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.

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.

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 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.

Superchilling is an emerging technology for meat preservation; however, the temperature changes during the process have been commonly ignored. Thus, the effects of temperature fluctuations on meat quality during superchilling are yet to be evaluated. In our study, pork loins and salmon fillets were stored for several days (0, 8, 15, 23, and 30 d) under different temperature fluctuations based on -3.5 ℃ as the target temperature. The results showed that after 15 d of superchilling storage, the values of total volatile basic nitrogen, total viable count, and lipid oxidation were significantly (P<0.05) altered in the ±2.0 ℃ fluctuation group compared with the constant temperature group. On the contrary, there was no significant difference in these parameters between the ±1.0 ℃ fluctuation group and the constant temperature group after 30 d of storage. In addition, irregular temperature changes significantly accelerated the modulation of various indicators. In brief, temperature fluctuations and irregular temperature changes accelerated the destruction of muscle structural integrity, increased the water loss, gradually widened the water loss channels, and thereby reduced the edibility by accelerating the spoilage of meat.
Animals ; Lipid Metabolism ; Pork Meat ; Red Meat ; Salmon ; Swine ; Temperature

Objective:To investigate the effects of oxycodone multimodal analgesia on quality of awakening and hemodynamics in patients undergoing laparoscopic gynaecological surgery.Methods:Ninety patients who underwent laparoscopic ovarian cyst removal in Weihai Central Hospital from September 2018 to March 2019 were included in this study. They were randomly divided into observation and control groups, with 45 patients in each group. Both groups were given intravenous flurbiprofen axetil (1 mg/kg) for preemptive analgesia. Combined intravenous and inhalation anesthesia was used. The depth of anesthesia was monitored. The observation group was intravenously given 0.10 mg/kg oxycodone and the control group was intravenously given 5 μg sufentanil. Quality of awakening, hemodynamic indexes, postoperative pain score, and incidences of nausea and vomiting were compared between the two groups.Results:Cough score in the observation group was significantly lower than that in the control group [(1.1 ± 0.4) points vs. (1.7 ± 0.7) points, t = -4.99, P < 0.05]. Ramsay Sedation Scale score in the observation group was significantly higher than that in the control group [(3.6 ± 1.0) points vs. (2.8 ± 0.8) points, t = 7.44, P < 0.05]. At 0 (T 1) and 5 minutes (T 2) after extubation, systolic blood pressure in the observation group was (117.7 ± 18.2) mmHg and (118.1 ± 16.2) mmHg, respectively, which were significantly lower than (134.2 ± 16.2) mmHg and (134.5 ± 15.2) mmHg in the control group ( t =-4.54, -4.95, both P < 0.05). There were no significant differences in the incidences of nausea and vomiting between the two groups (both P > 0.05). At 6 and 12 hours after surgery, visual analogue scale score in the observation group was (2.5 ± 0.8) points and (1.1 ± 0.5) points, respectively, which were significantly lower than (3.4 ± 0.9) points and (1.9 ± 0.8) points in the control group ( t = 5.01, -5.68, both P < 0.05). Conclusion:Oxycodone multimodal analgesia for laparoscopic gynaecological surgery can improve the quality of awakening, decrease systolic blood pressure, reduce the degree of postoperative pain, and does not increase the incidences of postoperative nausea and vomiting.

Objective:To investigate the effect of dexmedetomidine combined with butorphanol on perioperative analgesia in patients subjected to cardiac surgery.Methods:Sixty-three patients who underwent elective cardiac surgery in Weihai Central Hospital from June 2019 to August 2020 were included in this study. They were divided into propofol + sufentanil group ( n = 21), dexmedetomidine + sufentanil group ( n = 23) and dexmedetomidine + butorphanol group ( n = 19) according to different analgesic methods. Postoperative analgesic satisfaction, Visual Analogue Scale score, hemodynamic changes (heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure) and adverse reactions were compared among the three groups. Results:The satisfaction rate of postoperative analgesia in the dexmedetomidine + butorphanol group was 94.7% (18/19), which was significantly higher than 61.9% (13/21) in the propofol + sufentanil group and 60.8% (14/23) in the dexmedetomidine + sufentanil group ( χ2 = 6.16, 6.57, both P < 0.05). At 4, 12, 24 and 48 hours after tracheal extubation, Visual Analogue Scale score in the dexmedetomidine + butorphanol group were significantly lower than that in the propofol + sufentanil group and dexmedetomidine + sufentanil group (both P < 0.05). At the time of tracheal extubation and at 5 minutes after tracheal extubation, heart rate, respiratory rate, systolic blood pressure and diastolic blood pressure in the dexmedetomidine+butorphanol group were significantly lower than those in the propofol + sufentanil group and dexmedetomidine + sufentanil group (both P < 0.05). The incidence of adverse reactions in the dexmedetomidine + butorphanol group was 10.5% (2/19), which was significantly lower than 23.8% (5/21) in the propofol + sufentanil group and 30.43% (7/23) in the dexmedetomidine + sufentanil group [30.4% (7/23), χ2=21.94, P < 0.001]. Conclusion:Dexmedetomidine combined with butorphanol in cardiac surgery can not only stabilize postoperative blood pressure and heart rate, but also lower the degree of pain and is highly safe.

Objective:To study the safety and efficacy of endoscopic papillary balloon dilation for choledocholithiasis.Methods:A total of 60 patients with choledocholithiasis in Suqian People′s Hospital of Nanjing Drum Tower Hospital Group were included from January 2017 to December 2018 according to the inclusion and exclusion criteria. According to the random number table, the patients were divided into two groups: simple endoscopic papillary balloon dilation group (EPBD group, n=30) and endoscopic papillary sphincterotomy combined with balloon dilation group (ESBD group, n=30). Lithotripsy time, X-ray exposure time, one-time lithotripsy rate, lithotripsy rate, incidence of postoperative acute pancreatitis, intraoperative and postoperative bleeding rates were compared.Results:The time of stone extraction (8.5±2.4 min) in EPBD group was comparable with that of group ESBD (7.8±2.1 min) ( P=0.14). The time of X-ray exposure was 21.8±5.2 min in EPBD group and 19.7±6.3 min in ESBD group ( P=0.11). Stones were extracted at one time in all 60 patients, and no lithotripsy was conducted. The incidences of acute pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in the two groups were both 6.67% (2/30). The intraoperative bleeding rates were 3.33% (1/30) and 10.00% (3/30) in EPBD group and ESBD group ( P=0.042), respectively. The rate of postoperative bleeding was 3.33% (1/30) in ESBD group ( P=0.035). No other recent complications occurred in the two groups. Conclusion:Endoscopic papillary balloon dilation alone is safe and effective in the treatment of choledocholithiasis.