ObjectiveTo analyze the visual status and its influencing factors among preschool children in Tongzhou District. MethodsFrom March to August 2022， a stratified cluster sampling was used to include 2 199 preschool children as study subjects. Visual acuity examination and parental questionnaire surveys were conducted， and a multivariate logistic regression model was used to analyze the influencing factors for visual abnormalities. ResultsThe detection rate of abnormal naked-eye vision among 2 199 students was 13.60%. The rates of visual abnormalities in children aged 4， 5， and 6 were 9.02%， 18.01%， and 11.82%， respectively. Multivariate logistic regression revealed that compared with boys， children between 4 and 5 years old， children who first played with electronic products at the age of ≥4 ， those with good home lighting， those who often/always took a break and looked into the distance after using your eyes for 30 minutes， those who never watched TV at a distance < 2 meters， and children with parental knowledge-attitude-practice （KAP） scores above 0.7， girls （OR=1.411，95%CI： 1.095‒1.819）， children between 5 and 6 years old （OR=2.303，95%CI： 1.726‒3.071） ， children who first played with electronic products under 4 years old （OR=2.464，95%CI： 1.120‒5.424）， those with poor home lighting environment （OR=2.229，95%CI： 1.295‒3.835）， those who never （OR=1.862，95%CI：1.115‒3.110） or occasionally/ sometimes （OR=1.997，95%CI：1.268‒3.145） took a break and looked into the distance after using your eyes for 30 minutes， those who watched TV occasionally/sometimes at a distance < 2 meters （OR=1.369，95%CI： 1.011‒1.855）， and those with parental KAP scores under 0.7 （OR=1.780，95%CI： 1.005‒3.155） had a higher risk of abnormal visual acuity. ConclusionThe prevalence of abnormal visual acuity in preschool children is high， and there are multiple influencing factors. Attention should be paid to vision screening and healthy eye-use behavior education for preschool children to reduce the occurrence of visual abnormalities.

Objective: To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) . Methods: From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed. Results: A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved Conclusions The efficacy of dasatinib and nilotinib as second- or third-line TKI-therapy were active in the CML patients with TKI-resistance. The best response achieved on previous TKI-therapy, the disease phase before switching TKI, and the severe hematologic toxicity developing on the current TKI-therapy were associated with the responses and outcomes.

Objectives: To compare the efficacy and safety of Chinese generic imatinib with branded imatinib as frontline therapy in adults with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) (Frontline group) , and to explore the efficacy and safety of Chinese generic imatinib in CML-CP patients switching from branded imatinib (Switching group) . Methods: Frontline group: Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei^®) or branded imatinib (Glivec^®) between October 2013 and August 2018 were retrospectively collected and analyzed. Switching group: Data of adults diagnosed with CML-CP who received branded imatinib and then switched to Chinese generic imatinib after achieving at least complete cytogenetic response (CCyR) were retrospectively collected and analyzed. Results: Frontline group: In total, 409 adult patients receiving Chinese generic imatinib (n=201) or Glivec (n=208) were included in this study. Median age was 42 years (range, 18-83 years) . Comparison of baseline showed significant difference on demographic characteristics among two cohorts: lower education level (P<0.001) , and divorced or widowed status (P=0.004) and rural household registration (P<0.001) were more common in the generic imatinib cohort than those in the Glivec cohort. There was no significant difference on age, gender, Sokal risk score, WBC and HGB between the 2 cohorts. With a median follow-up of 25 months (range, 3-62 months) , there was no significant difference on the 3-year cumulative incidence of achieving CCyR (97.5% vs 94.5%, P=0.592) , major molecular response (MMR) (84.3% vs 93.1%, P=0.208) , molecular response^4.0 (MR^4.0) (42.7% vs 41.7%, P=0.277) , molecular response^4.5 (MR^4.5) (25.4% vs 33.0%, P=0.306) as well as the 3-year probabilities of failure free survival (FFS) (76.7% vs 81.0%, P=0.448) , progression free survival (PFS) (91.8% vs 96.3%, P=0.325) and overall survival (OS) (95.8% vs 98.5%, P=0.167) between the generic and branded imatinib cohorts. Multivariate analysis showed the type of imatinib was not associated with treatment responses and outcomes. The incidences of adverse effects were comparable in the 2 cohorts. Switching group: In total, 39 patients switching from branded imatinib to Chinese generic imatinib after achieving at least CCyR were included in this study. Median age was 42 years (range, 23-80 years) . With a median follow-up of 39 months (range, 6-63 months) , molecular responses were maintained in 23 (58.9%) patients and improved in 12 (39.8%) patients. Adverse effects were tolerable. Conclusion Demographic characteristics might influence the choice of the type of TKI used in CML-CP patients. There was a comparable efficacy and safety between the Chinese generic imatinib and the branded imatinib in adults with newly diagnosed CML-CP under standard management and closely monitoring. Patients could safely switch from the branded imatinib to the Chinese generic imatinib.

Objective: To observe changes in the molecular expression of the NLR Family Pyrin Domain Containing Protein 3 (NLRP3) pathway in depressed rats after treatment with Xiaoyaosan, and identify the regu-latory mechanism of this compound. Methods: Male Sprague-Dawley rats were randomly divided into five groups with 12 rats in each group, including the control group, model group, Fluoxetine group, Xiaoyaosan group, and MCC950 group. A depression model was generated by chronic immobilization stress (induced by 3 h of restraint immo-bilization every day), and the drugs were administered at the same time in each group for 21 days. The effects of Xiaoyaosan on behavioral changes of depressed rats were observed through macroscopic characterization, body mass, open field experiments, and a sucrose preference test. The mRNA and protein expression of the NLRP3 signaling pathway was examined by fluorescence real-time quantitative PCR and Western blot assays. Results: The Xiaoyaosan group, Fluoxetine group, and MCC950 group rats showed improved depressive behavior and an increased weight of sucrose water consumption. The protein and mRNA expression levels of NLRP3, Caspase-1, and IL-1β were also decreased in the Fluoxetine, Xiaoyaosan, and MCC950 groups. Conclusion: NLRP3, Caspase-1, and IL-1β protein and mRNA expression levels were increased in the cortex of depressed rats, while Xiaoyaosan protected cortical tissue in these rats by decreasing NLRP3, Caspase-1, and IL-1βprotein and mRNA expression.

DNA methylation studies the natural modification of DNA that occurs when the nucleotide sequence is unchanged. At present, DNA methylation is used in the field of biomedicine to focus on the characteristics and regularity of disease-wide genome methylation and the DNA methylation biomarkers for disease. Based on the systematic review of DNA methylation research techniques, this paper summarizes and analyzes the current status of DNA methylation technology in basic research of TCM (traditional Chinese medicine) syndromes, and a suggestion to screen the TCM syndrome biomarkers from whole genome DNA methylation is proposed.

ObjectiveTo describe the neuropsychological development screening of 0‒2 years in Tongzhou from 2017 to 2021 so as to understand the status and trend of developmental delay （DD）. MethodsAnnual report data of 21 community health service centers in Tongzhou District from 2017 to 2021 were clustered， Chi square test was used to analyze the differences in positive rate and DD rate of children aged 0‒2 years with different ages and household registration， and Chi square trend test was used to analyze the linear trend of each age group and household registration. The Gesell test results in 762 children with developmental delay were analyzed， and Chi square test was used to compare the age distribution differences in gross motor， fine motor， language and personal-social behaviors. ResultsThe DD rate of children aged 0‒2 years in 2017‒2021 was 0.43％. A decreasing trend of DD rate in the 0‒ age group was observed （χ²=14.135， P<0.001）， while an increasing trend of DD rate in the 1‒ and <3 age groups was observed （χ²=5.375， P=0.020； χ²=5.558， P=0.018）. The DD rate of children aged 0‒2 years with Beijing household registration was higher （χ²=12.504， P<0.001）. The DD rate of gross motor was the highest in the 0‒ age group （64.60%）， the DD rate of language was the highest in the <3 age group （85.97%）， and a statistically significant difference of gross motor and language was separately found in the three age groups （χ²=183.061， P<0.001； χ²=78.450， P<0.001）. ConclusionAge and Beijing household registration are the influencing factors of DD for children aged 0‒2， and 0‒ years and <3 years are the critical periods for guidance and intervention to promote the development of gross motor and language abilities.

Objective:To explore the clinical characteristics, treatment patterns, and outcomes in newly diagnosed patients with chronic myeloid leukemia in the chronic phase (CML-CP) by age.Methods:Clinical data of consecutive ≥14 years old newly diagnosed CML-CP patients were retrospectively analyzed.Results:This study included 957 patients. Of the patients, 597 (62.4%) were male. The median age was 40 years (range, 14-83 years) . The patients were stratified into three age groups: <40 years ( n=470; 49.1%) , 40-59 years ( n=371; 38.8%) , and ≥60 years ( n=116; 12.1%) . The proportions of the patients who had splenomegaly ( P<0.001) , WBC ≥100 × 10 9/L ( P<0.001) , anemia ( P<0.001) , PLT<450 × 10 9/L ( P=0.022) , more blasts in the blood ( P=0.010) , and clonal chromosome abnormalities in Philadelphia chromosome-positive cells ( P=0.006) at diagnosis significantly decreased with age. However, the proportions of those with comorbidities ( P<0.001) , intermediate or high Sokal risk ( P<0.001) , and receiving imatinib as front-line therapy ( P<0.001) significantly increased with age. No significant differences in gender and the EUTOS Long-Term Survival risks were noted across the three age groups. The multivariate analysis showed that ≥60 years was an adverse predictor for overall survival. However, age was not significantly associated with tyrosine kinase inhibitor (TKI) therapy responses and other outcomes. The incidences of nonhematological toxicity were significantly increased with age during TKI therapy ( P<0.001) . However, those of hematological toxicity was similar across the three age groups. The proportions of the patients maintaining imatinib therapy ( P=0.026) and receiving low-dose TKI therapy ( P<0.001) significantly increased with age at the end of follow-up. Conclusions:Significant differences exist in clinical characteristics, TKI response, overall survival rates, and nonhematological toxicity among newly diagnosed CML-CP patients of different ages.

Objective:To explore dasatinib-related pulmonary adverse events in patients with chronic myeloid leukemia (CML) .Methods:We retrospectively analyzed the incidence of pleural effusion (PE) and pulmonary arterial hypertension (PAH) in patients with CML treated with dasatinib at Peking University People's Hospital from April 2008 to January 2020.Results:A total of 280 patients were collected. The median dasatinib treatment time was 26 (1-142) months. Ninety (32.1%) patients developed PE, including 40 (44.4%) in grade 1, 44 (48.9%) in grade 2, and 6 (6.7%) in grade 3. The incidence of PE increased gradually with the prolongation of treatment. The multivariate analysis showed that increasing age (every 10 years, HR=1.6; P<0.001) , advanced phase when starting dasatinib therapy ( HR=2.2; P=0.008) , and cardiovascular comorbidity (ies) ( HR=1.9; P=0.018) were significantly associated with developing PE. The advanced phase when starting dasatinib therapy ( HR=3.4; P=0.001) , interval from diagnosis to taking TKI for ≤6 months ( HR=2.2; P=0.015) , and dose < 100 mg/d when PE was found ( HR=3.1; P=0.001) were associated with more severe PE. PE relieved or disappeared after intervention in half of the patients. Among 60 patients with symptoms of cough, chest tightness, and shortness of breath, 49 underwent ultrasonic cardiography; 8 (16.3%) had high probability of PAH, approximately 3.5% in all patients; and 6 (75.0%) of them had PE. PAH was reversible. There was no difference in the incidences of PE and PAH between branded and Chinese generic dasatinib. Conclusion:PE is a common dasatinib-related pulmonary adverse event, and PAH is rare in patients with CML. The identification of individuals with high risk, close monitoring, and timely intervention may help to alleviate PE and PAH.

Objective: To explore Fertility and disease outcomes in patients with chronic myeloid leukemia (CML) . Methods: Clinical and fertility outcomes of male (from Jul. 1998 to Feb. 2018) and female CML (from Sep. 2009 to Feb. 2018) patients were retrospectively analyzed at Peking University People’s Hospital. Results: A total of 49 male CML patients and their spouses were enrolled. Before their spouses conceived, 34 patients were receiving tyrosine kinase inhibitor (TKI) imatinib, 9 with nilotinib, and 6 with dasatinib. At the time of conception, the median age of these male patients was 32 years (range, 25-48 years) , and the median TKI treatment duration was 36 months (range, 0.2-198 months) . One male patient having achieved complete hematologic response yet discontinuing TKI for a year developed a disease progression to blast crisis. The other 48 patients sustained stable disease. The total conception times were 61 and finally 55 infants were born including one with premature birth, two with low birth weight, and one with hypospadias receiving surgery. The other 18 female patients after pregnancy were enrolled. Two patients developed spontaneous abortions. Two received induced abortions. Fourteen gave birth to healthy infants without congenital malformation. The interval from diagnosis of CML to initiation of TKI was 4 months (range, 0.3-16 months) . During a median follow-up of 45 months (range from 7-114 months) , the estimated complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate and molecular response^4.5 (MR^4.5) rate by 5 years were 88.9%, 85.3% and 35.1%, respectively. The estimated failure-free survival, progression-free survival and overall survival were 64.2%, 90.9% and 90.9%, respectively. All 14 babies developed as normal. Conclusions It seems that TKIs do not affect pregnancy outcome in the spouses of male CML patients, suggesting that withdrawal of TKIs is not necessary. Female CML patients have good pregnancy and disease outcomes in the TKI era.

Objective: To compare the cytogenetic and molecular responses, outcomes and severe hematologic toxicity of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: Newly diagnosed CML-CP patients were consecutively recruited from January 2006 to December 2018 who received nilotinib and imatinib as first-line treatment. Clinical data were retrospectively analyzed. Results: A total of 524 patients were classified into 439 (83.8%) receiving imatinib and 85 (16.2%) receiving nilotinib. Comparing with imatinib group, patients in nilotinib group were much younger (P=0.019) and more with intermediate and high Sokal risks (P<0.001) , WBC ≥100×10⁹/L (P<0.001) , HGB<120 g/L (P<0.001) , blast cells in bone marrow (P=0.026) , splenomegaly (P<0.001) by physical examination at diagnosis, and longer interval from diagnosis to TKI treatment (P=0.003) . With a median TKI duration of 57 (range 3-153) months, the probabilities of complete cytogenetic response (CCyR) (P=0.011) , major molecular response (MMR) (P=0.001) and MR^4.5 (P=0.046) were much higher in nilotinib group than those in imatnib according to each risk group. There is no statistical significance on probabilities of failure free survival (FFS) , progression free survival (PFS) and overall survival (OS) at 6 years between the two groups. Multivariate analyses showed that imatinib was an adverse factor associated with achieving CCyR (OR=0.6, 95% CI 0.5-0.8, P=0.001) , MMR (OR=0.6, 95% CI 0.5-0.9, P=0.032) and MR^4.5 (OR=0.6, 95%CI 0.5-0.9, P=0.032) and poor FFS (OR=1.9, 95%CI 1.0-3.4, P=0.041) . In addition, Sokal score was an independent factor affecting cytogenetic and molecular responses, treatment failure, disease progression and survival. Male, WBC ≥100×10⁹/L or HGB<120 g/L at diagnosis were significantly associated with lower cytogenetic and molecular response rates and/or poor FFS. The severe hematologic adverse events were not associated with different TKIs. Conclusions Nilotinib reaches to the faster and deeper cytogenetic and molecular responses and significantly improves FFS than imatinib in newly diagnosed patients with CML-CP.