Parkinson's disease（PD） is the second most common neurodegenerative disease in the world， which seriously affects the lives of patients. With the acceleration of aging process， the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However， the pathogenesis of PD is still unclear. According to reports， the brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra， which is closely related to neurophysiological processes such as neurogenesis， synaptic plasticity， neuroinflammation， and oxidative stress. It plays an important role in the occurrence and development of PD. At present， the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms， but with the increase of dose， the adverse reactions are significantly enhanced. Traditional Chinese medicine（TCM） has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food， economy， minor adverse reactions and multi-target action. Therefore， this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas， extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad， so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.

Objective:To investigate the clinical characteristics and prognosis of T-lymphoblastic lymphoma (T-LBL).Methods:A retrospective case series study was conducted. Clinical data of patients diagnosed with T-LBL at the Affiliated Hospital of Jining Medical University from January 2013 to March 2023 were retrospectively analyzed, and their clinical characteristics and prognosis were statistically analyzed.Results:A total of 22 T-LBL patients were included. Among them, there were 19 males (86.4%) and 3 females (13.6%), and the median age at onset was 19.5 (15, 28) years old. Based on Ann Arbor staging, 3 cases (13.6%) were classified as stage Ⅰ-Ⅱ, while 19 cases (86.4%) were stage Ⅲ-Ⅳ; 10 cases (45.5%) presented with B symptoms, 12 cases (54.5%) without B symptoms; 16 cases (72.7%) showed elevated lactic dehydrogenase (LDH) level. At onset, 7 patients (31.8%) had mediastinal masses, 3 patients (13.6%) had central nervous system involvement, and 17 patients (77.3%) had bone marrow involvement. The overall response rate (ORR) and complete remission rate among the 22 patients were 81.82% (18/22) and 31.82% (7/22), respectively. The ORR was 84.21% (16/19) in 19 patients treated with ALL-like regimens. Among 3 patients treated with NHL-like regimens, 1 case achieved complete remission and 1 case achieved partial remission. Seven patients received allogeneic hematopoietic stem cell transplantation, with a median overall survival (OS) time of 22 months; the median OS time of patients without allogeneic hematopoietic stem cell transplantation was 14 months. The 3-year OS rates in the allogeneic hematopoietic stem cell transplantation group and group without allogeneic hematopoietic stem cell transplantation were 64.30% and 16.00%, and the difference in OS between the two groups was statistically significant ( P = 0.043). Two patients with disease progression prior to transplantation died of multidrug-resistant bacterial infections after transplantation. Conclusions:T-LBL is rare, and it is a highly aggressive tumor that predominantly occurs in adolescent males. Allogeneic hematopoietic stem cell transplantation can prolong OS, reduce relapse and improve the prognosis of patients.

Objective To detect Serum metabolites with label-free surface-enhanced Raman spectroscopy(SERS)for quickly distinguishing the metabolic profiles of breast cancer patients and healthy subjects.Methods A kind of Plasma nano-material was synthesized as a probe for SERS,which has also been used to detect Raman reporter mol-ecules to assess its detection capability.Serum samples from breast cancer patients and healthy subjects were col-lected and the proteins were precipitated with methanol and removed to collect serum metabolites.Probe-based SERS was used to analyze the serum metabolites of patients and explore the changes in the metabolic profiles of breast cancer patients.Results The SERS probe was synthesized and validated.An analytical method based on SERS probe was established,which achieved a linear range(LR)of 4 orders of magnitude and a limit of detection(LOD)up to 10 nmol/L.Raman spectra of serum metabolites from 5 breast cancer patients and 5 healthy subjects were analyzed to study differences in metabolite changes.Conclusions In this study,the molecular spectrum differences of serum metabolites in breast cancer patients were screened by probe-based SERS method,which pro-vides a technology support research on the metabolic changes caused by breast cancer so potentially provide a new method for fast breast cancer screening.

【Objective】 To investigate the perioperative rate of allogeneic red blood cell (RBC) transfusion in patients who underwent total knee arthroplasty (TKA) and its risk factors, and to identify its cross-match to transfusion ratio (C∶T ratio). 【Methods】 Anesthetic data of patients who underwent TKA from January 2014 to October 2019 in Peking Union Medical College Hospital were collected and analyzed retrospectively. Perioperative allogeneic RBC transfusion rate was calculated, and binary Logistic regression analysis was performed to identify its risk factors in these patients. The overall C∶T ratio was calculated and divided into subgroups based on surgery type and age group. 【Results】 The study enrolled 2 903 patients. The perioperative rate of allogeneic RBC transfusion in TKA patients was 10.9% (95% CI 9.8%~12.0%) and overall C∶T ratio was 5.6∶1. The independent risk factors leading to perioperative allogeneic RBC transfusion included advanced age(OR=1.025, 95% CI 1.009~1.042, P<0.01), preoperative hemoglobin level(OR=0.966, 95% CI 0.954~0.978, P<0.001), preoperative anemia(OR=3.543, 95% CI 2.052~6.119, P<0.001), hematological diseases(OR=6.462, 95% CI 2.479~16.841, P<0.001), bilateral surgery(OR=7.681, 95% CI 5.759~10.245, P<0.01) and revision surgery(OR=9.584, 95% CI 4.360~21.065, P<0.001). 【Conclusion】 The risk factors for perioperative allogeneic RBC transfusion in TKA patients included advanced age, preoperative low hemoglobin level, preoperative anemia, hematological diseases, bilateral surgery and revision surgery. Only type and screen tests are recommended if patients receiving unilateral primary TKA surgery are less than 75 years old without anemia and hematological diseases, while at least one to four units of blood should be cross-matched if patients are with preoperative anemia and hematological diseases or will receive bilateral and revision arthroplasty.

BACKGROUND: Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS: Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS: We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION: The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION ClinicalTrials.gov, NCT01597232.
Humans ; Adult ; Postoperative Complications ; Erythrocyte Transfusion/adverse effects* ; Blood Transfusion ; Hospitals ; Hemoglobins/analysis*

Chinese hamster ovary (CHO) cells play an irreplaceable role in biopharmaceuticals because the cells can be adapted to grow in suspension cultures and are capable of producing high quality biologics exhibiting human-like post-translational modifications. However, gene expression regulation such as transgene silencing and epigenetic modifications may reduce the recombinant protein production due to the decrease of expression stability of CHO cells. This paper summarized the role of epigenetic modifications in CHO cells, including DNA methylation, histone modification and miRNA, as well as their effects on gene expression regulation.
Cricetinae ; Animals ; Humans ; Cricetulus ; CHO Cells ; Epigenesis, Genetic/genetics* ; DNA Methylation ; Gene Expression Regulation ; Recombinant Proteins/genetics*

Objective:To investigate the role of recombinant phospholipase A2 receptor (PLA2R) tandem dominant epitopes (PLA2RTD) in the removal of anti-PLA2R autoantibodies (anti-PLA2R) from primary membranous nephropathy (PMN).Methods:The recombinant protein PLA2RTD (cysteine-rich domain, C-type lectin like domain 1 and C-type lectin like domain 7) was expressed in bacmid-insect cell expression system. Circular dichroism was used to determine the secondary structure of PLA2RTD. Enzyme-linked immunosorbent assay and immunofluorescence were used to determine the biological activity of PLA2RTD. Epoxy activation method was used to couple the recombinant PLA2RTD and agarose gel CL-6B microspheres for preparing specific immune adsorbent of anti-PLA2R.Results:The study achieved the expression of PLA2RTD in the first time from the bacmid-insect cell system, demonstrating the good immunogenicity and high binding specificity of PLA2RTD. A single in vitro adsorption of PLA2RTD could averagely eliminate 76.66% of anti-PLA2R [(6.66±0.30) RU/ml vs. (28.54±2.10) RU/ml], the changes of IgG, IgA, albumin, β2 microglobulin, interleukin 6, and tumor necrosis factor α were all less than 4% after completion of adsorption, and the second or third repeated use of PLA2RTD could maintain the adsorption efficiency of about 65%. Conclusion:PLA2RTD-based specific immunosorbent can effectively remove anti-PLA2R in plasma, which provides a new way to specifically remove PMN-related autoantibodies.

Objective: A retrospective analysis aimed to identify the clinical features of patients with descending necrotizing mediastinitis (DNM) to improve the effects of treatment and prognosis. Methods: The clinical data of 59 patients with DNM who were treated in the Department of Oncology of Oral and Maxillofacial Surgery of the Affiliated Stomatology Hospital of Xinjiang Medical University and transferred to the intensive care unit (ICU) were retrospectively analyzed from March 2010 to March 2020. Statistical analysis was performed to identify the risk factors that were associated with mortality. Results : A total of 59 patients were identified: 21 cases of DNM typeⅠ (35.6%), 19 cases of DNM typeⅡA (32.2%), and 19 cases of DNM type ⅡB (32.2%). All patients with DNM received emergency surgery. Patients with typeⅠ and ⅡA underwent anterior mediastinal xiphoid incision and drainage combined with thoracic drainage. The thoracic mediastinum was completely debrided, and postoperative drainage was performed in type ⅡB patients. Pus samples from all 59 DNM patients were cultured for bacteria, and 19 of them were positive. Systemic antiinflammatory therapy was administered. Five patients died (8.5%), and 54 patients survived (91.5%). Compared with the survival group, the mortality group had a higher proportion of patients aged ≥ 65 years, with diabetes, with an interval from admission to ICU ≥ 6 days, with an APACHE Ⅱ score ≥ 20 days, with a duration of ICU treatment ≥ 10 days, and with septic shock, with statistically significant differences (P < 0.05). Conclusions Timely transfer to the intensive care unit for treatment combined with early active surgery and timely treatment of systemic diseases and systemic antimicrobial therapy is the key to reducing DNM mortality.

Adverse childhood experience (ACE) is potentially negative experience that occurs between 0 and 18 years old. The ACE adolescents have prominent mental health problems such as emotional regulation disorder, unstable interpersonal relationship, poor coping ability, and cognitive dysfunction. Until now, the factors affecting the mental health of ACE adolescents are not clear, but it is certain that the ecosystem in which ACE adolescents life affects their mental health. Specifically, the parent-child relationship, the school environment, the peer relationship in the micro-system, and the interaction between the parent-child relationship and other interpersonal relationship in the meso-system have been confirmed to be significantly related to the mental health of ACE adolescents. In the appearance system, the neighborhood cohesion, the level of family income, the educational level of parents and the different social and cultural background in the macro-system all have different degrees of impact on the development of ACE adolescents' psychological behaviors. In the diachronic system, the time and frequency of suffering from ACE have different effects on the mental health regarding the ACE adolescents.
Adolescent ; Adverse Childhood Experiences ; Child ; Child, Preschool ; Ecosystem ; Health Status ; Humans ; Infant ; Infant, Newborn ; Mental Health ; Parents

Inhibition of human epidermal growth factor receptor 2 mediated cell signaling pathway is an important therapeutic strategy for HER2-positive cancers. Although monoclonal antibodies are currently used as marketed drugs, their large molecular weight, high cost of production and susceptibility to proteolysis could be a hurdle for long-term application. In this study, we reported a strategy for the development of artificial antibody based on