[Diagnosis status and genetic characteristics analysis of Fanconi anemia in China].

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.

[Safety and effectiveness of Neuroform Atlas stent-assisted coiling in the endovascular treatment of intracranial aneurysms: a single-center observational study].

Objective: To investigate the safety and effectiveness of Neuroform Atlas stent-assisted coiling in the endovascular treatment of intracranial aneurysms. Methods: This was a retrospective, single-center observational study of 77 patients who underwent endovascular treatment of intracranial aneurysms using the Neuroform Atlas device at the Department of Neurology, People's Liberation Army General Hospital from July 2020 to May 2022. There were 34 males and 43 females, with a median (range) age of 59 (23-81) years. The degree and effect of aneurysm embolization were evaluated by modified Raymond grading post procedure and after 6 months. Complications occurring during the perioperative period were recorded. Vaso computed tomography was performed immediately after the operation to assess stent opening and adherence. Digital subtraction angiography was performed 6 months after discharge and the aneurysm was classified as cured, stable, or recurrent. Results: A total of 87 Atlases were successfully released in 77 cases. Angiography performed immediately after the embolization revealed 19 (24.7%) modified Raymond grade Ⅰ, 10 (13.0%) grade Ⅱ, and 48 (62.3%) grade Ⅲa cases. Three perioperative complications were observed including thrombotic events in 2 cases and stent migration in 1 case. A follow-up angiogram was available for 47 aneurysms, and showed that modified Raymond grade Ⅰ occlusion was achieved in 38 (80.9%) cases, grade Ⅱ in 2 (4.3%) cases, and grade Ⅲa in 7 (14.9%) cases. At the 6-month follow-up, 38 patients were cured and 7 were stable, whereas 2 patients experienced a recurrence of aneurysm. Stenosis of the parent artery occurred in 3 (6.4%) cases, including 2 at the head and 1 inside the stent. Conclusions: The results of this preliminary study suggest that Neuroform Atlas stent-assisted coiling has a high occlusion rate and low incidence of complications in the endovascular treatment of aneurysms. However, the effectiveness of this procedure for large aneurysms and long-term outcomes require further investigation.

[Independent and combined effects of pre-pregnancy BMI and gestational diabetes on early adiposity rebound timing in children].

Objective: To examine the independent and combined effects of pre-pregnancy BMI and gestational diabetes (GDM) on early adiposity rebound (AR) timing in children. Methods: Based on the "Ma'anshan Birth Cohort Study", 2 896 eligible maternal and infant pairs were recruited. In the cohort, we collected pre-pregnancy height, weight, 24 to 28 weeks GDM diagnosis, follow-up at 42 days, three months, six months, nine months of age, and every six months after one year of age, and continuously followed up to 6 years old, and obtained the child's length/height, weight, and other data. The intensity of the association between pre-pregnancy BMI, GDM, and early AR timing was analyzed by the multivariate logistic regression model. Multiplication and additive models were used to analyze how pre-pregnancy BMI and GDM influenced early AR timing in children. Results: The prevalence of underweight, average weight, overweight, and obesity before pregnancy were 23.2% (672), 66.4% (1 923), 8.7% (251), and 1.7% (50). The prevalence of GDM was 12.4%. We found that 39.3% of children had AR, and the average age at AR was (4.38±1.08). The results of multifactorial logistic regression analysis showed that pre-pregnancy overweight (OR=1.67,95%CI:1.27-2.19), pre-pregnancy obesity (OR=3.05,95%CI:1.66-5.56), and maternal GDM (OR=1.40,95%CI:1.11-1.76) were risk factors for early AR timing in children. In contrast, pre-pregnancy underweight (OR=0.60,95%CI:0.49-0.73) was a protective factor for early AR timing in children. Compared with the different effects of pre-pregnancy overweight/obesity and maternal GDM alone, the combined effect caused a higher risk of early AR timing in children, with OR values (95%CI) were 2.03 (1.20-3.44), 3.43 (1.06-11.12), respectively. The multiplication and additive models showed no interaction between pre-pregnancy BMI and GDM-influenced early AR timing in children. Conclusion: Higher pre-pregnancy BMI and maternal GDM are the independent risk factors for the early AR timing in children, and the co-occurrence of the two is higher risks, but there was no statistical interaction.

Alkaline semen diluent combined with R848 for separation and enrichment of dairy goat X-sperm.

A large number of female goats are needed for the dairy goat industry; therefore, the development of a method to ensure the birth of more females than males in a single pregnancy will lead to economic benefits. Increasing the number of X-sperm would be an effective way to increase the proportion of female offspring. In this study, goat semen was incubated at pH 7.4 in alkaline diluent combined with resiquimod (R848) and the number of X-sperm was enriched by the swim-up method. The percentage of X-sperm was determined using the double TaqMan qPCR method. Sperm total motility, progressive motility, average path velocity, straight-line velocity, and curvilinear velocity were measured using a computer-aided sperm analysis system, and the functional parameters of the sperm plasma membrane, the acrosome, mitochondrial activity, ATP content, and reactive oxygen species levels were also measured. Lastly, the ratio of female embryos was determined by in vitro fertilization, and the number of female kids and the pregnancy rate of does was assessed by artificial insemination. The results showed that dilution of semen in an alkaline buffer containing R848 could enrich the number of X-sperm to 85.57% ± 3.27%. The progressive motility, average path velocity, straight-line velocity, curvilinear velocity, mitochondrial activity, and ATP level of the collected X-sperm-enriched semen were significantly reduced, but its total motility, plasma membrane, and acrosome were not affected. The in vitro fertilization experiments showed that the rate of female embryo production using X-sperm-rich seminal fluid could reach 83.25% (174/209), which was significantly higher than the proportion of female embryos in the control group, 47.71% ± 1.80% (104/218). As determined by artificial insemination, the number of female kids in the test group increased by 62.79% (243/387), which was significantly higher than that in the control group (47.65%, 193/405). There was no significant difference in pregnancy rate between the test group and the control group (71.71% vs. 78.48%). Therefore, this study demonstrated that use of a pH 7.4 diluent containing R848 is a simple and effective method of X-sperm enrichment for dairy goat production. Its application would allow does to produce more female offspring for herd expansion and milk production.

[Endovascular stenting for idiopathic intracranial hypertension with different types of venous sinus stenosis].

Objective: To evaluate the efficacy of endovascular stenting of various types of venous sinus stenosis in idiopathic intracranial hypertension (IIH). Method: Clinical, radiological, and manometric data before and after stenting in venous sinus stenosis were retrospectively analyzed in 99 IIH patients who were refractory to medical therapy or rapidly progressed between July 2004 to July 2019. The follow-up period was between 2.3 months to 11 years. Results: Our study enrolled 21 men (21.2%)and 78 women (78.8%) with average body mass index (BMI) 19.2-40.6(27.0±4.4) kg/m2 and median age 37 years. Before stent placement, the mean transverse sinus stenosis gradient was 1-59(26±8) mmHg. Patients with extrinsic stenosis were younger than those with intrinsic and mixed stenosis. In all cases, stenting was effective for papilledema. Fifty patients complained of headaches. Pulsatile tinnitus in twenty-eight patients completely alleviated after stenting. In one patient, replacement of stent did not improve symptoms, and a subsequent CSF diversion procedure was performed and effective. Conclusion: Irrespective of the type of stenosis, stenting of venous sinus stenosis is an effective treatment for IIH. Patients with persistent papilledema post-stenting and elevated transverse pressure pre-stenting should be followed closely as high risk of stenting failure may occur and further diversion procedure is needed.

[CART therapy followed by allo-HSCT for patients with B-cell acute lymphoblastic leukemia relapsing after the first hematopoietic stem cell transplantation].

Objective: To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT. Methods: Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia. Results: A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95%CI 23.0%-70.6%) , 41.8% (95%CI 17.3%-64.9%) , 8.8% (95%CI 2.9%-26.4%) , and 51.1% (95%CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95%CI 12.7%-73.5%) and 75.0% (95%CI 51.4% -88.8%) (P=0.017) , respectively. Conclusion: CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

[Comparison of the clinical outcomes of haploidentical and matched-sibling donor stem cell transplantation for T cell acute lymphoblastic leukemia in complete remission].

Objective: To compare the efficacy of haplotype hematopoietic stem cell transplantation (HIDT) and sibling matched hematopoietic stem cell transplantation (MSDT) in the treatment of complete remission (CR) acute T-lymphoblastic leukemia (T-ALL) . Methods: We retrospectively analyzed the clinical characteristics and outcomes of 98 patients who underwent HSCT in Hebei Yanda Ludaopei hospital with HID (n=81) or ISD (n=17) between May 2012 and May 2016. Results: The incidence of grades 2-4 and 3-4 acute-versus-host disease 100 days after HSCT were 51.9% (95% Confidence interval [CI] 42.0%-64.0%) vs 29.4% (95% CI 14.1%-61.4%) (P=0.072) and 9.8% (95% CI 5.1%-19.1%) vs 11.8% (95% CI 3.2%-43.3%) (P=1.000) for HIDT and MSDT. The 100-day cumulative incidences of CMV and EBV viremia were 53.1% (95% CI 43.3%-65.2%) vs 29.4% (95% CI 14.1%-61.4%) (P=0.115) and 35.8% (95% CI 26.8%-47.9%) vs11.8% (95% CI 3.2%-43.3%) (P=0.048) . The 5-year overall survival, leukemia-free survival, cumulative incidences of relapse, and no-relapse mortality were 60.5% (95% CI 5.4%-49.0%) vs 68.8% (95% CI 11.8%-40.0%) (P=0.315) , 58.0% (95% CI 5.5%-46.5%) vs 68.8% (95% CI 11.8%-40.0%) (P=0.258) , 16.1% (95% CI 9.8%-26.4%) vs 11.8% (95% CI 3.2%-43.3%) (P=0.643) , 25.9% (95% CI 17.9%-37.5%) vs 19.4% (95% CI 6.9%-54.4%) (P=0.386) for HIDT and MSDT, respectively. Conclusion: HID could be a valid alternative donor for patients with T-ALL in CR lacking an identical donor.

[The effect of TP53 mutations on the clinical outcomes of Ph-negative B-acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the association of TP53 mutations with the clinical outcomes of Ph-negative B-ALL following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Total 300 patients with Ph-negative B-ALL who underwent allo-HSCT at the Hebei Yanda Ludaopei Hospital from May 2012 to May 2017 were retrospectively analyzed; their clinical characteristics, TP53 gene mutation type, and association between TP53 mutations and transplantation outcomes, including leukemia-free survival (LFS) , overall survival (OS) , non-relapse mortality (NRM) , relapse, and GVHD, were evaluated. Results: Total 23 patients had TP53 mutations; all the TP53 mutations affected P53'DNA-binding domain. The 5-year-LFS, OS, and RI were 34.8% and 62.3% (P=0.001) , 41.9% and 65.1% (P=0.020) , and 47.8% and 14.8% (P=0.000) , respectively, for TP53 mutations and wild-type TP53 patients. However, there were no significant differences in NRM and GVHD. Multivariate analysis showed that TP53 mutations remained adverse prognostic factors for LFS, OS, and RI after allo-HSCT. Conclusion: Some patients with TP53 mutations can achieve long-term survival with allo-HSCT. TP53 mutations are adverse prognostic factors for Ph-negative B-ALL patients who undergo allo-HSCT.

[Prognostic analysis of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in complete remission in the era of tyrosine kinase inhibitors].

Objective: To study the clinical results and prognostic factors for allo-HSCT of Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in complete remission (CR) in the era of tyrosine kinase inhibitors (TKI) . Methods: We performed a retrospective analysis of the clinical characteristics of 116 patients with Ph(+)ALL who underwent allo-HSCT while in CR. Results: The study population included 72 men and 44 women. The median patient age was 20 years (4-64 years) . The patients received sibling-identical donor (n=21) , haplo (n=77) , and unrelated donor (n=18) HSCT. The overall survival (OS) rate at 5 years was 73.2% (95% CI 63.8% -80.5% ) . In particular, the 5-year OS can reach 87.5% when the time from diagnosis to transplant is <180 days. The 5-years DFS was 61.4% (95% CI 51.8% -69.7% ) , the 5-year molecular and morphology cumulative relapse incidence was 18.5% (95% CI 12.6% -27.3% ) , and the 5-year TRM was 19.9% (95% CI 13.8% -28.7% ) . A multivariate analysis showed that an age range of 15-39 years (HR=2.730, P=0.044) , time from diagnosis to HSCT ≥ 180 days (HR=4.534, P=0.010) , and Ⅲ-Ⅳgrade aGVHD (HR=7.558, P=0.000) were significantly associated with an inferior overall survival. Limited cGVHD subgroup had better OS (HR=0.300, P=0.034) . Sex, WBC count at diagnosis, type of BCR-ABL fusion genes, somatic gene mutations, CR(1) or >CR(1), MRD negative or positive, conditioning regimen based on TBI or Bu, conditioning intensity, donor source, GVHD prophylactic proposal using cyclosporine or tacrolimus, presence/absence of CMV viremia, and presence/absence of EBV viremia were not significantly different in terms of the OS and DFS. Conclusion: Factors influencing the overall survival of Ph(+) ALL patients who underwent allo-HSCT in CR in the TKI era include age, time form diagnosis to HSCT, and aGVHD severity.

[The analysis of clinical characteristics of 34 novel coronavirus pneumonia cases in Ningxia Hui autonomous region].

Objective: To analyze the clinical characteristics of 34 COVID-19 cases and to provide the basis for the prevention and control of the epidemic disease. Methods: Thirty-four COVID-19 patients diagnosed with RT-PCR in the isolation ward of the Fourth People's Hospital of Ningxia Hui autonomous region (infectious diseases hospital) from the January 22 to February 4, 2020 were selected as the research subjects. The clinical data were collected. Excel was used to describe the relationship between clinical classification and age distribution, contact history and date of onset. SPSS 25.0 statistical software was used for analysis. The general information, clinical symptoms, blood test, virus nucleic acid test results, epidemiology, CT imaging, treatment and prognosis were analyzed. Results: There were 5 mild cases (5/34), 24 ordinary cases (24/34), 5 severe cases (5/34). The elderly was more common in severe patients. The main clinical symptoms were fever (27/34)and dry cough(26/34). The peripheral blood showed normal or decreased leukocyte count (33/34), decreased lymphocyte count (12/34). The increase of C-reactive protein (CRP) and D-dimer was related to the severity of the disease. Some patients had mild liver and kidney damage. Six patients were diagnosed through 3 or more times of nucleic acid tests. Sixteen cases had Wuhan related history,13 cases were close contacts, 5 cases had no confirmed route. The clustered infections were found in 6 families. In typical cases, CT showed single or multiple patchy ground glass shadow with thickening of interlobular septum. In severe cases, diffuse lesions of both lungs were found, with ground glass shadow, consolidation shadow and strip shadow coexisting. Thirty-four patients were treated with interferon-α and Lopinavir/Ritonavir with good prognosis. Conclusions: The clinical characteristics of COVID-19 were similar to that of general viral pneumonia but with strong infectivity. Close contact and family aggregation caused disease outbreaks. COVID-19 could not be excluded if two nucleic acid tests were negative and high-resolution CT was helpful for differential diagnosis. Early detection, early isolation, early diagnosis and early treatment are important for good prognosis. The effectiveness of antiviral drugs needs to be further verified.

[The 476th case: skin rash, edema, thrombocytopenia and anemia].

The 21-year-old male patient was admitted to the Department of Rheumatology and Immunology at Peking Union Medical College Hospital with chief complaints of "skin rash for 1 year and edema for 2 months". He was diagnosed with systemic lupus erythematosus (SLE) with renal, cardiac and hematological involvement. Remission was not achieved after glucocorticoid pulse treatment. The patient experienced oliguria, malignant hypertension, accompanied by thrombocytopenia and low serum complements, and elevated lactate dehydrogenase and serum creatinine. Schistocytes were seen in the peripheral blood smear. Thrombotic microangiopathy (TMA) secondary to SLE was diagnosed. Though plasma exchange was partially effective, TMA could not be controlled yet. The activity of serum von Willebrand factor -cleaving protease (ADAMTS 13) was 100%, and ADAMTS 13 inhibitor was negative. Finally, remission of the disease was achieved after second glucocorticoid pulse therapy and rituximab treatment. At the 3-month follow-up, the patient's condition was stable with mild anemia and normal platelet count. Patients with TMA secondary to SLE are heterogenous, while normal ADAMT 13 activity indicates poor prognosis. Early and aggressive treatment is important for disease control, and plasma exchange is helpful as a supportive care.

Anatomical study of the anterior neurovascular interval approach to the elbow: observation of the neurovascular interval and relevant branches.

BACKGROUND: The aim of the study was to investigate the anatomy of the anterior nerve and artery of the elbow joint to provide reference on the relevant surgical approach to the elbow joint, and determine a simple better surgical approach for the treatment of part of the fractures of the elbow joint. MATERIALS AND METHODS: The upper extremities of 10 adult cadavers fixed by formaldehyde and perfused with red latex in the artery were observed to investigate the anatomic structure of the anterior approach to the elbow joint. From the clearance of the brachioradialis and pronator teres muscle to the approach of the neurovascular interval, we observed the states of the median nerve, the brachial, radial and ulnar arteries, and its branches through anatomical layers and measurement methods. RESULTS: Through the anterior neurovascular interval approach to the elbow, nerve and artery can be protected, and the anterior structures of the elbow, such as the ulna coronoid process, humeroulnar joint and trochlea of the humerus, can be exposed. CONCLUSIONS: This study demonstrates that the anterior anatomical structure of the elbow joint including the trochlea of the humerus, coronoid process of the ulna and the front capsule of the elbow can be exposed through the anterior neurovascular approach to the elbow.

MiR-137-5p alleviates inflammation by upregulating IL-10R1 expression in rats with spinal cord injury.

OBJECTIVE: This study aims to explore the potential functions of miR-137-5p and interleukin-10R1 (IL-10R1) in mediating the immune inflammation after spinal cord injury (SCI). MATERIALS AND METHODS: Firstly, primary microglia were isolated from the spinal cord of newborn rats. Expression levels of miR-137-5p and IL-10R1 in LPS-induced microglia were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). In addition, mRNA expressions of Janus kinase (Jak1) and signal transducer and activator of transcription 3 (STAT3) were also examined by qRT-PCR. SCI model in rats was established and randomly assigned to three different groups: Sham group, SCI group and miR-137-5p mimic group. Within one week of spinal injury, relative levels of miR-137-5p and IL-10R1 in rats of different groups were detected by qRT-PCR. The mRNA levels of JAK1, tyrosine kinase (Tyk2) and STAT3 in rats were also measured. Moreover, protein expression of IL-1ß, TNF-α and IL-6 in rats was measured by Western blotting. Finally, the improvement of locomotor function in three groups of rats within 4 weeks via BBB rating scale. RESULTS: Transfection of miR-137-5p mimics upregulated relative levels of IL-10R1, JAK1 and STAT3 in in vitro cultured microglia. Similarly, IL-10R1/JAK1/STAT3 pathway was activated in rats administrated with miR-137-5p mimics. Nevertheless, relative levels of classical inflammatory stimulators IL-1ß, TNF-α and IL-6 were downregulated accordingly by miR-137-5p overexpression. Moreover, miR-137-5p effectively improved the locomotor function of rats after SCI. CONCLUSIONS: MiR-137-5p exerts an anti-inflammatory response by upregulating IL-10R1, thus improving locomotor function and alleviating spinal cord injury.

Effects of MiR-146a on repair and inflammation in rats with spinal cord injury through the TLR/NF-κB signaling pathway.

OBJECTIVE: This study aims to investigate the effects of micro ribonucleic acid-34a (miR-34a) on repair and inflammation of rats with spinal cord injury (SCI) through the toll-like receptor (TLR)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. MATERIALS AND METHODS: In this study, 12 healthy rats (control group (CG)) and 24 SCI rats (experimental group (EG-1)) were selected as subjects. A total of 12 experimental rats randomly selected from EG-1 were injected with 5 µL agomiR-146 as EG-2 group. Serum levels of miR-146a, TLR, NF-κB, interleukin-8 (IL-8) and IL-6 of rats in CG and EG-1 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Furthermore, the protein levels of miR-146a, TLR, NF-κB, IL-8 and IL-6 in rats of CG and EG were detected via Western blotting. Spinal cord tissue sections of SCI rats after treatment with agomiR-146 were observed by hematoxylin and eosin staining (H&E) staining. RESULTS: The mRNA level of miR-146a in SCI rats was significantly lower than that in healthy rats, and the difference was statistically significant (p < 0.05). The mRNA levels of TLR, NF-κB, IL-8 and IL-6 in SCI rats were markedly higher than those in healthy rats, showing significant differences (p < 0.05). However, the relative mRNA level of miR-146a in EG-2 group was significantly higher than that in EG-1 group, with a significant difference (p < 0.05). Relative level of miR-146a was not significantly different between EG-2 group and CG group (p > 0.05). Meanwhile, the mRNA levels of TLR, NF-κB, IL-8 and IL-6 in EG-2 group were evidently lower than those in EG-1 group, displaying significant differences (p < 0.05). CONCLUSIONS: MiR-146a can promote the repair of SCI and reduce inflammatory responses in rats through the TLR/NF-κB signaling pathway.

[The 469th case: multiple cutaneous abscesses, pelvic mass, and lung cavities].

A 28-year-old woman with multiple abscesses for 2 month and fever for 1 month was admitted in Peking Union Medical College Hospital. The skin abscesses gradually developed at skull, face, abdominal wall and pelvis. Laboratory examinations related to inflammatory reactions were strongly high including erythrocyte sedimentation rate 99 mm/1 h,C-reactive protein160.28 mg/L and ferritin 1 584 µg/L. Multiple nodules and cavities were detected in lungs. And vesico-cervical fistula was found during exploratory laparotomy. The pathological tests of abdominal tissues demonstrated necrosis and granuloma. Evidence of infectious diseases was not definite. Positive anti-proteinase 3 (PR3) antibody confirmed the diagnosis of granulomatosis with polyangiitis. After treated with glucocorticoid and immunosuppressants, the patient's symptoms improved remarkably. This case suggested that systemic vasculitis should be considered as a differential diagnosis of multiple abscesses which are not explained by infections.

microRNA-144-3p suppresses human neuroblastoma cell proliferation by targeting HOXA7.

OBJECTIVE: Dysregulation of microRNAs (miRNAs) expression often resulted in abnormal cell behaviors. It has been demonstrated that miRs may serve as oncogenic or tumor suppressive functions in tumor. We investigated whether or not miR-144-3p has a role in the progression of human neuroblastoma (NB). PATIENTS AND METHODS: 46 NB patients were enrolled in this study. miR-144-3p expression in NB tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction. The biological functions of miR-144-3p in NB were detected by cell counting kit-8 assay, flow cytometry assay, and wound-healing assay. Luciferase activity assay and Western blot assay were performed to validate the direct targets of miR-144-3p. RESULTS: We found miR-144-3p expression was reduced in NB tissues and cell lines and resulted in the stimulation of cell proliferation, cell cycle progression, and cell migration in vitro. Furthermore, we validated homeobox protein A7 (HOXA7) as a direct target of miR-144-3p. CONCLUSIONS: Taken together, these results demonstrated the tumor suppressive role of miR-144-3p in NB and may advance the understanding of the underlying mechanisms of miR-144-3p and HOXA7 in NB.

[Clinical characteristics and prognosis of 34 cases of acute myeloid leukemia with FLT3 internal tandem duplication and MLL gene rearrangement].

Objective: To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) and MLL gene rearrangement. Methods: The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stem cell transplantation (allo-HSCT). Results: Of the thirty-four cases with median age 41 (4-71) years old, 63.6% presented with white blood cells (WBC) greater than 30×10(9)/L, 39.4% greater than 50 × 10(9)/L respectively on admission. M(5) (35.3%) made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients (32.35%) had both FLT3-ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients (67.6%) had one or more other gene abnormalities (multiple gene abnormalities). Of the 34 cases, 29.4% patients went into complete remission (CR) after two courses of chemotherapy. 20.6% (7 patients) went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC>50×10(9)/L or multiple gene abnormalities had a lower remission rate (7.7%, 5.4%) after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival (OS) in the 34 patients was 28.8% (95% CI 13.5%-46.0%) and the disease-free survival (DFS) was 27.1% (95% CI 12.5%-44.0%). Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% (95% CI 13.7%-70.4%) and DFS 42.7% (95% CI 13.4%-69.7%). Conclusion: AML patients with FLT3-ITD and MLL gene rearrangement often presented with M(5), accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.

UV-curable ladder-like diphenylsiloxane-bridged methacryl-phenyl-siloxane for high power LED encapsulation.

A UV curable ladder-like diphenylsiloxane-bridged methacryl-phenyl-siloxane (L-MPS) was synthesized from phenyltrichlorosilane, diphenylsilanediol and methacryloxypropyldimethylmethoxysilane via dehydrochlorination precoupling, supramolecular architecture-directed hydrolysis-condensation and end-capping reactions. The L-MPS has a condensation degree of ∼100%, and can be complete crosslinked by UV curing. XRD, TEM and molecular simulation suggest that the ladder-like molecules are close packed with a periodic distance of ca. 1.2 nm. The L-MPS shows transmittance of 98% and a refractive index of ca. 1.61 at 450 nm. The cured L-MPS with a T d5% value of 465.5 °C showed excellent anti-yellowing and anti-sulfidation properties. The cured L-MPS film and the encapsulated LED samples were compared with those of Dow Corning OE-6630 and OE-7662. It is believed that the dense nano-ladder unit also contributes to the thermal, gas barrier and even optical properties. L-MPS shows promising potential as a high power LED encapsulant and optical coating for use in harsh environments. This work provides an approach to integrate this novel ladder structure with advanced properties.

[Experts consensus on the management of the right heart function in critically ill patients].

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.