Exploring the Autoimmune Pathogenesis in Severe Asthma.

INTRODUCTION: Severe asthma has a poor response to hormone therapy and a poor level of control, so the discovery of new pathogenetic mechanisms is important for diagnosing and treating severe asthma. IL-35 may play a protective role in autoimmune diseases by directly or indirectly inhibiting the secretion of IL-17, which is an important proinflammatory factor involved in the occurrence and development of autoimmune diseases. The autologous serum skin test (ASST) is a good sensitivity and specificity screening test for autoimmune functional autoantibodies. We compared the levels of IL-35 and IL-17 in serum samples, the positive rate of ASST, the level of exhaled nitric oxide (FeNO), and the atopic constitution in patients with severe asthma to those with mild-to-moderate asthma so as to explore the possible autoimmune pathogenesis of severe asthma. METHODS: Patients with mild-to-moderate and severe asthma were enrolled. Their age, gender, smoking history, family history of asthma, history of allergic rhinitis, positive allergen results, serum total IgE (TlgE), allergen-specific IgE (slgE), routine blood, ASST results, and FeNO test results were compared and analyzed. The IL-35 and IL-17 levels in serum samples from both groups were measured by enzyme-linked immunosorbent assay for comparison and analysis. The SPSS 22.0 software package was used for statistical analysis. RESULTS: A total of 50 patients with mild-to-moderate asthma and 31 patients with severe asthma were included in this study. The proportion of patients with a history of smoking and a family history of asthma was significantly higher in the severe asthma group compared to the mild-to-moderate asthma group (all p < 0.05); the number of positive allergen tests was significantly lower in patients with severe asthma compared to those with mild-to-moderate asthma (p < 0.001). The rate of positive ASST was significantly higher in patients with severe asthma than in patients with mild-to-moderate asthma (p < 0.05). Serum IL-17 levels were significantly higher in patients with severe asthma than in patients with mild-to-moderate asthma (p < 0.05), but serum IL-35 level between the two group was not significantly different (p = 0.113). ASST-positive patients had a statistically significant increase in the risk of developing severe asthma, while patients with allergen positive were less likely to develop severe asthma (positive ASST: OR = 5.277, p = 0.024; allergen positivity: OR = 0.123, p = 0.001). CONCLUSIONS: IL-35 has a weaker inhibitory effect on high IL-17 expression in patients with severe asthma, and the rate of positive ASST was significantly higher in patients with severe asthma, which all suggested the possibility of autoimmune pathogenesis in patients with severe asthma.

Allergen Differences and Correlation Analysis in Siblings Diagnosed with Respiratory Allergic Diseases.

INTRODUCTION: Many parents of children with allergies are worried whether their subsequent children will have allergic reactions to the same allergens. Much of the current research on sibling allergens has been focused on twins; however, in real life, very few children are twins. Our study provides an opportunity to initially explore the sensitivity to allergens in siblings diagnosed with respiratory allergic diseases. METHODS: Siblings diagnosed with bronchial asthma and/or allergic rhinitis in the Outpatient Department of Allergy Department of Yantai Yuhuangding Hospital from January 2018 to December 2021 were selected. The siblings were divided into elder group and younger group. Data of gender, age, feeding history, serum total IgE (TIgE), absolute eosinophil counts, and allergen-specific IgE (sIgE) were collected and analyzed. The sIgEs of allergens were divided into six categories and analyzed. RESULTS: A total of 98 sibling pairs of patients were included in this study. There were no differences in the positive rates of the different types of allergens, TIgE values, and the absolute eosinophil values between the elder and younger groups and between different genders. Logistic regression analysis indicated that the elder siblings allergic to dust mites, fungi, weed pollens, or food had a statistically significant increased risk of having their younger sibling sensitive to these types of allergens (all p <0.05), and the risk of allergy to dust mites, weed pollens, and tree pollens of younger group increased with age (all p <0.05). Except for the sIgE values of dust mites, the sIgE values of the other allergens were significantly correlated between the two groups (all p <0.05). CONCLUSION: The positive rates of different allergens were similar between siblings. Elder siblings with dust mites, fungi, weed pollen, or food allergen positivity will have younger siblings sensitive to the same types of allergens.

Elevated INR in a COVID-19 patient after concomitant administration of azvudine and anticoagulants.

Background: Azvudine (FNC) is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). However, drug interactions with azvudine have been poorly studied, especially with no reported cases of azvudine with anticoagulants such as warfarin and rivaroxaban. Case summary: The patient was diagnosed with lower limb venous thrombosis and took warfarin regularly. The international normalized ratio (INR) was stable (2.0-3.0). However, the INR increased to 7.52 after administering azvudine. The patient had no other factors justifying this change. This increase in INR occurred again with the administration of azvudine in combination with rivaroxaban, and the INR increased to 18.91. After azvudine administration was stopped, the INR did not increase when rivaroxaban was used alone. Conclusion: Azvudine, warfarin, and rivaroxaban might have previously unidentified drug interactions that increased the INR. Therefore, the INR must be closely monitored when they are concomitantly administered in COVID-19 patients.

CCL3-CCR5 axis promotes cell migration and invasion of colon adenocarcinoma via Akt signaling pathway.

BACKGROUND: Infiltration of tumor-associated macrophages (TAMs) can promote tumorigenesis and development. C-C motif chemokine ligand 3 (CCL3) was reported to be derived from TAMs and tumor cells and facilitate the progression of several cancers. Nevertheless, whether CCL3 can be derived from TAMs and tumor cells of colon adenocarcinoma (COAD) is unclarified. METHODS: Peripheral blood monocytes-derived macrophages were polarized by the conditioned medium from COAD cells to establish TAM-like macrophages (TAM1/2). RT-qPCR and western blotting were used for detection of expression levels of CCL3 and its receptors C-C motif chemokine receptor 1 (CCR1) and CCR5 in TAM1/2 and COAD cells. Immunofluorescence staining was utilized for evaluating CCL3, CD163 and CCR5 expression. The Akt signaling pathway-associated protein levels were measured by western blotting. Transwell assays were used for assessing cell migration and invasiveness. RESULTS: CCL3 displayed a high level in TAMs and cancer cells of COAD. CCL3 activated the Akt signaling pathway by binding to CCR5. CCL3-CCR5 axis facilitated COAD cell migration and invasiveness by activating the Akt signaling. CCL3 derived from both TAMs and cancer cells contributed to the malignant behaviors of COAD cells. High expression of CCL3/CCR5 was closely associated with poor prognoses of COAD patients. CONCLUSION: CCL3-CCR5 interaction promotes cell migration and invasiveness, and functions as a prognostic biomarker for COAD.

The efficacy and safety of traditional Chinese medicine physiotherapy combined with acupoint injection on diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of traditional Chinese medicine physiotherapy combined with acupoint injection in treating diabetic peripheral neuropathy remains unknown. As a result, we will conduct a systematic review and meta-analysis to assess the evidence. METHODS: We will look for pertinent randomized controlled trials in the following databases: China National Knowledge Infrastructure, WanFangData, Chinese biological medical database, Medline, Cochrane Library, PubMed, and Embase up to January 2022. Following the standards of Cochrane Review 6.2, 2 researchers independently evaluated the quality of the evidence in the relevant papers. Data analysis will be conducted by using Review Manager 5.4, including statistical analysis, subgroup analysis, making forest plot and funnel chart. RESULTS: The results will be submitted to a peer-reviewed journal. CONCLUSION: The research will verify the safety and efficacy of traditional Chinese medicine physiotherapy in combination with acupoint injection for diabetic peripheral neuropathy.

Quantification of clofarabine in urine and plasma by LC-MS/MS: suitable for PK study and TDM in pediatric patients with relapsed or refractory ALL.

Clofarabine is approved for the treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in pediatric patients aged 1 to 21 years. Its pharmacokinetic (PK) exposure is strongly related to clinical outcomes and high risk of adverse reactions. PK-guided dosing of nucleoside analogs has the potential to improve survival and reduce toxicity in children. Considering that blood collection is an invasive operation and that the volume of blood collected is usually limited in pediatric ALL patients, a convenient and efficient method for the quantification of clofarabine in human urine and plasma was established with an LC-MS/MS system. Standard curves were shown to be liner in the range of 2.00-1000.00 ng mL-1 in both urine and plasma. Analytical validation of the assay included the assessment of linearity, accuracy (RE: -6.62% to 2.32%), intra-assay precision (RSD: 0.81% to 3.87%) and inter-assay precision (RSD: 1.88% to 5.69%). The absolute recovery rates of clofarabine were 85.50 ± 4.80%, 89.40 ± 0.70% and 98.00 ± 0.40% in urine and were 80.76 ± 1.88%, 86.81 ± 0.75%, 88.10 ± 0.61% in plasma at 5.00, 30.00 and 800.00 ng mL-1, respectively. The selectivity, stability and matrix effects conformed to the biological sample analysis requirements. The cumulative urine excretion rates for 24 hours of the three children with relapsed and refractory acute lymphoblastic leukemia were 72.22%, 87.88%, 82.16%, respectively. The PK data of the pediatric patient numbered lflb13-05 are very inconsistent with that of the other two children subjects, demonstrating that there may be an individual variation in Chinese pediatric patients, so the dose should be individualized based on the monitoring of drug concentration. The method is convenient, sensitive, and accurate, and it is suitable for the determination of clofarabine urine and plasma concentration. This is the first report on the pharmacokinetics of clofarabine in Chinese ALL children. Furthermore, it could be an alternative method to clinical monitoring of clofarabine.

Simultaneous Determination of RDX and HMX in Rat Plasma by LC-MS/MS and its Applications.

Background: 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) can cause serious toxicity problems in humans and animals, but direct analyses of RDX and HMX in biological samples are very limited. A rapid and efficient liquid chromatography-electrospray quadrupole linear ion trap mass spectrometry (LC-MS/MS) method suitable for the simultaneous determination of RDX and HMX in rat plasma after intravenous administration of two nitramine compound mixed solutions has been developed. Methods: Plasma samples were pretreated with one-step protein precipitation, the plasma consumption is as low as 100 µl. RDX, HMX, and internal standard mycophenolic acid were eluted for 8.0 min on a reversed-phase C18 analytical column with a water/acetonitrile mixture as the mobile phase. An electrospray ionization (ESI) source was applied and operated in negative ion mode. The optimized mass transition ion pairs (m/z) monitored for RDX, HMX, and internal standard mycophenolic acid were m/z 284.1→61.7, m/z 331.0→108.8, and m/z 319.2→191.1, respectively. Results: The detection ranges of both RDX and HMX in plasma were 5.00-200.00 ng⋅ml-1 with an LOD of 1.00 ng⋅ml-1. The extraction recoveries of RDX and HMX were 60.04 ± 4.18% and 79.57 ± 3.35%, respectively. The precision and accuracy met the requirements, and the method was stable under all tested conditions. Conclusion: The present method is miniaturized, effective, portable, rapid and can be easily used for simultaneous quantification of RDX and HMX in rat plasma.

RNA-binding protein RBM38 inhibits colorectal cancer progression by partly and competitively binding to PTEN 3'UTR with miR-92a-3p.

RNA-binding motif protein 38 (RBM38) belongs to the RNA recognition motif family of RNA-binding proteins (RBPs). RBM38 was previously identified to suppress tumorigenesis in colorectal cancer (CRC). RBM38 was also reported to bind to the 3'UTR of phosphatase and tensin homolog gene on chromosome 10 (PTEN), a tumor suppressor involved in many cellular processes, to stabilize PTEN transcripts. In the present study, we investigated the mechanisms underlying the regulation of RBM38 in CRC. Reverse transcription quantitative polymerase chain reaction and western blotting detected the expression of RBM38, PTEN, and miR-92a-3p. Colony formation, EdU, sphere formation, Transwell invasion, and in vivo assays examined the influence of RBM38 on CRC progression. Furthermore, RNA immunoprecipitation (RIP) assay determined the binding site of RBM38 on PTEN 3'UTR. The binding of miR-92a-3p or RBM38 on PTEN 3'UTR was assessed by luciferase reporter and RIP assays. We discovered that RBM38 was downregulated in CRC cells and tissues. RBM38 repressed CRC progression in vitro and in vivo. Furthermore, RBM38 upregulated and stabilized PTEN expression. Interestingly, the overexpression of PTEN reversely attenuated the promotion of RBM38 depletion on CRC progression. Additionally, RBM38 competed with miR-92a-3p in binding to PTEN 3'UTR. In conclusion, RBM38 inhibits CRC progression by competitively binding to PTEN 3'UTR with miR-92a-3p.

A five-layer deep convolutional neural network with stochastic pooling for chest CT-based COVID-19 diagnosis.

Till August 17, 2020, COVID-19 has caused 21.59 million confirmed cases in more than 227 countries and territories, and 26 naval ships. Chest CT is an effective way to detect COVID-19. This study proposed a novel deep learning model that can diagnose COVID-19 on chest CT more accurately and swiftly. Based on traditional deep convolutional neural network (DCNN) model, we proposed three improvements: (i) We introduced stochastic pooling to replace average pooling and max pooling; (ii) We combined conv layer with batch normalization layer and obtained the conv block (CB); (iii) We combined dropout layer with fully connected layer and obtained the fully connected block (FCB). Our algorithm achieved a sensitivity of 93.28% ± 1.50%, a specificity of 94.00% ± 1.56%, and an accuracy of 93.64% ± 1.42%, in identifying COVID-19 from normal subjects. We proved using stochastic pooling yields better performance than average pooling and max pooling. We compared different structure configurations and proved our 3CB + 2FCB yields the best performance. The proposed model is effective in detecting COVID-19 based on chest CT images.

Extramedullary melanotic schwannoma recurrence in the cervical vertebral arch: a case report and review of the literature.

Melanotic schwannoma (MS), a slowly growing nerve sheath tumor, is not a purely benign tumor. MS accounts for less than 1% of all nerve sheath tumors. We herein describe a rare case of MS and present a literature review focusing on the treatment of this disease. Twelve years before presentation at our hospital, a 41-year-old woman was examined because of an 8-month history of neck pain and 6-month history of upper extremity numbness and weakness. She underwent surgery to remove a tumor, and the pathological examination confirmed a diagnosis of MS. Twelve years later, at 53 years of age, the patient presented to our hospital with a 2-year history of neck pain and upper extremity numbness and weakness. Posterior cervical tumor resection was performed along with posterior cervical laminectomy, decompression and intraspinal space-occupying internal fixation, and radiotherapy. MS recurrence was confirmed. No tumor recurrence or metastasis was found after 7 months of follow-up. Recurrence of MS is rare, and its diagnosis depends on pathological features. Radical excision is the primary treatment for MS. Incomplete resection of MS is a risk factor for postoperative recurrence and metastasis. Furthermore, postoperative adjuvant radiotherapy should be performed to prevent recurrence and metastasis of MS.

Scheuermann's Disease as a Risk Factor for Lumbar Disc Herniation Recurrence.

OBJECTIVE: To verify whether Scheuermann's disease (SD) is a risk factor for patients with recurrent lumbar disc herniation (rLDH) than in patients without recurrence. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Department of Orthopaedics, Yantaishan Hospital, China, from December 2016 to September 2019. METHODOLOGY: The demographics (age, gender, body mass index [BMI], alcohol abuse, and current smoking), diabetes mellitus, and radiological data (affected levels, herniated side, herniation type, Pfirrmann grade, and the presence of SD) of 602 patients were retrospectively analysed, who underwent surgery for symptomatic LDH from December 2016 to August 2018. They were underwent one-year follow-up and were divided into LDH and rLDH groups. Both typical and atypical SD criteria were used to diagnose SD. Independent-sample t-test was used to analyse the role of age and BMI in both groups, and the Chi-square test was conducted to analyse other parameters. Logistic regression analysis was performed to evaluate various factors. RESULTS: There was a significant difference in age (p=0.026), BMI (p=0.007), current smoking (p=0.001), and SD (p<0.001) between the groups. When these parameters were included in the logistic regression analysis, age, current smoking status, and SD were found to be risk factors for rLDH. CONCLUSION: Age, current smoking, and SD are risk factors for rLDH. Older patients with radiological characteristics of SD should quit smoking to prevent rLDH. Key Words: Scheuermann's disease, Kyphosis, Disc herniation, Recurrence, Age, Smoking, Risk factor.

Retracted: Minimally Invasive Unilateral vs. Bilateral Pedicle Screw Fixation and Lumbar Interbody Fusion in Treatment of Multi-Segment Lumbar Degenerative Disorders.

We have retracted this publication because we were informed that an image used by the authors was copied from the following article: J Korean Neurosurg Soc. 2011 Nov; 50(5): 441-445. Minimally Invasive Multi-Level Posterior Lumbar Interbody Fusion Using a Percutaneously Inserted Spinal Fixation System: Technical Tips, Surgical Outcomes (https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3259464/pdf/jkns-50-441.pdf) (https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3259464/). Reference: 1. Xiaoyang Liu, Guangrun Li, Jiefeng Wang, Heqing Zhang: Minimally Invasive Unilateral vs. Bilateral Pedicle Screw Fixation and Lumbar Interbody Fusion in Treatment of Multi-Segment Lumbar Degenerative Disorders. Med Sci Monit, 2015; 21: 3652-3657. DOI: 10.12659/MSM.894890.

Buformin suppresses osteosarcoma via targeting AMPK signaling pathway.

BACKGROUND: Buformin has been reported to be a powerful anticancer drug by activating the AMPK signal. Herein, we aimed to investigate the effects of buformin on osteosarcoma. MATERIAL AND METHODS: Cellular proliferative abilities were determined by cell counting kit-8 and colony formation assays. Cellular invasion was investigated using a transwell system. Cell cycle was examined by flow cytometry. Western blot was performed to measure the expression of key proteins. Synergistic effects of buformin and cisplatin were validated in seven fresh osteosarcoma tissues. RESULTS: Buformin suppressed the growth of U-2 OS cells in a dose-dependent manner (IC50 = 69.1 µM). Moreover, buformin induced cell cycle arrest (P < 0.001) and impaired cellular invasion (P = 0.038). Phosphorylation of AMPK was upregulated by buformin, while phosphorylation of S6, cyclin D1, and MMP9 were significantly downregulated. In addition, buformin notably induced accumulation of reactive oxygen species and lactate and eventually decreased ATP production. In both U-2 OS cells and the primary cultured osteosarcoma tissues, buformin increased tumor sensitivity to cisplatin. CONCLUSIONS: Buformin could suppress tumor growth and invasion of osteosarcoma through directly targeting the AMPK signaling pathway. Moreover, buformin inhibited the abnormal metabolism and notably increased the cytotoxicity of cisplatin, and therefore represents a new potential treatment option for osteosarcoma.

miR­204 inhibits the osteogenic differentiation of mesenchymal stem cells by targeting bone morphogenetic protein 2.

Mesenchymal stem cells (MSCs) are used to investigate regeneration and differentiation. MicroRNA­204 (miR­204) in involved in the Runt­related transcription factor 2/alkaline phosphatase/bone morphogenic protein 2 (Runx2/ALP/BMP2) signaling pathway that regulates bone marrow mesenchymal stem cell (BMSC) differentiation; however, the mechanisms underlying the effects of miR­204 are yet to be determined. The aim of the present study was to investigate the effects of miR­204 on BMSC differentiation. BMSCs were derived from rat bone marrow. The expression levels of Runx2, ALP and BMP2 were measured via reverse transcription­quantitative polymerase chain reaction and western blot analyses following transfection of BMSCs with miR­204 agomir or BMP2 expression vector. The ability of the miR­204 gene to directly bind BMP2 mRNA was assessed using dual­luciferase assays. Ossification was measured via alizarin red stain assays. It was observed that the expression levels of Runx2 and ALP increased over time, whereas those of miR­204 decreased; additionally, miR­204 agomir upregulation inhibited the expression of Runx2, ALP and BMP2 in BMSCs. It was revealed that miR­204 directly interacted with BMP2 mRNA, and that transfection with miR­204 agomir suppressed ossification in BMSCs by targeting the BMP2/Runx2/ALP signaling pathway.

Effect of estradiol on high glucose­induced osteoblast injury.

Estradiol (E2) serves an important role in the changes of postmenopausal bone turnover rate and the development of osteoporosis. The present study aimed to investigate the effects of E2 on high glucose (HG)­induced osteoblast injury. Cell Counting Kit­8 was used to determine cell viability. Reverse transcription­quantitative PCR (RT­qPCR) and western blotting was used to analyze the mRNA and protein expression levels of osteocalcin, Runt­related transcription factor 2 (Runx2), nuclear factor E2­related factor 2 (Nrf2) and heme oxygenase­1 (HO1). Flow cytometry was performed to analyze apoptosis. The results revealed that cell viability was lower in cells treated with HG (100, 200 or 300 mg/dl) compared with the control group. Cell viability was decreased in cells treated with 200 mg/dl HG on days 3, 5 and 7. In addition, cell viability was increased by 0.1 µM E2. E2 with HG co­treatment increased cell viability, osteocalcin and Runx2 mRNA expression levels and nuclear Nrf2 and HO1 protein expression levels compared with the HG­only group. All these changes, with the exception of Runx2, were reversed by silencing Nrf2 expression using small interfering (si)RNA (siNrf2). Additionally, apoptosis was reduced by E2 in HG­treated cells, which was reversed by siNrf2 transfection. These results demonstrated that E2 may prevent HG­induced osteoblast injury by activating Nrf2/HO1 signaling pathways.

Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation.

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)-induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho-mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA-mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD.

Minimally Invasive Unilateral vs. Bilateral Pedicle Screw Fixation and Lumbar Interbody Fusion in Treatment of Multi-Segment Lumbar Degenerative Disorders.

BACKGROUND The choice for instrumentation with minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in treatment of degenerative lumbar disorders (DLD) remains controversial. The goal of this study was to investigate clinical outcomes in consecutive patients with multi-segment DLD treated with unilateral pedicle screw (UPS) vs. bilateral pedicle screw (BPS) instrumented TLIF. MATERIAL AND METHODS Eighty-four consecutive patients who had multi-level MIS-TLIF were retrospectively reviewed. All data were collected to compare the clinical outcomes between the 2 groups. RESULTS Both groups showed similar clinical function scores in VAS and ODI. The two groups differed significantly in operative time (P<0.001), blood loss (P<0.001), and fusion rate (P=0.043), respectively. CONCLUSIONS This study demonstrated similar clinical outcomes between UPS fixation and BPS procedure after MIS-TLIF for multi-level DLD. Moreover, UPS technique was superior in operative time and blood loss, but represented lower fusion rate than the BPS construct did.

Airway wall thickness of allergic asthma caused by weed pollen or house dust mite assessed by computed tomography.

PURPOSE: Little was known about Airway wall thickness of asthma patients with different allergen allergy. So we explored the possible difference of Airway wall thickness of asthma patients mono-sensitized to weed pollen or HDM using high-resolution computed tomography. MATERIALS AND METHODS: 85 severe asthma patients were divided into weed pollen group and HDM group according to relevant allergen. 20 healthy donors served as controls. Airway wall area, percentage wall area and luminal area at the trunk of the apical bronchus of the right upper lobe were quantified using HRCT and compared. The values of pulmonary function were assessed as well. RESULTS: There were differences between HDM group and weed pollen group in WA/BSA,WA% and FEF25-75% pred, and no significant difference in FEV1%pred, FEV1/FVC and LA/BSA. In weed pollen group, WA/BSA was observed to correlate with the duration of rhinitis, whereas in HDM group, WA/BSA and LA/BSA was observed to correlate with the duration of asthma. In weed pollen group, FEV1/FVC showed a weak but significant negative correlation with WA%, but in HDM group FEV1/FVC showed a significant positive correlation with WA% and a statistical negative correlation with LA/BSA. FEV1/FVC and FEF25-75% pred were higher and WA/BSA and LA/BSA were lower in healthy control group than asthma group. FEV1%pred and WA% was no significant difference between asthma patients and healthy subjects. CONCLUSION: There are differences between HDM mono-sensitized subjects and weed pollen mono-sensitized subjects, not only in airway wall thickness, but also small airway obstruction.

Protective effects of Akebia saponin D against rotenone-induced hepatic mitochondria dysfunction.

Akebia saponin D (ASD) is a typical bioactive triterpenoid saponin obtained from the rhizome of Dipsacus asper Wall. Previous studies have found that ASD has a hepatoprotective effect in a mouse model. The purpose of this paper was to explore the molecular mechanism of the hepatoprotective effects of ASD on BRL cells and isolated rat liver mitochondria. We investigated the effects of ASD on rotenone-induced toxicity in BRL cells. The results showed that ASD inhibited the accumulation of reactive oxidant species, ATP deficiency, and mitochondrial membrane potential dissipation; ameliorates mitochondrial respiratory dysfunction, and improved the activity of complex I in a concentration-dependent manner, indicating that ASD likely improved mitochondrial function. ASD suppressed rotenone-induced BRL cell apoptosis and increased Bcl-2/Bax ratio. These results suggest that ASD may exert hepatoprotective effects against rotenone-induced toxicity through mitochondria. This study supports our previous research that ASD possesses hepatoprotective activity in vivo and it is worthy of further study.

Association between co-stimulatory molecule gene polymorphism and acute rejection of allograft.

Co-stimulatory molecules play important roles in T cell-mediated immune response and transplantation. Numerous epidemiological studies have evaluated the association between CD28, CTLA-4 gene variant and allograft rejection. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CD28 IVS3 +17T/C variant, CTLA-4, CD86 and PDCD1 gene polymorphisms were associated with allograft rejection susceptibility. PubMed and Embase (before 2014-3-25), were searched for studies on the relationship of CD28, CTLA-4, CD86 and PDCD1 gene polymorphisms and the incidence of allograft rejection susceptibility. Eligible articles were included for data extraction. The main outcome was the frequency of co-stimulate molecule gene polymorphisms between rejection and non-rejection populations. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. Significant associations of the CD28 IVS3 +17T/C variant with acute allograft rejection susceptibility were found (CC +CT/TT OR, 1.45; 95% CI, 1.08-1.94; P=0.01). Also we found an association of the CD28 IVS3 +17T/C variant with kidney allograft rejection cases (CC +CT/TT OR, 1.72; 95% CI, 1.19-2.49; P=0.004) and (C allele OR, 1.74; 95% CI, 1.11-2.75; P=0.02), but not established for liver allograft rejection cases (CC +CT/TT OR, 1.19; 95% CI, 0.47-2.98; P=0.72) and (C allele OR, 0.96; 95% CI, 0.67-1.39; P=0.84). And we found an association of the CD86 +1057G/A variant with non-allograft rejection cases (AA +AG/GG OR, 0.35; 95% CI, 0.14-0.85; P=0.02). This meta-analysis demonstrates that the CD28 IVS3 +17T/C variant might increase acute allograft rejection risk in kidney transplant but not in liver transplant, and there was an association between CD86 +1057G/A variant and reduced acute rejection risk. Further studies will be needed to confirm our findings.