Nuclear modifier YARS2 allele correction restored retinal ganglion cells-specific deficiencies in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted eye disease due to the degeneration of retinal ganglion cells (RGCs). Mitochondrial 11778G > A mutation is the most common LHON-associated mitochondrial DNA (mtDNA) mutation. Our recent studies demonstrated some LHON families manifested by synergic interaction between m.11778G > A mutation and YARS2 allele (c.572G > T, p.Gly191Val) encoding mitochondrial tyrosyl-tRNA synthetase. However, the RGC-specific effects of LHON-associated mtDNA mutations remain elusive and there is no highly effective therapy for LHON. Here, we generated patients-derived induced pluripotent stem cells (iPSCs) from fibroblasts derived from a Chinese LHON family (both m.11778G > A and c.572G > T mutations, only m.11778G > A mutation, and control subject). The c.572G > T mutation in iPSC lines from a syndromic individual was corrected by CRISPR/Cas9. Those iPSCs were differentiated into neural progenitor cells and subsequently induced RGC-like cells using a stepwise differentiation procedure. Those RGC-like cells derived from symptomatic individual harboring both m.11778G > A and c.572G > T mutations exhibited greater defects in neuronal differentiation, morphology including reduced area of soma, numbers of neurites and shortened length of axons, electrophysiological properties than those in cells bearing only m.11778G > A mutation. Furthermore, these RGC-like cells revealed more drastic reductions in oxygen consumption rates, levels of mitochondrial ATP and increasing productions of reactive oxygen species than those in other cell models. These mitochondrial dysfunctions promoted the apoptotic process for RGC degenerations. Correction of YARS2 c.572G > T mutation rescued deficiencies of patient-derived RGC-like cells. These findings provide new insights into pathophysiology of LHON arising from RGC-specific mitochondrial dysfunctions and step toward therapeutic intervention for this disease.

D-A Conjugated Polymer/CdS S-Scheme Heterojunction with Enhanced Interfacial Charge Transfer for Efficient Photocatalytic Hydrogen Generation.

Owing to the improved charge separation and maximized redox capability of the system, Step-scheme (S-scheme) heterojunctions have garnered significant research attention for efficient photocatalysis of H2 evolution. In this work, an innovative linear donor-acceptor (D-A) conjugated polymer fluorene-alt-(benzo-thiophene-dione) (PFBTD) is coupled with the CdS nanosheets, forming the organic-inorganic S-scheme heterojunction. The CdS/PFBTD (CP) composite exhibits an impressed hydrogen production rate of 7.62 mmol g-1 h-1 without any co-catalysts, which is ≈14 times higher than pristine CdS. It is revealed that the outstanding photocatalytic performance is attributed to the formation of rapid electron transfer channels through the interfacial Cd─O bonding as evidenced by the density functional theory (DFT) calculations and in situ X-ray photoelectron spectroscopy (XPS) analysis. The charge transfer mechanism involved in S-scheme heterojunctions is further investigated through the photo-irradiated Kelvin probe force microscopy (KPFM) analysis. This work provides a new point of view on the mechanism of interfacial charge transfer and points out the direction of designing superior organic-inorganic S-scheme heterojunction photocatalysts.

Confined In-Situ Encapsulation of Co/C Composites with Increased Heterogeneous Interface Polarization for Enhanced Electromagnetic Performance.

It is an urgent problem to realize reliable microwave absorption materials (MAMs) with low density. To address this issue, a series of controlled experiments w ere carried out, which indicated that the tubular structure enables excellent microwave absorption properties with a lower powder filling rate. This performance is attributable to the combined dielectric and magnetic loss mechanisms provided by Co/C and the interface polarization facilitated by multiple heterogeneous interfaces. Particularly, Co@C nanotubes, benefiting from the enhanced heterointerface polarization due to their abundant specific surface area and the reduced electron migration barrier induced by their 1D stacked structure, effectively achieved a dual enhancement of dielectric loss and polarization loss at lower powder filling ratios. Furthermore, the magnetic coupling effect of magnetic nanoparticle arrays in tubular structures is demonstrated by micromagnetic simulation, which have been few reported elsewhere. These propertied enable Co@C nanotubes to achieve minimum reflection loss and maximum effective absorption broadband values of 61.0 dB and 5.5 GHz, respectively, with a powder filling ratio of 20 wt% and a thickness of 1.94 mm. This study reveals the significance of designing 1D structures in reducing powder filling ratio and matching thickness, providing valuable insights for developing MAMs with different microstructures.

Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.

This article provides an overview of the background knowledge of ferroptosis in the nervous system, as well as the key role of nuclear factor E2-related factor 2 (Nrf2) in regulating ferroptosis. The article takes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as the starting point to explore the close association between Nrf2 and ferroptosis, which is of clear and significant importance for understanding the mechanism of neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links ferroptosis to the pathogenesis of NDs. As the disease progresses, damage to the antioxidant system, excessive OS, and altered Nrf2 expression levels, especially the inhibition of ferroptosis by lipid peroxidation inhibitors and adaptive enhancement of Nrf2 signaling, demonstrate the potential clinical significance of Nrf2 in detecting and identifying ferroptosis, as well as targeted therapy for neuronal loss and mitochondrial dysfunction. These findings provide new insights and possibilities for the treatment and prevention of NDs.

Tooth movement analysis of maxillary dentition distalization using clear aligners with buccal and palatal mini-screw anchorages: A finite element study.

OBJECTIVE: To assess the tooth movement trends during the three stages of maxillary dentition distalization with clear aligners (CA) and to compare the efficacy of different mini-screw anchorage systems. MATERIALS AND METHODS: Three-dimensional (3D) finite element models of three anchorage systems (A, control group; B, buccal mini-screw anchorage group; C, palatal mini-screw anchorage group) were established. Three stages of simulating maxillary dentition distalization with CA included maxillary molar distalization (stage 1), maxillary premolar distalization (stage 2) and maxillary anterior teeth retraction (stage 3). Therefore, a total of nine models were constructed to analyse the 3D displacement of maxillary teeth during the distalization process. RESULTS: The displacement pattern of maxillary dentition during distalization was similar across the three groups, but with varying magnitudes. During stage 1, groups B and C exhibited greater amounts of molar distalization compared to group A. Group C also demonstrated the least amount of labial movement of the maxillary central incisor compared to the other two groups. During stage 2, the mesial displacement of the maxillary first molar was less significant in groups B and C than in group A. In the final stage, group C exhibited a greater amount of maxillary anterior retraction compared to groups A and B. CONCLUSION: The palatal mini-screw anchorage system was effective in reducing anchorage loss and improving the efficacy of maxillary dentition distalization with CA.

Biomechanical analysis of miniscrew-assisted molar distalization with clear aligners: a three-dimensional finite element study.

BACKGROUND/OBJECTIVES: To compare the biomechanical characteristics of maxillary molar distalization with clear aligners in conjunction with three types of miniscrew anchorage. MATERIALS/METHODS: Three-dimensional (3D) finite element models of maxillary molar distalization with clear aligners and three types of miniscrew anchorage were established, including (A) control group, (B) direct buccal miniscrew anchorage group, (C) direct palatal miniscrew anchorage group, and (D) indirect buccal miniscrew anchorage group. The 3D displacement of maxillary teeth and the principal stress (maximum tensile and compressive stress) on the root and periodontal ligament (PDL) during molar distalization were recorded. RESULTS: The tooth displacement pattern during maxillary molar distalization in the four groups showed similarities, including labial tipping of anterior teeth, mesial and buccal tipping of premolars, and distal and buccal tipping of molars, but with varying magnitudes. Group C exhibited the greatest molar distalization, with the first molar achieving 0.1334 mm of crown distalization. Group D demonstrated a notable buccal crown movement (0.0682 mm) and intrusion (0.0316 mm) of the first premolar. Compared to Groups A and B, Groups C and D showed less labial crown tipping of the central incisor. Group B showed the greatest amount of maxillary incisor intrusion (central incisor: 0.0145 mm, lateral incisor: 0.0094 mm). Moreover, Groups C and D displayed significantly lower levels of compressive and tensile stress in the roots and PDL of the maxillary central and lateral incisors. LIMITATION: Molar distalization is a dynamic process involving sequential tooth movement stages; however, our research primarily examined the tooth movement patterns in the initial aligner. CONCLUSIONS/IMPLICATIONS: The use of miniscrew anchorage, especially direct palatal miniscrew anchorage, may enhance the treatment efficacy of maxillary molar distalization with clear aligners, leading to increased molar distalization, reduced mesial movement of premolars, and minimized labial tipping of anterior teeth.

Epitranscriptomic profiling of N4-acetylcytidine-related RNA acetylation in the spinal dorsal horn of rat with cancer-induced bone pain.

Recently, epigenetics involved in the regulation of gene expression has become a research hotspot. This study evaluated N4-acetylcytidine (ac4c) RNA acetylation in the spinal dorsal horn (SDH) of rats with cancer-induced bone pain (CIBP). The ac4C-specific RIP sequencing and NAT10-specific RIP sequencing were performed to identify the differences in ac4C acetylation and gene expression in the SDH between CIBP and sham groups, the relationship with the acetylation-modifying enzyme NAT10, and association analysis was performed. By interfering with the NAT10 expression, the relationship between some up-regulated genes and ac4C acetylation in CIBP was verified. In this study, we demonstrated that bone cancer increases the levels of NAT10 and the overall acetylation, inducing differential ac4C patterns in the SDH of rats. Through verification experiments, it was found that ac4C acetylation of some genes is regulated by NAT10, and differential ac4C patterns in RNA determine the expression of this RNA. We exposed that some CIBP-related gene expression was altered in the SDH of rats, which was regulated by differentially expressed ac4C acetylation.

NDGA enhances the physicochemical and anti-biodegradation performance of dentin collagen.

OBJECTIVES: Collagen fibrils from carious dentin matrix are prone to enzymatic degradation. This study investigates the feasibility and mechanism of nordihydroguaiaretic acid (NDGA), as a collagen crosslinker, to bio-modify the demineralized dentin matrix. METHODS: The physicochemical properties of the crosslinked dentin matrix were characterized by swelling ratio, ninhydrin assay, Fourier Transform Infrared spectroscopy, and atomic force microscopy. The collagenase degradation resistance was evaluated by measuring loss of dry mass, hydroproline release, loss of elasticity, and micro-nano structure integrity. The cytotoxicity of NDGA-crosslinked dentin collagen was evaluated by flow cytometry. RESULTS: NDGA crosslinked dentin matrix without destroying the integrity of collagen. Mechanistically, NDGA formed bisquinone bond between two adjacent o-quinone groups, resulting in NDGA polymeric matrix in which collagen fibrils were embedded. NDGA modification could significantly enhance the stiffness of dentin matrix at macro-nano scale. The NDGA-crosslinked dentin matrix exhibited remarkably low collagen degradation and sustained bulk elasticity after collagenase challenge, which were attributed to decreased water content, physical masking of collagenase bind sites on collagen, and improved stiffness of collagen fibrils. Notably, NDGA-crosslinked dentin matrix exhibited excellent biocompatibility. CONCLUSION: NDGA, as a biocompatible collagen crosslinker, improves the mechanical properties and biodegradation resistance of demineralized dentin matrix.

Pattern of lifestyle behaviors and associated risk of being bullied at schools: A latent class analysis of 25,379 adolescents in Jiangsu Province of China.

School bullying is a worldwide problem. Although previous studies examined the association between different lifestyle behaviors and bullying victimization, the complex co-occurrence of these behaviors was not identified, and their association with the risk of being bullied remains unclear. We aimed to identify the behavioral patterns of adolescents and to explore their association with bullying victimization. This cross-sectional study employed data from the "Surveillance for Common Diseases and Health Risk Factors among Students" project implemented in Jiangsu Province of China in 2019, and a total of 25,379 school-enrolled students were included. We used a latent class analysis to identify behavioral patterns and a regression mixture model to explore various demographic characteristics, such as age, sex, and family structure in relation to bullying victimization across different patterns. We considered respondents having targeted behaviors, including smoking, alcohol consumption, illicit drug use, sugar consumption, no fruit consumption, low physical activity, electronic media use, and insufficient sleep. Four behavioral patterns were identified, including the "adolescents without apparent targeted behaviors" (19.65%), "substance and electronic media users" (12.76%), "typical electronic media users" (54.49%), and "typical substance users" (8.10%). The risk of being bullied was the highest in the "substance and electronic media users" (probability: 0.33), tripled that in "adolescents without apparent targeted behaviors" (odds ratio: 3.60, 95% confidence interval: 3.01-4.30). Risk of being bullied was reduced for those "substance and electronic media users" living with a nuclear family. Behavioral patterns and their association with being bullied differ between groups of school-aged adolescents. To better inform decision-making based on the current real-world findings, the implementation of bullying prevention programs could target specific behavioral patterns.

HP1γ Prevents Activation of the cGAS/STING Pathway by Preserving Nuclear Envelope and Genomic Integrity in Colon Adenocarcinoma Cells.

Chronic inflammatory processes in the intestine result in serious conditions such as inflammatory bowel disease (IBD) and cancer. An increased detection of cytoplasmic DNA sensors has been reported in the IBD colon mucosa, suggesting their contribution in mucosal inflammation. Yet, the mechanisms altering DNA homeostasis and triggering the activation of DNA sensors remain poorly understood. In this study, we show that the epigenetic regulator HP1γ plays a role in preserving nuclear envelope and genomic integrity in enterocytic cells, thereby protecting against the presence of cytoplasmic DNA. Accordingly, HP1 loss of function led to the increased detection of cGAS/STING, a cytoplasmic DNA sensor that triggers inflammation. Thus, in addition to its role as a transcriptional silencer, HP1γ may also exert anti-inflammatory properties by preventing the activation of the endogenous cytoplasmic DNA response in the gut epithelium.

Different degeneration patterns of paraspinal muscles in degenerative lumbar diseases: a MRI analysis of 154 patients.

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate the different degeneration patterns of paraspinal muscles in degenerative lumbar diseases and their correlation with lumbar spine degeneration severity. The degeneration characteristics of different paraspinal muscles in degenerative lumbar diseases remain unclear. METHODS: 78 patients diagnosed with single-level degenerative lumbar spondylolisthesis (DLS) and 76 patients with degenerative lumbar kyphosis (DLK) were included as DLS and DLK groups. Paraspinal muscle parameters of psoas major (PS), erector spinae (ES) and multifidus muscle (MF) were measured, including fatty infiltration (FI) and relative cross-sectional area (rCSA), namely the ratio of the paraspinal muscle CSA to the CSA of the vertebrae of the same segment. Sagittal parameters including lumbar lordosis (LL) and sagittal vertical axis (SVA) were measured. The paraspinal muscle parameters and ES/MF rCSA ratio were compared between the two groups. Paraspinal muscles parameters including rCSA and FI were also compared between each segments from L1 to L5 in both DLS and DLK groups. In order to determine the influence of sagittal spinal alignment on paraspinal muscle parameters, correlation analysis was conducted between the MF, ES, PS rCSA and FI and the LL in DLS and DLK group. RESULT: MF atrophy is more significant in DLS patients compared with DLK. Also, MF fatty infiltration in the lower lumbar spine of DLS patients was greater compared to DLK patients. DLK patients showed more significant atrophy of ES and heavier ES fatty infiltration. MF FI was significantly different between all adjacent segments in both DLS and DLK groups. In DLS group, ES FI was significantly different between L2/L3 to L3/L4 and L4/L5 to L5/S1, while in DLK group, the difference of ES FI between all adjacent segments was not significant, and ES FI was found negatively correlated with LL. CONCLUSIONS: Paraspinal muscles show different degeneration patterns in degenerative lumbar diseases. MF degeneration is segmental in both DLS and DLK patients, while ES degenerated diffusely in DLK patients and correlated with the severity of kyphosis. MF degeneration is more significant in the DLS group, while ES degeneration is more significant in DLK patients. MF is the stabilizer of the lumbar spine segments, while the ES tends to maintain the spinal sagittal balance.

Chevalones H-M: Six New α-Pyrone Meroterpenoids from the Gorgonian Coral-Derived Fungus Aspergillus hiratsukae SCSIO 7S2001.

Six new α-pyrone meroterpenoid chevalones H-M (1-6), together with six known compounds (7-12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and X-ray diffraction data. Compounds 1-5 and 7 showed different degrees of antibacterial activity with MIC values of 6.25-100 µg/mL. Compound 8 exhibited potent cytotoxicity against SF-268, MCF-7, and A549 cell lines with IC50 values of 12.75, 9.29, and 20.11 µM, respectively.

The self-assembled zein hydrolysate-curcumin nanocomplex: improvement on the stability and sustainable release of curcumin.

BACKGROUND: The bioavailability of curcumin (Cur) is generally limited by its poor stability. However, it is beneficial to improve the stability of Cur by using self-assembled zein hydrolysate (ZH) as delivery carrier. This paper aimed to explore the formation mechanism of zein hydrolysate-curcumin nanocomplexes as a function of critical micelle concentration (CMC). RESULTS: In this work, The CMC of ZH (0.535 mg mL-1 ) was obtained by the pyrene fluorescent probe method. ZH-Cur nanocomplexes undergo hydrogen bonding and hydrophobic interactions, and the fluorescence quenching effect was concentration dependent with the process of static quenching. Moreover, the differences of colloidal properties on ZH and ZH-Cur nanocomplexes were systematically compared by dynamic light scattering and scanning electron microscopy near CMC. ZH presented irregular spherical shapes and would aggregate to form micelles at the CMC and above. The tight micellar structure promoted more uniform size distribution (double peaks reduced) and higher potentials (over -30 mV) within 10 days. In addition, the nanocomplexes demonstrated an obvious core-shell structure. Within 10 days of storage, the particle size distributions were uniform and the potentials increased significantly, indicating that the micellar nanostructure made the Cur stably embedded in the hydrophobic core of ZH. Finally, ZH-Cur nanocomplexes effectively improved the water solubility and encapsulation rate (over 70%) of Cur. Moreover, over 90% of Cur was released steadily within 91 h. CONCLUSION: This work provided a theoretical basis for the application of amphiphilic peptide micellar nanostructure as novel food-grade nanocarriers to transport hydrophobic bioactive substances. © 2022 Society of Chemical Industry.

Hybrid endoscopic submucosal dissection: An alternative resection modality for large laterally spreading tumors in the cecum?

BACKGROUND: Endoscopic resection for large, laterally spreading tumors (LSTs) in the cecum is challenging. Here we report on the clinical outcomes of hybrid endoscopic submucosal dissection (ESD) in large cecal LSTs. METHODS: We retrospectively reviewed data from patients with cecal LSTs ≥ 2 cm who underwent ESD or hybrid ESD procedures between January of 2008 and June of 2019. We compared the baseline characteristics and clinical outcomes, including procedure time, the en bloc and complete resection rates, and adverse events. RESULTS: A total of 62 patients were enrolled in the study. There were 27 patients in the ESD group and 35 patients in the hybrid ESD group, respectively. Hybrid ESD was more used for lesions with submucosal fibrosis. No other significant differences were found in patient characteristics between the two groups. The hybrid ESD group had a significantly shorter procedure time compared with the ESD group (27.60 ± 17.21 vs. 52.63 ± 44.202 min, P = 0.001). The en bloc resection rate (77.1% vs. 81.5%, P = 0.677) and complete resection rate (71.4% vs. 81.5%, P = 0.359) of hybrid ESD were relatively lower than that of the ESD group in despite of no significant difference was found. The perforation and post-procedure bleeding rate (2.9% vs. 3.7%, P = 0.684) were similar between the two groups. One patient perforated during the ESD procedure, which was surgically treated. One patient in the hybrid ESD group experienced post-procedure bleeding, which was successfully treated with endoscopic hemostasis. Post-procedural fever and abdominal pain occurred in six patients in the ESD group and five patients in the hybrid ESD group. One patient in the ESD group experienced recurrence, which was endoscopically resected. CONCLUSION: The results of this study indicate that hybrid ESD may be an alternative resection strategy for large cecal LSTs with submucosal fibrosis.

The value of contrast-enhanced three-dimensional isotropic T2-weighted turbo spin-echo SPACE sequence in the diagnosis of patients with lumbosacral nerve root compression.

PURPOSE: To investigate the diagnostic value of contrast-enhanced three-dimensional (3D) T2-weighted turbo spin-echo SPACE (T2-SPACE) sequence in LNRC. METHODS: A total of 90 surgically confirmed LNRC patients with 165 explored nerve roots were enrolled in this study. Diagnostic values were quantified using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. The consistency between 2D MRI and 3D T2-SPACE MRI was quantified using kappa test. The compression of specific branch in nerve root was evaluated on 2D MRI, 3D T2-SPACE MRI, and surgical findings. The pedicle height, vertebral body height (VH), proximal tilting angle of nerve root (PTA) were measured on MR images. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy by 2D MRI were 78.3%, 72.7%, 94.9%, 34.0%, and 77.6%, respectively. For 3D T2-SPACE MRI imaging, the sensitivity, specificity, PPV, NPV, and accuracy were 91.6%, 86.4%, 97.8%, 61.3%, and 90.9%, respectively. 2D MRI and 3D T2-SPACE MRI for detection of intra-foramen and extra-foramen nerve compression showed poor homogeneity (Kappa = 0.333, Kappa = 0.276, respectively). Smaller VHs and larger PTAs could be indicators for the diagnosis of foraminal nerve root compression. CONCLUSIONS: 3D T2-SPACE MRI had a higher sensitivity, specificity, PPV, NPV, and accuracy than 2D MRI for detecting LNRC. The 3D T2-SPACE scan could be a good substitute to routine 2D MRI in LNRC diagnosis, especially for foraminal nerve root compression patients. LEVEL OF EVIDENCE: III.

BMAL1 Knockdown Leans Epithelial-Mesenchymal Balance toward Epithelial Properties and Decreases the Chemoresistance of Colon Carcinoma Cells.

The circadian clock coordinates biological and physiological functions to day/night cycles. The perturbation of the circadian clock increases cancer risk and affects cancer progression. Here, we studied how BMAL1 knockdown (BMAL1-KD) by shRNA affects the epithelial-mesenchymal transition (EMT), a critical early event in the invasion and metastasis of colorectal carcinoma (CRC). In corresponding to a gene set enrichment analysis, which showed a significant enrichment of EMT and invasive signatures in BMAL1_high CRC patients as compared to BMAL1_low CRC patients, our results revealed that BMAL1 is implicated in keeping the epithelial-mesenchymal equilibrium of CRC cells and influences their capacity of adhesion, migration, invasion, and chemoresistance. Firstly, BMAL1-KD increased the expression of epithelial markers (E-cadherin, CK-20, and EpCAM) but decreased the expression of Twist and mesenchymal markers (N-cadherin and vimentin) in CRC cell lines. Finally, the molecular alterations after BMAL1-KD promoted mesenchymal-to-epithelial transition-like changes mostly appeared in two primary CRC cell lines (i.e., HCT116 and SW480) compared to the metastatic cell line SW620. As a consequence, migration/invasion and drug resistance capacities decreased in HCT116 and SW480 BMAL1-KD cells. Together, BMAL1-KD alerts the delicate equilibrium between epithelial and mesenchymal properties of CRC cell lines, which revealed the crucial role of BMAL1 in EMT-related CRC metastasis and chemoresistance.

Activation of the Intrinsic Pain Inhibitory Circuit from the Midcingulate Cg2 to Zona Incerta Alleviates Neuropathic Pain.

Neuropathic pain is one of the most common and notorious neurological diseases. The changes in cerebral structures after nerve injury and the corresponding contributions to neuropathic pain are not well understood. Here we found that the majority of glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) were inhibited by painful stimulation in male mice. Optogenetic manipulation revealed that these neurons were tonically involved in the inhibitory modulation of multimodal nociception. We further identified the projections to GABAergic neurons in the zona incerta (ZIGABA) mediated the pain inhibitory role. However, MCC Cg2Glu became hypoactive after nerve injury. Although a brief activation of the MCC Cg2Glu to ZIGABA circuit was able to relieve the aversiveness associated with spontaneous ongoing pain, consecutive activation of the circuit was required to alleviate neuropathic allodynia. In contrast, glutamatergic neurons in the area 1 of MCC played opposite roles in pain modulation. They became hyperactive after nerve injury and only consecutive inhibition of their activity relieved allodynia. These results demonstrate that MCC Cg2Glu constitute a component of intrinsic pain inhibitory circuitry and their hypoactivity underlies neuropathic pain. We propose that selective and persistent activation of the MCC Cg2Glu to ZIGABA circuit may serve as a potential therapeutic strategy for this disease.SIGNIFICANCE STATEMENT Glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) are tonically involved in the intrinsic pain inhibition via projecting to GABAergic neurons in the zona incerta. They are hypoactive after nerve injury. Selective activation of the circuit compensates the reduction of its analgesic strength and relieves neuropathic pain. Therefore, MCC Cg2Glu and the related analgesic circuit may serve as therapeutic targets for neuropathic pain. In contrast, MCC Cg1Glu have an opposite role in pain modulation and become hyperactive after nerve injury. The present study provides novel evidence for the concept that neuropathic pain is associated with the dysfunction of endogenous pain modulatory system and new perspective on the treatment of neuropathic pain.

The outcomes of modified endoscopic mucosal resection and endoscopic submucosal dissection for the treatment of rectal neuroendocrine tumors and the value of endoscopic morphology classification in endoscopic resection.

BACKGROUND: To compare the outcomes of modified endoscopic mucosal resection (m-EMR) and endoscopic submucosal dissection (ESD) for rectal neuroendocrine tumors (NETs) and evaluate the value of endoscopic morphology classification in endoscopic resection (ER). METHODS: Patients with rectal NET diameters less than 2 cm who were treated between April 2007 and January 2019 were enrolled. The endoscopic morphology of rectal NETs was classified based on the endoscopic views. Patients who underwent ESD and m-EMR were compared. Baseline characteristics as well as en bloc resection, complete resection, the procedure time, adverse events and the risk factors associated with incomplete resection were analyzed. RESULTS: A total of 429 patients with 449 rectal NETs were enrolled for the classification of endoscopic morphology and were classified into four types (Ia, IIb, II, and III). There were 79 patients in the m-EMR group and 259 patients in the ESD group before matching. Propensity score matching created 77 pairs between the two groups that were well balanced. The mean procedure time was significantly shorter for m-EMR than for ESD (9.1 ± 4.4 min vs 16.0 ± 7.9 min, P = 0.000). The rates of en bloc resection (98.7% vs 100%; P = 1.000), complete resection (90.9% vs 93.5%, P = 0.548) and adverse events (2.6% vs 2.6%, P = 1.000) were similar between the two groups. Univariate and multivariate analyses showed that histopathological grade and endoscopic morphology were associated with incomplete resection. CONCLUSION: Both ESD and m-EMR are effective and safe for the treatment of rectal NETs. Endoscopic morphology should be considered along with histopathological grade for ER.

The distribution of refraction by age and gender in a non-myopic Chinese children population aged 6-12 years.

BACKGROUND: The Prevalence of myopia is increasing in China. This study aimed to explore the distribution of spherical equivalent (SE) and its association with age, body mass index (BMI), gender in a non-myopic Chinese children population aged 6 to 12 years. METHODS: A total of 6362 students were recruited for ophthalmological investigation. Demographic and myopia related behavioral information was collected. SE value was measured by the Topcon RM-8900 or KR-800autorefractors. Potential independent risk factors were determined with Odds Ratio (OR) and 95% Confidence Interval (CI) by logistic regression analysis. We further constructed the nomogram model to predict future onset of myopia. RESULTS: Among the study population, 3900 (61.3%) were non-myopic. The prevalence of myopia is 38.0% for boys and 39.5% for girls. The average SE values were 0.50 ± 0.70 D for boys and 0.60 ± 0.80 D for girls. The mean SE values decreased with age, and the value of height and BMI took on a stable trend. Threshold values for myopia varied across age groups and gender. Paternal myopia (OR: 1.22, 95%CI: 1.01-1.48), near-work activities on weekends (2.56, 1.17-5.61), and outdoor activities (0.68, 0.54-0.86) were associated with potential myopic in students. CONCLUSION: A series of age-gender based SE threshold values were established to predict myopia in Chinese children aged 6 to 12 years. High risk factors for myopia included paternal myopia, near-work activities on weekends, and outdoor activities. Countermeasures are encouraged to reverse the increasing trend of myopia in children.

The ratio of C2-C7 Cobb angle to T1 slope is an effective parameter for the selection of posterior surgical approach for patients with multisegmental cervical spondylotic myelopathy.

BACKGROUND: To our knowledge, laminectomy with fusion (LCF) and laminoplasty alone (LP) are both effective posterior surgical approaches for decompression of cervical spondylotic myelopathy (CSM). However, which one is suitable for patients has no standard answer. This study estimated whether the ratio of C2-C7 Cobb angle to T1 slope (CL/T1S) could be an indication of posterior surgical approach. METHODS: We retrospectively reviewed 128 patients with at least 6 months of follow-up who underwent LCF or LP. Radiological measurements, including C2-C7 Cobb angle, decompressed Cobb angle, T1 slope, cervical sagittal vertical axis, and curvature index (CI), and clinical outcomes, including Japanese Orthopedic Association score and visual analogue scale were evaluated. ROC curve analysis was used to identify discriminative power of CL/T1S ratio to predict kyphotic deformity and severe lordosis loss. The t-test and Mann-Whitney U-test were used to evaluate the difference between LCF and LP. Kruskal-Wallis H - test and ANOVA were used to evaluate the difference among different ratio CL/T1S groups. RESULTS: The cervical lordosis decreased after LCF or LP (p < 0.001, p < 0.001, respectively). Based on ROC curve analysis, CL/T1S ratio had a good discriminative power to predict kyphotic deformity and severe lordosis loss (AUC = 0.70, AUC = 0.88, respectively). According to CI value changes, cervical lordosis losses in group LP were larger than that in group LCF (p = 0.006). However, there was no significant difference in CI changes of fair-ratio CL/T1S group between LCF and LP. For patients with low CL/T1S ratio or high CL/T1S ratio, CI changes in group LP were greater than that in group LCF (p = 0.037, p = 0.042, respectively). CONCLUSIONS: CL/T1S ratio could be an indication of posterior surgical approach. Compared with LP, LCF reduces postoperative cervical lordosis losses in low-ratio and high-ratio CL/T1S groups.