Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

This article aims to analyze LI Fei's academic thinking and experience in treating facial paralysis.LI Fei proposes that the diagnosis and treatment of facial paralysis should follow the principle of"identify the cause of the disease when it is occured at first time,followed by exploring the pathogenesis of the disease,then differentiating the syndrome and treating the disease,and recognizing the syndrome and treating the disease",and that the basic treatment principle should be"dispelling wind and unblocking the collaterals,regulating the tendons and meridians".In clinical treatment,"put emphasis on anatomy,treat the disease according to symptoms"is the basic policy;meanwhile,integrating Chinese and western theories,combining the anatomical structure of the expression muscle,dynamically judging the recovery of nerves and muscles,and selecting the corresponding empirical acupoints according to the symptoms.LI Fei emphasizes the integration of theories and summarizes the"triple"methods of differentiation by reasoning,staging and symptoms,and the"triple"theory of treatment by regulating menstruation,tendon and spirit,which is worthy of reference in the clinic.

Objective To investigate the distribution characteristics of pathogens in adult community-acquired pneumonia(CAP)patients who visited the fever clinic before and after the outbreak of the novel coronavirus infection,and to provide theoretical basis for the diagnosis,treatment,and prevention of CAP.Methods CAP patients who visited the fever clinic of Peking University Third Hospital from June 2017 to July 2022 were included in the study and divided into pre-outbreak and post-outbreak groups based on the time point(January 24,2020,when Beijing entered the first-level COVID-19 prevention and control).Respiratory samples were collected and pathogen nucleic acid detection was performed using real-time fluorescence quantitative polymerase chain reaction.The detection and distribution of pathogens were analyzed.Results A total of 415 CAP patients were included,divided into pre-outbreak group(312 cases)and post-outbreak group(103 cases).Mycoplasma pneumoniae,Streptococcus pneumoniae,and Influenza A virus were the three most common pathogens in the pre-outbreak CAP group.In the post-outbreak community-acquired pneumonia,Influenza B virus,Klebsiella pneumoniae and Streptococcus pneumoniae were the three most common pathogens.The incidence of Influenza A virus,Parainflluenza virus,and Mycoplasma pneumoniae was significantly higher in the pre-outbreak period than in the post-outbreak period,and the differences between the two groups were statistically significant(all P＜0.05).Conclusion Before and after the epidemic,viral infection are the main pathogens of CAP patients,which is of great significance for future empirical treatment,protection of susceptible population and control of infectious diseases.

Objective: To understand the relationship between residential neighborhood green space and mental health of middle school students, so as to provide a theoretical basis for mental health promotion among of middle school students at the level of residential environment. Methods: From October to December 2023, 1 258 students from three junior high schools and two general high schools in Panlong, Wuhua, Chenggong, and Guandu districts of Kunming City were selected by stratified cluster random sampling method. Conducting onsite questionnaire survey using the Mental Health Inventroy of Middle School students, residential neighborhood green space were evaluated using normalized difference vegetation index (NDVI). Analysis of variance, Pearson correlation analysis and linear regression analysis were used to analyze the relationship between as green space in residential neighborhoods and the mental health of middle school students. Results: The average mental health score of middle school students in Kunming was (2.02± 0.69 ), of which 447 (37.92%) had mild mental health problems, 107 (8.51%) had moderate mental health problems, and 12 ( 0.95% ) had more severe mental health problems. Mental health scores of middle school students varied significantly by gender, grade, and family income ( t/F =6.99, 7.15, 3.70, P <0.05). Correlation analysis showed that NDVI_250 m, NDVI_500 m, and NDVI_1 000 m were all negatively correlated with the total mental health scores of middle school students ( r =-0.07,-0.09, -0.10 , P <0.05). Multiple linear regression analysis showed that gender, grade, NDVI_250 m, NDVI_500 m, and NDVI_1 000 m were infuencing factors on the mental health of middle school students( B =0.25，0.05，-0.47，-0.67，-0.78, P <0.05). Conclusions Mental health of middle school students in Kunming is related to green space in different buffer zones around residences. The mental health education of middle school students should be strengthened, especially for girls and senior students, optimizing resources to reduce pressure, and improving the quality of green space in residential communities to improve the mental health of adolescents.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

OBJECTIVE To investigate the predictive value of prognostic nutritional index(PNI) and lymphocyte-monocyte ratio(LMR) in severe radiotherapy-induced oral mucositis(RIOM) during treatment of patients with head and neck cancer,and to construct a risk prediction model and test the prediction effect. METHODS A total of 502 patients with head and neck cancer who underwent radiotherapy were recruited from September 2021 to October 2023 in Xiangya Hospital Central South University. The participants were randomly divided into training group and validation group at a ratio of 7:3. According to whether severe RIOM occurred,they were divided into severe RIOM group and non-severe RIOM group. Univariate analysis and logistic regression analysis were used to screen the risk factors of severe RIOM. The receiver operating characteristic(ROC) curve was used to evaluate its prediction effect and R4.3.2 software was used to draw nomograms and decision curve. RESULTS The risk prediction model for patients with head and neck cancer during treatment had five factors,including the number of comorbidities(OR=2.221,95％CI=1.185-4.165),surgical history(OR=2.938,95％CI=1.393-6.198),the degree of tumor differentiation(OR=1.511,95％CI=1.090-2.094),PNI(OR=0.892,95％CI=0.852-0.934),LMR(OR=0.512,95％CI=0.254-1.030). Model formula:Y=2.102+0.413×degree of differentiation+0.798×number of comorbidities+1.078×surgical history-0.114×PNI-0.669×LMR. The validation results of the prediction model showed that the area under the ROC curve of the training group was 0.847(P<0.001),the area under the curve of the validation group was 0.808(P<0.001),and the P values of the Hosmer-Lemeshow test of the modeling group and the validation group were both greater than 0.05. The decision curve was above the reference line within most of the high-risk thresholds. CONCLUSION The risk prediction model constructed in this study has good effect,which can predict the risk of severe RIOM during radiotherapy in patients with head and neck cancer,providing the reference for taking preventive intervention measures for high-risk patients.

Heterotypic cell-in-cell structures(heCICs)mediate unique non-autonomous cell death,which are widely involved in a variety of important pathological processes,such as tumorigenesis,pro-gression and clinical prognosis.Methylenetetrahydrofolata dehydrogenase 2(MTHFD2),one of the key enzymes of one-carbon metabolism,is highly expressed in a variety of tumor cells.In this study,in order to investigate the effect of MTHFD2 on the formation of heCICs,liver cancer cells and immune cells were first labeled separately by live cell dyes,and the heCIC model was established by using fluorescence mi-croscopy for cell imaging and analysis.After transiently knocking down MTHFD2 in cells by RNAi,we found that the ability of PLC/PRF/5 and Hep3B to form heCICs with immune cells was significantly in-creased(all P＜0.01).MTHFD2 recombinant expression plasmid was constructed by the homologous re-combination method,and MTHFD2 overexpression cell lines were further constructed.Then,the effect of MTHFD2 overexpression on the ability to form heCICs was detected by co-culturing the overexpression cell lines with immune cells.The results showed that the rate of heCIC formation was significantly re-duced after overexpression of MTHFD2(all P＜0.001).In conclusion,this study demonstrated that MTHFD2 is a negative regulator of heCIC formation,providing a research basis for targeting MTHFD2 to promote heCIC formation and enhance the in-cell killing of immune cells.

Objective:To analyze the clinical features and laboratory indicators in patients with solid malignant tumor-associated venous thromboembolism(Ta-VTE),and to study the risk factors for Ta-VTE.Methods:The hospitalized patients with VTE in Guizhou Provincial People's Hospital from January to December 2020 were enrolled,and they were divided into Ta-VTE group and pure VTE group based on the presence or absence of solid malignant tumor.The differences in clinical data and laboratory indicators between the two groups were analyzed,and the indicators with significant differences were included in logistic regression model to analyze the risk factors of Ta-VTE.Results:A total of 288 patients with VTE were included in this study,including 64 cases in Ta-VTE group and 224 cases in pure VTE group,respectively.There were significant differences in the following indexes between the two groups,including the hospitalization time(14.20±15.29 d vs 10.05±6.90 d,t=3.112,P=0.002),pain(35.94％vs 65.18％,x2=17.554,P=0.000),recent surgery(75.00％vs 37.50％,X2=28.196,P=0.000),D-dimer[2.8(0.92,7.55)μg/ml vs 5.69(2.25,13.91)μg/ml,Z=-2.710,P=0.007],PLR[198.59(139.54,312.16)vs 149.76(114.08,233.66),Z=-2.924,P=0.003]and TBIL[10.90(7.63,15.68)μmol/Lvs 12.90(9.33,18.28)μmol/L,Z=-2.066,P=0.039].There was no significant difference in the other indicators(P＞0.05).The result of multivariate logistic regression analysis showed that elevated PLR(OR=1.003,95％CI:1.000-1.006,P=0.027),recent surgery(OR=4.312,95％CI:2.093-8.885,P=0.000)and prolonged hospitalization(OR=1.037,95％CI:1.002-1.074,P=0.038)were independent risk factors for Ta-VTE.However,pain(OR=0.274,95％CI:0.133-0.564,P=0.000)was a protective factor.Conclusion:Elevated PLR level,recent surgery and prolonged hospital stay are independent risk factors for Ta-VTE patients,and rational use of these indicators is helpful for the clinical diagnosis and treatment of Ta-VTE patients.

Objective To observe the value of CT radiomics for differentiating spinal bone islands(BI)and osteoblastic metastases(OBM).Methods Data of 109 BI lesions in 98 patients and 282 OBM lesions in 158 patients(including 103 OBM in 48 lung cancer cases,86 OBM in 52 breast cancer cases and 93 OBM in 58 prostate cancer cases)from 3 medical institutions were retrospectively analyzed.Data obtained from institution 1 were used as the internal dataset and divided into internal training set and internal validation set at a ratio of 7∶3,from institution 2 and 3 were used as external dataset.All datasets were divided into female data subset(including OBM of female lung cancer and breast cancer)and male data subset(including OBM of male lung cancer and prostate cancer).Radiomics features were extracted and screened to construct 3 different support vector machine(SVM)models,including model1 for distinguishing BI and OBM,model2 for differentiating OBM of female lung cancer and breast cancer,and model3 for differentiating OBM of male lung cancer and prostate cancer.Diagnostic efficacy of model1,CT value alone and 3 physicians(A,B,C)for distinguishing BI and OBM were assessed,as well as differentiating efficacy for different OBM of model2 and model3.Receiver operating characteristic(ROC)curves were drawn,and area under the curves(AUC)were calculated and compared.The differential diagnostic efficacy of model2 and model3 were also assessed with ROC analysis and AUC.Results AUC of model1 for distinguishing spinal OBM from BI in internal training set,internal validation set and external dataset was 0.99,0.98 and 0.86,respectively.In internal training set,model1 had higher AUC for distinguishing BI and OBM than that of physician A(AUC=0.78),B(AUC=0.87)and C(AUC=0.93)as well as that of mean CT value(AUC=0.78,all P＜0.05).AUC in internal training set,internal validation set and external dataset of model2 for identifying female lung cancer and breast cancer OBM was 0.79,0.75 and 0.73,respectively,of model3 for discriminating male lung cancer from prostate cancer OBM was 0.77,0.74 and 0.77,respectively.Conclusion CT radiomics SVM model might reliablely distinguish OBM and BI.

Objective To investigate the prevalence and severity of symptoms and to construct symptom networks in head and neck cancer patients during treatment to identify core symptoms and symptom clusters.Methods 366 patients who were hospitalized in 3 tertiary hospitals in Changsha were selected using convenience sampling from March to October 2022 and asked to complete the M.D.Anderson Symptom Inventory-Head & Neck.Exploratory factors analysis was used to extract the symptom clusters,and R packages were used to construct the symptom severity network and symptom clusters network.The centrality indexes of the networks,including strength,closeness,and betweenness,were analyzed to identify core symptoms and core symptom cluster.Results The most common symptoms in head and neck cancer patients during treatment were dry mouth(93.44％),fatigue(89.07％),loss of appetite(86.34％),and difficulty swallowing or chewing(85.79％),and the most severe symptoms were dry mouth,loss of appetite,oral or pharyngeal mucus,and difficulty swallowing or chewing.4 symptom clusters were extracted,namely oral-pharyngeal,gastrointestinal,emotional-sleep,and sickness-sensing behavioral,which could explain 67.415％of the total variance.In the symptom severity network,oral or pharyngeal mucus(rs=9.60)was a symptom with the highest strength.In the symptom clusters network,oral or pharyngeal mucus(rs=1.20),nausea(rs=1.00),fatigue(rs=1.10),and drowsiness(rs=0.97)were the symptoms with the highest strength across 4 symptom clusters.Conclusion Oral or pharyngeal mucus,nausea,fatigue,and drowsiness are the core symptoms of symptom clusters in head and neck cancer patients during treatment.Oral-pharyngeal symptom cluster is the core symptom cluster.It is recommended that clinical staff should develop interventions based on the core symptoms and symptom cluster to implement precise symptom management and improve symptom management efficiency.