Cardiovascular diseases(CVDs) are a major cause of morbidity and mortality in the world.So far,there has been substantial progress toward understanding the pathophysiology and treatment of CVDs.There are multiple cell signaling cascades,some of which are beneficial or compensatory and others deleterious.The balance between these pathways determines the outcome as a diseased or non-diseased state.Protein phosphorylation,which is mediated by enzymes,called protein kinases,is a major mechanism for transducing external stimuli into intracellular signals.Electively targeting of signaling pathways using protein kinase inhibitors would have a potential advantage over receptor blockers.By now,there are types of protein kinase inhibitiors available for treating several diseases.The success of kinase inhibitors in cancer treatment has strongly supported application in the treatment of CVDs.Here,we will review several kinds of protein kinases as potential targets for CVDs and some difficulty in identifying a protein kinase as a putative therapeutic target for CVDs.

Objective To evaluate the diagnosis and treatment of intestinal neuronal dysplasia type B (IND) in childhood. MethodsForty-five patients underwent preoperative barium enema examination, 23 patients underwent electromanometry, and mucosal biopsy and immunohistochemical staining for S100 protein were performed in 17 cases. All 45 patients underwent resection of the invalid segment with coloproctostomy. Whole layer was sampled on several sites of the resected segment and examined by two independent pathologists. All patients were followed up from 3 months to 9 years (mean 4.6 years).ResultsTwenty eight patients were complicated with Hirschsprung′s disease, one patient with hypogangliosis, and isolated IND was diagnosed in the other 16 children. The narrowed distal segment with proximal dilatation was merely noted in 4 children with isolated IND. Internal sphincter relaxations were missing in 6 children with isolated IND. The indicative diagnosis might be merely gained in 7 patients by the mucosa biopsy. The correct diagnosis can be established by whole layer biopsy of the resected segment. Three children with enterocolitis after operation were cured by conservative treatment. One patient suffering from postoperative sluice syndrome underwent second resection. Postoperative continence was achived in all patients. ConclusionThe correct diagnosis of IND can be obtained by biopsy of whole layer, and resection of invalid bowel segment with coloproctostomy is the choice of therapy.

Objective To study the induction of imiquimod on interferon-gamma (IFN-γ) in the peripheral blood of patients with condyloma acuminatum. Methods Twenty-two adult patients with condyloma acuminatum and twenty health control were sequentially enrolled in this study. Serum levels of IFN-γmRNA were measured by realtime polymerase chain reaction in 22 cases with condyloma acuminatum before and after treatment with imiquimod for 8 weeks and 20 health control. Results The serum level of IFN-γ mRNA before treatment was significantly lower than that of health control (t = - 2.87, P = 0.0071). Expression of serum IFN-γmRNA in condyloma acuminatum was significantly increased after 8 weeks imiquimod treatment (t = - 2.51 ,P = 0.0159). The serum level of IFN-γmRNA had no significant difference compared with after treatment group and health control group (t = - 1. 07, P =0. 2922). Conclusion Imiquimod could increase the low expression of IFN-γ mRNA in patients with condyloma acuminatum.

Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality in the world. So far, there has been substantial progress toward understanding the pathophysiology and treatment of CVDs. There are multiple cell signaling cascades, some of which are beneficial or compensatory and others deleterious. The balance between these pathways determines the outcome as a diseased or non-diseased state. Protein phosphorylation, which is mediated by enzymes, called protein kinases, is a major mechanism for transducing external stimuli into intracellular signals. Electively targeting of signaling pathways using protein kinase inhibitors would have a potential advantage over receptor blockers. By now, there are types of protein kinase inhibitiors available for treating several diseases. The success of kinase inhibitors in cancer treatment has strongly supported application in the treatment of CVDs. Here, we will review several kinds of protein kinases as potential targets for CVDs and some difficulty in identifying a protein kinase as a putative therapeutic target for CVDs.

OBJECTIVE: To observe the physiological and biochemical effects of intermittent fasting combined with hunger-resistant food on mice, and to evaluate the safety and beneficial effects of this regimen. METHODS: One hundred and forty-four adult ICR mice were divided into 4 groups: standard feed AL group (ad libitum intake of standard feed), hunger-resistant food AL group (ad libitum intake of hunger-resistant food), standard feed IF group (feeding standard feed and fasting on alternate days), and hunger-resistant food IF group (feeding hunger-resistant food and fasting on alternate days). The experiment lasted for 4-8 weeks and all mice drank water freely. The quality of life, body weight, fasting blood glucose, serum lipid, blood routine test, liver and kidney functions as well as the viscera indexes were examined. RESULTS: Compared to the standard feed AL group, the caloric taking and the increment of body-weight were reduced (P<0.01), and the viscera indexes of the liver and kidney were elevated (P<0.05) in the hunger-resistant food AL group and the hunger-resistant food IF group, the values of fasting blood glucose were reduced in standard feed IF group and hunger-resistant food IF group (P<0.01), the value of triglycerides was reduced in hunger-resistant food IF group (P<0.05), while the quality of life, blood routine test as well as the liver and kidney functions were not obviously affected in the hunger-resistant food AL group, standard feed IF group and hunger-resistant food IF group. CONCLUSION: The regimen of intermittent fasting combined with hunger-resistant food is safe and beneficial to metabolic regulation, such as controlling body-weight and adjusting blood glucose and serum lipid. It is expected that development of this regimen will be helpful to the control of obesity and diabetes, etc.

Objective To screen down regulated genes and find down regulated novel genes in gastric cancer. Methods Genes mRNA expression were detected between gastric cancer and normal gastric mucous membrane of five patients using cDNA microarray. Genes mRNA expression signals on hybridization membranes were analysized with computer software. Down regulated genes in gastric cancer were screened. cDNA suppression subtraction library was established by counterpart normal gastric mucous membrane mRNA(Tester) subtracting gastric cancer tissues mRNA(Driver) of five patients. After identification of the subtraction library, positive clones choosen randomly were sequenced , and down regulated novel genes in gastric cancer were screened. Some of the genes were identified by RT PCR.Results Down regulated genes in gastric cancer consist of 60 genes including tumor suppressing genes, apoptosis related genes, DNA replication and transcript or translate related genes, cell cycle related genes, cell migration related genes, etc. Two unknown gene fragments in gastric cancer were cloned. Conclusions Sixty down regulated genes in gastric cancer are confirmed. They are involved in gastric tumorigenicity and metastasis. cDNA subtraction library of gastric cancer was constructed successfully. Two down regulated novel gene fragments in gastric cancer was found.

Objective To observe the effect of conditional knocking out (KO) vascular endothelial growth factor (VEGF) gene on the mouse model of oxygen induced retinopathy (OIR). Methods The conditional VEGF KO mice were generated using Cre-Loxp technology, resulting in the deletion of VEGF in a portion of Müller cells permanently in mouse retina. Cre positive was CKO mice, Cre negative was NKO mice. OIR was induced by keeping mice in 75% oxygen at postnatal 7 days (P7) to P12 and in room air from P12 to P17 (each 20 mice for CKO and NKO, respectively). The mice mortality was analyzed. At day P17, the percentage of retinal avascular area was calculated using retinal flat-mounting with fluorescence angiography, the number of vascular endothelial cell nucleus breaking through retinal inner limiting membrane was counted with hematoxylin eosin (HE) staining of retinal sections, and the expression of hypoxia-inducible factor-1α (HIF-1α) was detected by immunofluorescence analysis. Results During the development of OIR, the mortality rate of CKO mice (65.00%) was higher than that of NKO mice (30.00%) with the significant difference (x2=4.912, P=0.027). At day P17, all the mice retinas were harvested. The retinal fluorescence angiography displayed that the normal retinal vascularization of CKO mice was delayed, and large avascular areas were observed. Meanwhile, rare new vascular plexus was found in CKO mice and the thickness of whole retina decreased dramatically. In contrast, NKO mice developed larger area of normal retinal vascular network structure with higher blood vessel density and more new vascular plexus with obvious fluorescein leakage. The percentage of avascular area in CKO mice [(28.31±11.15)%] was higher than NKO mice [(16.82±7.23)%] with the significant difference (t=2.734,P=0.014). The HE staining of retinal sections indicated smaller counts of vascular endothelial cell nucleus breaking through retinal inner limiting membrane in CKO mice (26.10±6.37) when compared to NKO mice (28.80±7.59) , the difference was significant (t=2.437,P=0.016). The immunofluorescence analysis showed stronger expression of HIF-1α in CKO mice than NKO mice, which was mainly located in the retinal ganglion cell layer. Conclusions The local VEGF gene knockout partially inhibits retinal neovascularization in OIR mice. However, it also suppresses the normal retinal blood vascular development with a decrease of OIR mice survival ability.

Objective To assess the clinical results of crossing cannulated screw fixation for intra-articulsr calcaneal fractures.Methods A total of 65 patients (72 sides) were retrospectively studied from July 2012 to June 2015 by case-control study,including 63 males and two females at age range of 18-70 years [(45.7 ± 12.2) years].According to the Sanders classification,there were 49 fractures of type Ⅱ (25 type Ⅱa,17 type Ⅱb,7 type Ⅱc) and 23 fractures of type Ⅲ (12 type Ⅲab,6 type Ⅲac,5 type Ⅲ bc).The cases had been divided into two groups,namely,the crossing caunulated screw fixation group (CCSFG group,30 cases) and plate fixation group (PFG group,42 cases).The results were compared with regard of the hospitalization time,fracture reduction and union,AOFAS score system,and complications.The calcaneal shape was assessed by the length,width,height,Bhler angle and Gissane angle.The foot function was assessed by the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hind foot score system.Results All were followed up for 6-24 months [(15.2 ± 4.7)months],and presented fracture healing.The time of hospitalization was (10.2 ± 2.3)days (7-14 days) and (18.6 ±3.3)days (13-28 days) in CCSFG and PFG groups,respectively(P ＜0.05).At the first and final visits during follow-up,the changes in calcaneal width and B(o)hler angle of CCSFG group were smaller than that of PFG group (P ＜ 0.05).For Sanders Ⅱ type cases,the average AOFAS function scores in CCSFG and PFG groups were (89.3 ± 6.8) points and (90.1 ± 8.1) points,respectively (P ＞ 0.05).For Sanders type Ⅲ cases,the corresponding scores in CCSFG and PFG groups were (83.5 ± 10.8) points and (82.5 ±7.3)points,respectively (P ＞0.05).The complication rate in the CSFG and PFG groups was 20％ and 19％,respectively (P ＞ 0.05).Conclusions Compared with the plate fixation,the crossing cannulated screw fixation has advantages of less invasion,better stability,shorter hospitalization time,faster functional recovery and can be recommended as the first choice for mild to moderate comminuted calcaneal fractures.

Objective: To identify confounding factors associated with dental caries prevention, as the basis for the development of subsequent health management plan for dental caries prevention in young children. Methods: From June to September 2019, a questionnaire survey was conducted among parents of young children enrolled in five kindergartens in the district of Shanggang Steel Community, Pudong New District, Shanghai, using the convenience sampling method. The survey included basic demographic characteristics on parents and children, as well as information factor, motivation factor, behavioral skills, and caries prevention behavior. Results: Among 718 parents surveyed, the median information factor score was 8 (7, 9), the median personal motivation factor score was 20 (19, 20), the median social motivation factor score was 9 (8, 10), the median behavioral skills score was 25 (24, 25), and the median caries prevention behavior score was 7 (5, 8). Motivation factor was positively associated with behavioral skills, both information factor and behavioral skills were positively associated with dental caries prevention (P<0.05). Personal motivation factor had a direct influence factor of 0.80 on behavioral skills and an indirect influence factor of 0.15 on dental caries prevention behavior; behavioral skills and information factor had a direct influence factor of 0.19 and 0.26 respectively on dental caries prevention. Conclusion The finding suggest that in addition to oral hygiene information and education for parents of young children, mental support should be a key component of any community-based dental caries prevention program.

Objective To preliminarily explore the clinical features,treatment,and outcomes of moyamoya disease in the elderly.Methods The clinical data of the elderly patients with moyamoya disease (aged ＞ 60 years) admitted to the Department of Neurosurgery,the 307th Hospital of PLA from May 2007 to July 2016 were collected retrospectively.Their clinical features,imaging features,and surgical outcomes were analyzed.Results A total of 68 patients were enrolled,including 35 females (51.47％) and 33 males (48.53％).The ratio of male to female was 1:1.06.The age at the time of diagnosis of moyamoya disease was 62.82 ±3.08 years.Fifty-two patients (76.5％) had vascular risk factors.The most common clinical manifestation was cerebral ischemia (n =61,89.7％).Thirty of them (44.1％) presented as transient ischemic attack.The Suzuki staging of most patients was 4-6 (71.6％),12 patients (17.6％) complicated with posterior cerebral artery stenosis or occlusion.Thirty-one patients were treated with encephalo-duroarterio-synangiosis (EDAS).Among them,17 patients underwent bilateral surgery and 14 underwent unilateral surgery.The incidence of perioperative infarction or hemorrhage was 5.6％ (2 patients developed cerebral infarction and 1 patient developed cerebral hemorrhage);37 patients received conservative treatment.During the follow-up period,5 patients developed cerebral infarction (1 in the surgical treatment group and 4 in the conservative treatment group);there was no significant difference between the 2 groups.There were no significant differences in age,sex,vascular risk factor,clinical symptoms,and preoperative modified Rankin Scale (mRS) scores between the 2 groups.Cerebral angiography was performed 6-9 months after operation in the surgical treatment group.A total of 24 cerebral hemispheres were evaluated by Matsushima typing,of which 17 (70.8％) were excellent.During the follow-up period,the proportion of patients with clinical outcome excellent (the mRS score was 0) (Z =-5.268,P ＜ 0.00l) and clinical improvement (the mRS score was improved ≥ 1 compared to the baseline) (Z =-3.780,P ＜ 0.001) were significantly higher than the conservative treatment group.Conclusions The clinical symptoms of old patients with moyamoya disease were mainly cerebral ischemia.Most of them had vascular risk factors,and the imaging manifestations showed higher Suzuki staging.The perioperative risk of EDAS in the old patients with moyamoya disease was lower.It might be an effective method to prevent clinical symptoms progress and improve the outcomes.