Objective:To investigate the clinical characteristics and survival analysis of myelodysplastic syndromes(MDS)with RUNX1 gene mutation.Methods:Clinical data of 177 newly diagnosed MDS patients admitted to the Department of Hematology,the Second Affiliated Hospital of Air Force Military Medical University from October 1,2015 to October 31,2022 were retrospectively analyzed.Gene mutation detection was performed by second-generation sequencing technology,and clinical characteristics and prognosis of patients with RUNX1 gene mutation were analyzed.Results:A total of 30 cases(16.95％)of RUNX1 gene mutations were detected,including 15 missense mutations(50.0％),9 frameshift deletion mutations(30.0％),4 splice site mutations(13.3％),1 insertion mutation(3.3％),and 1 nonsense mutation(3.3％).Patients with RUNX1 mutations had a median age of 68.5 years at diagnosis(range:62.25-78.50 years old).There were no significantly differences between RUNX1 mutations and wild type patients in age distribution,gender,peripheral blood white blood cell count,hemoglobin level,bone marrow and peripheral blood blasts ratio,IPSS-R cytogenetics,IPSS-R stage,etc.(P＞0.05).However,there were statistically significant differences in platelet count and whether complicated karyotype.Compared with patients without RUNX1 gene mutation,patients with RUNX1 gene mutation had lower platelet count(P=0.018),and were less likely to have complicated karyotype at initial diagnosis(P=0.01).Cox proportional hazards model analysis showed that when other co variates remained unchanged,the higher the platelet count,the better the survival of patients(HR=0.995,95％CI:0.990-0.999,P=0.036);In the IPSS-M prognostic stratification,keeping other covariates unchanged,the risk of progression or death of myelodysplastic syndrome was significantly lower in the medium to high-risk and low-risk groups compared with the high-risk group(HR=0.149,95％CI:0.031-0.721,P=0.018;HR=0.026,95％CI:0.003-0.234,P=0.001).Survival analysis showed that MDS patients with RUNX1 gene mutation had worse overall survival time(P＜0.001).Patients with RUNX1 mutation had worse OS than non-mutation patients in the early WHO group.RUNX1 mutation and IPSS-M risk stratification mean OS and mean LFS were worse in low-risk patients than in non-mutated patients.Conclusion:RUNX1 gene mutation is an adverse prognostic factor in MDS patients,especially in the IPSS-M prognosis stratification group of low-risk,medium-low risk,medium-high risk and WHO classification of early patients.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

Abstract: Objective　To develop a real-time fluorescent quantitative RT-PCR (qRT-PCR) method for qualitative and quantitative Chikungunya virus (CHIKV) analysis. Methods Based on the systematic analysis of the genomic sequences of Chikungunya and its related arboviruses, the specific nucleic acid sequences for Chikungunya virus were screened and identified, and then the primers and TaqMan probe were designed. Meanwhile, the human GAPDH gene was used as an internal reference. The reaction system for qRT-PCR was systematically optimized by L9(34) orthogonal design, and a rapid detection method for Chikungunya by qRT-PCR based on TaqMan probe methods was established. The sensitivity, specificity, reproducibility, and coverage of the established method were analyzed in detail. The standard curve was made, and the absolute quantitative method was established using the cloned nucleic acid fragments as positive samples. Results　A real-time fluorescent quantitative RT-PCR assay was developed for the qualitative and quantitative analysis of Chikungunya virus. The reaction system included Chikungunya virus and reference internal gene specific primers and probe, RT/Taq enzyme mixture, reaction buffer, and negative and positive reference. The established method obtained positive results with the ROSS strain of ECSA subtype, LR2006 strain of IOL branch, 181/25 strain of Asian type and Dongguan 2010 epidemic strains of Chikungunya virus, but there was no cross-reaction with other 18 arboviruses belonging to Flaviviruses, Alphaviruses and Bunyavirus. The minimum detection limit of the established method was 5.80 copies/mL, and a linear relationship was observed between the amount of input plasmid DNA and fluorescence signal value over a range of 5.80×102 copies/mL to 5.80×1010 copies/mL, and the correlation coefficient was 0.999 5. The qRT-PCR amplification efficiency was 91%, and the intra-assay variations and inter-assay variations were 0.01-0.07 and 0.03-0.11, respectively. Conclusions　The TaqMan qRT-PCR method developed in this study can qualitatively and quantitatively detect Chikungunya virus rapidly with specificity and sensitivity, providing a technical method for the prevention and control of this viral disease.

Pregnancy ; Female ; Humans ; Milk, Human ; Overweight/genetics* ; Fatty Acids, Unsaturated ; Fatty Acids ; Adiponectin/genetics*

OBJECTIVE: To investigate the expression of fibroblast growth factor receptor 2 (FGFR2) in clear cell renal cell carcinoma (ccRCC; or kidney renal clear cell carcinoma, KIRC), to analyze the relationship between the expression of FGFR2 and the clinical pathological features and prognosis of ccRCC, to study the relationship between the expression of FGFR2 and other molecules, and to explore its role in the development of ccRCC. METHODS: Gene expressional and clinical information of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus(GEO) database. Next, the data were transformed and collated. In the study, 104 clinical ccRCC samples and corresponding paracancerous normal tissue samples were collected from Department of Urology, Peking University First Hospital. Immunohistochemistry (IHC) was performed and the staining results were scored, so as to compare the expression of FGFR2 in ccRCC and paracancerous normal tissues. Besides, quantify real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of FGFR2 in normal renal epithelial cell lines (293) and ccRCC cell lines (786-O, 769-P, OSRC-2, Caki-1, ACHN, and A498). In addition, the relationship between FGFR2 expression and clinical pathological characteristics (including TNM staging and pathological grading) and survival prognosis in ccRCC patients was further analyzed. Furthermore, the relationship between FGFR2 expression and B cells, T cells, natural killer (NK) cells and neutrophil infiltration in the ccRCC patients was analyzed, and the Biological General Repository for Interactionh Datasets (BioGRID) was used to builds protein-protein interaction (PPI) networks to study molecules that interacted with the FGFR2 protein. RESULTS: In the TCGA database, the expression of FGFR2 was down-regulated in ccRCC tissue samples compared with normal tissue samples, and the expression in the GEO database also showed this differences. Furthermore, FGFR2 expression was downregulated in ccRCC clinical samples and ccRCC cell lines, compared with corresponding paracancerous normal tissue or normal renal epithelial cell lines. In addition, FGFR2 high expression was associated with earlier, lower-level ccRCC and was associated with a better prognosis in the patients with ccRCC. Moreover, FGFR2 expression was not significantly related to B cells, T cells, NK cells and neutrophil infiltration, and the PPI network showed that FGFR2 protein interacted with certain molecules. CONCLUSION Our work sheds light on the potential role of FGFR2 in the development of ccRCC, suggesting that FGFR2 may serve as a prognostic marker and potential therapeutic target for patients with ccRCC.
Biomarkers, Tumor/analysis* ; Carcinoma, Renal Cell/pathology* ; Humans ; Kidney Neoplasms/pathology* ; Prognosis ; Receptor, Fibroblast Growth Factor, Type 2/genetics*

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1β, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1β, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lβ, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; C-Reactive Protein ; Caspase 3/metabolism* ; Interleukin-10 ; Interleukin-6/metabolism* ; Lactate Dehydrogenases/metabolism* ; Myeloblastin/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; Network Pharmacology ; Procalcitonin/therapeutic use* ; Sepsis/genetics* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*

Objective:To investigate the clinical characteristics of old patients with spinal cord injury. Methods:From January 1, 2013 to December 31, 2019, totally 386 old (≥ 60 years) patients with spinal cord injury were enrolled. Their gender, age, etiology, American Spinal Injury Association Impairment Scale (AIS) and complications were analyzed. Results:In the old patients with spinal cord injury, traumatic spinal cord injury was more common in males (71.17%) and non-traumatic spinal cord injury was more common in females (56.19%). Fall on level surface was the most important cause of spinal cord injury both in old men (28.83%) and women (24.76%). Tumor (19.05%) was the most common non-traumatic cause of spinal cord injury in old female patients. Cervical segment (78.46%) was the most common site of injury in old traumatic spinal cord injury, while thoracic segment (52.14%) was the most common site of injury in non-traumatic spinal cord injury. Grade D (38.08%) was the most common AIS grade, followed by grades C (28.76%), A (21.50%), and B (11.66%). Spinal canal stenosis (23.31%) played an important role in the etiology of old spinal cord injury. Neuralgia, venous thrombosis of lower extremities and urinary tract infection were the most common complications in old patients with spinal cord injury. Conclusion:Fall on level surface is the leading cause of spinal cord injury in old patients, and the proportion of fall in the etiology of old spinal cord injury tends to increase with age. It is important to take effective measures to avoid falling in the old adults to prevent spinal cord injury.

Objective:To investigate the outcome of neurological function and the clinical characteristics of complications in children with spinal cord injury. Methods:From 2011 to 2019, children under 15 years old with spinal cord injury were selected in our hospital. Their level of injury and American Spinal Injury Association Impairment Scale (AIS) at one month, three months and one year were recorded. And the complications such as pressure ulcers/scald, urinary tract infection, hydronephrosis/vesicoureteral reflux, constipation, osteoporosis/fracture, deep vein thrombosis, neurodynia, heterotopic ossification, scoliosis and hip dysplasia were analyzed. Results:Of 159 individuals, 41 were boys and 118 were girls, the average age at injury was (6.08±2.57) years. The main cause of spinal cord injury was sports accidents (47.8%), and the main injury sites were thoracic spinal cord injury (89.3%). The cause of spinal cord injury was correlated with age at injury (r = -0.160, P = 0.044), gender (r = -0.458, P < 0.001) and injury sites (r = -0.249, P = 0.002). Complete spinal cord injury counted for 71.7%, and the AIS grade at one month was correlated with that at twelve months (r = 0.984, P < 0.001). The main complications were urinary tract infection (69.2%), constipation (67.9%), hydronephrosis/vesicoureteral reflux (37.7%), scoliosis (25.8%) and hip dysplasia (25.2%). The incidence of ulcers/scald was correlated with injury site (r = 0.179, P = 0.024). The AIS grade three months after injury was significantly correlated with urinary tract infection, constipation, scoliosis and hip dysplasia (|r| > 0.227, P < 0.01). The incidence of ulcers/scald was correlated with osteoporosis/fracture (r = 0.208, P < 0.01). The incidence of urinary tract infection was significantly correlated with hydronephrosis/vesicoureteral reflux, constipation, scoliosis and hip dysplasia (r > 0.261, P < 0.001), as well as osteoporosis/fracture (r = 0.195, P < 0.05). The incidence of hydronephrosis/vesicoureteral reflux was significantly correlated with constipation, osteoporosis/fracture, scoliosis and hip dysplasia (r > 0.146, P < 0.01). The incidence of constipation was significantly correlated with scoliosis and hip dysplasia (r > 0.313, P < 0.01), as well as osteoporosis/fracture (r = 0.160, P < 0.05). The incidence of osteoporosis/fracture was significantly correlated with scoliosis and hip dysplasia (r > 0.342, P < 0.01). The incidence of scoliosis was significantly correlated with hip dysplasia (r = 0.818, P < 0.001). Conclusion:The recovery of neurological function after spinal cord injury in children is closely correlated to AIS. The outcome of complete spinal cord injury is poor. The common complications after spinal cord injury in children demonstrate specific age characteristics, and the incidence of urinary tract infection, constipation, hydronephrosis/vesicoureteral reflux, scoliosis and hip dysplasia are common complications, which need more attention.

Objective:To explore the clinical manifestations and MRI features of pediatric spinal cord injury (SCI) after back bend. Methods:A retrospective study was performed. All the medical records and MRI images of children with SCI after back bend were identified in Beijing Bo'ai Hospital from January 1st, 2002 to August 31st, 2020. Results:A total of 120 SCI children after back bend were reviewed, out of whom 119 cases were girls, one case was boy. The age ranged from 38 to 162 months, with the median age of 76 months. More cases were discovered in July and September every year (32 cases, 26.7%), as well as in weekends (67 cases, 55.8%). The main clinical manifestations were sensory and motor dysfunction of both lower limbs (120 cases, 100%), bladder and bowl incontinence (120 cases, 100%). The common first symptoms included sudden attack of lumbar pain (39 cases, 32.5%), lower limbs paralysis (30cases, 25.0%) and leg pain (10 cases, 8.3%). The peak time of symptoms ranged from five minutes to two days, with the median time of 50 minutes. The MRI features of 104 children with SCI within one week after back bend were as follows: the abnormal signals of MRI in spinal cord involved lower cervical and all the following segments of spinal cord. The number of the segments of spinal cord with abnormal signals ranged from two to 15, with the median of seven segments. The most common segments with abnormal signals were T₉ (96 cases, 92.3%), T₁₀ (96 cases, 92.3%) and T₁₁ (90 cases, 86.5%). Among the cases followed up, 48 cases with complete injury demonstrated a vast and serous spinal cord atrophy (SCA) below the injury segments as early as 37 days after the injury, the SCA would become worse at the chronic stage and maybe involve the spinal cord above the injury segments. In 31 cases with incomplete injury, the abnormal signals of MRI in spinal cord were limited in the lumbar enlargement, with a various degree of SCA at the late stage. All the cases were diagnosed as SCI without radiologic abnormality, out of whom 89 (74.2%) cases suffered from thoracic complete SCI, 31 (25.8%) cases suffered thoracic or lumbar incomplete SCI. The common complications included scoliosis, hip joint dysplasia, urinary tract infection, hydronephrosis, osteoporosis, pathological fracture of lower limbs and valgus knee. Conclusion:The main clinical symptoms of pediatric SCI after back bend were sudden lumbar pain, sensory and motor dysfunction of both lower limbs, and bladder and bowl incontinence. Most of the cases were thoracic complete SCI, the MRI features at the early stage were multiple segments of abnormal signals of spinal cord around T₉ and T₁₀, and later an extensive severe SCA below the injury segments to the conus medullaris, accompanied by the SCA above the injury segments.

Objective:To investigate the occurrence and related factors of autonomic dysreflexia (AD) during intermittent catheterization in patients with spinal cord injury (SCI). Methods:Case control study was used in this study. Intermittent catheterization was performed on 44 SCI patients hospitalized from April, 2019 to April, 2020, The data of age, gender, time after injury, segment of injury, degree of injury, resting blood pressure, immediate blood pressure after catheterization, catheterization numbers, catheterization volume and duration of catheterization were collected. Descriptive analysis and binary Logistic regression analysis were used to analyze the occurrence and related factors of AD. Results:Totally, AD happened in 26 (59.1%) patients. Urethral catheterization was done 1738 times, out of which AD accounted for 187 times (10.8%). The risk of AD increased with the time after injury and age (P < 0.05). The probability of AD was lower in T₇ SCI and below than in T₆ SCI and above (P = 0.002). Catheterization numbers, gender, degree of injury, catheterization volume and duration of catheterization were not influencing factors of AD (P > 0.05). Conclusion:It is necessary to have a full understanding for the occurrence of AD in patients with SCI during intermittent catheterization. For patients with SCI in T₆ and above, long time after injury and elderly patients, routine monitoring of blood pressure during intermittent catheterization is recommended to detect and deal with AD in time.