Objective:To explore the interrelationship between brain functional networks and features in functional magnetic resonance imaging(fMRI)of patients with Alzheimer's disease(AD),and to construct mixed-function networks(MFN),and apply them in machine learning classification models to improve the accuracy of AD classification.Methods:102 AD patients and 227 healthy subjects in the Alzheimer's Neuroimaging Initiative(ADNI)dataset were retrospectively analyzed.The partial correlation brain network of the blood oxygen level dependent(BOLD)signal was calculated and fused with low-frequency wave amplitude(ALFF),fractional low-frequency wave amplitude(fALFF)and local consistency(ReHo)features to construct MFN.Network topology parameters were extracted,and a variety of machine learning classification models were constructed based on MFN topological parameters,accuracy,precision,recall and area under the curve(AUC)were used to evaluate the predictive efficiency of the models.Results:By constructed MFN and calculated intra group to inter group ratio(IIGR),35 features could be obtained from ALFF,fALFF and ReHo feature topological parameter analysis,after rank sum test and FDR correction,there were statistical differences among 28 features(P＜0.05).The classification results show that,all the five classifiers have high classification performance on the test data set.The accuracy,precision and recall rates of random forest(RF),adaptive lifting algorithm(AdaBoost),guided aggregation algorithm(Bagging)and support vector machine(SVM)were all 99.7％,and the AUC values were up to 100％,99.5％,99.1％and 99.5％,respectively.The accuracy(98.5％),precision(98.5％),recall(98.5％),and AUC(99.1％)of the multi-layer perceptron(MLP)were slightly lower than other models,but remained excellent.It was worth noting that RF has the highest AUC value of all models at 100.0％,while Bagging has the lowest AUC value(99.1％)in the integrated approach.The results of performance comparison show that,MFN classification model can significantly improve the recognition and classification of AD disease,and greatly improve the performance of various indicators of the classifier.The results showed that,MFN classification model was superior to intelligent classification based fusion,DBN-based multitask learning,PVT-TSVM,unsupervised learning and clustering,SVM and SVM of degree 3 polynomial kernel function in key indicators such as accuracy(99.13％),AUC(99.42％),recall rate(99.46％)and specificity(99.42％)with plasma proteins,machine learning algorithms.It was further proved that MFN classification model has good generalization ability and robustness in AD disease classification.Conclusion:The AD classification model constructed based on brain mixed function network topology parameters and machine learning can improve the accuracy of AD classification.

Objective:To investigate the effect of esketamine on the analgesic efficacy,arterial blood gas indicators and inflammatory factors of patients with severe mechanical ventilation.Methods:A prospective study was conducted on 66 patients with severe mechanical ventilation who were admitted to our hospital from December 2022 to June 2024,and they were divided into control group and study group according to the envelope lottery method,with 33 cases in each group.The control group received remifentanil analgesic treatment,and the study group received esketamine analgesic treatment on the basis of the control group.Critical-care pain observation tool(CPOT)score,blood gas indicators[Partial pressure of arterial oxygen(PaO2)and partial pressure of carbon dioxide(PaCO2)],offline success rate,mechanical ventilation time,maximum remifentanil dosage to achieve analgesic goals,inflammatory factors levels[Interleukin(IL)-6,interleukin(IL)-10,white blood cell count(WBC),procalcitonin(PCT)]and the incidence of adverse reactions were compared between the two groups.Results:PaCO2 and CPOT scores decreased,while PaO2 increased after treatment of both groups(P＜0.05).The CPOT scores of the study group was lower than that of the control group after treatment(P＜0.05).The offline success rate of the study group was higher than that of the control group,the mechanical ventilation time was shorter than that of the control group,and the maximum remifentanil dosage to achieve analgesic goals was lower than that of the control group (P＜0.05).IL-6,WBC and PCT levels of the study group after treatment were lower than those of the control group,while IL-10 was higher than that of the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Esketamine in the treatment of patients with severe mechanical ventilation,can effective analgesia,increase offline success rate,shorten mechanical ventilation time,reduce inflammatory factors levels.

Objective To construct a predictive model for high-grade pathological components of early invasive lung adenocarcinoma(ILAC)based on radiomics.Methods Collecting information on total 495 patients who underwent radical operation and were pathologically diagnosed as stage Ⅰ in the cardiothoracic surgery of Zhoushan Hospital from January 2015 to December 2019,including gender,age,pathological findings,tumor markers and preoperative chest CT images.The micropapillary and solid components in postoperative pathology were defined as"high-grade pathological components",while those without high-grade pathological components were classified into the low-grade group and those with high-grade pathological components were classified into the high-grade group.And patients were randomly divided into the training set(343 cases)and the validation set(152 cases)with a ratio of 7∶3 using the simple randomization grouping method.The region of interest of nodules on CT images were delineated layer by layer by scientific research platform and 1950 radiomics features were extracted.And then those features were filtrated by F-test,Pearson correlation coefficient,and L1 based feature selection.A model was built by using Logistic regression machine learning classifier,named mod 2,and radscore was also obtained.Differences between general information and CT features were analyzed.Binary Logistic regression analysis was used to construct a model for statistically significant variables,named mod 1.At the same time,Radscore was added to build the mod and named comb mod.The area under the curve(AUC),sensitivity and specificity of the three models were calculated.A nomogram was also drawn.Results A total of 495 patients were divided into the training set(n=343)and the validation set(n=152).Gender,carcinoma embryonic antigen(CEA),nodule,and maximum diameter were screened out in clinical features and involved in constructing the mod 1.Twelve features were selected from the radiomics features to build mod 2.Comb mod performed best,training set AUC:0.887,validation set AUC:0.875,and had good clinical practicability.Conclusion The model composed of general feature,CT feature and radiomics features could accurately predict high-grade pathological components in early ILAC,and provide references for clinicians to choose surgical method for patients.

Objective To explore the effects of physical activity(PA)on carotid intima-media thickness(CIMT)thickening in patients with type 2 diabetes mellitus(T2DM)with poor HbA1c control.Methods A total of 2505 T2DM inpatients with poor HbA1c control who visited the Endocrinology Department of the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine and Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2019 to February 2022 were enrolled in this study.The patients were categorized into the mild-intensity PA(1～599 MET-min/w,n=795),moderate-intensity PA(600～1499 MET-min/w,n=1107)and high-intensity PA(≥1500 MET-min/w,n=603)based on the metabolic equivalence level(MET).Logistic regression was performed to analyze the relationship between PA and CIMT thickening.Statified analysis was used to investigate the effects of blood pressure(BP)and low-density lipoprotein cholesterol(LDL-C)target status on CIMT thickness in different PA groups.Results Restricted cubic spline plots showed a nonlinear relationship between PA levels and the risk of CIMT thickening(P<0.05).Logistic regression showed that with moderate-intensity PA as the control,while high-intensity PA was the influence factor of CIMT thickening(OR 1.581,95%CI 1.244～2.010,P<0.05).Statified analyses showed that under mild-intensity PA,using neither BP nor LDL-C on target as reference,achievement of either index and both were the influence factor of CIMT thickening.Using BP on target as reference,achievements of both indexes,achievements of neither of both indexes,and achievement of LDL-C only were the influence factor of CIMT thickening.Using LDL-C on target as reference,achievement of neither of them and achievement of BP only were the influence factor of CIMT thickening.Under high-intensity PA,achievement of both indexes was negatively associated with CIMT thickening.Conclusions Moderate-intensity PA is the recommended scheme to prevent CIMT thickening in T2DM patients whose HbA1c is not up to standard.Mild-intensity PA is not related to the risk of CIMT thickening,while high-intensity PA is positively related to the risk of CIMT thickening,and focusing on LDL-C compliance is particularly important to avoid CIMT thickening.

Objective:To observe the application value of Yifei Fumai Tang in the treatment of difficulty offline and intensive care unit-acquired weakness(ICU-AW).Methods:Used random number table method,60 patients with difficulty offline and ICU-AW who were admitted to our hospital from June 2022 to June 2024 were divided into control group(received conventional Western medicine comprehensive treatment,n=30)and study group(received Yifei Fumai Tang treatment in addition to the control group,n=30).Medical Research Council(MRC),Barthel Index(BI)scores,clinical indicators(total mechanical ventilation time,weaning success rate,secondary intubation rate,ICU stay,and mobilization time),diaphragm thickness,diaphragm mobility,and incidence of adverse reactions between two groups were compared.Results:Compared with the control group at 7 d after treatment and 14 d after treatment,the MRC and BI scores in the study group were higher(P＜0.05).Compared with the control group,the study group had lower rate of secondary intubation rate,shorter total mechanical ventilation time,ICU stay time,and mobilization time,higher weaning success rate,and greater diaphragm thickness,diaphragm mobility(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Yifei Fumai Tang combined with Western Medicine in the treatment of Difficulty Offline and ICU-AW,can effectively improve the prognosis of patients,shorten total mechanical ventilation time,ICU stay,mobilization time,increase weaning success rate,and improve respiratory function.

Objective:To explore the incidence status,influencing factors and short-term prognosis characteristics of early onset coronary heart disease in women in Wansheng District of Chongqing,and to provide scientific basis for formulating regional prevention and treatment strategies.Methods:This study was a single-center retrospective study,100 coronary heart disease in women from January 2022 to December 2023 at Chongqing Wansheng Economic and Technological Development Zone People's Hospital were prospective selected,and they were divided into early onset group of 40 cases(≤ 65 years old)and late onset group of 60 cases(＞65 years old)based on their age of onset.Another 60 healthy women who underwent physical examinations during the same period to exclude coronary heart disease were selected as the control group.Univariate factor and multiple factor logistic regression analysis were used to identify independent risk factors for early onset coronary heart disease in women.Draw receiver operating characteristic(ROC)curve for the subjects,the efficacy of risk factors in predicting early onset coronary heart disease based on the area under the curve(AUC)of ROC curve were evaluated.Patients were followed up for 1 year to observe the occurrence of major adverse cardiovascular events(MACE).Result:Among 100 fcoronary heart disease in women,the early onset group accounted for 40.00％(40/100).Univariate analysis showed that age,hyperlipidemia history,smoking history,hypertension history,family history,diabetes history,total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)were related to the early onset coronary heart disease.Multivariate analysis showed that,hyperlipidemia history(OR=4.124,95％CI:2.343-7.217),smoking history(OR=3.564),hypertension(OR=3.253),family history(OR=2.981),diabetes history(OR=2.873)were independent risk factors.ROC curve analysis results showed that joint evaluation had the best predictive value,with AUC of 0.829,which was higher than the AUC of individual evaluation for each factor.The incidence of MACE in the early onset group(45.00％)was significantly higher than that in the late onset group(P＜0.05).Conclusion:Early onset coronary heart disease in women in Wansheng District of Chongqing is related to the hyperlipidemia history,smoking,hypertension history,family history and diabetes history.The incidence of MACE in early-onset patients followed up for 1 year is higher than that in late-onset patients.

Objective:To investigate the effect of esketamine on the analgesic efficacy,arterial blood gas indicators and inflammatory factors of patients with severe mechanical ventilation.Methods:A prospective study was conducted on 66 patients with severe mechanical ventilation who were admitted to our hospital from December 2022 to June 2024,and they were divided into control group and study group according to the envelope lottery method,with 33 cases in each group.The control group received remifentanil analgesic treatment,and the study group received esketamine analgesic treatment on the basis of the control group.Critical-care pain observation tool(CPOT)score,blood gas indicators[Partial pressure of arterial oxygen(PaO2)and partial pressure of carbon dioxide(PaCO2)],offline success rate,mechanical ventilation time,maximum remifentanil dosage to achieve analgesic goals,inflammatory factors levels[Interleukin(IL)-6,interleukin(IL)-10,white blood cell count(WBC),procalcitonin(PCT)]and the incidence of adverse reactions were compared between the two groups.Results:PaCO2 and CPOT scores decreased,while PaO2 increased after treatment of both groups(P＜0.05).The CPOT scores of the study group was lower than that of the control group after treatment(P＜0.05).The offline success rate of the study group was higher than that of the control group,the mechanical ventilation time was shorter than that of the control group,and the maximum remifentanil dosage to achieve analgesic goals was lower than that of the control group (P＜0.05).IL-6,WBC and PCT levels of the study group after treatment were lower than those of the control group,while IL-10 was higher than that of the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Esketamine in the treatment of patients with severe mechanical ventilation,can effective analgesia,increase offline success rate,shorten mechanical ventilation time,reduce inflammatory factors levels.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Objective:To explore the features of levels of lung cancer biomarkers in peripheral blood of adults in Beijing and surrounding areas, and establish personalized reference intervals for these biomarkers.Methods:A cross sectional study was conducted. The lung cancer biomarker data, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), neuron specific enolase (NSE), progastrin-releasing peptide (ProGRP), and squamous cell carcinoma antigen (SCC-Ag), collected from adults who underwent cancer prevention examinations at the Cancer Hospital of the Chinese Academy of Medical Sciences from July 2021 to July 2022 were retrospectively analyzed. The interquartile range method was used to eliminate outliers, and the P95 value was calculated. Upper limit of 5 lung cancer biomarkers in different gender and age groups were obtained by referring to the reference intervals of quantitative analytes in the clinical laboratory (WS/T 402-2024). By analyzing the data of 208 adults who underwent cancer prevention physical examinations at the same center in June 2021 and 140 patients with benign lung masses confirmed by surgical resection pathology from January 2016 to June 2022, the established reference intervals for biomarkers were validated. Results:Two thousand six hundred and twenty-six cases of apparently healthy physical examiners were included for constructing reference intervals, including 1 456 males (55.4%) and 1 170 females (44.6%); the age range was 20-88 years old. The serum levels [ M ( Q1, Q3)] of CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 in 2 626 cases were 1.63 (1.07, 2.43) ng/ml, 13.08 (11.44, 14.77) ng/ml, 34.93 (29.02, 42.19) pg/ml, 0.80 (0.60, 1.00) ng/ml and 1.96 (1.48, 2.63) ng/ml, respectively. The serum levels of CEA [1.88 (1.22, 2.76) ng/ml vs. 1.41 (0.93, 2.02) ng/ml], NSE [13.31 (11.87, 15.00) ng/ml vs. 12.69 (10.96, 14.53) ng/ml], SCC-Ag [0.9 (0.7, 1.1) ng/ml vs. 0.7 (0.6, 0.9) ng/ml], and CYFRA21-1 [2.02 (1.53, 2.71) ng/ml vs. 1.87 (1.40, 2.51) ng/ml] in males were higher than those in females, and ProGRP [34.00 (28.25, 41.55) pg/ml vs. 36.12 (29.97, 42.98) pg/ml] was lower than that in females, and the differences were statistically significant (all P < 0.001). There were statistically significant differences in serum CEA levels between the groups of ≤ 40 years old (458 cases), >40-50 years old (827 cases), >50-60 years old (783 cases), >60-70 years old (412 cases), and >70 years old (146 cases) in pairwise comparison (all P < 0.05). Except for the age groups of ≤ 40 years old and >40-50 years old and the age groups of >60-70 years old and >70 years old, there were statistically significant differences in serum NSE levels among the other age groups in pairwise comparison (all P < 0.05). There were statistically significant differences in serum ProGRP levels between the 5 age groups (all P < 0.05). There were statistically significant differences when comparing the serum SCC-Ag level in the >40-50 age group, >50-60 age group and >60-70 age group with that in the ≤40 age group and >70 age group, respectively (all P < 0.05). However, there was no statistically significant difference between the other age groups in pairwise comparison (all P > 0.05). There were statistically significant differences in serum CYFRA21-1 levels between the 5 age groups (all P < 0.05). When gender and age were not distinguished, the P95 values of serum CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 levels were 4.44 ng/ml, 16.61 ng/ml, 57.65 pg/ml, 1.50 ng/ml, and 4.21 ng/ml, respectively. Considering gender and age, except for the >70 age group with no statistically significant difference in the P95 value of serum CEA level between males and females ( P > 0.05), the P95 value of serum CEA level in males was higher than that in females in all other age groups (all P < 0.001); the P95 values of serum CEA level in both males and females increased with age, but showed a decreasing trend in males over the age of 70. The P95 value of serum NSE level in males was higher than that in females in the age groups of ≤ 40 years and >40-50 years (both P < 0.05), while there was no statistically significant difference in the P95 value of serum NSE level between males and females in other age groups (all P > 0.05). The P95 values of serum NSE level in both males and females decreased firstly and increased later with age, reaching their highest levels at the age of >70. The P95 values of serum ProGRP level in females aged ≤ 40 and >50-60 were higher than those in males (both P < 0.05), while there was no statistically significant difference in the P95 value of serum ProGRP level between genders in other age groups (all P > 0.05); the P95 values of serum ProGRP level in both males and females increased with age. There was no statistically significant difference in the P95 value of serum SCC-Ag level between males and females in the ≤ 40 age group ( P > 0.05), while the P95 value of serum SCC-Ag level in males was higher than that in females in all other age groups (all P < 0.05). The P95 values of serum SCC-Ag level in males increased with age, while they were stable in females. There was no statistically significant difference in the P95 value of serum CYFRA21-1 level between males and females in the >60-70 age group ( P > 0.05), while the P95 value of serum CYFRA21-1 level in males was higher than those in females in all other age groups (all P < 0.05); the P95 values of serum CYFRA21-1 level in both males and females increased with age. Based on data from 2 626 apparently healthy physical examiners, reference intervals for the levels of 5 lung cancer biomarkers were constructed in different age groups of different genders. Validation was conducted on 208 physical examiners and 140 patients with benign lung lesions, and it was found that the compliance rate of using newly created reference intervals for different gender and age groups to interpret detection results was >90%, and the validation was passed. Conclusions:There are gender and age differences in the reference intervals of CEA, CYFRA21-1, NSE, ProGRP, and SCC-Ag in peripheral blood of adults in Beijing and surrounding areas. The constructed reference intervals of gender and age for biomarkers have been validated and shown good results, providing reference for optimizing the clinical application of lung cancer-related biomarkers.