Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

[Objective]To evaluate the utility of left atrial(LA)volume and strain measured by 4D auto left atrial quantification(4D auto LAQ)in differentiating pre-capillary from post-capillary pulmonary hypertension(PH),and to compare its discriminative performance with echocardiographic pulmonary to left atrial global strain ratio(ePLAGS).[Methods]A total of ninety-eight subjects with intermediate to high probability of PH were prospectively enrolled.Clinical history and laboratory data were collected.All patients underwent comprehensive transthoracic echocardiography,and LA volume and strain parameters were measured by dedicated commercial software for LA 4D analysis.[Results]Based on pulmonary arterial wedge pressure,patients were divided into pre-capillary PH group[n=39;mean age(53±24)years]and post-capillary PH group[n=59;mean age(57±18)years].Compared to the pre-capillary PH group,the post-capillary PH group showed significantly higher LAVImax,LAVImin and LAVIpreA but markedly lower LASr and LAScd.Multivariate logistic regression identified LAVImax[OR:1.40;95%CI:(1.052,1.872);P=0.021]and LAScd[OR:1.76;95%CI:(1.183,2.489);P=0.004]as independent predictors of post-capillary PH.ROC analysis demonstrated that LAVImax(AUC=0.82,P＜0.001)and LAScd(AUC=0.78,P＜0.001)had strong discriminating power for predicting post-capillary PH group,with optimal cutoff values of 35.69 mL/m2(sensitivity 86%,specificity 74%)and-9%(sensitivity 80%,specificity70%).[Conclusion]LAVImax and LAScd measured with 4D auto LAQ are robust parameters for distinguishing pre-capillary PH from post-capillary PH.

[Objective]To evaluate the utility of left atrial(LA)volume and strain measured by 4D auto left atrial quantification(4D auto LAQ)in differentiating pre-capillary from post-capillary pulmonary hypertension(PH),and to compare its discriminative performance with echocardiographic pulmonary to left atrial global strain ratio(ePLAGS).[Methods]A total of ninety-eight subjects with intermediate to high probability of PH were prospectively enrolled.Clinical history and laboratory data were collected.All patients underwent comprehensive transthoracic echocardiography,and LA volume and strain parameters were measured by dedicated commercial software for LA 4D analysis.[Results]Based on pulmonary arterial wedge pressure,patients were divided into pre-capillary PH group[n=39;mean age(53±24)years]and post-capillary PH group[n=59;mean age(57±18)years].Compared to the pre-capillary PH group,the post-capillary PH group showed significantly higher LAVImax,LAVImin and LAVIpreA but markedly lower LASr and LAScd.Multivariate logistic regression identified LAVImax[OR:1.40;95%CI:(1.052,1.872);P=0.021]and LAScd[OR:1.76;95%CI:(1.183,2.489);P=0.004]as independent predictors of post-capillary PH.ROC analysis demonstrated that LAVImax(AUC=0.82,P＜0.001)and LAScd(AUC=0.78,P＜0.001)had strong discriminating power for predicting post-capillary PH group,with optimal cutoff values of 35.69 mL/m2(sensitivity 86%,specificity 74%)and-9%(sensitivity 80%,specificity70%).[Conclusion]LAVImax and LAScd measured with 4D auto LAQ are robust parameters for distinguishing pre-capillary PH from post-capillary PH.

【Objective】 To clarify the role and molecular mechanism of Tanshinone ⅡA (TanⅡA) in the pathological integration of granule cells in the dentate gyrus (DG) by using the mouse model of temporal lobe epilepsy (TLE). 【Methods】 Status epilepticus (SE) was induced in the mice with pilocarpine and treated with TanⅡA 5 mg/kg. After two months, Morris water maze was used to examine the spatial learning and memory ability and video surveillance was used to monitor spontaneous seizures. The DG was removed for staining of Timm, Prox-1, DCX and SynⅠ. PTEN, p-AKT, and p-S6 expressions were observed by Western blotting. 【Results】 TanⅡA decreased Timm score, SynⅠ, PSD-95 and pS6 levels, and increased the level of PTEN in the DG, and attenuated the formation of mossy fiber sproutings and basal dendrites of the granule cells. Video surveillance showed that TanⅡA reduced the frequency of Racine’ grade 5 seizures. 【Conclusion】 TanⅡA can effectively attenuate the abnormal integration of the granule cells in the DG by regulating PTEN/AKT/mTOR pathway and thus plays an anti-epileptic role.

Abstract: Objective　The method of "molecular docking - molecular dynamics - in vitro pharmacology" was used to screen and optimize small molecule polypeptide compounds that can block PD-1/PD-L1 binding and have high anti-tumor activity. Methods Using the 5-peptide compound database constructed by our team and the three-dimensional structure data of the PD-L1 protein downloaded from the protein database (PDB), the peptide compounds obtained by flexible molecular docking using Molecular Operating Environment software. The molecular dynamics calculation and analysis of the compounds with the highest GWVI/WSA (generalized Born volume integral/weighted surface area) free energy change value (ΔG) were carried out, including the root mean square deviation (RMSD) of the position change of the weight atom and the interaction energy (the sum of Lennard-Jones potential and Coulombic energy). The blocking effect of ligand compounds on PD-1/PD-L1 binding was analyzed by the homogeneous time-resolved fluorescence (HTRF) technique. The co-culture system of Jurkat T lymphocytes and melanoma B16-F10 cells was established to explore the effect of compound ligands on the killing effect of T cells on tumors and the effect on the secretion level of IL-2 in the co-culture supernatant. Results The selected polypeptide compounds were analyzed by molecular dynamics, and the binding of RGGHA to RGGHH and PD-L1 was stable. There are many kinds of interactions between RGGHA and PD-L1，which can compete with PD-1 ligands to bind Asp122, Try123 and Lys124 sites of the PD-L1 protein and block PD-1/PD-L1 signal transduction. HTRF experiments showed that the binding inhibition rate of RGGHA to PD-1 and PD-L1 was 58.38%, and that of RGGHH was 42.73%. In addition, we established a co-culture system of Jurkat T lymphocytes and melanoma B16-F10 cells to explore the immunostimulatory effect and mechanism of peptides. The results show that RGGHA and RGGHH can significantly increase the secretion level of IL-2, improve the killing ability of T cells against tumor cells and activate the tumor immune microenvironment. Conclusions The study found that the polypeptide compounds RGGHA and RGGHH can effectively block the PD-1/PD-L1 interaction and reactivate the anti-cancer immune response, which can be used as lead compounds for new drug development.

Objective:To find out the occurrence of anxiety and depressive symptoms, and the major risk factors, and the participation rate, as well as the experience of medical personnel who are involved in the intervention.Methods:Since January 2018, a pilot intervention had been carried out on pregnant women registered in the antenatal clinic. The Generalized Anxiety Disorder Scale and the Patient Health Questionnaires were used as screening tools for anxiety and depression symptoms, and risk factors were screened too. Interventions were carried out on the psychological moderate and high risk women by obstetric medical staff and mental health personnel. A qualitative interview was conducted on the intervention providers.Results:A total of 9 488 pregnant women were included, and the positive rate of moderate anxiety symptoms was 3.0%, the positive rate of severe anxiety symptoms was 1.4%; the positive rate of moderate depression symptoms was 18.1%, and the positive rate of severe depressive symptoms was 5.2%; the comorbidity rate of anxiety and depression symptoms was 3.4%. The first three risk factors for pregnant women with anxiety symptoms were: once had premenstrual stress symptom, excessive fear of fetal growth, previous abnormal maternal history; the first three risk factors for pregnant women with depressive symptoms: once had premenstrual stress symptom, previous abnormal maternal history, this pregnancy was cherished; the first three risk factors for pregnant women with moderate and above anxiety combined with depression were: once had premenstrual stress symptom, excessive fear of fetal growth, and fear the delivery process is not successful. Among the psychological moderate risk pregnant women, 19.1% participated in the midwife joint counselor clinic, and 1.7% participated in the obstetrician joint psychological specialist nurse clinic, 2.2% of the pregnant women with high risk participated in the psychological multidisciplinary consultation, and 1.7% referred to the psychiatric department. From the interviews, providers believed that it was necessary to further strengthen the ability of psychological intervention capacity, and the psychological screening tools needed to be improved, and the problems sought by pregnant women involved in physical, psychological and social aspects, and the influence of pregnant women's treatment compliance included multiple factors.Conclusions:The psychological health care service during pregnancy was feasible, but the screening scales needed further examination. The mental health care ability of obstetric medical staff needed to be strengthened, and the compliance of pregnant women with mental health services needed to be improved.

A limited number of microRNAs (miRNAs, miRs) have been reported to control postnatal cardiomyocyte proliferation, but their strong regulatory effects suggest a possible therapeutic approach to stimulate regenerative capacity in the diseased myocardium. This study aimed to investigate the miRNAs responsible for postnatal cardiomyocyte proliferation and their downstream targets. Here, we compared miRNA profiles in cardiomyocytes between postnatal day 0 (P0) and day 10 (P10) using miRNA arrays, and found that 21 miRNAs were upregulated at P10, whereas 11 were downregulated. Among them, miR-31a-5p was identified as being able to promote cardiomyocyte proliferation as determined by proliferating cell nuclear antigen (PCNA) expression, double immunofluorescent labeling for α-actinin and 5-ethynyl-2-deoxyuridine (EdU) or Ki-67, and cell number counting, whereas miR-31a-5p inhibition could reduce their levels. RhoBTB1 was identified as a target gene of miR-31a-5p, mediating the regulatory effect of miR-31a-5p in cardiomyocyte proliferation. Importantly, neonatal rats injected with a miR-31a-5p antagomir at day 0 for three consecutive days exhibited reduced expression of markers of cardiomyocyte proliferation including PCNA expression and double immunofluorescent labeling for α-actinin and EdU, Ki-67 or phospho-histone-H3. In conclusion, miR-31a-5p controls postnatal cardiomyocyte proliferation by targeting RhoBTB1, and increasing miR-31a-5p level might be a novel therapeutic strategy for enhancing cardiac reparative processes.
Animals ; Cell Count ; MicroRNAs ; Myocardium ; Myocytes, Cardiac* ; Negotiating ; Proliferating Cell Nuclear Antigen ; Rats

Objective To explore the relationship between achievement motivation,procrastination and positive mental health of college students.Methods A total of 348 students completed a survey that in-cluded Achievement Motivation Scale(AMS),General Procrastination Scale(GPS)and Mental Health Con-tinuum Short Form(MHC-SF).Results (1)The average scores of achievement motivation,procrastination and positive mental health in college students were 3.61±12.05,56.48±10.62 and 3.46±0.82 respectively. The proportion of flourishing student was accounted for 53.16%,44.83% for the moderately mentally healthy and 2.01% for the languishing.(2)College students' achievement motivation was positively correlated with positive mental health(r=0.399,P<0.01),achievement motivation was negatively correlated with procrasti-nation(r=-0.388,P<0.01)and procrastination was negatively correlated with positive mental health(r=-0.267,P<0.01).(3)Procrastination had a partial mediating effect between achievement motivation and positive mental health,and the proportion of mediating effect in total effect was 12.75%.In three dimensions of positive mental health,procrastination also had partial mediating effect between achievement motivation and psychological well-being and emotional well-being respectively,the proportion of mediating effect in total effect were 15.71% and 20.63% respectively.But the mediating effect between achievement motivation and social well-being was not significant.Conclusion College students with higher achievement motivation have higher positive mental health,but the procrastination has indirect negative effect between the two variables,which leads to the negative effect of emotional and psychological well-being in the positive mental health condition.

Objective To investigate the surgical strategy and outcome for occipitocervical extramedullary tumors.Methods 15 patients with occipitocervical extramedullary tumors from January 2007 to July 2010 were reviewed retrospectively.There were 7 males and 8 females with an mean age of 44.6 years (range,21-72 years).All cases were intradural tumors,including 7 cases in dorsolateral,5 cases in lateral side,and 3 cases in ventralis of spinal cord.Functional and neurological statuses were assessed using the Frankel grade and Japanese Orthopaedic Association (JOA) scale.According to Frankel grade system,there were 4 patients with Grade C,8 with Grade D,and 3 with Grade E.The mean preoperative JOA score was 10.5±3.6.Based on the tumor site,there were 5 cases in medulla oblongata-C1 and 10 cases in C1,2.Frankel grade and JOA score were used to evaluate neurological status and general health.The improvement of symptoms and characteristics of surgical strategies were analyzed.Results All cases were followed up for 2-4 years (mean 2.8 years).Complete resection of tumor and good fusion of bone graft were found in radiography postoperatively.The pathological diagnoses included 10 cases of schwannoma,3 cases of meningioma and 2 cases of neurofibroma.There was statistical difference between the preoperative and the final follow-up functional and neurological statuses including Frankel grade and JOA score.At the latest follow-up,2 cases improved from Frankel grade C to D,2from C to E,6 from D to E,but none in 2 cases with grade D.The mean JOA score at final follow-up was 15.6±1.6,and the average improvement rate was 80.7％± 17.4％.The mean preoperative C0-2 angle was 27.0°±4.1 °,and C2-7 angle was 16.8°± 12.7°.C0-2 angle was 27.6°±8.8°,and C2-7 angle was 10.2°±6.8° at the latest follow-up.However,these differences did not reach statistical significance.Conclusion Surgical treatment can effectively maintain or improve neurological function and improve quality of life.Extramedullary tumors can be resected completely by posterior approach,and spinal stabilization can be obtained satisfactorily through selecting appropriate surgical strategies.For medulla oblongata-C1 level,occipitocervical fusion is usually chosen after extirpation of tumor.For C 1,2 level,C1,2 fusion after tumor resection is useful in preventing atlantoaxial instability.