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Thirty-one phenolic constituents were isolated and purified from the 95% ethanol extract of Sanguisorbae Radix by using various chromatographic techniques, including macroporous resin, silica gel, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated by physicochemical properties, spectroscopic data (MS and NMR) and electronic circular dichroism (ECD) spectra, and identified as 3-methoxyl-2S,3S-epoxyflavanone (1a), 3-methoxyl-2R,3R-epoxyflavanone (1b), longifoin B (2), longifoin C (3), eriodictyol (4), naringenin (5), liquiritigenin (6), 5,3ʹ-dihydroxy-7,4ʹ-dimethoxyflavanone (7), naringenin-7-O-β-D-glucopyranoside (8), dihydroquercetin (9), dihydrokaempferol (10), (-)-garbanzol (11), (2R,3R)-4-methoxyl-distylin (12), kaempferol (13), quercetin (14), α,4,2′,4′-tetrahydroxydihydrochalcone (15), phloretin (16), (+)-catechin (17), ethyl (+)-cyanidan-3-ol-8-carboxylate (18), phyllocoumarin (19), methyl 3-methoxy-4,5-dihydroxybenzoate (20), 4,5-dimethoxy-3-hydroxybenzoic acid methyl ester (21), 3,4′-di-O-methylellagic acid (22), 3,4,3′-O-trimethylellagic acid (23), 3,3ʹ,4ʹ-O-trimethylellagic acid-4-O-β-D-xyloside (24), (3R)-thunberginol C (25), resveratrol (26), 1-hydroxypinoresinol (27), (7S,8S)-3-methoxy-3′,7-epoxy-8,4′-oxyneoligna-4,9,9′-triol (28), emodin-8-O-β-D-glucoside (29), phloracetophenone (30) and 4-(4′-hydroxyphenyl)-butan-2-one (31). Among them, compound 1a and 1b is a pair of new flavonoid enantiomers, compounds 2 and 3 are a pair of new epimers, while compounds 4, 5, 6, 9, 10, 13, 16 and 26 were obtained from S. officinalis for the first time, compounds 7, 8, 27, 30 and 31 were isolated for the first time from the S. officinalis genus, and compounds 11, 12, 15, 18, 19, 25, 28 and 29 were isolated for the first time from the Rosaceae. The antioxidant activities of compounds 1-24 were evaluated by activating the Nrf2 transcriptional pathway, which were measured by the dual-luciferase reporter gene assay in 293T cells. Compounds 4, 6-10, 12, 14, 17, 19, 20 and 22-24 showed significant Nrf2 agonistic effect compared with the control group at 25 μmol·L-1, which provided reference for the research of their antioxidant activity.
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Objective:To investigate the effect and mechanism of ionizing radiation on ferroptosis in mouse hepatocytes.Methods:Twenty-four C57BL/6J mice were divided into two groups by random number table method: healthy control group (control group, n=6) and irradiation group (whole liver was irradiated with a single dose of 30 Gy X-ray, n=18). Mice were sacrificed at 6, 24 and 72 h (6 mice per time point) after irradiation to obtain liver tissue and plasma samples. The contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma were measured by automatic biochemical analyzer. The prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured by automatic biochemical analyzer. Pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The iron deposition in liver tissues was detected by Prussian blue staining. The expression levels of 4-Hydroxynonenal (4HNE) and hepcidin in the liver were determined by immunohistochemical staining, and quantitative analysis was performed. Plasma malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC) and glutathione (GSH) content were determined by microplate reader analysis according to the kit instructions. The expression levels of transferrin receptor 1 (TfR1), p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the liver were measured by Western blot. Results:Compared with the control group, the plasma contents of ALT ( t=5.15, 5.47, both P<0.001) , AST at 6 and 24 h after irradiation were increased ( t=8.42, 2.50, both P<0.001), the plasma PT was prolonged ( t=3.12, P=0.011) and the APTT was shortened ( t=3.26, P=0.009) at 72 h after radiation in the irradiation group. Histopathological results showed that evident liver edema was observed at 6, 24 and 72 h after irradiation ( t=9.58, 10.09, 18.70, all P<0.001). Different degrees of iron deposition were observed ( t=8.57, 15.31, 32.11, all P<0.001). The infiltration of hepcidin positive cells was significantly increased after irradiation ( t=5.36, 13.17, 17.11, all P<0.001). The number of 4HNE positive cells was significantly increased ( t=18.86, 22.67, 9.12, all P<0.001). At the same time, ionizing radiation induced a significant increase in plasma MDA content ( t=4.36, 7.47, 8.22, all P<0.001), and a decrease in SOD ( t=4.52, 5.80, 7.60, all P<0.001), T-AOC ( t=13.24, 20.49, 24.96, all P<0.001) and GSH ( t=2.78, 6.07, 11.25, P=0.020, <0.001, <0.001), respectively. The expression level of TfR1 protein was significantly up-regulated ( t=3.46, 5.40, P=0.026, 0.006), whereas that of GPX4 protein was significantly down-regulated ( t=11.88, 30.63, both P<0.001) at 24 and 72 h after irradiation. At 6, 24 and 72 h after irradiation, the expression level of p53 protein was significantly up-regulated and maintained at a high level ( t=7.84, 4.25, 8.22, P=0.001, 0.013, 0.001), while that of SLC7A11 protein was significantly down-regulated ( t=9.29, 19.96, 9.09, all P<0.001). Conclusion:Ionizing radiation induces the ferroptosis in hepatocytes, and its mechanism may be related to the activation of p53-SLC7A11-GPX4 pathway.
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Objective:To analyze the clinical characteristics of infantile Takayasu Arteritis (TAK) complicated with cardiac involvements.Methods:The clinical data and cardiac lesions of infantile TAK were collected retrospectively, and the clinical characteristics of the disease were analyzed and summarized. Mainly using decriptive statistical methods.Results:In these 20 cases, 16 cases (80%) had cardiac involvements, only 2 cases had related symptoms. The common lesions were coronary artery lesion (CAL), valvular disease, and elevated myocardial enzymes, while the rare lesions were arrhythmia, pericardial effusion, hypertensive heart disease, and heart failure. One case had acute heart failure, which was systolic heart failure and was accompanied by hypertensive heart disease. All 14 patients with CAL were found by conventional coronary ultrasound screening. A total of 39 CAL were found, all of which were coronary artery dilation, and the left main coronary artery was involved. Five patients had heart valve disease, all of them were valve insufficiency. The involved valves were mitral and tricuspid valves, and one of them was severe insufficiency. Arrhythmias were found in 2 cases, of which P1 was found to have paroxysmal atrial tachycardia with high atrioventricular block at 3 months. All 20 children survived and were in stable condition after being treat with biological agents and/or glucocorticoids. A case of hypertensive heart disease complicated with heart failure was followed up for 4 years, and the cardiac function and blood pressure returned to normal. Fourteen children with CAL lesions were given oral aspirin disease, the CALs disappeared in 10 cases and retracted in 4 cases. During the follow-up of 5 children with heart valves, insufficiency disappeared in 4 cases and improved in 1. No child underwent valve replacement during the follow-up. One of the children with arrhythmia was treated with antiarrhythmic drugs. After treatment, the arrhythmia disappeared. Now they have been followed up for 5 years without recurrence.Conclusion:Infantile TAK has a high incidence of heart involvement, with extensive lesions but insidious clinical symptoms. CALs are common, and heart failure is rare. It should be evaluated and treated as early as possible.
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Objective:To compare the clinical efficacy between bone transport technique combined with bone grafting plus internal fixation and simple bone transport technique in the treatment of large segmental bone defects at lower limbs after trauma.Methods:A retrospective study was conducted to analyze the clinical data of 42 patients with large segmental bone defects at lower limbs after trauma who had been treated at Department of Trauma Orthopaedics, Honghui Hospital Affiliated to Medicine College, Xi'an Jiaotong University from September 2015 to September 2019. The patients were divided into 2 groups according to the different methods of repairing bone defects. In group A of 18 patients subjected to bone transport combined with bone grafting plus internal fixation, there were 11 males and 7 females with an age of (35.2±10.3) years, and 12 tibial defects and 6 femoral defects; in group B of 24 patients subjected to simple bone transport, there were 15 males and 9 females with an age of (37.3±9.4) years, and 17 tibial defects and 7 femoral defects. The external fixation time (EFT), external fixation index (EFI), total cure time and complications were recorded and compared between the 2 groups. At the last follow-up, the Ennecking score for limb functional recovery (score/total score 30) and Self-rating Anxiety Scale (SAS) were used to evaluate respectively the functional recovery of the limbs and postoperative anxiety.Results:The 2 groups were comparable because there was no significant difference between them in preoperative general data or follow-up time ( P>0.05). There was no statistically significant difference in the number of surgeries between the 2 groups ( P>0.05). The EFT [(5.9±1.5) months], EFI [(0.45±0.09) months/cm], total treatment time [(16.2±2.4) months], Ennecking score for limb functional recovery (87.0%±8.6%), SAS score [(43.2±9.0) points], and complications per capita [(0.4±0.2) times/case] in group A were significantly better than those in group B [(15.3±4.2) months, (1.19±0.28) months/cm, (19.7±3.5) months, (77.3%±9.2%), (58.2±9.3) points, and (1.2±0.5) times/case] (all P<0.05). Conclusion:In the treatment of large segmental bone defects at lower limbs, compared with simple bone transport technique, bone transport technique combined with bone grafting plus internal fixation has advantages of shorter external fixation time and overall cure time, a lower rate of complications, and better functional recovery of the limbs.
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Objective:To investigate the clinical effects of antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap in the one-stage treatment of chronic calcaneus osteomyelitis plus skin and soft tissue defects.Methods:From January 2013 to September 2019, 48 patients were admitted to Department of Orthopedic Trauma, Xi'an Honghui Hospital Affiliated to Xi'an Jiaotong University for chronic calcaneal osteomyelitis complicated with skin and soft tissue defects. They were divided into 2 groups according to different bone grafts. In group A of 26 patients treated at one stage by antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap, there were 16 males and 10 females with an age of (45.0±11.7) years and an area of skin defect of (56.0±16.7) cm 2. In group B of 22 patients treated at one stage by simple autologous iliac bone combined with sural neurocutaneous flap, there were 13 males and 9 females with an age of (43.6±9.6) years and an area of skin defect of (53.8±16.2) cm 2. The volume of the ilium harvested, fracture healing time, infection control, donor site complications, pain score of visual analogue scale (VAS) and function recovery of the ankle were compared between the 2 groups. Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The 48 patients were followed up for (15.3±6.0) months. Group A had a significantly smaller volume of the ilium harvested [(67.3±14.1) cm 3] than group B [(90.7±23.5) cm 3], a significantly lower rate of donor site complications [3.8% (1/26)] than group B [31.8% (7/22)], significantly lower VAS pain scores at 6, 12, 24, 48 and 72 hours than group B, and significantly lower WBC count, erythrocyte sedimentation rate and C-reactive protein at 2, 4, 8 weeks after operation than group B (all P<0.05). There was no statistically significant difference between the 2 groups in the infection control rate [96.2% (25/26) versus 77.3% (17/22)], the fracture healing time [(6.2±1.9) months versus (6.4±2.1) months], or the ankle-hindfoot score of AOFAS (The American Orthopaedic Foot and Ankle Society) (83.9±7.2 versus 82.5±8.7) at 6 months after operation (all P>0.05). Conclusion:In one-stage treatment of chronic calcaneal osteomyelitis complicated with skin and soft tissue defects, compared with simple autologous iliac bone combined with sural neurocutaneous flap, antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap can reduce the volume of the ilium harvested, pain score of VAS, and incidence of donor site complications, and improve the recovery of inflammatory indicators, leading to fine clinical effects.
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Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.
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Objective:To study the effect of iodine excess on antioxidant capacity and blood lipid in adult.Methods:A survey was conducted in areas with different iodine nutrition levels in Shandong and Shanxi provinces to collect fasting morning urine and venous blood samples of adults. Urinary iodine, serum levels of superoxide dismutase(SOD), malondialdehyde (MDA), total cholesterol (TCHO), triglyceride (TG), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were determined. According to the median urinary iodine of the population in the investigated village, they were divided into appropriate iodine group (100-299 μg/L) and iodine excess group (≥300 μg/L) . Multiple linear regression was used to analyze the effects of iodine nutrition and other factors on oxidative stress indexes and blood lipids. Partial correlation analysis was used to analyze the relationship between iodine nutrition and oxidative stress indexes and blood lipids.Results:A total of 1 049 subjects were included, including 471 in the appropriate iodine group and 578 in the iodine excess group. The median (quartile) urinary iodine of the appropriate iodine group and the iodine excess group was 228.70 (157.02, 341.49) and 558.73 (298.06, 985.06) μg/L, respectively. The serum SOD level of the appropriate iodine group and the iodine excess group was 12.60 (10.83, 14.10) and 11.29 (9.18, 13.10) U/ml, respectively, and the difference between the groups was statistically significant ( U = 92 697.50, P < 0.001). There were statistically significant differences in serum TG, HDL-C and apoB levels between the appropriate iodine group and the iodine excess group ( U = 108 879.50, 96 613.50, 99 050.50, P < 0.05). The results of multiple linear regression showed that after excluding age, gender and body mass index (BMI), there was a negative correlation between iodine nutrition and serum SOD and HDL-C levels [standard regression coefficient ( β) = - 0.196, - 0.294, P < 0.001]. Partial correlation analysis showed that there was a negative correlation between iodine nutrition and serum SOD and HDL-C levels [correlation coefficient ( r) = - 0.16, - 0.09, P < 0.05]. Conclusion:Excessive iodine intake affects oxidative stress and lipid metabolism in human body.
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Objective:To investigate the effect of T-lymphocyte and subpopulation counts on the prognosis of severe acute pancreatitis (SAP) patients.Methods:The clinical data of 90 patients with SAP diagnosed at the Shanghai General Hospital between January 2019 and June 2022 were retrospectively analyzed, and the patients were divided into good prognosis and poor prognosis group according to whether they were diagnosed for 28 d. The general information of the patients was recorded, including blood-related immunological indicators within 24 h of diagnosis, including leukocytes, neutrophils, lymphocytes, monocytes, CD 3+ , CD 4+ , CD 8+ T-lymphocyte count and CD 4+ /CD 8+ T-lymphocyte ratio, IgG4 level; blood inflammation index procalcitonin, albumin level and APACHEⅡ score at admission; survival and complication status of patients at 28 d of diagnosis. Non-parametric Mann-Whitney U test was used to analyze the correlation between each index and the prognosis of the patients. The subject operating characteristic curve (ROC) of patients was plotted, and area under curve (AUC) was calculated to assess the value of CD 3+ and CD 4+ T-lymphocytes in predicting the prognosis of SAP. Results:The majority of SAP patients were male (65.6%). The main cause of SAP was gallstone (56.7%), followed by hyperlipidemia (35.6%). At 28 days after diagnosis, 85(94.4%) patients survived, and 39 of them were cured and included in the good prognosis group. Forty-six cases were complicated with infection, multiple organ dysfunction syndrome (MODS) and local pancreatic complications, and 5 cases (5.56%) died; and a total of 51 cases were included in the poor prognosis group. Compared with the good prognosis group, the number of CD 3+ T-lymphocytes [366(268, 498) cells /μl vs 709(578, 999) cells /μl], CD 4+ T-lymphocytes [209(120, 298) cells /μl vs 486(303, 548) cells /μl] and albumin level (33.9 g/L vs 35.9 g/L) within 24 hours in the poor prognosis group were significantly lower, while the level of procalcitonin (1.02 ng/ml vs 0.43 ng/ml) and APACHEⅡ score [7(4, 10) vs 5(3, 8)] were significantly increased, and all the differences were statistically significant (all P value <0.05). ROC curve analysis showed that the AUC values for CD 3+ and CD 4+ T-lymphocyte counts within 24 hours for predicting poor prognosis of SAP were 0.857 (95% CI 0.696-1.000) and 0.867 (95% CI 0.708-1.000), respectively. The cut-off values were 524 cells /μl and 301 cells /μl, the sensitivity were both 85.7%, and the specificity were 78.6% and 85.7%, respectively. Conclusions:The significant decrease of peripheral blood CD 3+ and CD 4+ T-lymphocyte count within 24 h of SAP diagnosis has a certain predictive value for the prognosis of patients with SAP.
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A new siderophore chelate (1) and 8 known compounds were identified from the liquid co-cultures of the marine-derived Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 by a combination of chromatography methods, including C18 reversed-phase medium pressure chromatography, gel column chromatography and HPLC. Their structures were determined by spectroscopic analysis and chemical methods as aluminioxamine E (1), desferrioxamine E (2), ferrioxamine E (3), terragine E (4), capsimicin (5), cyclo(L-prolinyl-L-tyrosine) (6), anthranilic acid (7), (Z)-14-methylpentadec-9-enoic acid (8), and (Z)-hexadec-8-enoic acid (9). Compound 2 showed inhibitory activities against the expression of liver fibrosis related genes COL1A1, MMP2, and TIMP2. Compounds 5, 8, and 9 displayed antibacterial activities against methicillin-resistant Staphylococcus aureus, S. epidermidis and Bacillus subtilis, with MICs of 16-64 μg·mL-1. Compound 5 showed cytotoxicities against human pancreatic cancer MIA Paca-2 and human colon cancer HT-29 cell lines with IC50 of 2.9 and 6.3 μmol·L-1, respectively.
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AIM:To observe the effect of implantable collamer lens V4c(ICL V4c)implantation on high myopia, and the changes in anterior segment morphology.METHODS:A prospective study was conducted on 100 patients(200 eyes)with high myopia who were treated with ICL V4c implantation in the hospital from February 2018 to March 2021. The best corrected visual acuity(BCVA), uncorrected visual acuity(UCVA), intraocular pressure, higher-order aberration, anterior segment morphology [iridocorneal angle(ICA), central anterior chamber depth(ACD), anterior chamber volume(ACV), central corneal thickness(CCT)and K-value(K)], photopic and scotopic contrast sensitivity before operation and 6 and 12mo after operation were comparatively analyzed.RESULTS:All patients were followed-up. UCVA and BCVA were significantly improved at 6 and 12mo after operation(P<0.05). Total higher-order aberration, horizontal coma and vertical coma showed no significant difference before and after operation(P>0.05). Spherical aberration, ICA, ACD and ACV at 6 and 12mo after operation were significantly smaller than those before operation(P<0.05). Under photopic state, the contrast sensitivity of 3.0 and 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P<0.05). Under scotopic state, the contrast sensitivity of 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P<0.05); there was no significant difference in CCT, K, or intraocular pressure before and after operation(P>0.05).CONCLUSION:Although ICA, ACD and ACV in patients with high myopia are reduced after ICL V4c implantation, the operation can effectively improve visual acuity and visual quality.
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Diabetic retinopathy(DR)is the most common microvascular complication of patients with diabetes mellitus, and it has become one of the leading causes of visual impairment among working-age people worldwide. The pathogenesis of DR is complicated with multiple mechanisms. Plenty of studies have indicated that circadian rhythm and clock genes are closely related to the pathogenesis of DR. Circadian rhythm is a physiological process regulated by clock genes, which takes 24h as a cycle and is consistent with the changes of light and dark outside. Circadian rhythm regulates various physiological activities of the body. The disturbance of circadian rhythm induces DR by affecting the blood glucose level and the physiological homeostasis of the eye in patients with diabetes mellitus, and clock genes may be involved in the pathogenesis of DR by regulating oxidative stress response, inflammatory response, retinal autophagy rhythm, mitochondrial dysfunction and endothelial progenitor cell function. This paper will introduce the generation and regulation mechanism of circadian rhythm, as well as the internal circadian rhythm of retina, and further discuss the influence of circadian rhythm and clock genes on the occurrence and development of DR, aiming to provide a reference for the prevention and treatment of DR.
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Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.
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Mice , Animals , Zona Incerta/metabolism , Neurons/metabolism , Fear/physiology , Somatostatin/metabolismABSTRACT
Clinical data of a child with mevalonic aciduria (MA) who underwent stem cell transplantation (SCT) in the Department of Rheumatology and Immunology, Children′s Hospital, Capital Institute of Pediatrics in March 2019 were retrospectively analyzed.A girl aged 2 years and 11 months old presented with recurrent fever for 2 years and 11 months and swelling of both knees for 9 months was enrolled.The child also had specific facial features and development delay.The urinary mevalonic acid and inflammatory factor levels were increased.The whole exome sequencing showed compound heterozygous mutations c. 439G>A (p.A147T) and c. 976G>A(p.G326R) in the MVK gene.After achieving a partial remission following the treatment of Tocilizumab, the patient was treated with SCT and thus yielded the complete remission.Through literature review of a total of 39 children with MA, most of cases suffer MA since the infancy.All systems can be affected by MA.Clinical manifestations of the nervous system abnormalities, recurrent fever, hepatosplenomegaly, delayed physical development, gastrointestinal symptoms, and eye involvement were helpful for the diagnosis of MA.To date, 10 cases (including one case in this study) of MA have been reported to receive SCT after achieving a partial remission of other treatment, and 7 finally achieve a complete remission.This case report provided references that SCT is an effective treatment to children with MA who fail to achieve a complete remission after conventional treatment.
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Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.
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Objective:To analyze the therapeutic effect of sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft of chronic calcaneal osteomyelitis.Methods:A retrospective analysis was peformed in 29 patients with chronic calcaneal osteomyelitis treated with sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from April 2013 to January 2020. There were 19 males and 10 females, with the age of (45.38±12.85) years, ranged from 22 to 67 years. The course of disease was (16.00±6.96) months, ranged from 6 to 36 months. The skin defect area was (41.9±15.9) cm 2, ranged from 11.8 to 86.8 cm 2. The causes of injury: 18 cases of high fall, 6 cases of traffic accidents, 3 cases of heavy rolling, the remaining 2 cases were machine strangulation and sharp stab wounds. The inflammatory markers [white blood cell (WBC), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C reactive protein (CRP)] and bone healing time were recorded before operation, 2, 4, 8 weeks and 6 months after operation. During the follow-up period, the flap texture, survival were observed, and the ankle-posterior foot function recovery was evaluated by the American Association of Foot and Ankle Surgery (AOFAS) score were observed before and after the operation, and the incidence of complications were recorded. The measurement data were expressed as mean±standard deviation ( ± s), and the t-test was used for inter-group comparison; the levels of WBC, ESR, PCT and CRP at different time points before and after operation were compared by repeated measurement ANOVA, and the LSD t-test was used for pairwise comparison. Results:All the 29 patients were followed up for (14.51±6.10) months, ranged from 6 to 30 months. All the flaps survived without abrasion, ulceration, or skin protrusion, and all patients could walk normally with shoes. There were 28 cases of stage I bone healing, with an average of (5.87±2.07) months, ranged from 3 to 12 months. The inflammatory indexes was significantly decreased at different time points after operation ( P<0.05). There was no significant difference between 6 months and 8 weeks after operation ( P>0.05), while there was significant difference at other time points ( P<0.05). The ankle-posterior foot score of AOFAS at 6 months after treatment was significantly higher than that before treatment (83.44±7.93 vs 55.37±8.07), the differences was statistically significant ( P<0.05). The clinical efficacy of foot function recovery was excellent in 12 cases, good in 15 cases and fair in 2 cases among 29 patients .The excellent and good rate was 93.1% (27/29). One patient recurred 1 month after operation and was re-implanted with antibiotic-loaded calcium sulfate mixed autogenous iliac bone after debridement, no recurrence was found. The total complication rate was 31.0%, but there was no significant impact on the patient's life in the later period. All patients returned to daily life and work. Conclusion:The treatment of chronic calcaneal osteomyelitis with sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft can effectively control infection, reconstruct calcaneal and soft tissue structure, promote functional recovery of affected limb, and ultimately improve the patient′s quality of life.
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Objective:To compare the clinical effects of acute shortening-lengthening technique with antibiotic calcium sulfate-loaded bone transport technique for the treatment of segmental tibial defects after trauma.Methods:The clinical data of 58 patients with large tibial defects treated by Ilizarov technique in Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from May 2014 to December 2019 were retrospectively analyzed. Thirty patients were treated by acute shortening-lengthening (group A), and they were divided into those who were successful in one-time shortening during operation (group A1) and those who needed gradual shortening after operation (group A2) according to different shortening conditions. And 28 patients by antibiotic calcium sulfate-loaded bone transport (group B). The external fixation time (EFT) and external fixation index (EFI) of the two groups were compared. Bone defect healing and limb functions were evaluated according to the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria. Complications were compared by Paley classification. The measurement data of normal distribution were expressed as ± s, and t-test was used for comparison between groups; the count data were expressed as n(%), and the chi-square test, Fisher exact probability method or Mann-Whitney U test were used for comparison between groups. Results:Patients were followed for(27.5±5.1)months. There was no significant difference in EFT, EFI, bone defect healing and limb functions between the two groups( P>0.05). The incidence of Grade-Ⅱ[41.2% (7/17)], Grade-Ⅲ [47.1% (8/17)] pin-tract infection in group A1 and Grade-Ⅱ[46.2% (6/13)], Grade-Ⅲ pin-tract [53.8% (7/13)] in group A2 was significantly higher than those in group B[14.3% (4/28)], [17.9% (5/28)] ( P<0.05). The number of complications per capita in group A1 [(1.4±0.3) times/case] and in group A2 [(1.5±0.3) times/case]was significantly higher than that in group B [(1.1±0.5) times/case]. Conclusions:Patients can be cured successfully by both acute shortening-lengthening and bone transport techniques. Compared with acute shortening-lengthening group, the complication incidence in antibiotic calcium sulfate-loaded bone transport group was lower, especially, the infection-related complications. Therefore, antibiotic calcium sulfate-loaded bone transport technique has a greater application prospect in patients with large segmental bone defects caused by infection or osteomyelitis.
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Objective:To prepare chitosan/gelatin hydrogel composite hemostatic materials loaded with Panax notoginseng (PN/CMC/GMs) and evaluate their performance. Methods:PN/CMC/GMs hydrogel composite hemostatic material were prepared by the freeze-drying method, and their morphology was observed by scanning electron microscopy. Their rheological properties were observed by a rheometer. Their water absorption rate was tested by dissolution. Their biocompatibility was detected by a cytotoxicity assay. Their rapid hemostatic effect was tested using a SD rat liver hemorrhage model.Results:PN/CMC/GMs composite hemostatic materials were prepared in a lattice-like structure with certain porosity. With the increase in Panax notoginseng powder content, the modulus of PN/CMC/GMs increased accordingly, and the mechanical strength increased. PN/CMC/GMs have better water absorption and expansion functions, which can form compression hemostasis and concentrated blood to achieve rapid hemostasis, and have good biocompatibility. Hemostasis experiments showed that the hemostatic time and hemostatic effect of PN, CMC/GMs hemostatic materials on liver injury in rats were better than those of the blank control group. Conclusions:PN/CMC/GMs have good hemostatic effect and biocompatibility and have the potential for further research and clinical application.
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Objective To study the stability of plate-assisted intramedullary nailing for fixing proximal third tibiafractures, compare and observe biomechanical characteristics of anterolateral or posteromedial plate-assisted intramedullary nailing after fixation of proximal third tibia fractures. Methods Eight artificial tibia of 4th-generation sawbones were divided into two groups based on location of the assisted plate, namely, anterolateral plate group and posteromedial plate group, with 4 specimens in each group. Each two locking bolts were fixed to theintramedullary nail proximally and distally, and each three bicortical screws were fixed to the plate proximally and distally. The specimens were osteotomized with a 10-mm defect which located 0. 5 cm to the proximal locking bolt of intramedullary nail or 5-6 cm distally to the knee joint line, in order to simulate an AO/ OTA 41-A2 type proximal third tibia fracture after fixation of intramedullary nail. After osteotomy was finished, axial compression test, three point bending test, cyclic loading and overstress test were conducted by mechanical testing machine. The results of axial stiffness and three-point stiffness between two groups were compared and analyzed. Results Axial compression test showed that the average axial stiffness in posteromedial plate group was lower than that in anterolateral plate group, but no significantly statistical differences were found between the two groups. Three point bending test showed that the average bending stiffness in posteromedial plate group was significantly higher than that in anterolateral plate group when stimulating either varus stress (plate located at pressure side of the fracture, t = 3. 679, P<0. 05) or valgus stress (plate located at tension side of the fracture, t = 8. 975, P<0. 05). Conclusions Plate-assisted intramedullary nailing for fixation of proximal third tibia fractures can minimize the angulation malalignment, improve the stability of nailed proximal tibial fragment and allow the early weight bearing. Both anterolateral and posteromedial plate-assisted intramedullary nail can provide satisfactory axial stability for proximal third tibia fractures, while posteromedial plate-assisted intramedullary nail shows better bending stability than anterolateral plate in countering varus or valgus stress deformity. This study provides an essential basis for clinical decision making about plate-assisted intramedullary nailing for fixing proximal third tibia fractures.
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Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.
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Humans , Acute-On-Chronic Liver Failure , Prognosis , Retrospective Studies , End Stage Liver Disease , Severity of Illness IndexABSTRACT
Objective: To explore the clinical features and prognosis of children with histiocytic necrotizing lymphadenitis (HNL). Methods: The clinical data of 118 children with HNL diagnosed and treated in the Department of Rheumatology and Immunology of Children's Hospital, Capital Institute of Pediatrics from January 2014 to December 2021 were retrospectively analyzed. The clinical symptoms, laboratory examination, imaging examination, pathological findings, treatment and follow-up were analyzed. Results: Among the 118 patients, 69 were males and 49 were females. The age of onset was 10.0 (8.0, 12.0) years, ranging from 1.5 to 16.0 years. All the children had fever lymph node enlargement, blood system involvement in 74 cases (62.7%), skin injury in 39 cases (33.1%). The main manifestations of laboratory examination were increased erythrocyte sedimentation rate in 90 cases (76.3%), decreased hemoglobin in 58 cases (49.2%), decreased white blood cells in 54 cases (45.8%) and positive antinuclear antibody in 35 cases (29.7%). Ninety-seven cases (82.2%) underwent B-mode ultrasound of lymph nodes, showing nodular lesions with low echo in the neck; 22 cases (18.6%) underwent cervical X-ray and (or) CT; 7 cases (5.9%) underwent cervical magnetic resonance imaging. Lymph node biopsy was performed in all 118 cases, and the pathological results did not support malignant diseases such as lymphoma or Epstein-Barr virus infection, suggesting HNL. Fifty-seven cases (48.3%) recovered without treatment, 61 cases (51.7%) received oral steroid therapy, and 4 cases (3.4%) received indomethacin as anal stopper. The 118 cases were followed up for 4 (2, 6) years, ranging from 1 to 7 years, 87 cases (73.7%) had one onset and did not develop into other rheumatological diseases, and 24 cases (20.3%) had different degrees of recurrence, 7 cases (5.9%) had multiple system injuries, and all of the tested autoantibodies were positive for medium and high titers. All of them developed into other rheumatic immune diseases, among which 5 cases developed into systemic lupus erythematosus and 2 cases developed into Sjogren's syndrome; 7 cases were given oral steroid therapy, including 6 cases plus immunosuppressant and 2 cases receiving methylprednisolone 20 mg/kg shock therapy. Conclusions: The first-onset HNL portion is self-healing, hormone-sensitive and has a good prognosis. For HNL with repeated disease and multiple system injury, antinuclear antibody titer should be monitored during follow-up, and attention should be paid to the possibility of developing into other rheumatological diseases, with poor prognosis.