Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Research Progress on Mechanisms of Triggeringreceptor Expressed on Myeloid Cells-2 in Cognitive Dysfunction / 中山大学学报(医学科学版)

The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses / 中华儿科杂志

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Incidence and clinical characteristics of engraftment syndrome after syngeneic hematopoietic stem cell transplantation in patients with hematological diseases / 中华血液学杂志

Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes / 亚洲男科学杂志(英文版)

Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

Effect of Yin Yang protein 1 transcriptionally regulating acetyl-CoA carboxylase 1 on the cell migration and lipogenesis in ovarian cancer / 肿瘤研究与临床

Objective:To investigate the expression of acetyl-CoA carboxylase 1 (ACC1) in ovarian cancer tissues and cells, and the related mechanisms of the effect of ACC1 on cell migration and lipogenesis in ovarian cancer.Methods:Samples including 1 case of normal ovarian tissue, 1 case of ovarian cancer primary lesion tissue and 1 case of ovarian cancer omentum metastatic tissue diagnosed by pathology examination of patients undergoing surgery resection who admitted to Linyi Cancer Hospital between January 2019 and December 2021 were collected. Immunohistochemistry was used to detect the protein levels of ACC1 and Yin Yang protein 1 (YY1) of all tissues. The PROMO database was used to predict the possible binding sites of YY1 and ACC1 promoter region. Through the assembled viral vector, the HEY cells of human ovarian cancer with ACC1 or YY1 expression [the untreated cells were treated as the negative control (NC)], or knocked down ACC1 or YY1 (the interference sequence sh1, sh2, sh3 was transferred to the target gene, and the negative control sequence shNC was transferred to the interference sequence). Double luciferase reporter gene assay was used to verify the binding sites of YY1 and ACC1 promoter and the activity of transcriptional regulation. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of ACC1 and YY1 in the treated HEY cells, respectively. Transwell assay was used to detect the migration ability of HEY cells. Oil red O staining and Nile red staining were used to detect the lipid droplets in HEY cells.Results:The immunohistochemical scores of ACC1 and YY1 were 0, 2, 8 scores and 0, 4, 6 scores, respectively in normal ovarian tissue, primary lesion of ovarian cancer, and omentum metastatic tissue. Transwell assay showed that the number of invasive HEY cells in ACC1 overexpression group was more than that in NC group [(87.7±7.4) vs. (52.2±4.2), t = 5.19, P = 0.003]. The number of invasive HEY cells in ACC1-sh1 group, and ACC1-sh2 group with the knockdown of ACC1 was less than that in shNC group [(21.2±1.5), (29.7±2.3) vs. (56.2±5.3); t value was 6.41, 3.77; P < 0.001, P < 0.005]. The number of lipid droplets in HEY cells in the ACC1 overexpression group was more than that in the control NC group [Oil red O staining: (301±25) vs. (215±21); Nile red staining: (287±15) vs. (207±10); all P < 0.05]; the number of lipid droplets in HEY cells in ACC1-sh1 and ACC1-sh2 group with the knockdown of ACC1 was less than that in ACC1-shNC group [Oil red O staining: (113±8), (119±12) vs. (195±18); Nile red staining: (82±8), (117±11) vs. (165±17); all P < 0.05]. The result of dual luciferase reporter assay showed that overexpression of YY1 promoted the luciferase activity of the wild type ACC1 promoter region report gene ( P = 0.003), while the luciferase activity of the report gene was inhibited compared with the wild type after the mutation of binding sites of YY1 in ACCI promoter region ( P = 0.008). Western blot results showed that the expression levels of YY1 and ACC1 protein in HEY cells with YY1 overexpression group were higher than those in NC group, which indicated a synergistic increasing trend of both YY1 and ACC1; the expression levels of YY1 and ACC1 protein in YY1-sh1 group, YY1-sh2 group and YY1-sh3 group with the knockdown of YY1 were lower than those in the control YY1-shNC group, which indicated a synergistic decreasing trend of both YY1 and ACC1. Conclusions:ACC1 and YY1 are highly expressed in ovarian cancer metastatic tissues and both show a positive correlation trend. The expression level of ACC1 in vitro has an impact on cell migration and lipogenesis in ovarian cancer via YY1 transcriptionally regulating ACC1.

A nomogram based on CT enterography signs for prediction of intestinal penetrating lesions in patients with Crohn disease / 中华放射学杂志

Objective:To explore the value of a nomogram model based on the CT enterography (CTE) signs for prediction of intestinal penetrating lesions in patients with Crohn disease (CD).Methods:The clinical and CTE data of CD patients who underwent at least two CTE examinations from January 2010 to June 2020 in the First Affiliated Hospital of Sun Yat-sen University were retrospectively collected. A total of 112 patients were enrolled, and according to whether there was intestinal wall penetration in the last CTE observation were divided into non-penetration group (84 cases) and penetration group (28 cases). First, the clinical and CTE data for the first examination was analyzed by using univariate and multivariate Cox proportional hazards regression to screen out high-risk factors that could effectively predict intestinal wall penetrating lesions in CD patients and established a nomogram model. Then the change trend of CTE data (ΔCTE) between the first and last clinical and CTE signs was analyzed by using univariate and multivariate Cox proportional hazards regression, and built a nomogram model to sort out ΔCTE that may accompany the development of penetrating lesions in CD patients. The Harrell concordance index was used to evaluate the discriminative ability of the nomogram model.Results:In the first time clinical and CTE signs, multivariate Cox proportional hazards regression results showed that numbers of diseased bowel segments (HR=0.686, 95%CI 0.475-0.991, P=0.045) and the shortest diameter of the largest lymph node (HR=0.751, 95%CI 0.593-0.949, P=0.017) were independent protection factors for penetrating lesions, and rough bowel wall surface (HR=5.626, 95%CI 2.466-12.839, P<0.001) was an independent risk factor for penetrating lesions. The specificity and sensitivity of the nomogram model to predict non-penetration lesions were 82.1% and 59.5% respectively, and the Harrell concordance index was 0.810 (95%CI 0.732-0.888). In the ΔCTE signs, multivariate Cox proportional hazards regression showed that Δrough bowel wall surface (always rough bowel wall surface HR=12.344, 95%CI 2.042-74.625, P=0.006; slide bowel wall surface becomes rough bowel wall surface HR=28.720, 95%CI 4.580-180.112, P<0.001) and Δthe shortest diameter of the largest lymph node (HR=1.534, 95%CI 1.091-2.157, P=0.014) were independent risk factors for penetrating lesions. The specificity and sensitivity of the nomogram model were 89.3% and 79.2% respectively, and the Harrell concordance index was 0.876 (95%CI 0.818-0.934). Conclusion:The nomogram based on CTE signs of numbers of diseased bowel segments, the shortest diameter of the largest lymph node and rough bowel wall surface and ΔCTE can effectively predict the intestinal wall penetrating lesions of CD patients.

Status quo and influencing factors of grief in maternal spouses after perinatal loss / 中国实用护理杂志

Objective:To investigate the status of grief among maternal spouse after perinatal loss, and analyze its influencing factors, so as to provide some reference for male grief supporting strategic.Methods:Using the convenient sampling method, 180 male spouses of hospitalized women in the Department of Obstetrics from Nanjing Maternity and Child Health Care Hospital from March to October 2022 were recruited. A cross-sectional survey was conducted by the general questionnaire, the Perinatal Grief Scale, the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version, the Social Support Rating Scale, and the Simplified Coping Style Questionnaire.Results:The overall score of the Perinatal Grief Scale in male spouses of women who experienced a perinatal loss was (61.57 ± 14.14) points. The score of the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version was (121 ± 14.42) points, the score of the Social Support Rating Scale was (34.23 ± 7.21) points, and the score of the Simplified Coping Style Questionnaire was (36.08 ± 7.64) points. Multiple linear regression analysis showed that participation in fetal interaction, loss of fetal age, social support and family adaptability were the main factors affecting male grief ( P<0.05). Conclusions:The grief among male spouses of women who experienced a perinatal loss is at a low level. The clinical medical staff can refer to the influencing factors and implement effective support, such as respecting the male's father status, coordinating social support resources, and improving the family's coping ability, in order to alleviate men's grief and help them return to normal life.

Risk factors and complication of hemodynamically significant patent ductus arteriosus in preterm infants with gestational age <32 weeks / 国际儿科学杂志

Objective:To study the risk factors and complications of hemodynamically significant patent ductus arteriosus(hsPDA)in preterm infants <32 weeks.Methods:From January 2021 to March 2022, a total of 150 premature infants with gestational age <32 weeks admitted to the Neonatal Intensive Care Unit of Liaocheng People′s Hospital were enrolled.Nine patients who did not meet the requirements were excluded and a total of 141 infants were finally analyzed retrospectively, including PDA group with 95 cases and non-PDA group with 46 cases.According to whether hsPDA existed or not, PDA group were dirided into hsPDA group with 42 cases and non-hsPDA group with 53 cases.Univariate and regression analyses were used to determine the risk factors and complication of hsPDA.Results:Univariate analysis showed that gestational age( t=-6.861, P<0.01), birth weight( t=-4.392, P<0.01), mode of delivery( χ2=9.018, P<0.01), caffeine( χ2=4.337, P<0.05) and suffocation( χ2=7.918, P<0.01)were associated with hsPDA.Logistic regression analysis showed that gestational age( OR=2.435, P<0.01, 95% CI: 1.669~3.552)was an independent risk factor for hsPDA in gestational age <32 weeks preterm infants.The incidences of necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity in the hsPDA group were higher than those in the non-hsPDA group( P<0.05). Conclusion:Gestational age is an independent risk factor for hsPDA with gestational age <32 weeks.Necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity are related complications of hsPDA.

Voltage Dependent Anion Channel 1 Mediated Inflammation and Obstructive Sleep Apnea Syndrome / 中山大学学报(医学科学版)

VDAC1（voltage dependent anion channel 1）is an important channel protein on the outer mitochondrial outer membrane， which regulates mitophagy， participates in the regulation of inflammatory cytokines and the activation of the inflammasome， hence being crucial to the inflammatory response. Patients with obstructive sleep apnea syndrome （OSAS） suffer neuroinflammation due to intermittent hypoxia and increased oxidative stress， leading to chronic damage and neuronal cell apoptosis， and eventually develop cognitive impairment. Since OSAS patients' cognitive impairment is significantly influenced by inflammation， and VDAC1 regulates the activation of the inflammasome， the relationship between OSAS and VDAC1， mitophagy， as well as inflammation are reviewed here. We hope that this study can provide a new breakthrough in mitophagy and inflammation in patients with cognitive dysfunction caused by OSAS.

Structural distribution and mechanism of elastic fibers and collagen fibers in ventricular interstitium of aged rats / 解剖学报

Objective To investigate the structural distribution features and mechanism of elastic fibers and collagen fibers in ventricular interstitium of aged rats. Methods Five young SD rats (24 weeks) and five old SD rats (104 weeks) were used,and their cardiac function was examined by echocardiography. Modified Weigert elastic fiber staining, immunohistochemistry, immunofluorescence and Western blotting techniques were used to detect the expression changes of type I and IH collagen fibers and their proteins, elastic fibers and their proteins, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 2 (TIMP-2), respectively. Results The type I and type IH collagen in the ventricular interstitium of aged rats was very sufficient and wrapped around the cardiomyocytes. Compared with the young rats, the content of collagen protein in the ventricular interstitium of the aged rats significantly increased (P<0. 05). Elastic fibers in the ventricular interstitium of the aged rats were and widely distributed. Compared with the young rats, the number of elastic fibers and the level of elastin in the ventricular interstitium of the aged rats significantly decreased (P<0. 05), and the expression levels of MMP-2 and MMP-9 in ventricular muscle of aged rats increased, and the)' were correlated with the level of elastin. The level of TIMP-2 in ventricular muscle of aged rats decreased with age. Conclusion The number of collagen fibers and elastic fibers in ventricular interstitium of aged rats is fluctuated with each other. With the increase of age, the contents of TIMP-2 and elastic fibers in the ventricular interstitium gradually decreased, and the ratio of collagen fibers to elastic fibers is out of balance.

Astragaloside IV inhibits Ang H-induced cell proliferation and collagen expression in cardiac fibroblasts by activating short-chain acyl-CoA dehydrogenase / 中国药理学通报

Aim To explore the effect of astragaloside IV (AS-IV) on cell proliferation and collagen expression in cardiac fibroblasts (CFs) of rats induced with angiotensin II (Ang II) and its mechanism. Methods CFs were pretreated with short-chain acyl-CoA dehydrogenase (SCAD) siRNA1186 for 12 h and then co-treated with Ang TJ and AS-IV for 36 h. The expressions of SCAD, α-SMA, collagen I and collagen III in CFs were detected by Western blot. mRNA expression levels of SCAD, a-SMA, collagen I and collagen III in CFs were detected by quantitative real-time PCR. The SCAD enzymatic activity, the content of ATP, hydroxyproline and free fatty acid were measured by detection kits. Results The expression of α-SMA, collagen I and collagen III were up-regulated (all P < 0. 01) in CFs induced by Ang II compared with the control cells, and the expression and enzymatic activity of SCAD significantly decreased (P < 0. 01, P< 0. 05). The content of ATP decreased (P < 0.01), and the content of hydroxyproline and free fatty acids increased (all P < 0.01). Compared with Ang II group, SCAD expression and enzymatic activity, and ATP content were significantly increased (all P < 0.01) in Ang II + AS-TV group, but the content of hydroxyproline and free fatty acids, and the expression of α-SMA, collagen I and collagen III significantly decreased (all P < 0.01). However, compared with the Ang II + NC group, there was no significant difference in all indices in the Ang II + SiRNA1186 + AS-TV group. The protective effect of AS-TV on Ang II -induced cell proliferation and collagen expression in CFs was eliminated by the interference of SCAD SiRNA1186. Conclusions AS-IV may inhibit Ang II-induced cell proliferation and collagen expression in CFs by activating SCAD.

Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model / 中华儿科杂志

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.

Diagnosis status and genetic characteristics analysis of Fanconi anemia in China / 中华儿科杂志

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.

Impact of SARS-CoV-2 infection on graft composition and early transplant outcomes following allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.

Clinical significance of Epstein-Barr Virus detection in the cerebrospinal fluid of patients who underwent hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.

Stigma and Efficacy of Zhizhu Kuanzhong Capsules Versus Doxepin in the Treatment of Refractory Functional Dyspepsia: A Randomized Controlled Trial

Background/Aims@#Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy.Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD). @*Methods@#Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire). @*Results@#The MPR values for ZZKZ were significantly higher than those for doxepin (P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma (P < 0.001). The MPR values were negatively correlated with posttreatment stigma scores in both groups (P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups. @*Conclusion@#ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD.