classic chromosomal variation observed in bladder tumors, reveal the specific effects of TNF in KRT15 epithelial cells, and identify a new population of PIGR epithelial cells with high immunogenicity. In addition, we confirmed the activation difference of various kinds of T cells during chronic bladder inflammation and discovered a new group of CD27-Switch memory B cells expressing a variety of immunoglobulins. Discussion: CG was regarded as a rare disease and its basic study is still weak.Our study reveals, for the first time, the different kinds of cell subgroups in CG and provides the necessary basis for the clinical treatment of cystitis glandularis. Besides, our study significantly advances the research on cystitis glandularis at the cellular level and provides a theoretical basis for the future treatment of cystitis glandularis.