ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To investigate the clinical characteristics and treatment of patients with CD4+CD8-T-cell large granular lymphocytic leukemia(T-LGLL).Methods:The clinical manifestations,diagnosis and treatment of 1 case of CD4+CD8-T-LGLL patient were reported,and relevant literatures were reviewed.Results:The patient was a 70-year-old woman with slow clinical progress,mainly manifested by thrombocytopenia and myelodysplasia.The blood smear was mainly composed of large granular lymphocytes.Immunotyping and T-cell receptor gene rearrangement analysis showed that it was in line with T-LGLL.Partial remission(PR)was achieved through the treatment of cyclophosphamide(50 mg/d)combined with prednisone(gradually reduced and stopped later).Conclusion:CD4+CD8-T-LGLL is very rare in clinical practice,and its clinical manifestations are different from those of CD4-CD8+T-LGLL.

Objective To investigate effect of toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) p56 pathway on liver damage in children with rotavirus (RV) enteritis. Methods A total of fifty children with RV enteritis were selected as RV group, while another 50 children with RV negative enteritis during the same period were selected as control group. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured by automatic biochemical analyzer. TLR4 mRNA and NF-κB mRNA expression in peripheral blood mononuclear cells (PMBC) were detected by polymerase chain reaction (PCR); the expression level of NF-κB p65 protein was detected by Western Blot. The levels of serum AST, ALT and the incidence of liver damage were compared between the two groups. TLR4 mRNA, NF-κB mRNA and NF-κB p65 protein expression in PMBC were compared between the two groups. The expression levels of TLR4 mRNA, NF-κB mRNA and NF-κB p65 protein in PMBC were compared between children with and without liver damage in RV group. The correlation between liver function and TLR4/NF-κB p65 pathway in children with RV enteritis was analyzed by Pearson correlation method. Results The levels of serum AST and ALT as well as the incidence of liver injury in the RV group were significantly higher than those in the control group (P < 0.05). The expressions of TLR4 mRNA, NF-κB mRNA and NF-κB p65 protein of PBMC in the RV group were significantly higher than those in the control group (P < 0.05). In the RV group, the expressions of TLR4 mRNA, NF-κB mRNA and NF-κB p65 protein of PBMC in children with liver damage were significantly higher than those in children without liver damage (P < 0.05). Serum AST and ALT were positively correlated with TLR4 mRNA, NF-κB mRNA and NF-κB p65 protein expression in children with RV enteritis (P < 0.05). Conclusion The incidence of liver damage is higher in children with RV enteritis, which is related to TLR4/NF-κB p65 pathway. Overactivation of TLR4/NF-κB p65 pathway may be one of the causes of liver damage in children with RV enteritis.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective:To investigate the risk factors associated with mortality in patients with severe traumatic liver injury (TLI) and to establish and validate an early prediction model for mortality.Methods:A retrospective cohort study was conducted to analyze the clinical data of 273 patients with severe TLI admitted to the ICU from the medical information mart for the intensive care-IV (MIMIC-IV) database. The cohort consisted of 176 males and 97 females, with age ranging from 18 to 83 years [35.6 years(25.7,57.5)years]. The patients were divided into two groups based on in-hospital mortality: the survival group (253 patients, 92.7%) and the death group (20 patients, 7.3%). The two groups were compared with regards to gender, age, cause and type of injury, treatment method, massive blood transfusion, comorbidities as well as vital signs and laboratory tests measured within 24 hours of ICU admission. Univariate analysis was used to screen for risk factors associated with mortality in severe TLI patients. Independent risk factors for mortality were determined using multivariate Logistic regression analysis. Lasso regression was used to screen for predictors of mortality, and a nomogram prognostic model was then established through a multivariate Logistic regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the discrimination of the model, while the Hosmer-Lemeshow goodness-of-fit test and calibration curve were used to evaluate the calibration of the model. The model′s clinical applicability was evaluated through decision curve analysis (DCA). Internal validation was performed by the 200 Bootstrap samples, and external validation was performed by using 163 patients with severe TLI from the emergency ICU collaborative research database (eICU-CRD). Finally, the predictive efficacy of the nomogram model was compared to other trauma or severity scores.Results:Univariate analysis showed that the age, cause of injury, massive blood transfusion, chronic liver disease and laboratory tests measured within 24 hours of ICU admission, including temperature, systolic blood pressure, diastolic blood pressure, mean arterial pressure, shock index, platelets, red blood cell distribution width (RDW), mean red blood cell hemoglobin concentration (MCHC), blood glucose, blood urea nitrogen, creatinine, anion gap, bicarbonate, prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) were associated with the mortality of severe TLI patients ( P<0.05 or 0.01). Multivariate Logistic regression analysis revealed that age ( OR=1.08, 95% CI 1.03, 1.12, P<0.01), body temperature <36 ℃ ( OR=8.00, 95% CI 2.17, 29.53, P<0.01), shock index ( OR=9.59, 95% CI 1.76, 52.18, P<0.01) and anion gap ( OR=1.32, 95% CI 1.15, 1.53, P<0.01) were significantly associated with mortality in severe TLI patients. Lasso regression analysis selected 7 predictors, including age, body temperature<36 ℃, shock index, anion gap, chronic liver disease, creatinine and APTT. Based on these 7 predictors, a nomogram prediction model was developed. The AUC of the nomogram for predicting mortality was 0.96 (95% CI 0.94, 0.99), and the Hosmer-Lemeshow goodness-of-fit test indicated a good fit ( P>0.05). The calibration curve demonstrated excellent consistency between the predicted and actual probabilities, and DCA demonstrated that the model had good clinical net benefit at all risk threshold probability ranges. Internal validation confirmed the stability of the model ( AUC=0.96, 95% CI 0.92, 0.98), and external validation demonstrated good generalization ability ( AUC=0.95, 95% CI 0.91, 0.98). Moreover, the nomogram exhibited superior predictive efficacy compared with injury severity score (ISS), revised trauma score (RTS), trauma injury severity score (TRISS), sequential organ failure score (SOFA), acute physiological score III (APS III), Logistic organ dysfunction score (LODS), Oxford acute severity of illness score (OASIS) and simplified acute physiological score II (SAPS II). Conclusions:Age, body temperature <36 ℃, shock index and anion gap are independent risk factors for mortality in severe TLI patients. A nomogram prognosis model based on 7 predictors, namely age, body temperature <36 ℃, shock index, anion gap, chronic liver disease, creatinine and APTT exhibits good predictive efficacy and robustness, and is contributive to accurately assess the risk of mortality in severe TLI patients at an early stage.

The central nervous system is one of the most sensitive targets of microwave radiation. Microwave radiation can affect spatial learning and memory and neural information transmission. The effects of microwave radiation on neurotransmitters in the hippocampus and the underlying mechanisms are still unclear. This paper reviews the effects of microwave radiation on learning/memory and neurotransmitters as well as the mechanisms of action on neurotransmitters. This paper aims to provide a scientific basis for future research in this area.

AIM: To investigate the difference, correlation, and consistency of corneal thickness and the thinnest point position detected by Pentacam HR corneal topography map and RTVue optical coherence tomography(OCT)in patients with keratoconus.METHODS: Cross-sectional comparative study. The corneal curvature map, corneal thickness map, thinnest point position, and thinnest point thickness were detected by Pentacam HR and RTVue OCT. Paired sample t-test was used for data consistent with normal distribution, and paired sample rank sum test was used for data inconsistent with normal distribution. Spearman correlation analysis and Bland-Altman analysis were used for the correlation and consistency of the two measurement methods.RESULTS: A total of 63 patients(105 eyes)with keratoconus were included in this study, including 49 males(77.8%)and 14 females(22.2%), aged 22.24±6.19 years; among them, relevant data of Pentacam HR topographic map: Km was 47.85±4.73D and Kmax was 55.43±8.72D. In measuring central corneal thickness and the thinnest point thickness of keratoconus, the Pentacam HR was 4.70μm and 19.46μm thicker than the mean value measured by RTVue OCT(P<0.05). There was no significant difference between the horizontal and vertical coordinates of the thinnest points measured by the two devices(P>0.05). The central corneal thickness and the thinnest point thickness measured by the two devices were highly correlated, the horizontal coordinate of the thinnest point was moderately correlated, and the vertical coordinate of the thinnest point was weakly correlated. Bland-Altman analysis showed that the central corneal thickness, the thinnest point thickness, the horizontal coordinate of the thinnest point, and the vertical coordinate of the thinnest point were 95.2%(100/105)and 93.3%(98/105), 95.2%(100/105), 95.2%(100/105)respectively, which were within the 95% consistency limit, while the consistency ranges were -36.00～+26.62μm, -42.27～+3.36μm, -0.80～+0.84mm, and -1.95～+1.06mm, respectively.CONCLUSION: In keratoconus, the central corneal thickness and the thinnest point thickness measured by Pentacam HR were higher than those measured by RTVue OCT. It is not recommended that the central corneal thickness and the thinnest point thickness measured by the two instruments be interchangeable in clinical use because of the wide range of consistency between the two instruments' results. The position of the thinnest corneal point measured by the two instruments is similar and consistent, so it could be considered to replace the measured values of the two instruments in clinical use.