Objective:To investigate the efficacy and safety of SIMPLE regimen in the treatment of extranodal NK/T-cell lymphoma (ENKTCL).Methods:The clinical data of 11 patients with ENKTCL who were admitted to the University of Hong Kong-Shenzhen Hospital from January 2012 to January 2022 were retrospectively analyzed. The patients received 4-6 courses of SIMPLE (cisplatin, gemcitabine, ifosfamide, etoposide, dexamethasone, and pegasparaginase) regimen chemotherapy, and stage Ⅰ and Ⅱ patients who also received local radiotherapy after 2 or 3 courses of chemotherapy. Patients were evaluated for mid-treatment and end-of-treatment outcomes, and the adverse effects of patients were evaluated in each treatment cycle. The Kaplan-Meier method was used to analyze the progression-free survival (PFS) and overall survival (OS) of the 11 patients.Results:All 11 patients were nasal type, with the median age of 41 years old (26-67 years old), including 5 males and 6 females, 3 relapsed cases and 8 newly treated cases. Of the 10 patients evaluated for efficacy, 9 achieved complete remission and 1 achieved at least partial remission (efficacy was assessed based on follow-up). All 11 patients were followed up for a median time of 50 months (15-72 months) and 2 relapsed patients died due to disease progression. The expected 5-year PFS rate and OS rate of 11 patients were both 90.0%, and the expected 5-year OS rate was 100.0% and 66.6% in newly treated and relapsed patients, respectively. Common adverse effects were hematologic adverse reactions, infections, gastrointestinal symptoms, elevated transaminases, and hypofibrinogenemia, all of which were curable. There is no treatment-related death.Conclusions:The SIMPLE regimen for the treatment of ENKTCL has a high remission rate, the patients have long survival time, and the regimen is moderately well tolerated.

ObjectiveTo analyze the research hotspots and frontier trends in the field of early screening tools of autism spectrum disorder (ASD) over the past two decades. MethodsThe literature on early screening tools for ASD was searched in Web of Science core collection database from 2002 to 2022. CiteSpace was used for cluster analysis of keywords, to draw knowledge mapping. Research disciplines were analyzed and comprehensively interpreted. ResultsA total of 115 articles were included. The number of researches on early screening tools for ASD had been increasing over the past two decades. The research disciplines with higher publication volume included pediatrics, neurology and neuroscience, and psychology. A total of 191 keywords were identified, and the LLR keyword clustering analysis yielded eleven clusters. ConclusionModified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) and Brief Infant-Toddler Social and Emotional Assessment (BITSEA) have been subjected to large-scale sample screening and follow-up observation for validity, demonstrating good psychometric properties and high clinical diagnostic value. The development of new early screening tools for ASD, validation of the reliability and validity of different language versions of the M-CHAT-R/F, and research on digital and networked M-CHAT-R/F are current research hotspots. Cultural adaptation of early screening tools for ASD and their application within the developmental monitoring framework may represent frontier research trends.

Objective:To optimize the Manchester needs tool for injured children (MANTIC) scale , and evaluate its reliability and validity among injured children. Methods:The MANTIC scale was optimized through Delphi expert consultation and pre-tests. From March 2023 to June 2023 , a total of 317 injured children admitted in 7 level A tertiary hospitals in Zhejiang and Shandong provinces and their families were surveyed with general data, optimized MANTIC scale, and EuroQol 5-dimension health questionnaire for youth (EQ-5D-Y). Item analysis was conducted on the data of the 317 patients collected with optimized MANTIC scale through the test for homogeneity and value-based decision-making method and the content validity test of the scale was evaluated with item-level content validity index (I-CVI) and scale-level content validity index (S-CVI). It was evaluated with KMO test values and Bartlett′s test of sphericity to determine whether the scale was suitable for exploratory factors. The number of common factors was determined based on the K1 criterion and scree plot to further obtain the structural validity of the scale of the item load value. The correlation validity of the scale was evaluated with the correlation coefficient of the optimized MANTIC scale and EQ-5D-Y. The reliability of the scale was tested with Cronbach alpha coefficient and Guttman split-half reliability coefficient. Results:A total of 332 questionnaires were distributed, among which 317 valid ones were collected, with a response rate of 95.6%. The test of homogeneity in the item analysis showed that the correlation coefficient between each item and the total score of the scale was 0.40-0.80. The results of the value-based decision-making method showed that the critical ratio of high-and low-scored groups was 6.08-28.01. The quality of all the items met the retention requirements so that the reliability and validity tests could be continued. Validity test found that I-CVI was 0.83-1.00, consistent S-CVI was 0.83, and mean S-CVI was 0.95. In structural validity analysis, the KMO value was 0.96, and the Chi-square value of Bartlett′s test of sphericity was 10755.76 ( P<0.01). A total of 9 common factors were extracted with the K1 criterion (eigen value>1), and the scree plot indicated 9 common factors with a cumulative variance contribution rate of 73.46%. Factor extraction and rotation showed that the load value of each item of the scale ranged from 0.589 to 0.874. The correlation coefficient of the optimized MANTIC scale and EQ-5D-Y was r= 0.55 ( P<0.01).Reliability test showed that the Cronbach alpha coefficient of the total scale and all dimensions was 0.96 and 0.77-0.98, and the Guttman split-half reliability coefficient was 0.76 and 0.73-0.98. Conclusion:The optimized MANTIC scale can attain good reliability, validity, consistency and stability, and can reflect the concept to be expressed and the content to be evaluated, indicating that it can be used to evaluate the injury rehabilitation needs of injured children and their families throughout the entire treatment process.

Objective:To develop the Elderly Inpatient Falls Prevention Knowledge, Attitude and Practice Scale for Full-time Caregivers, so as to provide a measurement tool for investigating the current situation of knowledge, attitude, and practice of full-time caregivers in preventing falls in elderly inpatients.Methods:A test version of the scale was formed through literature review, expert consultation, and pre investigation. From January to April 2022, convenience sampling was used to select 312 full-time caregivers from 5 accompanying companies in 6 ClassⅢ Grade A hospitals in Qingdao as the research subject, to test the reliability and validity, and to revise the final scale. A total of 312 questionnaires were distributed, and 300 valid questionnaires were collected, with an effective response rate of 96.154% (300/312) .Results:The Elderly Inpatient Falls Prevention Knowledge, Attitude and Practice Scale for Full-time Caregivers had a total of 35 items, including 3 dimensions, including 11 items in the knowledge dimension, 10 items in the attitude dimension, and 14 items in the practice dimension. The total Cronbach's α coefficient of the scale was 0.926, with Cronbach's α coefficients of 0.914 to 0.944 for each dimension, 0.998 for test-retest reliability coefficient, and 0.681 for split half reliability coefficient of the scale. The content validity index of the scale level was 0.984, and the cumulative variance contribution rate was 59.688%.Conclusions:The reliability and validity of the Elderly Inpatient Falls Prevention Knowledge, Attitude and Practice Scale for Full-time Caregivers are good, and can be used as a tool to evaluate the full-time caregiver knowledge, attitude and practice for preventing falls in elderly inpatients.

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

Objective:To systematically analyse the blood coagulation features of coronavirus disease 2019 (COVID-19) patients.Methods:An electronic search in PubMed, Scopus, Web of Science, EMbase, and CNKI to collect studies related to the blood coagulation features of COVID-19 patients from 1 January 2020 to 1 May 2020. Two reviewers independently screened literatures, extracted data and assessed the risk of bias of included studies. Then, the platelet count, D-dimer value, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen of patients with different types of diseases were analyzed by using Stata12.0 software.Results:Thirty-nine retrospective studies involving 6 994 COVID-19 patients were included. The results of meta-analysis showed that:(1) compared with severe group, the platelet count (Weighted mean difference; WMD=20.11, 95% CI 11.53 to 28.69, P<0.001) and APTT (WMD=1.30, 95%CI 0.31 to 2.30, P=0.01) were found to be higher while D-dimer (WMD=-0.41, 95%CI-0.58 to-0.24, P<0.001), fibrinogen (WMD=-0.58, 95% CI-0.76 to-0.39, P<0.001) and PT (WMD=-0.51, 95%CI-0.92 to-0.10, P<0.001) were lower in mild group; the platelet count (WMD=-14.75, 95% CI-29.73 to-0.23, P=0.044) was found to be lower while D-dimer (WMD=1.06, 95% CI 0.65 to 1.47, P<0.001) was found to be higher in critical ill patients. (2)Compared with the survival group, the patients in death group displayed elevated levels of D-dimer (WMD=6.86, 95% CI 4.15 to 9.57, P<0.001) and PT (WMD=1.37, 95% CI 0.73 to 2.02, P<0.001) while platelet count (WMD=-36.40, 95% CI-63.23 to-9.58, P=0.008) remained low. Conclusion:Coagulation dysfunction was common in severe, critical ill and dead COVID-19 patients. Platelet count, D-dimer and PT levels were associated with the severity of the disease, and thus could be used as early warning indicators for the deterioration of the disease during hospitalization.

Brachytherapy ; Carcinoma, Hepatocellular/drug therapy* ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Humans ; Iodine Radioisotopes ; Liver Neoplasms/drug therapy* ; Portal Vein ; Retrospective Studies ; Sorafenib/therapeutic use* ; Thrombosis ; Treatment Outcome

Objective: To synthesize a folic acid (FA)-modified pH-sensitive nanomicelle containing sorafenib (SF) and superparamagnetic iron oxide (SPIO), and to access its visibility in MRI and anti-cancer efficacy on hepatocellular carcinoma (HCC) in vitro. Methods: The copolymer FA-PEG-Pasp (DBA/DIP) of FA, poly(ethylene glycol), N,N-dibutylethylenediamine and N,N-diisopropylethylenediamine grafted poly (L-aspartic acid) were prepared. SF and SPIO were encapsulated inside the copolymer to synthesize the targeting micelle FA-PEG-PAsp (DBA/DIP)-SPIO/SF (FPASS). The folate-free micelle[PEG-PAsp (DBA/DIP)-SPIO/SF (PASS)] was used as nontargeting micelle. The physicochemical properties and drug release behavior of the micelles were analyzed. MRI of HepG2 cells incubated with FPASS and PASS with different Fe concentrations and Prussian blue staining of cells treated with the micelles (Fe concentration of 20 μg/ml) was performed to assess the drug delivery capability and imaging function of the micelles. For the FA competitive inhibition assay in these experiments, HepG2 cells were pre-treated with an excess amount of free FA prior to the incubation with FPASS. Cell viability, cell apoptosis, cell cycle and tube formation assays were conducted for evaluating the anti-HCC effects of the micelles. Comparison between groups was analyzed by one-way ANOVA, and multiple comparisons correction was performed by LSD test. Results: The diameters of FPASS and PASS were (102.3±5.2) nm and (107.1±5.7) nm, respectively; the δ potentials of them were (29.7±1.6) mV and (31.5±1.4) mV, respectively. The T₂ relaxivity of both the micelles was (5.2±0.4) ml·μg^-1·s^-1, which was much higher than that of water soluble Fe₃O₄ nanoparticles [(2.3±0.1) ml·μg^-1·s^-1; F=76.45, P<0.01]. SF released from the micelles was much faster at pH5.0 than at pH7.4, which indicated that the micelles had a pH-triggered drug release behavior. MRI of HepG2 cell samples revealed the signal intensity on T₂WI images and the T₂ value on T₂-map images decreased with the increasing Fe concentrations in the micelles. At the same Fe concentration (5, 10, 20 and 40 μg/ml), the cells of FPASS group exhibited a more significant decrease in T₂ signal intensity and T₂ value compared with those of PASS group or FA competitive inhibition group (F=8.69, 14.03, 27.27, 32.25 and 19.80, 45.76, 113.20, 66.80; P<0.01). Prussian blue staining verified the existing of SPIO in the cytoplasm of cells. Compared with PASS, FPASS presented significantly higher anticancer effects on inducing apoptosis, causing G0/G1 phase arrest on HepG2 cells and inhibiting tube formation on human umbilical vein endothelial cells (t=7.905, 4.399 and 3.454, respectively; P<0.01). Conclusions The pH-sensitive nanomicelle FPASS was successfully constructed. This micelle possessed a hypersensitive MRI-visible function and a targeting SF delivery capability which may contribute to a significant anti-HCC effect.

Objective To investigate the radiosensitization effects and mechanisms of novel benzothiadiazole derivatives HL-095 to KRAS-mutant non-small cell lung cancer ( NSCLC ) H358 , A549 , and H460 cell lines . Methods The benzothiadiazole derivative HL-095 was designed and synthesized with AZD6244 as the lead compound. The ability of HL-095 to inhibit the activity of MEK kinase was detected by the mitogen-activated extracellular signal-regulated kinase 1 (MEK1). H358, A549 and H460 cells were inoculated and cultured at appropriate density, and divided into control group, HL-095 group, irradiation group and HL-095 combined irradiation group. One-time irradiation with 137Cs gamma rays was used with a dose rate of 1.02 Gy/min. The expression of phosphorylated extracellular regulatory protein kinase ( p-ERK ) in H358 , A549 and H460 cells was detected by Western Blot. The cell proliferation was detected by cloning assay. The degree of DNA damage was analyzed by Comet assay. The G2/M phase cells were detected by flow cytometry. The level of the checkpoint kinase 1 (CHK1) protein and its phosphorylation in A549 and H358 cells was detected by Western Blot. Results HL-095 can inhibit the activity of MEK1. Compared with the control group, the expression levels of p-ERK protein of H358, A549, and H460) cells in HL-095 group were decreased, the percentages of cells in the G2/M phase were also decreased, and the differences were statistically significant (all P<0.01). The expression and phosphorylation of CHK1, a key protein of DNA damage repair, was down-regulated in A549 and H358 cells. Compared with the irradiated group, the proliferation of the three kinds of cell in HL-095 combined irradiation group was inhibited, the DNA damage was more serious, the Olive tail moment, tail length, tail length and tail DNA percentage were significantly increased, and the differences were statistically significant (all P<0.05). Conclusion As a MEK inhibitor, the novel benzothiadiazole derivative HL-095 can enhance the radiosensitivity of KRAS mutant NSCLC cells by inhibiting DNA damage repair and reducing G2/M arrest.

Objective To investigate the epidemiological characteristics of cerebral palsy(CP)in children aged 1-6 years in China,including the incidence,prevalence,type of CP,etiology,prevention and rehabilitation status. Methods The survey was carried out by standard questionnaires,multi-center collaboration,stratified-cluster ran-dom sampling method.The surveyed adopted the following principles:streets in the city and villages in the rural areas, and the number of the urban and rural children was the same,and the proportion of children in each age group was balanced.The investigation areas included provinces and autonomous regions,including Heilongjiang,Beijing,Henan, Shandong,Shanxi,Shaanxi,Anhui,Hunan,Guangxi,Guangdong,Chongqing and Qinghai,and 323 858 children were in-vestigated.Results The incidence of CP was 2.48‰(155/62 591 cases),and the prevalence was 2.46‰(797/323 858 cases)(1-6 years old).The prevalence varied in different regions,in which the highest prevalence was 5. 40‰(54/9 998 cases)in Qinghai province,and the lowest prevalence was 1.04‰(47/45 133 cases)in Shandong province.The prevalence of the males(2.64‰,461/174 391 cases)was higher than that of the females(2.25‰, 336/149 467 cases),and the difference was statistically significant(P<0.05).The types of CP were spastic type (58.85%,469/797 cases),mixed type(13.17%,105/797 cases),dyskinetic(9.79%,78/797 cases),hypotonic (8.28%,66/797 cases),ataxia(6.25%,52/797 cases)and rigid(3.39%,27/797 cases)respectively in 797 CP children.The first three risk factors for CP were long -term exposure to harmful physical factors during pregnancy, whether there were birth defects among the three generations of relatives of the children,such as children's peers, parents or grandparents,whether there were birth defects among the children's peers,parents or grandparents,and neonatal jaundice or persistent jaundice.Among 797 CP children,79.67% of the children with CP were timely detected and treated in the local hospitals,while the other 19.93% of them were not timely treated.The places which could give them timely detection and early diagnosis and treatment were general hospitals(42.97%),Maternity and Infant Hospitals (27.03%)and Children's Hospitals(20.31%). The main rehabilitation methods for 797 children with CP were 34.58% in the hospitals or rehabilitation centers,31.61% in the communities(including at home),33.80% mainly in the medical institution,and in the communities they could also receive partially rehabilitation services. Conclusions The prevalence of CP in China is coincident with international levels.The prevalence rate of CP in males is higher than that in females.The types of CP distribution are accorded with international distribution characteristics.There were still some children with CP who could not receive timely detection and treatment.Rehabilitation at the medical institutions is the chief way and proper rehabilitation guidance should be carried out in the communities.