[Disseminated nocardiosis caused by Nocardia otitidiscaviarum in an immunocompetent host: a case report].

Nocardiosis can be caused by various Nocardia spp., including Nocardia asteroides, Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica and Nocardia otitidiscaviarum. As compared with the other Nocardia spp., Nocardia otitidiscaviarum appears to be rare which can spread through the bloodstream and affect multiple organs. The disease is usually seen in immunocompromised patients' but may also occur in immunocompetent patients. The clinical symptoms and laboratory and imaging examinations of the disease are nonspecific.Here, we reported a case of disseminated nocardiosis caused by infection with Nocardiosis otitidiscaviarum in an immunocompetent host to improve the knowledge and diagnosis of nocardiosis.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.

[Efficacy comparison among high risk factors questionnaire and Asia-Pacific colorectal screening score and their combinations with fecal immunochemical test in screening advanced colorectal tumor].

Objective: To investigate the effects of high risk factors questionnaire (HRFQ), Asia-Pacific colorectal screening (APCS) score and their combinations with fecal immunochemical test (FIT) in screening advanced colorectal neoplasia, in order to provide an evidence for further optimization of cancer screening program. Methods: A retrospective cohort study method was used to summarize and analyze the results of colorectal tumor screening in Jiashan County, Zhejiang Province from March 2017 to July 2018. Those with severe diseases that were not suitable for colonoscopy and those with mental and behavioral abnormalities who can not cooperate with the screening were excluded. Those who met any one or more of the followings in the HRFQ questionnaire were classified as high-risk people of HRFQ: (1) first-degree relatives with a history of colorectal cancer; (2) subjects with a history of cancer or any other malignant tumor; (3) subjects with a history of intestinal polyps; (4) those with two or more of the followings: chronic constipation (constipation lasted for more than 2 months per year in the past two years), chronic diarrhea (diarrhea lasted for more than 3 months in the past two years, and the duration of each episode was more than one week), mucus and bloody stools, history of adverse life events (occurring within the past 20 years and causing greater trauma or distress to the subject after the event), history of chronic appendicitis or appendectomy, history of chronic biliary disease or cholecystectomy. In this study, those who were assessed as high risk by HRFQ were recorded as "HRFQ (+)", and those who were not at high risk were recorded as "HRFQ (-)". The APCS questionnaire provided risk scores based on 4 risk factors including age, gender, family history and smoking: (1) age: 2 points for 50-69 years old, 3 points for 70 years old and above; (2) gender: 1 point for male, 0 point for women; (3) family history: 2 points for first-degree relatives suffering from colorectal cancer; (4) smoking: 1 point for current or past smoking, 0 point for non-smokers. The population was divided into low-risk (0-1 point), intermediate-risk (2-3 points), and high-risk (4-7 points). Those who were assessed as high risk by APCS were recorded as "APCS (+)", and those with intermediate and low risk were recorded as "APCS (-)". The hemoglobin threshold for a positive FIT was set to 100 µg/L. Those who were assessed as high risk by APCS with positive FIT were recorded as "APCS+FIT (+)". Those who were assessed as high risk by APCS with negative FIT, those who were assessed by APCS as low-middle risk with positive FIT, and those who were assessed by APCS as low-middle with negative FIT were all recorded as "APCS+FIT(-)". Observation indicators in this study were as follows: (1) the screening compliance rate of the cohort and the detection of advanced colorectal tumors; (2) positive predictive value, negative predictive value, sensitivity and specificity of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors; (3) comparison of the detection rate between HRFQ and APCS questionnaire for different colorectal lesions. Using SPSS 21.0 software, the receiver operating characteristic (ROC) curve was drawn to evaluate the clinical value of HRFQ and APCS combined with FIT in screening advanced colorectal tumors. Results: From 2017 to 2018 in Jiashan County, a total of 53 268 target subjects were screened, and 42 093 people actually completed the questionnaire, with a compliance rate of 79.02%. A total of 8145 cases underwent colonoscopy. A total of 3607 cases among HRFQ positive population (5320 cases) underwent colonoscopy, and the colonoscopy compliance rate was 67. 80%; 8 cases were diagnosed with colorectal cancer and 88 cases were advanced colorectal adenoma. A total of 2977 cases among APCS positive population (11 942 cases) underwent colonoscopy, and the colonoscopy compliance rate was 24.93%; 17 cases were diagnosed with colorectal cancer and 148 cases were advanced colorectal adenoma. The positive rate of HRFQ screening was lower than that of APCS [12.6% (5320/42 093) vs. 28.4% (11 942/42 093), χ2=3195. 547, P<0.001]. In the FIT positive population (6223 cases), a total of 4894 cases underwent colonoscopy, and the colonoscopy compliance rate was 78.64%; 34 cases were diagnosed with colorectal cancer and 224 cases were advanced adenoma. The positive predictive values of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors were 2.67%, 5.54%, 5.44%, and 8.56%; negative predictive values were 94.89%, 96.85%, 96.11% and 96.99%; sensitivity was 29.27%, 50.30%, 12.20 % and 39.02%; specificity was 55.09%, 64.03%, 91.11% and 82.51%, respectively. The ROC curves constructed by HRFQ, APCS, FIT, HRFQ+FIT and APCS+FIT indicated that APCS+FIT presented the highest efficacy in screening advanced colorectal tumors (AUC: 0.608, 95%CI: 0.574-0.642). The comparison of the detection rates of different colorectal lesions between HRFQ and APCS questionnaires showed that there were no significant differences in detection rate of inflammatory polyps and hyperplastic polyps between the two questionnaires (both P>0.05). However, as compared to HRFQ questionnaire, APCS questionnaire had higher detection rates in non-advanced adenomas [26.10% (777/2977) vs. 19.43% (701/3607), χ2=51.228, P<0.001], advanced adenoma [4.97% (148/2977) vs. 2.44% (88/3607), χ2=30.249, P<0.001] and colorectal cancer [0.57% (17 /2977) vs. 0.22% (8/3607), χ2=5.259, P=0.022]. Conclusions: APCS has a higher detection rate of advanced colorectal tumors than HRFQ. APCS combined with FIT can further improve the effectiveness of advanced colorectal tumor screening.

[Effects of protein disulfide isomerase on hyperglycemia and hypoxia/reoxygenation injury in H9c2 cardiomyocytes].

Objective: To explore the effect of protein disulfide isomerase (PDI) in diabetic ischemic heart disease. Methods: We established an in vitro model of high glucose and hypoxia/reoxygenation in H9c2 rat myocardial cells. Cultured cells were divided into four groups: Control, high glucose (HG), hypoxia/reoxygenation (H/R) and HG+H/R. Changes in PDI expression mediated by PDI adenovirus(Ad-PDI) infection and siRNA(PDI-siRNA) transfection in myocardial cells were observed by inverted fluorescence microscopy. We also measured lactate dehydrogenase(LDH) activity and malondialdehyde(MDA) and high molecular weight(HMW)-APN concentrations. PDI, APN, cleaved caspase-3, and glucose regulated protein 78 (Grp78) protein expression were detected. Results: PDI expression was significantly decreased in the HG, H/R and HG+H/R groups compared to the Control group; however, LDH activity[(179.7±10.4) U/L、(218.4±18.4) U/L、(328.2±5.3) U/L vs (91.0±11.0) U/L], MDA concentration[(7.0±0.4) µmol/L、(10.0±1.0) µmol/L、(11.7±1.0) µmol/L vs (4.2±1.8) µmol/L], cleaved caspase-3, and Grp78 expression were increased. Interestingly, APN and HMW-APN expression were decreased [(2.01±0.21) µg/L、(1.64±0.27) µg/L、(1.20±0.14) µg/L vs (2.62±0.12) µg/L, all P<0.05]. Over expression of PDI attenuated high glucose and hypoxia/reoxygenation induced apoptosis and oxidative stress in H9c2 cardiomyocytes(all P<0.05), and simultaneously increased APN and HMW-APN expression [(2.86±0.03) µg/L vs (3.03±0.10) µg/L、(2.06±0.05) µg/L vs (2.31±0.06) µg/L、(1.83±0.07) µg/L vs (1.96±0.11) µg/L、(1.20±0.06) µg/L vs (1.39±0.09) µg/L]. PDI-siRNA transfection increased LDH activity, MDA concentration, and cleaved caspase-3 and Grp78 expression, and decreased APN and HMW-APN expression [(0.75±0.09) µg/L vs (0.59±0.09) µg/L、(0.62±0.04) µg/L vs (0.53±0.05) µg/L、(0.55±0.14) µg/L vs (0.51±0.12) µg/L、(0.48±0.12) µg/L vs (0.35±0.08) µg/L] in response to different treatments in cultured H9c2 cardiomyocytes (all P<0.05). Conclusion: PDI may regulate the expression of APN and HMW-APN, and play an important role in the function of diabetic ischemia-reperfusion cardiomyocytes.

Identification and characterization of circRNAs in maize seedlings under deficient nitrogen.

Here, deep sequencing results of the maize transcriptome in leaves and roots were compared under high-nitrogen (HN) and low-nitrogen (LN) conditions to identify differentially expressed circRNAs (DECs). Circular RNAs (circRNAs) are covalently closed non-coding RNA with widely regulatory potency that has been identified in animals and plants. However, the understanding of circRNAs involved in responsive nitrogen deficiency remains to be elucidated. A total of 24 and 22 DECs were obtained from the leaves and roots, respectively. Ten circRNAs were validated by divergent and convergent primers, and 6 DECs showed the same expression tendency validated by reverse transcriptase-quantitative PCR. Integrating the identified differentially expressed miRNAs, 34 circRNAs could act as miRNA decoys, which might play important roles in multiple biological processes, including organonitrogen compound biosynthesis and regulation of the metabolic process. A total of 51 circRNA-parent genes located in the genome-wide association study identified loci were assessed between HN and LN conditions and were associated with root growth and development. In summary, our results provide valuable information regarding further study of maize circRNAs under nitrogen deficiency and provide new insights into screening of candidate genes as well as the improvement of maize regarding nitrogen deficiency resistance. CircRNA-miRNA-mRNA co-expression networks were constructed to explore the circRNAs that participated in biological development and nitrogen metabolism.

TGFß1I1 suppressed cell migration and invasion in colorectal cancer by inhibiting the TGF-ß pathway and EMT progress.

OBJECTIVE: Colorectal cancer (CRC) is the fourth leading cause of death worldwide and there is a need for more specific therapeutic targets and biomarkers for the disease. Transforming growth factor ß1-induced transcript 1 (TGFΒ1I1) was reported to be downregulated in CRC tissues; however, the precise roles of TGFΒ1I1 in CRC remain unclear. PATIENTS AND METHODS: The expression of TGFΒ1I1 in CRC cell lines and tissues was assessed by quantitative Polymerase Chain Reaction (qPCR). TGFΒ1I1 was overexpressed in SW620 and RKO cells. Cell viability was analyzed by a CCK-8 assay. The proportion of apoptotic cells was analyzed by flow cytometry. The EdU cell proliferation assay of SW620 and RKO cells after transfection was performed via flow cytometry. The migration potency of SW620 and RKO cells was analyzed using a cell migration assay. A wound healing assay was performed to assess the migration potency of SW620 and RKO cells. The invasion potency of SW620 and RKO cells after TGFΒ1I1 overexpression was analyzed. The protein levels of VEGF, TGF-ß, MMP9, p-Smad2/3, N-cadherin, and E-cadherin were analyzed by Western blot. RESULTS: Decreased expression of TGFΒ1I1 was found in CRC tissues and cell lines. Overexpression of TGFΒ1I1 inhibited the proliferation and induced the apoptosis of CRC cells. The overexpression of TGFΒ1I1 inhibited the migration and invasion of CRC cells. We also found that the overexpression of TGFΒ1I1 in CRC cells inhibited the TGF-ß pathway and epithelial-mesenchymal transition (EMT) progress. CONCLUSIONS: TGFΒ1I1 suppressed cell migration and invasion in CRC by inhibiting the TGF-ß pathway and EMT progress.

[Efficacy and safety of anti-tumor necrosis factor α monoclonal antibodies in 16 patients with severe/refractory vasculo Behcet's disease].

Objective: To explore the efficacy and safety of anti-tumor necrosis factor alpha (TNFα) monoclonal antibodies (mAbs) for severe/refractory vasculo-Behcet's disease (BD). Method: The clinical data of severe/refractory vasculo-BD patients treated with anti-TNFα mAbs were retrospectively analyzed. Response of anti TNFα mAbs was analyzed. The dosage changes of glucocorticoid, the level of erythrocyte sedimentation rate (ESR) and hypersensitive C-reactive protein (hsCRP) before and after treatment were recorded, as well as side effects. Result: Sixteen patients were enrolled. Arterial lesions were reported in 12 patients, including 9 with arterial aneurysm, 6 with arterial dilation, 2 with stenosis and 2 with occlusion. Seven patients presented venous thrombosis, including lower extremity veins (n=6), cerebral venous sinus (n=2) and inferior vena cava system (n=2). Two cases had both arterial and venous involvement. Before the application of TNFα mAbs, all 16 patients failed to response to prednisone or its equivalent dose of 40 (7.5-90) mg/d in combination with cyclophosphamide, methotrexate, thalidomide or azathioprine for median 4 (0-156) months. After a mean duration of treatment for (17.1±6.5) months, 15 patients achieved complete remission and 1 patient achieved partial remission. Three patients received surgery without any postoperative complications. After using anti TNFα mAbs, the dosage of prednisone [5(0-12.5)mg/d vs. 40(7.5-90)mg/d, P<0.01], ESR [(7.3±4.6) mm/1h vs. (33.5±26.7) mm/1h, P<0.01] and hsCRP [1.9(0.2-11.4) mg/L vs. 24.3(0.4-113.9) mg/L, P<0.01] were significantly decreased. Side effects were observed in 2 patients. One developed pulmonary infection 12 months after adalimumab with conventional treatment. Another patient had allergy to infliximab then switched to adalimumab. Conclusion: In combination with corticosteroids and immunosuppressants, anti-TNF α mAbs are effective and well-tolerated in severe/refractory vasculo-BD, with a favorable steroid -sparing effect and rare postoperative complications.

Clinical outcomes and predictive relapse factors of IgG4-related disease following treatment: a long-term cohort study.

OBJECTIVES: The aim of this study was to investigate the predictive factors for relapse of IgG4-related disease (IgG4-RD) and observe the long-term clinical outcomes in patients with IgG4-RD. METHODS: We included in the present analysis 122 patients who were newly diagnosed with IgG4-RD, treated with glucocorticoid (GC) monotherapy or GC and immunosuppressant combination therapy, and followed for at least 3 years. Clinical relapse, response and side effects were recorded. RESULTS: The cumulative relapse rates of patients in this study were 10.66%, 22.95% and 27.87% at 12, 24 and 36 months, respectively. Complete drug withdrawal was an independent risk factor for disease relapse. Higher serum IgG4 concentrations, involvement of more organs, higher IgG4 RI scores and elevation of eosinophils at baseline were closely associated with disease relapse. Re-elevation of serum IgG4 concentrations and low GC maintenance dosage during the follow-up period were significantly associated with clinical relapse. The GC dosage should be more than 6.25 mg day-1 as monotherapy during the maintenance stage; moreover, combining with immunosuppressants can reduce the GC dosage. Adding GC or immunosuppressants for patients with re-elevation of serum IgG4 levels could prevent later disease relapse. No serious complications were noted during long-term follow-up. CONCLUSIONS: The combination of GC with immunosuppressants was more effective than GC monotherapy during the steroid tapering and maintenance stages. Higher serum IgG4 levels, involvement of more organs, higher IgG4 RI scores, history of allergy, eosinophil elevation at baseline, re-elevation of serum IgG4 levels and lower GC maintenance dosage at follow-up might be predictive of relapse.

[Disputes and exploration of neoadjuvant and adjuvant therapy for colon cancer].

Perioperative treatment combined with radical resection is the major approach to cure non-metastatic colon cancer. A precise evaluation and perioperative treatment would probably improve the R0 resection rate, recurrence-free survival and overall survival of colon cancer patients. Recently, individualized treatment is the mainstream due to the development of molecular pathology and multi-disciplinary therapy. The indications and course of perioperative treatment and preoperative neoadjuvant therapy of colon cancer are still in intense discussion. The present review will mainly discuss three topics. Firstly, the various reaction of adjuvant therapy to stage II colon cancer is caused by patients' heterogeneity. Choosing stratified treatment for these patients according to clinical and molecular pathological features is the future. Secondly, we discuss the adjuvant chemotherapy course for stage III colon cancer according to the Chinese Society of Clinical Oncology (CSCO) guideline and the progress of this field. Lastly, we summarize the status and significance of colon cancer neoadjuvant therapy.

MicroRNA-770-5p is involved in the development of diabetic nephropathy through regulating podocyte apoptosis by targeting TP53 regulated inhibitor of apoptosis 1.

OBJECTIVE: Diabetic nephropathy (DN) is a major diabetic micro-vascular complication, and podocyte apoptosis induced by high glucose (HG) is a typical early feature of DN. Studies have shown that microRNAs (miRNAs) play a crucial role in the pathogenesis of DN. The purpose of the current study was to explore the role and molecular mechanism of miR-770-5p in podocyte apoptosis in DN. PATIENTS AND MATERIALS AND METHODS: In vitro podocyte model of DN was conducted by treatment conditionally immortalized mouse podocytes with HG (30 mM D-glucose). The level of miR-770-5p in podocytes was detected using quantitative real-time PCR (qRT-PCR), and protein levels were measured using Western blot assay in our current study. The relationship between miR-770-5p and TP53 regulated inhibitor of apoptosis 1 (TRIAP1) was revealed by TargetScan and dual luciferase reporter assay. Cell proliferation ability and cell apoptosis were determined by using cell counting kit-8 (CCK-8) assay and flow cytometer (FCM), respectively. RESULTS: We found that miR-770-5p was significantly upregulated in podocytes under HG condition. TRIAP1 was a target gene of miR-770-5p and it was down-regulated in podocytes by HG treatment. Further analysis indicated that HG induced cell proliferation ability reduction, cell apoptosis enhancement and apoptotic peptidase activating factor 1(APAF1)/Caspase9 pathway exaltation in podocytes were prevented by miR-770-5p down-regulation. More importantly, the results showed that all the effects of miR-770-5p inhibitor on HG induced podocytes were eliminated by TRIAP1 silencing. S.-Z. Zhang, X.-J. Qiu, S.-S. Dong, L.-N. Zhou, Y. Zhu, M.-D. Wang, L.-W. Jin We showed that miR-770-5p was upregulated in the in vitro model of DN, and it might promote the development of DN through regulating podocyte apoptosis by targeting TRIAP1.

Synergistic antinociception between ZC88, an N-type voltage-dependent calcium channel blocker, and ibuprofen in mouse models of visceral and somatic inflammatory pain.

BACKGROUND: A combination of analgesic agents with different mechanisms can induce additive or synergistic analgesia. The N-type voltage-dependent calcium channel (N-VDCC) is a novel therapeutic target for pain control. In addition to providing effective pain relief when used alone, N-VDCC blockers produce synergistic analgesia when used in combination with opiates. However, the interaction between N-VDCC blockers and nonsteroidal anti-inflammatory drugs (NSAIDs) remains unclear. METHODS: Using isobolographic analysis and composite additive curve analysis, the antinociceptive interaction between ZC88, a selective N-VDCC blocker and ibuprofen, a classical NSAID, was investigated in two mouse models of visceral and somatic inflammatory pain. RESULTS: In the acetic acid writhing test, both ZC88 (10.5-42 mg/kg, intraperitoneally) and ibuprofen (50-200 mg/kg, orally) produced dose-dependent antinociception, with ED50 values of 27.2 and 100.5 mg/kg, respectively. ZC88 in combination with ibuprofen (ZC88 + ibuprofen) also induced significant antinociception, and isobolographic analysis revealed a synergistic interaction at 50% effect level. The experimental ED50 (ED50 mix ) of this combination (34.5 mg/kg) was significantly lower than the theoretical ED50 (ED50 add ; 63.8 mg/kg). Additionally, composite additive curve analysis displayed synergistic interaction at other effect levels. In the formalin test, ZC88 or ibuprofen alone significantly reduced late-phase rather than early-phase pain, with ED50 values of 31.3 and 123.9 mg/kg, respectively. Similarly, both isobolographic analysis and composite additive curve analysis revealed synergistic antinociception of ZC88 + ibuprofen (40.6 mg/kg of ED50 mix vs. 77.6 mg/kg of ED50 add ). CONCLUSION: ZC88 in combination with ibuprofen produces synergistic antinociception in mouse models of somatic and visceral inflammatory pain. SIGNIFICANCE: Because ZC88 + ibuprofen achieves the same antinociceptive effect at lower doses, the use of this combination could result in fewer dose-related untoward effects. The potentiation of ZC88 on ibuprofen-induced antinociception indicates that N-VDCC blocker has potential benefit to treat severe inflammatory pain.

Isolation and identification of pathogenic Aeromonas veronii from a dead Yangtze finless porpoise.

Diseases caused by Aeromonas veronii in freshwater fish have been widely reported, but other species such as aquatic mammals have probably been overlooked. Here, we identified one isolate of A. veronii from a Yangtze finless porpoise Neophocaena asiaeorientalis asiaeorientalis exhibiting disease and mortality, and subsequently confirmed its virulence in artificial infection of BALB/c mice. The bacterial isolate was identified as A. veronii based on physiological, biochemical, and phenotypic features, and homology of the 16S rRNA, cpn60, rpoB, dnaJ and gyrB genes. Our results expand the known host spectrum of A. veronii, which is of great importance for the etiology of porpoise, dolphin, and other cetacean diseases.

Transcriptomic differential lncRNA expression is involved in neuropathic pain in rat dorsal root ganglion after spared sciatic nerve injury.

Dorsal root ganglia (DRG) neurons regenerate spontaneously after traumatic or surgical injury. Long noncoding RNAs (lncRNAs) are involved in various biological regulation processes. Conditions of lncRNAs in DRG neuron injury deserve to be further investigated. Transcriptomic analysis was performed by high-throughput Illumina HiSeq2500 sequencing to profile the differential genes in L4-L6 DRGs following rat sciatic nerve tying. A total of 1,228 genes were up-regulated and 1,415 down-regulated. By comparing to rat lncRNA database, 86 known and 26 novel lncRNA genes were found to be differential. The 86 known lncRNA genes modulated 866 target genes subject to gene ontology (GO) and KEGG enrichment analysis. The genes involved in the neurotransmitter status of neurons were downregulated and those involved in a neuronal regeneration were upregulated. Known lncRNA gene rno-Cntnap2 was downregulated. There were 13 credible GO terms for the rno-Cntnap2 gene, which had a putative function in cell component of voltage-gated potassium channel complex on the cell surface for neurites. In 26 novel lncRNA genes, 4 were related to 21 mRNA genes. A novel lncRNA gene AC111653.1 improved rno-Hypm synthesizing huntingtin during sciatic nerve regeneration. Real time qPCR results attested the down-regulation of rno-Cntnap lncRNA gene and the upregulation of AC111653.1 lncRNA gene. A total of 26 novel lncRNAs were found. Known lncRNA gene rno-Cntnap2 and novel lncRNA AC111653.1 were involved in neuropathic pain of DRGs after spared sciatic nerve injury. They contributed to peripheral nerve regeneration via the putative mechanisms.

[The application value of suppression head pulse paradigm (SHIMP) in vestibular examination].

Objective:To summarize different results of suppression head impulse paradigm (SHIMP) and head impulse paradigm (HIMP) in patients with bilateral and unilateral vestibular loss and to evaluate the practicability of SHIMP in clinical vestibular examination. Method: Seventy subjects with unilateral vestibular loss, bilateral vestibular loss and healthy were included. Morphological characteristics of HIMP and SHIMP results were analyzed. The differences of VOR gains were compared with the paired t test. Result: Almost all SHIMP showed anti-compensatory saccades in healthy group. Less anti-compensatory saccades occurred in the affected side of patient with vestibular loss. The VOR gains showed there was a significant correlation(P<0.05) between HIMP and SHIMP. Conclusion: Different to compensatory saccades in HIMP indicate potential loss in vestibular function, anti-compensatory saccades in SHIMP shows vestibular function in patients. The combination of these two mthods will benefit disease screening and vestibular rehabilitation in clinical examination.

STEEL participates in fracture healing through upregulating angiogenesis-related genes by recruiting PARP 1.

OBJECTIVE: To explore the effect of STEEL on fracture healing and its underlying mechanism. PATIENTS AND METHODS: A total of 31 patients with long bone fracture and who received reoperation because of bone nonunion, delayed union or healing disorder in the Wuxi Nine Hospital Affiliated to Soochow University from July 2016 to February 2018 were selected. The bone callus at the fracture site was collected from each patient during the reoperation. QRT-PCR (Quantitative Real-Time Polymerase Chain Reaction) was used to detect STEEL expression in the callus tissues of the treatment group (bone nonunion or delayed union) and the control group. In addition, we measured the number of blood vessels in the fracture tissues by immunohistochemistry. After the construction of tibial fracture model in mice, STEEL expression and the total number of blood vessels in the treatment group (sawing treatment) and the control group (sham operation) were detected, respectively. For in vitro experiments, CCK-8 (cell counting kit-8) assay was performed to detect cell proliferation after knockdown or overexpression of STEEL in the vascular endothelial cells. The binding condition of STEEL and its interacting proteins were detected by RIP (RNA binding protein immunoprecipitation), and the binding of PARP 1 [poly (ADP-ribose) polymerase 1] with gene promoter was observed by ChIP (chromatin immunoprecipitation assay). Western blot was used to detect the expression level of VEGF (vascular endothelial growth factor). RESULTS: STEEL expression and the vascular density in the callus tissues of the treatment group were significantly lower than those of the control group. Downregulated STEEL remarkably decreased the proliferation ability of HUVEC cells. Meanwhile, the vascular density was also significantly decreased in mice with a tibial fracture. Overexpressed STEEL obtained the opposite results. STEEL could interact with PARP 1 to regulate expressions of downstream genes. Moreover, STEEL could also promote angiogenesis by elevating VEGF expression. CONCLUSIONS: We showed that STEEL expression could partly represent the angiogenesis of fracture sites. Moreover, it promoted angiogenesis by elevating VEGF expression.

High-Density Genetic Map Construction and Identification of QTLs Controlling Oleic and Linoleic Acid in Peanut using SLAF-seq and SSRs.

The cultivated peanut, A. hypogaea L., is an important oil and food crop globally.High-density genetic linkage mapping is a valuable and effective method for exploring complex quantitative traits. In this context, a recombinant inbred line (RIL) of 146 lines was developed by crossing Huayu28 and P76. We developed 433,679 high-quality SLAFs, of which 29,075 were polymorphic. 4,817 SLAFs were encoded and grouped into different segregation patterns. A high-resolution genetic map containing 2,334 markers (68 SSRs and 2,266 SNPs) on 20 linkage groups (LGs) spanning 2586.37 cM was constructed for peanut. The average distance between adjacent markers was 2.25 cM. Based on phenotyping in seven environments, QTLs for oleic acid (C18:1), linoleic acid (C18:2) and the ratio of oleic acid to linoleic acid (O/L) were identified and positioned on linkage groups A03, A04, A09, B09 and B10. Marker2575339 and Marker2379598 in B09 were associated with C18:1, C18:2 and O/L in seven environments, Marker4391589 and Marker4463600 in A09 were associated with C18:1, C18:2 and O/L in six environments. This map exhibits high resolution and accuracy, which will facilitate QTL discovery for essential agronomic traits in peanut.

Transcriptomic differential lncRNA expression is involved in neuropathic pain in rat dorsal root ganglion after spared sciatic nerve injury

Dorsal root ganglia (DRG) neurons regenerate spontaneously after traumatic or surgical injury. Long noncoding RNAs (lncRNAs) are involved in various biological regulation processes. Conditions of lncRNAs in DRG neuron injury deserve to be further investigated. Transcriptomic analysis was performed by high-throughput Illumina HiSeq2500 sequencing to profile the differential genes in L4-L6 DRGs following rat sciatic nerve tying. A total of 1,228 genes were up-regulated and 1,415 down-regulated. By comparing to rat lncRNA database, 86 known and 26 novel lncRNA genes were found to be differential. The 86 known lncRNA genes modulated 866 target genes subject to gene ontology (GO) and KEGG enrichment analysis. The genes involved in the neurotransmitter status of neurons were downregulated and those involved in a neuronal regeneration were upregulated. Known lncRNA gene rno-Cntnap2 was downregulated. There were 13 credible GO terms for the rno-Cntnap2 gene, which had a putative function in cell component of voltage-gated potassium channel complex on the cell surface for neurites. In 26 novel lncRNA genes, 4 were related to 21 mRNA genes. A novel lncRNA gene AC111653.1 improved rno-Hypm synthesizing huntingtin during sciatic nerve regeneration. Real time qPCR results attested the down-regulation of rno-Cntnap lncRNA gene and the upregulation of AC111653.1 lncRNA gene. A total of 26 novel lncRNAs were found. Known lncRNA gene rno-Cntnap2 and novel lncRNA AC111653.1 were involved in neuropathic pain of DRGs after spared sciatic nerve injury. They contributed to peripheral nerve regeneration via the putative mechanisms.

MEG3 long non-coding RNA prevents cell growth and metastasis of osteosarcoma.

OBJECTIVE: This study aimed to investigate the role of long non-coding RNA MEG3 (lncRNA MEG3) in osteosarcoma (OS) and further explore the underlying molecular mechanism. MATERIALS AND METHODS: The expression profiles of MEG3 in OS cell lines and normal osteoblast cell line were detected by qRT-PCR. MEG3 was over-expressed in OS cell line by using LV-MEG3. MTT and colony-formation assays were applied for cell proliferation analysis. Cell migration assay was applied to investigate the cell migration ability. In addition, the expression levels of cell growth and metastasis related factors (Notch1, Hes1, TGF-ß, N-cadheren and E-cadheren) were determined to illustrate the mechanisms. RESULTS: We found that compared with normal osteoblast hFOB1.19 cell line, MEG3 was significantly down-regulated in MG63 and U2OS cell lines, particularly in MG-63 cells. MEG3 was significantly up-regulated in MG63 cells by LV-MEG3. Cell proliferation and migration ability were obviously repressed by MEG3 over-expression. In addition, MEG3 over-expression markedly inhibited Notch1, Hes1,TGF-ß and N-cadheren expression, and the expression level of E-cadheren was improved. CONCLUSIONS: These results indicated that MEG3 could prevent cell growth and metastasis of OS by repressing Notch and TGF-ß signaling pathway, thus providing a potential therapeutic target for OS treatment (Tab. 1, Fig. 4, Ref. 30).