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.

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.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

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.

Objective: To investigate the clinical characteristics and the risk factors of severe human metapneumovirus (hMPV)-associated community acquired pneumonia (CAP) in children. Methods: A retrospective case summary was conducted. From December 2020 to March 2022, 721 children who were diagnosed with CAP and tested positive for hMPV nucleic acid by PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at the Yuying Children's Hospital, the Second Affiliated Hospital of Wenzhou Medical University were selected as the research objects. The clinical characteristics, epidemiological characteristics and mixed pathogens of the two groups were analyzed. According to CAP diagnostic criteria, the children were divided into the severe group and the mild group. Chi-square test or Mann-Whitney rank and contrast analysis was used for comparison between groups, while multivariate Logistic regression was applied to analyze the risk factors of the severe hMPV-associated CAP. Results: A total of 721 children who were diagnosed with hMPV-associated CAP were included in this study, with 397 males and 324 females. There were 154 cases in the severe group. The age of onset was 1.0 (0.9, 3.0) years, <3 years old 104 cases (67.5%), and the length of hospital stay was 7 (6, 9) days. In the severe group, 67 children (43.5%) were complicated with underlying diseases. In the severe group, 154 cases (100.0%) had cough, 148 cases (96.1%) had shortness of breath and pulmonary moist rales, and 132 cases (85.7%) had fever, 23 cases (14.9%) were complicated with respiratory failure. C-reactive protein (CRP) was elevated in 86 children (55.8%), including CRP≥50 mg/L in 33 children (21.4%). Co-infection was detected in 77 cases (50.0%) and 102 strains of pathogen were detected, 25 strains of rhinovirus, 17 strains of Mycoplasma pneumoniae, 15 strains of Streptococcus pneumoniae, 12 strains of Haemophilus influenzae and 10 strains of respiratory syncytial virus were detected. Six cases (3.9%) received heated and humidified high flow nasal cannula oxygen therapy, 15 cases (9.7%) were admitted to intensive care unit, and 2 cases (1.3%) received mechanical ventilation. In the severe group, 108 children were cured, 42 children were improved, 4 chlidren were discharged automatically without recovery and no death occurred. There were 567 cases in the mild group. The age of onset was 2.7 (1.0, 4.0) years, and the length of hospital stay was 4 (4, 6) days.Compared with the mild group, the proportion of children who age of disease onset <6 months, CRP≥50 mg/L, the proportions of preterm birth, congenital heart disease, malnutrition, congenital airway malformation, neuromuscular disease, mixed respiratory syncytial viruses infection were higher (20 cases (13.0%) vs. 31 cases (5.5%), 32 cases (20.8%) vs. 64 cases (11.3%), 23 cases (14.9%) vs. 44 cases (7.8%), 11 cases (7.1%) vs. 18 cases (3.2%), 9 cases (5.8%) vs. 6 cases (1.1%), 11 cases (7.1%) vs. 12 cases (2.1%), 8 cases (5.2%) vs. 4 cases (0.7%), 10 cases (6.5%) vs. 13 cases (2.3%), χ²=0.42, 9.45, 7.40, 4.94, 11.40, 8.35, 3.52, 6.92, all P<0.05). Multivariate Logistic regression analysis showed that age<6 months (OR=2.51, 95%CI 1.29-4.89), CRP≥50 mg/L (OR=2.20, 95%CI 1.36-3.57), prematurity (OR=2.19, 95%CI 1.26-3.81), malnutrition (OR=6.05, 95%CI 1.89-19.39) were the independent risk factors for severe hMPV-associated CAP. Conclusions: Severe hMPV-associated CAP is most likely to occur in infants under 3 years old and has a higher proportion of underlying diseases and co-infection. The main clinical manifestations are cough, shortness of breath and pulmonary moist rales, fever. The overall prognosis is good. Age<6 months, CRP≥50 mg/L, preterm birth, malnutrition are the independent risk factors for severe hMPV-associated CAP.
Infant ; Male ; Female ; Humans ; Child ; Infant, Newborn ; Child, Preschool ; Retrospective Studies ; Cough ; Coinfection ; Premature Birth ; Respiratory Sounds ; Metapneumovirus ; Pneumonia, Viral/epidemiology* ; Respiratory Syncytial Virus, Human ; Community-Acquired Infections/epidemiology* ; Risk Factors ; Dyspnea ; Malnutrition

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.