Background and purpose:Exogenous bone morphogenetic protein 9(BMP9)inhibits the malignant progression of human breast cancer,but its expression is often abnormally low in breast cancer.In this study,we intended to explore the expression and role of epigenetically-modified histone lysine-specific demethylase 4A(KDM4A)in breast cancer,and to investigate the relationship between KDM4A and BMP9 and its possible regulatory mechanism.Methods:The expression of KDM4A in breast cancer and its relationship with BMP9 were analyzed by bioinformatics and verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Chromatin immunoprecipitation(ChIP)verified the regulatory role of KDM4A on BMP9,and RNA stability experiments and CHX protein stability experiments verified the effect of KDM4A in BMP9 expression.Exogenous recombinant MDA-MB-231 cells transfected with KDM4A small interfering RNA(siKDM4A)or infected with siBMP9 adenovirus(Ad-siBMP9)were constructed using RNA interference technology and adenoviruses knocking down BMP9,and the migratory and invasive abilities of the cells were detected by scratch healing assay and transwell assay,respectively.Results:Bioinformatics analysis showed that the expression of KDM4A was significantly higher in breast cancer than in normal tissues,and there was a negative correlation between the expression of KDM4A and that of BMP9 in breast cancer;RTFQ-PCR and Western blot showed that KDM4A was highly expressed in different breast cancer cell lines,and the knockdown of KDM4A significantly up-regulated BMP9.ChIP experiment confirmed that KDM4A could be significantly enriched in the promoter region of BMP9 gene,reducing its histone lysine 36 position instead of position 4 methyl status,thus silencing the expression of BMP9.RNA stability assay and CHX protein stability assay confirmed that KDM4A had no significant effect on the mRNA of BMP9,but could affect its protein degradation.After knocking down KDM4A,the migration and invasion abilities of breast cancer cells MDA-MB-231 were significantly inhibited,and this effect could be partially reversed by knocking down BMP9.Conclusion:KDM4A is highly expressed in breast cancer and breast cancer cell MDA-MB-231,and can silence its expression by down-regulating the level of histone methylation in the promoter region of the BMP9 gene,as well as affecting the stability of BMP9 at the protein level rather than at the level of mRNA,and promoting the migration and invasion of breast cancer.

Objective:To evaluate myocardial microcirculation perfusion with myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction after percutaneous coronary intervention (PCI), and to explore the prognostic value of different types of myocardial microcirculation perfusion.Methods:This is a prospective cohort study. Patients with acute myocardial infarction who underwent successful PCI in Nanfang Hospital of Southern Medical University and Kanghua Hospital of Dongguan City from October 2019 to June 2021 were selected. All the enrolled patients completed MCE examination within 72 hours after PCI. According to the examination results, the patients were divided into normal microcirculation perfusion group, delayed microcirculation perfusion group, and blocked microcirculation perfusion group. Adverse cardiovascular events including all-cause death, cardiovascular death, and angina re-hospitalization were followed up, and left ventricular ejection fraction (LVEF) review results were collected at six months to one year after surgery. Kaplan-Meier survival curve was used to investigate the difference in the incidence of adverse cardiovascular events in different myocardial perfusion groups, and Cox regression analysis was used to evaluate the effect of myocardial perfusion on adverse cardiovascular events.Results:A total of 113 patients with acute myocardial infarction were included, aged (56.3±11.5) years, with 88(78%) males. There were 31 cases in the normal microcirculation perfusion group, 43 cases in the delayed microcirculation perfusion group and 39 cases in the blocked microcirculation perfusion group. LVEF was reviewed in 49 patients, and LVEF in the delayed microcirculation perfusion group was significantly improved compared with baseline at follow-up ((63.3±1.2) % vs. (58.6±1.8) %, P=0.043), and there was no statistically significant difference between the other two groups (all P>0.05). The median follow-up time was 473 days, during follow-up period 30 adverse cardiovascular events occurred. Kaplan-Meier survival curve analysis showed that there was a statistically significant difference in the incidence of adverse cardiovascular events among the three groups ( Plog-rank=0.029). Cox regression analysis showed that abnormal microcirculation perfusion (defined as delayed and blocked microcirculation perfusion) was an independent predictor of adverse cardiovascular events in patients with acute myocardial infarction after PCI ( HR=1.90, 95% CI1.16-3.12, P=0.011). Conclusions:Microcirculatory perfusion decrease or lost is common in patients with acute myocardial infarction after PCI. Timely restoration of blood flow reconstruction can save heart function when microcirculatory perfusion decreases. Microcirculatory perfusion is a predictor of adverse cardiovascular events in patients with acute myocardial infarction, and patients with poor myocardial perfusion are more likely to experience adverse cardiovascular events.

Objective To explore the neuroprotective role of Rab10 gene in depression and the mechanism mediating its effect.Methods Forty-eight male SD rats were randomized into a control group and 3 chronic unpredictable mild stress(CUMS)groups(n=12).The rats in the latter 3 groups were subjected to injections of normal saline,an adeno-associated viral(AAV)vector,or a Rab10-overexpressing AAV vector in the lateral ventricle after CUMS modeling.The depressive behavioral changes of the rats were assessed using behavioral tests.The TargetScan database was used to predict the miRNA interacting with Rab10 and the binding sites.The interaction between miRNA-103-3p and Rab10 was investigated using dual-luciferase and radioimmunoprecipitation(RIP)assay.The effect of corticosterone treatment on PC12 cell viability was assessed with CCK-8 assay.In corticosterone-stimulated PC12 cells,the changes in BDNF,CREB,p62,Beclin-1,Wnt3a,Gsk3β,phosphorylated(p)-Gsk3β,and β-catenin protein expressions following transfection with the Rab10-overexpressing AAV vector and a miRNA-103-3p inhibitor,alone or in combination,were analyzed using qRT-PCR and Western blotting.Results Injection of Rab10-overexpressing AVV vector into the lateral ventricle significantly improved depressive behaviors of CUMS rats.The mRNA and proteins expression of Rab10 were significantly down-regulated in the hippocampus of CUMS rats and in corticosterone-stimulated PC12 cells.Bioinformatics analysis and the results of double luciferase and RIP experiments confirmed the targeting relationship between miRNA-103-3p and Rab10.In PC12 cells,overexpression of Rab10 or silencing miRNA-103-3p activated the Wnt/β-catenin signaling pathway,up-regulated the expressions of BDNF,CREB and Beclin-1,and down-regulated the expression of p62 protein;silencing Rab10 obviously blocked the effect of miRNA-103-3p inhibitor.Conclusion In mouse models of depression,miRNA-103-3p activates Wnt/β-catenin signaling via targeting rab10 to improve neural plasticity and promotes neural cell autophagy.

Objective To explore the neuroprotective role of Rab10 gene in depression and the mechanism mediating its effect.Methods Forty-eight male SD rats were randomized into a control group and 3 chronic unpredictable mild stress(CUMS)groups(n=12).The rats in the latter 3 groups were subjected to injections of normal saline,an adeno-associated viral(AAV)vector,or a Rab10-overexpressing AAV vector in the lateral ventricle after CUMS modeling.The depressive behavioral changes of the rats were assessed using behavioral tests.The TargetScan database was used to predict the miRNA interacting with Rab10 and the binding sites.The interaction between miRNA-103-3p and Rab10 was investigated using dual-luciferase and radioimmunoprecipitation(RIP)assay.The effect of corticosterone treatment on PC12 cell viability was assessed with CCK-8 assay.In corticosterone-stimulated PC12 cells,the changes in BDNF,CREB,p62,Beclin-1,Wnt3a,Gsk3β,phosphorylated(p)-Gsk3β,and β-catenin protein expressions following transfection with the Rab10-overexpressing AAV vector and a miRNA-103-3p inhibitor,alone or in combination,were analyzed using qRT-PCR and Western blotting.Results Injection of Rab10-overexpressing AVV vector into the lateral ventricle significantly improved depressive behaviors of CUMS rats.The mRNA and proteins expression of Rab10 were significantly down-regulated in the hippocampus of CUMS rats and in corticosterone-stimulated PC12 cells.Bioinformatics analysis and the results of double luciferase and RIP experiments confirmed the targeting relationship between miRNA-103-3p and Rab10.In PC12 cells,overexpression of Rab10 or silencing miRNA-103-3p activated the Wnt/β-catenin signaling pathway,up-regulated the expressions of BDNF,CREB and Beclin-1,and down-regulated the expression of p62 protein;silencing Rab10 obviously blocked the effect of miRNA-103-3p inhibitor.Conclusion In mouse models of depression,miRNA-103-3p activates Wnt/β-catenin signaling via targeting rab10 to improve neural plasticity and promotes neural cell autophagy.

Objective:To analyze the medication law of TCM oral prescriptions in the treatment of postherpetic neuralgia (PHN).Methods:The effective cases and clinical studies about TCM oral prescriptions in the treatment of PHN were retrieved from CNKI, Wanfang Data, VIP, and CBM from January 1, 2002 to December 31, 2021. The medication frequency and drug properties were counted through the Ancient and Modern Medical Record Cloud Platform, and correlation analysis, cluster analysis and complex network analysis were performed.Results:A total of 233 articles were included, involving 243 prescriptions and 191 kinds of Chinese materia medica. There were 20 kinds of Chinese materia medica with frequency >40, most of which have the efficacy of promoting blood circulation to remove blood stasis. The Chinese materia with heat-clearing and detoxifying efficacy were also often used. The properties were mainly warm, mild, slight cold, and cold, tastes were mainly bitter, pungent and sweet, and meridians were mainly liver, spleen and heart meridians. The association rule analysis was used to obtain 15 commonly used TCM groups. The commonly used Chinese materia medica could be clustered into 4 categories. The core prescription obtained by complex network analysis was Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Corydalis Rhizoma, Bupleuri Radix, Carthami Flos, Paeoniae Radix Alba, Persicae Semen, Chuanxiong Rhizoma, and Rehmanniae Radix.Conclusion:TCM oral prescriptions for the treatment of PHN put promoting blood circulation to remove blood stasis and activating meridians to stop pain in priority, taking into account the clearing heat, regulating qi and blood.

Objective:To compare the efficacy and safety of biologics versus methotrexate in the treatment of severe pediatric plaque psoriasis.Methods:A retrospective matched case-control study was carried out. Twenty children with severe plaque psoriasis from Beijing Children′s Hospital, Capital Medical University from June 2016 to November 2021 were included in this study, and the patients treated with biologics (adalimumab or secukinumab) were matched with those treated with methotrexate at a ratio of 1∶1 according to the psoriasis area and severity index (PASI) score and age. PASI, physician′s global assessment (PGA) , and body surface area (BSA) scores were assessed at weeks 4, 8 and 12 after the start of treatment, and adverse drug reactions were recorded. Statistical analysis was mainly carried out by using Mann-Whitney U test, Fisher′s exact test and generalized estimating equations. Results:At weeks 4 and 8, the proportions of patients achieving PASI75 and PASI90 were significantly higher in the biologics group (PASI75: 7/10, 10/10, PASI90: 5/10, 9/10, respectively) than in the methotrexate group (PASI75: 1/10, 5/10, PASI90: 0, 1/10, respectively; all P < 0.05) , while there was no significant difference between the biologics group and methotrexate group at week 12 (PASI75: 10/10 vs. 8/10, PASI90: 9/10 vs. 4/10, both P > 0.05) . There were no significant differences in the PASI, BSA or PGA scores between the two groups at baseline (all P > 0.05) , while the biologics group showed significantly decreased PASI and BSA scores at weeks 4, 8 and 12, and significantly decreased PGA score at week 8 compared with the methotrexate group (PASI: Z = 2.50, 3.56, 2.63, respectively; BSA: Z = 2.87, 3.57, 2.40, respectively; PGA: Z = 2.81; all P<0.05) . Analysis of changes over time showed that the PASI, PGA and BSA scores in the biologics group significantly decreased at weeks 4, 8 and 12 compared with those at baseline (all P<0.01) ; the PASI and PGA scores significantly decreased at weeks 8 and 12 compared with the corresponding scores at week 4 (all P<0.05) ; however, there were no significant differences in the PASI, PGA or BSA scores between week 12 and 8 (all P>0.05) . In the methotrexate group, the PASI, PGA and BSA scores at weeks 4, 8 and 12 were all significantly lower than the corresponding scores at the previous adjacent time points (all P<0.05) . There was no significant difference in the incidence of adverse reactions between the two groups ( P = 0.650) , and no serious adverse reactions occurred in either group. The main adverse reaction was infection in the biologics group, while infection and elevation of transaminase levels were common in the methotrexate group. Conclusion:Biologics and methotrexate were both effective and safe for the treatment of severe pediatricplaque psoriasis, and biologics facilitated rapider achievement of PASI75 and PASI90 compared with methotrexate.

Objective : To screen the target of helicid in the intervention of depression based on network pharmacol- ogy and molecular docking，and to study the effect of helicid on the expression level of related targets in hippocam- pus，prefrontal cortex，striatum and habenular nucleus of chronic unpredictable mild stress ( CUMS) rats． Methods : The target of helicid was predicted by SwissTargetPrediction database ，and the depression related targets were screened by GeneCards、DisGeNet、TTD and DRUGBANK databases ; the metascape platform was used for gene en- richment analysis ，and the " helicid-depression-pathway " network was constructed ; Autodock Vina was used for molecular docking research ; qRT-PCR was used to detect the effect of helicid on the mRNA expression of HTR1A， ADORA1 and ADORA2A in rat tissues. Results : The 81 helicid targets and 1 640 depression targets were ob- tained，including 40 intersecting targets ; the key targets were mainly enriched in cAMP signal pathway，PI3K-Akt signal pathway，MAPK signal pathway and so on ; the results of molecular docking showed that the binding activity of helicid with most targets was good ; helicid up-regulated the expression levels of HTR1A ，ADORA1 and ADORA2A mRNA in hippocampus，prefrontal cortex ，striatum and habenular nucleus of CUMS rats． Conclusion Helicid may act on cAMP，PI3K-Akt，MAPK and other signal pathways to intervene depression through HTR1A， ADORA1 and ADORA2A.

Objective:To compare the growth speed of pulmonary artery and left ventricle after the repair of tetralogy of Fallot(TOF) with valve-sparing and transannular patch.Methods:The clinical data of children with tetralogy of Fallot admitted to our hospital from January 2015 to October 2020 were reviewed. According to the way of relieving right ventricular outflow tract stenosis, they were divided into two groups: valve-sparing and transannular patch. Independent sample t test or non- parametric test was used to compare the pulmonary artery and left ventricular growth indexes before operation and at the last follow-up between the two groups. The paired t test was used to compare preoperative and postoperative indexes. Results:A total of 104 children with tetralogy of Fallot, including 58 males and 46 females, had surgery at a median age and weight of 6.7(4.1, 10.3) months and 7.0(5.8, 8.4) kg, respectively. The preoperative Nakata index, McGoon ratio, pulmonary artery Z-score, left ventricular end diastolic volume(LVEDV) index and Z-score in valve-sparing were higher than those in transannular patch( P=0.001, 0.000, 0.003, 0.000, 0.000). At the last follow-up, the Z-scores of pulmonary arteries in both groups were greater than those before operation( P=0.016, 0.000), the LVEDV Z-score in transannular patch was greater than that before surgery( P=0.000), while the LVEDV Z-score of valve-sparing was not significantly different from that before operation( P=0.581), there was no significant difference in pulmonary artery Z-score and LVEDV Z-score between two groups( P=0.468, 0.884). The difference between the last follow-up and preoperative of pulmonary artery Z-score and LVEDV Z-score in valve-sparing was smaller than that in transannular patch( P=0.000, 0.000). Conclusion:Compared with valve-sparing, the pulmonary artery and left ventricle grow faster in transannular patch during the early stage after TOF repair.

Objective    To summarize the experience and lessons of right ventricular decompression in children with pulmonary atresia and intact ventricular septum (PA/IVS) and to reflect on the strategies of right ventricular decompression. Methods    The clinical data of 12 children with PA/IVS who underwent right ventricular decompression in our hospital from March 2015 to December 2019 were reviewed retrospectively. There were 10 males and 2 females with a median age at the time of surgery was 5 d (range, 1-627 d). Correlation analysis between the pulmonary valve transvalvular pressure gradient and changes in Z score of tricuspid valves after decompression was performed. Results    One patient died of refractory hypoxemia due to circulatory shunt postoperatively and family members gave up treatment. There were 2 (16.67%) patients received postoperative intervention. The pulmonary transvalvular gradient after decompression was 31.95±21.75 mm Hg. Mild pulmonary regurgitation was found in 7 patients, moderate in 2 patients, and massive in 1 patient. The median time of mechanical ventilation was 30.50 h (range, 6.00-270.50 h), and the average duration of ICU stay was 164.06±87.74 h. The average postoperative follow-up time was 354.82±331.37 d. At the last follow-up, the average Z score of tricuspid valves was 1.32±0.71, the median pressure gradient between right ventricle and main pulmonary artery was 41.75 mm Hg (range, 21-146 mm Hg) and the average percutaneous oxygen saturation was 92.78%±3.73%. Two children underwent percutaneous balloon pulmonary valvoplasty at 6 and 10 months after surgery, respectively, with the rate of reintervention-free of 81.8%. There was no significant correlation between pulmonary transvalvular gradients after decompression and changes in Z score of tricuspid valves (r=–0.506, P=0.201). Conclusion    For children with PA/IVS, the simple pursuit of adequate decompression during right ventricular decompression may lead to  severe pulmonary dysfunction, increase the risk of ineffective circular shunt, and induce refractory hypoxemia. The staged decompression can ensure the safety and effectiveness for initial surgery and reduce the risk of postoperative death.

OBJECTIVE：To eva luate the anticoagulant effect of clinical pharmacist management in clinic. METHODS ：Retro- spective analysis was performed on medical records of 481 patients in anticoagulant clinic of Nanjing Drum Tower Hospital （herein- after referred as “our hospital ”）from Aug. 2019 to Jan. 2020. The general information （gender，age，patient grading ）of patients ， anticoagulant drug ，anticoagulant causes ，anticoagulant examination [prothrombin time ，international standardized ratio results （INR）]，warfarin dose ，NOACs usage and ADR were recorded. RESULTS ：Totally 481 patients visited anticoagulant clinic of our hospital for 1 587 times in total. The case number of primary ，secondary and tertiary patients were 401，547 and 639，respectively. 470 patients received warfarin ，and 11 patients received NOACs （including 6 cases of riva roxaban，5 cases of dabigatran etexi - . The valve replacement was the main cause of anticoagu - lation（65.28％），followed by atrial fibrillation （14.97％）， valve ring repairment （12.47％）. The main detection method NDYG2017012） of prothrombin time was POCT （83.44％）. Their average dose of warfarin was （3.03±1.28）mg. The average INR of outpa - tients receiving warfarin was 1.99±0.56，and time within treat - E-mail：xiaochongzi78@sina.com ment range （TTR）was 72.79％. The average INR of the first grade was 2.12±0.84 and the TTR was 44.33％；the average INR of the second grade was 1.95±0.52 and the TTR was 72.34％； the average INR of the third grade was 1.94±0.33 and the TTR was 90.42％. There were 102 cases（6.43％）of small bleeding ， and 2 cases（0.13％）of clinical related non major bleeding ；no major bleeding and thromboembolism was observed. CONCLU - SIONS：Clinical pharmacists of anticoagulant clinic in our hospital formulate scientific management and provide individualized con - sultation for patients through implementing hierarchical management of patients. Patients show mild symptoms and low incidence of adverse reactions ；the patients taking warfarin have higher TTR ；clinical pharmacist management has significant anticoagulant effect.