ObjectiveTo investigate the current status of first aid knowledge among middle-aged and elderly residents aged 50 and above in a community in Shanghai， in order to provide reference for improving the self-rescue and mutual aid capabilities of middle-aged and elderly residents. MethodsA multi-stage stratified random sampling method was used to conduct a survey on 335 residents aged 50 and above in a community in Shanghai using a self-made survey questionnaire. The current situation and related factors of emergency knowledge level of residents aged 50 and above in the community were comprehensively analyzed. ResultsFirst aid knowledge level of 335 residents aged 50 and above was low， and the rate of high cognitive level was only 24.18%. Univariate analysis showed that male residents had a higher awareness rate than female residents （P=0.044）， while residents aged 70 and above and 60‒ had lower awareness rates than residents aged 50‒ （P<0.05）. Residents with chronic diseases had a higher awareness rate than those who did not （P=0.031）. Residents with family members suffering from chronic diseases had a higher awareness rate than those without （P<0.001）. Experience of first aid training affected residents’ awareness of first aid （P=0.003）. ConclusionThe level of first aid knowledge among middle-aged and elderly residents aged 50 and above in the community is low. Age， the presence of chronic diseases in family members， and emergency training are independent and relevant factors that affect the awareness of first aid knowledge among middle-aged and elderly residents. The government and relevant institutions should explore the establishment of a standardized emergency response training system， implement classification and grading for middle-aged and elderly groups with different characteristics， and provide targeted emergency training to strengthen their self-rescue and mutual aid capabilities and improve the success rate of pre-hospital emergency care.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group， model group， Tamiflu group， and BD-77 groups of 75 and 37.5 g·L^-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group， model group， chloroquine phosphate group， and BD-77 groups of 75， 37.5， 18.75， and 9.375 g·L^-1， with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect related inflammatory factors in lung tissue， and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group， the lung index of mice in each infection group was significantly increased （P<0.01）， and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the lung tissue of mice infected with human coronavirus 229E were all significantly increased （P<0.01）. BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 （P<0.05， P<0.01）， cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 （P<0.01）， and lower the contents of IL-6， IL-10， and TNF-α in the lung tissue of mice infected with human coronavirus 229E （P<0.01）. Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway， TNF signaling pathway， NOD-like signaling pathway， IL-17 signaling pathway， Forkhead box protein O （FoxO） signaling pathway， transforming growth factor-β （TGF-β） signaling pathway， and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism， enhancing the immune function of the host， and attenuating inflammatory responses.

Objective To investigate the effects of sugammadex on postoperative pulmonary com-plications(PPCs)and postoperative recovery after thoracoscopic lung resection surgery.Methods A total of 263 patients scheduled for thoracoscopic lung resection surgery between November 2021 and July 2023,112 males and 151 females,aged 18-64 years,BMI 18.5-28.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were randomly divided into three groups:the sugammadex group(group S,n=88),the neostigmine group(group N,n=87),and the control group(group C,n=88).The patient was sent to postanesthesia care unit(PACU)after operation,when the train of four(TOF)count reached 2,group S was given sugamma-dex 2 mg/kg,group N was given neostigmine 0.04 mg/kg+atropine 0.02 mg/kg,and group C was given equal volume of normal saline.The incidence of PPCs from the end of the surgery to the time of discharge was recorded.The time from the end of surgery to extubation,the time from drug administration to recovery of the train of four ratio(TOFr)to 0.9,the TOFr immediately after extubation,the length of stay in PACU,hypoxemia after extubation(SpO2＜90％)were recorded,and the incidence rate of postoperative residual neuromuscular block(PRNB)was calculated.The time of first getting out of the bed for activity,the number of total and effective compressions by the analgesia pump within 48 hours after surgery,the inci-dence of rescue analgesia,the clinical pulmonary infection score(CPIS),the numbers of postoperative nau-sea and vomiting(PONV),total drainage of the chest tube,duration of the chest tube insertion,and the length of postoperative hospital stay were recorded.Results Compared with group C,the incidence of PPCs,PRNB and hypoxemia after extubation were significantly decreased,time from the end of surgery to extubation,time from drug administration to recovery of TOFr to 0.9,the length of stay in PACU,and the first postoperatively out of bed activity time were significantly shortened,the TOFr immediately after extuba-tion was significantly increased,and CPIS was significantly decreased in group S(P＜0.05);the time from the end of surgery to extubation,time from drug administration to recovery of TOFr to 0.9,the length of stay in PACU were significantly shortened,the TOFr immediately after extubation was significantly in-creased,PRNB after extubation were significantly decreased in group N(P＜0.05).Compared with group N,the incidence of PRNB after extubation were significantly decreased,the time from the end of surgery to extubation,the time from drug administration to recovery of TOFr to 0.9,the length of stay in PACU,and the first postoperatively out of bed activity time were significantly shortened,the TOFr immediately after ex-tubation was significantly increased in group S(P＜0.05).There was no significant difference in other in-dexes between the three groups.Conclusion Sugammadex can rapidly antagonize the residual muscle re-laxation,decrease the rate of PPCs and PRNB,and promote rapid recovery of patients after thoracoscopic lung resection surgery.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Rheumatoid arthritis(RA)is a chronic and progressive autoimmune disease.Current clinical treatments for RA often exhibit inadequate drug responses and severe adverse effects,underscoring the necessity for alternative therapies.Baicalin,a flavonoid derived from Scutellaria baicalensis roots,possesses anti-inflammatory,antioxidant,and immunomodulatory properties.Research suggests that baicalin can inhibit the release of inflamma-tory mediators,thereby reducing inflammation.Moreover,it demonstrates antioxidant effects by decreasing reactive oxygen species production and mitigating synovial damage induced by oxidative stress.Baicalin may impede the activation of inflammatory cytokines through pathways such as NF-κB,MAPKs,and JAK-STAT signaling cascades while inducing apoptosis,regulating immune cell activity,and balancing immune mediators to impact synovitis progression.Clinically,both monotherapy with baicalin or its combination with other formulations have exhibited efficacy and safety profiles.The advancement in targeted drug delivery systems has improved its bioavailability further suggesting promising clinical applications.This review provides an overview of research progress on baicalin's mechanisms in inhibiting RA synovitis along with its clinical applications.

Objective:To compare the results of invasive prenatal diagnosis and preimplantation genetic testing (PGT) and explore the underlying mechanism.Methods:Clinical data of pregnant women undergoing PGT and invasive prenatal diagnosis at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022 were collected. The results of PGT and invasive prenatal diagnosis were compared, and the outcomes of pregnancies were followed up. This study has been approved by the Medical Ethics Committee of the the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022SLYEC-491).Results:A total of 172 couples were included in this study, and 26 non-targeted variants were discovered upon prenatal diagnosis, including 10 cases (38.5%) by chromosomal karyotyping, 15 (57.7%) by chromosomal microarray analysis (CMA), and 1 (3.8%) by whole exome sequencing. The 10 karyotypic anomalies had included 6 chromosomal polymorphisms, 2 chromosomal mosaicisms, 1 paternally derived translocation, and 1 missed maternal chromosomal inversion. CMA has identified 15 copy number variations (CNVs), which included 11 microdeletions and microduplications, 3 loss of heterozygosity, and 1 low-level mosaicism of paternal uniparental disomy. One CNV was classified as pathogenic, and another one was likely pathogenic, whilst the remaining 13 were classified as variants of uncertain significance. Therefore, 8.7% of CNVs was detected by invasive prenatal diagnosis after PGT. 92.3% (24/26) of the non-targeted variants have been due to technological limitations of next-generation sequencing (NGS).Conclusion:Invasive prenatal diagnosis after PGT can detect non-targeted variants, which may further reduce the incidence of birth defects.

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

The purpose of this study was to investigate the damage mechanism of pathogenic E.coli on mouse brain microvascular endothelial cells(BMEC cells)and mouse alveolar macrophages(MH-S cells),as well as the lung and brain of healthy mice.In this study,BMEC cells and MH-S cells were infected with pathogenic E.coli strains,and cell morphological changes were observed.Plate counting method was used to detect the adhesion and invasion ability of the strains to cells and the number of bacteria in the lungs and brains of mice.RT-qPCR was used to detect the ex-pression of TNF-α,IL-1β and IL-6 genes in cells and mouse organs at different time periods.West-ern blot was used to detect the expression of p-NF-κB,p-JAK2 and p-STAT3 proteins related to inflammation in cells and mouse organs after infection.The results showed that the cell culture medium of the infection group was turbid,the cell vision became dark and blurred,some cells shrank and died,and more fragments were produced.The adhesion rate and invasion rate of BMEC cells at 3 h were significantly lower than those at 6 h(P＜0.050),and the adhesion rate and inva-sion rate of MH-S cells at 3 h were significantly higher than those at 6 h(P＜0.010).Infected mice had a large area of swelling and bleeding in the brain,and the lungs had different degrees of swell-ing and bleeding.The bacterial load in the brain and lung was the highest at 12 h.Compared with the control group,the mRNA expression levels of IL-1β,IL-6 and TNF-α in the infection group were significantly increased at 3 h and 6 h(P＜0.050),and the mRNA expression levels of inflam-matory factors in BMEC cells and MH-S cells were the highest at 6 and 3 h,respectively.The mR-NA expression of inflammatory factors in the brain and lung of infected mice showed a trend of in-creasing first and then decreasing with time,with the highest expression at 12 h after infection.The expression levels of p-NF-κB protein in BMEC cells,MH-S cells,lung and brain tissues of mice in the infection group were significantly higher than those in the control group(P＜0.001),and the expression levels of p-JAK2 protein and p-STAT3 protein were significantly lower than those in the control group(P＜0.050).The above results showed that pathogenic E.coli could adhere and invade BMEC cells and MH-S cells,colonize in lung and brain tissues of mice,promote the expres-sion of NF-κB protein in cells and tissues,inhibit the expression of JAK2 protein and STAT3 pro-tein,and then stimulate cells and tissues to produce inflammatory response.

Objective To explore the relationship between serum iron(SI)metabolism and glucose and lipid metabolism in patients with type 2 diabetes mellitus(T2DM).Methods A total of 170 T2DM patients hospitalized in the Department of Endocrinology,Lanzhou University First Hospital from 2019 to 2021 were included.During the same period,30 healthy individuals from physical examination center were selected as the normal control(NC)group.Based on HbA1c control,T2DM patients were divided into subgroups with good blood glucose control(H1,HbA1c＜7%,n=39),poor glucose control(H2,7%＜HbA1c＜9%,n=63)and very poor glucose control(H3,HbA1c＞9%,n=68).According to the level of blood lipids,T2DM patients were divided into subgroups with normal blood lipids(L1,n=36)and high blood lipids(L2,n=134).Results Compared with NC group,age,SBP,DBP,BMI,serum ferritin(SF),FPG,FIns,HOMA-IR,TyG,TG,LDL-C and SUA increased inT2DM group(P＜0.05),while SI,TF,total iron binding capacity(TIBC),DI,HDL-C and eGFR decreased(P＜0.05).The levels of TF and TIBC in H3 subgroup were lower than those in H1 subgroup(P＜0.05).LDL-C of L2 subgroup was higher than that of L1 subgroup(P＜0.05),while HDL-C was lower than that of L1 subgroup(P＜0.05).Pearson correlation analysis showed that SF was positively correlated with HbA1c,TyG,TG and SUA(P＜0.05),and negatively correlated with HDL-C and eGFR(P＜0.05).TF was positively correlated with HDL-C and eGFR(P＜0.05),but negatively correlated with age,SBP,DBP,TyG and SUA(P＜0.05).Multiple linear regression analysis showed that SF and FPG were influencing factors for HbA1c in T2DM patients.Conclusion SI metabolism is closely related to glucose and lipid metabolism in T2DM patients.