Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.

In order to give full play to the important role of multi-disciplinary treatment (MDT) in oncology teaching in talent training and discipline development, an oncology teaching and research section has been established, the textbook Clinical Oncology has been compiled, excellent teaching workers in affiliated hospitals have been selected to form an MDT teaching team, and a multi-tutorial system has been established for the discipline related to specific tumor types. The multi-tutorial system of disciplines combines lecture-based learning (LBL) with case-based learning (CBL) and problem-based learning (PBL). Students are arranged to observe and participate in clinical MDT consultation during the inter-class practice, and compared with the traditional assessment form, MDT case discussion questions, review writing, classroom simulation of the MDT process and real participation in clinical MDT discussions are added. The questionnaire for students who participated in MDT teaching showed that more than 93% of the students believed that the MDT teaching model was helpful for systematically mastering the knowledge of the chapters they had learned and understanding the cutting-edge progress, improving learning initiative, thinking and problem-solving ability, clinical comprehensive analysis ability and teamwork spirit. The majority of students' expression skills [89%(169/190)] and literature review skills [79%(150/190)] were improved; 94%(178/190) of students expressed their willingness to accept this teaching method. The teaching practice experience of the Department of Oncology of Jilin University based on the MDT model helps to improve the teaching level of oncology.

ObjectiveTo find out the problems and deficiencies in colposcopy through the quality control of colposcopy in 19 hospitals in Zibo City， so as to put forward constructive opinions and suggestion to improve the accuracy and standardization of colposcopy by the doctors in local hospitals. MethodsA total of 21 hospitals with colposcopy examination in Zibo City were selected as the research object. The quality control standards were formulated and the case data in the early stage were evaluated. Two hospitals had less than 10 cases completed each year and no on-site quality control.A total of 19 hospitals had on-site quality control with the operation process of colposcopy instrument on site， the configuration of colposcopy， the proportion of colposcopy examination reagents used in the department of pathology， and the operation period of colposcopy examination， as well as the on-site observation report. The qualified rate of each hospital were counted and analyzed. ResultsThe quality control results of 19 hospitals showed that the qualifications and the clinical practice of obstetrics and gynecology for more than 3 years reached 100.00%. Those who complete more than 100 new diagnosis cases each year and those who have been trained for more than 3 months are gradually increasing. The pathological specimens met the needs and the positive predictive value of high-grade squamous intraepithelial lesion was significantly improved in the quality evaluation indicators of colposcopy （all P<0.05）.In the basic elements of the colposcopy report， there were statistically significant differences in 5 aspects：adequacy of the examination， the description of specific images， the interpretation of key images， the diagnosis of the colposcopy， and the post-examination processing through 2 colposcopy quality control comparisons （all P<0.05）. ConclusionThe overall level of colposcopy in Zibo City has been significantly improved through the comparison of the quality control results of two colposcopy. We can improve the quality of colposcopy effectively through regular quality control.

ObjectiveTo explore the differences of cognitive function in patients with treatment-resistant depression and drug-naive first-episode major depressive disorder， and to examine the relationship between severity of clinical symptoms and cognitive function， so as to provide references for prognosis improvement. MethodsFrom November 2016 to December 2019， 119 patients with drug-naive first-episode major depressive disorder and 82 patients with treatment-resistant depression in a hospital in Guangzhou were enrolled， meantime， another 71 healthy individuals recruited from the community were set as healthy control group. Clinical symptoms were assessed using Hamilton Depression Scale-17 item （HAMD-17） and Hamilton Anxiety Scale （HAMA）. Cognitive domains， including speed of processing， working memory， verbal learning and memory， and visual learning and memory were measured with the MATRICS Consensus Cognitive Battery （MCCB）. Multiple covariance analysis was used to compare the differences in cognitive function among three groups. Thereafter， partial correlation analysis was performed within patient groups to explore the relationship of HAMD-17/HAMA score with the four dimensions of MCCB. ResultsThe speed of processing， visual learning and memory scores of treatment-resistant depression group and drug-naive first-episode depression group were lower than those of healthy control group， and the working memory score of the treatment-resistant depression group was lower than that of the healthy control group， with statistical significance （P<0.05 or 0.01）. The speed of processing， visual learning and memory scores of treatment-resistant depression group were significantly lower than those of drug-naive first-episode depression group （P<0.05 or 0.01）. Partial correlation analysis within patient groups found that HAMD-17/HAMA total score had no correlation with the four dimensions of MCCB （P>0.05）. ConclusionCompared with drug-naive first-episode major depressive disorder patients and healthy controls， the impairments of speed of processing， visual learning and memory are more severe in patients with treatment-resistant depression. Moreover， the cognitive function impairment in patients with drug-naive first-episode major depressive disorder and treatment-resistant depression has no correlation with the severity of depressive and anxious symptoms.

Objective:To investigate the clinical features and prognosis of pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 (GAD65) antibody.Methods:Clinical data of 2 patients diagnosed as autoimmune encephalitis associated with anti-GAD65 antibody at Department of Neurology, Beijing Children′s Hospital in 2019 were analyzed retrospectively. A literature search with “anti-GAD65 antibody”“encephalitis”“epilepsy” or “cerebellar ataxia” as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to January 2020). The clinical features and prognosis of pediatric cases with complete clinical data were retrieved and summarized.Results:Two patients with positive anti-GAD65 antibody of serum and cerebrospinal fluid were both females. The onset age of case 1 was 57 months and her main clinical manifestations were fever and unconsciousness. The cranial magnetic resonance imaging (MRI) showed diffuse T2 weighted imaging (T2WI) abnormal signals, and the electroencephalogram (EEG) showed slow waves. The onset age of case 2 was 80 months and her main clinical manifestations of were recurrent focal seizures, memory loss, and headache. The MRI showed high T2WI signal in bilateral hippocampus, and the EEG showed abnormal discharge involving the temporal area. Both cases were treated with methylprednisolone and intravenous immunoglobulin, the short-term symptoms of them were both improved. They were followed up for 6 months and 1 year respectively, the case 1 recovered completely, and the case 2 still had focal seizures. Six English reports which included 6 cases were retrieved. Together with these 2 cases, a total of 8 cases were analyzed. The clinical symptoms included seizures (6 cases), memory loss (4 cases), loss of consciousness (3 cases), behavioral abnormalities (3 cases), cognitive impairment (2 cases), headache (2 cases), autonomic symptoms (1 case), ataxia (1 case), dysphagia (1 case), and aphasia (1 case). There were 5 cases with cranial MRI abnormalities in the acute phase or sub-acute phase, of whom 3 cases had the limbic system involvement, and 2 cases were mainly had extra limbic area involvement. Three cases had hippocampal atrophy or sclerosis during follow-up. All 8 patients were treated with immunotherapy. After immunotherapy, all patients had short-term improvement. Follow-up for 6 months to 6 years showed that 3 cases with extra limbic encephalitis improved to baseline levels, and 5 limbic encephalitis cases had poor outcomes, including 1 death and 4 cases still had focal epilepsy.Conclusions:Pediatric anti-GAD65 antibody associated autoimmune encephalitis is a rare but treatable disease, including limbic encephalitis and extra limbic encephalitis. The most common clinical manifestations are seizures and memory impairment. Early diagnosis and immunotherapy can improve the symptoms in a short time. But patients with limbic encephalitis often had refractory epilepsy in the chronic phase, and have a poor long-term outcome.

Objective:To establish an air-pouch bladder cancer (APBCa) model and investigate whether it could be a new animal model to evaluate the efficacy of intravesical therapy through chemotherapeutics and BCG instillation.Methods:Filtered sterile air was injected subcutaneously into the backs of BALB/c Nude mice to create a 2.5 cm×3.5 cm air pouch. After 24 hours, human bladder cancer cells EJ were seeded on the inner face of the pouch wall to establish APBCa of human cancer (H-APBCa). Gemcitabine instillation was used to investigate whether chemotherapy could inhibit tumor growth in the H-APBCa model, and Tunel staining was used to verify the apoptosis of tumor cells 20-day treatment. Filtered sterile air was injected subcutaneously into the backs of C57BL/6 mice to create a 2.5 cm×3.5 cm air pouch. After 24 hours, mice bladder cancer cells MB49 were seeded on the inner face of the pouch wall to establish APBCa with intact immunity (I-APBCa). BCG instillation was used to investigate whether BCG could inhibit tumor growth in the APBCa model. Immunofluorescence was used to verify the infiltration of immune cells after 20-day treatment.Results:H-APBCa and I-APBCa mice models could be established by immune deficiency and intact mice. At day 20, chemotherapeutic instillation therapy could inhibit tumor growth (781.02±241.02 vs. 1213.88±214.02 mm 3, P<0.05) by inducing tumor cell apoptosis with statistically significant differences (77.33±4.63 vs. 14.67±2.60, P<0.05). BCG instillation was able to inhibit tumor growth (645.02±156.63 vs. 948.84±221.76, P<0.05) by increasing CD80 + macrophage (49.67±7.57 vs. 16.33±5.69, P<0.05) and T cells in the tumor with statistically significant differences (18.00±3.46 vs. 4.67±1.45, P<0.05). Conclusions:APBCa model could evaluate the efficacy of drug instillation and was expected to be a new animal model for studying drug for intravesical therapy.

Objective:To investigate the clinical and laboratory characteristics of subacute sclerosing panencephalitis (SSPE).Methods:The clinical, laboratory and electroencephalogram (EEG) data of eight patients with SSPE who admitted to the Department of Neurology, Beijing Children's Hospital, Capital Medical University, from May 2014 to February 2019 were retrospectively analyzed and followed up.Results:Four of the patients were male and four were female, who aged from two years and seven months to 13 years and five months with a median onset age of five years and six months. All of the eight cases had disease onset with progressive mental and physical regression, then developed periodic myoclonic seizures at the course of 11 days to 11 months. Video EEG examinations showed persistent generalized periodic complex waves with long interval (3-20 s). The IgG titers of measles virus in blood and cerebrospinal fluid of all cases were significantly increased. There was no significant abnormality in blood/urine metabolism screening nor head magnetic resonance imaging for the first time. Five cases performed head magnetic resonance imaging again, in which two cases with deepening hemispheric sulcus, two cases with cerebral white matter signal abnormalities. Antiepileptic drugs, gamma globulin, adrenocortical hormone and antiviral drugs were used after diagnosis though all were ineffective. All patients presented progressive deterioration. During the follow-up period of three months to two years and seven months, four patients died, of which three patients died at the time of five months, one year and two months, two years and six months after onset respectively, and the other one was unknown.Conclusions:The diagnostic clues of SSPE are progressive mental and physical regression, recurrent myoclonic seizures during period Ⅱ, as well as the extensive periodic complex waves of EEG. It is necessary to detect measles virus IgG antibody in blood and cerebrospinal fluid to make a definite diagnosis. There is no specific treatment for SSPE and its prognosis is very poor.

Objective: To explore the clinical characteristics and genotyping results of childhood-onset myoclonus dystonia syndrome caused by SGCE variants. Methods: The clinical data of 9 children with SGCE-related myoclonus dystonia syndrome admitted at either the Department of Neurology, Beijing Children′s Hospital, Capital Medical University or the Department of Pediatrics, Peking University First Hospital from May 2018 to October 2019 were collected and the patients were followed up. The definite diagnosis was made on the basis of whole exome sequencing and multiple ligation-dependent probe amplification. The clinical features and gene test results were analyzed retrospectively. Results: Data of 9 patients (4 boys and 5 girls) diagnosed as myoclonus dystonia syndrome caused by SGCE variants were collected. The onset age ranged from 1 year to 3 years and 2 months. The first symptom was myoclonus in 4 cases, while dystonia in the remaining 5 cases. In the course of the disease, 9 cases had myoclonus and 8 had dystonia. Myoclonic jerks were characterized by involuntary jerks in both upper limbs in 8 patients. Six patients had involuntary jerks of lower limbs, resulting in gait instability or even falling. The myoclonus was exacerbated during the fine motor activities, emotional stress or fatigue. Dystonia was characterized by abnormal gait, including 5 cases with right leg dystonia, and 3 cases with the left leg dystonia. Three probands had a positive family history. Intellectual development was normal in all cases. There was no obvious abnormality in video-electroencephalogram (EEG) during both ictal and interictal periods. Electromyography (EMG) and brain magnetic resonance imaging (MRI) of 9 patients were normal. Nine patients carried SGCE gene variants, including 3 frame shift variants, 2 nonsense variants, 2 missense variants, 1 fragment deletion variant and 1 splice site variant. Seven variants were inherited paternally, and 2 variants were de novo. Madopar was used in 8 patients, and nitrazepam in 4 patients, leading to the decrease in the myoclonus jerks and improvement of gait in 6 and 2 patients, respectively. Conclusions SGCE gene variants can cause myoclonus dystonia syndrome. The onset of the disease may occur at infancy or preschool age, with either myoclonic jerks or dystonia as the initial symptom. Non-epileptic myoclonus is the prominent symptom, with upper limb mainly involved. Most of the patients have the accompanying symptoms of dystonia, and some of them may have spontaneous symptom relief. SGCE gene is imprinted maternally, and the inherited variants of SGCE are paternal in origin.

Objective: To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods: Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children′s Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ² test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results: Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic-clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged-red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex Ⅰ deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m.3243A>G variants, 6 cases had m.8344A>G variants, and 3 cases had m.8993T>G/C variants, m.3271T>C, m.3481G>A, m.3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complex Ⅰ were in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty-three patients were followed up, and the follow-up time was 20 (3-84) months. According to the follow-up results, the anti-epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group (t=1.662, 0.860; P=0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non-first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ²=2.794, 0.164, 3.380; P=0.095, 0.686, 0.066). Conclusions The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic-clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.

Objective: To investigate the clinical significance of different samples (the peripheral blood, urine and skeletal muscle) that could be detected the large-scale single deletions directly by using next-generation sequencing in the diagnosis of Kearns-Sayre syndrome (KSS) by concluding the clinical and genetic features of KSS, in order to explore a non-invasive method for diagnosis. Methods: The clinical data, skeletal muscle′s pathology and enzymology and genetic results of individuals with KSS, who were hospitalized from October 2016 to October 2017 in Department of Neurology, Beijing Children′s Hospital, Capital Medical University, were collected.The gene tests were performed by using next generation sequencing technology and long-PCR technology of mitochondrial DNA(mtDNA) and the whole exon in the peripheral blood, urine and skeletal muscle. Results: Four patients were all consistent with the diagnosis criteria of KSS, among whom the age of onset was 8.2 years old on average, and the initial symptoms were statue, ptosis, headache and vomiting, and visual impairment.The common symptoms of the 4 cases were ophthalmoplegia, exercise intolerance, development delay, loss of appetite, hypotonia, muscle weakness, with cerebrospinal fluid protein concentration over 1 000 mg/L, the cerebral magnetic resonance imaging showed that abnormal signals in the brainstem, in addition, white matter, thalamus, basal ganglia, cerebrum and cerebellum atrophy could be found.Moreover, 3 cases had cardiac conduction block.Two cases had maternal family history.Molecular analysis of the 4 cases revealed the large-scale single deletions of mtDNA from the peripheral blood, the urine, the skeletal muscle through the next-generation sequencing, which were m. 6460-15590(9 131 bp del), m.8482-13446(4 964 bp del), m.6831-14981(8 151 bp del), m.7983-15495(7 513 bp del), respectively.Among 3 cases who did pedigree analysis, only the mother of case 4 was detected with the same variation of the proband. Conclusions KSS is a rare mitochondrial disease, which could be detected with the single large scale mtDNA deletions in the peripheral blood, urine and skeletal muscle.With the development of the methodology, the diagnosis of KSS maybe no longer than depends on the muscle biopsy with the next-generation sequencing.And the possibility to get the positive results in the peripheral blood and urine by the non-invasive method could improve the molecular diagnosis of KSS.