Objective To mine the adverse drug events(ADE)signal of avatrombopag,an effective drug for thrombocytopenia treatment,based on real world data in order to provide reference for its clinical safety application.Methods The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system(FAERS).The ADE signals were classified and described by the system organ class(SOC)and preferred term(PT)of the ADE terminology set in the Medical Dictionary for Regulatory Activities(MedDRA),and reporting odds ratio(ROR)and UK Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard were used to detect the positive ADE signals.Results A total of 1 879 ADE reports related to avatrombopag were obtained,24 SOCs were involved,and 28 positive ADE signals were detected at PT level.Among these signals,the strongest ones were renal vein thrombosis,portal vein thrombosis and graft versus host disease,while the reports accounting for the largest numbers were headache,fatigue and asthenia.There were 8 ADE signals discovered newly,that is,seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea.Conclusion For clinical use of avatrombopag,clinicians should not only concern the risk of thrombosis,but also pay close attention to ADE signals such as seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea that are not documented in the instructions.

OBJECTIVE To provide reference for the clinically safe application of acalabrutinib by mining and analyzing the risk signals of adverse drug events （ADE）. METHODS The acalabrutinib-induced ADE reports were extracted from the U.S. FDA adverse event reporting system using the OpenVigil 2.1 platform from November 1， 2017 to March 31， 2023. The reporting odds ratio （ROR） method and composite criteria method from the Medicines and Healthcare Products Regulatory Agency （MHRA） were used for detection of ADE signals. RESULTS There were 7 869 ADE reports of acalabrutinib as the primary suspect drug and 142 ADE positive signals were detected from them， involving 20 system organ classes， which was generally consistent with the ADE recorded in the drug instruction of acalabrutinib， mainly involving general disorders and administration site conditions， various inspection， blood and lymphatic system disorders， various neurological disorders and cardiac disorders. In addition， this study identified several new potential ADE signals that were not mentioned in the drug instruction， including sudden cardiac death， pulmonary toxicity， tumor lysis syndrome， pleural effusion， dyspepsia， gastroesophageal reflux disease， bone pain， decreased blood pressure， and abnormal blood sodium， etc. CONCLUSIONS When using acalabrutinib， in addition to paying attention to the ADE recorded in its instructions， the risk of serious ADE that may lead to death， such as sudden cardiac death and pulmonary toxicity， should also be evaluated to avoid or reduce the occurrence of ADE as much as possible.

OBJECTIVE To prepare Lonicerae japonicae flavonoids liposome membrane （LFLM）， and to study the mechanism of its anti-methicillin-resistant Staphylococcus aureus （MRSA）. METHODS L. japonicae flavonoids liposome （LFL） were prepared by ethanol injection with phospholipids and cholesterol as carriers. LFLM was prepared by loading LFL in mixed membranes of chitosan and polyvinyl alcohol. The particle size of LFL， polydispersity index （PDI） and release rate of LFLM were measured. A control group， LFLM low-concentration group （2.5 mg/mL）， LFLM-medium concentration group （5 mg/mL）， LFLM high-concentration group （10 mg/mL）， positive group （10 μg/mL vancomycin）， and combination therapy group （10 mg/mL LFLM and 10 μg/mL vancomycin） were set up. The effects of LFLM on MRSA colony formation and survival as well as the formation of MRSA biofilm were evaluated. The contents of K+， Mg2+， lactic dehydrogenase （LDH）， and alkaline phosphatase （AKP） in the supernatant of MRSA were determined. mRNA expressions of mecA and mecR1 in MRSA were determined. RESULTS The particle size of LFL was （80.91±3.96） nm， and the PDI was 0.26±0.07. The release rate of LFLM was 55% within 12 h and 73% within 36 h. Compared with the control group， the number of MRSA colony formation decreased significantly in LFLM medium-concentration and high-concentration groups， and the positive group （P＜0.05）. The ratio of dead to live bacteria， biofilm inhibition rate， and the contents of K+， Mg2+， LDH and AKP were increased significantly （P＜0.05）， while the mRNA expressions of mecA and mecR1 were decreased significantly （P＜0.05）. The combination of LFLM and vancomycin further enhanced the anti-MRSA effect. CONCLUSIONS LFLM is prepared successfully in the study and has good drug release characteristics. LFLM can exert anti-MRSA activity by promoting cell wall and membrane damage， and suppressing the mRNA expression of mecA and mecR1.

Objective:To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A.Methods:It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed.Results:The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband′s father had knee joint pain. The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions:High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

Objective:To compare the safety and efficacy of terbutaline and nifedipine for acute intrapartum fetal resuscitation (IUFR).Methods:This was a prospective randomized controlled study involving 110 pregnant women with non-reassuring fetal heart rate tracings (NRFHT) during delivery at Guangzhou Women and Children's Medical Center between January and April 2021. These women were randomly allocated to receive subcutaneous terbutaline sulphate (0.25 mg, terbutaline group) or oral nifedipine (10 mg, nifedipine group), with 55 subjects in each group. Hemodynamic parameters including blood pressure, heart rate, and oxygen saturation before and 5, 15 and 30 min after treatment as well as the success rate of intrapartum resuscitation, the onset time of medication, and the incidence of postpartum hemorrhage were analyzed using t test, Chi-square test or Fisher's exact test. Results:Two groups both showed no significant difference in the mean arterial pressure or oxygen saturation before or after treatment (all P>0.05). The heart rate was not affected in nifedipine group at any time points ( P>0.05). While the patients treated with terbutaline showed accelerated maternal heart rate 5, 15 and 30 min after administration as compared with the baseline[(97.0±20.2), (99.2±13.8), (91.8±12.6) vs (81.7±11.3) bpm, all P<0.001], but it began to decrease at 30 min, with a drop of 6.4 bpm compared with that at 15 min (95% CI: 1.5-11.2, P<0.05). None of the pregnant women had adverse reactions requiring medical intervention. The rates of successful acute resuscitation were similar in the two groups [terbutaline: 78.2% (43/55) vs nifedipine: 70.9% (39/55), χ 2= 0.77, P=0.381]. Terbutaline had a shorter onset time than nifedipine in slowing the frequency of contractions and returning fetal heart rate to class Ⅰ category [2(1-6) vs 6(1-10) min, U=2 348.50, P<0.001]. No significant difference was found between the two groups in terms of NRFHT-indicated cesarean section, assisted vaginal delivery, or second dose of tocolysis within 1 h (all P>0.05) nor in blood loss volume, postpartum hemorrhage rate, low Apgar score, low umbilical artery pH value (pH<7.2), neonatal asphyxia rate, or neonatal intensive care admission rate (all P>0.05). Conclusion:Terbutaline spends less time than nifedipine to take effect and may be an alternative for acute IUFR without significant adverse outcomes.

Purpose To explore the predictive value of myocardial perfusion in assessing myocardial systolic function recovery after primary percutaneous coronary intervention (PPCI),in order to improve poor prognosis by early detection of myocardial no-reflow.Materials and Methods Forty nine patients with acute myocardial infarction (AMI) who had received PPCI were chosen as subjects.All the patients underwent two-dimensional strain (2DS) images and resting real-time myocardial contrast echocardiography (MCE) within one week after surgery,and 2DS measurement was repeated after three months.2DS imaging was used to acquire longitudinal peak systolic strain (LPSS) at all myocardial segments.Based on the graphs of LPSS,left ventricular myocardium was divided into normal contractile function myocardium (red) and impaired contractile function myocardium (light red,blue).According to the myocardial perfusion scores (MPS) qualitatively assessed by MCE visual interpretation,the myocardia with impaired systolic function were categorized into three groups with different perfusion level.The changes of LPSS within one week and three months after surgery (△ LPSS) among the three groups were analyzed.The correlation between MPS and LPSS within one week and three months after PPCI was also analyzed respectively.Results The △ LPSS increased significantly among the three groups with the improvement of myocardial perfusion level [(-5.78±6.23)％ vs.(-4.37±6.60)％ vs.(-1.21 ±4.77)％,all P＜0.05].The MPS measured one week after PPCI was both positively correlated with the LPSS detected within one week after surgery and that after three months (r=0.47,0.58,P＜0.001).The consistence of myocardial perfusion scores given by two evaluators was good (Kappa=0.785,P＜0.05).Conclusion The level of myocardial perfusion after PPCI in patients with AMI is closely related to regional myocardial systolic function,and the improvement of myocardial perfusion can forecast the recovery of regional systolic function.

Objective To evaluated the value of myocardial perfusion before delayed percutaneous coronary intervention (PCI) for predicting the recovery of systolic function of patients with acute myocardial infarction (AMI).Methods A total of 64 patients with AMI receiving delayed PCI treatment in the First People's Hospital of Foshan from January 2014 to June 2015 were selected.One day prior to delayed PCI,all of the patients underwent two dimensional strain to measure the longitudinal peak systolic strain (LPSS) of each left ventricular segment and the global longitudinal strain (GLS) of the left ventricle.The myocardial perfusion score (MPS) and the perfusion score index (PSI) were measured by myocardial contrast echocardiography (MCE).Left ventricular myocardial perfusions were classified as good,reduced,or absent.The two dimensional strain measurements were again conducted at 6 months after the delayed PCI to assess LPSS and GLS.The change of GLS and LPSS between one day prior to delayed PCI and six months after delayed PCI was assessed by paired t-test.The differences of LPSS among good,reduced,or absent myocardial perfusion groups were analyzed by one-way ANOVA.LSD-t test was used to compare in pairs of groups that had different values.The correlations between PSI and GLS,MPS and LPSS were assessed by Spearman's rank-correlation test.Results The GLS of all patients were higher at six months after delayed PCI than at one day prior to delayed PCI [(-15.39±7.80)％ vs (-12.44±8.38)％,t=14.398,P ＜ 0.001].The LPSS of myocardial perfusion in good,reduced and absent groups at one day prior to delayed PCI were (-2.64±5.60)％,(-6.19±6.87)％ and (-12.07±5.86)％,respectively.The LPSS of myocardial perfusion in good,reduced and absent groups at six months after delayed PCI were (-2.97 ± 4.93)％,(-11.38± 7.26)％ and (-15.82 ± 5.97)％,respectively.The myocardial LPSS of left ventricular segment with good or reduced perfusion was significantly higher at six months after delayed PCI (t=13.013,10.821,both P ＜ 0.001),but the LPSS of left ventricular segment with absent perfusion was similar to that of pre-PCI.Whether at one day prior to delayed PCI or six months after delayed PCI,there were significant differences in LPSS parameters among the three groups (at one day prior to delayed PCI,myocardial perfusion absent vs reduced or good,t=4.201 and 11.771,both P ＜ 0.001;myocardial perfusion reduced vs good,t=12.561,P ＜ 0.001;at six months after delayed PCI,myocardial perfusion absent vs reduced or good,t=9.714 and 15.646,both P ＜ 0.001;myocardial perfusion reduced vs good,t=9.254,P ＜ 0.001).The LPSS both at one day prior to delayed PCI and six months after delayed PCI in myocardial perfusion good group ＞ those of myocardial perfusion reduced group ＞ those of myocardial perfusion absent group.PSI was positively correlated with GLS at both one day prior to delayed PCI and six months after delayed PCI (r=0.69,0.72,both P ＜ 0.001).MPS was positively correlated with LPSS at both one day prior to delayed PCI and six months after delayed PCI (r=0.49 and 0.45,both P ＜ 0.001).Conclusion Myocardial perfusion before delayed PCI,monitored by MCE,is correlated well with myocardial systolic function,and may be used to predict the recovery of myocardial systolic function after delayed PCI.

OBJECTIVE:To study the effect of Typhae pollen decoction on isolated uterine smooth muscle(USM)contraction of rats at postconceptual stage. METHODS:16 Wistar rats at postconceptual stage were selected and USM strips were isolated. T. pollen decoction 0(blank control),2,4,8 and 12 mg(medicinal material)/ml were added respectively;the effects of T. pollen de-coction on USM strips contraction were observed,and mean tension,duration of contraction and frequency were measured and re-corded. The effects of T. pollen decoction on USM strips contraction were investigated after pretreatment of prostaglandin synthase inhibitor indometacin(1×10-7 mol/ml)and calcium channel blocker verapamil(1×10-7 mol/ml);USM tension,duration of contrac-tion and frequency were measured and recorded. RESULTS:Compared with blank control group,T. pollen decoction 4,8 and 12 mg(medicinal material)/ml could increase USM tension,duration of contraction and frequency(P<0.05);after added verapamil and indometacin,T. pollen decoction decreased USM tension,shortened duration of contraction and decreased frequency (P<0.05). CONCLUSIONS:T. pollen decoction can strengthen USM strips contraction,and the effect is inhibited by prostaglandin syn-thase inhibitor and calcium channel blocker.

Objective To evaluate the apphcation value of peripheral blood neutrophil CD64 expression in early differential diagnosis of etiology in children with community-acquired pneumonia.Methods From June 2014 to June 2015 in our hospital,total of 99 cases of different pathogen infection were divided into three groups,bacterial pneumonia group (n =41),non-bacterial pneumonia group(n =38),healthy children group (n =20);and the non-bacterial pneumonia group was divided into two subgroups,viral pneumonia group (n =22) and mycoplasma pneumoniae pneumonia group(n =16).Flow cytometry was used to test the median fluorescence intensity (MFI) of peripheral blood neutrophil CD64.The levels of peripheral blood CRP,WBC and neutrophil percentage were detected.Results The levels of CD64 expression,CRP and WBC in bacterial pneumonia group were statistically higher than those of non-bacterial pneumonia group and healthy children group respectively (both P ＜ 0.01).The optimal cutoff value of CD64 was 6 519 MFI when using ROC curve,and the sensitivity and specificity of the diagnosis of bacterial pneumonia were 87.8％ and 89.7％ respectively.The levels of CD64 expression in bacterial pneumonia group were significantly higher than those in viral pneumonia group,mycoplasma pneumoniae pneumonia group and healthy children group (all P ＜ 0.01).Conclusion The expression of peripheral blood neutrophil CD64 increases in children with community-acquired pneumonia of bacteria infection.It can be used to guide early diagnosis of children with bacterial pneumonia and the using of antibiotics.

Objective To study tirofiban intravenous injection,coronary artery injection of the two different methods in acute ST segment elevation myocardial infarction,the application of emergency PCI.Methods Patients underwent emergency PCI with acute ST segment elevation myocardial infarction as the research subjects,a total of 108 cases,the patients were randomly divided into the observation group and control group,54 patients in each group. In the observation group,the first dose of tirofiban was injected into the coronary artery.The control group was treated by intravenous injection.The results of the two groups were compared.Results Before treatment,TIMI level 2 and level 3 ratio,initial corrected TIMI frame count of the observation group were significantly lower than the control group (χ2 /t =4.32,4.59,5.25,all P <0.05).After treatment,MBG level 2 or level 3 ratio,post -operative corrected TIMI frame count of the observation group were significantly higher than the control group (χ2 /t =4.11,4.85,5.87, all P <0.05).1 h after PCI treatment,the number of cases of ST fully back,the added value of EF,plague index scores of observation group were 53 cases,(8.02 ±6.94)%,(0.41 ±0.28)respectively,which were significantly higher than those of the control group 36 cases,(5.87 ±6.54)%,(0.28 ±0.27)(χ2 /t =5.32,4.32,3.65,all P <0.05).Adverse events of the two groups had no significant difference (χ2 =0.52,P >0.05).Conclusion Compared with intravenous injection,tirofiban in the treatment of acute ST segment elevation myocardial infarction by intracoronary injection can improve the level of myocardial perfusion after PCI operation,promote the recovery of left ventricular function,and has high security.