Synthesis and Antifungal Activity of Norbornene Carboxamide/sulfonamide Derivatives as Potential Fungicides Targeting Laccase.

To explore more potential fungicides with new scaffolds, thirty-seven norbornene carboxamide/sulfonamide derivatives were designed, synthesized, and assayed for inhibitory activity against six plant pathogenic fungi and oomycetes. The preliminary antifungal assay suggested that the title derivatives showed moderate to good antifungal activity against six plant pathogens. Especially, compound 6 e presented excellent in vitro antifungal activity against Sclerotinia sclerotiorum (EC50=0.71 mg/L), which was substantially stronger than pydiflumetofen. In vivo antifungal assay indicated 6 e displayed prominent protective and curative effects on rape leaves infected by S. sclerotiorum. The preliminary mechanism research displayed that 6 e could damage the surface morphology and inhibit the sclerotia formation of S. sclerotiorum. In addition, the in vitro enzyme inhibition bioassay indicated that 6 e displayed pronounced laccase inhibition activity (IC50=0.63 µM), much stronger than positive control cysteine. Molecular docking elucidated the binding modes between 6 e and laccase. The bioassay results and mechanism investigation demonstrated that this class of norbornene carboxamide/sulfonamide derivatives could be promising laccase inhibitors for novel fungicide development.

Design, synthesis, antifungal evaluation and mechanism study of novel norbornene derivatives as potential laccase inhibitors.

BACKGROUND: To discover novel fungicide candidates, five series of novel norbornene hydrazide, bishydrazide, oxadiazole, carboxamide and acylthiourea derivatives (2a-2t, 3a-3f, 4a-4f, 5a-5f and 7a-7f) were designed, synthesized and assayed for their antifungal activity toward seven representative plant fungal pathogens. RESULTS: In the in vitro antifungal assay, some title norbornene derivatives presented good antifungal activity against Botryosphaeria dothidea, Sclerotinia sclerotiorum and Fusarium graminearum. Especially, compound 2b exhibited the best inhibitory activity toward B. dothidea with the median effective concentration (EC50) of 0.17 mg L-1, substantially stronger than those of the reference fungicides boscalid and carbendazim. The in vivo antifungal assay on apples revealed that 2b had significant curative and protective effects, both of which were superior to boscalid. In the preliminary antifungal mechanism study, 2b was able to injure the surface morphology of hyphae, destroy the cell membrane integrity and increase the intracellular reactive oxygen species (ROS) level of B. dothidea. In addition, 2b could considerably inhibit the laccase activity with the median inhibitory concentration (IC50) of 1.02 µM, much stronger than that of positive control cysteine (IC50 = 35.50 µM). The binding affinity and interaction mode of 2b with laccase were also confirmed by molecular docking. CONCLUSION: This study presented a promising lead compound for the study of novel laccase inhibitors as fungicidal agrochemicals, which demonstrate significant anti-B. dothidea activity and laccase inhibitory activity. © 2024 Society of Chemical Industry.

COVID-19 in patients with myasthenia gravis: a single-center retrospective study in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been a great concern since 2019. Patients with myasthenia gravis (MG) may be at higher risk of COVID-19 and a more severe disease course. We examined the associations between COVID-19 and MG. METHODS: This single-center retrospective cohort study involved 134 patients who were diagnosed with MG from June 2020 to November 2022 and followed up until April 2023. They were divided into a COVID-19 group and non-COVID-19 group. Logistic regression analysis was used to detect factors potentially associating COVID-19 with MG. RESULTS: Of the 134 patients with MG, 108 (80.6%) had COVID-19. A higher number of comorbidities was significantly associated with an increased risk of COVID-19 (p = 0.040). A total of 103 patients (95.4%) had mild/moderate COVID-19 symptoms, and 4 patients (3.7%) were severe/critical symptoms (including 2 deaths). Higher age (p = 0.036), use of rituximab (p = 0.037), tumors other than thymoma (p = 0.031), Hashimoto's thyroiditis (p = 0.011), more comorbidities (p = 0.002), and a higher baseline MG activities of daily living (MG-ADL) score (p = 0.006) were risk factors for severe COVID-19 symptoms. The MG-ADL score increased by ≥ 2 points in 16 (15.7%) patients. Dry cough and/or expectoration (p = 0.011), use of oral corticosteroids (p = 0.033), and use of more than one kind of immunosuppressant (p = 0.017) were associated with the increase of the post-COVID-19 MG-ADL score. CONCLUSION: Most patients with MG have a mild course of COVID-19. However, patients with older age, many comorbidities, a high MG-ADL score, and use of a variety of immunosuppressants during COVID-19 may be more prone to severe symptoms.

Pathological findings with vacuoles in anti-mitochondrial antibody-positive inflammatory myopathy.

BACKGROUND: A few patients with inflammatory myopathy showed anti-mitochondrial antibody (AMA) positivity. This study aimed to report the clinical and pathological findings with vacuoles in 3 cases of such patients. METHODS: Three cases with myositis from the Myositis Clinical Database of Peking University First Hospital were identified with AMA positivity. Their clinical records were retrospectively reviewed and the data was extracted. All the 3 cases underwent muscle biopsy. RESULTS: Three middle-aged patients presented with chronic-onset weakness of proximal limbs, marked elevation of creatine kinase, and AMA-positivity. Two of the 3 cases meet the criteria of primary biliary cholangitis. All the 3 cases presented with cardiac involvement and proteinuria. Two cases developed type 2 respiratory failure. MRI of the thigh muscle showed multiple patches of edema bilaterally in both cases, mostly in the adductor magnus. Pathological findings include degeneration of muscle fibers, diffused MHC-I positivity, and complement deposits on cell membranes. Vacuoles without rims of different sizes were discovered under the membrane of the muscle fibers. A few RBFs were discovered in case 1, while a diffused proliferation of endomysium and perimysium was shown in case 2. CONCLUSIONS: AMA-positive inflammatory myopathy is a disease that could affect multiple systems. Apart from inflammatory changes, the pathological findings of muscle can also present vacuoles.

Homozygous missense variants in YKT6 result in loss of function and are associated with developmental delay, with or without severe infantile liver disease and risk for hepatocellular carcinoma.

PURPOSE: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases. METHODS: We report three unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs (GRs) of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6KozakGAL4 allele to assess the expression pattern of dYkt6. RESULTS: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual is homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] and exhibited neurodevelopmental disorders and optic atrophy. Fly dYkt6 is essential and is expressed in the fat body (analogous to liver) and central nervous system. Wild-type GR can rescue the lethality and autophagic flux defects whereas the variants are less efficient in rescuing the phenotypes. CONCLUSION: The YKT6 variants are partial loss-of-function alleles and the p.(Tyr185Cys) is more severe than p.(Tyr64Cys).

De novo variants in PLCG1 are associated with hearing impairment, ocular pathology, and cardiac defects.

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol, important signaling molecules involved in many cellular processes. PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here we describe three unrelated individuals with de novo heterozygous missense variants in PLCG1 (p.Asp1019Gly, p.His380Arg, and p.Asp1165Gly) who exhibit variable phenotypes including hearing loss, ocular pathology and cardiac septal defects. To model these variants in vivo, we generated the analogous variants in the Drosophila ortholog, small wing (sl). We created a null allele slT2A and assessed the expression pattern. sl is broadly expressed, including in wing discs, eye discs, and a subset of neurons and glia. Loss of sl causes wing size reductions, ectopic wing veins and supernumerary photoreceptors. We document that mutant flies exhibit a reduced lifespan and age-dependent locomotor defects. Expressing wild-type sl in slT2A mutant rescues the loss-of-function phenotypes whereas expressing the variants causes lethality. Ubiquitous overexpression of the variants also reduces viability, suggesting that the variants are toxic. Ectopic expression of an established hyperactive PLCG1 variant (p.Asp1165His) in the wing pouch causes severe wing phenotypes, resembling those observed with overexpression of the p.Asp1019Gly or p.Asp1165Gly variants, further arguing that these two are gain-of-function variants. However, the wing phenotypes associated with p.His380Arg overexpression are mild. Our data suggest that the PLCG1 de novo heterozygous missense variants are pathogenic and contribute to the features observed in the probands.

3D Spine Model Reconstruction Based on RGBD Images of Unclothed Back Surface.

Most 3D spine reconstruction methods require X-ray images as input, which usually leads to high cost and radiation damage. Therefore, these methods are hardly ever applied to large scale scoliosis screening or spine pose monitoring during treatment. We propose a novel, low-cost, easy-to-operate and none-radioactive 3D spine model reconstruction method, which is based on human back surface information without requiring X-ray images as input. Our method fits a pre-built Spine Priors Model (SPrM) to human back surface information and reconstructs the main part of spine with 17 vertebrae: lumbar vertebrae L1-L5 and thoracic vertebrae T1-T12. The Spine Priors Model is constructed according to human spine priors, including Statistical Spine Shape Model (SSSM), Spine Pose Model (SPM) and Spine Biomechanical Simplified Model (SBSM). The spine-related information on back surface, including back surface spinous curve and local symmetry nearby spinous curve is extracted from the RGBD images of human back surface. We formulate the spine optimization constraints from spine-related feature on back surface and spine priors, then optimize the spine model by gradient descent to get the optimal personalized shape parameters and pose parameters of the Spine Priors Model (SPrM). We assess our reconstruction by scoliosis Cobb angle error, and the result is comparable to current X-ray based methods.

Impact of interaction between interleukin-6 gene polymorphism and Helicobacter pylori infection on susceptibility to gastric cancer.

OBJECTIVE: This study aimed to evaluate the association between four single nucleotide polymorphisms (SNPs) of the interleukin-6 (IL-6) gene and gastric cancer (GC), and impact of interaction between IL-6 SNPs and Helicobacter pylori (H. pylori ) infection on susceptibility to GC. METHODS: Logistic regression was used to test the relationships between four SNPs of IL-6 gene and GC susceptibility. A generalized multifactor dimensionality reduction (GMDR) model was employed to assess the interaction effect between IL-6 gene and H. pylori infection on GC risk. RESULTS: Logistic regression analysis indicated that the rs1800795-C allele was associated with increased GC risk, adjusted ORs (95% CI) were 1.80 (1.21-2.41) (CC vs. GG) and 1.68 (1.09-2.30) (C vs. G), respectively. The rs10499563-C allele was associated with decreased risk of GC, and adjusted ORs (95% CI) were 0.62 (0.31-0.93) (TC vs. TT), 0.52 (0.18-0.89) (CC vs. TT) and 0.60 (0.29-0.92) (C vs. T), respectively. GMDR methods found a two-dimensional model combination (including rs1800795 and H. pylori infection) was statistically significant. The selected model had testing balanced accuracy of 59.85% and the best cross-validation consistencies of 10/10 ( P  = 0.0107). Compared with H. pylori -negative subjects with rs1800795- GG genotype, H. pylori -positive participants with GC or CC genotype had the highest risk of GC, the OR (95% CI) was 3.34 (1.78-4.97). CONCLUSION: The rs1800795-C allele was associated with increased GC risk and the rs10499563-C allele was associated with decreased GC risk. The interaction between rs1800795 and H. pylori infection was also correlated with increased risk of GC.

Varicella-zoster virus meningitis with hypoglycorrhachia: A case report.

BACKGROUND: Varicella-zoster virus (VZV) is a common viral infection, but meningitis is a rare complication of VZV infection. The cerebrospinal fluid glucose of viral meningitis is usually within the normal range, which is different from bacteria, fungi, and cancerous meningitis. This paper reports a case of VZV meningitis with hypoglycorrhachia and the relevant literature was reviewed. CASE SUMMARY: We report a case of an immunocompetent 39-year-old male, presenting with severe headache and fevers, without meningeal signs or exanthem, found to have VZV meningitis by the metagenomic next-generation sequencing of cerebrospinal fluid. The cerebrospinal fluid analysis revealed hypoglycorrhachia (cerebrospinal fluid glucose of 2.16) and he was treated successfully with intravenous acyclovir. Our literature review identified only ten cases diagnosed with VZV meningitis with hypoglycorrhachia previously reported to date in the English literature whose cerebrospinal fluid glucose was from 1.6 to 2.7mmol/L, with a ratio of cerebrospinal fluid to serum glucose from 0.30 to 0.49. CONCLUSION: Although rare, the cerebrospinal fluid of patients with VZV meningitis may have hypoglycorrhachia, which broadens the understanding of the disease.

Factors associated with postoperative muscle reconnection in children's congenital muscular torticollis.

Background: In prior studies, there has been no report of clinical observation of postoperative reconnection of the sternocleidomastoid muscle (SCM) in children with congenital muscular torticollis (CMT). Therefore, the objective of this study is to investigate the factors associated with postoperative reconnection of the SCM in children with CMT, and to provide clinical evidence. Methods: A retrospective study was conducted, wherein 83 CMT children without any missing data were followed up from November 2019 to June 2021. The age at the time of surgery, sex, preoperative and postoperative follow-up duration, laterality, neck mass history, preoperative physical therapy history, and severity type were recorded. The severity classification of CMT was based on clinical features and ultrasound images of SCM. The postoperative reconnection of SCM was measured. Results: Out of 83 patients, ten had postoperative reconnection. The rate of postoperative reconnection of SCM in children with CMT who had undergone unipolar SCM release surgery was 18.994 times higher than in patients who had not undergone such surgery. This difference was statistically significant [odds ratio (OR) =18.994, 95% confidence interval (CI): 1.583 to 227.897, P=0.020]. Conclusions: The history of SCM release surgery in CMT children can predict the postoperative reconnection of SCM, which will aid in determining the optimal surgical approach for recurrent CMT patients.

What should we expect when two myositis-specific antibodies coexist in a patient.

BACKGROUND: The coexistence of two myositis-specific autoantibodies (MSA) is considered extremely rare. We describe three patients with both anti-signal recognition particle (SRP) antibodies and another MSA in serum. METHODS: We performed a retrospective clinical data collection and follow-up studies of the clinical manifestations and treatment outcome of three patients positive with anti-SRP antibodies and other MSAs. IgG antibodies against MSAs were detected using commercial line immunoblot assay. RESULTS: The tests of MSA showed positive result of anti-SRP antibodies and another one MSA including anti-TIF1-γ, anti-Jo1, or anti-EJ antibodies, respectively. The proximal muscle weakness appeared in 2 patients; interstitial lung disease presented in 2 patients. The serum CK level was elevated in 1 patient. The muscle biopsy showed necrotizing myopathy in 1 patient and deposition of membrane attack complex on scattered myofibers in the other one patient. One of the two patients with interstitial lung disease died because of respiratory failure. One patient had completely improved and the other one showed partial remission after immunosuppressive therapy. CONCLUSIONS: The patients with anti-SRP antibodies co-occurred with the other MSA may have various clinical characteristics. The clinicopathological phenotypes of these patients seem to be mainly caused by one of the MSAs, namely the responsible antibody.

Design, Synthesis, and Biological Evaluation of Novel Camphor-Based Hydrazide and Sulfonamide Derivatives as Laccase Inhibitors against Plant Pathogenic Fungi/Oomycetes.

To discover novel natural product-based fungicidal agrochemicals, 41 novel camphanic acid hydrazide and camphor sulfonamide derivatives were designed, synthesized, and tested for their antifungal profile against four plant pathogenic fungi and three oomycetes. As a result, some derivatives presented pronounced inhibitory activities toward Botryosphaeria dothidea, Fusarium graminearum, Phytophthora capsici, and Phytophthora nicotianae. Especially, compound 4b demonstrated the most potent anti-B. dothidea activity (EC50 = 1.28 mg/L), much stronger than positive control chlorthalonil. The in vivo assay showed that 4b displayed significant protective and curative effects on apple fruits infected by B. dothidea. The primary antifungal mechanism study revealed that 4b could obviously enhance the cell membrane permeability, destroy the mycelial surface morphology and the cell ultrastructure, and reduce the ergosterol and exopolysaccharide contents of B. dothidea. Further, 4b showed potent laccase inhibitory activity in vitro with an IC50 value of 11.3 µM, superior to positive control cysteine. The molecular docking study revealed that 4b could dock well into the active site of laccase by forming multiple interactions with the key residues in the pocket. The acute oral toxicity test in rats presented that 4b had slight toxicity with an LD50 value of 849.1 mg/kg bw (95% confidence limit: 403.9-1785.3 mg/kg bw). This research identified that the camphanic acid hydrazide derivatives could be promising leads for the development of novel laccase-targeting fungicides.

Synthesis and Antifungal Activity of Novel L-Menthol Hydrazide Derivatives as Potential Laccase Inhibitors.

To discover novel laccase inhibitors as potential fungicides, twenty-six novel L-menthol hydrazide derivatives were designed and synthesized. In the in vitro antifungal assay, most of the target compounds displayed pronounced antifungal activity against Sclerotinia sclerotiorum, Fusarium graminearum, and Botryosphaeria dothidea. Especially, the EC50 of compounds 3 b and 3 q against B. dothidea was 0.465 and 0.622 mg/L, which was close to the positive compound fluxapyroxad (EC50 =0.322 mg/L). Scanning electron microscopy (SEM) analysis showed that compound 3 b could significantly damage the mycelial morphology of B. dothidea. In vivo antifungal experiments on apple fruits showed that 3 b exhibited excellent protective and curative effects. Furthermore, in the in vitro laccase inhibition assay, 3 b showed outstanding inhibitory activity with the IC50 value of 2.08 µM, which is much stronger than positive control cysteine and PMDD-5Y. These results indicated that this class of L-menthol derivatives could be promising leads for the discovery of laccase-targeting fungicides.

Investigation on Adsorption of Polar Molecules in Vegetable Insulating Oil by Functional Fossil Graphene.

As a new engineering dielectric, vegetable insulating oil is widely used in electrical equipment. Small polar molecules such as alcohol and acid will be produced during the oil-immersed electrical equipment operation, which seriously affects the safety of equipment. The polar molecule can be removed by using functional fossil graphene materials. However, the structural design and group modification of graphene materials lack a theoretical basis. Therefore, in this paper, molecular dynamics (MD) and quantum mechanics theory (Dmol3) were utilized to study the adsorption kinetics and mechanism of graphene (GE), porous graphene (PGE), porous hydroxy graphene (HPGE), and porous graphene modified by hydroxyl and carboxyl groups (COOH-HPGE) on polar small molecules in vegetable oil. The results show that graphene-based materials can effectively adsorb polar small molecules in vegetable oil, and that the modification of graphene materials with carboxyl and hydroxyl groups improves their adsorption ability for polar small molecules, which is attributed to the conversion of physical adsorption to chemical adsorption by the modification of oxygen-containing groups. This study provides a theoretical basis for the design and preparation of graphene materials with high adsorption properties.

CircRNA circSLIT2 is a novel diagnostic and prognostic biomarker for gastric cancer.

BACKGROUND: Many diseases can mimic the symptoms of gastric cancer (GC). Therefore, misdiagnosis of GC is common. Our preliminary sequencing analysis revealed the altered expression of circSLIT2 in GC. In this study, we further explored the role of circSLIT2 in GC. METHODS: The research subjects included GC patients, patients with irritable bowel syndrome (IBS), patients with gastric ulcer (GU), patients with gastric tuberculosis (GT), patients with Crohn's disease (CD), and healthy controls (HC). Accumulation of circSLIT2 RNA in both tissue and plasma samples was determined with RT-qPCR. The diagnostic and prognostic values of circSLIT2 for GC were explored by performing ROC and survival curve analysis. The χ2-test was applied for association analysis. RESULTS: Increased circSLIT2 RNA accumulation was observed in GC tissues compared to non-tumor tissues. Compared to the HC group, increased plasma circSLIT2 RNA accumulation was only observed in the GC group, but not in the IBS, GU, GT, and CD groups. Plasma circSLIT2 showed a positive correlation with circSLIT2 in GC tissues but not circSLIT2 in non-tumor tissues. Using increased plasma circSLIT2 as a biomarker, GC patients were effectively separated from other disease groups and the HC group. Survival curve analysis revealed that most patients who died during the 5­year follow-up had high levels of circSLIT2 accumulation in GC tissues and plasma. CircSLIT2 in plasma and GC tissue was only closely associated with distant tumor metastases, but not other clinical factors. CONCLUSION: Increased circSLIT2 accumulation may serve as a novel diagnostic and prognostic biomarker for GC.

Novel variants, muscle imaging, and myopathological changes in Chinese patients with VCP-related multisystem proteinopathy.

OBJECTIVE: The objective of this research was to study the clinical features, genetic characteristics, muscle imaging, and muscle pathological changes of a cohort of Chinese patients with mutations in the valosin-containing protein (VCP) gene. METHODS: Nine patients from seven Chinese pedigrees were recruited. Variants were detected by next-generation sequencing and confirmed by Sanger sequencing. Thigh muscle MRIs were performed in five patients. All the patients received muscle biopsies. RESULTS: Seven variants in VCP were identified, and two were novel. All the patients presented with adult-onset muscle weakness. The appearance of "isolated island sign" or "contra-isolated island sign" was observed in four of the five the patients on muscle MRIs. Muscle biopsies demonstrated the combination of neuropathic and myopathic changes in seven patients and muscle dystrophic changes in two patients. Notably, rimmed vacuoles and cytoplasmic VCP and p62-positive protein aggregates were observed in all the patients. CONCLUSION: Our finding of novel variants expanded the mutational spectrum of the VCP gene. This cohort of Chinese patients with VCP mutations mainly present with inclusion body myopathy with predominant limb-girdle distribution. The characteristic pattern of fatty infiltration, especially the "isolated island" and "contra-isolated island" on muscle MRI, along with rimmed vacuoles in muscle biopsy, provides valuable clues for guiding genetic diagnostic workup.

Comparison of antegrade robotic assisted VS laparoscopic inguinal lymphadenectomy for penile cancer.

BACKGROUND: Minimally invasive modifications of inguinal lymphadenectomy (IL), including laparoscopic IL (LIL) and robotic-assisted IL (RAIL), have been utilized for penile cancer. Comparative study is necessary to guide the decision about which minimally invasive technique to select for IL. Therefore we compared RAIL with LIL performed via an antegrade approach in terms of perioperative outcomes. METHODS: We conducted a retrospective study of 43 patients who underwent RAIL (n = 20) or LIL (n = 23) for penile cancer from 2016 to 2020. The key surgical procedures and techniques are described. Complications were graded by the Clavien-Dindo classification, and operative time, estimated blood loss (EBL), lymph nodal yield, nodal positivity, postoperative drain duration, and disease recurrence during follow-up were assessed. Categorical variables were compared using chi-squared whereas continuous variables were compared by t-tests. RESULTS: The operative time for RAIL was significantly shorter than that of LIL (median 83 vs 95 min). Significantly less blood loss was reported with RAIL than with LIL (median 10 vs 35 ml). Lymph node yield, pathological positive nodes, the hospital stay, postoperative drain duration, postoperative complications and recurrence were similar for RAIL and LIL. CONCLUSIONS: For patients with penile cancer, perioperative outcomes of RAIL and LIL were similar, but there was less blood loss, a shorter operative time for robotic cases.

Comparison of cytokine/chemokine profiles between dermatomyositis and anti-synthetase syndrome.

Objectives: Dermatomyositis (DM) and anti-synthetase syndrome (ASS) are autoimmune diseases with multisystem involvement. Despite sharing some clinical and myopathological features, these are two diseases with different pathogeneses and prognoses. We aimed to clarify and compare cytokine/chemokine profiles in both disorders, which may help in the differential diagnosis. Materials and methods: We collected clinical data and serum samples of consecutive patients with DM and ASS. Quantibody® Human Inflammation Array 3 for cytokines/chemokines was performed in the serum of all participants. Receiver operating characteristic analysis with the area under the curve and Youden's index were performed. Results: Eight newly diagnosed and treatment-naïve patients with DM, nine newly diagnosed and treatment-naïve patients with ASS, and 14 healthy controls were enrolled. Serum C-C motif chemokine ligand (CCL) 2, CCL4, C-X-C motif chemokine ligand (CXCL) 13, and tumor necrosis factor receptor 2 (TNFR2) were increased in patients with both DM and ASS. Serum interleukin (IL)-1 receptor type 1 (IL-1ra), IL-1b, CCL1, CXCL11, and CCL3 were modulated in patients with DM only, and IL-8, CXCL9, and tissue inhibitors of metalloproteinases-1 (TIMP-1) in patients with ASS only. Serum CCL2, CXCL13, and TNFR2 accurately distinguished patients with DM and ASS from healthy controls, as shown by the area under the curve >0.80. Moreover, receiver operating characteristic analysis showed that, as biomarkers for discrimination between DM and ASS, the combination of IL-1ra and TIMP-1, had an area under the curve of 0.944, a sensitivity of 87.5%, and a specificity of 88.9%. Conclusion: Our study demonstrated that serum levels of cytokines/chemokines showed a different pattern in newly diagnosed patients with DM and ASS, in which serum IL-1ra and TIMP-1 could be used to distinguish between the two diseases.

Better vertebrae remodeling in pediatric spinal eosinophilic granuloma patients treated with kyphoplasty and short-term posterior instrumentation: A minimal two-year follow-up with historical controls.

Objective: To assess the validity and safety of kyphoplasty combined with short-term posterior instrumentation to treat children with vertebrae plana due to eosinophilic granuloma (EG). Patients and Methods: Clinical data of EG patients, who received kyphoplasty and short-term instrumentation from March 2019 to March 2020, were retrospectively reviewed. The recovery of diseased vertebrae was assessed and compared with historical case data. Results: Nine patients with EG had received kyphoplasty and short-term posterior instrumentation. The mean age at initial treatment was 66.7 months old (range, 28-132 months). The average number of follow-up months was 26.7. (range, 24-30 months).Four and 5 cases presented with thoracic and lumbar vertebral destruction, respectively. Under Garg's classification, 7 and 2 cases were classified as Grade IIA and IIB, respectively. The average diseased vertebral heights at 1-year and 2-year after surgery were significantly higher than the preoperative heights. The average percentages of diseased vertebral heights to references at 1-year and 2-year after surgery were 72.0% and 86.0%, respectively. The average percentage of diseased vertebral heights to the references at 2-year after surgery was significantly higher than that of the historical cases at the same time. No minor or major adverse events were observed. Conclusions: Transpedicular balloon kyphoplasty for the direct restoration of vertebrae plana seems feasible and safe in combination with short-term posterior instrumentation. Better short-time vertebrae remodeling was observed 2 years after surgery. Active surgical treatment is suggested for children who have vertebrae plana as a result of EG in order to maintain the ability to recover vertebral height.

Interaction Between Vascular Endothelial Growth Factor Gene Polymorphism and Smoking on Gastric Cancer Risk in Chinese Han Population.

Aim: In this study, we aimed to evaluate the associations of vascular endothelial growth factor (VEGF) gene single nucleotide polymorphisms (SNPs) and its interaction with current smoking with gastric cancer (GC) risk in the Chinese Han population. Methods: We used logistic regression model to test the association between VEGF gene polymorphism and the risk of GC. The association strength was evaluated by odds ratio (OR) and 95% confidence interval (CI) calculated using logistic regression. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the effect of the interaction between VEGF gene and current smoking on GC risk. Results: Logistic regression analysis showed that the risk of GC was significantly higher in rs10434 -G allele carriers than that in AA genotype carriers (AG + GG and AA), and the adjusted OR (95% CI) = 1.64 (1.24-2.08). In addition, we found a significantly higher GC risk in subjects with rs833061-T allele than those with CC allele (CT + TT and CC), adjusted or (95% CI) = 1.43 (1.10-1.87). We also found a statistically significant two- locus model (p = 0.018), including rs10434 and current smoking, indicating a significant interaction between rs10434 and current smoking on the risk of GC. Hierarchical analysis found that current smokers with AG or GG genotype have the highest GC risk, compared to never- smokers with AA genotype, OR (95% CI) = 2.43 (1.64-3.28). Conclusion: We found that rs10434 -G and rs833061-T alleles, gene- environment interaction between rs10434, and current smoking were all related to increased GC risk.