Background::NOTCH1 mutation is an essential molecular biologic aberration in chronic lymphocytic leukemia (CLL). CLL patients with NOTCH1 mutation have shown an unfavorable survival and a poor response to chemoimmunotherapy. This study aims to present the mechanisms of adverse prognosis caused by NOTCH1 mutation from the perspective of the splicing factor heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Methods::The microarray data in Gene Expression Omnibus datasets were analyzed by bioinformatics and the function of hnRNPA1 was checked by testing the proliferation and apoptosis of CLL-like cell lines. Afterward, quantitative reverse transcription-polymerase chain reaction and Western blotting were applied to explore the relationship among NOTCH1, c-Myc, and hnRNPA1.Results::RNA splicing was found to play a vital part in NOTCH1-mutated CLL cells; hence, hnRNPA1 was selected as the focus of this study. Higher expression of hnRNPA1 validated in primary NOTCH1-mutated CLL samples could promote proliferation and inhibit apoptosis in CLL. The expression of hnRNPA1 increased when NOTCH1 signaling was activated by transfection with NOTCH1 intracellular domain (NICD)-overexpressed adenovirus vector and declined after NOTCH1 signaling was inhibited by NOTCH1-shRNA. Higher expression of c-Myc was observed in NICD-overexpressed cells and hnRNPA1 expression was downregulated after applying c-Myc inhibitor 10058-F4. Moreover, in NICD-overexpressed cells, hnRNPA1 expression decreased through c-Myc inhibition. Conclusion::Overexpression of c-Myc-dependent hnRNPA1 could promote proliferation and inhibit apoptosis in NOTCH1- mutated CLL cells, which might partly account for the poor prognosis of patients with NOTCH1 mutation.

Objective: To learn the epidemiological characteristics of coronavirus disease 2019（COVID-19）in Huzhou,so as to provide reference for prevention and control of COVID-19. Methods: All the confirmed cases of COVID-19 in Huzhou,diagnosed according to the COVID-19 Diagnosis and Treatment Plan（Sixth Version Trial）and reported from January 25 to February 7,2020,were recruited. The process of diagnosis and treatment,clinical manifestation,exposure history and close contacts were collected to analyze the epidemiological characteristics. Results: On January 25,the first confirmed cases of COVID-19 in Huzhou was reported. By February 7,totally 10 confirmed cases were reported and no asymptomatic infection was found. They were all imported,including three Wuhan residents,two with a trip to Wuhan,three with a trip to Suizhou,one with a trip to Hangzhou and one with a trip to Thailand（two Wuhan passengers on the same flight）. The ratio of male to female cases was 1∶1. The median age was 32 years old. Seven cases were found when they went to a doctor by themselves,and three cases were found during the quarantine. The main clinical manifestations were fever,dry cough and fatigue. The median time from onset to diagnosis was 3 days. By March 3,all the cases were discharged,with median course of 24 days. There were 312 close contacts,and all of them were released after 14 days of quarantine. Conclusions To prevent imported cases from outside and stop spread inside taken by Huzhou government was proved to be effective. All the COVID-19 cases in Huzhou were imported,mostly from Wuhan. No local cases were reported.

Scoliosis seriously affects the physical and mental health of children and adolescents. Without timely screening and intervention,it will lead to increased deformity,decreased labor capacity,cardiopulmonary complications,back pain and even paraplegia. This article reviews screening and intervention strategies for scoliosis at home and abroad. It concludes that there is lack of scoliosis screening in children and adolescents in China,and the screening results are difficult to compare horizontally because of the significant differences between strategies. It is suggested that scoliosis screening should be included in school healthcare work and formulate strategies with higher accuracy and safety. At the same time,three-dimension technology has good prospects in scoliosis screening and intervention,which is worthy of further development.

Objective To find a reliable, simple, and easily-operated method for the screening of neonatal congenital heart disease (CHD). Methods A total of 7 105 neonates born from January 2017 to July 2017 were selected. The validity and reliability of physical examination, pulse oximetry screening (POS), and perfusion index (PI) in the screening of neonatal CHD were evaluated according to the diagnosis made by color Doppler echocardiography. Results When physical examination, POS or PI was used separately in screening for CHD, the sensitivities were in the range of 13.11%~73.77%, specificities 50.20%~99.34%, Youden indexes 0.12~0.70, the total coincidence rates 50.40%~98.86%, positive predictive values 1.27%~40.70%, and negative predictive values 99.29%~99.70%. When physical examination, POS and PI were combined (two or three indexes were positive) for screening, the sensitivities and Youden indexes were 85.25% and 0.82 respectively, which were higher than those of single indicators and suggested that the combination had higher authenticities. The total coincidence rate of the combination was 97.07%, and, although it was lower than POS group (98.86%) and PI screening group (98.58%), it still had a good reliability. Conclusions The combination of physical examination, POS and PI has a certain clinical value in neonatal CHD screening.

Objective: To validate the prognostic value of chronic lymphocytic leukemia-international prognostic index (CLL-IPI) for Chinese CLL patients. Methods: Two hundred and fifteen CLL patients who were initially diagnosed and treated in Jiangsu Province Hospital from January 2002 to November 2017 were included in the retrospective analysis. Risk stratification and prognosis were evaluated by CLL-IPI scoring system. Results: ①Of the 215 patients, 143 were males and 72 were females, with a median age of 60 (16-85) years old. The median treatment-free survival (TFS) and overall survival (OS) was 16 months (4-24 months) and 180 months (145-215 months), respectively. ② The median TFS for low (n=60), intermediate (n=50), high (n=45) and very high risk group (n=60) according to the CLL-IPI scoring system was 56, 15, 12 and 5 months, respectively (P<0.001). ③ The median follow-up was 48 months (1-192 months). The median OS for low risk group was not reached and for intermediate, high, and very high risk group was 180, 89 and 74 months, respectively. The estimated 5-year OS rate was 97.6%, 83.7%, 67.8% and 55.2%, respectively (P<0.001). ④ Multivariate analysis indicated that unmutated immunoglobulin heavy chain variable region (IGHV) gene and β₂-microglobulin>3.5 mg/L(P<0.001) were independent prognostic factors of TFS, while TP53 deletion and/or mutation(P=0.008), unmutated IGHV (P=0.017) and age>65 years(P=0.045) were independent prognostic factors of OS. Conclusion CLL-IPI is the powerful tool for risk stratification in Chinese CLL patients.

AIM: To investigate the expression and significance of MAPK-interacting kinase-2 ( Mnk2 ) and eukaryotic initiation factor 4E ( eIF4E) in the patients with resected esophageal squamous cell carcinoma ( ESCC ). METHODS:The protein expression of Mnk2 and eIF4E in ESCC tissues (98 cases) and normal esophageal tissues (20 cases) were assessed by immunohistochemistry (IHC), and their correlations with clinicopathological features were statisti-cally analyzed.RESULTS:The over-expression rate of Mnk2 and eIF4E was 68.4%(67/98) and 61.2%(60/98), re-spectively.The expression of Mnk2 had a positive correlation with eIF4E (P<0.05).Clinicopathologic analysis showed that Mnk2 expression was significantly correlated with T classification ( P<0.05 ) and clinical stage ( P<0.05 ) .CON-CLUSION:The over-expression of Mnk2 was significantly related to the tumor invasive depth , TNM stages and expression of eIF4E in ESCC.Expression of Mnk2 and eIF4E may have a cooperative formation mechanism in the development of ESCC.

Objective To evaluate the application value of confocal laser scanning microscopy(CLSM)in the differentiation between seborrheic keratosis and Bowen′s disease. Methods CLSM was used to observe typical skin lesions in 88 patients clinically diagnosed with seborrheic keratosis and 18 patients clinically diagnosed with Bowen′s disease. Then, tissue specimens were resected from these lesions and subjected to histopathological examination. Results CLSM imaging of seborrheic keratosis lesions showed gyrus?like structures and keratin?filled inclusion cysts in the epidermis with trabecula?like extension of rete ridges in all the 88 cases, basal cells arranged in a cordike or radial pattern in 9 cases, and bright reflective structures in the basal layer and dermis in 6 cases. CLSM imaging of Bowen′s disease lesions revealed disorderly arrangement of large, irregularly shaped atypical cells in some areas in the middle and lower epidermis, and infiltration of scattered mononuclear cells in the superficial dermis. Conclusion CLSM images of seborrheic keratosis are different from those of Bowen′s disease, and CLSM may be helpful for their differential diagnosis.

Chimeric antigen receptor-T cell (CAR-T) therapy is one of the effective novel immunotherapy for malignancies, and it has a great effect on leukemia and lymphoma. More researches are needed to improve the understanding of CAR-T therapy and promote the development of this technology in order to treat hematological malignancies from a novel perspective.

AIM:ToinvestigatetheeffectofP21-activatedkinase1(PAK1)andlymphoidenhancer-binding factor 1(LEF1) on the proliferation of esophagus cancer cells .METHODS:Real-time PCR was applied to detect the mR-NA expression of PAK1 and LEF1 in the esophagus cancer tissues .MTT assay were used to measure the proliferation of hu-man esophagus cancer cell line KYSE transfected with PAK 1 and LEF1.RESULTS: The mRNA expression of PAK1 in the esophagus cancer tissues was lower than that in control group (P<0.05).The mRNA expression of LEF1 and tran-scription factor 4 (TCF4) in the esophagus cancer tissues was higher than that in control group (P<0.05).The prolifera-tion of KYSE cells with over-expression of PAK1 and LEF1 was higher than that in control group .No significant change of apoptosis between the KYSE cells with over-expression of PAK1 and LEF1 and control group was observed .CONCLU-SION:The expression of PAK1 decreases and the expression of LEF 1 increases in esophagus cancer tissues .LEF1 domi-nantly regulates the proliferation of esophagus cancer cells .

The role of consolidating radiation therapy (RT) is very controversial in Hodgkin lymphoma (HL),especially in adolescents and young adults (AYA) HL.The key problem is how to achieve better therapeutic effect but bear less toxicities in chemotherapy and radiotherapy,which will be hopefully solved by clinical trials adopting interim positron emission tomography (iPET) scanning to guide therapy for HL.The new technologies including whole genome amplification (WGA),high-throughput gene sequencing (NGS) assay and genome-wide association study (GWAS) further illustrate abnormal signaling pathways in HL,such as NF-κB,JAK/STAT and PI3K pathway,which may provide new therapeutic targets for the disease.