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Objective@#To understand the prevalence of Lying Flat behaviors and its association with depressive symptoms among Chinese college students, so as to provide a scientific basis for promoting the physical and mental health development of adolescents.@*Methods@#From July to October 2023, three universities were selected through convenient sampling from Jiangxi Province, Liaoning Province and Beijing City, respectively. Selfdesigned questionnaire links were distributed on campus to collect basic information and Lying Flat behaviors among college students, and the Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for students with depressive symptoms. Finally, a total of 4 225 valid questionnaires were obtained. Chisquare was used to compare of report rates of Lying Flat behaviors across different demographic characteristics. Ordered Logistic regression analysis was used to explore the association between Lying Flat behaviors and depressive symptoms, with Z test used to assess variations in the strength of associations.@*Results@#The reporting rates of academic, life, and social Lying Flat were 32.7%, 17.8% and 17.5%, respectively. And 6.7% of the participants were found of all three Lying Flat behaviors simultaneously.Among college students with three Lying Flat behaviors, the constituent ratios of no, mild, moderate and above depressive symptoms were 9.9%, 30.5% and 59.6%, respectively. Additionally, college students who had three Lying Flat behaviors were more likely to show mild, moderate and above depressive symptoms [OR(95%CI)=2.49(1.60-3.87), 7.69(5.01-11.79), P<0.01].@*Conclusions@#Academic Lying Flat behavior is most prevalent among college students. Academic, life and social Lying Flat behaviors are all significantly positively correlated with depressive symptoms. Attention should be paid to the Lying Flat behaviors and college students psychological health conditions to promote their physical and mental health development.
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@#Abstract: Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in the activation of B cells and granulocytes, operating downstream of B cell and Fcγ receptors, and is considered an attractive target for treating autoimmune diseases. Preclinical investigations have demonstrated that inhibition of BTK activity holds promise as a potential therapeutic strategy for inflammatory immune responses such as autoimmune diseases and allergies. This review provides an overview of the mechanisms by which BTK contributes to immune-related diseases and summarizes current research on the development of BTK inhibitors for treating these conditions, aiming to offer novel insights into non-oncology applications for BTK inhibitors.
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Objective:To investigate the effect of ultrasound monitoring of inferior vena cava collapse index (IVC-CI) guiding fluid replacement on circulation in elderly patients during induction of general anesthesia.Methods:A total of 71 elderly patients who underwent elective surgery under general anesthesia and tracheal intubation at Hunan Provincial People′s Hospital from April 2021 to September 2022 were randomly divided into control group (35 cases) and observation group (36 cases) using a random number table method. Before anesthesia, both groups of patients underwent IVC ultrasound examination and calculated the IVC-CI value. For patients with IVC-CI≥40%, the observation group was given 8 ml/kg of crystal solution before anesthesia induction, while the control group was not treated. The incidence of hypotension, the use of vasoactive drugs, and the total infusion volume from anesthesia induction to skin incision were recorded in two groups. Mean arterial blood pressure (MBP), heart rate (HR), oxygen saturation (SpO 2), cardiac index (CI), and cardiac volume variability (SVV) before anesthesia (T 0), 5 min after induction (T 1), 1 min after tracheal intubation (T 2), 5 min after tracheal intubation (T 3), 10 min after tracheal intubation (T 4), and 1 min before skin incision (T 5) were recorded and compared between the two groups. Results:The incidence of hypotension (27.8% vs 60.0%) and utilization rate of vasoactive drugs (25.0% vs 48.6%) in the observation group were lower than those in the control group, and the total infusion volume during anesthesia induction was higher than that in the control group, with statistical significance (all P<0.05). SVV, CI and MBP at T 1, T 3, T 4 and T 5 were significantly different from those at T 0 in the control group ( F=3.85, 14.66, 3.96, all P<0.05). SVV, CI and MBP at T 1, T 3, T 4 and T 5 in the observation group were significantly different from those at T 0 ( F=3.51, 13.20, 4.35, all P<0.05). There was no significant difference in SVV, CI, MBP, HR and SpO 2 between 2 groups (all P>0.05). Conclusions:For the elderly patients with preoperative IVC-CI≥40%, pre-filling with 8ml/kg crystal solution before anesthesia induction can significantly reduce the incidence of hypotension and the utilization rate of vasoactive drugs in the elderly patients during anesthesia induction.
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The prognosis for pancreatic cancer is extremely poor. To improve the prognosis of pancreatic cancer, it is urgently needed to improve early detection to advance treatment. And basically, it is also necessary to emphasise basic research to find novel therapies. By promoting the disease-centered multidisciplinary team model, researchers should achieve high-quality closed-loop process management of the entire life cycle which consists of prevention, screening, diagnosis, treatment, rehabilitation,and follow-up, with the objective of establishing a standard clinical process to improve the outcome in essence. This article summarized the progress of pancreatic cancer at different stages of the whole cycle management recently and shared the experience of pancreatic cancer treatment from the author's team in the past ten years.
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Humans , Pancreatic Neoplasms/therapy , Pancreas , PrognosisABSTRACT
Objective: To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (auto-HSCT) in elderly patients (≥65 years old) with multiple myeloma (MM) . Methods: From June 1, 2006 to July 31, 2020, 22 MM patients (≥65 years old) who were diagnosed in the First Affiliated Hospital, Sun Yat-sen University and received novel drug induction followed by auto-HSCT were analyzed retrospectively. These patients were evaluated for important organ functions before transplantation, and the International Myeloma Working Group frail score was used in 2016 to screen out transplant-eligible patients. Results: The median (interquartile range, IQR) age at the time of transplantation of the 22 patients was 66.75 (IQR 4.50) years. A total of 20 patients received stem cell mobilization. The median number of mononuclear cells collected was 4.53×10(8)/kg, that of CD34(+) cells was 3.37×10(6)/kg, and the median number of apheresis procedures performed was 2. After stem cell transfusion, the median time of neutrophil implantation was 11 days, that of platelet implantation was 13 days, and the treatment-related mortality was 0 at 100 days after transplantation. The median follow-up was 48.7 months. The median time to progression time was not reached, and the median overall survival time was 111.8 months. Conclusion: Auto-HSCT is a safe and effective treatment for selected elderly patients of 65 years or older with MM.
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Aged , Humans , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Multiple Myeloma/drug therapy , Retrospective Studies , Transplantation, Autologous/methods , Treatment OutcomeABSTRACT
Objective:To observe the effect of esketamine on cardiac index in patients undergoing lumbar surgery in prone position under general anesthesia.Methods:Forty-five patients with prone lumbar surgery after general anesthesia in Hunan Provincial People′s Hospital from March to July 2021 were divided into observation group (24 cases, group A) and control group (21 cases, group B) according to random number table method. Group A received 0.5 mg/kg esketamine intravenously during induction, and 0.15 mg/(kg·h) esketamine intravenously for 2 h after prone position. Group B received the same amount of normal saline. Both groups were given sevoflurane and remifentanil during operation to maintain anesthesia, and sufentanil was given intermittently during operation. The mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic pressure (DBP), cardiac index (CI), and heart rate (HR) before induction (T 0), during endotracheal intubation (T 1), 5 minutes after intubation (T 2), 5 minutes after prone position (T 3), 10 minutes after prone position (T 4), 30 minutes after prone position (T 5), 45 minutes after prone position (T 6), 60 minutes after prone position (T 7), 90 minutes after prone position (T 8), and 120 minutes after prone position (T 9) were recorded; The total dosage of norepinephrine 2 hours after anesthesia to prone position and extubation time after operation were also recorded. The Visual Analogue Scale (VAS) was performed 15 minutes after extubation, 6 and 24 hours after operation. Results:There was no significant difference in CI between T 3-T 9 and T 2 in group A ( P>0.05); the CI of group B at T 3-T 7 was significantly lower than that at T 2 (all P<0.05); there was no significant difference in CI between T 8-T 9 and T 2 in group B (all P>0.05); There was no significant difference in CI between group A and group B at T 0-T 2 (all P>0.05). The CI of group A at T 3-T 9 was significantly higher than that of group B (all P<0.05); The dosage of norepinephrine in group A was significantly lower than that in group B ( P<0.05); There was no significant difference in HR, MAP, SBP and DBP between the two groups at different time points (all P>0.05); there was also no significant difference in extubation time and VAS scores at 15 minutes, 6 hours and 24 hours after extubation between the two groups (all P>0.05). Conclusions:Intraoperative application of esketamine can increase CI after prone position and reduce the amount of norepinephrine during lumbar surgery.
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With multi-drug-resistant bacteria being more prevalent over years, diabetic foot complicated with multi-drug-resistant bacteria infection emerges as a significant challenge for clinicians and patients. Diabetic foot is predisposed to multi-drug resistant bacterial infection. Growing body of evidence shows that ulcer type, ulcer grade, ulcer area, history of antibiotics treatment, previous hospitalization history, osteomyelitis, and proliferative retinopathy are risk factors. Among multi-drug-resistant bacteria, methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing bacteria are the most common strains. Infection with multiple drug-resistant bacteria contributes to the amputation rate and mortality in patients with diabetic foot ulcers. The aim of this review is to give an update on multi-drug resistant bacteria infection and clinical outcome of diabetic foot, with a goal to improve clinical awareness and management.
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@#Poly-adenosine diphosphate ribose polymerases (PARPs) play an important role in DNA repair and apoptosis.Among them, mono-(ADP-ribosyl) transferase (MARTs) can regulate various cell reactions by catalyzing and transferring single ADP-ribose.Most MARTs are highly expressed in cancers, which is closely related to the occurrence and progression of cancers.This review introduces the MARTs that are highly expressed in cancers, classifies them according to the differences of their structural domains, and reviews their known mechanism, their close relationship with cancers, their potential value in cancer therapy and the research progress of corresponding inhibitors.These targets are expected to provide new research ideas for cancer therapy in the era of precision medicine.
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Objective:To investigate the clinical characteristics and outcome of novel coronavirus pneumonia (COVID-19)patients with different body mass index (BMI), and to provide the basis for disease assessment and prognosis.Methods:The clinical data of 541 patients with COVID-19 diagnosed in Xiaogan Hospital Affiliated to Wuhan University of Science and Technology from January 16 to March 28, 2020 were collected. The patients were divided into normal weight group, overweight group, and obesity group according to BMI. The clinical characteristics and outcomes of the three groups were compared. The correlation between BMI and clinical classification was analyzed by ordinal logistic regression.Results:There were 288 cases (53.23%) in normal weight group, 193 cases (35.67%) in overweight group, and 60 cases (11.09%) in obesity group. Compared with normal weight group, overweight and obesity groups displayed higher proportion of hypertension, with increased levels of white blood cells, neutrophils, C reactive protein, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and triglyceride in laboratory test results, and higher proportion of severe and critical illness ( P<0.05 or P<0.01). After adjusting for age, gender, and underlying diseases, regression analysis showed that higher BMI predicted more severe clinical classification ( OR=1.079, 95% CI 1.010-1.154). Conclusion:In COVID-19 patients, overweight and obese patients are more likely to develop into severe and critical illness, suggesting that obesity may be an important risk factor affecting the clinical outcome of COVID-19.
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Background: Peripheral blood test is a routine clinical examination item. Granulocytes and platelets are often used to measure the severity of inflammatory response, and it is worthy to investigate the value of various inflammatory indices ratio for predicting the prognosis of disease. Aims: To compare and analyze the diagnostic efficacy of platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), red blood cell distribution width to platelet ratio (RPR), C-reactive protein to lymphocyte ratio (CLR) and C-reactive protein (CRP) in evaluating the severity of hyperlipidemic acute pancreatitis (HLAP). Methods: The clinical and laboratory data of 104 patients with HLAP from January 2018 to December 2020 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to the revised Atlanta classification, HLAP patients were divided into mild HLAP, moderate to severe/severe HLAP. Forty-four healthy subjects during the same period were served as the controls. PLR, NLR, MLR, RPR, CLR and CRP were compared between HLAP group and control group. The ROC curve was used to analyze the diagnostic efficacy of PLR, NLR, MLR, RPR, CLR and CRP for the diagnosis of moderate to severe/severe HLAP. Results: PLR, NLR, MLR, RPR, CLR and CRP were significantly increased in HLAP group than in control group (P<0.05); PLR, NLR, MLR, RPR, CLR and CRP were significantly increased in moderate to severe/severe HLAP group than in mild HLAP group (P<0.05). The cut-off values of PLR, NLR, MLR, RPR, CLR, CRP and combined PLR, NLR, MLR, RPR, CLR were 220.48, 10.95, 0.84, 0.12, 76.66, 87.44 mg/L, 0.37, respectively, the sensitivity for diagnosing moderate to severe/severe HLAP were 0.73, 0.45, 0.47, 0.82, 0.65, 0.65 and 0.88, respectively, the specificity were 0.85, 0.87, 0.90, 0.81, 0.83, 0.83 and 0.85, respectively, AUC were 0.84, 0.65, 0.67, 0.87, 0.77, 0.75 and 0.94, respectively. Conclusions: PLR, NLR, MLR, RPR, CLR and CRP can evaluate the severity of HLAP, and the combined PLR, NLR, MLR, RPR and CLR has higher sensitivity and diagnostic efficacy in the diagnosis of moderate to severe/severe HLAP.
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The estimation of postmortem interval (PMI) is a core issue in forensic practice. A large amount of time-dependent data can be produced in the decomposition process of a body, however, such multidimensional data cannot be comprehensively and effectively analyzed and utilized by any existing conventional PMI estimation method. As a rapidly developing information technology, artificial intelligence (AI) has significant advantages in big data processing, due to it's comprehensiveness, efficiency and automation. Some scholars have already applied it to researches on the estimation of PMI, showing it's significant advantages in terms of accuracy and development prospect. This article reviews the significance, mode and progress of application of AI in PMI estimation and provides some suggestions and prospects for future study.
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Humans , Artificial Intelligence , Big Data , Forensic Pathology , Postmortem Changes , Time FactorsABSTRACT
PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
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Humans , Adenocarcinoma , Chromogranin A , Classification , Immunohistochemistry , Lymph Nodes , Neoplasm Metastasis , Neural Cell Adhesion Molecules , Prognosis , Stomach , Stomach Neoplasms , SynaptophysinABSTRACT
Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
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Humans , Antineoplastic Combined Chemotherapy Protocols , Bortezomib/therapeutic use , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Induction Chemotherapy , Multiple Myeloma/therapy , Retrospective Studies , Stem Cell Transplantation , Transplantation, Autologous , Treatment OutcomeABSTRACT
Objective: To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) . Methods: Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively. Results: ①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3(rd) month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) . Conclusion: HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.
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Humans , Busulfan , Cyclophosphamide , Drug Combinations , Etoposide , Hematopoietic Stem Cell Transplantation , Melphalan , Multiple Myeloma/therapy , Retrospective Studies , Stem Cell Transplantation , Transplantation Conditioning , Transplantation, AutologousABSTRACT
Mycophenolic acid (MPA, ) and its derivatives are first-line immunosuppressants used in organ transplantation and for treating autoimmune diseases. Despite chemical synthetic achievements, the biosynthetic formation of a seven-carbon carboxylic acid pharmacophore side chain of , especially the processes involving the cleavage of the prenyl side chain between DHMP () and DMMPA (), remains unknown. In this work, we identified a membrane-bound prenyltransferase, PgMpaA, that transfers FPP to to yield FDHMP (). Compound undergoes the first cleavage step a new globin-like enzyme PgMpaB to form a cryptic intermediate . Heterologous expression of genes in demonstrates that the second cleavage step (from to ) of is a cluster-independent process . Our results, especially the discovery of the broad tolerance of substrates recognized by PgMpaB, set up a strategy for the formation of "pseudo-isopentenyl" natural products using fungal globin-like enzymes.
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OBJECTIVE: To investigate the characteristics and regularity of gestational (including perinatal period) adverse drug reactions (ADR) in Sichuan province, and to provide evidence for ensuring the safety and effectiveness of drug use in clinic. METHODS: Gestational ADR reported to Sichuan provincial ADR monitoring center from Nov. 2016 to Nov. 2017 were statistically analyzed in respects of report source, personnel distribution, general information of patients, route of administration, drug types and main drugs, involved system/organ, grading and outcome, etc. RESULTS: A total of 1 309 gestational ADR cases (1 340 case time) were collected, in which 1 305 were from medical institutions, 3 from enterprises and 1 from manufacturer. There were 986 physicians, 188 nurses, 133 pharmacists and 2 commissioners for drug safety. 859 cases (65.62%) were 21-30 years old, accounting for the largest proportion. 867 case time were caused by intravenous administration (64.70%). ADR-inducing drug types mainly included reproductive system drugs (491 case time, 36.64%), antimicrobial drugs (479 case time, 35.75%) and blood system drugs (110 case time, 8.21%). Main of them were Carboprost tromethamine injection (187 case time, 13.96%), Cefazolin sodium for injection (122 case time, 9.10%) and Oxytocin injection (105 case time, 7.84%). ADR mainly involved skin and its appendants (517 case time, 33.95%), gastrointestinal system (387 case time, 25.41%), whole body (175 case time, 11.49%). In 1 309 gestational ADR, 1 251 cases (95.57%) were general ADR; 58 cases (4.43%) were severe ADR, including 14 life-threatening cases, 7 extended hospital stay and 37 others; 592 (45.22%) patients improved, 716 (54.70%) recovered and 1 (0.08%) did not improve. CONCLUSIONS: In clinical practice, it is necessary to strengthen the monitoring of drug use in patients during gestational, especially monitor ADR of uterine contraction drugs and antimicrobial drugs during gestational, use drug cautiously and promote clinical medication safety in gestational patients.
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Based on the reported IDO1 inhibitor U-3i,11 phenylsulfonamide derivatives were designed and syn-thesized by adopting bioisosterism and molecular docking technology.The inhibitory activities of the target compounds against IDO1 were determined by the HeLa cell-based kynurenine assay.The results demonstrated that most compounds showed different degrees of inhibitory effects on IDO1.Among them,compounds 3b and 3e displayed the most potent activity and could reverse IDO1-mediated immune suppression,which might be worth of further investigation.
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Aim To prepare hyaluronic acid nanoparti-cles(Ade/GA-HA) using glycyrrhetinic acid modified hyaluronic acid as the carrier and adenine as a model drug, and analyze their physicochemical property and proliferation effect on Bel-7402 cells. Methods Gly-cyrrhetinic acid and hyaluronic acid were combined by chemical cross-linking method, dialysis and freeze-dr-ying,based on which Ade/GA-HA was prepared using ultrasonic method, and the particle size and Zeta po-tential were determined by Malvern laser particle analy-zer,and the morphology was observed by transmission electron microscopy, and the absorbance was deter-mined by ultraviolet-visible spectrophotometer, high performance liquid chromatograph and microplate read-er to caculate drug load, encapsulation efficiency and in vitro release. MTT assays were utilized to determine the proliferation of nanoparticles treated Bel-7402 cells. Results GA-HA nanoparticles had spherical shape with a good dispersion, at diameters of 398.1 nm, of which Zeta potential was - 34.2 mV, and presented good short term stability. The drug load and encapsulation efficiency of Ade/GA-HA nanoparticles were (22.5 ± 5.8)% and (87.27 ± 0.33) %, re-spectively. Burst release was observed in Ade/GA-HA nanoparticles within 4 h, while controlled release 4 h later. Compared with free adenine,Ade/GA-HA nano-particles had a stronger inhibitory effect on cell prolif-eration with statistically significant difference. Conclu-sion GA-HA nanoparticles has excellent physico-chemical properties and meet the design requirement.
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<p><b>OBJECTIVE</b>To investigate the potential signaling pathway that regulates the proliferation of human CD34cells stimulated by prostaglandin E2 receptor 4 agonist (EP4A) in vitro.</p><p><b>METHODS</b>Twenty samples of peripheral blood containing stem cells were collected from the G-CSF mobilized healthy donors in our department of hematology. Human CD34cells were isolated by magnetic activated cell sorting (MACS) microbeads kit. The Cell Counting Kit-8 (CCK8) assay was used to determine the optimal concentration and time of EP4A to promote human CD34cell proliferation in vitro. Under the optimal condition, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect mRNA level of β-catenin, and Western blot was used to assay protein expression of β-catenin and P-GSK-3β in human CD34cells treated with EP4A.</p><p><b>RESULTS</b>Culturing with 10 µmol/L EP4A for 72 h, it was found that EP4A promoted human CD34cell proliferation significantly, and the proliferation rate of human CD34cells was 1.36 times higher than that of the control(P=0.002). Under the optimal condition, it was also found that EP4A enhanced the β-catenin expression at both mRNA and protein levels, and up-regulated phosphorylation of GSK-3β in human CD34cells, but these effects could be inhibited by the EP4A antagonist EP4AA.</p><p><b>CONCLUSION</b>EP4A can enhance human CD34cell proliferation in vitro by activating Wnt/β-catenin signaling pathway.</p>
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Objective:To observe the effect of herbal cake-partitioned moxibustion on the expressions of mitogen-activated protein kinase (MEK1/2) and extracellular regulatory protein kinase (ERK1/2) in gastric tissues of rats with spleen deficiency syndrome, and to explore the possible mechanisms of herbal cake-partitioned moxibustion in treating spleen deficiency syndrome. Methods:Sixty Sprague-Dawley (SD) rats were randomly divided into a blank control group (group A), a model group (group B), a ranitidine group (group C), and a herbal cake-partitioned moxibustion group (group D) by random digit, 15 rats in each group. Rat models of spleen deficiency syndrome were made by intragastric administration of 4℃ 200% concentrated Da Huang (Radix et Rhizoma Rhei). After successful modeling, the rats in group C were treated with 25 mg/(kg·bw) ranitidine by intragastric adminstration and rats in group D were treated with herbal cake-partitioned moxibustion at Zusanli (ST 36) and Zhongwan (CV 12), for 8 d. Excepted for rats in group A, all the other rats were treated with indomethacin at 5 mg/(kg·bw) at 8:00 a.m. on the second day after finishing all the intervention and sacrificed 7 h later to isolate the stomach. Histopathological changes of the gastric tissues were observed under light microscope after hematoxylin-eosin (HE) staining. The protein expressions of MEK1/2 and ERK1/2 in the gastric tissues were detected by immunohistochemistry. Results:After intervention, the gastric mucosal injury in group B was significantly severer than that in group A, with large breakage and ablating; the damage of gastric mucosa was decreased in group C compared with group B; the gastric mucosal surface remained relatively complete, and the status of breakage and ablating was significantly improved. After intervention, compared with group A, the protein expressions of MEK1/2 and ERK1/2 in gastric tissues of the other groups were significantly higher (P<0.01). Compared with group B, the protein expressions of MEK1/2 and ERK1/2 in group C and D were significantly higher (allP<0.01). Compared with group C, the protein expressions of MEK1/2 and ERK1/2 in group D were significantly higher (P<0.01). Conclusion: Herbal cake-partitioned moxibustion promotes the repair of gastric mucosa in rats with spleen deficiency syndrome, via improving protein expressions of MEK1/2 and ERK1/2 in gastric tissues, as well as activating MEK/ERK signaling pathway.