Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages.@*METHODS@#In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table.@*RESULTS@#Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-β2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%.@*CONCLUSION@#Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

Correlation analysis between body mass index and clinical characteristics of rheumatoid arthritis / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical features of overweight and obese rheumatoid arthritis (RA)patients, and the relationship between body mass index (BMI) and disease characteristics.@*METHODS@#The demographic data, extra-articular manifestations, comorbidities, and disease activity of RA patients admitted to the Rheumatology and Immunology Department of Peking University Third Hospital from January 2015 to December 2020 were collected, and the above characteristics of overweight and obese RA patients were retrospectively analyzed. According to the WHO, BMI≥30 kg/m2 referred to obese individuals, 25≤BMI < 30 kg/m2 referred to overweight individuals, 18.5≤BMI < 25 kg/m2 referred to normal individuals, BMI < 18.5 kg/m2 referred to reduced body mass individuals. t test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non-normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, Chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. Analyzing whether overweight or obesity was associated with comorbidities using Logistic regression adjusted confounding factors.@*RESULTS@#A total of 481 RA patients were included in this study, with an average BMI value of (23.28±3.75) kg/m2.Of the patients, 31 cases (6.5%) were with BMI < 18.5 kg/m2, 309 cases (64.2%) with 18.5≤ BMI < 25 kg/m2, amounting to 340 cases (70.7%). There were 119 overweight individuals (25≤ BMI < 30 kg/m2, 24.7%) and 22 obese individuals (BMI≥30 kg/m2, 4.6%), totaling 141 (29.3%).The proportion of the overweight and obese RA patients suffering from hypertension (57.4% vs. 39.1%, P < 0.001), diabetes (25.5% vs. 15.0%, P=0.006), hyperlipidemia (22.7% vs. 10.9%, P=0.001), fatty liver (28.4% vs. 7.4%, P < 0.001), osteoarthritis (39.0% vs. 29.4%, P=0.040) was significantly higher, and the proportion of the patients with osteoporosis(59.6% vs. 70.9%, P=0.016) and anemia (36.2% vs. 55.6%, P < 0.001) was significantly lower. However, there was no difference between the two groups in coronary heart disease (5.7% vs. 7.6%, P=0.442), cerebrovascular disease (6.4% vs. 8.8%, P=0.372) and peripheral atherosclerosis (9.2% vs. 7.6%, P=0.565).The median C-reactive protein (CRP, 1.52 mg/dL vs. 2.35 mg/dL, P=0.008), median erythrocyte sedimentation rate (ESR, 34.0 mm/h vs. 50.0 mm/h, P=0.003), pain visual simulation score (VAS) (3.66±3.08 vs. 4.40±2.85, P=0.011), and 28 joint disease activity scores (DAS-28, 5.05±1.60 vs. 5.45±1.52, P=0.010) in the overweight and obese RA group were all lower than those in the normal and reduced weight groups. Multivariate regression analysis showed that overweight and obesity was an independent risk factor for hypertension, diabetes, hyperlipidemia and fatty liver, and had protective effects on osteoporosis and anemia.@*CONCLUSION@#In RA patients, RA disease activity is lower in overweight and obesity patients. Overweight and obesity is associated with hypertension, diabetes and hyperlipidemia, but not with cardiovascular and cerebrovascular diseases.

A preliminary study on the prevention of hemorrhage after laparoscopic pancreaticoduodenectomy by wrapping gastroduodenal artery stump in the left external liver lobe and the left caudate lobe / 中华外科杂志

Objective: To investigate the safety and efficacy of embedding the stump of gastroduodenal artery between the left lateral lobe of the liver and the left caudate lobe to prevent bleeding after laparoscopic pancreaticoduodenectomy. Methods: The clinical data of 41 patients who underwent laparoscopic pancreaticoduodenectomy at the second Hospital of Hebei Medical University from October 2021 to April 2022 were analyzed retrospectively.There were 27 males and 14 females, aged (63.0±9.2)years (range: 48 to 78 years), and the body mass index was (24.1±3.2)kg/m2 (range: 15.4 to 31.6 kg/m2). After routine laparoscopic pancreaticoduodenectomy, the stump of gastroduodenal artery was embedded between the left lateral lobe and the left caudate lobe of the liver, and the hepatic parenchyma of the left lateral lobe and the left caudate lobe were sutured with absorbable sutures.The occurrence and recovery of postoperative complications (pancreatic fistula, biliary fistula, postoperative abdominal bleeding, abdominal infection, liver abscess) were observed. Results: All the operations of 41 patients were completed successfully.The operation time was (277.5±52.0) minutes (range: 192 to 360 minutes). The entrapment time of gastroduodenal artery stump was (3.1±0.6) minutes (range: 2.3 to 4.2 minutes), and the intraoperative blood loss (M(IQR)) was 300 (200) ml (range: 50 to 800 ml).The results of ultrasound examination of hepatic artery on the first day after operation showed that the blood flows of hepatic artery were unobstructed.Postoperative pancreatic fistula occurred in 3 cases, including grade B pancreatic fistula in 2 cases (1 case with abdominal infection) and biochemical leakage in 1 case. Three patients with pancreatic fistula were discharged successfully after continuous abdominal drainage. There was no biliary fistula, abdominal bleeding, abdominal infection, liver abscess or postoperative liver dysfunction. Conclusion: The encasement of the gastroduodenal artery stump by the left outer and left caudate lobes of the liver may be an effective way to prevent bleeding from the rupture of the gastroduodenal artery stump after laparoscopic pancreatoduodenectomy, which is easy and safe to perform.

Risk factors for multiple debridements of the patients with deep incisional surgical site infection after spinal surgery / 北京大学学报(医学版)

OBJECTIVE@#To investigate the risk factors that contribute to multiple debridements in patients suffering from deep incisional surgical site infection after spinal surgery and advise medical personnel to pay special attention to these risk factors.@*METHODS@#We retrospectively enrolled 84 patients who got deep incisional surgical site infection after spinal surgery from Jan. 2012 to Dec. 2017. The infections occurred within 30 days after the surgery, and the identification met the criteria of deep incisional surgical site infection of Centers of Disease Control (CDC). Early debridement with first stage closure of the wound and a continuous inflow-outflow irrigation system was used, and reasonable antibiotics were chosen according to the bacterial culture results. During the treatment, the vital signs, clinical manifestations, blood test results, drainage fluid colour and bacterial culture results were acquired. If the infection failed to be controlled or relapsed, a second debridement was performed. Of the 84 cases, 60 undergwent single debridement which included 36 male cases and 24 female cases, and the age ranged from 36 to 77 years, with a mean of 57.2 years. Twenty four had multiple debridements (twice in 14 cases, three times in 6 cases, four times in 1 case, five times in 2 cases, six times in 1 cases) which included 17 male cases and 7 female cases, and the age ranged from 21 to 70 years, with a mean of 49.5 years. Risk factors that predispose patients to multiple debridements were identified using univariate analysis. Risk factors with P values less than 0.05 in univariate analysis were included together in a multivariate Logistic regression model using back-forward method.@*RESULTS@#Multiple debridements were performed in 28.6% of all cases. The hospital stay of multiple debridements group was (82.4±46.3) days compared with (40.4±31.5) days in single debridement group (P=0.018). Instrumentation was removed in 6 cases in multiple debridements group and 4 cases in single debridement group (P=0.049). Flap transplantation was performed in 7 cased in multiple debridements group while none in single debridement group (P < 0.001). Diabetes, primary operation duration longer than 3 hours, primary operation blood loss more than 400 mL, bacteriology examination results, distant site infection were significantly different between the two groups in univariate analysis. In multivariate analysis, primary operation duration longer than 3 hours (OR=3.60, 95%CI: 1.12-11.62), diabetes (OR=3.74, 95%CI: 1.06-13.22), methicillin-resistant Staphylococcus aureus (MRSA) infected (OR=16.87, 95%CI: 2.59-109.73) were the most important risk factors related to multiple debridements in the patients with deep incisional surgical site infection after spinal surgery.@*CONCLUSION@#Diabetes, primary operation duration more than 3 hours, MRSA infected are independent risk factors for multiple debridements in patients suffering from deep incisional surgical site infection after spinal surgery. Special caution and prophylaxis interventions are suggested for these factors.

Clinical and laboratory characteristics of rheumatoid arthritis with positive antinuclear antibody / 北京大学学报(医学版)

OBJECTIVE@#To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients.@*METHODS@#The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1.@*RESULTS@#The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ2=20.355, P < 0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ2=6.414, P < 0.05). The incidence of secondary Sjögren's syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ2=23.300, P < 0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ2=25.743, P < 0.01, 74.9% vs. 59.4%, χ2=11.694, P < 0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P < 0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P < 0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[(109.64±17.98) vs. (114.47±18.48) g/L, t=-2.734, P < 0.01; (266.4×109±104.6×109) vs. (295.9×109±100.1×109) /L, t=-2.970, P < 0.01, respectively].@*CONCLUSION@#The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.

Hypophosphatemic osteomalacia caused by urinary mesenchymal tumor: A case report / 北京大学学报(医学版)

This case report concerns a 34-year-old woman who had been diagnosed with ankylosing spondylitis (AS), fibromyalgia syndrome (FMS), osteoarthritis (OA), lumbar disc herniation and the like in different hospitals during the past 18 months. She had progressive osteoarthrosis, significant muscle weakness, gait abnormalities in weightbearing areas, however without typical inflammatory low back pain, while the treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was invalid, with normal inflammation index, negative results for rheumatic factor (RF) and human leukocyte antigen (HLA)-B27, and normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). She had hyphosphatemia, normal serum calcium, 1,25-(OH)2-D3 reduction, elevated alkaline phosphatase (ALP) and normal parathyroid hormone (PTH), however with elevated urinary phosphorus. Finally, the medial thigh nodule was found in the subcutaneous of her inner leg by careful examination and imaging scans including B-ultrasound and PET/CT. The final pathology confirmed that the nodule was phosphate urinary mesenchymal tumors. After the tumor was removed, the patient was treated with anti-osteoporosis and phosphorus supplementation. The symptoms of bone pain and muscle weakness were alleviated, and hypophosphatemia was corrected. It was confirmed that the patient had low-phosphorus osteomalacia due to tumor. Tumor-induced hypophosphatemia osteomalacia (TIO) was a rare paraneoplastic syndrome which was caused by excessive phosphorus excretion induced by the tumor, and was thus categorized as an acquired hypophosphatemic osteomalacia. TIO had an occult onset and was associated with a high rate of misdiagnosis, although TIO has some typical clinical features. Early diagnosis, correctly positioning of the tumor, and surgical resection can achieve good outcomes.

Magnetic resonance imaging features and differential diagnosis of multiple gliomas / 医学研究生学报

Objective The magnetic resonance imaging (MRI) patterns of multiple gliomas are insufficiently understood because the related studies are rarely reported and mostly with small-size samples. This article summarizes the MR manifestations of multiple gliomas, analyzes their imaging features and proposes some diagnostic ideas. Methods We retrospectively reviewed 303 cases of diffuse glioma pathologically confirmed in our hospital from January 2014 to December 2018, including 240 cases of solitary (79.2%) and 63 cases of multiple gliomas (20.8%). We analyzed the MRI manifestations, summarized the MRI patterns, and investigated the differential diagnosis of multiple gliomas. Results According to the growth patterns, 4 of the 63 cases of multiple gliomas were classified as multicentric and the other 59 as multifocal glioma, and of the 59 cases of multifocal glioma, 35 spread along the white matter fiber bundle, 24 along the subependymal and small vessel space, 6 along the meningia-subarachnoid space, and 41 in a mode of direct invasion. The manifestations of cortical involvement included cortical tubers (37.2% [16/43]), multiple cortical tubers with high-intensity signals on T2WI, diffuse cortical swelling (44.2% [19/43]), frontal cortical swelling with high-intensity signals on T2FLAIR, and enhancement along the cortex (37.2% [16/43]). Interfocal heterogeneity was observed in 45 of 63 cases (71.4%). The imaging features of the lesions were classified into 5 types: metastasis (69.8%), granulomatosis (4.8%), abscess (12.7%), encephalitis (6.3%) and metabolic encephalopathy (6.3%). Conclusion The specific MRI presentations of multiple gliomas are cortical involvement and interfocal heterogeneity. The 5 MRI features of multiple gliomas may help improve the differential diagnosis of the lesions.

Severity grading of grade B pancreatic fistula after pancreaticoduodenectomy: A single-center study / 中国实用外科杂志

OBJECTIVE: To discuss whether grade B pancreatic fistula after pancreaticoduodenectomy(PD)can be graded according to the severity and to provide reference for accurate evaluation and treatment.METHODS: The clinical data of 343 patients underwent PD surgery in the First Affiliated Hospital of Harbin Medical University from December2012 to June 2016 were retrospectively collected,among which 72 cases followed grade B pancreatic fistula. Grade B pancreatic fistula after operation was divided into severe groups of which imaging-assisted interventional therapy was needed and mild group. The total medical cost,length of hospital stay,drainage time,ICU transfer,introperitoneal effusion,introabdominal infection,abdominal hemorrhage,biliary fistula,delayed gastric emptying,number of types and incidence of complications except pancreatic fistula,incidence of pancreatic fistula as the most serious complications,postoperative morbidity index(PMI),fistula average complication burden(ACB)were statistically analyzed between two groups.RESULTS: Univariate analysis revealed that there were significant differences between two groups in the total medical cost(84,000 yuan vs. 132,000 yuan),length of hospital stay(29.0 days vs. 42.0 days),drainage time(20.5 d vs.53.0 d),introperitonal effusion rate(41.1% vs. 87.5%),introabdominal infection rate(10.7% vs. 43.8%),abdominal hemorrhage rate(7.1% vs. 56.3%),the number of other types of complications except pancreatic fistula(1 vs. 4),pancreatic fistula as the most serious complications(53.6% vs. 87.5%),PMI(0.22±0.08 vs. 0.37±0.00),ACB(0.19±0.08 vs. 0.37±0.00),and the P-values were less than 0.05 respectively.CONCLUSION: The severity of grade B pancreatic fistula of ISGPS update classification is heterogeneous,which can be divided into mild and severe groups. It provides a reference for precise and individualized treatment for grade B pancreatic fistula.

Preparation of fusion protein of PD-L1 single-chain antibody and verification of its antitumor activity / 中国免疫学杂志

Objective: Using yeast surface presentation technology, secreted anti-PD-L1 single-chain antibody fragment ( sc Fv), then purify the sc Fv that specifically binds PD-L1 antigen. The sc Fv antibody gene sequence was synthesized based on the single chain antibody gene sequence. We express this sc Fv-mFc protein by using p Fuse eukaryotic expression vector to study its affinity and in vitro and in vivo inhibition of lung adenocarcinoma cells ( A549). Methods: Recombinant plasmid p Fuse-scFv was constructed by gene engineering. The recombinant plasmid p Fuse-scFv was transfected into 293 F ( human embryonic kidney cells) and cultured in serum-free Pro293 a-CDM for 72 hours, then the fusion protein was collected, and use the Rapid Protein Liquid Phase Separation and Purification System to purify the sc Fv-mFc fusion protein. Then the fusion protein and the tumor cells were detected by immunohistochemistry; the affinity of fusion protein and tumor cells was analyzed by flow cytometry; ADCC was used to determine the proliferation of tumor cells in vitro. The nude mice inoculated with lung adenocarcinoma cells, and use the fusion protein to verify its anti-tumor effect in vivo. Results: sc Fv-mFc fusion protein was secreted into serum-free culture medium by recombinant plasmid transfection into the 293 F cells; immunohistochemistry and flow cytometry showed that the fusion protein was highly expressed with the surface of PD-L1 protein;ADCC showed that the fusion protein inhibited the proliferation of tumor cells in vitro; the results of tumor-bearing mice showed that the fusion protein inhibited the growth of the tumor. At the dose of 5 mg/kg, The tumor volume growth rate decreased from 14. 90％ to3. 72％, the two independent samples t test P＜0. 05, the difference was statistically significant. Conclusion: The fusion protein containing single chain antibody was successfully prepared, which had good binding ability to A549 cells and inhibited the proliferation of tumor cells in vitro and in vivo, and provided the laboratory basis for the development of targeted anti-tumor drugs.

High-risk factors for early failure of high-flow nasal cannula oxygen therapy in children / 中国当代儿科杂志

OBJECTIVE@#To determine the high-risk factors for early failure of high-flow nasal cannula (HFNC) oxygen therapy in children with acute respiratory insufficiency (ARI).@*METHODS@#The clinical data of 123 children with ARI were reviewed who received HFNC oxygen therapy in the pediatric intensive care unit from January to June, 2018. The children who did not require an upgrade of respiratory support during hospitalization and were successfully weaned from HFNC were classified as HFNC success group (69 cases). Of the remaining children (54 cases) who required an upgrade of their respiratory support during hospitalization, those that needed to upgrade their respiratory support within 48 hours of receiving HFNC were classified as early HFNC failure group (46 cases). Risk factors for early failure of HFNC were determined using multivariate logistic regression analysis.@*RESULTS@#The incidence rates of shock, sepsis, intracranial hypertension syndrome, and multiple organ dysfunction syndrome were significantly higher in the early HFNC failure group than in the HFNC success group (P4.5 and PaCO/PaO ratio >0.64 were independent risk factors for early HFNC failure (OR=5.535 and 9.089 respectively; P4.5 or PaCO/PaO ratio >0.64 have relatively high risk of early HFNC failure.

Efficacy and safety of antifibrinolytic agents in spinal surgery: a network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Significant blood loss is still one of the most frequent complications in spinal surgery, which often necessitates blood transfusion. Massive perioperative blood loss and blood transfusion can create additional risks. Aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The aim of this study was to evaluate the efficacy and safety of aprotinin, EACA, and low/high doses of TXA in spinal surgery, and assess the use of which agent is the most optimal intervention using the network meta-analysis (NMA) method.@*METHODS@#Five electronic databases were searched, including PubMed, Cochrane Library, ScienceDirect, Embase, and Web of Science, from the inception to March 1, 2018. Trials that were randomized and compared results between TXA, EACA, and placebo were identified. The NMA was conducted with software R 3.3.2 and STATA 14.0.@*RESULTS@#Thirty randomized controlled trial (RCT) studies were analyzed. Aprotinin (standardized mean difference [SMD]=-0.65, 95% credibility intervals [CrI;-1.25, -0.06]), low-dose TXA (SMD = -0.58, 95% CrI [-0.92, -0.25]), and high-dose TXA (SMD = -0.70, 95% CrI [-1.04, -0.36]) were more effective than the respective placebos in reducing intraoperative blood loss. Low-dose TXA (SMD = -1.90, 95% CrI [-3.32, -0.48]) and high-dose TXA (SMD = -2.31, 95% CrI [-3.75, -0.87]) had less postoperative blood loss. Low-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) and high-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) significantly reduced total blood loss. However, only high-dose TXA (SMD = -2.07, 95% CrI [-3.26, -0.87]) was more effective in reducing the amount of transfusion, and was significantly superior to low-dose TXA in this regard (SMD = -1.67, 95% CrI [-3.20, -0.13]). Furthermore, aprotinin (odds ratio [OR] = 0.16, 95% CrI [0.05, 0.54]), EACA (OR = 0.46, 95% CrI [0.22, 0.97]) and high dose of TXA (OR = 0.34, 95% CrI [0.19, 0.58]) had a significant reduction in transfusion rates. Antifibrinolytics did not show a significantly increased risk of postoperative thrombosis. Results of ranking probabilities indicated that high-dose TXA had the greatest efficacy and a relatively high safety level.@*CONCLUSIONS@#The antifibrinolytic agents are able to reduce perioperative blood loss and transfusion requirement during spine surgery. And the high-dose TXA administration might be used as the optimal treatment to reduce blood loss and transfusion.

Progressive pseudorheumatoid dysplasia misdiagnosed as ankylosing spondylitis: a case report / 北京大学学报(医学版)

In this study, we reported a case of progressive pseudorheumatoid dysplasia in Peking University Third Hospital. A 56-year-old male patient presented with hip joint pain for more than 40 years and multiple joints pain with limitation of movements of these joints for 28 years. This patient suffered from joint pain and impaired range of motion of the hip, knee, elbow and shoulder gradually, associated with difficulty in walking and inability to take care of himself. He was diagnosed with "femoral head necrosis" or "ankylosing spondylitis" in local hospitals, but the treatment of nonsteroidal antiinflammatory drugs (NSAIDs) and sulfasalazine was not effective. Up to the age of 14, the patient displayed normal physical development, with the highest height was about 158 cm, according to the patient recall. However, his height was 153 cm at present. There was no history of similar illness in any family member. Physical examinations descried limitation of movement of almost all joints. Enlargement and flexion deformity of the proximal interphalangeal (PIP) joints of the hands resulted in the claw hand appearance. Limited abduction and internal and external rotation of the shoulder and hip could be find. He had normal laboratory findings for blood routine test, biochemical indexes and acute phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Furthermore, HLA-B27 and autoimmune antibodies such as rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody and antinuclear antibody (ANA) were all negative. X-ray of the hip showed loss of the joint space and irregularities of the femoral head, both femoral head were flattened, it could be see hyperplasia, osteophytes, bilateral femoral neck thicken, neck dry angle turned smaller. The radiological findings of the spinal vertebra indicated kyphosis deformity, narrowing of the intervertebral discs, vertebral syndesmophytes and flattening of the vertebra. However, there was no clues of bone marrow edema in the lumbar MRI. At last, genetic testing for the Wnt1-inducible signaling pathway protein 3 (WISP3) gene was done and indicated compound heterozygous mutations: 756C>G and c.866dupA. These two mutations were derived from the patient's mother and father (the patient's parents each had a heterozygous mutation). Two exons of the WISP3 gene had nucleotide changes leading to amino acid mutations. According to the patient's history, symptoms, physical examinations, radiological findings and genetic testing, the final definitive diagnosis was progressive pseudorheumatic dysplasia.

Preparation of doxorubicin modified silver nanoparticle and its anti-tumor activity in vitro / 天津医药

Objective To design and synthesize a novel type of combined anti-tumor drug-doxorubicin modified silver nanoparticles(DOX-Ag NPs)with pH response,characterize its physical and chemical properties,and investigate its drug responsive release and anti-tumor activity in vitro.Methods DOX-Ag NPs were prepared by coupling silver nanoparticles (Ag NPs) with doxorubicin (DOX) via a LA-NHNH2linker. The structure of LA-NHN=DOX was confirmed by nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS).The particle size and micromorphology of the nanoparticles were detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The optical properties of the nanoparticles were characterized by UV-vis absorption spectroscopy and fluorescence spectroscopy.The DOX release kinetics of DOX-Ag NPs under different pH conditions were examined by dialysis method combined with fluorescence spectroscopy. The in vitro anti-tumor effects of DOX-Ag NPs were evaluated by MTT assay. Results DOX-Ag NPs were spherical nanoparticles with a particle size of (40.4 ± 3.8) nm. DOX-Ag NPs could rapidly release DOX under weak acid condition.DOX-Ag NPs significantly inhibited the proliferation and cell viability of HepG2 cells in concentration dependent manner.When DOX concentration was 0.5-20 mg/L(Ag concentration was 0.45-18 mg/L), the cell survival rate was significantly lower in DOX-Ag NPs group than that of DOX group and Ag NPs group(P<0.05). Conclusion DOX-Ag NPs are a combined anti-tumor nano-drug with pH-responsive ability, which can release DOX rapidly in tumor tissues and play an anti-tumor effect through synergistic treatment with Ag NPs in vitro.

Role of c-Jun N-terminal kinase-mediated FOXO3a nuclear translocation in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the mechanisms of neuroprotective effects of c-Jun N-terminal kinase (JNK)/FOXO3a transcription factor signaling pathway inhibition on hypoxic-ischemic neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage (HIBD).</p><p><b>METHODS</b>Sixty-four 7-day-old Sprague-Dawley rats were divided into four groups: hypoxia-ischemia (HI), sham-operated, JNK specific inhibitor AS601245-treated, and DMSO vehicle. Rats' cerebral cortexes were collected at 24 hours after HI. Western blot was used to detect the protein expression of JNK, p-JNK, FOXO3a, nuclear and cytoplasmic FOXO3a, Bim, and CC3. TUNEL staining was used to detect the apoptotic cells.</p><p><b>RESULTS</b>Compared with the sham-operated group, p-JNK protein increased (P<0.01), nuclear protein of FOXO3a increased (P<0.01), cytoplasmic protein decreased (P<0.01), and pro-apoptotic proteins Bim and CC3 increased 24 hours after HI (P<0.01). Compared with the HI and DMSO vehicle groups, p-JNK protein was reduced (P<0.01), nuclear protein of FOXO3a was also reduced (P<0.01), cytoplasmic protein increased (P<0.01), and Bim and CC3 proteins decreased (P<0.01) in the AS601245-treated group 24 hours after HI. TUNEL positive cells were reduced in the AS601245-treated rats compared with the HI and DMSO vehicle groups 24 hours after HI (P<0.01).</p><p><b>CONCLUSIONS</b>JNK activity increases in the neonatal rat brain with HI damage. JNK activity inhibition can inhibit FOXO3a translocation from cytoplasm to nucleus and downregulate the levels of pro-apoptotic proteins Bim and CC3, leading to the reduction of neuronal apoptosis.</p>

Clinical effects of different therapeutic regimens for Helicobacter pylori infection in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical effects of sequential therapy, triple therapy, sequential therapy combined with Lactobacillus, and triple therapy combined with Lactobacillus in the eradication of Helicobacter pylori (H.pylori) infection in children.</p><p><b>METHODS</b>A total of 416 children with H.pylori infection were randomly assigned to sequential group (102 children), triple group (100 children), sequential-Lactobacillus group (109 children), and triple-Lactobacillus group (105 children). The clinical outcome, H.pylori eradication rate, cost-effect ratio, and incidence of adverse events were compared between the four groups.</p><p><b>RESULTS</b>The sequential-Lactobacillus and triple-Lactobacillus groups had significantly better clinical outcomes than the sequential group and the triple group (P<0.05). The sequential-Lactobacillus group had the highest marked response rate, followed by the triple-Lactobacillus group. The triple group had the lowest marked response rate. The sequential-Lactobacillus group also had the highest H.pylori eradication rate, followed by the triple-Lactobacillus group. The triple group had the lowest H.pylori eradication rate (P<0.05). The sequential group had the lowest cost-effect ratio, followed by the sequential-Lactobacillus group. The triple group had the highest cost-effect ratio (P<0.01). The sequential-Lactobacillus group had the lowest incidence rate of adverse events, followed by the triple-Lactobacillus group. The triple group had the highest incidence rate.</p><p><b>CONCLUSIONS</b>Sequential therapy combined with Lactobacillus seems to be the best regimen for the eradication of H.pylori infection in children.</p>

Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS. RESULTS: A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes. CONCLUSIONS: Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS

Effect of NF-κB on proliferation of rat pulmonary artery smooth muscle cells inhibited by simvastatin / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the effects of NF-κB on proliferation of rat pulmonary artery smooth muscle cells (PASMC) inhibited by simvastatin.</p><p><b>METHODS</b>PASMC isolated from rats and cultured in vitro were randomly divided into four groups (n=6 each): control, platelet-derived growth factor (PDGF) treatment, PDGF+simvastatin treatment, and PDGF+simvastatin+parthenolide (NF-κB inhibitor) treatment. MTT colorimetric assay and flow cytometry were performed to detect cell proliferation and cell cycle distribution. Immunohistochemistry was performed to detect the expression of NF-κB protein. Real-Time PCR was performed to detect NF-κB mRNA expression.</p><p><b>RESULTS</b>Compared with the control group, MTT values of PASMC at all time points, cell proportion at the S phase and G2+M phase, NF-κB protein and mRNA expression increased significantly in the PDGF group (P<0.05). With the intervention of simvastatin, the levels of above indexes decreased compared with the PDGF group (P<0.05). With the intervention of simvastatin and parthenolide, the levels of above indexes decreased more obviously, but were not significantly different from those in the simvastatin intervention group.</p><p><b>CONCLUSIONS</b>Simvastatin can inhibit proliferation of PASMC and cell cycle process. NF-κB may play an important role in the inhibitory effect of simvastatin on the proliferation of PASMC.</p>

Effect of nuclear transcription factor kappaB pathway on proliferation in rat pulmonary artery smooth muscle cells induced by platelet-derived growth factor / 中华实用儿科临床杂志

Objective To explore the effect of nuclear transcription factor kappaB(NF-κB) pathway on proliferation of rat pulmonary artery smooth muscle cells (PASMC) induced by platelet-derived growth factor (PDGF).Methods PASMC isolated from rats and cultured in vitro were divided into 3 groups according to the randomization principle:control group(cultured by M199),PDGF treatment group(cultured by M199 and stimulated by PDGF),PDGF + parthenolide treatment group (cultured by M199 and stimulated by PDGF,and intervented by the NF-κB inhibitors parthenolide).MTT colorimetric assay and flow cytometry were performed to detect cell proliferation and cell cycle distribution.Immunohistochemistry was performed to detect the expressions of NF-κB and COX-2 protein.Fluorescence quantitative RT-PCR was performed to detect NF-κB and COX-2 mRNA expressions.One-way ANOVA was used for statistical analysis,multiple comparisons were analyzed by LSD.Results Compared with the control group,MTT value of PASMC was increased significantly when induced by PDGF at each time points(all P ＜ 0.05).MTT value decreased dramatically after the intervention of NF-κB inhibitor parthenolide(P ＜0.05).Data from flow cytometry detection showed that cell proportion of S phase and G2 + M phase increased significantly in PDGF treatment group,which had statistical difference compared with control group (all P ＜ 0.05).Compared with PDGF induced group,after the intervention of parthenolide,cell proportion of S phase and G2 + M phase ratio decreased dramatically (P ＜ 0.05).The expressions of NF-κB and COX-2 protein and mRNA were promoted in the PDGF induced group compared with the control group (all P ＜ 0.05).Compared with PDGF induced group,after the intervention of parthenolide,the expressions of NF-κB and COX-2 protein and mRNA decreased dramatically(all P ＜ 0.05).Conclusions PDGF can induce proliferation of PASMC,promote cell cycle process and enhance the expressions of NF-κB and COX-2 protein and mRNA.NF-κB pathway involves in the proliferation of PASMC induced by PDGF.

Study of enterovirus 71-induced autophagy in human malignant glioma cell line U251 / 中华实用儿科临床杂志

Objective To show evidences that autophagy is induced in human malignant glioma cell line U251 by enterovirus(EV71) and its effect on the expression of microtubule-associated protein 1 lightchain 3 (LC3) in vitro.Methods U251 cells were cultured in RPMI 1640 for 24 hours,then randomly divided into experimental group and control group.In experimental group,EV71 were added in cell culture holes at multiplicity of infection (MOI) equal to 1,and cultured continuously.After 12 hours post infection of U251 cells with EV71,autophagic vacuoles of U251 cells were marked by monodansylcadaverine staining and observed under fluorescence microscope.After 24 hours post infection,expression and intracellular distribution of LC3 protein in U251 cells were observed under fluorescence microscope by immunofluorescence.Expressions of LC3-I and LC3-Ⅱ protein were measured by Western blot and analysis of LC3-Ⅱ protein expression was performed with semi-quantitative calculation at 2,4,8,12,24 and 48 hours post infection of U251 cells with EV71,respectively.Results Autophagic vacuoles stained by MDC in U251 cells appeared as distinct dot-like structures distributed under fluorescence microscope.The number of autophagic vacuoles were increased significantly at 12 hours post infection of U251 cells with EV71 when compared with control group.The morphological features of these cells became significantly shrunken,smaller and irregular shape at 24 hours post infection of U251 cells,and the expressions of LC3 protein were significantly higher in experimental group than those in control group.Under a fluorescence microscope,LC3 protein distributed within the cytoplasm or localizing in the perinuclear regions.At 4 hours post infection of U251 cells with EV71,the expression of LC3-Ⅱ protein started to increase,and was significantly higher than that in control group (P ＜ 0.01).Conclusion These results indicate that EV71 can effectively induce autophagy of human malignant glioma cell line U251,and play its oncolytic effect.