Advances in clinical and safety studies of phosphodiesterase 4 inhibitors / 药学学报

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Antibody prevalence and immunotherapy response in Chinese patients with epilepsy and encephalopathy scores for patients with different neuronal surface antibodies / 中华医学杂志(英文版)

BACKGROUND@#The scale assessment was helpful in predicting the presence of antibodies to autoimmune encephalitis. This study aimed to evaluate the application of antibody prevalence in Chinese patients with epilepsy and encephalopathy (APE2-CHN) and response to immunotherapy in Chinese patients with epilepsy and encephalopathy (RITE2-CHN) for patients with different neuronal surface antibodies.@*METHODS@#A total of 1365 patients with epileptic seizures as the prominent feature in Xuanwu Hospital, Capital Medical University, from June 2016 to June 2020 were enrolled in our study. Of these, 915 patients with epilepsy of unknown etiology whose serum and/or cerebrospinal fluid samples were examined for autoimmune antibodies were selected. All patients were scored with antibody prevalence in patients with epilepsy and encephalopathy (APE2), response to immunotherapy with epilepsy and encephalopathy (RITE2), APE2-CHN, and RITE2-CHN scores.@*RESULTS@#Of the 915 patients, 191 patients were positive for neural-surface specific antibodies (115 N-methyl-D-aspartate receptor (NMDAR) Ab, 47 leucine-rich glioma-inactivated protein 1 (LGI1) Ab, 8 contactin-associated protein 2 (CASPR2) Ab, 4 AMPA2R-Ab, and 11 GABAR-B-Ab; 3 CASPR2-Ab and LGI1-Ab, 2 NMDAR-Ab and CASPR2-Ab, and 1 NMDAR-Ab and myelin-oligodendrocyte glycoprotein [MOG] Ab). The sensitivity and specificity of APE2 ≥4 in predicting the presence of neural-surface specific antibodies in our study were 74.35% and 81.77%, respectively, and the sensitivity and specificity of APE2-CHN ≥4 were 75.92% and 84.53%, respectively. Eight cases had an APE2 score <4 and APE2-CHN score ≥5; all these patients had memory decline as the prominent manifestation. We divided the patients into six groups according to the different antibodies. APE2-CHN scores showed higher sensitivity for the prediction of NMDAR-Ab, but lower sensitivity for LGI1-Ab. A total of 187/191 (97.91%) patients received immunotherapy and 142/191 (74.35%) patients benefited from the treatments. The patients who were positive for LGI1-Ab with RITE2-CHN ≥8 responded well to immunotherapy.@*CONCLUSIONS@#APE2-CHN had the highest value for predicting the positivity of NMDAR-Ab and RITE2-CHN evaluated the response of immunotherapy for anti-LGI1 encephalitis appropriately. However, RITE2 and RITE2-CHN do not appear to be good predictors of immunotherapy outcomes for patients with specific neuronal-surface antibodies and high APE2-CHN scores are often indicative of a poor response to immunotherapy.

P38 Inhibition Prevents Herpes Simplex Virus Type 1 (HSV-1) Infection in Cultured Corneal Keratocytes.

Purpose: To evaluate keratocyte viability and proinflammatory cytokine secretion induced by HSV-1 infection. Methods: Keratocytes were separated from corneal tissues obtained with the SMILE procedure, and an in vitro system was established to study HSV-1 infection in human keratocytes. Cell viability, HSV-1 genomic DNA copy number, and the expression levels of α-SMA, ALDH1A1, phospho-p38, p38, phospho-IRF3, and IRF3 were evaluated. Antibody array and ELISA kits were used to measure the production of proinflammatory cytokines and chemokines. Results: We found that HSV-1 infection reduced cell viability and activated keratocyte transdifferentiation into corneal fibroblast-like cells. Furthermore, p38 inhibition improved cell viability and IFN-ß production and played an anti-inflammatory role by reducing the production of proinflammatory cytokines and chemokines. Conclusions: Our study reveals an important role played by keratocytes during innate immune responses and identifies p38 inhibition as a potential therapeutic approach to control ocular HSV-1 infection.

Performance of Posture Control for Professional Dancers / 中国康复理论与实践

Objective:To explore the posture control of professional dancers. Methods:From April to August, 2017, 21 professional dancers from an international famous club were as experimental group. Matching the height and age, etc., 21 medical workers were recruited as control group. They were tested with Tetrax Balance Evaluation System, and assessed with Trunk Stability Test (TST) and the Star Excursion Balance Test (SEBT). Results:There was no significant difference on fail-time of TST and maximum distance of SEBT between right and left sides in both groups. The fail-time of TST was less in the experimental group than in the control group (t =-2.667, P < 0.05), as well as the maximum distance of SEBT (t = -3.991, P < 0.001). There was no significant difference on falling index between both groups (t = 1.810, P > 0.05). Conclusion:Compared with medical workers, professional dancers do better in static balance, but worse in dynamic balance. Their performance of posture control is almost the same as the others.

Application of Single-breath Counting in Assessment of Pulmonary Function after Spinal Cord Injury / 中国康复理论与实践

Objective:To investigate the correlation between single-breath counting (SBC) and standard measures of pulmonary function in patients with spinal cord injury, to evaluate the value for predicting pulmonary function. Methods:Forty-two patients (24 with cervical injury and 18 with thoracic injury) were selected from October, 2018 to February, 2019 in outpatients and inpatients. SBC and standard laboratory spirometer tests were performed separately. The correlation of the outcome of SBC and lung function indicators including forced vital capacity (FVC), forced respiratory capacity in the first second (FEV1), FEV1/FVC, slow expiratory vital capacity (EVC) and all the predicted values on the percentage (%pred) were analyzed. A receiver operating characteristic (ROC) curve was constructed according to the lung function classification criteria. Results:The outcome of SBS was correlated with FVC, EVC as well as the percentage of predicted values (r = 0.723 to 0.760, P < 0.01 for the whole patients; r = 0.549 to 0.657, P < 0.01 for cervical ones; r = 0.623 to 0.847, P < 0.01 for thoracic ones), and was also correlated with FEV1 as well as the percentage of predicted values (r = 0.622 to 0.760, P < 0.01 for whole patients and cervical ones). The area under the ROC curve was 0.864 to 0.941. Conclusion:There is a good correlation between SBC and standard lung function for patients with spinal cord injury, suggesting an assistive diagnostic value for patients with reduced lung function.

Test-retest Reliability of Lumbar Spine Position Sense for Aging People / 中国康复理论与实践

Objective:To determine the test-retest reliability of lumbar passive reposition accuracy for older people. Methods:A total of 58 healthy older people stood on an isokinetic dynamometer, and passively moved their trunk forward and backward to the target positions as accurately as possible. The targeted positions were set as flexion forward 15°, 30° and 60°, and flexion backward 15°. The absolute error (AE) was recorded. They were tested again a week latter. The intraclass correlation coefficient (ICC) and standard errors of measurement (SEM and SEM%) were calculated. Results:The ICC of AE was 0.699 to 0.833 for all the subjects, SEM was 1.18 to 3.26, and SEM% was 26.84% to 37.13%. For the men, the ICC was 0.462 to 0.818, SEM was 1.60 to 3.68, and SEM% was 36.37% to 48.78%. For the women, the ICC was 0.782 to 0.891, SEM was 1.48 to 2.71, and SEM% was 28.48% to 33.34%. Conclusions:Lumbar passive reposition accuracy is some reliable to assess the position sense for older people. However, there are too large errors for clinical measurement, which need further improvment.

Effects of Early Rehabilitation on Expectation and Perception for Inpatients with Work Injury / 中国康复理论与实践

Objective:To compare the expectation and perception of rehabilitation services for patients with work injury with or without early intervention. Methods:From August, 2017 to February, 2018, 350 inpatients with work injury accepted early intervention and non-early intervention were investigated with the modified ServQual scale. Results:There was no significant difference in the expectation between the inpatients accepted early intervention and non-early intervention (t < 1.904, P > 0.05). In both groups, expectation was the highest in assurance and responsiveness dimension, and the lowest in reliability dimension. The perception was higher in the early intervention group than in the non-early intervention group. In both groups, perception was the highest in tangibility, and the lowest in empathy. Conclusion:Early intervention of rehabilitation may improve the perception of services.

Effect of Comprehensive Pulmonary Exercise on Respiratory Function of Patients Suffered from Cervical Spinal Cord Injury / 中国康复理论与实践

Objective To observe the short-term effect of comprehensive pulmonary exercise on the impaired respiratory function of convalescence patients suffered from cervical spinal cord injury. Methods From November, 2011 to December, 2016, 100 patients with cervical spinal cord injury (C3-C6,ASIA A-D) were randomly divided into control group(n=50)and observation group(n=50).The control group received rou-tine rehabilitation training,and the observation group added comprehensive pulmonary exercise.They were ex-amined with forced vital capacity(FVC),forced expiratory volume in first second(FEV1),maximum expiratory flow rate with remaining 25% vital capacity (MEF25%) and maximum ventilation volume (MVV) before and two months after intervention. Results The FVC,FEV1,MEF25% and MVV improved significantly in the observation group(t>4.110,P<0.001),and the D-value was more in the observation group than in the control group before and after intervention(t>4.390, P<0.001). Conclusion Comprehensive pulmonary exercise has short-term effect on pulmonary function in convalescent patients survived from cervical spinal cord injury.

Effects of Baltimore Therapeutic Equipment on Traumatic Upper Extremity Injury from Work / 中国康复理论与实践

Objective To apply the Baltimore Therapeutic Equipment (BTE), a kind of vocational training and evaluation system, in rehabilitaion of patients post traumatic upper extremity injury from work, and to observe the effects. Methods Inpatients from September, 2014 to August, 2015 for rehabilitation of traumatic upper extremity injury from work were selected as control group (n=42), and inpatients from September, 2015 to August, 2016 were selected as intervention group (n=36). Both groups received routine rehabilitation, while the control group received con-ventional work simulation training, and the intervention group received work simulation training with BTE, for four weeks. They were measured the standing lifting strength (elbow), squatting lifting strength, dynamic lifting strength (floor to waist), dynamic lifting strength (floor to shoulder), and grip strength of the injured hand and the healthy hand with BTE, before and after rehabilitation; while they were assessed with Disability of Arm Shoul-der and Hand (DASH). The incidence of return to work was investigated at six months of follow-up. Results The standing lifting strength (elbow) (t=4.290, P<0.001), squatting lifting strength (t=2.645, P=0.010), dynamic lifting strength (floor to waist) (t=2.639, P=0.010), dynamic lifting strength (floor to shoulder) (t=5.361, P<0.001), and grip strength of the injured hand (t=2.320, P=0.023) and the healthy hand (t=3.130, P=0.002) im-proved better in the intervention group than in the control group after rehabilitation. However, there was no sig-nificant difference between two groups in score of DASH (t=-0.851, P=0.398), as well as incidence of return to work (χ2=0.05, P=0.944). Conclusion BTE may help to improve the body function in patients post traumatic upper extremity injury from work. However, vocational rehabilitation should focus on the factors other than body function, to improve their return to work.

Heparin-derived oligosaccharide inhibits vascular intimal hyperplasia in balloon-injured carotid artery / 中国天然药物

The aims of the present study were to determine the effects of heparin-derived oligosaccharides (HDOs) on vascular intimal hyperplasia (IH) in balloon-injured carotid artery and to elucidate the underlying mechanisms of action. An animal model was established by rubbing the endothelia within the common carotid artery (CCA) in male rabbits. The rabbits were fed a high-cholesterol diet. Arterial IH was determined by histopathological changes to the CCA. Serum lipids were detected using an automated biochemical analysis. Expressions of mRNAs for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), scavenger receptor class B type I (SR-BI), and ATP-binding cassette transporter A1 (ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were analyzed by Western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and bFGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the mRNA and protein expression levels of VEGF, bFGF, VCAM-1, MCP-1, and SR-BI in the arterial wall; however, ABCA-1 expression level was elevated. HDO treatment led to a reduction in serum lipids (total cholesterol, triglycerides, high-density and low-density lipoproteins). Our results from the rabbit model indicated that HDOs could ameliorate IH and underlying mechanism might involve VEGF, bFGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.

Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected.</p><p><b>METHODS</b>A clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography (EMG), serum creatine kinase (CK), bone X-rays, and brain magnetic resonance imaging (MRI) were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out.</p><p><b>RESULTS</b>Disease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found.</p><p><b>CONCLUSIONS</b>We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study.</p>

Effects of Kinesio Taping on Muscle Strength of Knees in Female Students / 中国康复理论与实践

@#Objective To investigate the effects of Kinesio taping on function of knees in girls. Methods 20 female students were tested the peak torque of centripedal and eccentric contraction of knee flexion and extension with Biodex isokinetic testing at 60°/s angular velocity, with Kinesio taping, placebo taping and without taping. Their amplitude root of mean square (RMS) of surface electromyography of vastus medialis (VM), rectus femoris (RM) and vastus lateralis (VL) were also recorded. Results For centripedal isokinetic contraction, the relative extensors peak torque was the most as Kinesio taping (P<0.01). There was no significant difference in relative flexor peak torque (P> 0.05). Standardized RMS of VM and VL were the least as Kinesio taping (P<0.01), but not significantly different of RF among all the conditions (P>0.05). For eccentric isokinetic contraction, the relative extensor peak torque of both extensors and flexors were the most as Kinesio taping (P<0.01), while the Standardized RMS of VM and VL were the least (P<0.01), but no significant difference was observed in RF (P> 0.05). Conclusion Kinesio taping may enhance the strength of centripedal, eccentric contractions of quadriceps and eccentric contractions of hamstring, and increase the muscle fibers recruitment of VM and VL.

The mechanisms of heparin-derived oligosaccharide on the inhibition of smooth muscle cells proliferation induced by platelet-derived growth factor / 药学学报

In this study, the effect of heparin-derived oligosaccharide (HDO) on platelet-derived growth factor (PDGF) induced vascular smooth muscle cells (VSMCs) proliferation and the related signal transduction mechanisms were investigated. MTT assays were used to measure VSMCs proliferation. Cell cycle distribution was analyzed by flow cytometry. The level of key regulatory proteins in PKC, MAPK and Akt/PI3K pathways were determined by RT-PCR, Western blot and immunocytochemical methods. Meanwhile, mRNA expressions of some proto-oncogenes were assayed by RT-PCR method. Our data showed that HDO (0.01, 0.1 and 1 μmol · L(-1)) inhibited 30 ng · mL(-1) PDGF-induced VSMCs proliferation in a dose-dependent manner, blocked the G1/S transition and inhibited the level of key regulatory proteins and some proto-oncogenes (P < 0.05). The results showed that HDO may decrease the key regulatory proteins expression, hence suppress the transcription of proto-oncogene and G1/S transition, finally inhibiting VSMCs proliferation.

Relief of urinary retention after radical hysterectomy for cervical cancer patients by acupressure: a randomized controlled trial / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study whether acupressure could relieve urinary retention after radical hysterectomy in cervical cancer patients.</p><p><b>METHODS</b>A randomized controlled prospective double-blinded trial was carried out in 107 urinary retention patients undergoing grade III radical hysterectomy. They were assigned to Group A (positive acupoints, 40 cases), Group B (negative acupoints, 32 cases) , and Group C (with no acupoints, 35 cases). All patients received protective 115 000 potassium permanganate sitz bath, 15 - 20 min each time, 3 times per day. Patients in Group A received acupressure at positive points [liniao point and Qihai (RN6)] combined points by syndrome typing [Guanyuan (RN4) , Zhongji (RN3) , Shenshu (BL23) , Zusanli (ST36), Sanyinjiao (SP6), and Taixi (K13)]. Patients in Group B received negative acupressure at sham-acupoints (for adjusting gastrointestinal functions). Patients in Group C only received conventional sitz bath. All medication was performed 3 times per day, 7 days as one therapeutic course, 21 days in total. The residual urine volume was detected. The recovery time for bladder function was recorded. The average residual urine volume was also recorded at day 7, 14, and 21.</p><p><b>RESULTS</b>Compared with Group B and C, the time for ureter retention was shortened for mild and severe CKD patients in Group A (P <0. 01). The residual urine volume was also lessened for mild and severe CKD patients in Group A at day 7, 14, and 21 (P <0.01).</p><p><b>CONCLUSION</b>Cervical cancer patients could relieve urinary retention by self-acupressure after radical hysterectomy.</p>

Morbidity and risk factors of microalbuminuria among 1 259 hospitalized patients / 第二军医大学学报

Objective: To evaluate the prevalence and risk factors of microalbuminuria (MAU) in hospitalized patients. Methods: A total of 1 259 hospitalized patients undergoing detection of urinary microalbumin in 2012 were recruited from Tongji Hospital. They were divided into two groups according to the level of urinary microalbumin, with 907 cases in the normal albuminuria (NAU) group and 352 in the MAU group. The clinical data of the two groups were compared and the risk factors of MAU were analyzed. Results: The MAU prevalence was 27.9% in our study. Patients in the MAU group had an elder age and higher prevalence rates of type 2 diabetes mellitus, hypertension, and type 2 diabetes combined with hypertension compared with the NAU group (P80 years old,OR=1.668,95%CI 1.185-2.348) and type 2 diabetes mellitus (OR=1.718,95%CI 1.334-2.211) increased the risk for MAU in hospitalized patients. Conclusion: MAU is closely related to age and type 2 diabetes mellitus in hospitalized patients, which suggests that strict control of blood glucose and timely treatment can slow down diabetic nephropathy and cardiovascular disease in hospitalized patients.

Mechanism of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture against influenza immune inflammatory injury / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the impact of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture on mRNA expression of lung inflammatory cytokines and pulmonary pathological injury of mice infected by influenza virus, in order to discuss the mechanism of tonifying Qi traditional Chinese medicines against pulmonary immune inflammatory injury of infected mice.</p><p><b>METHOD</b>In different time phases after mice were infected with influenza virus FM1, the RT-PCR method was adopted to observe the impact of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture on five inflammatory cytokines TNF-α, IL-1, IL-6, IL-10 and IFN-γ, and the changes in pulmonary pathological injury of mice with viral pneumonia after intervention with tonifying qi traditional Chinese medicines.</p><p><b>RESULT</b>(1) Tonifying Qi traditional Chinese medicines significantly reduced the mRNA expression of TNF-α at 1-5 d and IL-1 mRNA expression at 7 d, may increase IL-1 mRNA expression in mouse lung at 3 d, significantly reduced IL-6 mRNA expression in mouse lung and increased IL-10 mRNA expression at 3-7 d, and significantly increased IFN-γ mRNA expression at 1 d. (2) Tonifying Qi traditional Chinese medicines could significantly inhibited and repaired pulmonary immune inflammatory injury of mice infected by FM1, which was most remarkable at 3-7 d after the infection with influenza virus FM1.</p><p><b>CONCLUSION</b>Tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture could resist pulmonary immune inflammatory injury and repair inflammatory injury by regulating the mRNA expression of imbalance inflammatory cytokines of organisms infected with influenza virus.</p>

Relative performance of two equations for estimation of glomerular filtration rate in a Chinese population having chronic kidney disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed to address the systematic underestimation of glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with relatively well-preserved kidney function. Performance of the new equation in the Chinese population is unknown. The goal of the present study was to compare performance of these two equations in Chinese patients with chronic kidney disease (CKD).</p><p><b>METHODS</b>We enrolled 450 Chinese patients (239 women and 211 men) with CKD in the present study. The renal dynamic imaging method was used to measure the referenced standard GFR (rGFR) for comparison with estimations using the two equations. Their overall performance was assessed with the Bland-Altman method and receiver-operating characteristics (ROC) analysis. Performance of the two equations in lower and higher estimated GFR (eGFR) subgroups was further investigated.</p><p><b>RESULTS</b>Both eGFRs correlated well with rGFR (r = 0.88, 0.81, P < 0.05). In overall performance, the CKD-EPI equation showed less bias, higher precision and improved accuracy, and was better for detecting CKD. In the higher-eGFR subgroup, the CKD-EPI equation corrected the underestimation of GFR by the abbreviated MDRD equation.</p><p><b>CONCLUSIONS</b>The CKD-EPI equation outperformed the abbreviated MDRD equation not only in overall performance but also in the subgroups studied. For the present, the CKD-EPI equation appears to be the first-choice prediction equation for estimating GFR.</p>

Murine corneal stroma cells suppress bone marrow-derived dendritic cells maturation in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prostaglandin E2 (PGE(2)) is a key modulator of dendritic cells (DCs) function, and cornea-derived transforming growth factor beta 2 (TGF-β(2)) promotes the generation of phenotypically and functionally immature DCs. Therefore, this study was carried out to investigate whether PGE(2) is involved in the suppressive effect on DCs maturation mediated by corneal stroma cells (CSCs) and whether PGE(2) and TGF-β(2) have additive effects in this immunosuppressive mechanism.</p><p><b>METHODS</b>Bone marrow-derived DCs (BM-DCs), splenic T cells and CSCs culture supernatant were obtained from mice via various protocols. After that, the level of PGE(2) in CSCs culture supernatant was analyzed by enzyme-linked immunosorbent assay. Then, immature BM-DCs pretreated by E-prostanoid 2 receptor antagonist AH6809 or dimethyl sulfoxide were induced to mature in the presence of lipopolysaccharide, with or without CSCs culture supernatant. In parallel experiments, neutralizing TGF-β(2) antibody or normal goat IgG was added into the supernatant. Next, the cellular surface markers for DCs maturation, including CD80, CD86, and major histocompatibility complex class II (MHCII), were analyzed by flow cytometry; the capability of stimulating the proliferation of T lymphocytes was evaluated by allogeneic mixed lymphocyte reactions and the function of endocytosis was assessed by fluorescein isothiocyanate-dextran uptake.</p><p><b>RESULTS</b>Higher concentration of PGE(2) was detected in CSCs culture supernatant than in the fresh medium. In addition, compared with control group, after treated with the supernatant in the mature stage, BM-DCs displayed lower expression of CD80, CD86 and MHC II, lower T cell stimulatory capacity and higher endocytosis function. However, after the application of AH6809, BM-DCs partially regained T cell stimulatory capacity and expression of CD86 and MHC II, but partially lost endocytic activity. Moreover, after the application of AH6809 and neutralizing TGF-β(2) antibody, the result of statistical analysis indicated that there was a statistical difference of interaction in the expression of MHC II and T cell stimulatory capacity.</p><p><b>CONCLUSIONS</b>PGE(2) contributes to the suppressive effect on BM-DCs maturation mediated by CSCs in vitro, and PGE(2) and TGF-β(2) have additive effects on the immunosuppression of BM-DCs.</p>

Study on the effect of realgar nanoparticles on reducing the respiratory syncytial virus type A (RSV-a) replication in vitro / 病毒学报

This study was to establish a model to explore anti- RSV effect of different administration method of Chinese medicine realgar on respiratory syncytial virus type A (RSV-A) replication in Hep-2 cells. Using high-energy ball milling with distilled water to prepare realgar nanoparticles,the concentration of nanometer realgar was tested by molybdenum blue staining method and the size of realgar nanoparticles was tested on Nano Series. Cell culture with ribavirin as a positive control was applied to observe the effect of anti-respiratory syncytial virus type A replication through prevention, treatment or direct inactivation of three different drug administration methods. Realgar nano-particles was found to be a potential inhibitor of RSV-A in a concentration-dependent manner with the median toxic concentration(TC50) of 0.649 microg/mL in Hep-2 cell culture. The median inhibition concentration (IC50) was 0.20 microg/mL when drug was added before virus infection. The IC50 was 0.13 microg/mL when drug was added after virus infection,and it was 0.16 microg/mL when the drug was mixed with virus and added. The therapeutic index (TI) was 3.18, 4.99 and 4.11, respectively. The results showed realgar nanoparticles could inhibit the replication of the RSV and inactivate the RSV in vitro.