OBJECTIVES: Genetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC. METHODS: A total of 31 patients with advanced NPC, who came from the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University/Hunan Provincial Cancer Hospital, were enrolled. All of the exons of 288 genes, introns of 38 genes and promoters or fusion breakpoint regions from the nasopharyngeal biopsy tissues before treatment were detected by the gene sequencing platform Illumina NextSeq CN500. The coding regions of 728 genes were carried out a high-depth sequencing of target region capture, and the 4 variant types of tumor genes (including point mutations, insertion deletions of small fragments, copy number variations, and currently known fusion genes) were detected. All of 31 patients received platinum-based induction chemotherapy combined with concurrent chemoradiotherapy and were followed up for a long time. RESULTS: The 3-year regional failure-free survival (RFFS) and disease-free survival (DFS) in patients with PI3K-Akt pathway mutation were significantly lower than those in unmutated patients (χ²=6.647, P<0.05). The 3-year RFFS and DFS in patients with mTOR pathway mutations were significantly lower than those in unmutated patients, and there was significant difference (χ²=5.570, P<0.05). The rate of complete response (CR) in patients with unmutated AMPK pathway was significantly higher than that in patients with mutation at 3 months after treatment (P<0.05), and the 3-year RFFS and DFS in patients with AMPK pathway mutation were significantly lower than those in unmutated patients (χ²=4.553, P<0.05). PI3K-Akt/mTOR/AMPK signaling pathway mutations and pre-treatment EB virus DNA copy numbers were independent prognostic factors for 3-year RFFS and DFS in patients with NPC (both P<0.05). CONCLUSIONS The NPC patients with PI3K-Akt/mTOR/AMPK signaling pathway mutation have poor prognosis, and the detection of PI3K-Akt, mTOR, AMPK driver genes and signaling pathways by next-generation sequencing is expected to provide new idea for basic research and targeted therapy of NPC.
AMP-Activated Protein Kinases/metabolism* ; DNA Copy Number Variations ; Humans ; Mutation ; Nasopharyngeal Carcinoma/genetics* ; Nasopharyngeal Neoplasms/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Prognosis ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Sirolimus ; TOR Serine-Threonine Kinases/metabolism*

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Percutaneous coronary intervention is an important method for the treatment of coronary heart disease. Postoperative dual antiplatelet therapy is an important prerequisite to ensure the safety of surgery. Antiplatelet therapy with clopidogrel still has a high risk of thrombosis, which may be related to CYP2C19 genotyping. Therefore, a brief review of the impact of CYP2C19 genotyping on clopidogrel hyperresponsiveness is made.

Objective:To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS).Methods:The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children′s Hospital from January 2011 to April 2019 were analyzed retrospectively.Results:A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases).Conclusions:MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.

Objective: To describe the clinical manifestations of central nerve system inflammatory demyelinating disease associated with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IDD) in children, and to explore the clinical characteristics of the children. Methods: The clinical and laboratory characteristics of the patients diagnosed in Beijing Children′s Hospital, Capital Medical University, from October 2016 to August 2018 were described, and the clinical data of the patients with unipolar and recurrent diseases were compared. Results: A total of 50 patients were included, among whom the ratio of male to female was 24:26, and the average age of onset was (6.7±3.1) years old (0.4-12.6 years old). There was no significant difference in the age of onset between boys and girls(t=0.712, P=0.480). The main symptoms included fever (31/50 cases), encephalopathy (26/50 cases) and optic neuritis (22/50 cases), etc.In the last follow-up, 26 patients (52.0%) had a monophasic course and 24 patients (48.0%) had a recurrent course.There were age differences in encephalopathy and ataxia in the first episode of [(5.7±2.8) years old vs.(8.1±3.0) years old, (5.0±2.5) years old vs. (7.7±3.0) years old](t=2.746, P=0.009; t=2.837, P=0.007). The average number of recurrence was (2.1±1.4) times (1-7 times), in which 17 cases (70.8%) of recurrence presented within 12 months and 20 cases (83.3%) of recurrence presented within 24 months after onset.Convulsion incidences of recurrent cases were 10 cases and 13 cases respectively in the first episode and recurrent courses, which were significantly higher than those of monophasic cases (4 cases, 4 cases)(χ²=7.912, P=0.005; χ²=8.365, P=0.004). All patients were sensitive to first-line immunotherapy.Seven patients with recu-rrence were treated with mycophenolatemofetil, and 17 patients with repeated first-line therapy.In the last follow-up, all patients were in remission and 2 patients had mild neurological dysfunction. Conclusions MOG-IDD can occur in childhood.Encephalopathy and optic neuritis are the most common symptoms.Encephalopathy and ataxia are more common in young children.Convulsions may indicate the course of recurrence.

Objective To investigate the feasibility of a novel molecular probe 99Tcm-3P4-RGD2 in evaluating arterial plaque stability after atorvastatin intervention in rabbits with SPECT/CT. Methods Eighteen male New Zealand rabbits were randomly divided into group A (stable plaque), group B (vulnerable plaque), and group C (vulnerable plaque with statin intervention). All rabbits were fed with high-fat food for 12 weeks. After high-fat feeding for two weeks, sham surgery was performed on group A. In the meantime, abdominal aorta injury was performed on group B and group C. After that, rabbits of group C were given oral atorvastatin (2.5 mg·kg-1·d-1). 99Tcm-3P4-RGD2 SPECT/CT imaging was performed on each group at the end of 4, 8 and 12 weeks. T/NT ratios were calculated. Animals were sacrificed at the end of 12 week after imaging studies. The abdominal aortas were collected, imaged with SPECT/CT, and evaluated by pathological HE staining and immunohistochemical analysis. MVD was calculated. Differences among 3 groups were analyzed using one-way analysis of variance. Results There was no significant radioactive uptake in the abdominal aortas of three groups on the 4th week′s imaging. The radioactive uptake in abdominal aortas increased slightly on the 8th week, with the highest radioactive uptake in group B. The radioactivity in abdominal aortas of the 3 groups maintained increasing on the 12th week, with T/NT ratios of 1.579±0.217, 1.873±0.226 and 1.524±0.237, respectively (F=8.984, P<0.05). In ex vivo abdominal aorta images, especially images of group B, radioactivity in lesion sites was higher than that in normal tissue. Accordingly, results of HE staining showed that artery plaques of group A and group C were grade Ⅱ and group B was grade Ⅳ. The MVD of group A, B and C was 8.17±1.17, 15.86±1.07 and 7.17±1.60, respectively (F=9036, P<0.05). Conclusion 99Tcm-3P4-RGD2 SPECT/CT imaging has a high sensitivity in the evaluation of arterial plaque stability after statin intervention in rabbits.

BACKGROUND: In alveolar cleft patients, the amount of bone stock after alveolar bone grafting is mostly measured and analyzed by two-dimensional imaging, which can result in a large error. OBJECTIVE: To evaluate the 6-month osteogenesis of alveolar bone graft in alveolar cleft patients using cone beam CT. METHODS:Alveolar bone grafting was performed in 25 patients with unilateral complete alveolar cleft. The patients were folowed up for 6 months after surgery and the osteogenesis of the bone graft was evaluated by CBCT. RESULTS AND CONCLUSION:After the surgery, the labial bone support was better than the palatal one. There were significant differences in the alveolar bone thickness of the cleft region and the normal region of the central incisor as wel as the alveolar bone thickness of the cleft region and the normal region of the canine tooth 0 mm distant to the alveolar crest. These findings indicate that the palatal bone support is less than the labial one, and the bone support of the central incisor is not satisfactory, which provide the basis for the tooth movement in the alveolar bone grafting and the orthodontics treatment.

Objective To investigate the prevalence and influencing factors of dysmenorrhea among female college students in Changchun city, so as to provide scientific basis for health promotion and effective preventive measurement. Methods Non-randomized convenience sampling and face to face interview were used to collect information from female college students aged between 17 and 25 years in 14 universities in Changchun. Chi-square test and logistic regression model were used to analyze influencing factors of dysmenorrhea. Results The average age of 1 071 subjects was 21.21 ± 1.83 years. The prevalence of dysmenorrhea was 86.55%. The proportion of mild dysmenorrhea among the subjects was 62.56%, followed by 33.01% with moderate dysmenorrhea and 4.43% with severe dysmenorrhea; 80.76% of subjects paid attention to keep warm in the daily life. Normal BMI, sleeping before 23 o'clock or between 23 to 24 o'clock, taking exercise frequently or everyday might be the protective factors of dysmenorrhea, and the OR values (95% CI) were respectively as 0.60 (0.37-0.97), 0.56 (0.37-0.84), 0.42 (0.22-0.78) and 0.63(0.42-0.97). Tension and the family history of dysmenorrhea might be the risk factors, and the OR values (95%CI) were respectively 1.63 (1.10-2.41), 4.84 (2.80-8.35). Conclusion The prevalence of dysmenorrhea is high among female college students. Lacking exercise, BMI less than 18.5 kg/m2, staying up late, tension and the family history of dysmenorrhea may be the influencing factors of dysmenorrhea among female college students.

OBJECTIVE:To provide reference for the further implementation of employment guidance for graduate students ma-joring in Chinese pharmacy. METHODS:According to literature analysis,questionnaires,field visits and other ways,the current status and problems of employment guidance for graduate students majoring in Chinese pharmacy were investigted and the employ ment guidance pattern for graduate students majoring in Chinese pharmacy was explored and constructed. RESULTS:Theone body and three wingsemployment guidance pattern centered by taxonomy guiding and establishment of employment guidance institu-tions,graduate tutor selection evaluation mechanism and employment services platform were established. CONCLUSIONS:The em-ployment guidance pattern for graduate students majoring Chinese pharmacy established by the institute has great significance for im-plementing the work.

Objective To investigate the value of 99Tcm-Duramycin SPCET/CT in the detection of vulnerable plaque (VP) in atherosclerotic (AS) rabbit models.Methods Sixteen New Zealand male rabbits were randomly divided into three groups:group A (sham-operated group,n =4),group B (stable plaque group,n =4) and group C (VP group,n =8).Group A was fed on normal diet,and the other 2groups were fed on cholesterol diet for 12 weeks.Femoral artery dissection sham-operation was done in group A and group B,while balloon-induced abdominal aorta wall injury was produced in group C after 2 weeks'feeding.Animals were injected with 99Tcm-Duramycin (74 MBq/kg) and then SPECT/CT imaging was performed at the end of 4,8,and 12 weeks,respectively.Abdominal aortas were explanted for ex vivo imaging and histological characterization of plaque.The apoptosis index (AI) was calculated.One-way analysis of variance was used to analyze data.Results There was no radioactive uptake by the abdominal aorta in each group at the end of 4 weeks and no uptake in group A and group B at the end of 8 weeks.There was slightly uptake radioactive uptake by the abdominal aorta in group B at the end of 12 weeks and in group C at the end of 8 weeks.There was intense uptake at the lesions of AS rabbits in group C at the end of 12 weeks,and the T/NT value significantly higher than that of the other two groups (3.40±0.22 vs 2.12±0.65,2.68±0.18,F=198.775,P＜0.05).The result was confirmed in the ex vivo imaging of the explanted aorta.The AI of group C was significantly higher than that of group A and B ((25.4±6.32) ％ vs (0±0.02)％,(5.3± 1.97)％,F=70.260,P＜0.05).Conclusions 99Tcm-Duramycin scimigraphy could identify the apoptosis of VP in the rabbit AS models.It is a promising non-invasive method to diagnose AS plaques.