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 report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

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 This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection. Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120 after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05). Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14-28 d)on the immunization potential.

Objective:To compare the difference between the Evidence Quality Grading System for Public Health Decision-making(PHE-Grading)and the Grading of Recommendations Assessment,Development and Evaluation(GRADE)System in evaluating the quality of evidence for public health decision-making.Methods:Systematic reviews about topic"Public health"were electronically searched in the Cochrane Library database from inception to February 27,2024.EndNote 20 software was used for literature screening,Excel 2021 and SPSS 22.0 software were used for data collation and analysis,and the forest plot was drawn by RevMan 5.4.1 software.Results:A total of 61 systematic reviews were finally included for evidence quality evaluation.The forest plot of GRADE and PHE-Grading evidence grading results showed that high grade[OR:2.39,95%CI(1.21 to 4.75)],moderate grade[OR:0.40,95%CI(0.31 to 0.52)],low grade[OR:0.37,95%CI(0.29 to 0.46)],and extremely low grade[OR:85.11,95%CI(34.80 to 208.11)],and the differences in evidence quality grading results between the two systems were statistically significant.Conclusions:Compared with GRADE,PHE-Grading may be more accurate in grasping the certainty of public health decision-making evidence.Currently,the quality of public health decision-making evidence is still concentrated in low and middle level,and high-quality research still needs to be strengthened to support scientific decision-making.

Objective To reveal the clinical characteristics of heterotopic pregnancy(HP)and enhance the understanding of its complexity.Methods A retrospective study was conducted among all 390 852 pregnant women who were treated in two tertiary hospitals of obstetrics and gynecology in Shanghai from Jan 2011 to May 2021.We screened and collected patients who were diagnosed as HP,and analyzed their clinical characteristics including menopause time,conception method,location of ectopic pregnancy(EP)and clinical manifestations.Results A total of 185 HP cases enrolled and 14 EP site rupture cases were recognized.Among the 185 cases,84.9%had their EP site in fallopian tube,12.4%were cornual HP.In vitro fertilization-embryo transfer(IVF-ET)ranked first in conception method with rate of 83.8%,followed by ovulation induction with rate of 10.3%and spontaneous conception ranked last with rate of 5.4%.Vaginal bleeding was appeared in 38.4%HP patients,21.1%patients experienced abdominal pain and 12.4%patients had vaginal bleeding complicated by abdominal pain.It is worth mentioning that,25.4%patients had no clinical manifestation.The incidence of EP site rupture was 7.6%.In 14 EP rupture cases,71.4%had abdominal pain as their first clinical manifestation.The post-operation live birth rate of EP site rupture patients was 78.6%,and abortion rate was 14.3%.Conclusion The clinical manifestations of HP are diverse.For patients with vaginal bleeding and abdominal pain,conception method is IVF-ET or ovulation induction,detailed and dynamic transvaginal ultrasound examination should be careful carried out in the uterus and adnexal areas.Patients with abdominal pain should be alert to EP site rupture and early intervention was needed.

Objective To investigate the prevalence of post-traumatic stress disorder(PTSD)in patients during the postoperative period following cardiac surgery and to identify its influencing factors.Methods Post-cardiac surgery patients hospitalized during Sep to Nov,2023 were surveyed using questionnaires consisting of a general information questionnaire,PTSD checklist,resilience scale,social support rating scale,anxiety and depression self-rating scale,and simple coping style questionnaire.Then we analyzed the factors influencing PTSD symptoms after cardiac surgery.Results A total of 267 cases were enrolled.The mean PTSD score of the post-cardiac surgery patients was 16.51±12.31,with 29 patients at high risk for developing PTSD.Stepwise regression analysis revealed that low educational level,use of cardiopulmonary bypass,long stay in ICU,high pain scores,low levels of psychological resilience and social support,as well as high depression score were associated with higher PTSD scores in post-cardiac surgery patients(P<0.05).Conclusion The occurrence of PTSD symptoms in patients after cardiac surgery is common and varies in severity.The influencing factors include the patient's educational level,use of extracorporeal circulation during surgery,length of ICU stay,duration of ventilator use,pain,patient's depression score,psychological resilience,and social support.Medical staff should pay more attention to the mental health level of high-risk patients and take targeted intervention measures in a timely manner.

Helicobacter pylori(HP),a well-established carcinogenic factor,is implicated in the pathogenesis of gastric ulcer,gastric cancer,and other related diseases.Recent studies have unveiled a significant association between HP infection and an increased prevalence of non-alcoholic fatty liver disease(NAFLD).Furthermore,it has been observed that eradication of HP can ameliorate metabolic disorders and relieve NAFLD.Some studies have explored the possible mechanism,which may be related to energy metabolism disorder and gut microbiota imbalance caused by HP.This review outlined the current research status regarding the association between HP and NAFLD,as well as elucidated the potential mechanisms through which HP promoted the onset and progression of NAFLD.

Objective To explore the relationship between serum ferritin levels and body fat distribution in patients with type 2 diabetes mellitus(T2DM).Methods A retrospective analysis was conducted on 151 patients with T2DM who were hospitalized in the Department of Endocrinology of the First Hospital of Lanzhou University from June to November 2020,and all the patients were divided into high serum ferritin(n=50)and normal serum ferritin(n=101)groups according to their serum ferritin levels.The visceral fat area(VFA),subcutaneous fat area(SFA),liver fat,height,weight and waist circumference(WC)were measured,as well as blood glucose,lipid indexes,body mass index(BMI)and visceral adiposity index(VAI)were also calculated.t-test or nonparametric test was used to compare the differences between the two groups,and the relationship between serum ferritin levels and body fat distribution was analyzed by Pearson or Spearman correlation analysis,multiple linear regression and logistic regression.Results The VAI and WC were significantly higher in high serum ferritin group[3.13(2.16,4.58)and(96.66±7.78)cm]than in normal serum ferritin group[2.66(1.66,3.81)and(91.96±9.75)cm,P<0.05].The prevalence of central obesity and dyslipidemia was higher in high serum ferritin group(88.0%and 90.0%)than in normal serum ferritin group(68.3%and 75.2%);and the composition ratios of poor glycemic control and insulin resistance(96.0%and 62.0%)were also higher than in normal serum ferritin group(78.2%and 40.6%)(P<0.05),there were no statistically significant differences in BMI,VFA,and SFA levels,as well as antidiabetic drug use and chronic complications of diabetes mellitus between the two groups(P>0.05).Serum ferritin levels in T2DM patients were positively correlated with VAI,WC,triglyceride(TG),fasting blood glucose(FPG),HbA1c,dyslipidemia and serum creatinine(r=0.171,0.207,0.187,0.243,0.270,0.162,0.162;P<0.05),and negatively correlated with age,sex and diabetes course(r=-0.191,-0.434,-0.352;P<0.05).Multivariate linear regression analysis showed that in male T2DM patients,duration of diabetes and FPG were risk factors for increased levels of serum ferritin.However,WC and VAI did not significantly affect serum ferritin levels.In female patients with T2DM,the course of diabetes,TG and VAI were the factors influencing serum ferritin(P<0.05).Conclusion Dyslipidemia and visceral fat accumulation are risk factors for elevated serum ferritin levels in female T 2DM patients.