The plant immune receptor SNC1 monitors helper NLRs targeted by a bacterial effector.

Plants deploy intracellular receptors to counteract pathogen effectors that suppress cell-surface-receptor-mediated immunity. To what extent pathogens manipulate intracellular receptor-mediated immunity, and how plants tackle such manipulation, remains unknown. Arabidopsis thaliana encodes three similar ADR1 class helper nucleotide-binding domain leucine-rich repeat receptors (ADR1, ADR1-L1, and ADR1-L2), which are crucial in plant immunity initiated by intracellular receptors. Here, we report that Pseudomonas syringae effector AvrPtoB suppresses ADR1-L1- and ADR1-L2-mediated cell death. ADR1, however, evades such suppression by diversifying into two ubiquitination sites targeted by AvrPtoB. The intracellular sensor SNC1 interacts with and guards the CCR domains of ADR1-L1/L2. Removal of ADR1-L1/L2 or delivery of AvrPtoB activates SNC1, which then signals through ADR1 to trigger immunity. Our work elucidates the long-sought-after function of SNC1 in defense, and also how plants can use dual strategies, sequence diversification, and a multi-layered guard-guardee system, to counteract pathogen's attack on core immunity functions.

The Sagittal Parameters and Efficacy of Pedicle Subtraction Osteotomy in Patients with Ankylosing Spondylitis and Kyphosis Under Different Lumbar Sagittal Morphologies.

OBJECTIVE: This study aimed to compare the changes in sagittal parameters and the efficacy of pedicle subtraction osteotomy (PSO) in patients with ankylosing spondylitis (AS) and kyphosis under different lumbar sagittal morphologies and to explore the effect of sagittal morphology on the selection of PSO levels. METHODS: A total of 24 patients with AS and thoracolumbar kyphosis (TK) who were admitted to the First Affiliated Hospital of Xinjiang Medical University between 2008 and 2019 were enrolled in this study. They were divided into two groups: a lumbar lordosis group (n = 14) and a lumbar kyphosis group (n = 10). Changes in sagittal parameters, lumbar Japanese Orthopaedic Association (JOA) scores, and visual analog scale (VAS) scores for lumbar pain before and after operation were compared between the two groups to evaluate postoperative efficacy. RESULTS: The preoperative lumbar lordosis (LL) was -29.29 ± 5.40 (lordosis) and 13.50 ± 3.65 (kyphosis) (P < 0.01), and the preoperative sagittal vertical axis (SVA) was 171.35 ± 25.46 (lordosis) and 223.58 ± 21.87 (kyphosis) (P < 0.01). Preoperative global kyphosis (GK) was 75.71 ± 5.26 (lordosis) and 86.30 ± 10.32 (kyphosis) (P < 0.05). All patients in the lordosis group underwent PSO surgery at the twelfth thoracic vertebra (T12) or the first lumbar spinal vertebra (L1), while all patients in the kyphosis group underwent the surgery at the second or third lumbar spinal vertebra (L2 or L3). The differences in postoperative GK, LL, and SVA between the two groups were not significant (P > 0.05). The JOA scores of the two groups increased from 13.00 ± 0.83 (lordosis) and 11.30 ± 0.93 (kyphosis) before surgery to 21.00 ± 0.67 and 19.70 ± 0.60 after surgery (P < 0.05). CONCLUSION: Preoperative lumbar sagittal morphology needs to be considered when selecting the optimal osteotomy plane. An osteotomy can achieve the greatest success in patients with lumbar kyphosis at L2/L3; for patients with lumbar lordosis, it can achieve satisfactory outcomes at T12/L1.

Anatomy and Imaging Studies on Cortical Bone Screw Freehand Placement Applying Anatomical Targeting Technology.

OBJECTIVES: A series of constant anatomical structures were used as guide targets for screw placement to improve the accuracy of cortical screw placement and reduce surgical injury and fluoroscopy radiation. The most commonly used angles and distances between the cortical bone screw insertion point and the lateral margins of the isthmus were selected as the contents of the questionnaire. METHODS: A total of 40 physicians were selected to determine the specific values for each angle and distance. Screw placements were performed on four dry and six wet lumbar spine specimens according to the proposed anatomical target guidance technique. A total of 100 cortical bone trajectories were evaluated using X-ray and CT scanning of the specimens to verify the practicability, accuracy, and safety of the anatomical target guidance technique in screw placement. RESULTS: The average deviation rates for angle and distance determination were 105.5% and 14.33%, respectively, indicating a significant difference between the estimated and actual values from other angles (P < 0.05). Based on visual inspection, probe penetration, X-ray, and CT examination of 100 cortical bone trajectories, the excellent rate of 40 trajectories on four dry specimens was 95%, while that of 60 trajectories on six wet specimens was 88.7%. CONCLUSION: Use of lumbar constant anatomical structures as targeting guidance could assist cortical bone screw placement and reduce surgical damage.

In-vitro characterisation of a novel antimicrobial agent, TNP-2092, against Helicobacter pylori clinical isolates.

BACKGROUND AND OBJECTIVES: TNP-2092 is a novel dual-action lead compound consisting of rifamycin SV and 4H-4-oxo-quinolizine pharmacophores, with a broad spectrum of antibacterial activities. This compound is currently in the early stage of clinical development for Helicobacter pylori infection. The aim of the present study was to determine the antibacterial activity of TNP-2092 against H. pylori isolated from primary patients. METHODS: A total of 100 H. pylori clinical isolates from primary patients were selected. The minimum inhibitory concentrations (MICs) for clarithromycin, levofloxacin, rifampin and TNP-2092 were determined using an agar dilution method. A time-kill study was performed with different concentrations of TNP-2092 relevant to MIC against H. pylori ATCC strain 43504 for up to 24 hours. The time-kill study with drug concentrations of 0-4 × MIC was also used to determine the antibacterial activity of TNP-2092 against H. pylori under different pH conditions (pH 4-7). RESULTS: The primary resistance percentages to clarithromycin, levofloxacin, rifampin and TNP-2092 were 13, 18, 1 and 1%, respectively. TNP-2092 killing kinetics were both concentration and time dependent. The effectiveness of TNP-2092 against H. pylori was gradually reduced with a decrease in pH. CONCLUSIONS: TNP-2092 is highly active against H. pylori and against strains resistant to clarithromycin or levofloxacin. Its antibacterial activity is both concentration- and time-dependent .The antibacterial activity of TNP-2092 appears to be pH-dependent and is more active under neutral pH. TNP-2092 represents a promising new therapy for the treatment of H. pylori infection in primary patients.

Acupuncture intervention in ischemic stroke: a randomized controlled prospective study.

Stroke is one of the most common causes of death and few pharmacological therapies show benefits in ischemic stroke. In this study, 290 patients aged 40-75 years old with first onset of acute ischemic stroke (more than 24 hours but within 14 days) were treated with standard treatments, and then were randomly allocated into an intervention group (treated with resuscitating acupuncture) and a control group (treated using sham-acupoints). Primary outcome measures included Barthel Index (BI), relapse and death up to six months. For the 290 patients in both groups, one case in the intervention group died, and two cases in the control group died from the disease (p = 0.558). Six patients of the 144 cases in the intervention group had relapse, whereas 34 of 143 patients had relapse in the control group (p < 0.001). The mean values for BI at six months were 70.25 ± 20.37 and 57.43 ± 19.61 for the two groups, respectively (p < 0.01). Acupuncture resulted in a significant difference between the two groups for the National Institute of Health Stroke Scale (NIHSS), not at two weeks (7.03 ± 3.201 vs. 8.13 ± 3.634; p = 0.067), but at four weeks (4.15 ± 2.032 vs. 6.35 ± 3.131, p < 0.01). The Chinese Stroke Scale (CSS) at four weeks showed more improvement in the intervention group than that in the control group (9.40 ± 4.51 vs. 13.09 ± 5.80, p < 0.001). Stroke Specific Quality of Life Scale (SS-QOL) at six months was higher in the intervention group (166.63 ± 45.70) than the control group (143.60 ± 50.24; p < 0.01). The results of this clinical trial showed a clinically relevant decrease of relapse in patients treated with resuscitating acupuncture intervention by the end of six months, compared with needling at the sham-acupoints. The resuscitating acupuncture intervention could also improve self-care ability and quality of life, evaluated with BI, NIHSS, CSS, Oxford Handicap Scale (OHS), and SS-QOL.

[Experimental study of the correlation of telomerase and intramedullary scar after spinal cord injury in rats].

OBJECTIVE: To detect the expression of telomerase in glial scar and its correlation with glial scar. METHODS: There were 120 Sprague Dawley rats were randomly divided into non-interference group of telomerase, interference group of telomerase and control group. Non-interference group and interference group were for spinal cord injury, which adopted Allen's Weight Dropping to make molding; control group was for sham operation to open the vertebral plate and expose spinal marrow, in which spinal cord injury would not be caused. The expression of telomerase and glial fibrillary acidic profein (GFAP) was detected by PCR-ELISA and Western blot, and the formation of glial scar was observed by immunofluorescence on the 1st, 3rd, 5th, 7th, 14th, 28th, 42 th and 56th day after the spinal injury, and analyzed its relativity. RESULTS: The expression of telomerase in non-interference group was (0.180 ± 0.004 - 1.217 ± 0.072), which was significantly higher than those in interference group (0.028 ± 0.007 - 0.092 ± 0.004, χ(2) = 28.753 - 37.518, P < 0.05) and control group (0.072 ± 0.007 - 0.075 ± 0.004, χ(2) = 18.618 - 41.093, P < 0.05) at all the time, with statistical significance. The expression of GFAP in non-interference group was (1.98 ± 0.15 - 19.40 ± 0.55) which was significantly higher than those in interference group (1.10 ± 0.13 - 16.64 ± 1.02, χ(2) = 14.538 - 37.366, P < 0.05) and control group (0.44 ± 0.05 - 0.48 ± 0.04, χ(2) = 16.733 - 34.041, P < 0.05) at all the time, with statistical significance. The expression of GFAP showed a linear correlation with that of telomerase in non-interference group, and with statistical differences (r = 0.755, P < 0.01). The expression of telomerase in interference group and control group were always negative. Glial scar observed by immunofluorescence in non-interference group was heavier than that in interference group, and control group showed no formation of glial scar. CONCLUSIONS: Telomerase shows a dynamic expression in glial scar and has positive correlational linear relationship with GFAP which shows the formation of glial scar. And the telomerase may be an important factor in promoting the formation of glial scar.

[Clinical characteristics and treatment for patients with low back and leg pain caused by lumbar annular tears].

OBJECTIVE: To investigate whether annular tears is a cause of low back and radiating leg pain and explore the clinical characteristics and treatment for patients with this condition. METHODS: A total of 34 patients with low back and radiating leg pain, but without lumbar disc herniation on CT (computed tomography) or MRI (magnetic resonance imaging), were examined by electrophysiological studies and discography to identify whether there were or not annular tears and nerve root injury and decipher the relations between them. The series included 15 males and 19 females with an average age of 45.6 years old and the average duration of symptoms was 25.8 months. All patients with annular tears and positive pain provocation test were treated by local windowing decompression and debridement of nucleus pulposus after failed conservative treatment. The pre- and post-operative functions and pain were evaluated by JOA (Japanese Orthopedic Association) and VAS (visual analog scale) scores respectively. The average follow-up was 17.4 months. RESULTS: The clinical manifestations included low back and radiating leg pain, intermittent claudication and nerve root injury. No significant abnormalities were discovered on X-ray and CT scan. T2W images of magnetic resonance demonstrated a low intensity or black disc in all patients and high-intensity zone (HIZ) (n = 21). Electromyography showed nerve root injury (n = 27). Abnormality of conduction velocities of common peroneal nerve (n = 7) and tibial nerve (n = 3) were found. Thirty-four patients with 38 discs displayed pain reproduction on contrast injection during discography and the sites of annular tears were confirmed on CT scan after discography. Pre- and post-operative average JOA scale score was 8.7 points and 13.5 points, the recovery ratio 76.2% and the excellent and good outcomes 88.2%. Pre- and post-operative average VAS score was 8.6 points and 2.8 points. And the recovery rate was 80.5%. CONCLUSION: The annular tears result in low back and radiating leg pain. And the typical characteristics are low back and radiating leg pain, intermittent claudication and nerve root injury. MRI and electrophysiological studies play an important role in diagnosing this condition. Lumbar discography is the decisive method and prerequisite of selecting surgery. Local windowing decompression and debridement of nucleus pulposus is a simple and effective method.

[Intraobserver and interobserver reliability of the King, Lenke, and PUMC classification systems for idiopathic scoliosis].

OBJECTIVE: To evaluate the intraobserver and interobserver reliability and main influencing factors of the King, Lenke, and PUMC classification systems for idiopathic scoliosis (IS) using radiographs that had not been premeasured. METHODS: Fifty-six patients with IS, 9 male and 47 female, aged 15.4 (11 - 18), underwent preoperative X-ray photography of spine standing full-length posteroanterior and lateral films and left and right supine side-bending radiographs. The films were read by four orthopedic surgeons independently to do measurement and typing according to the King, Lenke, and PUMC classification systems respectively. Two weeks later, the sequence of the X-ray films was re-ordered and the 4 surgeons read them and did measurement and typing once more. The average percentage of intraobserver and interobserver agreement was calculated. Kappa coefficients were used to determine the intraobserver and interobserver reliability. RESULTS: King classification demonstrated fair interobserver reliability and excellent intraobserver reliability. The mean interobserver reliability was 65.8% (Kappa coefficient = 0.542), while the intraobserver reliability was 82.6% (Kappa coefficient = 0.767). The main reason of disagreement was distinguishment of the King type II and type III. Another reason was assessment of King type V. The complete Lenke classification demonstrated poor reliability. The mean interobserver reliability was 50.0% (Kappa coefficient = 0.438), and the intraobserver reliability was 47.0% (Kappa coefficient = 0.402). The 3 components of Lenke classification had fair interobserver and intraobserver reliability when they were examined separately. The main reasons for disagreement arose from judging whether there was a structural upper thoracic curve and assigning sagittal thoracic modifier. The PUMC type demonstrated excellent intraobserver and interobserver reliability with a mean interobserver reliability of 87.8% (Kappa coefficient = 0.757), and a mean intraobserver reliability of 92.9% (Kappa coefficient = 0.958). Its subtypes demonstrated fair agreement with the mean interobserver reliability of 70.2% (Kappa coefficient = 0.629), and a mean intraobserver reliability of 74.1% (Kappa coefficient = 0.674). The main reasons for disagreement were definition of a curvature and Cobb angle measurement. CONCLUSION: King and PUMC classification systems have higher interobserver and intraobserver reliability than Lenke classification. The reliability levels of the 3 classification systems are all influenced by many factors. Judgment of an upper thoracic curve, variable of Cobb angle measurement, and relationship of the central vertical sagittal line to apex of curve are the common reasons for disagreement in these 3 classifications.