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.

Objective:To determine the diagnostic accuracy and prognosis of fetal congenital heart disease (CHD) detected by ultrasound at 11-13 weeks gestation.Methods:Fetuses at 11 to 13 + 6 weeks gestation in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and December 2022 were prospectively collected. Standrardized ultrasound was used to examine the fetuses. For the suspected fetal CHD, the section of cardiac ultrasound was improved as far as possible, and ultrasonic results, prenatal diagnosis, pathological anatomy and pregnancy outcome were followed up. Results:A total of 539 cases of CHD were detected in 72 242 fetuses with mixed risk in the first trimester, the incidence was 0.75% (539/72 242). The incidence of CHD in the fetuses with positive soft markers was 9.20% (287/3 118), and the incidence of multiple fetal malformations was 16.22% (235/1 449). The diagnostic accordance rate of complex CHD was 97.42%. For complex CHD, the sensitivity, specificity, false positive rate and false negative rate of first-trimester ultrasound were 90.41%, 99.98%, 0.02%, 9.59%. Combined with the results of this study, the abnormal section model of complex CHD was recommended. A total of 252 cases underwent staining chromosomal microarray or gene sequencing, of which 42.46% (107/252) were positive.Conclusions:Standardized ultrasound examination has a very high detection rate for fetal CHD in the first trimester. Transverse scanning of the heart can significantly improve the display of gray scale cardiac section, and reference to the cardiac section pattern map is beneficial to the early diagnosis of fetal CHD.

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 observe the clinical efficacy of Sanjiao Tiaoqi Acupuncture in the treatment of post-stroke respiratory dysfunction.Methods Seventy-two patients with post-stroke respiratory dysfunction were randomly divided into observation group and control group,36 cases in each group.The control group was given routine treatment,and the observation group was treated with Sanjiao Tiaoqi Acupuncture on the basis of the control group,both groups were treated for 14 consecutive days.After 2 weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of white blood cell count(WBC),C-reactive protein(CRP)and clinical pulmonary infection score(CPIS)were observed before and after treatment.The changes of diaphragmatic activity were compared before and after treatment between the two groups.Results(1)After treatment,the WBC and CRP levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the WBC and CRP levels,with statistically significant differences(P＜0.05).(2)After treatment,the CPIS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving CPIS scores,with a statistically significant difference(P＜0.05).(3)After treatment,the diaphragm mobility of patients in the two groups was significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving diaphragm mobility,and the difference was statistically significant(P＜0.05).(4)The total effective rate was 91.67％(33/36)in the observation group and 75.00％(27/36)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Sanjiao Tiaoqi Acupuncture for post-stroke respiratory dysfunction can significantly promote the absorption of inflammatory factors in patients and improve diaphragm mobility,with remarkable clinical efficacy.

Objective:The incidence of infections in patients with malignant hematologic diseases is extremely high and significantly affects their prognosis.Identifying early and precise biomarkers for infection is crucial for guiding the treatment of infections in these patients.Previous studies have shown that procalcitonin(PCT)can serve as an early diagnostic marker for bloodstream infections in patients with malignant hematologic diseases.This study aims to compare serum PCT levels in these patients with different pathogens,disease types,infection sites,and severity levels. Methods:Clinical data and laboratory results of infected patients with malignant hematologic diseases treated at the Department of Hematology,the Third Xiangya Hospital of Central South University from January 2018 to August 2023 were collected.General patient information was retrospectively analyzed.Serum PCT levels were compared among patients with different pathogens,types of malignant hematologic diseases,infection sites,and infection severity;Receiver operator characteristic(ROC)curves were used to determine the cut-off values and diagnostic value of serum PCT levels in diagnosing bloodstream infections versus local infections and severe infections versus non-severe infections.Mortality rates after 4-7 days of anti-infective treatment were compared among groups with rising,falling,and unchanged PCT levels. Results:A total of 526 patients with malignant hematologic diseases were included.The main pathogens were Gram-negative bacteria(272 cases,51.7%),followed by Gram-positive bacteria(120 cases,22.8%),fungi(65 cases,12.4%),viruses(23 cases,4.4%),and mixed pathogens(46 cases,8.7%).The main types of malignant hematologic diseases were acute myeloid leukemia(216 cases,41.1%),acute lymphoblastic leukemia(107 cases,20.3%),and lymphoma(93 cases,17.7%).Granulocyte deficiency was present in 68.3%(359 cases)of the patients during infection,with severe infection in 24.1%(127 cases).Significant differences in serum PCT levels were found among patients with different types of pathogens(P<0.001),with the highest levels in Gram-negative bacterial infections.Significant differences in serum PCT levels were also found among patients with different types of malignant hematologic diseases(P<0.05),with the highest levels in lymphoma patients.Serum PCT levels were significantly higher in systemic infections and severe infections compared to local infections and non-severe infections(both P<0.001).ROC curve analysis showed that the cut-off values for diagnosing bloodstream infections and severe infections were 0.22 and 0.28 ng/mL,with areas under the curve of 0.670 and 0.673,respectively.After 4-7 days of anti-infective treatment,the mortality rates of the PCT declining,PCT unchanged,and PCT rising groups were 11.9%,21.2%,and 35.7%,respectively,and pairwise comparisons were statistically significant(all P<0.05). Conclusion:PCT can be used as an auxiliary indicator for early identification of different pathogens,infection sites,and severity levels in patients with malignant hematologic diseases combined with infections.Dynamic monitoring of PCT levels after empirical antibiotic treatment provides important guidance for assessing patient's prognosis.

The nasal swab samples of swine influenza(SI)suspected pigs were collected and tested for H3 subtype swine influenza virus(SIV)positive by RT-qPCR.The positive samples were inoc-ulated into SPF chicken embryos for virus isolation.The full genome sequencing and sequence anal-ysis of the isolated H3N2 subtype SIV were conducted,and its pathogenicity was studied.The re-sults showed that a strain of SIV was successfully isolated and identified as H3N2 subtype by RT-PCR,named A/Swine/Yunnan/KM/06/2023(H3N2).The BLSAT results showed that the eight segments of SIV H3N2 KM had the highest homology with eight different strains of swine influ-enza or human influenza viruses,reaching 95.41％-97.49％.The HA and NA segments were de-rived from H3N2 subtype SIV,the NP segment was derived from H1N1 subtype human influenza virus,the M segment was derived from H1N2 subtype SIV,and all other segments were derived from H1N1 subtype SIV.The key receptor sites(190D,223V,226I,228S)of HA protein remained unchanged.The pathogenicity experiment results showed that infected piglets exhibited symptoms such as fever,sneezing,runny nose,the virus could be detoxified to the outside through the nasal cavity,and the lungs had different degrees of lesion.Immunohistochemistry(IHC)showed that the virus could replicate in the lungs.In conclusion,a strain of H3N2 subtype SIV was successfully iso-lated,and the genetic evolution,molecular characteristics and pathogenicity of the virus were stud-ied.It revealed that H3N2 subtype SIV is constantly evolving and had pathogenicity to piglets,pro-viding a reference for monitoring and preventing SIV epidemics in China,and provided a candidate strain for SI vaccine development.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective The aim of this study was to investigate the impact and mechanisms of emodin on oxidative stress response in lipopolysaccharide(LPS)-induced murine mononuclear macrophages(RAW264.7).Methods Involved the use of LPS,RAW264.7 cells,and emodin.Experimental groups included a control group,LPS(1 μg/mL)group,and LPS(1 μg/mL)+emodin(15 μmmol/L)pretreatment group.Aldehyde malondialdehyde(MDA)content,intracellular reactive oxygen species(ROS)levels,and silent information regulator 2(Sirt2)expression were evaluated at 6,12,and 18 hours after LPS exposure.Additionally,RAW264.7 cells were pretreated with Sirt2 inhibitor AGK2(20 μmol/L)followed by LPS stimulation,and the above-mentioned parameters were assessed at 6 hours.Results Compared to the control group,MDA content,ROS levels,Sirt2 mRNA,and protein expression in RAW264.7 cells in the LPS group increased at all time points(all P<0.05).At 6 and 18 hours,MDA content and ROS levels in RAW264.7 cells in the LPS+emodin group decreased significantly(all P<0.05),while at 12 hours,ROS levels were lower in the LPS group compared to the LPS+emodin group(P<0.05).Sirt2 mRNA and protein levels significantly increased at all time points(all P<0.05)compared to the LPS group.In the LPS+emodin+AGK2 group,Sirt2 mRNA and protein levels decreased,and MDA content and ROS levels increased compared to the LPS+emodin group(all P<0.05).Conclusion LPS-induced oxidative stress in RAW264.7 cells and emodin attenuate LPS-induced oxidative stress in RAW264.7 cells through Sirt2.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.