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Objective:To analyze the risk factors for premature infants with hemodynamically significant patent ductus arteriosus (hs-PDA) requiring surgical treatment, and to explore the indications for surgical treatment in premature infants with hs-PDA.Methods:A nested case-control study was conducted.The data of premature infants with gestational age<30 weeks who were diagnosed with hs-PDA in the Neonatal Intensive Care Unit of Peking Union Medical College Hospital from January 2007 to May 2020 were analyzed retrospectively.The hs-PDA patients treated surgically were included in the operation group.The hs-PDA patients of the same gestational age and gender who were not treated surgically were taken as the control group.The ratio of the case number between the operation and control groups was 1∶2.The clinical data during pregnancy, at birth and after birth of premature infants were compared between the 2 groups.The measurement data were tested by the independent sample t test or Mann- Whitney U test.The classification and enumeration data were compared by the Fisher′ s exact probability method.The risk factors for premature infants with hs-PDA requiring surgical treatment were analyzed by the conditional Logistic regression method. Results:A total of 182 premature infants with hs-PDA were enrolled in the study, including 10 in the operation group and 20 in the control group.The patients underwent PDA ligation 30.5(22.7, 37.0) d after birth, and the median preo-perative invasive ventilation duration was 9.7(17.5, 27.2) d. Compared with the control group(20 cases), the preterm infants in the operation group had a lower birth weight [(891.5±118.0) g vs.(1 054.4±230.2) g, t=2.091], a wider arterial duct diameter [3.2(2.8, 4.0) mm vs.2.0(2.0, 3.0) mm, Z=-3.300], and longer invasive ventilation duration [25.0(18.7, 38.2) d vs.3.0(1.0, 7.5) d, Z=-3.688]. Besides, the operation group applied the pulmonary surfactant for more times [2(1, 3) times vs.1(1, 2) times, Z=-2.440], and inhaled a higher concentration of oxygen on the 14 th day after birth [29(25, 36)% vs.21(21, 29)%, Z=-2.358] than the control group.Moreover, compared with the control group, the operation group took longer to achieve adequate enteral feeding [48.2(51.5, 63.5) d vs.42.5(23.5, 48.0) d, Z=2.789], and gained a higher maximum vasoactive inotropic score (VIS) [3.0(0, 3.5) points vs.0(0, 0) points, Z=-2.630]. The difference in all the above-mentioned indicators between the 2 groups was statistically significant (all P<0.05). Univariate Logistic regression analysis showed that the arterial duct diameter, application times of the pulmonary surfactant, the maximum VIS score, and the time taken to achieve sufficient enteral feeding were all related to the need for surgical treatment of hs-PDA in the operation group (all P<0.05). Multivariate Logistic regression analysis revealed that the invasive ventilation duration ( OR=0.747, 95% CI: 0.560-0.998, P=0.048) was an independent risk factor for hs-PDA premature infants requiring surgical treatment. Conclusions:The factors related to the need for surgical treatment in preterm infants with hs-PDA include a wide arterial duct diameter, multiple applications of the pulmonary surfactant, a high concentration of inhaled oxygen on the 14 th day, and the long time to achieve sufficient enteral feeding.The independent risk factor for the surgical treatment in hs-PDA children is the long invasive ventilation duration.
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Objective:To explore the risk factors of bortezomib-related peripheral neuropathy (BIPN) and the clinical and electrophysiological characteristics of patients in treatment of multiple myeloma (MM).Methods:The clinical data of 71 newly diagnosed MM patients treated with BD (bortezomib + dexamethasone) regimen in Yancheng First People's Hospital from March 2016 to December 2019 were retrospectively analyzed. The bone marrow morphology, immunology, cytogenetics, molecular biology (MICM), routine electrophysiological examination before and after treatment were performed. All patients were divided into the peripheral neuropathy (PN) group and the non-PN group according to the presence or not of BIPN, and the clinicopathological differences of both groups were also compared; a binary logistic regression model was used to analyze the factors affecting the occurrence of PN. The electrophysiological characteristics were summarized and fluorescence in situ hybridization (FISH) was used to detect karyotype of BIPN patients.Results:Among 71 MM patients, there were 40 cases (56.3%) of PN and 31 cases (43.7%) of non-PN. The proportion of patients at international staging system (ISS) staging Ⅲ, and the levels of IgA, IgG, IgM, serum creatinine, β 2-microglobulin (β 2-MG) in the PN group were higher than those in the non-PN group, and hemoglobin (Hb) level in the PN group was lower than that in the non-PN group, and the differences were statistically significant (both P < 0.05). Binary logistic regression analysis showed that increased IgA ( OR = 1.151, 95% CI 1.012-1.309, P = 0.033), increased IgG ( OR = 1.055, 95% CI 1.000~1.112, P = 0.049), increased IgM ( OR = 1.010, 95% CI 1.001-1.018, P = 0.022), increased serum creatinine ( OR = 1.037, 95% CI 1.011~1.065, P = 0.005), increased β 2-MG ( OR = 1.564, 95% CI 1.039-2.354, P = 0.032) were risk factors for BIPN. Among 40 patients with BIPN, 33 cases (82.5%) of sensory nerve conduction velocity (SCV) were abnormal, 23 cases (57.5%) of motor nerve conduction velocity (MCV) were abnormal; 31 cases (77.5%) showed demyelination damage, 9 cases (22.5%) had axonal damage. Among 40 patients with BIPN, 24 cases underwent FISH detection, including 19 cases (79.2%) with chromosomal mutations, of which 12 cases (50.0%) were mixed subtype abnormal. Conclusions:MM patients with high levels of β 2-MG, IgA, IgG, IgM and serum creatinine are more prone to PN when treated with bortezomib. The electrophysiology of patients with BIPN is mainly characterized by demyelination of sensory nerves.
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N7-methylguanosine （m7G） is one of the most popular RNA modifications at present and has attracted wide attention from researchers in China and globally. By influencing the metabolism of various RNA molecules （including messenger RNA， ribosomal RNA， microRNA， and transfer RNA）， m7G modification actively participates in many biological processes such as cell proliferation， differentiation， and apoptosis. More and more evidence has shown that m7G plays a key role in the development of cancer， and abnormal m7G levels are closely associated with the development and progression of cancer by regulating the expression of multiple oncogenes and tumor suppressor genes. Hepatocellular carcinoma is the most common gastrointestinal tumor in China， and current treatment methods tend to have an unsatisfactory therapeutic effect. At present， the potential molecular mechanism of m7G modification in hepatocellular carcinoma remains unclear. This article reviews the potential mechanism of action of m7G modification in hepatocellular carcinoma and the m7G-related diagnosis and treatment strategies.
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Objective: To investigate the analgesic mechanism of Tuina (Chinese therapeutic massage) by observing the effect of the N-methyl-D-aspartate receptor subunit 2B (NR2B)/postsynaptic density-95 (PSD-95) pathway on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation. Methods: Fifty Sprague-Dawley rats were randomly divided into a blank group, a model group, a Tuina group, a blocker agent group, and a blocker agent + Tuina group. The sciatic nerve chronic constriction injury (CCI) model was prepared by the sciatic nerve ligation method. From the 4th day after modeling, rats in the Tuina group and the blocker agent + Tuina group were subject to daily Tuina intervention, and those in the blocker agent group and the blocker agent + Tuina group were daily intrathecally injected with NR2B blocker agent (MK-801). The spontaneous pain score was used to observe the pain behavior of all rats. The expression levels of NR2B and downstream PSD-95 were measured by immunohistochemistry, and the dendritic structure changes were observed by Golgi staining for rat spinal cord dorsal horn after 14 d of continuous intervention. Results: Compared with the blank group, the degree of rat spontaneous pain after CCI was elevated in both the model and the Tuina groups (P<0.01) and was reduced in the Tuina group after the Tuina intervention compared with the model group (P<0.05). Compared with the model group, the rat spontaneous pain level after blocking NR2B was reduced in both the blocker agent group and the blocker agent + Tuina group (P<0.05). The NR2B and PSD-95 protein levels were significantly higher in the model group compared with the blank group (P<0.01); the total number of dendritic branches was increased (P<0.01), and the total dendritic length became longer (P<0.01) in the spinal cord dorsal horn. The rat NR2B and PSD-95 protein levels were significantly decreased in the Tuina group compared with the model group (P<0.01); the total dendritic branch number was reduced (P<0.01) and the total length was shortened (P<0.01) in the spinal cord dorsal horn. After blocking NR2B, the expression levels of NR2B and downstream PSD-95 protein were significantly lower in both the blocker agent group and the blocker agent + Tuina group compared to the model group (P<0.01). The total branch number was significantly reduced (P<0.01), and the total length was significantly shortened (P<0.01) of the dendrites in the spinal cord dorsal horn. Conclusion: Tuina may exert an analgesic effect by remodeling the dendritic structure in the spinal cord dorsal horn in rats with lumbar disc herniation, and its mechanism may be related to the inhibition of NR2B/PSD-95 signaling pathway.
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Objective:To preliminary observe the clinical efficacy of vedolizumab (VDZ) in the treatment of active Crohn′s disease (CD).Methods:From March 2021 to October 2022, a total of 22 patients with active CD who received VDZ treatment at Zhongda Hospital, Southeast University were retrospectively enrolled. The general clinical data, laboratory indicators, imaging finding and endoscopic images of the patients were collected. The Crohn′s disease activity index (CDAI), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), clinical remission rate were evaluated at week 0, 2, 6 and 14 of VDZ administration. Meanwhile, the response rate under endoscopy and remission rate under endoscopy were evaluated after 14 weeks of VDZ administration. The related factors affecting the efficacy of VDZ were further analyzed. Kruskal-Wallis H test and Mann-Whithey U test were used for statistical analysis. The multiple logistic regression analysis was used to find the related factors affecting the clinical remission after VDZ treatment. Results:The CDAI at week 0, 2, 6 and 14 after treatment were 181.01 (160.11, 231.56), 148.05 (134.88, 200.52), 127.46 (91.44, 163.62), and 82.35 (63.50, 121.84), respectively, and the differences were statistically significant ( H=34.23, P<0.001); there were statistically significant differences between week 0 and week 2, 6, 14 after treatment ( U=130.00, 80.00, 33.00; P=0.017, <0.001, and<0.001). The hs-CRP levels were 5.72 mg/L (3.59 mg/L, 11.10 mg/L), 2.86 mg/L (0.86 mg/L, 5.27 mg/L), 1.55 mg/L (0.86 mg/L, 9.89 mg/L) and 2.86 mg/L (0.86 mg/L, 3.12 mg/L), respectively, and the differences were statistically significant ( H=9.69, P=0.021); there were statistically significant differences between week 0 and week 2, 6, 14 after treatment ( U=102.00, 109.00, 98.00; P=0.026, 0.045, and 0.011) .The level of ESR after 14 weeks of VDZ treatment was 8.00 mm/1 h (4.00 mm/1 h, 17.00 mm/1 h), which significantly decreased compared with that before treatment (17.00 mm/1 h(12.25 mm/1 h, 21.75 mm/1 h)), and the difference was statistically significant ( U=132.50, P=0.020). The clinical remission rates at week 2, 6 and 14 after VDZ treatment were 54.5% (12/22), 68.2% (15/22) and 86.4% (21/22), respectively, and the clinical response rates were 18.2% (4/22), 54.5% (12/22) and 95.5% (21/22), respectively. After 14 weeks of VDZ treatment, among 17 patients who underwent endoscopic re-examination, 9 patients achieved response under endoscopy and 3 patients achieved remission under endoscopy. Stenotic type and penetrating type of CD, previous use of glucocorticoids or immunosuppressants were risk factors of no clinical remission after VDZ treatment ( β=-4.586, -5.005 and -3.371; OR=0.010, 0.007 and 0.034; P=0.010, 0.025 and 0.045). While VDZ treatment for 14 weeks was a protective factor ( β=2.475, OR=11.885, P=0.011). Conclusions:VDZ can effectively relieve disease activity in patients with active CD. The disease behavior of CD, previous medication treatment of patients, and the duration of VDZ treatment may be related to the efficacy of VDZ.
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We report a family of glucocorticoid-remediable aldosteronism (GRA). A 20-year-old man presented with early-onset hypertension accompanied by hypokalemia was admitted to our hospital. Clinical data and family history were collected. Following genetic analyses with PCR and Sanger sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located in 264-380 nucletide, which was considered as GRA. There were 4 cases of GRA in the family, the average age of onset was 28 years, and all had different degrees of hypertension. Among them, the proband′s uncle suffered from moyamoya disease and died 6 months later due to sudden cerebral hemorrhage. In order to improve the understanding of this rare disease, the pathogenesis, biochemical profiles, diagnosis and treatment of GRA were summarized and analyzed.
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Objective:To observe any effect of supplementing continuous static stretching (CSS) with extracorporeal shock wave therapy (ESWT) in treating triceps surae spasm after a stroke.Methods:Sixty-four stroke survivors with triceps surae spasm were randomly divided into a conventional rehabilitation group, a shock wave group and a combined treatment group. In addition to conventional rehabilitation, the shock wave group received extracorporeal shock wave therapy twice a week and the combined treatment group received the shock waves during continuous static stretching. After 6 weeks of treatment all of the subjects were assessed using the Modified Ashworth Scale (MAS), the Fugl-Meyer Assessment (FMA) and Brunnstrom classification of their functional recovery stage.Results:Before treatment there was no significant difference among the three groups. After the 6 weeks of treatment the average triceps surae tension in all three groups had eased significantly. At that point the average MAS and FMA scores of the shock wave group and the combined treatment group were significantly better than those of the conventional group. The combined treatment group then showed significantly better therapeutic effect than the shock wave group.Conclusions:Applying extracorporeal shock waves during continuous static stretching can significantly improve the stretching′s ability to reduce spasticity and improve motor functioning, at least of the triceps surae. Combining shock waves with modern traction methods is recommended for clinical application.
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We present a case of a postmenopausal women with hyperandrogenic symptoms and virilization signs , such as hirsutism, alopecia, acne and clitoromegaly, which was pathologically confirmed to be an ovarian steroid cell tumor, not otherwise specified(NOS). The levels of testosterone, dehydroepiandrosterone sulfate and estradiol in serum were increased, while the levels of luteinizing hormone and follicle stimulating hormone were decreased. Computed tomography(CT) scan and magnetic resonance imaging(MRI) identified a solid, left ovarian tumor and detected an additional tumor of hypodensity in the left adrenal gland. ACTH stimulation test, hCG stimulation test, adrenal and ovarian vein sampling indicated that excessive androgens were derived from the ovary. After the injection of gonadotropin hormone analogues(GnRHa), testosterone levels dropped to the normal range. Laparoscopic bilateral adnexectomy was performed, and pathology indicated NOS. The purpose of this report is to improve the understanding of NOS with hyperandrogenic presentation.
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Objective:To analyze clinical characteristics of 17α-hydroxylase deficiency, and to facilitate the understanding and management of the disease.Methods:A retrospective analysis of the clinical characteristics and biochemical results of 5 cases with 17α-hydroxylase deficiency diagnosed and treated from 2018 to 2020.Results:All 5 patients were female as social gender, and reached adulthood upon first clinic visit to our department and got diagnosed. All 5 cases had hypertension, hypokalemia, bilateral adrenal hyperplasia or adenoma, osteoporosis, and typical hormone changes related to steroid synthesis.Conclusion:Steroid hormone tests with liquid chromatography tandem mass spectrometry(LC-MS/MS) enable early diagnosis of 17α-hydroxylase deficiency, assessment of the type and degree of enzyme deficiency, and choice of treatment. For such patients, it is necessary to give appropriate anti-osteoporosis therapy.
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Objective:To assess the effectiveness and safety of adalimumab in Crohn′s disease (CD) patients.Methods:We retrospectively reviewed the charts of 41 CD patients who received adalimumab in Zhongda Hospital Southeast University from January 2020 to August 2021. General clinical data, laboratory results, endoscopy and radiologic findings were collected, meanwhile, disease activity and safety events were evaluated at baseline and at 12, 24 and 48 weeks of administration. Adalimumab was given subcutaneously once every 2 weeks in doses of 160 mg for the first time, 80 mg for the second time, and 40 mg for each subsequent time.Results:The clinical remission rates at 12, 24, and 48 weeks of treatment were 43.9% (18/41), 60.6% (20/33), 60.9% (14/23), and the clinical response rates were 75.6% (31/41), 69.7% (23/33), and 56.5%( 13/23), respectively. The proportion of endoscopic remission at 12, 24 and 48 weeks were 4/14, 2/6, 1/4 in patients undergoing endoscopy, and 1/14 patients achieved mucosal healing at 24 weeks. Primary nonresponse rate (PNR) was 17.1% (7/41), loss of response (LOR) rate was 14.6% (6/41). The incidence of adverse reactions was 9.8%(4/41).Conclusion:Adalimumab can effectively relieve the clinical symptoms and intestinal disease activities of Crohn′s disease, and deserves to be popularized clinically. Patients with disease course <2 years, first-line biologics, low baseline HBI score, and longer duration of medication may have better results.
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Salvianolic acid injection play an important role in cardiovascular diseases by promoting angiogenesis, improving hemorheology, anti-platelet aggregation, anti-inflammatory, anti-oxidative stress, improving endothelial cell function, and inhibiting atherosclerosis. However, mechanismstudies focusing on molecular level are quite few. Although there are many adverse reactions and many factors causing adverse reactions, the incidence rate of adverse reactions is low with safety.
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There is accumulating evidence to suggest that immunoglobulin E(IgE)plays a significant role in autoimmunity and inflammation in recent years, and the most concerned is the role of IgE in systemic lupus erythematosus(SLE). Multiple studies demonstrated a pathogenic role of autoreactive IgE in SLE, including direct damage on tissue-containing autoantigens, activation and migration of basophils to lymph nodes, and induction of type Ⅰ interferon responses from plasmacytoid dendritic cells(pDCs). It is now recognized that autoimmune diseases such as bullous pemphigoid(BP), chronic spontaneous urticaria(CSU)and hyperthyroid Graves′ disease are partly mediated by IgE.The situations in other conditions with increased IgE levels, such as autoimmune uveitis, multiple sclerosis, as far less clear and some studies have pointed towards IgE autoantibodies as the main culprit.Now anti-human IgE monoclonal antibody is approved for use in asthma and CSU.And autoreactive IgE and FcεRI-bearing effector cells are as new promising therapeutic targets in autoimmune diseases.In this review, the mechanism and clinical effects of IgE mediated inflammation and autoimmune response will be discussed.
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Objective:To establish an automatic colorimetric method for determination of iodine in drinking water by enzyme-labeled instrument (hereinafter referred to as this method).Methods:The water iodine was measured in the range of 0 - 10 μg/L and 0 - 100 μg/L, experiments were carried out on linear relationship, detection limit, precision and accuracy of this method. And the results were compared with the National Reference Laboratory for Iodine Deficiency Disorders recommended arsenic cerium catalytic spectrophotometry method.Results:In the range of 0 - 10 μg/L and 0 - 100 μg/L, all│ r│ > 0.999 0, the detection limits were 0.6 and 1.1 μg/L (samples were 200 and 100 μl), respectively; the relative standard deviation ( RSD) of water samples of low, medium and high iodine mass concentrations were < 3%, the recovery rates ranged from 92.5% to 108.3% and 93.2% to 108.9%, with a total average recovery of 100.0% and 100.3%, respectively. This method and arsenic cerium catalytic spectrophotometry method were used to detect 40 water samples in the range of 0 - 10 μg/L and 0 - 100 μg/L, there was no significant difference in water iodine content between the two methods ( t = 0.99, P > 0.05). Conclusion:This method has good linear curve relationship for determination of water iodine content, good precision and high accuracy, and it is suitable for wide application.
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Objective:To investigate the clinical features, diagnosis and treatment of lymphoplasmacytic lymphoma (LPL) with biclonal M protein.Methods:The clinical data of one LPL patient with biclonal M protein at Yancheng First People's Hospital in January 2018 was retrospectively analyzed, and relevant literature was reviewed.Results:The patient was an elderly woman with clinical manifestations of lymphadenopathy, kidney damage, anemia, and bone destruction. The diagnosis was confirmed based on lymph node biopsy, immunofixation electrophoresis, bone marrow cytology, and genetic mutation testing (MYD88 L265P mutation-positive). Partial remission was achieved after 4 courses of treatment with bortezomib-based regimen.Conclusions:Clinically, LPL with biclonal M protein shows one characteristic of M protein, and the immunoglobulin IgM and IgA biclonal LPL is even rarer. The treatment scheme based on bortezomib has a certain therapeutic effect.
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Objective@#Retrospective analysis of clinical data of patients with primary aldosteronism in the past 2 years, to assess the value of liquid chromatography-mass spectrometric method (LC-MS/MS) aldosterone to renin ratio(ARR) and saline infusion test and its optimal cutoff in the diagnosis of primary aldosteronism(PA).@*Methods@#A total of 124 healthy volunteers were recruited to determine the normal reference range for LC-MS/MS aldosterone. 375 patients with high risk of primary aldosteronism were enrolled during March 2016 to November 2017. Among them, 241 patients underwent the saline infusion test. Receiver operating characteristic (ROC) analysis was performed to compare the diagnostic accuracie and the cutoff value of random ARR and post saline infusion test.@*Results@#The average level of LC-MS/MS aldosterone in healthy volunteers was(9.16±6.73)ng/dl (95% CI 2.34-22.18 ng/dl). Among 375 patients with high risk of PA, 143 patients with PA and 232 patients with essential hypertension (EH) were diagnosed. The area under the ROC curve(AUC ROC) of random ARR was 0.837(0.787-0.886), the cutoff point was 13.84 (ng/dl)/(ng/ml·h), with a sensitivity of 78.3% and a specificity of 79%. Using post-test plasma aldosterone concentration (PAC) for diagnosis, AUC ROC of the saline infusion test was 0.807(0.747-0.867), the cutoff point was 4.29 ng/dl, with a sensitivity of 90.6% and a specificity of 69.6%.@*Conclusion@#The normal range of LC-MS/MS aldosterone is 2.34-22.18 ng/dl. In our research, random ARR value above 13.84(ng/dl)/(ng/ml·h) can be the cutoff point in screening the suspected PA patients.PAC post- saline infusion test more than 4.29 ng/dl is recommended to confirm PA.
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Objective@#To summarize the clinical characteristics of patients with haploinsufficiency of A20 (HA20).@*Methods@#The clinical manifestations, laboratory examinations, treatment, outcome and genetic analysis of 4 cases with HA20 hospitalized in Peking Union Medical College Hospital were analysed.Further literature review was done after searching articles in PubMed and Wangfang databases with the key words "HA20" "A20 haploinsufficiency" "TNFAIP3" up to the date of September 2019.@*Results@#The 4 patients were a father and a daughter, as well as a mother and a daughter. Their phenotypes were quite variable, but all of them have been suffering from recurrent oral ulcer since childhood. Elevation of C-reactive protein (13-33 mg/L) and erythrocyte sedimentation rate (21-60 mm/1h) were found in these 4 patients, and there was positive antinuclear antibody in proband 1.The father in pedigree 1 and the 2 patients in pedigrees 2 have been diagnosed with Behçet disease and the proband 1 with undifferentiated connective tissue disease. The 2 patients in pedigree 1 have developed Hashimoto′s thyroiditis. After gene sequencing analysis, it was found that all the 4 patients have heterozygous nonsense mutations in TNFAIP3 gene, that is, c.811C>T, p.R271X in pedigree 1 and c.133C>T, p.R45X in pedigree 2.The diagnosis of HA20 was eventually established when sequencing results and their clinical manifestations were both compatible with this disease.A total of 21 articles were retrieved, all in English, with a total of 91 cases from 39 families (including the 4 cases reported in this paper). HA20 was reported more often in female (57, 64.8%). Most patients develop symptoms from childhood, but as many as 53.4% (47 cases) are not correctly diagnosed until adulthood. Oral ulcers, genital ulcers, periodic fever, gastrointestinal symptoms, rashes, and arthritis are the primary manifestations.Hashimoto′s thyroiditis is the most common autoimmune diseases that HA20 patients coexist with. Laboratory tests were characterized by significantly elevated inflammatory markers and low to moderate titers of autoantibodies in some patients.Most HA20 patients were reported to have nonsense mutations or shift mutations of TNFAIP3 gene, which leads to truncation of A20 protein, and only a small number of patients have missense mutation. In terms of treatment, anti-TNF treatment and anti-interleukin 1 is believed to be an effective and the most optimal therapy. The treatment effect is variable and requires long term observations.@*Conclusions@#The clinical phenotypes of HA20 are complex. For patients with both autoinflammatory and autoimmune characteristics, family history should be inquired in detail and gene sequencing should be performed if necessary.
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Objective@#To evaluate the role of 2B-containing NMDA receptors (NR2B) in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.@*Methods@#Thirty-two healthy male Sprague-Dawley rats, aged 18 months, weighing 570-630 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), sevoflurane anesthesia plus NR2B specific inhibitor Ro 25-6981 group (group S+ RO) and Ro 25-6981 group (group RO). S and S+ RO groups inhaled 3% sevoflurane for 4 h. Ro 25-6981 1 mg/kg was intraperitoneally injected at 15 min before inhaling sevoflurane in group S+ RO.Morris water maze test was performed at 2 days after the end of anesthesia to assess cognitive function.The rats were then sacrificed, and hippocampal tissues were obtained for determination of the expression and phosphorylation of ERK1/2 by Western blot.@*Results@#Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was reduced, the time of staying at the original platform quadrant was shortened, and the phosphorylation of ERK1/2 was decreased in group S (P<0.05), and no significant change was found in the escape latency in S+ RO and RO groups (P>0.05). Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, and the phosphorylation of ERK1/2 was increased in group S+ RO(P<0.05). There was no significant difference in ERK1/2 expression among the four groups (P>0.05).@*Conclusion@#The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is related to up-regulating the expression of NR2B and inhibiting the activity of ERK1/2 in aged rats.
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Objective To evaluate the role of 2B-containing NMDA receptors(NR2B)in sevoflu-rane anesthesia-induced cognitive dysfunction in aged rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 18 months,weighing 570-630 g,were divided into 4 groups(n＝8 each)using a ran-dom number table method: control group(group C),sevoflurane anesthesia group(group S),sevoflurane anesthesia plus NR2B specific inhibitor Ro 25-6981 group(group S+RO)and Ro 25-6981 group(group RO).S and S+RO groups inhaled 3％sevoflurane for 4 h.Ro 25-6981 1 mg/kg was intraperitoneally injec-ted at 15 min before inhaling sevoflurane in group S+RO.Morris water maze test was performed at 2 days af-ter the end of anesthesia to assess cognitive function.The rats were then sacrificed,and hippocampal tis-sues were obtained for determination of the expression and phosphorylation of ERK1/2 by Western blot.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was reduced,the time of staying at the original platform quadrant was shortened,and the phosphorylation of ERK1/2 was decreased in group S(P＜0.05),and no significant change was found in the escape latency in S+RO and RO groups(P>0.05).Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the time of staying at the original platform quadrant was prolonged,and the phosphorylation of ERK1/2 was increased in group S+RO(P＜0.05).There was no significant difference in ERK1/2 expression among the four groups(P>0.05).Conclusion The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is re-lated to up-regulating the expression of NR2B and inhibiting the activity of ERK1/2 in aged rats.
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Proteases are important molecules that are involved in many physiological and pathological processes of the human body, such as growth, apoptosis and metastasis cancer cells. They are potential targets in cancer diagnosis and biotherapy. In this study, we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC), oral benign masses and chronic periodontitis, as well as that of health, using human protease array kits, enzyme-linked immunosorbent assay, western blot and immunofluorescence. The salivary protease spectrum was found to be associated with oral diseases. For example, the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health. The levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-10, MMP-12, A disintegrin and metalloprotease (ADAM)9, A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13), cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups. Taking MMP-1, cathepsin V, kallikrein 5 and ADAM9 as biomarkers of OSCC, cutoff values were199, 11.34, 9.29 and 202.55 pg·mL, respectively. From the area under the curve, sensitivity and specificity, the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC. Thus, analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity. Specifically, increases in cathepsin V, kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.
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Humans , ADAM Proteins , Biomarkers, Tumor , Carcinoma, Squamous Cell , Diagnosis , Metabolism , Matrix Metalloproteinase 9 , Membrane Proteins , Mouth Neoplasms , Diagnosis , Metabolism , Saliva , ChemistryABSTRACT
Objective@#To identify the function of 91-112 amino acids (aa) fragment, the interaction domain of head and stalk of Newcastle disease virus(NDV) HN glycoprotein, and clarify the role of the fragment in promoting cell specific membrane fusion.@*Methods@#The specific gene sequences were identified by aligning 91-112 amino acids of NDV HN protein with amino acids of MeV H, RSV G, hPIV3 HN protein. The fragment deletion, fragment substitution and intermolecular homologous recombination method were combined to construct the deletion mutant, De(HN), and three chimeras, Ch(MeV), Ch(RSV), Ch(hPIV3). Cationic transfection reagent was used to transfect the plasmids into baby hamster kidney cells (BHK-21), in which vaccinia virus-T7 RNA polymerase expression system was expressed. Indirect immunofluorescence assay (IIFA) and flow cytometry (FCM) were executed to analyze the cell surface expression level. Cell fusion promotion activity, receptor recognition activity and neuraminidase activity of each mutant were also detected.@*Results@#Cell surface expression efficiency of De(HN) and Ch(MeV), Ch(RSV), Ch(hPIV3) proteins were 9.04%, 82.20%, 70.16%, 75.65% of that of wild-type (wt) HN. Fusion promotion activity of De(HN), Ch(MeV), Ch(RSV), Ch(hPIV3) were 3.83%, 24.76%, 29.42%, 57.84% of that of wt HN. The fusion promotion activity of De(HN) almost disappeared and syncytium couldn’t be found under the microscope. Hemadsorption activity was 13.48%, 36.25%, 34.93%, 65.22%, respectively (P<0.05), which was consistent with the fusion promotion activity of mutant proteins. Neuraminidase activity was 10.81%, 54.42%, 50.13%, 60.35% of that of wt HN, respectively (P<0.05).@*Conclusions@#The amino acids fragment (91-112) of NDV HN protein plays an important role in promotion fusion. The loss of fusion promotion activity of De(HN) protein was related to the failure of effective cell surface expression of the mutant.