Objective To investigate and assess the risk signals of adverse drug events(ADEs)associated with the post-marketing 4 long-acting anticholinergic antagonists(LAMA),including adionium bromide,glycopyrronium bromide,umeonium bromide,and tiotropium bromide,to provide references for clinically safe prescribing practices.Methods Four LAMA drugs-related ADE records were selected by searching the FAERS database from the first quarter of 2004 to the first quarter of 2024 and standardizing the drug name of adionium bromide,glycopyrronium bromide,umeonium bromide,and tiotropium bromide,with the primary suspected drug as a restriction.Potential ADE signals were mined using the reporting odds ratio(ROR)method,medicines and healthcare products regulatory agency(MHRA)method and Bayesian confidence propagation neural network(BCPNN)method,and Medical Dictionary for Drug Regulatory Activities 26.1 was used to classify the results systematically.Results A total of 80 680 reports of four LAMA drugs-related ADE were collected,including 4 287 reports for aclidinium bromide,3 584 reports for glycopyrronium bromide,3 084 reports for umeclidinium bromide and 69 725 reports for iotropium bromide.The reports predominantly involved female patients(47 725 cases,59.15％)over male patients(27 525 cases,34.11％).The United States emerged as the principal reporting country,with consumers,pharmacists,and physicians as the primary reporters.Serious ADE outcomes included life-threatening conditions,hospitalizations,disabilities,deaths.A total of 902 signals were identified,mainly affecting 27 systems or organs.Specifically,aclidinium bromide(180 signals),glycopyrronium bromide(210 signals),umeclidinium bromide(142 signals),and tiotropium bromide(370 signals)exhibited signals predominantly in the respiratory,thoracic and mediastinal disorders,investigations,injury,poisoning and procedural complications,eye and organ diseases cgastrointestinal disorders.Conclusion When using LAMA drugs for respiratory conditions,clinicians should implement preventive measures to monitor respiratory diseases,thoracic and mediastinal diseases,eye and organ changes and various laboratory examination indicators,to reduce the risk of medication.

Objective To investigate the effect of evodiamine(EVO)on retinal injury in diabetic rats by regulating the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)signaling pathway.Methods Totally 96 Sprague-Dawley rats(192 eyes)were divided into the negative control(NC)group,Model group,low-dose EVO(EVO-L)group,medium-dose EVO(EVO-M)group,high-dose EVO(EVO-H)group,calcium dobesilate(CD)group,SQ22536 group and EVO-H+SQ22536 group,with 12 rats in each group.Rats in the NC group were intraperitoneally injected with physiological saline instead of streptozotocin,and diabetic retinopathy models were established in all other groups.After successful mod-eling,the drug was administered once a day for 4 weeks.The blood glucose level of rats in each group was measured by blood glucose meter;HE staining was applied to detect the pathological changes of the retina of rats;TUNEL staining was adopted to detect the apoptosis of ganglion cells in the retina of rats;the levels of superoxide dismutase(SOD),malondial-dehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and cAMP in the retina of rats were detected;West-em blot was used to detect the protein expressions of Bcl-2 associated X protein(Bax),P53 and phosphorylated protein ki-nase A(p-PKA)in the retina of rats.Results Compared with the NC group,the pathological injury of the retina in the Model group was more serious;the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions increased,and the SOD,cAMP and p-PKA/PKA protein expression decreased,with statistically significant differences(all P＜0.05).Compared with the Model group,the pathological injury of the retina was relieved,the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions decreased,and the SOD,cAMP and p-PKA/PKA protein expression increased in the EVO-L group,EVO-M group,EVO-H group and CD group,with statistically significant differences(all P＜0.05).Compared with the Model group,the retinal tissue of the SQ22536 group was severely damaged,the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions increased,and the SOD,cAMP,p-PKA/PKA protein expression decreased,with statistically significant differences(all P＜0.05).Compared with the EVO-H group,the EVO-H+SQ22536 group showed more serious pathological injury of retinal tissue,increased blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions,and decreased SOD,cAMP and p-PKA/PKA protein expression,and the differences were statistically significant(all P＜0.05).Conclusion EVO may alleviate retinal injury in diabetic rats by activating the cAMP/PKA signaling pathway.

ObjectiveTo establish the identification method of Dalbergiae Odoriferae Lignum（DOL） and its counterfeits by nuclear magnetic resonance hydrogen spectrum（¹H-NMR） combined with multivariate statistical analysis. Method¹H-NMR spectra of DOL and its counterfeits were obtained by NMR， and the full composition information was established and transformed into a data matrix， and the detection conditions were as follows：taking dimethyl sulfoxide-d₆（DMSO-d₆） containing 0.03% tetramethylsilane（TMS） as the solvent， the constant temperature at 298 K（1 K=-272.15 ℃）， pulse interval of 1.00 s， spectrum width of 12 019.23 Hz， the scanning number of 16 times， and the sampling time of 1.08 s. Similarity examination and hierarchical cluster analysis（HCA） were performed on the data matrix of DOL and its counterfeits， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to analyze the data matrix and identify the differential components between them. In the established OPLS-DA category variable value model， the category variable value of DOL was set as 1， and the category variable value of the counterfeits was set as 0， and the threshold was set as ±0.3， in order to identify the commercially available DOL. The OPLS-DA score plot was used to determine the types of counterfeits in commercially available DOL， and it was verified by thin layer chromatography（TLC）. ResultThe results of similarity analysis and HCA showed that there was a significant difference between DOL and its counterfeits. OPLS-DA found that the differential component between DOL and its counterfeits was trans-nerolidol. The established category variable value model could successfully identify the authenticity of the commercially available DOL. The results of the OPLS-DA score plot showed that there were heartwood of Dalbergia pinnata and D. cochinchinensis in the commercially available DOL， and were consistent with the TLC verification results. ConclusionThere is a phenomenon that heartwood of D. pinnata and D. cochinchinensis are sold as DOL in the market. ¹H-NMR combined with multivariate statistical analysis can effectively distinguish DOL and its counterfeits， which can provide a reference for the identification of them.

ObjectiveTo analyze the migrating components absorbed into blood of the aqueous extract of Euphorbia helioscopia， and to explore the pharmacodynamic material basis of the aqueous extract of E. helioscopia against chronic obstructive pulmonary disease（COPD）. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detecte the migrating components absorbed into blood of rats after intragastric administration of aqueous extract of E. helioscopia. An Agilent RRHD SB-C₁₈ column（3 mm×100 mm， 1.8 μm） was used with 0.1% formic acid aqueous solution（A）-acetonitrile（B） as the mobile phase for gradient elution（0-15 min， 5%-30%B； 15-20 min， 30%-50%B； 20-30 min， 50%-95%B； 30-35 min， 95%-5%B）， and the detection wavelength of 190-800 nm， column temperature of 40 ℃， flow rate of 0.3 mL∙min^-1 and injection volume of 4 μL. The electrospray ionization（ESI） was used in positive and negative ion modes， and the detection range was m/z 50-1 250. Network pharmacology was used to screen out the key components and the key targets of COPD through the interaction analysis. Metascape database was used to predict the molecular function， biological process， cellular composition and signal pathways mainly involved in the anti-COPD effect of E. helioscopia. Molecular docking technique was used to determine the affinity of key targets with key components. ResultA total of 29 migrating components absorbed into blood of rats were identified after intragastric administration of aqueous extract of E. helioscopia， 9 of which were prototype components and 20 were metabolites. Network pharmacological analysis showed that luteolin， quercetin， apigenin， naringenin and helioscopinolide C were the key components of E. helioscopia against COPD， and vascular endothelial growth factor A（VEGFA）， albumin（ALB）， protein kinase B1（Akt1）， tumor necrosis factor（TNF） and interleukin-6（IL-6） were the key targets. Molecular docking results showed that one diterpene lactone（helioscopinolide C） and three flavonoids（naringenin， luteolin， apigenin） in the migrating components absorbed into blood all had strong binding activity to the key targets of E. helioscopia against COPD. ConclusionNaringenin， helioscopinolide C， luteolin and apigenin may be the main anti-COPD active substances of E. helioscopia.

【Objective】 To construct and validate a risk prediction model for cognitive impairment after stroke based on demographic, clinical, and neuroimaging characteristics. 【Methods】 Through the medical record system, we collected all data of the patients. We finished cognitive function testing three months after the indexed stroke. The Mini-Mental State Examination Scale score≤26 was defined as cognitive dysfunction. Optimal subset regression analysis was used to screen variables, Logistic regression analysis was used to construct a predictive model for cognitive impairment, and C-index, calibration chart and clinical decision curve analyses were used to evaluate the discrimination, consistency, and clinical availability of the model. And nomograms were used to express the performance of the model. 【Results】 Seven variables were selected: cognitive function before stroke, age, years of education, National Institutes of Health Stroke Scale score at admission, history of ischemic heart disease, the number of old lacunar infarct lesions, and medial temporal lobe atrophy scale. The prediction model had a C-index of 0.845 (95% CI: 0.805-0.885). The clinical decision curve showed that the model had a positive net benefit when the threshold probability was 9.0%-90.0%. 【Conclusion】 The predictive model of cognitive impairment in stroke patients has good predictive efficiency and provides an effective assessment tool for screening high-risk cases of cognitive impairment in patients with stroke of various subtypes.

Objective:Hepatocellular carcinoma(HCC)patients at the same stage exhibit different prognosis,and the underlying molecular mechanism remains unclear.This study aims to identify the key genes impacting the prognosis of HCC patients. Methods:Differentially expressed gene analyses were performed between HCC samples and normal ones,and between patients with long overall survival(OS)and those with short OS,in TCGA-LIHC and GSE14520 datasets.The Kaplan-Meier method with log-rank test was used to evaluate the role of secreted phosphoprotein 2(SPP2)in the prognosis of HCC patients.Gene set enrichment analysis(GSEA)was used to understand the difference of enriched signaling pathways between SPP2-stratified HCC subgroups.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed to predict the potential functional pathways in which SPP2 might participate. Results:SPP2 was significantly down-regulated in tumors when compared with normal tissues,or in tumor samples with short OS when compared with those with long OS[fold change(FC)>2 and false discovery rate(FDR)<0.05].Low expression of SPP2 was associated with worse clinicopathological features like vascular invasion(P=1.6e-05),poor cancer status(with tumor,P=0.021),advanced T stage(T3 or T4,P=4.5e-04),advanced TNM stage(stage Ⅲ or Ⅳ,P=3.1e-04),and with unfavorable prognosis(shorter OS,P= 0.002).Gene enrichment analyses revealed that SPP2 might involve in the metabolic homeostasis of HCC and in the development of liver fibrosis and cirrhosis. Conclusion:SPP2 might inhibit the development of liver fibrosis and cirrhosis and the tumorigenesis of HCC,and analogs of SPP2 might be potential drugs in the prevention of these diseases.

Objective:To evaluate the emergency iliosacral screw fixation assisted by TiRobot for unstable posterior pelvic ring fracture.Methods:The 26 patients with unstable pelvic fracture were analyzed retrospectively who had undergone emergency iliosacral screw fixation at Department of Orthopedics & Traumatology, Beijing Jishuitan Hospital from June 2018 to December 2020. They were divided into 2 groups depending on whether orthopaedic TiRobot was used to assist screw insertion. In the observation group of 14 cases subjected to TiRobot-assisted insertion of iliosacral screws, there were 10 males and 4 females with an age of (45.9 ± 10.1) years; in the control group of 12 cases subjected to conventional manual insertion of iliosacral screws, there were 9 males and 3 females with an age of (49.2 ± 11.3) years. All the surgeries were conducted within 24 hours after injury. The 2 groups were compared in terms of screw insertion time, pin insertion, intraoperative blood loss, fluoroscopy time, postoperative screw position, fracture reduction and Harris hip score at the final follow-up.Results:The 2 groups were comparable because there was no significant difference between them in their preoperative general clinical data or follow-up time ( P>0.05). The screw insertion time [(16.1 ± 3.4) min] and fluoroscopy time [(8.1 ± 3.3) s] in the observation group were significantly shorter than those in the control group [(26.4 ± 5.4) min and (25.2 ± 7.4) s], and the pin insertions [1 (1, 2) times] and intraoperative blood loss [(10.5 ± 6.4) mL] in the former were significantly less than those in the latter [6 (3, 8) times and (24.8 ± 6.7) mL] (all P<0.05). Postoperatively, the sacroiliac screw position was excellent in 18 cases and good in 2 in the observation group while excellent in 14 cases, good in 2 and poor in 2 in the control group; the fracture reduction was excellent in 12 cases, good in one and fair in one in the observation group while excellent in 10 cases, good in one and fair in one in the control group, showing insignificant differences in the above comparisons ( P>0.05). There was no significant difference either in the Harris hip score at the final follow-up between the 2 groups ( P>0.05). Conclusion:Compared with conventional manual insertion of iliosacral screws, emergency iliosacral screw fixation assisted by TiRobot can effectively decrease surgical time and reduce operative invasion due to a higher accuracy rate of screw insertion.

【Objective】 To investigate the main causes of blood donor deferral in domestic blood center. 【Methods】 The causes of donor deferral were classified into 12 categories as previous medical history, drug use, alcohol consumption, menstrual period, underweight, abnormal blood pressure, abnormal body temperature, abnormal hemoglobin (Hb), lipemic blood, positive hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) and others according to the comparison indicators of Asia-Pacific Blood Network (APBN) and the national standard Blood Donor Health Examination Requirements. The relevant data of the top 3 causes of donor deferral, voluntarily reported by the members of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions from 2014 to 2019, were collected and a histogram was generated. 【Results】 The median donor deferral rate of 20 domestic blood centers from 2014 to 2019 was 12.14%, with the lowest at 0.18% and highest at 32.32%, respectively. The top three causes for donor deferral were elevated ALT, abnormal Hb and abnormal blood pressure in year 2014, 2015, 2018 and 2019; elevated ALT, lipemic blood and abnormal blood pressure in 2016; elevated ALT, abnormal Hb, and lipemic blood in 2017. 【Conclusion】 The main causes of donor deferral were elevated ALT, abnormal Hb, abnormal blood pressure and lipemic blood.

【Objective】 To investigate the establishment of multi-center haemovigilance (HV) and the monitoring of adverse reactions to blood donation (ARBD), in order to provide basis for the management of blood donors. 【Methods】 The operation of HV was investigated by questionnaire. The total number of blood donations (including plateletpheresis) and ARBD cases occurred in each blood center from 2014 to 2018 were analyzed. 【Results】 Among the 24 blood centers in this survey, only nine got HV operated. The incidence of ARBD of 19 blood centers that fulfilled the questionnaire was in the range of (0.003~1.151) %. The change trend of number and incidence of ARBD cases were indeterminate. 【Conclusion】 Most blood centers did not got HV established. The incidence of ARBD varied greatly and was indeterminate. The application of HV should be further improved to strengthen ARBD management.

Objective:To understand the social support, social network, and sexual behavior characteristics of foreigners living in Guangzhou, analyze factors relating to aspects of online social interactions and sexual behaviors of foreigners in Guangzhou, and provide references for targeted HIV intervention services for foreigners.Methods:A cross-sectional survey (both online and offline), among those who met the inclusion criteria was conducted between November 2019 and January 2020. Data were collected on demographics, social support, online social interactions, sexual behaviors, and so on. Statistics were compiled to analyze the factors that may influence casual sexual behaviors.Results:A total of 434 participants were included in the study (241 offline and 193 online). The majority of the participants were male 68.4% (297/434), age (31.0±8.8) years old, African 79.0% (343/434), business people 46.5% (202/434), students 48.2% (209/434), who have business partners and family members in China were 59.4% (258/434) and 28.1% (122/434) separately. They also had the following features: less than 10 close friends 57.1% (248/434); spend 1-3 hours on social applications per day 43.3% (188/434), had casual sexual behaviors in the last 3 months 15.2% (55/363). Multiple logistic regression model analysis showed that compared with those who used social applications for less than 1 hour per day, participants who used social applications for more than 6 hours per day were more likely to have casual sexual behaviors in the last 3 months ( OR=3.63, 95% CI: 1.31-10.08). Conclusions:Participants who used social applications for a longer period every day were more likely to have casual sexual behaviors among foreigners in Guangzhou. Good use of social applications for health promotion and education of HIV can increase the health awareness of foreigners in China.