ABSTRACT
Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.
Subject(s)
Humans , Fecal Microbiota Transplantation/methods , Treatment Outcome , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , SteroidsABSTRACT
OBJECTIVE@#To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).@*METHODS@#The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored.@*RESULTS@#The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients.@*CONCLUSION@#VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Subject(s)
Adult , Humans , Retrospective Studies , Neoplasm, Residual/drug therapy , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Recurrence , Leukemia, Myeloid, Acute/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Background@#This study analyzed the practice of dental medical dispute prevention rules of dental hygienists to present an improvement plan for improving perceived importance and practice and provide data for the development of effective medical dispute prevention programs. @*Methods@#A self-administered questionnaire survey was conducted targeting dental hygienists who were providing assistance at dental hospitals and dental clinics in Seoul and Gyeonggi-do regions from March 22 to April 28, 2022. The questionnaire collected from 273 dental hygienists consisted of eight questions on general characteristics, 30 questions on medical dispute experience, and 14 questions on medical dispute prevention. @*Results@#Complaints showed a high experience rate in ‘Consultation & reservation’, medical disputes in ‘Patient handling (unkind) related’, and ‘Prosthesis installation and cement removal’. In both the importance and practice of medical dispute prevention rules, Preservation of medical records and other medical-related data’ was high, and ‘Management of patients on standby for a long time’was low in terms of practice. ‘Lack of time’ and ‘Lack of manpower’ were cited as reasons for not resolving dental treatment disputes. The importance of dental dispute prevention rules was found to be significant according to age and position, and it was also found to affect the level of practice. @*Conclusion@#Seventy-six-point six percent of the respondents said that education on the prevention of medical disputes was necessary, although they lacked recognition of prevention rules compared to their perceptions and experiences. This study suggested specifying prevention rules in dental hygiene subjects and expanding education, improvement of dental treatment system, revise the law on the range of work to improve the recognition and practice of prevention rules.
ABSTRACT
Abstract@#Public physical education teaching has adopted modern concepts and approachs of physical training to highlight the importance and effectiveness of physical education in colleges and universities in China. These courses have placed an emphasis on the need to attend to the structural integrity of the human body, optimizing the basic action mode and the efficient transmission of the power chain in motion. From the perspective of curriculum education, it is helpful to update ideas surrounding the public physical education curriculum in colleges and universities to enrich the content of public physical education courses provided by these institutions and to improve the scientific nature of training, while also enhancing the physical fitness of college students and promoting lifelong sports consciousness. However, there is insufficient explanation and implementation of modern physical training concepts and approachs into the teaching and process of public sports in colleges and universities. It will be beneficial to improve its top level design, increase policy support, provide better facilities, strengthen the construction of teachers, actively organize enjoyable physical fitness competitions, enrich the teaching content system and clear on the positioning of college physical education, in order to promote the fundamental tasks of school based physical education and the value of school sports. This is also important to ensure a renewal of the concept of the public physical education curriculum in our country, and encourage reform of the curriculum content, teaching mode and teaching methods, while also highlighting the essential function of physical training.
ABSTRACT
OBJECTIVE@#To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients.@*METHODS@#The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively.@*RESULTS@#In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides(hyper-TG)> hyper fasting glucose(hyper-FBG)> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups.@*CONCLUSION@#The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.
Subject(s)
Humans , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Metabolic Syndrome , Retrospective Studies , Transplantation, HomologousABSTRACT
BACKGROUND@#The open reduction and internal fixation (ORIF) was a standard treatment approach for fracture at distal humerus intercondylar, whereas the optimal way before ORIF remains inconclusive. We, therefore, performed a systematic review and meta-analysis to assess the efficacy and safety of olecranon osteotomy vs. triceps-sparing approach for patients with distal humerus intercondylar fracture.@*METHODS@#The electronic searches were systematically performed in PubMed, EmBase, Cochrane library, and Chinese National Knowledge Infrastructure from initial inception till December 2019. The primary endpoint was the incidence of excellent/good elbow function, and the secondary endpoints included Mayo elbow performance score, duration of operation, blood loss, and complications.@*RESULTS@#Nine studies involving a total of 637 patients were selected for meta-analysis. There were no significant differences between olecranon osteotomy and triceps-sparing approach for the incidence of excellent/good elbow function (odds ratio [OR]: 1.37; 95% confidence interval [CI]: 0.69-2.75; P = 0.371), Mayo elbow performance score (weight mean difference [WMD]: 0.17; 95% CI: -2.56 to 2.89; P = 0.904), duration of operation (WMD: 4.04; 95% CI: -28.60 to 36.69; P = 0.808), blood loss (WMD: 33.61; 95% CI: -18.35 to 85.58; P = 0.205), and complications (OR: 1.93; 95% CI: 0.49-7.60; P = 0.349). Sensitivity analyses found olecranon osteotomy might be associated with higher incidence of excellent/good elbow function, longer duration of operation, greater blood loss, and higher incidence of complications as compared with triceps-sparing approach.@*CONCLUSIONS@#This study found olecranon osteotomy did not yield additional benefit on the incidence of excellent/good elbow function, while the duration of operation, blood loss, and complications in patients treated with olecranon osteotomy might be inferior than triceps-sparing approach.
Subject(s)
Humans , Elbow Joint/surgery , Fracture Fixation, Internal , Humeral Fractures/surgery , Humerus , Olecranon Process/surgery , Osteotomy , Range of Motion, Articular , Treatment OutcomeABSTRACT
OBJECTIVE: In our organization, it has been necessary in our organization to calculate the risk categories according to the American Thyroid Association (ATA), the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) classification systems for each patient, from the year 2019; these are also required to be registered in the database. This creates a barrier to medical collaboration in everyday radiological practice because using multiple rating systems can be confusing for both readers and patients. For the change in routine practice, this study aimed to compare diagnostic parameters of the ATA, AACE/ACE/AME, and ACR TIRADS classification systems for the detection of suspicious thyroid nodule(s) considering the results of fine-needle aspiration cytopathology as the reference standard. METHODS: Data on ultrasound characteristics (2,000 nodules) and fine-needle aspiration cytopathology (39 nodules) were included in the analysis. The decision making of fine-needle aspiration biopsies was evaluated from the ultrasound characteristics as per the ATA, AACE/ACE/AME, and ACR TIRADS classification systems. RESULTS: The ATA, AACE/ACE/AME, and ACR TIRADS recommended 26, 32, and 37 nodules for fine-needle aspiration biopsies, respectively. Considering the results of fine-needle aspiration cytopathology as the reference standard, the ATA, AACE/ACE/AME, and ACR TIRADS classification systems had 0.993, 0.996, and 0.998 sensitivity, respectively. The accuracies were 0.641, 0.795, and 0.923, respectively. CONCLUSION: The ACR TIRADS classification system is less invasive and can identify suspicious nodules more accurately than that of ATA and AACE/ACE/AME.
Subject(s)
Humans , Thyroid Neoplasms/diagnostic imaging , Thyroid Nodule/diagnostic imaging , United States , Cross-Sectional Studies , Ultrasonography , Biopsy, Fine-NeedleABSTRACT
OBJECTIVE@#To analysis clinical effects of open reduction and internal fixation in treating Gustilo type I and II patients with open distal humeral fracture.@*METHODS@#From 2013 May to 2017 June, 24 patient with Gustilo grade I and II open distal humeral fractures were treated with open reduction and internal fixation, including 20 males and 4 females, aged from 14 to 65 years old with an average of (41.3±13.1) years old. According to Gustilo classification, 16 patients were type I, 8 patients were typeII. Range of motion, complications and secondary surgery were recorded; elbow function were evaluated with VAS (visual analogue scale), MEPS (Mayo elbow performance score) and QuickDASH (quick disabilities of the arm, shoulder, and hand) at 12 months after operation.@*RESULTS@#All patients were followed up from 15 to 60 years with an average of (34.1±11.9) months. VAS score was 0(0, 2); flexion and extension ranged from 50 °to 145° with an average of (115.2±26.1)°; the range of rotation ranged from 100° to 160° with an average of (147.7±17.0)°. MEPS score was for 75 to 90 (90.0±9.1), and 14 patients got excellent result, 10 patients moderate. Quick DASH score was 4.6(0, 14.8). There were 22 patients occurred complications, such as ulnar nerve symptom and internal fixation irritation, and 10 patients accepted the second operation.@*CONCLUSIONS@#Open reduction and internal fixation is a safe and efficient method in treating Gustilo type I and II patients with open distal humeral fractures, which has an advantages of good range of movement and function score.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Bone Plates , Elbow Joint , Fracture Fixation, Internal , Humeral Fractures , General Surgery , Range of Motion, Articular , Treatment OutcomeABSTRACT
OBJECTIVE@#To explore clinical effect of olecranon sled in treating olecranal fracture.@*METHODS@#Four patients with olecranal fracture treated by olecranon sled in March 2017, including 2 males and 2 females, age of 40, 46, 47, 72 years old, 3 patients on the left side and 1 patient on the right side. All patients were caused by falling down. Fracture were transverse, oblique and slightly compressive articular surface fracture. The time from injury to operation ranged from 1 to 3 days. Operative time, blood loss, complications and flexion and extension of elbow joint, and function of forearm were observed, VAS score was used to evaluate relieve degree of pain, and Mayo score was applied to assess recovery of elbow function.@*RESULTS@#Four patients were followed up until September 2018. Operative time ranged from 40 to 60 min, blood loss was for 20 to 40 ml, and no complications occurred. All fracture were healed at 4 months after operation. Elbow flexion was for 140° to 150°, extension of elbow was from 0° and extend to 10°, activity of flexion and extension ranged from 140 ° to 160°, MEPS score was 100. No pain occurred during doing activity, and VAS score was 0.@*CONCLUSIONS@#Low-profile design and integrated design of olecranon sled could avoid irritation of tension band and plate, and it is a simple and ideal internal fixation method for simple and mildly comminuted olecranon fracture, which is not suitable for severely comminuted olecranon fracture.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Bone Plates , Elbow Joint , Fracture Fixation, Internal , Fractures, Comminuted , Olecranon Process , Range of Motion, Articular , Treatment Outcome , Ulna FracturesABSTRACT
OBJECTIVE@#To compare activity, function and postoperative ulnar nerve function of elbow joint by anterior transposition of ulnar nerve or not during open reduction and internal fixation for intercondylar humerus fractures.@*METHODS@#From January 2013 to May 2017, 168 patients with intercondylar humerus fractures were treated surgically with open reduction and internal fixation (ORIF). The patients were divided into anterior subcutaneous transposition group and simple decompression group according to handling method of ulnar nerve. There were 48 patients in transposition group, including 23 males and 25 females with an average age of (42.5±15.7) years old ranging from 14 to 77 years old, and ulnar nerve treated enough free and anterior subcutaneous transpostion after reduction of intercondylar humerus fractures; while there were 120 patients in simple decompression group, including 62 males and 58 females with an average age of (43.4±17.3) years old ranging from 14 to 81 years old, ulnar nerve returned to sulci nervi ulnaris. Activity of flexion and extension of elbow joint, range of rotation of forearm were recorded at the latest following-up, Mayo score of elbow joint was used to evaluate clinical effect, McGowan grading was used to assess dysfunction of unlnar nerve.@*RESULTS@#There was 1 patient delayed union, and 2 patients occurred joint stiffness in transposition group; while 1 patient suffered from incision infection, 1 fracture nonunion, and 4 joint stiffness in simple decompression group; and there was no statistical difference between two groups(>0.05). Forty-eight patients in transposition group were followed-up from 12 to 59 months with an average of (32.2±14.2) months, activity of flexion and extension of elbow joint was (116±28)°, range of rotation of forearm was (152±12)°, MEPS score was 88.6±11.6; and 28 patients got excellent results, 16 good, 3 moderate and 1 poor. There were 17 patients occurred injury of ulnar nerve, and 7 patients still occurred dysfunction of ulnar nerve, and 6 patients were grade I, 1 patient was grade II according to McGowan grading. In simple decompression group, there were 120 patients were followed-up from 13 to 61 months with an average of (32.0±14.9) months, activity of flexion and extension of elbow joint was (119±27)°, range of rotation of forearm was (154±16)°, MEPS score was 88.9±12.5; and 67 patients got excellent results, 44 good, 7 moderate and 2 poor. There were 42 patients occurred injury of ulnar nerve, and 22 patients still occurred dysfunction of ulnar nerve, and 18 patients were grade I, 4 patients were grade II according to McGowan grading. There were no statistical differences in following time, activity of flexion and extension of elbow joint, range of rotation of forearm, MEPS score and dysfunction of ulnar nerve.@*CONCLUSIONS@#Whether anterior transposition of ulnar nerve or not has no clarified effects for open reduction and internal fixation for intercondylar humerus fractures.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Elbow Joint , Fracture Fixation, Internal , Humeral Fractures , Humerus , Range of Motion, Articular , Treatment Outcome , Ulnar NerveABSTRACT
Tissue plasminogen activator (tPA) thrombolysis remains the gold standard for the treatment of ischemic stroke. However, the time window of tPA treatment and the fatal side effects caused by application beyond the time window limit clinical application of tPA. In order to address the limitations, combined use of tPA with other drug or non-drug interventional approaches has been proposed and some combination therapies have been experimentally validated to decrease the complications beyond the time window, especially hemorrhagic transformation (HT). The mechanisms by which the combined drugs act include protecting the blood-brain barrier, enhancing angiogenesis, protecting cerebral blood vessels, etc. Non-drug interventions include stem cell transplantation and gas therapy with multiple biological effects. The combination of tPA and the above treatments intends to alleviate the side effects of delayed tPA treatment and the neurological deficits and behavioral impairment induced by stroke. Therefore, adjuvant therapy is an innovative form of treatment which addresses the limiting factors of tPA therapy and may prolong the time window of ischemic stroke.
ABSTRACT
Low transcondylar fractures of the distal humerus in adults is rarely seen and reported in literatures. It has a bimodal distribution in terms of age, affecting the elderly and younger patients. The fracture is characterized by a very low transverse intra-capsular and extra-articular fracture lines extending from the level of lateral epicondyle to medial epicondyle. Standard elbow plain films and CT scans are crucial and indispensable for diagnosis. Conservative treatment is suitable for undisplaced fractures, patients who are intolerant of anesthesia, or people with advanced dementia. Open reduction and internal fixation (ORIF) is preferred. Parallel and orthogonal plate fixation are widely adopted while some researchers preferred crisscross-type screw fixation or bicolumnar 90-90 plating. In addition, some customized posterolateral plates are specially designed to be able to insert a transverse screw, functioning as lateral support. However, most of the recent researches conducted on low transcondylar fractures of the distal humerus are retrospective studies with relatively lower level of evidence compared to prospective and randomized controlled ones which remain a vacancy in this field. Therefore, further studies comparing the biomechanical properties and clinical prognosis of different configurations of internal fixation or total elbow arthroplasty for the treatment of low transcondylar fractures are needed in the future.
Subject(s)
Humans , Bone Plates , Fracture Fixation, Internal , Humeral Fractures , Diagnosis , Therapeutics , Humerus , Prospective Studies , Retrospective Studies , Treatment OutcomeABSTRACT
Aberrant oxidative metabolism in cells is one of the hallmarks of cancer. Overproduction of reactive species promotes carcinogenesis by inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy is considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, is involved in not only the formation of the caveolae, vesicular transport, maintaining cholesterol homeostasis directly, but also many cellular physiological and pathological processes including growth, regulation of mitochondrial antioxidant level, apoptosis and carcinomas by interacting with a lot of signaling molecules through caveolin scaffolding domain. Cav-1 has also been shown to mediate tumor genesis and progression through oxidative stress modulation, while Cav-1-targeted treatment could scavenge the reactive species. Intracellular reactive species could modulate the expression, degradation, post-translational modifications and membrane trafficking of Cav-1. More importantly, emerging evidence has indicated that multiple antioxidants could exert antitumor activities in cancer cells by modulating the signaling of Cav-1. This paper reviewed the research progresses on the roles of Cav-1 and oxidative stress in tumorigenesis and development, and would provide new insights on designing strategies for cancer prevention or treatment.
Subject(s)
Humans , Antioxidants , Apoptosis , Carcinogenesis , Carcinoma , Pathology , Caveolin 1 , Mitochondria , Neoplasms , Pathology , Oxidative Stress , Signal TransductionABSTRACT
Abstract Owing to the high content of lignocellulose, desiccated coconut become a healthy material for dietary fiber supplementation. In this study, the changes in solubility of the fibers of desiccated coconut were evaluated. The changes of the pHs and weight losses were studied. Furthermore, variations of the ingredient structures of desiccated coconut by hydrolysis by hydrochloric acid were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). After hydrolysis 30 s, the pHs of all systems increased, while six hours later, the pH of only system with initial pH = 1.00 decreased. The decline of pH only existed in hydrolysis systems with initial pH = 1.00, there is no relevant with the quantities of desiccated coconut. The lower initial pH of hydrolysis system was, the less the intrinsic viscosity of the desiccated coconut after hydrolysis was, the small the crystallinity was. After hydrolysis, the microstructure of the desiccated coconut become looser, and the secondary structure of the coconut protein became more stable and ordered. The results suggest that the hydrolysis of desiccated coconut mainly occurred in the branched chain and the non-crystalline region of lignocellulose, which transforms some insoluble dietary fiber into soluble dietary fiber. This improves the nutritional value of desiccated coconut.
ABSTRACT
Caveolin-1 (Cav-1), as an important structural protein of caveolae, has been proven to be correlated with several signal transduction pathways. Recent studies have shown that Cav-1 may play a critical role in response to DNA damage in irradiated pancreatic cancer cells. However, it is not known whether down-regulation of Cav-1 is required to enhance the damage of other kinds of human cells exposed to X-radiation. In this study, the role of Cav-1 in Chang liver cell line (CHL) exposed to X-radiation was investigated. Cav-1 knockdown cell line (CHL-CAV7) was stably established by the siRNA plasmids transfection, and Cav-1 expression was suppressed by 60%, compared with that of control group (CHL-C) which was transfected with non-targeting plasmids. Cellular survival ability and the expressions of proteins related to DNA damage and repair were examined by colony formation assay and Western blot, respectively. Down-regulation of Cav-1 expression induced a significant decrease of the survival rate in CHL-CAV7 cells exposed to 8 and 10 Gy X-radiation. Compared with CHL-C cells, CHL-CAV7 cells showed increased γH2AX expression, as well as decreased p-ATM, DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) and p53 protein expressions when treated with X-radiation. Meanwhile, the colocalization of Mdm2 and Cav-1 was decreased in CHL-CAV7 cells compared with that in CHL-C cells. These results suggest that the down-regulation of Cav-1 may aggravate DNA damage of CHL cells through reducing the interaction of Cav-1 and Mdm2, which results in the promotion of p53 degradation.
ABSTRACT
To study the correlation between the spatial cognitive impairment and different subtypes of estrogen receptor α (ERα) of hippocampus in diabetic mice, we used alloxan (intraperitoneal injection) to induce type 1 diabetes in male Kunming mice and compared the spatial cognitive ability of the model mice with that of control mice through Morris water maze test. Meanwhile, using Western blot, we detected the protein expressions of ER-α36, ER-α66, caveolin-1, PKCα, cAMP-response element binding protein 2 (CREB2), and synaptophysin (Syn) in the hippocampus of the mice. The results showed that on the 3rd and 5th days of training, the ability of spatial learning and memory in the diabetic mice was significantly inferior to that of the control mice (P < 0.05). In the diabetic mice, the protein expressions of caveolin-1 and PKCα were decreased (P < 0.05), but ER-α66 expression was unaffected, while ER-α36 and CREB2 expressions were significantly increased (P < 0.05) compared with those of the control mice. The results suggest that abnormal expression of ER-α36 and related signal molecules may be important factors for diabetes-induced spatial cognitive impairment.
Subject(s)
Animals , Male , Mice , Caveolin 1 , Metabolism , Cognitive Dysfunction , Cyclic AMP Response Element-Binding Protein , Metabolism , Diabetes Mellitus, Experimental , Estrogen Receptor alpha , Metabolism , Hippocampus , Metabolism , Maze Learning , Memory , Protein Kinase C-alpha , Metabolism , Synaptophysin , MetabolismABSTRACT
<p><b>BACKGROUND</b>Infection and aseptic loosening are common complications of total elbow arthroplasty (TEA) and often require revision surgery. However, bone defects, along with other complications, bring an extra difficulty to the second surgery, especially for patients with a massive bone defect in the proximal ulna. Several methods including allograft or autograft have been introduced into practice, but none sufficiently solves these problems.</p><p><b>METHODS</b>We conducted a new surgical method for patients with a massive ulnar bone defect needing revision TEA. During revision arthroplasty, the ulnar prosthesis was inserted into the radius as a salvage procedure. Four consecutive patients received revision arthroplasty with this method between 2013 and 2016. Patients' data were collected to evaluate the clinical outcome.</p><p><b>RESULTS</b>All patients had a Grade III ulnar bone defect. At the last follow-up session, all patients reported a painless, functional elbow joint. Three patients suffered from a periprosthetic infection that was completely cured using the two-stage method. No major complications, including infection, aseptic loosening, or wound problems were found. One patient had a transient ulnar neuritis, and another had a transient radial neuritis. Both patients had full recovery at the last follow-up session.</p><p><b>CONCLUSIONS</b>Inserting an ulnar prosthesis into the radius is a novel procedure for patients with a massive bone defect due to infection or aseptic loosening. It is a safe, quick, and effective treatment with a promising short-term outcome. This method should be provided as a salvage procedure for patients with a nonreconstructable ulnar bone defect.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Arthroplasty, Replacement , Methods , Elbow , General Surgery , Prostheses and Implants , Radius , General Surgery , Range of Motion, Articular , Reoperation , Methods , Retrospective Studies , Treatment Outcome , Ulna , General SurgeryABSTRACT
NADPH oxidases (NOXs) are the key enzymes of redox signaling in vivo and also the main source of reactive oxygen species (ROS) in the body. ROS plays a role of double-edged sword. On the one hand, ROS, at the level of physiological amount, has the effect of immune defense and also acts as a second messenger involved in the regulation of cellular signaling pathways. On the other hand, excessive ROS can cause oxidative stress, leading to the disorder of cellular functions. Recently, studies showed that ROS plays an important role in acceleration of some pathological reactions such as inflammation, fibrosis and tumor formation. As a major source of ROS, NOX has become a popular target in treating oxidative stress, inflammation, fibrosis and tumor. Herein, the role of NOX in these pathological processes and the research progress of NOX inhibitors are reviewed.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical and laboratory features of very long chain acyl-CoA dehydrogenase deficiency ( VLCADD ) and the correlations between its genotype and phenotype.</p><p><b>METHOD</b>Eleven patients diagnosed as VLCADD of Shanghai Jiaotong University School of Medicine seen from September 2006 to May 2014 were included. There were 9 boys and 2 girls, whose age was 2 d-17 years. Analysis was performed on clinical features, routine laboratory examination, and tandem mass spectrometry (MS-MS) , gas chromatography mass spectrometry (GC-MS) and genetic analysis were conducted.</p><p><b>RESULT</b>All cases had elevated levels of blood tetradecanoylcarnitine (C14:1) recognized as the characteristic biomarker for VLCADD. The eleven patients were classified into three groups: six cases in neonatal onset group, three in infancy onset group form patients and two in late onset group. Neonatal onset patients were characterized by hypoactivity, hypoglycemia shortly after birth. Infancy onset patients presented hepatomegaly and hypoglycemia in infancy. The two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis. Six of the eleven patients died at the age of 2-8 months, including four neonatal onset and two infant onset patients, with one or two null mutations. The other two neonatal onset patients were diagnosed since early birth through neonatal screening and their clinical manifestation are almost normal after treatments. Among 11 patients, seventeen different mutations in the ACADVL gene were identified, with a total mutation detection rate of 95.45% (21/22 alleles), including eleven reported mutations ( p. S22X, p. G43D, p. R511Q, p. W427X, p. A213T, p. C215R, p. G222R, p. R450H, p. R456H, c. 296-297delCA, c. 1605 + 1G > T) and six novel mutations (p. S72F, p. Q100X, p. M437T, p. D466Y, c. 1315delG insAC, IVS7 + 4 A > G). The p. R450H was the most frequent mutation identified in three alleles (13.63%, 3/22 alleles), followed by p. S22X and p. D466Y mutations which were detected in two alleles (9.09%, 2/22 alleles).</p><p><b>CONCLUSION</b>The ACADVL gene mutations were heterozygous in our patients. The mortality of neonatal onset form and infant onset form is much higher than the late onset form patients, suggesting a certain correlation between the genotype and phenotype was found. The earlier diagnosis and treatment of VLCADD are of vital importance for the improvement of the prognosis of the patients.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Acyl-CoA Dehydrogenase, Long-Chain , Genetics , Age of Onset , Alleles , Asian People , China , Genetic Testing , Genotype , Heterozygote , Lipid Metabolism, Inborn Errors , Genetics , Mitochondrial Diseases , Genetics , Muscular Diseases , Genetics , Mutation , Neonatal Screening , Phenotype , Prognosis , Rhabdomyolysis , Spectrum Analysis , Tandem Mass SpectrometryABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism of immunomodulatory activity of triptolide on primary immune thrombocytopenia (ITP)patients-derived plasmacytoid dendritic cells (pDCs).</p><p><b>METHODS</b>pDCs in peripheral blood of ITP patients before therapy (group 1), ITP patients in complete response (ITP-CR, group 2) and healthy donors (group 3) were sorted by flow cytometry, then incubated with triptolide at 0, 5, 10 or 30 µg/L. After 24 hours, we collected the supernatants and then detected the concentrations of IFN-α, IL-6 and TNF-α using ELISA. After 5 days, the cultured cells were collected and CD11c, CD80 and CD86 expressions of myeloid dendritic cells (mDCs) were analyzed by flow cytometry, the morphology of mDC was observed by light microscope and electron microscope.</p><p><b>RESULTS</b>After incubation with triptolide at 10 µg/L, the levels of IFN-α, IL-6 and TNF-α in group 1 \[(451.32 ± 85.77) ng/L, (105.68 ± 23.85) ng/L and (135.78 ± 30.62) ng/L\] and group 2 \[(391.71 ± 72.49) ng/L, (84.73 ± 17.77) ng/L and (108.16 ± 23.21) ng/L\] were significantly higher than those in group 3 \[(335.51 ± 67.54) ng/L, (73.62 ± 21.82) ng/L and (95.58 ± 32.85) ng/L\] (all P < 0.05); the levels of IFN-α, IL-6 and TNF-α in group 1 were significantly higher than those in group 2 (all P < 0.05) in a dose-dependent manner (P < 0.05). CD11c, CD80 and CD86 expressions of mDC in group1 and group 2 were significantly higher than those in group 3 (all P < 0.05); CD11c, CD80 and CD86 expressions of mDC in group 1 were significantly higher than those in group 2 (all P < 0.05) also in a dose-dependent manner (all P < 0.05). Triptolide could inhibit pDCs from differentiation into mDCs, the latter displayed more immature morphology than untreated-pDCs.</p><p><b>CONCLUSION</b>Triptolide could decrease the immune function of pDCs from ITP, inhibit pDCs from differentiation and maturation.</p>