OBJECTIVE To re-evaluate the use of systematic evaluation/meta-analysis of anti-VEGF drugs in the treatment of diabetic macular oedema （DME）， aiming to provide evidence-based support for the clinical application of this medication. METHODS A comprehensive search was conducted across a range of databases， including CNKI， Wanfang data， VIP， CBM， PubMed， Web of Science， Embase， and Cochrane Library. The objective was to identify systematic evaluation/meta-analysis of anti- VEGF drugs for DME， with search time from the inception of the databases to March 2024. The report quality， methodological quality， and evidence quality were assessed by using PRISMA2020 statement， AMSTAR2 scale and GRADE tool. A comprehensive analysis of systematic evaluation/meta-analysis results was also conducted. RESULTS A total of 22 articles were included. According to the PRISMA2020 statement evaluation， 13 studies provided relatively complete information （≥21 points）， while 9 studies had information deficiencies （18-＜21 points）. The AMSTAR 2 scale evaluation revealed that 21 studies had very low methodological quality， and one study had low methodological quality. The GRADE tool evaluation showed that out of 89 outcome indicators， 28（ 31.46%） were classified as high-quality evidence， 34（ 38.20%） as moderate-quality evidence， 24（ 26.97%） as low- quality evidence， and 3 （3.37%） as very low-quality evidence. The comprehensive quality analysis results demonstrated that， compared with laser photocoagulation， anti-VEGF drugs significantly enhanced the improvement in best-corrected visual acuity （BCVA）， as well as significant change in retinal thickness at 1 and 6 months， and 1 and 2 years post-treatment， and also in BCVA and retinal thickness at 1， 3， and 6 months post-treatment （P＜0.05）. Compared with placebo， patients treated with anti-VEGF drugs showed significant improvement in BCVA after 1 year of treatment （P＜0.05）. However， when compared with corticosteroid drugs， patients treated with anti-VEGF drugs exhibited a significant increase in retinal thickness after 6 months of treatment （P＜0.05）. Compared with corticosteroid drugs， the incidence of adverse events related to the eyes， cataract formation and intraocular pressure were significantly decreased in patients treated with anti-VEGF drugs （P＜0.05）. Compared with laser photocoagulation， the incidence of ocular adverse events was significantly decreased in patients treated with anti-VEGF drugs， while the incidence of fatal adverse events was significantly increased （P＜0.05）. CONCLUSIONS Anti-VEGF therapy for DME may possess certain advantages in terms of efficacy and safety， but it is associated with a higher risk of fatal adverse events； the evidence included in systematic reviews/meta-analyses is of moderate to high quality.

Objective To optimize the process conditions and analyze the components of alkaloids from Zanthoxylum bungeanum Maxim（Z. bungeanum）using macroporous resin. Methods Combining single factor tests and orthogonal tests, the content of hydroxy-α-sanshool（HAS）and hydroxy-β-sanshool（HBS）were considered as indexes to determine the best process parameters. Ultra-performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E）was used to identify the structures of alkaloids. Results The optimal conditions were Mitsubishi HP-20 macroporous resin, the loading solution concentration was 0.2 g crude drug/ml, the ratio of crude drug to resin volume was 1 g∶2.5 ml, the diameter/height ratio of resin column was 1∶7, the dynamic adsorption flow rate was 4 times of bed volume（BV）per hour, and the adsorption time was 1 h. Impurities were removed by using 2 BV of 20% ethanol, 5 BV of 80% ethanol was used to elution, and the content of HAS and HBS was 4.71% and 1.02%, respectively. A total of 20 alkaloids were identified from Z. bungeanum. Conclusion This method was stable and feasible, obtaining high purity and various kinds of alkaloids, which could be used for the enrichment and purification of alkaloids from Z. bungeanum.

ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

The writing of pharmacist-managed clinics documents （hereinafter referred to as “outpatient medication record”） is a necessary part of pharmacist-managed clinics service. Outpatient medication record is an important carrier to reflect the quality of pharmacist-managed clinics service. The Chinese Hospital Association Pharmaceutical Specialized Committee was entrusted by the Pharmaceutical Administration Department of the National Health Commission to lead the formulation of the Guidelines for the Pharmacist-managed Clinics Service and Document Writing and Usage （Reference） （hereinafter referred to as Guidelines） according to the compilation method of group standards and the technical route of “documentation combing→framework establishment→draft writing→opinion collection→Guidelines formation”. The Guidelines standardizes the basic requirements of pharmacist-managed clinics record management and the basic content of record， and provides a general template and two specialized templates including pregnant and lactating pharmacist-managed clinics record template and cough and asthma pharmacist-managed clinics record template， which provides a reference for medical institutions to write pharmacist-managed clinics record. This paper introduces the formulation process of Guidelines and analyzes the key contents of Guidelines， which is helpful for the application practice of Guidelines and further improves the quality of pharmacist-managed clinics work.

Objective To analyze the changes in myocardial injury markers and cardiac function in patients with hypertrophic obstructive cardiomyopathy (HOCM) after Liwen surgery. Methods A retrospective analysis was conducted on the clinical data of HOCM patients who underwent Liwen surgery at the Department of Cardiac Surgery, Wuhan Asia Heart Hospital from December 2019 to April 2023, mainly including preoperative and postoperative dynamic follow-up laboratory test results and echocardiograms. Results A total of 42 patients were included, with 25 males and 17 females, aged (44.76±17.72) years, and a postoperative follow-up time of (15.02±6.97) months. The myocardial troponin level of the patients decreased from preoperative 0.03 (0.02, 0.06) ng/mL to postoperative 0.02 (0.01, 0.05) ng/mL (P=0.006), and the N-terminal pro-brain natriuretic peptide level decreased from preoperative 748.95 (337.40, 1600.75) ng/L to postoperative 367.15 (126.93, 1030.25) ng/L (P<0.001). After surgery, the left atrial diameter of the patients decreased from preoperative (4.18±0.57) cm to postoperative (3.93±0.55) cm (P=0.004), the end-diastolic interventricular septum thickness decreased from preoperative 2.25 (1.90, 2.75) cm to postoperative 1.70 (1.50, 1.90) cm (P<0.001), the left ventricular mass index decreased from preoperative 211.73 (172.28, 261.54) g/m2 to postoperative 156.78 (132.34, 191.36) g/m2 (P<0.001), the left ventricular weight decreased from preoperative 368.89 (292.34, 477.72) g to postoperative 266.62 (224.57, 326.04) g (P<0.001), the end-diastolic posterior wall thickness of the left ventricle decreased from preoperative 1.30 (1.20, 1.60) cm to postoperative 1.20 (1.18, 1.40) cm (P<0.001), the relative wall thickness decreased from preoperative 0.78 (0.78, 1.02) to postoperative 0.63 (0.56, 0.72) (P<0.001), the end-systolic inner diameter of the left ventricle increased from preoperative (2.91±0.50) cm to postoperative (3.19±0.53) cm (P=0.001), and the end-diastolic inner diameter of the left ventricle increased from preoperative (4.41±0.48) cm to postoperative (4.66±0.52) cm (P=0.005). The left ventricular outflow diameter increased from preoperative (1.28±0.46) cm to postoperative (1.57±0.32) cm (P=0.001), the left ventricular outflow pressure gradient decreased from preoperative 58.50 (40.75, 92.50) mm Hg to postoperative 11.50 (7.75, 20.50) mm Hg (P<0.001), the left ventricular ejection fraction increased from preoperative 60.00% (56.75%, 65.00%) to postoperative 63.00% (62.00%, 66.00%) (P=0.024), and the degree of systolic anterior motion of the mitral valve leaflets decreased (P＜0.001). Conclusion The cardiac function of patients with HOCM is improved after Liwen surgery, myocardial injury marker levels are decreased, cardiac reverse remodeling occurres, and the surgical outcome is good.

Aim To clarify the differential proteins of mammary tissues in Xihuang pills(XHP)against hy-perplasia of mammary glands(HMG)based on quanti-tative proteomics technology and validate them,and to explore the mechanism of action.Methods SD rats were randomly divided into blank group,model group and XHP group,with 10 rats in each group.Except for the blank group,estrogen and progesterone were injec-ted intramuscularly to establish a rat model of mamma-ry hyperplasia for 30 d.After XHP was administered for 14 d,the rats in each group were observed to have morphological changes in the apparent morphology of the mammary tissues,and pathological changes in the mammary tissues were stained with hematoxylin-eosin staining(HE),and the differentially expressed pro-teins(DEPs)in the groups were screened by quantita-tive proteomics technology and subjected to bioinforma-tics analysis,and Western blot to verify the key DEPs.Results Compared with the model group,the appar-ent pathological morphology of the XHP group was sig-nificantly improved,the diameter of the nipple height of the rats was significantly reduced(P＜0.01),and the degree of histopathology was significantly allevia-ted.Quantitative proteomics identified 4,299 DEPs in mammary tissue,and bioinformatics analysis of 14 DEPs with consistent changes between the XHP group and the blank group relative to the model group re-vealed that they were related to the regulation of mus-cular systemic processes,regulation of muscle contrac-tion,DNA replication,and pre-initiation of DNA repli-cation.Western blot results showed that,compared with the model group,rat mammary tissue of the XHP group showed significantly lower levels of ACLY and ALDOC protein expression levels were significantly re-duced and BIN1 protein expression levels were signifi-cantly increased(P＜0.01).Conclusions XHP may exert its anti-mammary hyperplasia effect through the regulation of BIN1,ACLY and ALDOC protein lev-els,the regulation of DNA replication,the regulation of pre-initiation of DNA replication and muscular sys-temic processes,and the regulation of muscle contrac-tion.

Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

Objective:To explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge.Methods:This study was a retrospective cohort study that included 268 children with bacterial meningitis who were discharged from the infectious medicine ward of Beijing Children′s Hospital from September 2018 to September 2023. The children were managed with a multidisciplinary collaborative comprehensive healthcare management model after discharge. Outpatient data at 1 month and 6, 12 and 24 months after discharge were collected, including (height, weight, body mass index, nutritional feeding status, hearing and vision screening results, Gesell developmental assessment results and intervention guidance services. The follow-up interval or frequency was dynamically adjusted or increased according to the child′s situation. The paired sample t-test and chi square test were applied to compare the differences in Gesell developmental quotient (DQ) and developmental delay rate between the first and last assessments to preliminarily explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge. Results:All the 268 children completed their first assessment one month after discharge, and 37 children were found to have abnormal physical growth, mainly obesity (28 children), and another 9 children were malnutrition. Nutritional intervention and feeding guidance services were provided to all the 37 children, and as of the last follow-up, 20 children′s physical growth evaluations had turned normal. A total of 188 children completed at least 2 developmental assessments, with an interval of (14.2±9.4) months between the first and last assessments (range: 3.1-49.5 months). The DQ values of in the energy region of adaptability, gross motor skills, fine motor skills, language, and personal social skills at the last assessment were significantly higher than those at the first assessment [(91.93±13.28) vs (80.73±15.96) points, (91.69±12.96) vs (78.31±16.58) points, (89.32±16.11) vs (80.68±15.63) points, (90.10±16.65) vs (82.04±18.43) points, (92.01±14.05) vs (77.82±17.42) points]; moreover, the rates of developmental delay in each energy region were significantly lower than those at the initial assessment (9.6% vs 35.1%, 9.6% vs 42.0%, 18.1% vs 33.0%, 13.3% vs 31.9%, 9.6% vs 42.0%) (all P<0.05). Among the 200 children who completed the hearing screening, 18 were found with hearing abnormalities, and 2 were diagnosed with hearing loss in the Otolaryngology Department. Among 217 children who completed vision screening, 23 had abnormalities, and 5 were diagnosed with ophthalmic abnormalities in Ophthalmology Department (2 with strabismus, 2 with refractive errors, and 1 with optic nerve injury). Two children were found to have autism-like behavior during monitoring, and were referred to a developmental behavior clinic to be diagnosed with autism spectrum disorder and were given early diagnosis and intervention guidance. Conclusion:The comprehensive healthcare management model for children with bacterial meningitis after discharge can integrate clinical and healthcare resources, which is beneficial for improving the prognosis and enhancing the quality of life for children with special health status.

Objective To investigate the correlation between genetic polymorphisms and the risk of rivaroxaban bleeding events in elderly patients with nonvalvular atrial fibrillation(NVAF).Meth-ods A total of 180 elderly NVAF patients treated with rivaroxaban in our department from June 2019 to June 2022 were enrolled,and after 1 year of follow-up,finally,167 patients were included,according to whether bleeding events occurred,they were divided into hemorrhage group(n=31)and control group(n=136).The clinical data and genetic polymorphism were compared between the two groups.Multivariate logistic regression was used to analyze the association between genet-ic polymorphisms and bleeding events in the patients after rivaroxaban treatment.Results Higher frequencies of CYP2C9*1,CYP2C9*3 and VKORC1-GG,but lower frequencies of CYP2C9*2,VKORC1-AA and VKORC1-AG were observed in the bleeding group than the control group(all P＜0.01).Multivariate logistic regression analysis showed that CYP2C9*1,CYP2C9*3 and VKORC1-GG were independent risk factors for bleeding events in elderly NVAF patients taking rivaroxaban(OR=1.880,95％CI:1.126-1.997,P=0.030;OR=1.432,95％CI:1.044-1.964,P=0.026;OR=2.176,95％CI:1.173-4.037,P=0.014),while,CYP2C9*2,VKORC1-AA and VKORC1-AG were protective factors for bleeding events in elderly NVAF patients taking rivar-oxaban.Conclusion Genetic polymorphisms of CYP2C9 and VKORC1 are significantly correlated with the risk of bleeding events in elderly NVAF patients taking rivaroxaban.And CYP2C9*1,CYP2C9*3 and VKORC1-GG genotypes are independent risk factors,while CYP2C9*2,VKORC1-AA and VKORC1-AG genotypes are protective factors.