OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

[Objective]To develop a classification model based on complete blood count(CBC)parameters combined with clinical factors to predict severe respiratory infections caused by Human adenovirus(HAdV)in pediatric patients.[Methods]From September 2023 to September 2024,the CBC parameters and related clinical data from pediatric patients diagnosed with HAdV infection were collected.Principal component analysis and random forest models were used to identify potential predictors of severe cases.[Results]A total of 668 pediatric patients were included,with 564 cases assigned to the training cohort and 104 cases to the validation cohort.Severe cases were defined as pneumonia and/or fever lasting≥5 days(pneumonia or prolonged fever,PorPF).Principal component analysis and feature importance analysis(Mean Decrease Gini value)identified the monocytosis ratio(PMono),red blood cell count(RBC),and platelet count(PLT)as the most critical CBC parameters.Logistic regression analysis revealed that oxygen therapy(OR=4.367,95%CI:1.568-12.161)and increased work of breathing(OR=3.904,95%CI:2.146-7.101)were relative risk factors for PorPF.Meanwhile,higher PMono(OR=0.696,95%CI:0.640-0.757),RBC(OR=0.201,95%CI:0.124-0.325),and PLT(OR=0.990,95%CI:0.987-0.994)were protective factors.When PMono was used as a predictive marker for PorPF,the area under the receiver operating characteristic curve(AUC)was 0.648 and 0.705,respectively.A random forest model incorporating four risk factors[PMono,RBC,PLT,and hematocrit(HCT)]was constructed to classify PorPF and general cases,achieving AUCs of 0.688 and 0.768,respectively.[Conclusions]PMono,RBC,and PLT may serve as characteristic CBC indicators for predicting pneumonia or prolonged fever in children with HAdV infection.A risk factor model built using PMono,RBC,PLT,and HCT offers a relatively simple and accurate approach to predicting severe cases in pediatric HAdV infections.

Objective A binary Logistic regression model was developed to forecast the pathological grade of invasive adenocarcino-ma by utilizing the CT characteristics of lung nodules.Methods A retrospective analysis was conducted on the clinical data,pathological types,and imaging findings of 303 cases of ground-glass nodules diagnosed with postoperative pathological infiltrative adenocarcinoma at the First Affiliated Hospital of Henan Polytechnic University and the First Affiliated Hospital of Xinxiang Medical College from January 2021 to February 2023.Based on the pathological results,these lesions were categorized into two groups:the low-grade group(compri-sing 262 cases characterized by adherent,acinar,or papillary types as predominant forms of adenocarcinoma with no more than 20％high-grade pattern)and the high-grade group(consisting of 41 cases exhibiting any form of adenocarcinoma with over 20％high-grade components).The Mann-Whitney U test was employed to compare quantitative parameters between both groups,while qualitative parameters were analyzed using the x2 test.Additionally,binary Logistic regression models were utilized to identify independent predictors;further evaluation included area under curve(AUC)values,calibration curves,and decision analysis curves to assess model differentia-tion,calibration accuracy,and clinical applicability.Results Univariate analysis revealed that gender,air bronchial sign,vacuole sign,vascular cluster sign,pleural depression sign,long diameter,short diameter,and CT-enhanced net increment exhibited statistical signifi-cance(P＜0.05),whereas location,burr sign,and solid component ratio did not demonstrate statistical significance(P＞0.05).Binary Logistic regression analysis identified long diameter,CT-enhanced net increment,vascular cluster sign,pleural depression sign,and vacu-ole sign as independent predictors of the pathological grade model for invasive adenocarcinoma.The results of ROC curve analysis indicated that the AUC value of the Logistic regression model was 0.846 with a sensitivity of 81.25％and specificity of 86.52％.Conclusion The logistic regression model based on CT signs has excellent ability and stability in predicting the pathological grade of invasive adenocarcinoma.

Objective A binary Logistic regression model was developed to forecast the pathological grade of invasive adenocarcino-ma by utilizing the CT characteristics of lung nodules.Methods A retrospective analysis was conducted on the clinical data,pathological types,and imaging findings of 303 cases of ground-glass nodules diagnosed with postoperative pathological infiltrative adenocarcinoma at the First Affiliated Hospital of Henan Polytechnic University and the First Affiliated Hospital of Xinxiang Medical College from January 2021 to February 2023.Based on the pathological results,these lesions were categorized into two groups:the low-grade group(compri-sing 262 cases characterized by adherent,acinar,or papillary types as predominant forms of adenocarcinoma with no more than 20％high-grade pattern)and the high-grade group(consisting of 41 cases exhibiting any form of adenocarcinoma with over 20％high-grade components).The Mann-Whitney U test was employed to compare quantitative parameters between both groups,while qualitative parameters were analyzed using the x2 test.Additionally,binary Logistic regression models were utilized to identify independent predictors;further evaluation included area under curve(AUC)values,calibration curves,and decision analysis curves to assess model differentia-tion,calibration accuracy,and clinical applicability.Results Univariate analysis revealed that gender,air bronchial sign,vacuole sign,vascular cluster sign,pleural depression sign,long diameter,short diameter,and CT-enhanced net increment exhibited statistical signifi-cance(P＜0.05),whereas location,burr sign,and solid component ratio did not demonstrate statistical significance(P＞0.05).Binary Logistic regression analysis identified long diameter,CT-enhanced net increment,vascular cluster sign,pleural depression sign,and vacu-ole sign as independent predictors of the pathological grade model for invasive adenocarcinoma.The results of ROC curve analysis indicated that the AUC value of the Logistic regression model was 0.846 with a sensitivity of 81.25％and specificity of 86.52％.Conclusion The logistic regression model based on CT signs has excellent ability and stability in predicting the pathological grade of invasive adenocarcinoma.

Background::Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods::Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results::The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) ( χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2 = 6.95, P = 0.008), BDG ( χ2 = 10.43, P = 0.001), and fungal culture ( χ2 = 12.70, P < 0.001). Conclusions::Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

Objective: To investigate the efficacy and adverse effects of sustained lung inflation (SLI) combined with pulmonary surfactant (PS) in the treatment of neonatal respiratory distress syndrome (NRDS). Methods: This prospective randomized controlled trial included 124 premature infants (gestational age <34 weeks and birth weight <2 000 g) diagnosed with NRDS and in need of PS treatment in Shenzhen Maternity & Child Healthcare Hospital affiliated to Southern Medical University from July 1, 2016 to October 31, 2018. They were randomly divided into experimental or control group, with 62 cases in each. Infants in the experimental group were treated with SLI using T-piece and intratracheal PS, while those in the control group were given PS only. Blood gas analysis and measurement of fraction of inspiration O₂ (FiO₂) and ratio of partial pressure of oxygen (PO₂) over FiO₂ were performed before and 1 h after PS injection. Results of the treatments and incidence of complications were compared. Paired samples t-test, two independent samples t-test, rank-sum test and Chi-square test were used for statistical analysis. Results: There were 56 participants in the experimental group and 54 in the control group who were eventually analyzed. In the experimental group, the pH value, partial pressure of carbon dioxide (PCO₂), FiO₂ and PO₂/FiO₂ at 1 h after PS injection were all improved compared with those before treatment [pH value: 7.26±0.09 vs 7.19±0.09, t=3.814; PCO₂: (51.5±12.6) vs (59.8±16.3) mmHg (1 mmHg=0.133 kPa), t=2.610; FiO₂: 26.0 (21.0-31.5)% vs 40.5 (38.5-51.5)%, U=392.000; PO₂/FiO₂: (284.6±117.9) vs (173.4±59.7) mmHg, t=6.427; all P<0.05]. The overall decrement of FiO₂ after PS injection in the experimental group was more significant than that in the control group [-10.0 (-15.0 to -5.0)% vs -5.0 (-8.0 to 0.0)%, U=706.500, P<0.001]. The experimental group had a higher rate of extubation within 24 h than the control group [80% (45/56) vs 71% (32/54), χ²=5.830, P=0.016]. However, no significant differences were shown in total mechanical ventilation time, non-invasive/high-flow nasal cannula ventilation time, the ratio of re-intubation within 72 h, or the incidence of air leak, bronchopulmonary dysplasia, periventricular-intraventricular hemorrhage, necrotizing enterocolitis or patent ductus arteriosus between the two groups (all P>0.05). Conclusions SLI combined with PS for NRDS babies can increase the rate of extubation within 24 h and promote the down-regulation of FiO₂ without causing significant complications.

Objective: To establish real-time recombinase polymerase amplification（RPA）for the rapid detection of Vibrio parahaemolyticus（VP）. Methods: An exo probe and primers were designed according to the conserved sequence of thermolabile hemolysin（tlh）gene of VP and then RPA for detection of VP was established. The sensitivity of the assay was evaluated by detecting different concentration of VP;the specificity was evaluated by detecting different bacteria;the stability was evaluated by repeat trials;the application effect was evaluated by detecting food samples which were simultaneously tested with traditional culture method according to GB 4798.7-2013 Detection of VP. Results: A real-time RPA was established to complete VP amplification within 20 min at a constant temperature of 39 ℃. The analytical sensitivity of the assay was five pg per reaction and no cross-reactivity with other pathogenic bacteria observed. The RPA detection results with different concentration of VP and E. coli DNA templates at three time points were consistent. The detection results of 51 food samples by RPA were the same as those by traditional culture method. Conclusion The established real-time RPA can qualitatively detect VP,with simple operation and interpretation of results,which is suitable for rapid detection of VP in public health emergencies and food safety supervision.

Objective To establish a clinical nursing pathway for elderly parturients. Methods The clinical nursing pathway draft for elderly parturients were designed though the method of case analysis and literature review. Delphi method was used by 10 experts engaged in clinical medical or nursing with 2 rounds. Results The recovery rates of the two Delphi method were 100%, the experts who put forward the proposal on the 2 rounds of expert conclusion were 60.00% (6/10) and 20.00% (2/10) respectively. The expert's familiarity with the correspondence is 0.90, the coefficient of judgment is 0.80 and the coefficient of authority is 0.85.The mean value and standard deviation of the 2 rounds of correspondence were 3.60～5.05 (standard deviation 0.34～0.94) and 3.91～4.13 (standard deviation 0.26～0.60)respectively. The coordination coefficients of the 2 rounds of experts consultation were 0.441 and 0.592 (all P＜0.001). The clinical nursing pathway for elderly parturients with pregnancy management were three stages: confirmed pregnancy to 13+6weeks, 14 weeks to 27+6days pregnant and 28 weeks pregnant to childbirth, including a total of 74 projects for 4 modules such as medical history collection, physical examination, clinical laboratory and other examination and nursing measures. Conclusions The practicable clinical nursing pathway for elderly parturients was constructed because its high degree of familiarity,authority,coordination and concentration. The statistical analysis results are reliable,it is beneficial to standardize the pregnancy management for elderly parturients and improve the quality of clinical nursing.

To knock out β-lactoglobulin (BLG) gene and insert human lactoferrin (hLF) coding sequence at BLG locus of goat, the transcription activator-like effector nucleases (TALEN) mediated recombination was used to edit the BLG gene of goat fetal fibroblast, then as donor cells for somatic cell nuclear transfer. We designed a pair of specific plasmid TALEN-3-L/R for goat BLG exon III recognition sites, and BLC14-TK vector containing a negative selection gene HSV-TK, was used for the knock in of hLF gene. TALENs plasmids were transfected into the goat fetal fibroblast cells, and the cells were screened three days by 2 μg/mL puromycin. DNA cleavage activities of cells were verified by PCR amplification and DNA production sequencing. Then, targeting vector BLC14-TK and plasmids TALEN-3-L/R were co-transfected into goat fetal fibroblasts, both 700 μg/mL G418 and 2 μg/mL GCV were simultaneously used to screen G418-resistant cells. Detections of integration and recombination were implemented to obtain cells with hLF gene site-specific integration. We chose targeting cells as donor cells for somatic cell nuclear transfer. The mutagenicity of TALEN-3-L/R was between 25% and 30%. A total of 335 reconstructed embryos with 6 BLG-/hLF+ targeting cell lines were transferred into 16 recipient goats. There were 9 pregnancies confirmed by ultrasound on day 30 to 35 (pregnancy rate of 39.1%), and one of 50-day-old fetus with BLG-/hLF+ was achieved. These results provide the basis for hLF gene knock-in at BLG locus of goat and cultivating transgenic goat of low allergens and rich hLF in the milk.
Animals ; Animals, Genetically Modified ; genetics ; Female ; Fibroblasts ; Gene Knock-In Techniques ; Gene Knockout Techniques ; Goats ; genetics ; Humans ; Lactoferrin ; genetics ; Lactoglobulins ; genetics ; Milk ; chemistry ; Nuclear Transfer Techniques ; Plasmids ; Pregnancy ; Transfection

Objective To investigate the effect of growth differentiation factor 11 ( GDF11 ) on aorta in apolipoprotein E-Null( ApoE-/-) mice and its possible mechanisms. Methods Four-week-old healthy male ApoE-/-mice were fed with high-fat diet for 1 week and were then divided into 4 groups:vehicle group(n=10), GDF11 group (n=10),adeno-associated virus-green fluorescent protein group(AAV-GFP group, n=10), and AAV-GDF11 group ( n=10 ) . The mice received intraperitoneal injection with phosphate buffered saline, GDF11 protein, a single injection of purified AAV-GDF11 or AAV-GFP through the tail vein, respectively. After 4 weeks, serum GDF11/8 level and endothelium-dependent vasodilatation were detected. After 12 weeks, serum GDF11/8, interleukin-6 (IL-6), tumor necrosis factor-α( TNF-α), total cholesterol ( TC), triglycerides ( TG), oxidized low density lipoprotein(ox-LDL), and free fatty acids(FFA)levels were measured, the plaque areas in aortic enface and cross sections were measured by oil red O or HE staining, the macrophages/T lymphocytes infiltration in plaques were detected with immunohistochemistry, and the mRNA expressions of IL-6, TNF-α, and IL-10 were determined by real-time PCR. Results Compared with vehicle or AAV-GFP groups, GDF11 and AAV-GDF11 groups presented improved endothelium-dependent vasodilatation, decreased levels of blood inflammatory factors, blood lipid, reduced plaque on face area sections[Vehicle group : GDF11 group:(31. 23 ± 3. 12)% vs (17. 18 ± 2. 17) %;AAV-GFP group : AAV-GDF11 group:(38.01±4.43)% vs(14.54±2.86)%,P<0.05]andcrosssections[Vehiclegroup :GDF11 group:(19. 87 ± 2. 11)% vs (10. 32 ± 1. 47)%;AAV-GFP group : AAV-GDF11 group:(23. 02 ± 2. 76)%vs (9.06±1.63)%, P<0. 05]. There were less macrophages and T lymphocytes infiltration in plaques and lower mRNA expressions of inflammatory factors at aortic wall. Conclusion GDF11 reduces the area of atherosclerotic lesion in ApoE-/-mice, which may be involved in endothelial protection, such as to reduce inflammatory reaction, and to change cellular composition in plaques.