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Disseminated infection caused by Nocardia farcinica with primary nephrotic syndrome is exceedingly rare. A 66-year-old female visited the outpatient department due to fever and fatigue who had been diagnosed as membranous nephropathy and with a long-term prednisone and immunosuppressive therapy. After lung biopsy for many times, culture from space-occupying lesion of the right lung and species identification by mass spectrometry-based methods (MALDI-TOF) revealed Nocardia farcinica. By imaging examination, space-occupying lesions from the lungs, brain, abdominal cavity and kidney were found. After 2 weeks of meropenem intravenous and up to 6 months of trimethoprim-sulfamethoxazole (TMP-SMX) therapy, our patient has remained relapse-free at that time of writing. Disseminated infection caused by Nocardia farcinica is usually subacute with complex clinical manifestations. In addition, it can be easily confused with diseases such as tumor and mycobacterial infection, and lead to fatal consequences. Therefore, we hope that we can remind clinicians considering by discussing common features of disseminated Nocardia farcinica infection.

Previous studies have found follicle‐stimulating hormone (FSH) receptors on chondrocytes (cartilage cells), but the mechanism of FSH action on chondrocytes is not clear. The purpose of this experiment is to study whether FSH affects chondrocytes and how it causes changes in these cells. Our results show that osteoarthritis became worse after FSH injection in the knee joint of mice. After the stimulation of chondrocytes by FSH, a total of 664 up‐regulated genes, such as Col12a1 and Col1a1, and 644 down‐regulated genes, such as MGP, were screened by transcriptomics. A subset of extracellular matrix (ECM)‐related genes and pathways underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the downregulation of MGP, the upregulation of EGR1 and Col1a1, and the increase of IL‐6 were verified. It was also observed that FSH can inhibit the cAMP/PKA and MKK4/JNK signaling pathway. In conclusion, we demonstrated that FSH can increase cartilage inflammatory response and promote chondrocyte dedifferentiation by inhibiting the cAMP/PKA and MKK4/JNK signaling pathways., Here, we demonstrate through in vivo experiments, transcriptomic screening, and in vitro experiments that FSH can inhibit cAMP/PKA and MKK4/JNK signaling pathways and cause inflammatory response and dedifferentiation of chondrocytes, thereby aggravating osteoarthritis.

With the deepening of ultrasound imaging research, studying nonlinear phenomena in medical ultrasound will help people to further improve the existing diagnostic level. Harmonic imaging technology generated in recent years is an effective new technology for nonlinear acoustics in ultrasonic diagnosis. Patients with biliary tract lesions generally have few symptoms, which are often detected by chance during physical examination. Ultrasonography is currently the preferred diagnostic method for biliary tract disease. The application of tissue harmonic imaging (THI) can effectively eliminate many near-field misdiagnosed images, enhance the tissue echo of deep tissues or organs, and significantly improve signal-to-noise ratio and resolution. At the same time, it can better display the subtle features of biliary diseases, thereby reducing the rate of missed diagnosis and improving the accuracy of diagnosis. Therefore, this study aimed to observe the changes of ultrasound images in the lesions and surrounding tissues of several biliary lesions by ultrasound tissue harmonic imaging technology, and realized the diagnosis in the early stage of the disease by means of tissue harmonic imaging technology, then provided objective quantitative indicators for the diagnosis of biliary diseases. Also, this study confirmed that tissue harmonic imaging technology can significantly improve the ultrasound image resolution of biliary tract disease, clearly showing the sub-acute gallbladder wall, gallbladder wall, gallbladder cavity in the acute and chronic inflammation and the presence of subtle changes in the tumor. This can provide a rich diagnostic value for the clinic and has practical significance for clinical treatment.

AIM The purpose of this study was to compare percutaneous endoscopic lumbar discectomy (PELD) and the microscopic tubular technique and evaluate the outcomes of surgery. MATERIAL AND METHODS We collected information through retrospective analysis of patients with far-lateral lumbar disc herniation (FLLDH) from June 2015 to October 2018. Twenty-six patients underwent paraspinal muscle-splitting microscopic-assisted discectomy (MD) and thirty patients underwent PELD surgery by the same surgical team. Data included the duration of the operation, duration of intraoperative radiation exposure, and average duration of hospitalization. Pre- and postoperative pain scores and neurological functions were recorded using the visual analog scale (VAS) score and Oswestry disability index (ODI). RESULTS Fifty-six patients remained in the study over the 12-24 months period. The mean operating time was 65.83 ± 16.64 min in the PELD group, mean duration of radiation exposure was 154.98 ± 64.26 mGy, and average of hospitalization was 3.43 days. The mean operating time was 44.96 ± 16.87 min in the MD group, duration of radiation exposure was 42.12 ± 17.28 mGy, and duration of hospitalization was 4.12 days. There were two patients with postoperative transient dysesthesia and one underwent reoperation seven months after surgery in the PELD group. One patient had postoperative transient dysesthesia in the MD group. Except low back pain at three months (p 0.05), all patients in both groups showed significant improvement in VAS and ODI scores compared with pre-operation and until final follow-up (p 0.05). CONCLUSION Both techniques are minimally invasive, effective, and safe for treating FLLDH in selected patients. Compared with the PELD technique, the MD procedure offers a wider field of vision during operation, shorter operation time, fewer postoperative complications, and shorter learning curve.

Purpose There are few reports about minimally invasive decompression and fixation for patients with thoracolumbar fracture and neurological symptoms. The previously reported method requires complete laminectomy, and removal of the medial part of the pedicle to expose the spinal canal for reduction. Thus, some approach-related damage to the bony structure and soft tissue still occurs. This study was performed to describe a modified minimally invasive tube technique for decompression and reduction of thoracolumbar fracture with neurological symptoms. This modified technique preserves most of the posterior structures of the spine as well as the muscle. Methods Percutaneous pedicle screws were placed on the vertebrae superior and inferior to the fracture and at the fracture segment on the side with less severe symptoms. After retraction, the tube for decompression was placed on the facet joint where the decompression was needed. Under microscopic vision, part of the lamina and ligamentum flavum were removed to expose the spinal canal, and an L-shaped probe was used to reduce the bone fragment. Results The modified method was successfully used in eight patients. Complete decompression was achieved and the bone fragment was safely reduced through the tube under microscopy in all cases. Fluoroscopy confirmed that the positioning of the percutaneous pedicle screw was good and the bone fragment was reduced. The neurological status was improved in all patients at last follow up. Conclusion The modified method of minimally invasive decompression and fusion is effective in treating thoracolumbar fractures with neurological symptoms and preserves most of the ligaments and bone structure.

A comprehensive understanding of the effects of meteorology, emission and chemistry on severe haze is critical in the mitigation of air pollution. However, such understanding is largely hindered by the nonlinearity of atmospheric chemistry systems. Here, we developed a novel quantitative decoupling analysis (QDA) method to quantify the effects of emission, meteorology, chemical reaction, and their nonlinear interactions on the fine particulate matter (PM2.5) pollution based on the accompanying simulations for different atmospheric processes. Via embedding the QDA method into the Weather Research and Forecasting-Nested Air Quality Prediction Modeling System (WRF-NAQPMS) model, we first employed this method into a typical heavy haze episode in Beijing. Different from the previously sensitive simulation method, which usually linked to a certain period, the QDA achieves the fully decomposing analysis of PM2.5 concentration during any pollution event into seven different parts, including meteorological contribution (M), emission contribution (E), chemical contribution (C), and interactions among these drivers (i.e., ME, MC, EC and MCE). The results show that the meteorology contribution varied significantly at different stages of episode, from 0.21 µg·m−3·h−1 during accumulation period to −11.82 µg·m−3·h−1 during the removal period, dominating the hourly changes of PM2.5 concentrations. The chemical contributions were shown to increase with the level of haze, which become largest (0.37 µg·m−3·h−1) at the maintenance period, 25 % higher than that during the clean period. The contribution of primary emission is relatively stable in all stages due to the use of fixed emission during the simulation. Besides, the QDA method highlights that there exist nonnegligible coupling effects of meteorology, emission and chemistry on PM2.5 concentrations (−1.83 to 2.44 µg·m−3·h−1), which were commonly ignored in previous studies and the development of heavy-pollution control strategies. These results indicate that the QDA method can not only provide researchers and policy makers with valuable information for understanding of key factors to heavy pollution, but also help the modelers to find out the sources of uncertainties among numerical models.

To explore the expression profile and prognostic relevance of GLUT-1 in pancreatic cancer, a meta-analysis, bioinformatics analysis based on Gene Expression Omnibus (GEO), Oncomine dataset and The Cancer Genome Atlas (TCGA) database, and immunohistochemistry in tumor and normal tissue from 88 pancreatic ductal adenocarcinoma (PDAC) patients were performed. GLUT-1 was significantly overexpressed in pancreatic cancer but it could not be a significant biomarker for prognosis. TNM stage and pathological grade could be biomarker of poor prognosis of patients with pancreatic cancer.

Background Synovial sarcoma, a rare mesenchymal tumor type with unclear histological origin and direction of differentiation, accounts for 6%-10% of soft tissue tumors. It is mainly located near the joints and tendons of the limbs, and occurs primarily in children or young adults. Primary renal synovial sarcoma (PRSS) is very rare, accounting for approximately 1% of synovial sarcomas. It is a spindle cell tumor type affecting mesenchymal tissue, and has morphological, genetic, and clinical characteristics, and a certain degree of epithelial differentiation. It is highly malignant and has the fourth highest incidence among soft tissue sarcomas. Here, we report a case of PRSS and share some valuable information about the disease. Case summary A 54-year-old male patient was admitted to the hospital for a space-occupying lesion in the right kidney for 2 d upon ultrasound examination. The patient had no cold or fever; no frequency, urgency or pain of urination; and no other discomfort. The results of a hemogram, blood biochemistry, and tumor markers were in the normal range. The patient was examined by computed tomography (CT), which indicated the presence of a soft tissue density shadow with a diameter of approximately 6.8 cm in the right renal pelvis area, showing uneven enhancement. Ultrasound indicated a cystic solid mass of approximately 6.8 cm × 6.5 cm in the right kidney, with an unclear boundary and irregular shape. Meanwhile, color Doppler flow imaging showed dotted blood flow signals in the periphery and interior. Contrast-enhanced ultrasound (CEUS) showed "slow in and fast out" hyperenhancement of the right renal mass after contrast agent injection. The postoperative pathological diagnosis was (right kidney) synovial sarcoma. Despite postoperative adjuvant chemotherapy, tumor recurrence was detected two years later. Conclusion PRSS is a rare malignant tumor. To date, no characteristic imaging findings have been observed. The diagnosis is confirmed primarily through postoperative pathological immunohistochemistry and SS18 (SYT) gene detection. In this case, CEUS was used preoperatively. We found that PRSS has the characteristic of "slow in and fast out" hyperenhancement, and its particular characteristics have diagnostic value. Postoperative adjuvant chemotherapy is not very effective.

BACKGROUND In general, malignant tumors metastasize to the pancreas in < 1% of cases. Most patients miss the opportunity for further surgery due to distant metastases; however, for fibrosarcomas, aggressive surgery may be helpful even if distant metastases occur. Hence, we report such a case and share some valuable information about the disease. CASE SUMMARY A 45-year-old man was admitted with recurrent epigastric pain for 10 days. The abdominal pain was mainly related to bloating with nausea, but no other associated symptoms. No particular signs were found on abdominal examination or laboratory testing. In 2003, a local distal expanded resection of the primary fibrosarcoma in the left chest wall was performed. Then, a left pneumonectomy was performed in 2017 due to diffuse metastases from the fibrosarcoma to the left lung. Enhanced computed tomography (CT) and magnetic resonance imaging of the upper abdomen suggested multiple masses of different sizes involving the head and tail of the pancreas; no local lymph node enlargement was noted. The postoperative pathologic diagnosis revealed a fibrosarcoma of the pancreas. A CT re-examination 6 mo postoperatively showed no local recurrence or distant metastases. CONCLUSION A fibrosarcoma is a rare low-grade malignant tumor, and metastases to the pancreas are even rarer. Patients with a history of a fibrosarcoma should consider the possibility of metastasis when a pancreatic neoplasm is demonstrated. Surgical resection is the preferred treatment.

The present study aimed to investigate the long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in the progression of gallbladder cancer and explore the potential physiopathologic mechanisms of gallbladder cancer in terms of competing endogenous RNAs (ceRNAs). The original lncRNA and mRNA expression profile data (nine gallbladder cancer tissues samples and nine normal gallbladder samples) in GSE76633 was downloaded from the Gene Expression Omnibus database. Differentially expressed mRNAs and lncRNAs between gallbladder cancer tissue and normal control were selected and the pathways in which they are involved were analyzed using bioinformatics analyses. MicroRNAs (miRNAs) were also predicted based on the differentially expressed mRNAs. Finally, the co-expression relation between lncRNA and mRNA was analyzed and the ceRNA network was constructed by combining the lncRNA-miRNA, miRNA-mRNA, and lncRNA-mRNA pairs. Overall, 373 significantly differentially expressed mRNAs and 47 lncRNAs were identified between cancer and normal tissue samples. The upregulated genes were significantly enriched in the extracellular matrix (ECM)-receptor interaction pathway, while the downregulated genes were involved in the complement and coagulation cascades. Altogether, 128 co-expression relations between lncRNA and mRNA were obtained. In addition, 196 miRNA-mRNA regulatory relations and 145 miRNA-lncRNA relation pairs were predicted. Finally, the lncRNA-miRNA-gene ceRNA network was constructed by combining the three types of relation pairs, such as XLOC_011309-miR-548c-3p-SPOCK1 and XLOC_012588-miR-765-CEACAM6. mRNAs and lncRNAs may be involved in gallbladder cancer progression via ECM-receptor interaction pathways and the complement and coagulation cascades. Moreover, ceRNAs such as XLOC_011309-miR-548c-3p-SPOCK1 and XLOC_012588-miR-765-CEACAM6 can also be implicated in the pathogenesis of gallbladder cancer.

Low temperature and drought stress are the major constraints in rice productivity worldwide. This study investigated the influence of low soil temperature and/or drought stress on physiology and pollen traits of two rice genotypes viz., Guinongzhan and Yueza 763 at flowering stage. The experiment included four treatments, i.e., under the greenhouse natural growth conditions (UC) taken as control, drought stress (DS), the soil water potential was kept at −0.035 to −0.045 MPa (DS), low soil temperature (LT) maintained at 19 to 21°C, combined LT and DS (LT+DS, LD). Results showed that LT, DS, and LD substantially reduced net photosynthetic rate (Pn) and the maximal photochemical efficiency of PSII (Fv/Fm), whilst transpiration rate (Tr) was markedly enhanced by under LT in both rice genotypes. The malondialdehyde (MDA) contents were enhanced under LT, DS, and LD in Guinongzhan, whilst the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were regulated by LT, DS, and LD in both rice genotypes. Furthermore, anther dehiscence rate, pollen numbers on stigma, pollen viability and pollen germination rate, and anther starch contents were obviously reduced under LT and DS of both rice genotypes. Stress conditions substantially reduced the yield and yield components, i.e., effective panicles, seed set percentage, grain/panicles, 1000-grain weight, and grain yield of both genotypes and the effects were more apparent in Guinongzhan than those in Yueza 763 whilst combined LT and DS proved more damaging than individual stress.

In the present study, we aimed to identify specific lncRNAs and miRNAs, as well as mRNAs, involved in bile duct carcinoma (BDC) and to further explore the way in which lncRNA UCA1 regulates cell metastasis ability. Differentially expressed RNAs were screened out from the TCGA database. In in vitro experiments, qRT-PCR was used to measure lncRNA UCA1, miR-122 and CLIC1 expression. We performed a dual luciferase assay to validate the target relationships among UCA1, CLIC1 and miR-122. The cell migration ability was measured by a wound healing assay, and Transwell assays were applied to detect cell invasive ability. Western blot analysis was employed to detect the expression of related proteins in the MAPK signaling pathway. According to the bioinformatics analysis, lncRNA UCA1 and CLIC1 were both significantly upregulated in BDC, while the expression of miR-122 declined compared with the normal group. The target relationship among UCA1, CLIC1 and miR-122 was verified. UCA1 promoted BDC cell migration and invasiveness, while miR-122 inhibited their progression. CLIC1 served as the downstream target gene of miR-122 and had opposite effects. The ERK/MAPK signaling pathway was activated after upregulating UCA1. LncRNA-UCA1 promoted the metastasis of BDC cells by regulating the expression of miR-122 and its downstream gene mRNA CLIC1 and promoted the activation of the ERK/MAPK pathway, which expanded the horizons of targeted therapy of cholangiocarcinoma.

Objective. Spondyloepiphyseal dysplasia tarda (SEDT) is a rare hereditary bone disease characterized by spinal and epiphyseal anomalies. We identified the disease by gene sequencing in a Chinese pedigree with SEDT. Methods. We extracted genomic DNA from five members of a four-generation Chinese SEDT kindred with three affected males and then analyzed the genetic mutation by PCR and DNA sequencing. Results. DNA sequencing showed that the genetic missense mutation occurred one bp upstream of exon 6 in the SEDL gene in two families, and a heterozygous mutation was found in a female carrier. In addition, no mutation was found in the other members of the family. Conclusion. SEDT in this family was caused by a G/C missense mutation in exon 6 of the SEDL gene, previously not shown to be associated with X-linked SEDT.

Iron (Fe) deficiency is a common challenge in crop production. Screening and research of Fe-efficient cultivars could alleviate plant stress and increase crop yields in Fe-deficient soils. In the present study, we conducted two hydroponic culture experiments with a control (100 μmol/L Fe3+-EDTA) and low Fe treatment (10 μmol/L Fe3+-EDTA) to study the morphological and physiological mechanisms of response to low Fe stress in maize hybrids seedlings. In the first experiment, we investigated 32 major maize hybrids in Southwest China. We found that six of them, including Zhenghong 2 (ZH 2), were Fe-efficient. Fifteen other cultivars, such as Chuandan 418 (CD 418), were Fe-inefficient. In the second experiment, we investigated the Fe-efficient ZH 2 and Fe-inefficient CD 418 cultivars and found that low Fe stress resulted in significant decreases in root volume, root length, number of root tips, root surface area, and root dry weight, and increased root to shoot ratio, average root diameter, and Fe-dissolution ability per mass of roots in both maize cultivars. However, the increase in Fe-dissolution ability per mass of roots in ZH 2 was higher than that in CD 418, whereas for the other measurements, the low Fe stress-induced changes in ZH 2 were less pronounced than in CD 418. Therefore, under low Fe stress, the above-mentioned growth factors in ZH 2 were higher by 54.84%, 121.46%, 107.67%, 83.96%, 140.00%, and 18.16%, respectively, than those in CD 418. In addition, leaf area, chlorophyll content, net photosynthetic rate, soluble protein content, and Catalase (CAT) and Peroxidase (POD) activities in ZH 2 were higher by 274.95%, 113.95%, 223.60%, 56.04%, 17.01% and 21.13% than those in CD 418. Therefore, compared with the Fe-inefficient cultivar (CD 418), the Fe-efficient cultivar (ZH 2) had a more developed root system and greater Fe absorption capacity per mass of roots under low iron stress, promoted the efficient absorption of Fe, maintained a higher photosynthetic area and photosynthetic rate, thereby facilitating the accumulation of photosynthetic products. Moreover, higher soluble protein content and activities of CAT and POD permitted high osmotic regulation and scavenging ability, which is an important physiological mechanism for ZH 2 adaptation to low Fe stress.

Background: Minimally invasive surgery includes percutaneous endoscopic lumbar discectomy and the microscopic tubular technique. This study aimed to compare the two techniques and evaluate the outcomes of the procedures.Methods: We retrospectively analyzed patients with far-lateral lumbar disc herniation (FLLDH) from June 2015 to October 2018. Twenty-six patients underwent paraspinal muscle-splitting microscopic-assisted discectomy (MD) and 30 patients underwent percutaneous endoscopic lumbar discectomy (PELD) surgery by the same surgical team. Data included the duration of the operation, duration of intraoperative radiation exposure, and average duration of hospitalization. Pre- and postoperative pain scores and neurological functions were recorded using a visual analog scale (VAS) score and Oswestry disability index (ODI).Results: 56 patients remained in the study over the 12–24 months period. The mean operating time was 65.83 ± 16.64 min in the PELD group, mean duration of radiation exposure was 2.87 ± 1.19 min, and average of hospitalization was 3.43 days. The mean operating time was 44.96 ± 16.87 min in the MD group, duration of radiation exposure was 0.78 ± 0.32 min, and duration of hospitalization was 4.12 days. There were two patients with postoperative transient dysesthesia and one underwent reoperation 7 months after surgery in the PELD group. One patient had postoperative transient dysesthesia in the MD group. Except low back pain at 3 months (p >0.05), all patients in both groups showed significant improvement in VAS and ODI scores compared with pre-operation and until final follow-up (pConclusion: Both techniques are minimally invasive, effective, and safe for treating far-lateral lumbar disc herniation in selected patients. Compared with the PELD technique, the MD procedure offers a wider field of vision during operation, shorter operation time, fewer postoperative complications, and shorter learning curve.

Ammonia (NH3) emission inventories are an essential input in chemical transport models and are helpful for policy-makers to refine mitigation strategies. However, current estimates of Chinese NH3 emissions still have large uncertainties. In this study, an improved inversion estimation of NH3 emissions in China has been made using an ensemble Kalman filter and the Nested Air Quality Prediction Modeling System. By first assimilating the surface NH3 observations from the Ammonia Monitoring Network in China at a high resolution of 15 km, our inversion results have provided new insights into the spatial and temporal patterns of Chinese NH3 emissions. More enhanced NH3 emission hotspots, likely associated with industrial or agricultural sources, were captured in northwest China, where the a posteriori NH3 emissions were more than twice the a priori emissions. Monthly variations of NH3 emissions were optimized in different regions of China and exhibited a more distinct seasonality, with the emissions in summer being twice those in winter. The inversion results were well-validated by several independent datasets that traced gaseous NH3 and related atmospheric processes. These findings highlighted that the improved inversion estimation can be used to advance our understanding of NH3 emissions in China and their environmental impacts.

Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attributed to declining estrogen levels. Although follicle-stimulating hormone (FSH) levels become elevated in parallel, the effects of FSH on OA have been poorly explored. The present study aimed to study the effect of FSH on cartilage metabolism. Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections. We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice. Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.

Background Minimally invasive surgery includes percutaneous endoscopic lumbar discectomy and the microscopic tubular technique. This study aimed to compare the two techniques and evaluate the outcome of the procedure. Methods We retrospectively analyzed patients with far-lateral lumbar disc herniation (FLLDH) from June 2015 to October 2018. Twenty-six patients underwent paraspinal muscle-splitting microscopic-assisted discectomy (MD), and 30 underwent percutaneous endoscopic lumbar discectomy (PELD) surgery. Data included the duration of the operation, duration of intraoperative radiation exposure and average hospitalization. Pre- and postoperative pain scores and neurological functions were recorded using visual analogue scale (VAS) score and Oswestry disability index (ODI). Results A total of 56 patients remained in the study over the 12–24 months. The mean operating time was 65.83 ± 16.64 min in the PELD group, the mean duration of radiation exposure was 2.87±1.19 min and average hospitalization was 3.43 days. The mean operating time was 44.96 ± 16.87 min in the MD group, the mean duration of radiation exposure was 0.78±0.32 min and average hospitalization was 4.12 days. All patients in both groups showed significant improvement of VAS and ODI scores after surgery and until final follow-up. Conclusion Both techniques are minimally invasive, effective, and safe for treating far-lateral lumbar disc herniation in selected patients. Compared with the PELD technique, the MD procedure affords a wider field of vision during operation, shorter operation time, fewer postoperative complications, and a shorter learning curve.

AIM To introduce a visual surgical concept using a retrospective comparison of the outcomes between visualized percutaneous endoscopic lumbar discectomy (V-PELD) and conventional PELD techniques. MATERIAL AND METHODS Data from 61 patients in the conventional PELD group and 55 in the V-PELD group. Data included the duration of the operation, number of intraoperative radiation exposure events, and follow-up information for 24 months. The Oswestry Disability Index (ODI) and visual analog scale (VAS) scores were collected. RESULTS The mean (± SD) operating time for the V-PELD group was 57.82 ± 11.25 min, and the mean duration of radiation exposure was 0.74 ± 0.32 min. The mean operating time for the conventional group was 63.16 ± 14.49 min (p < 0.05), and the mean duration of radiation exposure was 2.81 ± 1.12 min (p < 0.001). All patients in both groups demonstrated significant improvement in the ODI and VAS scores after surgery (p < 0.05). CONCLUSION V-PELD is a minimally invasive surgical technique that involves less radiation exposure and is more efficient for treating lumbar disc herniation.

Objective The aim of this study was to investigate the regulation mechanism of HOTAIR on nucleus pulposus cell (NPC) apoptosis induced by inflammatory cytokines. Methods QRT-PCR was performed to analyze the expression of HOTAIR and miR-34a. Safranin O staining and immunohistochemical staining were measured to identify NPCs. ELISA assay was used to detect TNF-α level. Apoptosis was detected with TUNEL assay. Western blotting was measured to analyze the expression of caspase-3, Bax and Bcl-2. TargetScan was used to predict potential targets of miR-34a. Results HOTAIR was significantly low-expressed in degenerative nucleus pulposus (NP) tissues and cells of IDD patients, overexpressing HOTAIR obviously inhibited TNF-α level, NPCs apoptosis and the expression of caspase-3 and Bax, while promoted the expression of Bcl-2. MiR-34a was obviously expressed in degenerative NP tissues and cells of IDD patients. HOTAIR reduced miR-34a induced apoptosis. Apoptotic inhibition gene Bcl-2 is the target gene of miR-34a, and showed a negative relationship with miR-34a. Conclusion Our data suggest that lncRNA HOTAIR suppresses TNF-α induced NPCs apoptosis by regulating miR-34a/Bcl-2 axis in IDD patients.

Objective We sought to describe a novel modified guidewire technique used in the placement of percutaneous pedicle screws (PPSs), which enables safe and precise control of the depth of screw placement and prevents excessive advancement of the guidewire with low radiation exposure. PPSs have been widely used and have many advantages. However, inadvertent advancement of the guidewire may damage peripheral tissue or viscera, and repeated confirmation of the depth of screw and guidewire leads to extensive radiation exposure. Methods A modified guidewire with markers was used intraoperatively. The reading of the mark on the guidewire increased as the PPS advanced into the pedicle. The depth of the screw in the pedicle was calculated as the mark reading after each screw was rotated into the pedicle minus the initial mark reading. After all pedicle screws were placed, the positions of the screws were checked by C-arm or G-arm fluoroscopy. Results The modified guidewire was applied in 41 thoracic-lumbar fracture patients. The depths of the percutaneous screws were precisely controlled as planned. There were no inadvertent breaches of the anterior cortices of the vertebrae. No patients reported neurologic symptoms, and there was no screw misplacement detected. Surgeons had no radiation exposure, and patients were only exposed once to the radiation. Conclusions The modified guidewire with markers is an effective device to precisely control the depth of PPSs and prevent complications of the guidewire in the placement of pedicle screws.

Background Intervertebral disc degeneration (IDD) has high morbidity and high disability. Exosomes as a favorable candidate for IDD treatment is a hot spot of current research. Methods Exosomes were obtained from bone marrow mesenchymal stem cells (BM-MSCs) of patients with non-open femoral fractures. Then, annulus fibrosus (AF) cells were treated with IL-1β, IL-1β combined with exosomes or IL-1β combined with exosomes and rapamycin. Flow cytometry and CCK-8 assay were performed to explore the apoptosis and cell proliferation. Quantitative real-time PCR and western blot were performed to detect the gene and protein expression. Results Exosomes were obtained from BM-MSCs successfully. BM-MSC-derived exosomes suppressed IL-1β-induced inflammation and apoptosis and promoted cell proliferation of AF cells. BM-MSC-derived exosomes inhibited autophagy of AF cells by activating PI3K/AKT/mTOR signaling pathway. The effect of BM-MSC-derived exosomes on inflammation and apoptosis of AF cells was rescued by rapamycin. Conclusions In conclusion, our study revealed that BM-MSC-derived exosomes inhibited IL-1β-induced inflammation and apoptosis of AF cells by suppressing autophagy.

Systemic lupus erythematosus (SLE) is a protypical autoimmune disease and genetic factors play important roles in its pathogenesis. Since present SLE susceptibility loci are mainly studied through meta-analysis of genome-wide association study, we performed promoter activity analysis to examine the biological functions of SLE-associated single-nucleotide polymorphisms (SNPs). We found at SNP positions rs1341239, rs1800795, rs1800796, rs1800872, rs1800871, rs187238, rs360719, rs8178822, rs3761549, different alleles influenced respective promoter activities in different manners, and the effects also appeared under glucocorticoid treatment. In addition, some SNPs showed strong correlations with levels of respective serum factors, but in most cases the associations were only demonstrated in SLE individuals. Our study has further disclose the functional roles of SLE-associate SNPs in SLE pathogenesis.

Ischemic stroke (IS) is a disease caused by deficiency of blood and oxygen in focal or complete brain, followed by inflammation cascade and other pathological reactions, which finally lead to irreversible damage to the cerebrum. For the inflammation is a key progress at the initiation of ischemia and poststroke, and chemokines work as vital cytokines in inflammation, we focus the roles of chemokines in IS. Studies have shown cerebral ischemia is associated with marked induction of both CXC and CC chemokines which resulting in extensive leukocyte infiltration in the ischemic brain, and neutrophil infiltration may increase cerebral edema inducing injury in the ischemic area. In addition, chemokines also shows other functions such as promote neuroblast migration, hematogenous cell recruitment and functional brain repair. Thus, a similar chemokine ligand/chemokine receptor pair can mediate both beneficial and detrimental effects depending on the window of observation and pathophysiological conditions. This manuscript reviews the studies about chemokine-mediated effects in cerebral ischemia/reperfusion and discusses the potential significance of these interactions in injury and repair of ischemic tissues. We also refer drug development based on the chemokines and clinical applications using chemokines as diagnostic or prognostic biomarkers in ischemic stroke.

Backgrounds Evidence for the effects of temperature variability on risk of congenital anomalies is lacking. We aimed to examine the association of temperature variability during fetal organogenesis period (weeks 3-8 post-conception) with major congenital anomalies. Methods A retrospective cohort study comprising 4,787,356 singleton live-births and stillbirths in China was performed. We defined two temperature variability indices within gestational week i: the standard deviation (SD) of daily temperature (TVSDi) and the maximum day-to-day temperature difference (TVDi). At 6-week long timescales, we computed the SD of daily temperature (TVSD3-8) and the average value of TVDi (TVD3-8). We matched two temperature variability indices, pollutant exposure levels over entire exposure window and data of each mother-infant pairs. An extended generalized estimating equation log-binomial regression model was constructed to explore their associations after adjusting for individual characters, temperature extremes and air pollutants. Stratified and sensitivity analyses were also performed. Results 59,571 neonates were registered as major congenital anomalies besides genetic and chromosomal anomalies. At weekly levels, the highest risk estimates of two temperature variability indices occurred at the 5th week for most anomaly groups. All TVSD5, TVD5, and maximum weekly TVSD and TVD were significantly associated with all anomaly groups; with the increment of 1 °C, the estimated risk ratio (RR) and corresponding 95% confidence interval (CI) ranges from 1.03 (1.01-1.05) to 1.19 (1.08-1.31). At 6-week scales, TVSD3-8 and TVD3-8 were associated with most anomaly subgroups. Overall, the strongest associations were estimated for isolated defects among morphology subgroups and cardiac defects among type subgroups. Conclusions Exposure to temperature variability during fetal organogenesis period of pregnancy is associated with increased risk of major congenital defects. Our findings provide a research foundation for public health policies, and further mechanism investigation.

To assess the effect of saxagliptin monotherapy on blood glucose and islet β-cell function in obese patients with newly diagnosed pre-diabetes and abnormal fat metabolism.A 24-week, randomized controlled trial was conducted involving 25 obese subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (mean age 45years) to receive lifestyle intervention only (control group) or combined with saxagliptin 2.5mg or 5mg daily (S2.5 or S5 group), metformin 1500mg daily (Met group). Anthropometrics, body fat and biochemical parameters were measured before and after 4, 12 and 24weeks intervention.S5 group and Met group showed a significant decrease in fasting plasma glucose (FPG) and HbA1c compared with the control group (all P0.05) after 24-week intervention. However, the decrease in 2h postprandial plasma glucose levels (2hPPG) in S5 group were greater compared with control group (P0.01). Insulin resistance (HOMA-IR) was reduced in S5 group, Met group and control group (P0.05), and the β-cell function (HOMA-β) was improved in all groups (P0.05). However, the changes in obesity-related indicators including waist circumference, hip circumference, weight, BMI, body fat, percentage of body fat and waist-to-hip fat ratio were greate in Met group (all P0.05) compared with other groups (P0.05).Saxagliptin monotherapy may prevent or delay the progression of IGT or IFG to type 2 diabetes mellitus in obese patients with newly diagnosed pre-diabetes. ClinicalTrials.gov: NCT01960205.

This study evaluates the relationship between obstructive sleep apnea (OSA) and asthma. Literature search was carried out in several electronic databases and random effects meta-analyses were performed to obtain pooled estimates of the prevalence of OSA, OSA risk and sleep disordered breathing (SDB) in asthma patients and pooled odds ratios of the prevalence between asthma and non-asthma patients. In adult asthma patients, the prevalence [95% confidence interval] of OSA, OSA risk, and SDB was 49.50 [36.39, 62.60] %, 27.50 [19.31, 35.69] %, and 19.65 [14.84, 24.46] % respectively. The odds of having OSA, OS risk and SDB by the asthma patients were 2.64 [1.76, 3.52], 3.73 [2.90, 4.57] and 1.73 [1.11, 2.36] times higher (p

Background: Chronic obstructive pulmonary disease (COPD) is managed by three major classes of inhaled medications: inhaled corticosteroids (ICS), long-acting Beta 2-agonist (LABA), long-acting muscarinic antagonist (LAMA). Single inhaled medication is usually replaced by combined inhaled medications for efficacy enhancement. However, this practice should be supported by clinical evidence for large-scale implementations. Methods: The relative efficacy of inhaled medications is determined by three endpoints: changes in the trough forced expiratory volume in 1 second (tFEV1), changes in the St George’s Respiratory Questionnaire (SGRQ) score and the proportion of SGRQ responders which represents a reduction in SGRQ total score at week 24 of ≥4.0. A total of 76 eligible studies were identified in PubMed and Embase. Relevant data were extracted for the purpose of evidence synthesis. Then, raw mean differences (MD) and odds ratios (ORs) were produced by using the network meta-analysis. Results: Patients with ICS + LABA, ICS + LABA + LAMA, LABA, LABA + LAMA, LAMA exhibited significant increases in the tFEV1 compared to those with placebo (P < 0.05). Moreover, patients with ICS + LABA + LAMA exhibited the largest increase in the average tFEV1 and the largest decrease in the average SGRQ scores compared to those with placebo. COPD patients with ICS + LABA + LAMA were far more likely to achieve a significant reduction in the SGRQ scores compared to those with placebo or other inhaled medications (OR > 1). Conclusions: The combined inhaled medication of ICS + LABA + LAMA may be more efficacious than other inhaled medications for COPD patients.

Non-structural carbohydrates (NSCs) are an important energy source for plant growth and metabolism. Analysis of NSC changes can provide important clues to reveal the adaptation mechanisms of plants to a specific environment. Although considerable differences have been reported in NSCs in response to nitrogen (N) application among crop species and cultivars, previous studies have mostly focused on the differences in leaves and stems. However, the effects of N on the characteristics of accumulation and translocation of NSC in maize with different levels of N tolerance remain unclear. To determine differences in the N levels, two cultivars (N-efficient ZH311 and N-inefficient XY508) were grown in field pots (Experiment I) and as hydroponic cultures (Experiment II) and were supplemented with different concentrations of N fertilizer. In both experiments, low-N stress significantly increased the accumulation of NSCs in maize vegetative organs and increased the translocation rate of NSCs in the stems and their apparent contribution to yield, thereby reducing the yield loss caused by low-N stress. N application had a greater effect on starch content in the vegetative organs of ZH311, but had less effect on soluble sugar (SS) and NSC content in the whole plant and starch content in the ears. ZH311 could convert more starch into SS under low N conditions to adapt to low N environments than XY508, while ensuring that grain yield and starch quantity were not affected. This is evidently an important physiological mechanism involved in this cultivar's tolerance to low N conditions.

Disruption of blood-brain barrier (BBB) and subsequent edema are major contributors to the pathogenesis of ischemic stroke, and the current clinical therapy remains unsatisfied. Chemokine-like factor 1 (CKLF1), as a novel C-C chemokine, plays important roles in immune response. The expression of CKLF1 increased after focal cerebral ischemia and inhibition of CKLF1 activity showed neuroprotective effect by alleviating infiltration of neutrophil and neuron apoptosis in cerebral ischemia. However, few studies have focused on the role of CKLF1 on BBB integrity. The objective of present study was to investigate the role of CKLF1 on BBB integrity by applying anti-CKLF1 antibodies in rat focal cerebral ischemia and reperfusion model. Brain water content, Evans blue leakage and the expression of aquaporin-4 (AQP-4), matrix metalloproteinase-9 (MMP-9), Zonula Occludens-1 (ZO-1) and Occludin were measured. After treatment with anti-CKLF1 antibody, brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24h after reperfusion, but not changed in contralateral hemisphere. Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9, and upregulated the expression of ZO-1 and Occludin. These results suggest that CKLF1 is involved in BBB disruption after reperfusion. Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity, possibly via inhibiting the expression of AQP-4 and MMP-9, and increasing the expression of tight junction protein.

Purpose In this study, we used magnetic resonance imaging (MRI) to investigate the anatomical alterations of cerebral cortex in children with Tourette syndrome (TS) and explore whether such deficits were related with their clinical symptoms. Methods All subjects were scanned in a 3.0T MRI scanner with three-dimensional T1-weighted images (3DT1WI). Then, some surface-based features were extracted by using the FreeSurfer software. After that, the between-group differences of those features were assessed. Results Sixty TS patients and 52 age- and gender-matched healthy control were included in this study. Surface-based analyses revealed altered cortical thickness, cortical sulcus, cortical curvature and local gyrification index (LGI) in TS group compared with healthy controls. The brain regions with significant-group differences in cortical thickness included postcentral gyrus, superiorparietal gyrus, rostral anterior cingulate cortex in the left hemisphere and frontal pole, lateral occipital gyrus, inferior temporal gyrus in the right hemisphere. In addition, the superior temporal gyrus, medial orbitofrontal gyrus, supramarginal gyrus, medial orbitofrontal gyrus, superiorparietal gyrus and lateral occipital gyrus showed significant between-group differences for cortical sulcus. Moreover, the brain regions with significant between-group differences in cortical curvature were located in caudal anterior cingulate cortex, supramarginal gyrus, inferior parietal gyrus and lateral occipital gyrus. The alteration of LGI were most prominent in the inferior temporal gyrus and insula. Additionally, there was no statistical difference in brain surface area for TS children compared with controls. Conclusion The results of this study revealed that cortical thickness, sulcus, cortical curvature and LGI were changed in multiple brain regions for children with TS.

Air pollution (mainly PM2.5) is one of the main environmental problems about air quality. Air pollution prediction and early warning is a prerequisite for air pollution prevention and control. However, it is not easy to accurately predict the long-term trend because the collected PM2.5 data have complex nonlinearity with multiple components of different frequency characteristics. This study proposes a hybrid deep learning predictor, in which the PM2.5 data are decomposed into components by empirical mode decomposition (EMD) firstly, and a convolutional neural network (CNN) is built to classify all the components into a fixed number of groups based on the frequency characteristics. Then, a gated-recurrent-unit (GRU) network is trained for each group as the sub-predictor, and the results from the three GRUs are fused to obtain the prediction result. Experiments based on the PM2.5 data from Beijing verify the proposed model, and the prediction results show that the decomposition and classification can develop the accuracy of the proposed predictor for air pollution prediction greatly.

To investigate the apoptosis and inflammatory response of microRNA-27a-5p (miR-27a-5p) in pancreatic acinar cells of acute pancreatitis (AP) and its related mechanisms. Rat pancreatic acinar cell line AR42J was treated with caerulein (10nmol/L) to construct an acute pancreatitis cell model. Quantitative real-time polymerase chain reaction was performed to measure the expression of miR-27a-5p; The miR-27a-5p mimic was transfected into cell, and the apoptosis rate of the cells was detected by flow cytometry; The levels of TNF-α, IL-1, and IL-6 in the culture supernatant were determined by enzyme-linked immunosorbent assay; TargetScans database predicted and dual luciferase reporter gene assay verified the relationship between miR-27a-5p and the phosphatase and tensin homolog deleted on chromosome 10 (PTEN); The recovery experiment explored the apoptosis and the effects of inflammatory responses. The expression of miR-27a-5p decreased gradually (P < 0.05) and the expression of PTEN increased gradually (P < 0.05) with the prolongation of acting time. Upregulation of miR-27a-5p significantly promoted cell apoptosis (P < 0.05) and inhibited inflammatory response (P < 0.05); The TargetScans database predicted that the 3'UTR of PTEN contains a base complementary to the miR-27a-5p seed region. Cotransfection of wild-type vector (PTEN-WT) with miR-27a-5p mimic or miR-27a-5p inhibitor significantly affected the relative activity of luciferase (P < 0.05), and no significant impact was observed in mutant PTEN-MUT. Compared with miR-27a-5p + pcDNA group, transfection of miR-27a-5p mimic and pcDNA-PTEN significantly increased the expression of PTEN (P < 0.05), decreased the apoptotic rate (P < 0.05), and increased the inflammatory response (P < 0.05). miR-27a-5p induced apoptosis and inhibited the inflammatory response of pancreatic acinar cells in AP by targeting PTEN.

Sufficient decompression of the nerve root canal is still regarded as the method of choice when operating on patients with lumbar disc herniation (LDH) with lumbar lateral recess stenosis; however, tissue-sparing procedures are becoming more popular. Endoscopic techniques offer advantages and the benefits of rehabilitation, which have become the standard in many surgical operations when operating on the spine. A significant issue has been the upgrading of instruments to provide enough bone resection under continuous visual control.We examined patients who had LDH with lateral recess stenosis and compared the results of nerve root canal decompression using percutaneous endoscopic lumbar discectomy (PELD) with a microsurgical laminotomy (ML) technique. In this study 40 patients with full endoscopic decompression or microsurgery were followed up for 2 years. In addition to general and specific parameters, the following two parameters were also used for the investigation: the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI).Except for 1 patient in whom repair was done by fusion and 1 who was lost to follow-up, 38 patients remained in the study over the 2 years. The mean operating time in the PELD group was longer (p 0.05), but intraoperative and postoperative blood loss was less than in the ML group (p 0.05). The postoperative results were better than before surgery, and the VAS and ODI parameters indicated a clear improvement in leg pain and daily activities in both groups (p 0.05). Of the patients three suffered increasing back pain (2 ML, 1 PELD).The results indicated that the PELD can provide an effective supplement and serve as an alternative for LDH with lateral recess stenosis compared with the ML technique when the indication criteria are fulfilled. The PELD also has the advantage of being a minimally invasive intervention.

Organelles play crucial roles in cellular activities and the functions of organelles are related greatly to the pH values, therefore, the bio-imaging of targeted organelles and their related pH sensing is of great importance in biological assays. Herein we report the fluorescence imaging of specific organelles, i.e., lysosomes and endoplasmic reticulum, and their pH sensing with surface regulated carbon dots (CDs). Carbon dots functionalized with amine groups (ACDs) are first prepared by hydrothermal treatment of citric acid and urea, and then laurylamine functionalized CDs (LCDs) are obtained via the conjugation of laurylamine with ACDs. The as-prepared ACDs and LCDs provide clear and bright imaging results for the lysosome and endoplasmic reticulum, respectively. The subcellular targeting features of the two CDs are attributed to their surface chemistries and cellular uptake pathways. Moreover, both the CDs are pH responsive within a certain pH range, i.e., 4.0-5.4 for ACDs and 6.2-7.2 for LCDs. The ACDs and LCDs are thus successfully applied to visualize the pH fluctuations of the lysosome and endoplasmic reticulum in MCF-7 cells.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with strong genetic contributions. To provide a comprehensive resource for the genetic evidence of ASD, we have updated the Autism KnowledgeBase (AutismKB) to version 2.0. AutismKB 2.0 integrates multiscale genetic data on 1379 genes, 5420 copy number variations and structural variations, 11 669 single-nucleotide variations or small insertions/deletions (SNVs/indels) and 172 linkage regions. In particular, AutismKB 2.0 highlights 5669 de novo SNVs/indels due to their significant contribution to ASD genetics and includes 789 mosaic variants due to their recently discovered contributions to ASD pathogenesis. The genes and variants are annotated extensively with genetic evidence and clinical evidence. To help users fully understand the functional consequences of SNVs and small indels, we provided comprehensive predictions of pathogenicity with iFish, SIFT, Polyphen etc. To improve user experiences, the new version incorporates multiple query methods, including simple query, advanced query and batch query. It also functionally integrates two analytical tools to help users perform downstream analyses, including a gene ranking tool and an enrichment analysis tool, KOBAS. AutismKB 2.0 is freely available and can be a valuable resource for researchers.

Cipangopaludina chinensis which is a species of benthic macroinvertebrates was exposed to roxithromycin, and tested the erythromycin N-demethylase (ERND) of kidney, then explored the effect of roxithromycin on the biochemical indicator of C.chinensis. The results showed that roxithromycin had effect on the activity of ERND in the kidney of C.chinensis and the overall trend was promoting at the beginning then suppressing at the end, but the differences of the influence caused by different concentrations of roxithromycin was not obvious. In addition, it appeared from the survival condition of control group and experimental group, roxithromycin which is a kind of antibiotic, had no lethal effect on C.chinensis. But the concentration of roxithromycin which is more than 250 times, 500 times and 750 times of the environment used in this experiment had significant influence on the enzyme activity of the ERND in the kidney of C.chinensis.

Recurrent outbreaks of an epizootic in Chinese soft-shelled turtles ( Trionyx sinensis ) in Zhejiang province, China in 2013, caused severe economic losses to turtle culture industry. This disease was characterized by listless swimming, craned or twisted neck, hyperemic laryngeal mucosa, and intumescent and hyperemic intestinal canal accompanied by mass mortality. Eleven diseased turtles with typical signs were collected from three distinct representative farms. Eleven bacterial isolates were collected from the livers and kidneys of diseased turtles and identified as Bacillus thuringiensis based on Vitek biochemical test, observation of rhizoid growth and protein toxin crystal production, 16S rRNA gene sequence analysis and Bacillus group species-specific PCR. These isolates demonstrated highly pathogenic potential to juvenile Chinese soft-shelled turtles with natural-infection-like symptoms. To our knowledge, this is the first case of B. thuringiensis infection in Chinese soft-shelled turtles and even in aquatic animals.

This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n=64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1:1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P < 0.05), serum phosphorus decreased from 6.79 ± 1.05 to 5.46 ± 1.18 mg/dL (P < 0.05), and serum iPTH levels in the Group I and Group II were not significantly different from the baseline. There were no significant differences in CACS in either group. There were no significant differences in the BMD values between Group I and baseline. In Group II, the BMD values at the lumbar spine and femoral neck were significantly lower than those before the trial and significantly lower than the corresponding values of Group I (P

Neuroprotection strategies are of great importance in the treatment of ischemic brain injury. Screening of our in-stock coumarin derivatives identified compound 1 as exhibiting neuroprotective activity. Subsequently, a structural optimization was carried out, which led to the discovery of the potent compound 20 . This compound significantly attenuated the damage in a cell line derived from a pheochromocytoma of the rat adrenal medulla induced by oxygen–glucose deprivation in vitro . Furthermore, compound 20 exhibited clear neuroprotection in middle cerebral artery occlusion rats by reducing infarct size and brain-water content, improving neurological function, and suppressing neuronal loss and neuropathological changes in the cortex and hippocampus. Pharmacokinetic evaluation indicated that compound 20 could penetrate the blood–brain barrier of rats.

Objective IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-[4-methylpiperazin-1-yl]-2H-chromen-2-one) is a novel coumarin derivative that showed better effect in improving global cerebral ischemia in rats. However, the effects and mechanisms in focal cerebral ischemia were not clear. Blood–brain barrier (BBB) protection is a vital strategy for the treatment of cerebral ischemia. This study is to investigate whether IMM-H004 improves brain ischemia injury via BBB protection. Methods Focal brain ischemia model was induced by middle cerebral artery occlusion for 1 hour and reperfusion (MCAO/R) for 24 hours in rats. IMM-H004 (1.5, 3, 6 mg/kg) and edaravone (positive drug, 6 mg/kg) were administered after 5 minutes of occlusion. Neurological score and TTC staining were used to evaluate the effect of IMM-H004. Evans Blue (EB) staining and electron microscopy were used to assess BBB permeability. Western blot, reverse transcription-polymerase chain reaction, and immunohistochemistry were used to detect the expression of BBB structure-related proteins. Results Compared with the model group, IMM-H004 in the focal brain ischemia model improved neurological function and reduced cerebral infarction size and edema content. IMM-H004 sharply reduced the EB content and alleviated BBB structure. In addition, IMM-H004 increased the level of zonula occludens (ZO-1) and occluding, decreased the level of aquaporin 4 and matrix metalloproteinase 9, either in cortex or in hippocampus. And all of these changed were related to BBB protection. Conclusion IMM-H004 improved cerebral ischemia injury via BBB protection. For a potential therapy drug of cerebral ischemia, IMM-H004 merits further study.

The present study aimed to explore the correlation between the dynamic serum levels of phospholipase A2 receptor (PLA2R), aldose reductase (AR) and superoxide dismutase 2(SOD2) antibodies with disease activity and treatment response in patients with idiopathic membranous nephropathy (IMN). The present study included 56 patients with IMN who were diagnosed through a renal biopsy and presenting with nephrotic syndrome. The patients were divided into two treatment groups: One treated with cyclophosphamide (CTX) and one with tacrolimus (FK506). Serum was collected prior to treatment, and at 1, 3, 6, 9 and 12 months after the start of the 12-month-long therapy. Samples were tested by ELISA to measure anti-PLA2R, anti-AR and anti-SOD2 antibody titers. In addition, urinary protein excretion, serum albumin (Alb) and other blood biochemical indexes were measured. Theanti-PLA2R antibody positivity rate was 71.43% in the patients prior to treatment. After 12 months of treatment, proteinuria and PLA2R antibody levels were decreased, whereas serum Alb was increased. There was no significant difference of remission rates between the CTX and FK506 groups. In conclusion, the results of the present study indicate that the anti-PLA2R antibody level is correlated with the severity of IMN, whereas anti-AR and anti-SOD2 antibody levels are not. In addition, there was no significant difference between the CTX and FK506 groups in regards to the remission rates of patients with IMN.

Thienorphine (TNP) is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G) undergo significant bile excretion. The purpose of this study was to investigate the roles of efflux transporters in regulating biliary excretion and plasma exposure of TNP and TNP-G. An ATPase assay suggested that TNP and TNP-G were substrates of P-gp and MRP2, respectively. The in vitro data from rat hepatocytes showed that bile excretion of TNP and TNP-G was regulated by the P-gp and MRP2 modulators. The accumulation of TNP and TNP-G in HepG2 cells significantly increased by the treatment of mdr1a or MRP2 siRNA for P-gp or MRP2 modulation. In intact rats, the bile excretion, and pharmacokinetic profiles of TNP and TNP-G were remarkably changed with tariquidar and probenecid pretreatment, respectively. Tariquidar increased the Cmax and AUC0-t and decreased MRT and T1/2 of TNP, whereas probenecid decreased the plasma exposure of TNP-G and increased its T1/2. Knockdown P-gp and MRP2 function using siRNA significantly increased the plasma exposure of TNP and TNP-G and reduced their mean retention time in mice. These results indicated the important roles of P-gp and MRP2 in hepatobiliary excretion and plasma exposure of TNP and TNP-G. Inhibition of the efflux transporters may affect the pharmacokinetics of TNP and result in a drug-drug interaction between TNP and the concomitant transporter inhibitor or inducer in clinic.

There has been accumulating evidence that chemokines play an important role in cerebral ischemia. Chemokines-like factor 1 (CKLF1), as a novel C–C chemokine, is upregulated in cerebral ischemia. In this study we examined the protective effect of C19, a C-terminal peptide of chemokine-like factor 1, in an animal model of cerebral ischemia. Adult rats were anesthetized with chloral hydrate. C19 was given intracerebroventricularly immediately after 60 min middle cerebral artery occlusion. Animals were examined for their neurological function, infarct size and water content at 24 h after reperfusion. The result showed that C19 (0.1, 1, 10 or 50 μg) significantly improved neurological function, decreased infarct size and water content in a dose-dependent manner. In contrast, application of C19 (50 μg) showed no effect in normal rats. Taken together, our data suggest that C19 is protective against ischemic brain injury, and may be an ideal peptide drug for the treatment of cerebral ischemia.

To explore the clinical significance of seven diabetes-related serum microRNAs (miR-9, miR-29a, miR-30d, miR34a, miR-124a, miR146a and miR375) during the pathogenesis of type 2 diabetes (T2D), 56 subjects were recruited to this study: 18 cases of newly diagnosed T2D (n-T2D) patients, 19 cases of pre-diabetes individuals (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) and 19 cases of T2D-susceptible individuals with normal glucose tolerance (s-NGT). Serum miRNAs were determined by real-time RT-PCR. Expression levels of single miRNAs and the expression signatures of miRNAs as a panel were analysed among the three groups. In n-T2D, all 7 miRNAs were significantly up-regulated compared with s-NGT and five were significantly up-regulated compared with pre-diabetes, while miRNA expression was not significantly different between s-NGT and pre-diabetes. By Canonical discriminant analysis, 70.6% of n-T2D subjects (12/17) were recognized by canonical discriminant function, while s-NGT and pre-diabetes subjects could not be discriminated from each other. Similar results were found in Hierarchical Clustering analysis based on the expression levels of all seven miRNAs. In different statistical analysis, miR-34a always showed the most significant differences. We conclude that the expression levels of seven diabetes-related miRNAs in serum were significantly elevated in n-T2D compared with pre-diabetes and/or s-NGT, and the latter two groups featured similar expression patterns of these miRNAs, suggesting that during the pathogenesis of T2D, the peripheral diabetes-related miRNAs have not changed significantly from s-NGT at pre-diabetic stage.

Triptolide (TP) is the major active principle of Tripterygium wilfordii Hook f. and very effective in treatment of autoimmune diseases. However, TP induced hepatotoxicity limited its clinical applications. Our previous study found that TP was a substrate of P-glycoprotein and its hepatobiliary clearance was markedly affected by P-gp modulation in sandwich-cultured rat hepatocytes. In this study, small interfering RNA (siRNA) and specific inhibitor tariquidar were used to investigate the impact of P-gp down regulation on TP-induced hepatotoxicity. The results showed that when the function of P-gp was inhibited by mdr1a-1 siRNA or tariquidar, the systemic and hepatic exposures of TP were significantly increased. The aggravated hepatotoxicity was evidenced with the remarkably lifted levels of serum biomarkers (ALT and AST) and pathological changes in liver. The other toxicological indicators (MDA, SOD and Bcl-2/Bax) were also significantly changed by P-gp inhibition. The data analysis showed that the increase of TP exposure in mice was quantitatively correlated to the enhanced hepatotoxicity and the hepatic exposure was more relevant to the toxicity. P-gp mediated clearance played a significant role in TP detoxification. The risk of herb-drug interaction likely occurs when TP is concomitant with P-gp inhibitors or substrates in clinic.

As a cellular process that changes epithelial cells to mesenchymal cells, Epithelial-mesenchymal transition (EMT) plays important roles in development and cancer metastasis. Recent studies on cancer metastasis have identified many new susceptibility genes that control this transition. However, there is no comprehensive resource for EMT by integrating various genetic studies and the relationship between EMT and the risk of complex diseases such as cancer are still unclear. To investigate the cellular complexity of EMT, we have constructed dbEMT (http://dbemt.bioinfo-minzhao.org/), the first literature-based gene resource for exploring EMT-related human genes. We manually curated 377 experimentally verified genes from literature. Functional analyses highlighted the prominent role of proteoglycans in tumor metastatic cascades. In addition, the disease enrichment analysis provides a clue for the potential transformation in affected tissues or cells in Alzheimer’s disease and Type 2 Diabetes. Moreover, the global mutation pattern of EMT-related genes across multiple cancers may reveal common cancer metastasis mechanisms. Our further reconstruction of the EMT-related protein-protein interaction network uncovered a highly modular structure. These results illustrate the importance of dbEMT to our understanding of cell development and cancer metastasis and also highlight the utility of dbEMT for elucidating the functions of EMT-related genes.

Tillage practices can redistribute the soil profiles, and thus affects soil organic carbon (SOC), and its storage. The stratification ratio (SR) can be an indicator of soil quality. This study was conducted to determine tillage effects on the profile distribution of certain soil properties in winter wheat (Triticum aestivum L.) and summer maize (Zea mays L.) systems in the North China Plain (NCP). Three tillage treatments, including no till (NT), rotary tillage (RT), and plow tillage (PT), were established in 2001 in Luancheng County, Hebei Province. The concentration, storage, and SR of SOC and soil total nitrogen (TN) were assessed in both the wheat and maize seasons. Compared with RT and PT, the mean SRs for all depth ratios of SOC under NT increased by 7.85% and 30.61% during the maize season, and by 14.67% and 30.91% during the wheat season, respectively. The SR of TN for 0–5:30–50 cm increased by 140%, 161%, and 161% in the maize season, and 266%, 154%, and 122% in the wheat season compared to the SR for 0–5:5–10 cm under NT, RT and PT, respectively. The data indicated that SOC and TN were both concentrated in the surface-soil layers (0–10 cm) under NT but were distributed relatively evenly through the soil profile under PT. Meanwhile, the storage of SOC and TN was higher under NT for the surface soil (0–10 cm) but was higher under PT for the deeper soil (30–50 cm). Furthermore, the storage of SOC and TN was significantly related to SR of SOC and TN along the whole soil profile (P