Objective: To analyze the distribution and related factors of spherical equivalent(SE) anisometropia in school aged children in ethnic minority areas of Yunnan Province, so as to provide a scientific basis for the intervention and control of SE anisometropia. Methods: In October 2021,a total of 1 852 school aged children in three counties/cities(Lijiang City,Dali City,Xishuangbanna) in Yunnan Province were examined by multi stage cluster random sampling method for computer optometry visual acuity examination for non ciliary paralysis and questionnaire survey.Demographic characteristics, ocular biological parameters and SE data were obtained for SE anisometropia. Group comparisons were conducted using Mann-Whitney U test or Kruskal-Wallis H test, and Logistic regression was used to explore the related factors of anisometropia in SE. Results: The prevalence of SE anisometropia among school age children was 23.0%, and the prevalence was higher in girls (24.2%) than that in boys (21.6%). Compared with non anisometropic children, school aged children with SE anisometropia had longer axial length (AL) [24.03 (23.41, 24.76), 23.93 (23.26, 24.61) mm] and corneal curvature radius (CR) [43.42 (42.43, 44.42), 43.14 (42.23, 44.04)mm], SE[-1.75(-2.75,-1.00),-0.94(-2.63,-0.25)D], smaller spherical scope [-1.38(-2.38,-0.75),-0.75(-2.38,0)D], deeper anterior chamber depth(ACD)[3.77(3.62, 3.93), 3.72(3.55, 3.89)mm], and grater differences in AL[0.58(0.32,0.82), 0.13( 0.06 ,0.22)mm], ACD[0.05(0.02,0.08), 0.03(0.01,0.06)mm] and AL/CR[0.01(0.01,0.02), 0.01(0.00,0.01)]( Z =-22.47 to -2.41, all P <0.05). The results of Logistic regression showed that mild myopia( OR =2.74), moderate myopia( OR =3.52), and high myopia( OR =8.92) had a relatively high risk of anisometropia SE in school aged children(all P <0.05). Conclusion The prevalence of SE anisometropia in school aged children in ethnic minority areas of Yunnan Province is relatively high, and the prevalence and degree of anisometropia were closely related to myopia degree and related refractive parameters.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Background Improper settings of outdoor smoking points in public places may increase the risk of secondhand smoke exposure among the population. Conducting research on air pollution in and around smoking spots and related influencing factors can provide valuable insights for optimizing the setting of outdoor smoking points. Objective To investigate the influence of the number of smokers at outdoor smoking points and the distance on the diffusion characteristics of surrounding air pollutants, in order to optimize the setting of outdoor smoking points. Methods Surrounding the exhibition halls in the China International Import Expo (CIIE), two outdoor smoking points were randomly selected, one on the first floor (ground level) and the other on the second floor (16 m above ground), respectively. At 0, 3, 6, and 9 m from the smoking points in the same direction, validated portable air pollutant monitors were used to measure the real-time fine particulate matter (PM_2.5) and carbon dioxide (CO₂) concentrations for consecutive 5 d during the exhibition, as well as the environmental meteorological factors at 0 m with weather meters including wind speed, wind direction, and air pressure. An open outdoor atmospheric background sampling point was selected on each of the two floors to carry out parallel sampling. Simultaneously, the number of smokers at each smoking point were double recorded per minute. The relationships between the number of smokers, distance from the smoking points, and ambient PM_2.5 and CO₂ concentrations were evaluated by generalized additive regression models for time-series data after adjustment of confounders such as temperature, relative humidity, and wind speed. Results The median numbers of smokers at smoking points on the first and second floors were 6 [interquartile range (IQR): 3, 9] and 9 (IQR: 6, 13), respectively. Windless (wind speed <0.6 m·s⁻¹) occupied most of the time (85.9%) at both locations. The average concentration of ambient PM_2.5 at the smoking points (0 m) [mean ± standard deviation, (106±114) μg·m⁻³] was 4.2 times higher than that of the atmospheric background [(25±7) μg·m⁻³], the PM_2.5 concentration showed a gradient decline with the increase of distance from the smoking points, and the average PM_2.5 concentration at 9 m points [(35±22) μg·m⁻³] was close to the background level (1.4 times higher). The maximum concentration of CO₂ [(628±23) μmol·mol⁻¹] was observed at 0 m, and its average value was 1.3 times higher than that of the atmospheric background [(481±40) μmol·mol⁻¹], and there was no gradient decrease in CO₂ concentration with increasing distance at 0, 3, 6, and 9 m points. The regression analyses showed that, taking smoking point as the reference, every 3 m increase in distance was associated with a decrease of ambient PM_2.5 by 24.6 [95% confidence interval (95%CI): 23.5, 25.8] μg·m⁻³ (23.2%) and CO₂ by 54.1 (95%CI: 53.1, 55.1) μmol·mol⁻¹ (8.6%). Every one extra smoker at the smoking point was associated with an average increase of PM_2.5 and CO₂ by 2.0 (95%CI: 1.7, 2.8) μg·m⁻³ and 1.0 (95%CI: 0.7，1.2) μmol·mol⁻¹, respectively. The sensitivity analysis indicated that, under windless conditions, the concentrations of PM_2.5 and CO₂ at the smoking points were even higher but the decreasing and dispersion characteristics remained consistent. Conclusion Outdoor smoking points could significantly increase the PM_2.5 concentrations in the surrounding air and the risks of secondhand smoke exposure, despite of the noticeable decreasing trend with increasing distance. Considering the inevitable poor dispersion conditions such as windless and light wind, outdoor smoking points are recommended to be set at least 9 m or farther away from non-smoking areas.

Objective To screen differentially-expressed circRNA in plasma exosomes of patients with non-small cell lung cancer(NSCLC)and verify its diagnostic value for NSCLC.Methods The plasma exosomes of six patients with NSCLC and six healthy people were analyzed by circRNA sequencing.The expression of hsa_circ_0052513 in plasma exosomes of 60 NSCLC patients and 60 healthy controls was detected by qRT-PCR.The expression level of hsa_circ_0052513 in plasma exosomes of NSCLC patients before and after surgery was detected by qRT-PCR.The correlation between the expression of plasma exosomal hsa_circ_0052513 and clinical data of patients with NSCLC was statistically analyzed.Results Sequencing results showed that the expression of hsa_circ_0052513 in the plasma exosomes of NSCLC patients was higher than that of healthy controls,and the results were confirmed by qRT-PCR.Hsa_circ_0052513 was decreased in patients with NSCLC after tumor resection(P<0.05).The high expression of plasma exosomal hsa_circ_0052513 in patients with NSCLC was correlated with tumor size,distant metastasis,and TNM stage of NSCLC(all P<0.05).The area under the curve of plasma exosomal hsa_circ_0052513 in the diagnosis of patients with NSCLC was 0.7904(P<0.0001).Conclusion Hsa_circ_0052513 is highly expressed in the plasma exosomes of patients with NSCLC and is related to tumor size,metastasis,and TNM stage.Hence,Hsa_circ_0052513 could be a new diagnostic marker for NSCLC.

Objective:To explore the prognostic value of systemic immune-inflammatory index(SII)combined with tumor burden score (TBS) (hereinafter referred to as STS) in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection, and to construct a nomogram model.Methods:The clinical data (including the degree of tumor differentiation, vascular cancer thrombus, and lymph node metastasis, etc.) of 258 ICC patients who received radical resection at People′s Hospital of Zhengzhou University (170 cases, training set) and Cancer Hospital of Zhengzhou University (88 cases, validation set) from January 1, 2016 to January 31, 2020 were retrospectively analyzed and graded by SII, TBS and STS. Multivariate Cox regression analysis were used to identify independent factors affecting the prognosis of patients with ICC. Kaplan-Meier survival curve and receiver operating characteristic curve (ROC) were drawn to evaluate the predictive efficiency of SII, TBS and STS in the overall survival of patients with ICC after radical resection. The nomogram prediction model was constructed and evaluate the performance of nomogram model using consistency index (C-index) and calibration curve.Results:Among 170 ICC patients in the training set, there were 106 cases of SII grade 1 and 64 cases of SII grade 2; 137 cases of TBS grade 1 and 33 cases of TBS grade 2; and 98 cases of STS grade 1, 47 cases of STS grade 2, and 25 cases of STS grade 3. Among 88 ICC patients in the validation set, there were 33 cases of SII grade 1 and 55 cases of SII grade 2; 66 cases of TBS grade 1 and 22 cases of TBS grade 2; and 30 case of STS grade 1, 39 cases of TBS grade 2, and 19 cases of TBS grade 3.The multivariate Cox regression analysis showed that tumor differentiation degree (highly differentiated vs. moderately differentiated HR=0.157, 95% confidence interval(95% CI) 0.045 to 0.546, highly differentiated vs. poorly differentiated HR=0.452, 95% CI 0.273 to 0.750), STS (grade 3 vs. grade 2 HR=1.966, 95% CI 1.148 to 3.469; grade 3 vs. grade 1 HR=1.405, 95% CI 0.890 to 2.216), vascular cancer thrombus ( HR=2.006, 95% CI 1.313 to 3.066), nerve invasion ( HR=1.865, 95% CI 1.221 to 2.850), and lymph node metastasis ( HR=1.802, 95% CI 1.121 to 2.896) were independent influencing factors of overall survival in ICC patients after radical resection (all P<0.05). The Kaplan-Meier survival curve showed that SII, TBS, and STS were independent influencing factors of overall survival in ICC patients (all P<0.05). The results of ROC analysis showed that the areas under the curve of SII, TBS and STS in predicting overall survival of ICC patients after radical resection were 0.566 (95% CI 0.479 to 0.652), 0.585 (95% CI 0.499 to 0.672), and 0.657 (95% CI 0.522 to 0.692), respectively. Tumor differentiation, vascular tumor thrombus, nerve invassion, lymph node metastasis, and STS were included to constract the nomogram model. The C-indexes of the training set and validation set based on the nomogram model were 0.792 (95% CI 0.699 to 0.825) and 0.776 (95% CI 0.716 to 0.833), respectively. The calibration curves of the survival rate of the training set and the validation set were close to the reference lines, and the nomogram model had better predictive ability in both the training set and the validation set. Conclusions:Preoperative STS grading is an effective and practical predictor of overall survival in ICC patients after radical section. Compared with SII and TBS alone, it has better predictive value for the prognosis of patients with ICC.

Objective:A predictive nomogram model for the prognosis of intrahepatic cholangiocarcinoma (ICC) patients after curative resection was constructed based on the albumin-bilirubin score and tumor burden score (ATS) grade, and the predictive performance of the nomogram model was evaluated.Methods:Retrospective analysis of clinical data was made, from ICC patients who underwent curative resection at Zhengzhou University People's Hospital and Zhengzhou University Cancer Hospital from January 2016 to January 2020. A total of 258 patients were included in the study, with 140 males and 118 females, with an average age of (56.5±9.5) years. The 258 ICC patients were randomly divided into a training set ( n=174) and a testing set ( n=84) in a 7∶3 ratio. Single-factor and multi-factor Cox regression analyses were performed to identify prognostic factors for ICC patients of the training set, and then a nomogram model was constructed. The performance of the nomogram model was evaluated by using the concordance index (C-index), calibration curve, and risky decision curve analysis. Results:In the training set, univariate Cox regression analysis indicated that albumin-bilirubin (ALBI), tumor burden score (TBS), carcinoembryonic antigen (CEA), tumor differentitation, lymphvascular invasion and ATS significantly influenced overall survival after radical resection for ICC (all P<0.05). Multifactorial Cox regression analysis revealed that ATS grade, CEA, tumor differentiation, lymphovascular invasion, and AJCC N stage are independent risk factors for the prognosis of ICC patients after curative resection (all P<0.05). Assessment of the postoperative survival prediction model based on multifactorial Cox regression yielded a C-index of 0.775(95% CI: 0.747-0.841) for the training set and 0.731(95% CI: 0.668-0.828) for the testing set. The calibration curves for both the training and testing sets indicated strong predictive capability of the model. Additionally, the risk decision curve also suggested high net benefit of the model. Conclusions:The preoperative ATS grade is an independent factor affecting the survival after ICC radical resection. The nomogram model constructed based on ATS grade demonstrates excellent predictive value for postoperative prognosis in ICC patients.

Objective:To explore the efficacy and compliance of e-aid cognitive behavioral therapy (eCBTI) in patients with situational insomnia among different age groups.Methods:A total of 194 patients with situational insomnia were recruited via a campaign of the " Prevention and Protection Handbook Against Epidemic" from March to April 2020 in Guangzhou, China.Participants were divided into two groups according to age: under 35 years old ( n=87) and 35 years old and above ( n=107). They all received one-week eCBTI intervention.Insomnia severity index (ISI), Pre-sleep arousal scale (PSAS) and Hospital anxiety and depression scale (HADS) were used to evaluate the severity of insomnia for all participants pre- and post-intervention.The change of each scale within the group and the reduction rate of each scale between groups were compared using t test and one-way ANOVA. Results:(1) Intervention efficacy: in the <35-year-old group, compared with baseline, the scores of ISI scale ((9.2±4.1), (14.8±5.1)), PSAS cognitive arousal subscale ((18.5±8.4), (23.5±6.6)), PSAS((34.3±15.8), (40.3±10.7)), HADS depression subscale ((5.8±3.6), (8.5±4.6)) and HADS anxiety subscale((7.1±3.9), (9.5±4.5) )were statistically significant after eCBTI intervention ( t= 2.88-8.80, all P<0.01), but there was no significant difference in score of PSAS body subscale ((15.8±7.8), (16.8±5.7)). In ≥35-year-old group, compared with baseline, the scores of ISI scale ((9.7±4.2), (14.4±4.3)), HADS depression subscale ((4.6±2.2), (6.6±3.5))and PSAS cognitive arousal subscale ((16.9 ±8.5), (20.0±5.8))were significantly different after intervention ( t= 2.90-6.86, all P<0.01), meanwhile the scores of PSAS body subscale ((14.3±8.0), (13.9±5.2)), PSAS((32.2±16.5), (33.9±9.2)), HADS anxiety subscale((6.1±3.2), (7.0±3.5)) were not statistically significant (all P>0.05). There was no significant difference in the score reduction rate between the two groups before and after intervention (all P>0.05). (2) Compliance: 86 cases dropped out, and the dropout rate was 61.3%.Totally 75 cases (38.7%) completed the 7-day treatment, and 119 cases (61.3%) completed the treatment within 1-6 days.Further study found that there was statistically significant difference in the reduction rate of ISI total score among the three groups with excellent, good and poor compliance ( F=5.655, P=0.004). Conclusion:eCBTI has a good effect on situational insomnia in different age groups, and there is no difference in treatment compliance.

OBJECTIVE：To optimize the extraction technology of Zhideke granules. ME THODS：The extraction technology （water extraction ，alcohol extraction ，water extraction and ethanol precipitation ）of Zhideke granules was initially screened by ammonia-induced cough experiment and xylene-induced ear swelling experiment in mice. Based on its preparation route ，the immersion time of medicinal materials containing volatile oil was investigated with water absorption as index firstly. The single factor test was adopted to investigate the amount of water added and the extraction time taking the volatile oil yield as index to optimize the extraction technology of medicinal materials containing volatile oil. Taking the contents of irisflorentin and total flavonoids as indicators ，on the basis of single factor investigation ，orthogonal test was adopted to examine the influence of three factors including the amount of water added ，extraction time and extraction frequency ，so as to optimize the water extraction technology of Zhideke granules and the validation tests were conducted. RESULTS ：The results of pharmacodynamics experiment showed that the cough latency of mice in water extract low-dose and high-dose groups （6.34，12.68 g/kg，by crude drug ）and water-extraction alcohol-precipitation extract high-dose group （12.68 g/kg，by crude drug ）were significantly longer than those inmodel group ，and the number of cough within 2 minutes was significantly reduced （P＜0.05 or P＜0.01）. Compared with model group ， the ear swelling of mice in water extract low-dose and high-dose groups （6.34，12.68 g/kg，by crude drug），ethanol extract high-dose group （12.68 g/kg，by crude drug） and water-extraction alcohol-precipitation extract hig dose group （12.68 g/kg，by crude drug ） were decreased significantly （P＜0.05 or P＜0.01）. The swelling inhibition rates were 42.26％，55.08％，33.49％，51.56％，39.57％ and 44.36％ in low-dose and high-dose groups of water extract ，alcohol extract ， water-extraction and alcohol-precipitation extract respectively ，indicating that the water extract had better antitussive and anti-inflammatory effects. The optimal extraction technology of volatile oil was adding 5-fold water ，soaking for 30 minutes，and extracting for 3 hours. The optimal water extraction technology was adding 12-fold water ，extracting for 3 times after soaked for 50 min，lasting for 1 h each time. Results of 3 times of validation tests showed that average content of irisflorentin in the extract obtained by optimal technology was 76.47 μg/g（RSD＝ 2.15％，n＝3）and the average content of total flavonoids was 92.45 mg/g（RSD＝0.48％，n＝3）. CONCLUSIONS ：The optimal extraction technology of Zhideke granules is stable and feasible.

Acute-on-chronic liver failure (ACLF) is a clinical disease significantly different from acute liver failure and acute decompensation of simple liver cirrhosis, and it may have acute progression to liver failure and failure of other organs. ACLF has a high short-term mortality rate and has become a disease burden worldwide. In recent years, several international associations for the study of the liver have proposed different diagnostic criteria for ACLF and published their respective consensus or review on the diagnosis and treatment of ACLF, and there are still great differences in the comprehension of chronic liver diseases, acute injury, and organ failure. At present, there are still limited data for the key links of ACLF management in China, such as liver transplantation, intensive care unit, and palliative care, and in the context of no consensus on the diagnosis of ACLF around the world, it is necessary to further strengthen the application of existing international criteria and evidence and the accumulation of evidence-based data in China.

Objective To construct an objective analysis system of corneal nerve tortuosity and detect the changes of corneal subbasal nerve tortuosity in patients with dry eye and diabetes. Methods GradeⅠtoⅣnerve tortuosity were evaluated and 80 photos of each grade were randomly chosen from the in vivo confocal microscopy library. Nerve fibers were extracted,segmented and then analyzed by 6 tortuosity related parameters including L C, Seg L C mean,Cur mean,Specific p,ICM and SCC mean. After verifying the validaty of parameters above,a cross-sectional study was conducted. Subjects were collected from June,2018 to February,2019 in Peking University Third Hospital,and were divided into healthy control group (28 persons 56 eyes),dry eye without diabetes group (28 patients 56 eyes),diabetes without dry eye group(24 patients 48 eyes),diabetes with dry eye group (23 patients 46 eyes) . Basic and dry eye information includes sex,age,ocular surface disease index ( OSDI) ,tear film break-up time (TBUT),Schirmer Ⅰ test (SⅠt) and corneal fluorescence staining (CFS) score. Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were detected in diabetic patients. Cochet-Bonnet examination (C-BE) was detected to evaluate corneal sensation and 2 corneal subbasal nerve photos of each eye were selected for effective tortuosity and density related parameters analysis. Data was analyzed by SPSS and diagnostic test were perfomed by MedCalc. This study followed the Declaration of Helsinki. This study protocol was approved by Ethic Committee of Peking University Third Hospital ( No. IRB00006761-M2017354 ) . Written informed consent was obtained from each subject prior to entering study cohort. Results L C,Seg L C mean,Cur mean,Specific p,ICM and SCC mean increased as the nerve tortuosity increased from Grade Ⅰ to Grade Ⅳ,with an overall significance among 4 groups (F=39. 100, 36. 367,57. 743,4. 043,6. 818,33. 493;all at P<0. 01). Among the above 6 parameters,Cur mean and L C of any two groups were of significant difference (all at P<0. 01). Twenty three to twenty eight persons were enrolled in each group of the cross-sectional study. Sex and age were comparable among 4 groups. Diagnostic criteria were met in dry eye and diabetes. Corneal sensation parameter C-BE decreased in diabetes without dry eye group and diabetes with dry eye group compared with healthy control group ( all at Adj P<0. 05 ) , other than in dry eye without diabetes group (AdjP≥0. 05). Nerve density of diabetes without dry eye group and diabetes with dry eye group was lower compared with healthy control group(all at P<0. 001),while no significant difference between dry eye without diabetes group and healthy control group(P≥0. 05). Among the effective parameters of tortuosity,L C,Cur mean,Seg L C mean and SCC mean of dry eye without diabetes group,diabetes without dry eye group,diabetes with dry eye group were higher compared with healthy control group ( all at P<0. 05 ) . Diagnostic tests of tortuosity related parameters all showed an area under curve (AUC) from 0. 5 to 0. 7. Conclusions L C and Cur mean can be used to analyze corneal nerve curvature more reliably. Compared with normal volunteers,patients of dry eye or diabetes show higher corneal subbasal nerve tortuosity.