Preparation of Cellulose Nanofibers from Corn Stalks by Fenton Reaction: A New Insight into the Mechanism by an Experimental and Theoretical Study.

Agricultural biomass wastes are an abundant feedstock for biorefineries. However, most of these wastes are not treated in the right way. Here, corn stalks (CSs) were assigned as the raw material to produce cellulose nanofibers (CNFs) via in situ Fenton oxidation treatment. In order to probe the formation mechanism of an in situ Fenton reactor, the bonding interaction of hydrated Fe2+ ions and fiber has been systemically studied based on adsorption experiments, IR spectroscopy, density functional theory (DFT) calculations, and Raman spectroscopy. The results indicate that the coordination of the hydrated Fe2+ ion to the fiber generates a quasi-octahedral-coordinated sphere around the Fe center. The Jahn-Teller distortion effect of the Fe center promotes the Fe-O2H2 bonding interaction via reduction of the energy gap of the dz2 orbital of the Fe center and π2py/π2pz orbitals of the H2O2 molecule. The oxidation treatment of the pretreated CS by the in situ Fenton process shows the formation of a new carboxyl group on the fiber surface. The scanning electron microscopy image shows that the Fenton-treated fiber was scattered into the nanosized CNFs with a diameter of up to 50 nm. Both experimental and theoretical studies show that the pseudo-first-order kinetic reaction could describe the in situ Fenton kinetics well. Moreover, the proposed catalytic cycle shows that the large thermodynamic barrier is the cleavage of the O-O bond of H2O2 to generate the •OH radical, and the whole catalytic cycle is found to be spontaneous at room temperature.

Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).@*METHODS@#In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.@*RESULTS@#In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05).@*CONCLUSION@#ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

Construction of virtual simulation platform for PICC catheterization and evaluation of clinical training application / 中华医学教育探索杂志

Objective:To construct a virtual simulation training platform for peripheral inserted central catheter (PICC) catheterization and discuss its application in clinical training.Methods:A total of 118 nurses who attended the PICC professional and technical advanced training courses in a province in 2020 and 2021 were enrolled in this study. In 2020, the training was conducted in the form of theoretical teaching combined with practical training ( n=51), and in 2021, virtual simulation platform was introduced as a supplement on the basis of the original training ( n=67). SPSS 23.0 was used for independent-samples t-test to compare the theoretical and operational assessment results of the two years and evaluate the application effect of the platform. Through the satisfaction survey and learning log, the nurses' experience of using the platform was understood. Results:The theoretical performance and the operational performance of nurses who participated in the training in 2021 were (96.56±3.17) and (94.06±2.16) respectively, and the operational performance was better than that of nurses who participated in the training in 2020 ( t=-11.37, P<0.001), and the difference in theoretical performance was not statistically significant ( t=0.17, P=0.853). In 2021, 63 nurses (94.0%) who used the virtual simulation platform believed that the platform could assist to improve the training effect; 61 nurses (91.0%) expected the application of virtual simulation technology in the teaching and training of other knowledges. Conclusion:As a new teaching form, virtual simulation technology can significantly improve the training effect and satisfaction, and provide reference for the development of relevant teaching and training.

Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome / 中华儿科杂志

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Curative effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum β-EP level in puerpera / 中国针灸

OBJECTIVES@#To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (β-EP) level in puerpera.@*METHODS@#Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum β-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups.@*RESULTS@#At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), β-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the β-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05).@*CONCLUSIONS@#Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum β-EP level and the increase of pain threshold so that analgesia is obtained.

T cell immunotherapy mediated by dual-affinity aptamer targeted liposome / 药学学报

Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.

Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer.

Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

Characterization of degradation behaviors of PLA biodegradable plastics by infrared spectroscopy.

In this paper, the degradation behavior of two kinds of polylactic acid (PLA) biodegradable material products (pure PLA cup cover and modified PLA straw) was studied. It was found that under the composting environment specified in the International Standard, in the first 35 days, the degradation rate of the straw (with 50%-60% poly butylenes succinate (PBS)) was faster than that of the pure PLA cup cover, but in the later stage, the PLA cup cover exceeded the straw and disintegrated preferentially, and both could be degraded in about 70 days. After further analyzing the far-infrared (FIR, can also be called THz) and mid infrared (MIR) spectra of cup cover and straw, we observed that the material structure had not changed until disintegration, only the ester bond was hydrolyzed, the polymers became oligomers, which could be reflected in the change of the effective area of the characteristic peak at 7.15 THz (cup cover, labeled 1921) and 6.99 THz (straw, labeled 4386) in the THz spectrum. With the degradation, the effective area decreased continuously. Due to the strong absorption of the material in MIR band, most characteristic peaks were flattened and lost analytical value. The bivariate correlation of degradation time, biodegradation rate, total carbon dioxide release and the effective area of the characteristic peak at 7.15 THz (1921) and 6.99 THz (4386) in THz spectrum was analyzed by SPSS software. We discovered that the degradation time was significantly positively correlated with biodegradation rate and carbon dioxide release at the level of 0.01 and negatively correlated with the effective area of characteristic peak at the level of 0.05. The biodegradation rate was significantly negatively correlated with the effective area of characteristic peak at the level of 0.01. Taking the degradation time as the independent variable and the biodegradation rate, carbon dioxide release and effective area of characteristic peak as the dependent variables, we got that the THz spectrum could be used to describe the degradation behavior of PLA products as long as appropriate coefficient correction was made. In this way, we could separate from the laboratory environment, study the impact of environmental diversification on material degradation performance, and reduce the cost of material degradation performance identification. Using density functional theory (DFT), reduced density gradient (RDG) method and visualization software, the changes of weak interaction position and intensity in the molecule during the polymerization of lactic acid into PLA were further analyzed. We found that the vibration of ester bond corresponded to the characteristic peak with weak intensity in the spectrum, and the peak with large intensity mainly originated from the out-of-plane swing of O-H bond in the molecule.

Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing / 中华儿科杂志

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.

Replacement Therapy for Hemophilia Patients Undergoing Cardiac Surgery: Report of Three Cases / 中国医学科学杂志(英文版)

Hemophilia is an X-linked recessive inherited bleeding disorder. Despite the improved treatment in recent years with the advent of replacement therapies, the progression of atherosclerosis is not slowed down after the reduction of clotting factors in hemophilia. As life expectancy increases, more hemophilia patients will suffer from age-related cardiovascular diseases. Since cardiac surgery needs heparinization and cardiopulmonary bypass (CPB), it is extremely challenging to balance hemostasis and coagulation in patients with hemophilia. Here we report three cases of hemophilia patients who underwent cardiac surgery successfully.

Evolution and correlation of CT imaging signs and clinical features of non-severe COVID-19 patients / 西安交通大学学报(医学版)

【Objective】 To evaluate the evolution and correlation of CT imaging signs and clinical features of non-severe coronavirus disease 2019 (COVID-19). 【Methods】 We retrospectively analyzed CT images and clinical features of 24 non-severe COVID-19 patients from the onset at a 5-day interval. We recorded CT image signs, clinical manifestations and laboratory results at each stage, and analyzed their dynamic changes and correlations. Categorical variables were presented by rates. The correlation of the total CT score and the total number of lesions with clinical manifestations was analyzed. P20 days. The main CT signs of COVID-19 patients were subpleural and ground-glass opacity; the accompanying CT signs included paving stone sign, thickened blood vessels, fibrous cord shadow, air bronchial sign, leaflet center nodule, halo sign, reversed halo sign, bronchial wall thickening, and lung volume shrinking. On days 0-5, the number of lesions was the largest, acute symptoms were the most severe, the lymphocyte count and ratio were the lowest, and the concentration of high-sensitivity C-reactive protein (H-sCRP) was the highest. On days 5-10, the total CT score, the concentration of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were the highest, and the white blood cell count was the lowest. There were a positive correlation between the CT score and the number of lesions with temperature, ESR, CRP, H-sCRP, and negative correlation with WBC count. 【Conclusion】 CT imaging signs were similar to the change of the clinical features on days 0-10. The total CT score and the number of lesions had correlation with the clinical manifestations.

Effect of Jiedu Limai decoction in septic patients with syndrome of heat-toxin exuberance / 中华危重病急救医学

Objective:To investigate the clinical effect of Jiedu Limai decoction in septic patients with syndrome of heat-toxin exuberance.Methods:A prospective randomized controlled trial was conducted. From March 2019 to April 2020, septic patients with syndrome of heat-toxin exuberance admitted to intensive care unit (ICU) of Shanghai General Hospital and Songjiang Branch of Shanghai General Hospital were enrolled as the research objects, and they were divided into routine treatment group and Jiedu Limai decoction group by the random number table method. Patients in both groups were given standard treatment in accordance with the guidelines, and patients in the Jiedu Limai decoction group were given Jiedu Limai decoction in addition to the standard treatment, once a day for 14 days. The 28-day survival of patients of the two groups were recorded, the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, coagulation indexes, infection indexes, inflammatory cytokines and organ function indicators before treatment and 7 days after treatment in both groups were recorded, and the prognosis of the two groups were recorded.Results:A total of 259 patients with infection or clinical diagnosis of infection admitted during the experimental observation period were included, and those who did not meet the Sepsis-3 diagnostic criteria, more than 80 years old or less than 18 years old, with multiple tumor metastases, autoimmune system diseases, with length of ICU stay less than 24 hours, with acute active gastrointestinal bleeding and with incomplete data were excluded. One hundred patients were finally enrolled, with 50 patients in the routine treatment group and 50 patients in the Jiedu Limai decoction group. There were no statistically significant differences in coagulation indexes, infection indicators, inflammatory cytokines and organ function indicators before treatment between the two groups. After 7 days of treatment, the coagulation indexes, infection biomarkers and inflammatory cytokines in the Jiedu Limai decoction group were significantly lower than those in the routine treatment group [D-dimer (mg/L): 2.2 (1.8, 8.5) vs. 4.0 (1.5, 8.7), fibrinogen (Fib, g/L): 3.7 (3.4, 4.3) vs. 4.2 (3.7, 4.3), fibrinogen degradation product (FDP, mg/L): 7.2 (5.4, 10.2) vs. 13.2 (9.2, 15.2), procalcitonin (PCT, μg/L): 0.4 (0.2, 2.9) vs. 0.5 (0.2, 0.9), C-reactive protein (CRP, mg/L): 50.1 (9.5, 116.0) vs. 75.1 (23.5, 115.2), interleukin-6 (IL-6, ng/L): 31.6 (21.6, 81.0) vs. 44.1 (14.0, 71.3), all P < 0.05], and the levels of B-type brain natriuretic peptide (BNP) and kidney injury molecule-1 (KIM-1) were significantly lowered [BNP (ng/L): 261.1 (87.5, 360.3) vs. 347.3 (128.8, 439.4), KIM-1 (μg/L): 0.86 (0.01, 1.40) vs. 1.24 (1.05, 1.57), both P < 0.05]. Compared with the routine treatment group, the number of new organ failure in the Jiedu Limai decoction group was decreased (30.0% vs. 50.0%, P < 0.05). Although there was no significant difference in 28-day mortality between the two groups ( P > 0.05), the 28-day mortality in the Jiedu Limai decoction group was lower than that in the routine treatment group (18.0% vs. 24.0%). Conclusion:Combining Jiedu Limai decoction to the sepsis guideline in treating syndrome of heat-toxin exuberance can effectively improve patients' coagulation function, the situation of heart and renal injury, reduce the level of inflammatory cytokines, and fewer people develop new organ failure after treatment.

The status of nursing information ability and its relationships with information consciousness and information anxiety in intern nursing students / 中国实用护理杂志

Objective:To explore the status of nursing information ability and its relationships with information consciousness, information anxiety in intern nursing students, provide basis for the cultivation of nursing information ability of intern nursing students.Methods:From December 2019 to January 2020,185 nursing students working as interns in Jinan Central Hospital Affiliated to Shandong University were surveyed by general information questionnaire, information anxiety questionnaire, information consciousness questionnaire and nursing information ability assessment scale.Results:The total score of nursing information ability of nursing students in practice was 111.6±19.7; nursing information ability was positively correlated with information consciousness ( r=0.358, P<0.001), and not related to information anxiety ( r=0.136, P=0.065); information consciousness had a predictive effect on nursing information ability( β=0.287, P<0.001), and information anxiety could moderate the relationship between information consciousness and nursing information ability ( β=0.175, P=0.011). Conclusions:The score of nursing information ability is above the medium level, while improving the nursing information ability through the development of information consciousness, and the information anxiety level of nursing students should also be paid attention to.

SOCS1 Regulates the Immunomodulatory Roles of MSCs on B Cells.

BACKGROUND AND OBJECTIVES: The effective use of MSCs for the treatment of some B cell-mediated immune diseases is quite limited. The main reason is that the immunomodulatory effects of mesenchymal stem cells (MSCs) on B cells are unclear, and their underlying mechanisms have not been fully explored. METHODS AND RESULTS: By co-culturing B cells with MSCs without (MSC/CTLsh) or with suppressor of cytokine signaling 1 (SOCS1) knockdown (MSC/SOCS1sh), we found that MSCs inhibited B cell proliferation, activation and terminal differentiation. Remarkably, the highest inhibition of B cell proliferation was observed in MSC/SOCS1sh co-culture. Besides, MSC/SOCS1sh reversed the inhibitory effect of MSCs in the last stage of B cell differentiation. However, MSC/SOCS1sh had no effect on inhibiting B cell activation by MSCs. We also showed that IgA+ B cell production was significantly higher in MSC/SOCS1sh than in MSC/CTLsh, although no difference was observed when both MSCs co-cultures were compared to isolated B cells. In addition, MSCs increased PGE2 production after TNF-α/IFN-γ stimulation, with the highest increase observed in MSC/SOCS1sh co-culture. CONCLUSIONS: Our results highlighted the role of SOCS1 as an important new mediator in the regulation of B cell function by MSCs. Therefore, these data may help to develop new treatments for B cell-mediated immune diseases.

Factors associated with prolonged viral shedding and impact of Lopinavir/Ritonavir treatment in patients with SARS-CoV-2 infection

BackgroundThe duration of viral shedding is central to guide decisions around isolation precautions and antiviral treatment. However, studies about risk factors associated with prolonged SARS-CoV-2 shedding and the potential impact of Lopinavir/Ritonavir (LPV/r) treatment remain scarce. MethodsIn this retrospective study, data were collected from all SARS-CoV-2 infected patients who were admitted to isolation wards and had RT-PCR conversion at the NO.3 Peoples hospital of Hubei province between 31 January and 09 March 2020. We compared clinical features and SARS-CoV-2 RNA shedding between patients with LPV/r treatment and those without. Logistic regression analysis was employed to evaluate risk factors associated with prolonged viral shedding. ResultsOf 120 patients, the median age was 52 years, 54 (45%) were male and 78 (65%) received LPV/r treatment. The median duration of SARS-CoV-2 RNA detection from symptom onset was 23 days (IQR, 18-32 days). Older age (odd ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05, p=0.03) and lack of LPV/r treatment (OR 2.42, 95% CI 1.10-5.36, p=0.029) were independent risk factors for prolonged SARS-CoV-2 RNA shedding in multivariate logistic regression analysis. The median duration of viral shedding was shorter in the LPV/r treatment group (n=78) than that in no LPV/r treatment group (n=42) (median, 22 days vs. 28.5 days, p=0.02). Only earlier administration of LPV/r treatment ([≤]10 days from symptom onset) could shorten the duration of viral shedding. ConclusionsOlder age and lack of LPV/r treatment were independently associated with prolonged SARS-CoV-2 RNA shedding in patients with COVID-19. Earlier administration of LPV/r treatment could shorten viral shedding. Take home messageRisk factors for prolonged SARS-CoV-2 shedding included older age and lack of Lopinavir/Ritonavir treatment. Earlier administration of Lopinavir/Ritonavir treatment could shorten the duration of SARS-CoV-2 RNA shedding.

Effect of Polyethylene Glycol 400 on Bile Excretion of Baicalin and Its Main Metabolite / 中国实验方剂学杂志

Objective::To investigate the effect of polyethylene glycol 400 (PEG400) on rat bile excretion of baicalin and its main metabolite [baicalein 6-O-β-D-glucuronide (B6G)], and to analyze its mechanism of action. Method::Rats were randomly divided into baicalin+ water group and baicalin+ PEG400 group, the anesthesia was induced by intraperitoneal injection of 10% chloral hydrate (dose of 4 mL·kg-1) to prepare a rat bile duct intubation model. After the rats were fully awake, rats were given baicalin aqueous solution and baicalin PEG400 solution with dose of 168 mg·kg-1 for baicalin, respectively. And bile was collected from 0 h to 12 h after administration. UPLC-MS/MS was used to determine the concentration of drug excreted through bile at different time periods. Thermo Hypersil GOLD C18 column was used with acetonitrile (A)-0.1% formic acid solution (B) as the mobile phase for gradient elution (0-9 min, 90%-27%B; 9-10 min, 27%-90%B; 10-12 min, 90%B), the flow rate was 0.3 mL·min-1, the column temperature was 30 ℃, the injection volume was 5 μL. The mass spectra were obtained in positive ion mode with electrospray ionization (ESI). The effects of PEG400 on the activities and expressions in rat liver of uridine diphosphate glucuronyltransferase (UGT) 1A8 and UGT1A9 were studied in vitro incubation assay and enzyme linked immunosorbent assay (ELISA). Result::Compared with the baicalin+ water group, in the baicalin+ PEG400 group, the bile cumulative excretions of baicalin and B6G increased by 1.8 times and 2.1 times within 12 h, respectively. PEG400 increased the enzyme activities of UGT1A8 and UGT1A9 by 2.0 times and 1.5 times, and their concentrations in liver were increased by 2.2 times and 1.3 times, respectively. Conclusion::PEG400 can significantly increase the bile excretion of baicalin and its main metabolite B6G by enhancing the activities and expressions of UGT1A8 and UGT1A9, and its promoting effect on bile excretion of B6G is greater than that of baicalin, which provides a basis for the rational clinical application of PEG400 and the design of new dosage forms of flavonoids such as baicalin.

SOCS1 Regulates the Immunomodulatory Roles of MSCs on B Cells

Background and Objectives@#The effective use of MSCs for the treatment of some B cell-mediated immune diseases is quite limited. The main reason is that the immunomodulatory effects of mesenchymal stem cells (MSCs) on B cells are unclear, and their underlying mechanisms have not been fully explored. @*Methods@#and Results: By co-culturing B cells with MSCs without (MSC/CTLsh) or with suppressor of cytokine signaling 1 (SOCS1) knockdown (MSC/SOCS1sh), we found that MSCs inhibited B cell proliferation, activation and terminal differentiation. Remarkably, the highest inhibition of B cell proliferation was observed in MSC/SOCS1sh co-culture. Besides, MSC/SOCS1sh reversed the inhibitory effect of MSCs in the last stage of B cell differentiation. However, MSC/SOCS1sh had no effect on inhibiting B cell activation by MSCs. We also showed that IgA+ B cell production was significantly higher in MSC/SOCS1sh than in MSC/CTLsh, although no difference was observed when both MSCs co-cultures were compared to isolated B cells. In addition, MSCs increased PGE2 production after TNF-α/IFN-γ stimulation, with the highest increase observed in MSC/SOCS1sh co-culture. @*Conclusions@#Our results highlighted the role of SOCS1 as an important new mediator in the regulation of B cell function by MSCs. Therefore, these data may help to develop new treatments for B cell-mediated immune diseases.

Progress in the encoding characteristics and mechanisms of hippocampal neural assemble sequences in spatial memory / 生理学报

The formation, consolidation and retrieval of spatial memory depend on sequential firing patterns of place cells assembling in the hippocampus. Theta sequences of place cells during behavior play a role in acquisition of spatial memory, trajectory prediction and decision making. In awake rest and slow wave sleep, place cell sequences occur during the sharp wave-ripples (SWRs), called "replay", which is crucial for memory consolidation and retrieval. In this review, we summarize the functional significances of theta sequences and SWRs replay sequences and the mechanism of these sequences. We also discuss the relationship between theta and replay sequences with the formation of spatial memory. We propose the research direction in this field in future and aim to provide new ideas for related researches.

Mitsugumin 53 promotes mitochondrial autophagy through regulating Ambra1 expression in C2C12 myoblast cells.

In this study, we investigated the function of Mitsugumin 53 (MG53) in regulation of mitochondrial autophagy in skeletal muscle cells and explored its potential application in the prevention and treatment of skeletal muscle atrophy in rats with chronic kidney disease (CKD). The expression of autophagy beclin 1 regulator 1 (Ambra1) and MG53 in skeletal muscles of 5/6 nephrectomized rats was measured, and the effect of MG53 on mitochondrial autophagy of C2C12 myoblasts was investigated by in vitro experiments. Our results show the expression of Ambra1 and MG53 in the skeletal muscle of CKD rats was significantly decreased. In vitro experiments showed that MG53 overexpression could promote the expression of Ambra1 and mitochondrial autophagy in C2C12 cells, suggesting that recovery of autophagy by MG53 intervention may help remove abnormal mitochondria and alleviate muscle atrophy. In conclusion, the damaged or functionally incomplete mitochondria in CKD rats could not be effectively removed, which may be related to the low activity of Ambra1. In vitro experiments showed that MG53 overexpression could promote the expression of Ambra1 in C2C12 cells and restore mitochondrial autophagy. Whether MG53 can help remove abnormal mitochondria and relieve CKD-induced muscle atrophy requires further study.

Study on interventional treatment of Budd-Chiari syndrome in rat models / 中华肝胆外科杂志

Objective To explore the feasibility of interventional therapy in rat models of Budd-Chiari syndrome (BCS).Methods A total of 50 male clean SD rats were divided into model group and control group using random number table method,with 25 rats in each group.In the model group,BCS rat model was constructed by adopting partial ligation of the inferior vena cava (IVC),and the control group only had separation of surrounding tissues of IVC.Liver function was studied 12 weeks after postoperative raising,and digital subtraction angiography (DSA) and interventional therapy were performed,coupled with liver histopathology staining.Results Twenty BCS rats survived till the 12th week of raising,with the survival rate reaching 80.0％,and 22 survived in the control group.Compared with the control group,ALT [(43.1±5.5) U/L vs.(62.6±4.6) U/L] and AST [(84.7±26.5) U/L vs.(161.7±25.8) U/L)] in serum of rats in the model group increased,the differences were statistically significant (P＜0.05).HE staining showed that obvious hepatocyte necrosis and inflammatory cell infiltration were observed in BCS rats,and liver fibrosis was spotted via Masson staining.DSA examination found IVC obstruction in the model group,among which 14 (70.0％,14/20) received interventional therapy after successful probing of IVC obstructed segment,and 7 had balloon dilatation with a diameter of 3.5 mm,with 6 (85.7％,6/7) successfully dilatatedand the other 1 (14.3％,1/7) failed;the remaining 7 had balloon dilatation with a diameter of 4.5 mm,with 2 (28.6％,2/7) successfully dilatated,and the other 5 (71.4％,5/7) died of IVC rupture.Conclusion The BCS rat models by partial ligation of IVC can well simulate the pathophysiological changes and angiopathy characteristics of IVC obstructive BCS patients,which provide a platform for the basic research of interventional therapy of BCS.