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The vestibular system involves high-level sensory and cognitive processes, such as spatial perception, balance control, visual stability, and emotional control. Vestibular dysfunction can induce vertigo, blurred vision, postural imbalance, walking instability, and spatial discomfort, which causes serious damage to health. It has long been known that after peripheral vestibular lesion, vestibular dysfunction may spontaneously recover. This is known as vestibular compensation. However, at least 20% to 30% of patients with vestibular disorders cannot yield vestibular compensation and remain with vestibular dysfunction for the rest of their lives. The exploration of the biological characteristics and regulatory factors of the loss and reestablishment of vestibular function will establish a new understanding of the mechanism of vestibular compensation and provide new tools and strategies for promoting vestibular rehabilitation. We aim to comprehensively review the mechanism of vestibular compensation and discuss future directions in this field.

Rationale: The stress response of heart rate, which is determined by the plasticity of the sinoatrial node (SAN), is essential for cardiac function and survival in mammals. As an RNA-binding protein, CIRP (cold-inducible RNA-binding protein) can act as a stress regulator. Previously, we have documented that CIRP regulates cardiac electrophysiology at posttranscriptional level, suggesting its role in SAN plasticity, especially upon stress conditions. Objective: Our aim was to clarify the role of CIRP in SAN plasticity and heart rate regulation under stress conditions. Methods and Results: Telemetric ECG monitoring demonstrated an excessive acceleration of heart rate under isoprenaline stimulation in conscious CIRP-KO (knockout) rats. Patch-clamp analysis and confocal microscopic Ca 2+ imaging of isolated SAN cells demonstrated that isoprenaline stimulation induced a faster spontaneous firing rate in CIRP-KO SAN cells than that in WT (wild type) SAN cells. A higher concentration of cAMP—the key mediator of pacemaker activity—was detected in CIRP-KO SAN tissues than in WT SAN tissues. RNA sequencing and quantitative real-time polymerase chain reaction analyses of single cells revealed that the 4B and 4D subtypes of PDE (phosphodiesterase), which controls cAMP degradation, were significantly decreased in CIRP-KO SAN cells. A PDE4 inhibitor (rolipram) abolished the difference in beating rate resulting from CIRP deficiency. The mechanistic study showed that CIRP stabilized the mRNA of Pde4b and Pde4d by direct mRNA binding, thereby regulating the protein expression of PDE4B and PDE4D at posttranscriptional level. Conclusions: CIRP acts as an mRNA stabilizer of specific PDEs to control the cAMP concentration in SAN, maintaining the appropriate heart rate stress response.

Background SAPHO syndrome is a group of symptoms consisting of synovitis, acne, pustulosis, hyperostosis and osteosis. There is no specific laboratory index assist in the diagnosis of SAPHO because of its highly heterogeneous clinical manifestations. Pathogenic microorganisms had been identified in biopsies of some SAPHO cases and particular gene mutations were also linked to the occurrence of SAPHO. It is largely unknown whether intestinal microbiome plays a role in pathogenesis of SAPHO. To explore the intestinal microbiome structure of SAPHO syndrome, fecal samples from 17 SAPHO patients and 14 healthy controls (HC) were collected for 16S rDNA sequencing. Results Our results showed that there was no significant difference in alpha indexes and beta diversity between SAPHO and HC samples, while there were 14 operational taxonomic units (OTUs) in the Wilcoxon rank-sum test and 42 OTUs in the MetagenomeSeq analysis showed significant difference in distribution between the SAPHO and HC groups, 3 of which in Firmicutes were also observed in the random forest analysis and used to construct a receiver operating characteristic curve to evaluate the diagnostic value, the area under the curve was 0.86. Conclusion Fecal-associated microbiome in the SAPHO samples was characterized by the alteration in abundance of some nondominant species, and the 3 selected OTUs in Firmicutes could serve as candidate biomarkers for SAPHO syndrome diagnosis.

Background The present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC). Methods Totally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC. Results A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19–9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC. Conclusions The present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.

Background : The present study attempted to detect a specific circular RNA (circRNA) for the early diagnosis of gastric cancer (GC). Methods: We selected four patients with GC for this study. The total RNA of the malignant and adjacent tissues was extracted, and the circRNA was screened. The eight most upregulated and downregulated circRNAs with a statistically significant relation to GC and paired adjacent nontumorous tissues were identified using real-time fluorescent quantitative polymerase chain reaction (PCR). CircRNA expression was identified by quantitative reverse transcriptase PCR in 78 cases of GC and adjacent tissues, and in the gastric fluids of 30 patients with chronic nonatrophic gastritis, 30 patients with chronic atrophic gastritis, 21 with early GC, and 57 with advanced GC. Results: A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significant aberrant expression in GC tissues. A majority of the differentially expressed circRNAs originated from chr1, chr3, chr4, chr6, and chr11. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissues, and its level in GC tissues correlated with the tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen, and carbohydrate antigen 19-9 expression. A crucial observation was the presence of this circRNA in the gastric fluid of patients with early and advanced GC. Conclusions: The present study uncovered a new hsa_circRNA expression profile in human GC, of which hsa_circ_000780 was significantly downregulated in GC tissues and in gastric fluid. It can be potentially used as a novel biomarker for early GC screening.

Purpose To report the 1-year visual and keratometric results of epithelium-on corneal collagen crosslinking (CXL) for advanced keratoconus (median maximum keratometry [K] ≥58.0 diopters [D]). Setting School of Ophthalmology and Optometry and Eye Hospital of Wenzhou Medical College, Wenzhou, China. Design Prospective case series. Methods Patients with bilateral progressive keratoconus had tetracaine-enhanced epithelium-on CXL. The worse eye had CXL, and the fellow eye was not treated. Results were reported 1, 3, 6, and 12 months postoperatively. The outcomes were compared with those in the fellow untreated eyes. Results Twenty-one eyes of 21 patients with a median age of 20.4 years (interquartile range [IQR], 9.5 years) were treated. A significant improvement in postoperative uncorrected distance visual acuity was observed at 12 months ( P = .002). Postoperative corrected distance visual acuity improved at 6 months and 12 months ( P ≤ .009) compared with baseline values. The maximum K decreased by 1.63 D from the median preoperative maximum K of 62.7 D (IQR, 12.9 D) at 12 months ( P P = .001). Correlation analysis between the preoperative maximum K values and the change over 6 to 12 months between different studies showed a significant correlation ( r = −0.764, P Conclusions Epithelium-on CXL was an effective treatment for patients with advanced keratoconus. A higher preoperative maximum K value correlated with greater corneal flattening after CXL. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

Poly(U) polymerases (PUPs) catalyze 3′ uridylation of mRNAs and small RNAs, a modification often correlating with decreased RNA stability. We have investigated the importance of three proteins with in vitro PUP activity, PUP-1/CDE-1, PUP-2 and PUP-3, in C. elegans germline development. Genetic analysis indicates that PUP-1/CDE-1 and PUP-2 are developmentally redundant under conditions of temperature stress during which they ensure germline viability and development. Multiple lines of evidence indicate that pup-1/-2 double mutant germ cells fail to maintain their identity as distinct from soma. Consistent with phenotypic data, PUP-1 and PUP-2 are expressed in embryonic germ cell precursors and throughout germline development. The developmental importance of PUP activity is presumably in regulating gene expression as both a direct and indirect consequence of modifying target RNAs. PUP-3 is significantly overexpressed in the pup-1/-2 germline, and loss of pup-3 function partially suppresses pup-1/-2 germline defects. We conclude that one major function of PUP-1/-2 is to limit PUP-3 expression. Overall, the balance of PUP-1, PUP-2 and PUP-3 activities appears to ensure proper germline development.

To compare central corneal thickness (CCT), anterior chamber depth (ACD), and keratometry (K) readings measured using optical low-coherence reflectometry (OLCR) biometry and high-resolution rotating Scheimpflug photography.Eye Hospital of Wenzhou Medical College, Wenzhou, China.Comparative case series.The CCT, ACD endothelium to lens, ACD epithelium to lens, and K (mean; in flattest meridian; in steepest meridian) were measured 5 times using the LenStar/Biograph OLCR biometer and 3 times with the Pentacam Scheimpflug system in eyes of healthy volunteers. Concordance was evaluated using paired t tests, the Pearson correlation, and Bland-Altman analyses.The CCT, ACD endothelium to lens, and ACD epithelium to lens measured with the Scheimpflug system were slightly, albeit significantly, higher than with the OLCR biometer (P.05); the respective 95% limits of agreement (LoA) were -8.2 μm to 15.7 μm, -0.11 to 0.15 mm, and -0.13 to 0.17 mm. However, the Scheimpflug system gave significantly flatter readings for K in the flattest meridian (95% LoA, -0.54 to 0.32 diopters [D]), K in the steepest meridian (95% LoA, -0.63 to 0.45 D), and mean K (95% LoA, -0.53 to 0.33 D) (P.001). The CCT, ACD, and K readings were all highly correlated between the 2 devices (r0.95, P.001).The CCT and ACD measurements with the OLCR biometer and Scheimpflug system can be used interchangeably in healthy young subjects. However, for K measurements, these devices have wide LoA so may not be interchangeable under certain clinical circumstances.