Objective To explore the correlation between the expression of serum microRNA(miR)-1298-5p,miR-625-5p,and miR-155 with the degree of Helicobacter pylori(Hp)infection in elderly gastric cancer patients.Methods From January 2021 to November 2023,120 elderly patients with gastric cancer admitted to the hospital from January 2021 to November 2023 were selected as the gastric cancer group,and 130 non-gas-tric cancer patients who underwent gastroscopy were selected as the control group.The expression levels of miR-1298-5p,miR-625-5p and miR-155 in serum were detected by fluorescence quantitative PCR(qPCR).Car-bon 13 urea breath test was used to detect the positive rate of Hp infection in two groups,and the degree of Hp infection in elderly patients with gastric cancer were evaluated.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum miR-1298-5p,miR-625-5p,and miR-155 expression levels for Hp infection in elderly gastric cancer patients.Pearson method was applied to analyze the correlation between serum miR-1298-5p,miR-625-5p,miR-155 expression and positive rate of Hp infection in elderly gas-tric cancer patients.Results Compared with the control group,the expression levels of miR-1298-5p and miR-625-5p in serum of gastric cancer group decreased(P＜0.05),while the positive rate of Hp infection and the expression level of serum miR-155 increased(P＜0.05).The expression levels of serum miR-1298-5p and miR-625-5p in elderly gastric cancer patients with Hp grade Ⅰ,Ⅱ,and Ⅲ infection were lower than those without Hp infection,while the expression level of miR-155 was higher(P＜0.05).Patients with poor differ-entiation,lymph node metastasis,and TNM stage Ⅲ-Ⅳ had lower expressions of serum miR-1298-5p and miR-625-5p(P＜0.05),and higher expression of miR-155(P＜0.05)than those with moderate-high differen-tiation,no lymph node metastasis,and TNM stage Ⅰ-Ⅱ.The expression levels of serum miR-1298-5p and miR-625-5p were negatively correlated with the positive rate of Hp infection in elderly patients with gastric cancer(r=-0.443,-0.386,both P＜0.001),and the expression levels of serum miR-155 were positively correlated with the positive rate of Hp infection(r=0.525,P＜0.001).The area under the curve(AUC)of serum miR-1298-5p,miR-625-5p and miR-155 combined diagnosis of Hp infection in elderly gastric cancer pa-tients was higher than that of single diagnosis(P＜0.05).Conclusion The expression levels of miR-1298-5p and miR-625-5p in serum of elderly gastric cancer patients with Hp infection decrease,while the expression level of miR-155 increases.These three factors are related to the degree of Hp infection and have good diag-nostic value for the occurrence of Hp infection.

Objective: To explore the regulatory effects of ginkgo biloba extract on airway inflammatory injury and Toll⁃like receptor 4(TLR4)/nucleotide⁃binding oligomerization domain⁃containing 3(NLRP3) pathway in rats with vided into four groups : the normal control group , Methods: Thirty⁃six male SD rats were selected and randomly divided into four groups : the normal control group , the model group , the prednisone treatment group , and the ginkgo biloba extract treatment group , with 9 rats in each group. Except for the normal control group , the COPD rat mod⁃els in the other groups was constructed by intratracheal instillation of lipopolysaccharide (LPS) combined with ciga⁃rette smoke exposure. After successful modeling , the rats were continuously administered drugs for 12 weeks , fol⁃lowed by sampling. The general conditions and respiratory symptoms of the rats were observed. The pathological changes of lung tissues were observed by hematoxylin⁃eosin (HE) staining technique ; the mRNA and protein ex⁃pression levels of TLR4 , tumor necrosis factor⁃α (TNF⁃α ) , interleukin⁃1β (IL⁃1β) and NLRP3 in rat lung tissueswere detected by real⁃time quantitative polymerase chain reaction (RT⁃qPCR) and Western blot. Results: Com⁃pared with the normal control group , the lung tissues of rats in the model group were significantly damaged , and the protein and mRNA expression of TLR4 , TNF⁃α , IL⁃1β , and NLRP3 increased ( P < 0. 05 ) . Compared with the model group , lung tissue damage was reduced in the prednisone group and the ginkgo biloba extract group , and TLR4 , TNF⁃α , IL⁃1β , NLRP3 protein and mRNA expression decreased (P < 0. 05) . Conclusion Ginkgo biloba airway inflammatory response by inhibiting the TLR4/NLRP3 signaling pathway.

Objective To investigate and analyze the various reasons that affect the accuracy of ICD-9-CM-3 classifica-tion coding,identify key factors,and propose improvement strategies to enhance the accuracy and standardization level of surgical operation coding.Methods Using case analysis method,various factors affecting the accurate coding of ICD-9-CM-3 were sys-tematically listed and analyzed in detail.Through specific examples,this article analyzes the non-standard behavior of clinical physicians in writing surgical operation names,as well as the problems of coders relying on doctors to write,ignoring coding rules,and not fully reading medical records and surgical records during the coding process.It further explores how these factors lead to surgical classification errors.Results The main reasons affecting the accuracy of ICD-9-CM-3 coding include:lack of standardization in writing surgical operation names by clinical physicians,and failure to provide detailed descriptions of key ele-ments of the surgery;The coder overly relied on the doctor's written content during the coding process,failed to strictly follow the coding rules,and did not fully and deeply read and analyze medical records and surgical records,resulting in errors and devia-tions in surgical classification.Conclusion Each component of the surgical procedure name is an important factor affecting the accuracy of coding.Ensuring the completeness and accuracy of surgical operation names is crucial for improving the precision of ICD-9-CM-3 coding.In order to improve the quality of coding,clinical physicians need to enhance writing standards,while cod-ers need to strengthen their professional knowledge learning,strictly abide by coding rules,and comprehensively and meticulously review medical records and surgical records to achieve precise classification and coding of surgical operations.

Objective To investigate and analyze the various reasons that affect the accuracy of ICD-9-CM-3 classifica-tion coding,identify key factors,and propose improvement strategies to enhance the accuracy and standardization level of surgical operation coding.Methods Using case analysis method,various factors affecting the accurate coding of ICD-9-CM-3 were sys-tematically listed and analyzed in detail.Through specific examples,this article analyzes the non-standard behavior of clinical physicians in writing surgical operation names,as well as the problems of coders relying on doctors to write,ignoring coding rules,and not fully reading medical records and surgical records during the coding process.It further explores how these factors lead to surgical classification errors.Results The main reasons affecting the accuracy of ICD-9-CM-3 coding include:lack of standardization in writing surgical operation names by clinical physicians,and failure to provide detailed descriptions of key ele-ments of the surgery;The coder overly relied on the doctor's written content during the coding process,failed to strictly follow the coding rules,and did not fully and deeply read and analyze medical records and surgical records,resulting in errors and devia-tions in surgical classification.Conclusion Each component of the surgical procedure name is an important factor affecting the accuracy of coding.Ensuring the completeness and accuracy of surgical operation names is crucial for improving the precision of ICD-9-CM-3 coding.In order to improve the quality of coding,clinical physicians need to enhance writing standards,while cod-ers need to strengthen their professional knowledge learning,strictly abide by coding rules,and comprehensively and meticulously review medical records and surgical records to achieve precise classification and coding of surgical operations.

Objective:To explore significance of eosinophil and eosinophil/lymphocyte ratio(ELR)in predicting allergic asth-ma in children in different seasons.Methods:Retrospective analysis of children with asthma who visited pediatric respiratory depart-ment outpatient clinic and ward of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2021 to December 2021,whose allergen specific IgE(sIgE)and peripheral blood cell analysis were complete.sIgE≥0.35 kUA/L were included in allergic asthma group,sIgE<0.35 kUA/L and total allergen IgE<60 kUA/L were included in non-allergic asthma group.General data and changes in peripheral blood cells of two groups were analyzed.Results:There were 1 378 qualified subjeats,including 999(72.5%)in allergic asthma group and 379(27.5%)in non-allergic asthma group.Number of visits in allergic asthma group varied seasonally,with the most in autumn.Peripheral blood lymphocyte count(LYMPH),eosinophil count(EOS)and ELR were all higher in children with allergic asthma than in children with non-allergic asthma(P<0.05),and platelet/lymphocyte ratio(PLR)was lower than that in children with non-allergic asthma(P<0.05).Peripheral blood LYMPH,PLT,EOS and ELR of children with allergic asthma differed between four seasons,which were higher than those of non-allergic asthma in each season in EOS and ELR,LYMPH was significantly higher than that of children with non-allergic asthma in autumn,and PLT was significantly lower than that of children with non-allergic asthma in spring(P<0.05).EOS predicted AUC of spring,summer,autumn and winter were 0.79,0.77,0.71 and 0.64 in children with allergic asthma,and ELR predicted AUC were 0.72,0.48,0.73 and 0.68 in children with allergic asthma.Conclusion:Allergic asthma in children is seasonally variable and peaks in autumn.EOS and ELR in peripheral blood cells in children with allergic asthma are higher than in children with non-allergic asthma in each season of year,LYMPH is significantly higher than children with non-allergic asthma in the fall,and PLT is lower than in children with non-allergic asthma in spring,suggesting that allergic asthma type Ⅱinflammation persists,and EOS and ELR have predictive value for children's allergic asthma.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective: To investigate the influencing factors of depressive symptoms among rural elderly patients with chronic diseases in China, so as to provide insights into depression prevention and control among the rural elderly patients with chronic diseases. Methods: The basic demographics, health status, and lifestyle of rural residents at ages of 65 years and older who had at least one chronic disease were retrieved from The Chinese Longitudinal Healthy Longevity Survey (CLHLS) database in 2018, and participants' depressive symptoms were assessed with The Center for Epidemiological Studies Depression-10 (CES-D-10) scale. Factors affecting the depressive symptoms were identified with a multivariable logistic regression model. Results: Totally 5 146 rural elderly patients with chronic diseases were enrolled, including 2 373 men (46.11%) and 2 773 women (53.89%). The prevalence of depressive symptoms was 27.13%. Multivariable logistic regression analysis identified having two and more children (OR=0.614, 95%CI: 0.387-0.975), living alone (OR=1.450, 95%CI: 1.192-1.764), life satisfaction (general, OR=1.933, 95%CI: 1.651-2.264; low, OR=5.366, 95%CI: 3.488-8.254), self-assessed health status (general, OR=2.697, 95%CI: 2.284-3.185; poor, OR=5.338, 95%CI: 4.262-6.685), disability in instrumental activities of daily living (OR=1.592, 95%CI: 1.328-1.908), sleep duration (normal, OR=0.502, 95%CI: 0.429-0.586; too long, OR=0.494, 95%CI: 0.405-0.603), exercise (OR=0.721, 95%CI: 0.607-0.856), watching TV (OR=0.787, 95%CI: 0.664-0.933), and gardening activities (OR=0.781, 95%CI: 0.626-0.975) as factors affecting depressive symptoms among rural elderly patients with chronic diseases. Conclusions The prevalence of depressive symptoms was 27.13% among rural elderly patients with chronic diseases. Number of children, living style, life satisfaction, health status, sleep duration, exercise, watching TV, and gardening activities are associated with the development of depressive symptoms among rural elderly patients with chronic diseases.

Objective:To compare and analyze the effects of impulse oscillometry (IOS) and pulmonary function test (PFT) in the assessment of asthma control in children.Methods:A cross-sectional study of 323 children with bronchial asthma who visited the outpatient pediatric clinic of Shandong Provincial Hospital Affiliated to Shandong First Medical University from March to December 2020 was conducted.The patients were divided into the control group (123 cases) and the uncontrolled group (200 cases) according to the Childhood Asthma Control Test (C-ACT) score.In both groups, PFT and IOS were performed.The PFT test included the forced expiratory volume in one second (FEV 1), force expiratory volume in one second/forced vital capacity (FEV 1/FVC), peak expiratory flow (PEF), the instantaneous forced expiratory flow at 50% of forced vital capacity (FEF 50), the instantaneous forced expiratory flow at 75% of forced vital capacity (FEF 75), and maximum mid expiratory flow (MMEF). In the IOS test, the total respiratory impedance at 5 Hz (Z5), respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), reactance at 5 Hz (X5), respiratory resistance at 5 Hz-respiratory resistance at 20 Hz (R5-R20), reactance area (AX), and resonance frequency (Fres) were measured.The data obtained were analyzed statistically using SPSS 25.0 software. ANOVA or Mann- Whitney U rank-sum test was used to compare data between groups.Receiver′s operating characteristic (ROC) curves were drawn to determine the predictive value of PFT and IOS parameters for uncontrolled asthma. Results:(1) According to the comparison results of PFT indexes between the two groups of children with asthma, the levels of FEV 1, FEV 1/FVC, PEF, FEF 50, FEF 75, MMEF in the control group were all higher than those in the uncontrolled group [(104.41±12.38)% vs.(98.89±16.61)%, 100.50 (94.40, 103.50)% vs.96.00 (89.83, 101.88)%, (100.29±15.31)% vs.(93.19±18.43)%, 85.60(70.60, 96.60)% vs.72.35 (57.08, 91.10)%, 67.20 (53.60, 81.70)% vs.56.80 (41.10, 74.73)%, 80.70 (66.80, 95.10)% vs.69.50 (54.03, 90.05)%] (all P<0.01). (2) According to the comparison results of IOS indices between the two groups, the levels of Z5, R5, R20, R5-R20, X5, AX and Fres in the control group were lower than those in the uncontrolled group {68.58 (63.29, 77.43)% vs.81.27(70.93, 91.96)%, 68.91(62.94, 77.60)% vs.80.61 (70.02, 89.29)%, 75.78 (67.50, 87.55)% vs.82.97 (71.50, 95.50)%, 0.51 (0.43, 0.59) [kPa/(L·S)] vs.0.62 (0.53, 0.74) [kPa/(L·S)], 69.31 (59.93, 79.14)% vs.86.48 (70.00, 102.48)%, 1.11 (0.76, 1.60) kPa/L vs.2.14 (1.42, 2.85) kPa/L, 18.21 (16.06, 19.56) Hz vs.20.56 (18.92, 22.81) Hz} (all P<0.01). (3) In the control group, 31 children (25.20%) had pulmonary dysfunction.(4) In the uncontrolled group, 95 children (47.50%) had pulmonary ventilation dysfunction.Only 20 children (10.00%) had a R5 larger than 120% of the predicted value and/or a R20 larger than 120% of the predicted value.(5) According to the ROC analysis results of the IOS indices for predicting asthma exacerbations, all of the areas under the ROC (AUC) of Z5, R5, R5-R20, X5, AX and Fres were greater than 0.7.AX had the highest value in predicting asthma exacerbations (AUC=0.785, 95% CI: 0.735-0.835), with sensitivity of 78.50% and specificity of 64.20%.All of the AUCs of PFT indices were smaller than 0.7.FEF 50 and MMEF had the largest AUC. Conclusions:PFT and IOS have good sensitivity in evaluating the level of asthma control in children, and IOS has good value in predicting asthma exacerbations.AX has the highest predictive value for asthma exacerbations.Asthma control levels of children should be evaluated using not only subjective (such as C-ACT score) but also objective (e.g.PFT, IOS) indices.

Objective:To evaluate artificial intelligence constructed by deep convolutional neural network (DCNN) for the site identification in upper gastrointestinal endoscopy.Methods:A total of 21 310 images of esophagogastroduodenoscopy from the Cancer Hospital of Chinese Academy of Medical Sciences from January 2019 to June 2021 were collected. A total of 19 191 images of them were used to construct site identification model, and the remaining 2 119 images were used for verification. The performance differences of two models constructed by DCCN in the identification of 30 sites of the upper digestive tract were compared. One model was the traditional ResNetV2 model constructed by Inception-ResNetV2 (ResNetV2), the other was a hybrid neural network RESENet model constructed by Inception-ResNetV2 and Squeeze-Excitation Networks (RESENet). The main indices were the accuracy, the sensitivity, the specificity, positive predictive value (PPV) and negative predictive value (NPV).Results:The accuracy, the sensitivity, the specificity, PPV and NPV of ResNetV2 model in the identification of 30 sites of the upper digestive tract were 94.62%-99.10%, 30.61%-100.00%, 96.07%-99.56%, 42.26%-86.44% and 97.13%-99.75%, respectively. The corresponding values of RESENet model were 98.08%-99.95%, 92.86%-100.00%, 98.51%-100.00%, 74.51%-100.00% and 98.85%-100.00%, respectively. The mean accuracy, mean sensitivity, mean specificity, mean PPV and mean NPV of ResNetV2 model were 97.60%, 75.58%, 98.75%, 63.44% and 98.76%, respectively. The corresponding values of RESENet model were 99.34% ( P<0.001), 99.57% ( P<0.001), 99.66% ( P<0.001), 90.20% ( P<0.001) and 99.66% ( P<0.001). Conclusion:Compared with the traditional ResNetV2 model, the artificial intelligence-assisted site identification model constructed by RESENNet, a hybrid neural network, shows significantly improved performance. This model can be used to monitor the integrity of the esophagogastroduodenoscopic procedures and is expected to become an important assistant for standardizing and improving quality of the procedures, as well as an significant tool for quality control of esophagogastroduodenoscopy.

Objective:To construct standard strains representing the main epidemic clades of HIV-1 in China, amplify the virus strains, and establish a seed lot.Methods:Six isolates of HIV-1 virus were identified and analyzed in genotype and phenotype, according to " interpretation for the social organization of the Standard strains of pathogenic microorganism- technical specifications for establishment of HIV strains". The isolates were amplified and cultivated to generate the secondary generation primary seed lot and the third generation working seed lot as frozen storage in liquid nitrogen. Results:Six HIV-1 standard strains were obtained, of which 3 strains are CRF_ 07BC (NRPC2.4.9003, NRPC2.4.9005, NRPC2.4.9006), 1 strain is CRF_ 01AE (NRPC2.4.9001), 1 strain is CRF_ 08BC (NRPC2.4.9002), and 1 strain is URF (NRPC2.4.9004). Phenotypic detection showed that all six strains are CCR5 tropics and Non syncytia inducing virus. TCID 50 were all greater than 1 × 10 5/ml, and concentrations of p24 antigen were all higher than 2 ng/ml. A primary seed lot with no less than 20 vials per strain and a working seed lot with no less than 50 vials per strain were constructed. The standard virus strains were used in evaluating antiviral drugs PEG2kC34, PEG5kC34, LP-19, and neutralizing antibody LSEVh LS-F. Conclusions:Six standard strains of HIV-1 virus covering the three main epidemic subtypes of HIV-1 in China have been obtained, and a storage of HIV-1 standard strain was constructed. It meets the need of the preservation of HIV-1 standard strains in China and provides support for drug and vaccine evaluation.