Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

Objective:To evaluate the feasibility of using the Chinese version of Addenbrooke's cognitive examination ver-sion Ⅲ(ACE-Ⅲ)on cognitive assessment in patients with cerebellar infarction. Method:Forty patients with isolated cerebellar infarction were collected in the department of neurology,Bei-jing Tiantan Hospital,along with 40 healthy controls were recruited matched by age and education.The clini-cal demographics was collected and the severity of ataxia and balance dysfunction was assessed.ACE-Ⅲ was used to evaluate cognitive function.The Cronbach's alpha and receiver operating characteristic(ROC)curve were used to assess the reliability and validity of ACE-Ⅲ respectively.Furthermore,the correlation of ACE-Ⅲtotal score with age and education was examined by spearman analysis. Result:The total score of ACE-Ⅲ in patients'group and healthy controls was 88.3±6.0 and 93.1±3.0 respec-tively,showing a significant different(P＜0.001).Compared with healthy group,patients with cerebellar infarc-tion had lower performance in attention(P＜0.001),language fluency(P＜0.001)and visuo-spatial function(P=0.001).The overall Cronbach's alpha of ACE-Ⅲ was 0.58,and the area under curve was 0.79±0.05(95％con-fidence interval:0.69-0.89).According to Youden index,the optimal cut-off for ACE-Ⅲ was 88.Further-more,spearman analysis showed cognitive function was significant negative associated with age in patients'group(r=-0.52,P＜0.0001)and healthy controls(r=-0.67,P＜0.001),and was significant positive associated with education in patients'group(r=0.74,P＜0.01)and healthy controls(r=0.72,P＜0.0001) Conclusion:ACE-Ⅲ scale is a good tool to detect cognitive dysfunction in patients with isolated cerebellar in-farction.The total score of ACE-Ⅲ is associated with age and educational attainment.

Objective: To evaluate the effect of parametrial status on FIGO stage IIIC1 cervical cancer. Methods: A retrospective study was conducted from June 1, 2009, to December 31, 2018.Patients with stage IIIC1 cervical cancer were included and stratified into two groups based on the status of parametrial involvement. Patients with IIIA or IIIB were selected as control. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Results: Of 586 patients included, 377 patients were stage IIIC1 (group A) and 209 patients were stage IIIA/IIIB (group B). Compared control, stage IIIC1 was not associated with worse 5-year OS or PFS. Of the stage IIIC1 patients, 58.1% without parametrial involvement (group A1) and 41.9% with parametrial involvement (group A2). Patients of group A1 showed a better prognosis than group A2 both in 5-year rates of OS (79.09% vs. 59.43%, p<0.001) and PFS (73.27% vs. 56.95%, p=0.0002). However, patients of group A1 showed a better prognosis than group B both in OS and PFS. Also, patients of group A2 showed a comparable prognosis to group B both in OS and PFS. Conclusion Reclassification of stage IIIC1 cervical cancer without parametrial into a new stage is more appropriate and improves discriminatory ability.

BACKGROUND: Pathological cardiac hypertrophy is one of the main activators of heart failure. Currently, no drug can completely reverse or inhibit the development of pathological cardiac hypertrophy. To this end, we proposed a silicate ion therapy based on extract derived from calcium silicate (CS) bioceramics for the treatment of angiotensin II (Ang II) induced cardiac hypertrophy. METHODS: In this study, the Ang II induced cardiac hypertrophy mouse model was established, and the silicate ion extract was injected to mice intravenously. The cardiac function was evaluated by using a high-resolution Vevo 3100 small animal ultrasound imaging system. Wheat germ Agglutinin, Fluo4-AM staining and immunofluorescent staining was conducted to assess the cardiac hypertrophy, intracellular calcium and angiogenesis of heart tissue, respectively. RESULTS: The in vitro results showed that silicate ions could inhibit the cell size of cardiomyocytes, reduce cardiac hypertrophic gene expression, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and b-myosin heavy chain (b-MHC), decrease the content of intracellular calcium induced by Ang II. In vivo experiments in mice confirmed that intravenous injection of silicate ions could remarkably inhibit the cardiac hypertrophy and promote the formation of capillaries, further alleviating Ang II-induced cardiac function disorder. CONCLUSION This study demonstrated that the released silicate ions from CS possessed potential value as a novel therapeutic strategy of pathological cardiac hypertrophy, which provided a new insight for clinical trials.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To explore the clinical features of bloodstream infections (BSI) in children with acute myeloid leukemia (AML) during the first induction chemotherapy.Methods:The clinical data, pathogen of BSI, antibiotic susceptibility in vitro, complications and prognosis of 204 newly diagnosed AML children admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2009 to December 2015 were analyzed retrospectively. χ 2 test was used for the comparison between groups and Logistic regression was used for BSI risk factor analysis. Results:Among 204 patients, 116 were males and 88 were females. The age was 8 (ranged from 1 to 14) years. Among them, 170 patients received MAE chemotherapies (etoposide, mitoxantrone and cytarabine) and 25 received IAE chemotherapies (etoposide, idarubicin and cytarabine). The other 9 patients used granulocyte colony stimulating factor (G-CSF)-priming regimen (aclacinomycin or homoharringtonine, cytarabine and G-CSF) for induction treatments. A total of 28 patients experienced BSI and the incidence rate was 13.7% (28/204), 26 of them developed BSI once and 2 patients developed twice. Gram-positive bacteria were predominant pathogens accounting for 53.3% (16/30) while gram-negative bacteria accounting for 40.0% (12/30) and fungal accounted for 6.7% (2/30). The most common detected pathogens were Coagulase negative Staphylococcus (CoNS, 26.7% (8/30)), followed by Streptococcus spp. (13.3% (4/30)) and Escherichia coli (13.3% (4/30)). Among Gram-negative bacteria (GNB), 3 cases showed carbapenem resistance and 2 cases were Stenotrophomonas maltophilia. BSI-related mortality was 28.6% (8/28). Infections caused by drug-resistant GNB or fungi resulted in 6 fatal cases. The incidence rate of BSI in group with severe neutropenia was higher than in group without it (16.6% (25/151) vs. 5.7% (3/53), χ2=3.933, P=0.047). Multivariable analysis showed severe neutropenia at the onset of fever was independent risk factor of BSI ( OR=4.258,95% CI 1.097-16.524, P=0.036). Conclusions:During the first induction chemotherapy courses, Gram-positive bacteria cause most of the BSI. Drug-resistant bacteria related infection often result in fatal outcomes. Severe neutropenia is a significant risk factor.

Objective:To investigate the current status of family resilience of children with acute leukemia and explore its influencing factors.Methods:Using the convenient sampling method, the families of children with acute leukemia who were admitted to 2 wards of Department of Hematology and Oncology of a Children's Hospital in Zhengzhou from April to August 2019 were selected as the research objects. The survey was conducted using the general information questionnaire, the Chinese-Family Resilience Assessment Scale (C-FRAS) and Chinese version of Posttraumatic Growth Inventory (PTGI) . A total of 220 questionnaires were issued, 207 of which were valid, with an effective recovery rate of 94.1%.Results:The total score of C-FRAS of main caregivers of 207 children with acute leukemia was (122.86±13.97) , the total score of Chinese version of PTGI was (65.31±14.82) . The total score of C-FRAS was positively correlated with the total score of Chinese version of PTGI ( P<0.05) . Multiple linear regression analysis showed that treatment time, the relationship with the children, whether there was social assistance, whether there was only one child, and the posttraumatic growth of the main caregiver were the influencing factors of the family resilience of children with acute leukemia ( P<0.05) . Conclusions:The family resilience of children with acute leukemia is at a moderate level, and the posttraumatic growth of the main caregiver of the children is at a moderate to upper level. The treatment time, the relationship with the children, whether there is social assistance, whether there is only one childand the post-traumatic growth of the main caregiver are the influencing factors of the family resilience of children with acute leukemia. In the process of clinical nursing, the family advantage can be promoted by improving the post-traumatic growth level of the main caregivers and help the families of the children to adapt well.

OBJECTIVE:To investigate the compatible stability of cefpirome sulfate with ornidazole. METHODS:At room temperature [(20±1)℃],the appearances(color,clarity,sedimentation and gas)and pH changes of the mixtures by Cefpirome sulfate for injection with Ornidazole for injection in 0.9% Sodium chloride injection and 5% Glucose injection after 0,1,2,4,6 h were observed. RP-HPLC was adopted to determine its content changes. RESULTS:No significant change was noted for the mix-ture in appearance within 6 h,pH value ranged in 3.359-3.588;compared with the beginning(0 h),the contents of cefpirome sul-fate and ornidazole ranged in 100.2%-100.3%,99.9%-100.4% in 0.9% Sodium chloride injection at each time point,as well as 99.7%-99.9%,99.4%-99.6%in 5%Glucose injection. CONCLUSIONS:At room temperature,cefpirome sulfate mixed with orni-dazole show stable appearance,pH value and content in 0.9%Sodium chloride injection and 5%Glucose injection within 6 h.

Objective To investigate the clinical efficacy of trimebutine combined with Xiangsha Pingwei in the treatment of functional dyspepsia and its effect on gastrointestinal hormone.Methods One hundred and twenty cases of functional dyspepsia were randomly divided into the control group and observation group,60 cases in each group.The control group was treated with trimebutine 0.2 g,3 times/d and the observation group was treated with trimebutine 0.2 g,3 times/d and Xiangsha Pingwei 10 g,2 times/d.Both groups were treated for four weeks,a course of treatment.Clinical efficacy and the influence on gastrointestinal hormone levels were compared between the two groups.Results The symptoms scores in both groups all decreased significantly after treatment.While the postprandial fullness scores,early satiety scores and epigastric pain scores in the observation group were significantly lower than those in the control group (0.62±0.12 vs.1.85±0.25,0.56±0.14 vs.1.46±0.21,0.48±0.15 vs.1.32±0.12,t=34.36,27.62,33.87,P<0.05).The total effective rate in the observation group was significantly higher than that in the control group (90.00% vs.73.33%,χ2=5.57,P<0.05).MOT and GAS levels in both groups increased significantly.While MOT and GAS levels in the observation group were significantly higher than those in the control group (MOT: (355.2±78.1) ng/L vs.(288.7±82.4) ng/L;GAS:(96.5±17.6) ng/L vs.(88.4±16.0) ng/L,t=4.54,2.64,P<0.05).The somatostatin (SS) level in both groups decreased significantly.While the SS level in the observation group was significantly lower than that in the control group ((41.1±11.1) ng/L vs.(48.9±12.9) ng/L,t=3.55,P<0.05).Conclusion Trimebutine combined with Xiangsha Pingwei can significantly improve the clinical symptoms and gastrointestinal hormone in patients with functional dyspepsia.