OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

AIM: To establish a ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determination the plasma concentration of clozapine and compare the bioequivalence of a generic clozapine tablet with Clozaril

Objective:To explore the genetic causes of cerebellar hypoplasia (CH) diagnosed by prenatal ultrasound.Methods:This retrospective study involved 32 fetuses with CH diagnosed by prenatal ultrasound in Wuxi Maternal and Child Health Hospital from January 2014 to December 2022. Prenatal ultrasound findings and genetic testing results for amniotic fluid were collected and analyzed. The correlation between fetal CH and genetic abnormality was analyzed. A descriptive statistical method was used for data analysis.Results:(1) General data: The 32 mothers were (28.0±4.9) years old, ranging from 18 to 37 years old; the gestational age at amniocentesis was (24.2±4.0) weeks, ranging from 18 +3 weeks to 37 +2 weeks. Apart from one case lost to follow-up, the other 31 cases terminated the pregnancies, including 30 terminated before 28 weeks of gestation and one at 33 weeks of gestation due to unmarried status. (2) Ultrasonic features: Among the 32 cases, 30(93.8%) were complicated by intracranial or extracranial abnormalities including cardiac abnormalities (15 cases), dilated lateral ventricles (ten cases), and abnormalities in limbs (eight cases) and face (nine cases). Two CH cases (6.2%) were isolated. (3) Genetic testing: Among the 32 cases, 13 cases (40.6%) had normal results of amniotic fluid karyotype analysis and single nucleotide polymorphism (SNP) array. Among the 19 cases with abnormal amniotic fluid test results (59.4%), 16 cases have abnormal results in amniotic fluid karyotype analysis and SNP array detection [nine cases were numerical abnormalities, including five cases of trisomy-18, three of trisomy-21, and one of trisomy-13; seven cases were chromosomal structural abnormalities, including four cases of terminal deletion of chromosome 5 (Cri-du-Chat syndrome) and three cases of reciprocal translocation of chromosomes]. There was no abnormality in karyotype analysis of amniotic fluid in three cases. Still, their SNP array test results showed copy number variations (CNV) [one of 6q terminal deletion, one of 6q terminal deletion with 5p15.33 duplication, and one of 6q terminal deletion with 15q26.3 duplication; all variations were of unknown significance]. (4) Of the 19 cases with abnormal SNP array results, 17 were accompanied by abnormal intracranial/extracranial ultrasound findings. Among them, ten cases showed cardiac malformation, seven showed lateral ventricular widening, and seven showed limb abnormality. Conclusions:Numerical abnormalities, CDCS, and 6q terminal deletion are the most common genetic causes of CH diagnosed by prenatal ultrasound. Chromosome microarray analysis should be recommended for fetuses with ultrasound-diagnosed CH to evaluate fetal prognosis accurately.

At present, the teaching objects of clinical pharmacists have gradually changed from merely university students to complex and diverse groups including clinical pharmacist interns and others. However, the traditional teaching model cannot be tailored to different groups. In addition, it increases the burden of clinical pharmacists while not ensuring teaching quality. This study aims to classify teaching objects according to their characteristics, so as to provide individualized knowledge and service. Compared with the traditional way of teaching, this new method may make teaching more relevant and reduces the teaching load of teachers, which is of great significance to the training of clinical pharmacy personnel.

Objective : To explore whether the NLRP3 inflammasome is activated after Newcastle disease virus (NDV) exposure to esophageal cancer ECA109 cells , whether its activation is related to K + efflux , and the effect of ATP/P2X7 axis on the activation of NLRP3 inflammasome. Methods: The expression of NLRP3 and IL⁃1β was detected by Western blot; the content of IL⁃1β in the supernatant was detected by ELISA ; the formation of ASC spots was detected by fluorescence immunoassay; the change of intracellular K + concentration was detected by fluorescent probe technology; Interventions with ATPase , ATP and P2X7 receptor inhibitors were used to investigate their role in NLRP3 inflammasome activation. Results: Compared with the control group , the expression of NLRP3 , IL⁃1β and ASC protein in cells was up⁃regulated after NDV F3 infection ; the intracellular potassium concen tration decreased with the prolongation of infection time (P < 0. 05) . After the intervention of P2X7 receptor inhibitor, the efflux of intracellular K + was blocked. With the increase of inhibitor concentration , the efflux of K + was maximally inhibited at 10 μmol/L (P < 0. 05) . The results of ATPase and ATP intervention showed that ATPase inhibited K + efflux , while ATP promoted K + efflux. Western blot results showed that compared with the control group , P2X7 receptor was inhibited , and the expressions of NLRP3 and IL⁃1β were down⁃regulated ; after ATPase intervened cells , the expressions of NLRP3 and IL⁃1β decreased ; After ATP intervention in cells , the protein expressions of NLRP3 and IL⁃1β were up⁃regulated (P < 0. 05) . Conclusion NDV F3 infection of ECA109 cells can activate the NLRP3 inflammasome , the mechanism may be related to the ATP/P2X7 axis.

Objective:To explore the effect and mechanism of microRNA (miRNA)-4320 on the proliferation and migration of gastric cancer MGC803 cells.Methods:Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-4320 in four gastric cancer cell lines(MGC803, HS-746T, SGC7901, BGC823) MGC803 cells were infected with recombinant lentivirus carrying miR-4320 interference fragments or blank lentivirus, and set as si-miR-4320 group and NC group. Thiazole blue colorimetry and Transwell small box experiment were used to detect the proliferation and migration of MGC803 cells after miR-4320 was down-regulated. The bioinformatics software RNAhybrid was used to predict the target gene of miR-4320. The targeting relationship between miR-4320 and target gene was verified by dual-luciferase reporter gene experiment. qRT-PCR and Western blot were used to detect the expression of miR-4320 target gene. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test or one-way ANOVA was used for comparison between groups. Results:The expression of miR-4320 in the four gastric cancer cell lines was significantly higher than that of normal gastric mucosal epithelial cells ( P<0.01). The expression of miR-4320 in MGC803 cells in the NC group and the si-miR-4320 group were 8.19±1.00 and 1.09±0.31, respectively. The miR-4320 interference fragment significantly reduced the expression of miR-4320 ( P<0.01). The absorbance of MGC803 cells in the si-miR-4320 group was significantly lower than that of the NC group ( P<0.05), and the migration ability was significantly lower than that of the NC group ( P<0.01). Suppressor of cytokine signaling1 ( SOCSI) is the target gene of miR-4320. Compared with the NC group, the SOCS1 gene expression in the si-miR-4320 group was significantly up-regulated ( P<0.01). Conclusions:The expression of miR-4320 is increased in gastric cancer cell lines. Down-regulating the expression of miR-4320 can inhibit the proliferation and migration of gastric cancer MGC803 cells by inducing the expression of SOCS1 gene.

Objective:To explore the effect of down-regulation of long non-coding RNA (lncRNA) CTB-191K22.5 on the proliferation and invasion of colorectal cancer SW480 cells and the molecular mechanism.Methods:The TCGA database was used to analyze the expression differences of CTB-191K22.5 in colorectal cancer tissues and normal tissues. The CTB-191K22.5 inhibitor (Anti-CTB-191K22.5) and negative inhibitor (Control) were transfected into colorectal cancer SW480 cells, denoted as Observation group and Control group, real-time quantitative polymerase chain reaction (qRT) -PCR) was used to evaluate the inhibitory effect. MTT method and Transwell chamber method were used to evaluate the proliferation and invasion of SW480 cells. Western blot was used to evaluate the protein levels of PI 3K/AKT/mTOR signaling pathway in SW480 cells. The bioinformatics software starBase v2.0 was used to predict the target genes of CTB-191K22.5. qRT-PCR was used to evaluate the expression of CTB-191K22.5 target gene in SW480 cells. Measurement data were expressed as Mean±SD, and t-test was used for comparison between two groups. Results:Compared with normal tissues, the expression of CTB-191K22.5 in colorectal cancer tissues was significantly increased ( P<0.01). The expression of CTB-191K22.5 in SW480 cells of the Control group and Observation group were 6.60±0.85 and 1.08±0.21, respectively. The expression level of CTB-191K22.5 decreased after transfection with Anti-CTB-191K22.5 ( P<0.01). Compared with the Control group, the SW480 cell proliferation ability of the Observation group decreased ( P<0.01). The invasion numbers of SW480 cells in the Control group and Observation group were (135.4 ± 16.29) and (42.24±14.59), respectively. The invasion ability of SW480 cells decreased after transfection with Anti-CTB-191K22.5 ( P<0.01). Compared with the Control group, the expression levels of PI 3K/AKT/mTOR signaling pathway protein in SW480 cells in the Observation group decreased. miR-326 may be the target gene of CTB-191K22.5. Compared with the Control group, transfection with Anti-CTB-191K22.5 significantly increased the expression level of miR-326 in SW480 cells ( P<0.01). Conclusion:CTB-191K22.5 is highly expressed in colorectal cancer tissues, and down-regulation of CTB-191K22.5 may inhibit the proliferation and invasion of colorectal cancer SW480 cells by targeting miR-326.

OBJECTIVE：To overview the systematic review on the effectiveness of indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis （PEP），and to provide reliable evidence-based reference for the prevention of PEP. METHODS ：Retrieved from PubMed ，the Cochrane Library ，Embase，CBM，CNKI，Wanfang database and VIP，systematic review on indomethacin in the prevention of PEP were collected during the inception to Nov. 2020. The methodological quality ，report quality and evidence quality of the included studies were evaluated by AMSTAR 2 scale，PRISMA statement and GRADE method. The effectiveness of PEP prevention was described. RESULTS ：Finally，23 systematic reviews were obtained ，including 12 in Chinese and 11 in English. Tweenty-two systematic reviews showed that compared with placebo ， indomethacin could effectively reduce the incidence of PEP. Eight systematic reviews showed that indomethacin significantly reduced the incidence of moderate and severe PEP compared with placebo. Five systematic reviews showed that indomethacin could reduce the incidence of postoperative hyperamylasemia compared with placebo. Three systematic reviews showed that indomethacin also had a good preventive effect on people with high risk of PEP. PRISMA score of included systematic reviews ranged from 15 to 25. The quality evaluation of AMSTAR 2 methodology included in systematic reviews was low ，and the key items of complete report were 4，9，11 and 13. The GRADE evidence quality evaluation of the included systematic reviews showed that the quality of the evidence was concentrated in the low level. CONCLUSIONS ：Indomethacin has a certain effect in the prevention of PEP ，but the overall evidence quality of the included literatures is generally not high. It needs to be further validated by high-quality clinical research.