Increased Sparc release from subchondral osteoblasts promotes articular chondrocyte degeneration under estrogen withdrawal.

OBJECTIVE: The incidence of osteoarthritis (OA) in menopausal women is significantly higher than in same-aged men. Investigating the role of subchondral osteoblasts in estrogen deficiency-induced OA may help elucidate the pathological mechanism, providing new insights for the diagnosis and treatment of menopausal OA. METHODS: A classical ovariectomy-induced OA (OVX-OA) rat model was utilized to isolate primary articular chondrocytes and subchondral osteoblasts, which were identified and then cocultured in Transwell. The expression of chondrocyte anabolic and catabolic indicators was evaluated. The differentially expressed proteins in the conditioned medium (CM) of osteoblasts were identified by Liquid Chromatograph-Mass Spectrometer (LC-MS/MS). Normal chondrocytes were treated with osteoblast CM, and then RNA sequencing was performed on the treated chondrocytes. KEGG was used to identify significant enrichment of signaling pathways, and Simple Western was used to verify the expression of related proteins in the signaling pathways. RESULTS: Coculture of OVX-OA subchondral osteoblasts with chondrocytes significantly downregulated the expression of the anabolic indicators and upregulated the expression of the catabolic indicators in chondrocytes. 1,601 proteins were identified in both normal and OVX osteoblast culture supernatants. Protein-protein interaction network analysis revealed that Sparc was one of the hub proteins. The AMPK/Foxo3a signaling pathway of chondrocytes was downregulated by OVX-OA osteoblasts CM. AICAR, the AMPK agonist, partially reversed the catabolic effect of OVX-OA osteoblasts on chondrocytes. CONCLUSIONS: Sparc secreted by OVX-OA subchondral osteoblasts can downregulate the AMPK/Foxo3a signaling pathway of chondrocytes, thereby promoting chondrocyte degeneration.

[Clinical characteristics and their influences on the survival of leptomeningeal metastasis derived from lung adenocarcinoma harboring epithelial growth factor receptor mutation].

Objective: To analyze the clinical characteristics of leptomeningeal metastasis (LM) patients from epithelial growth factor receptor (EGFR)-mutated lung adenocarcinoma, and their impacts on the survival of the patients. Methods: From July 2018 to July 2022, the clinicopathological data of 81 patients diagnosed as EGFR-mutated lung adenocarcinoma LM by cytopathology who admitted to the Department of Oncology of Xiangya Hospital of Central South University were retrospectively analyzed, including 33 males and 48 females. The age ranged from 31 to 76 years, with a median age of 54 years. All the 81 patients were followed up, with a median follow-up of 21.0 months (95%CI: 12.5 to 29.5 months). The Kaplan Meier method was used to draw survival curve. Cox proportional hazards regression model was used to analyze the impact of the factors on the survival of patients. Results: Among the 81 patients, the interval between the initial diagnosis of lung cancer and the pathological diagnosis of LM in cerebrospinal fluid (CSF) was 0-108 months, with a median interval of 14 months. Fifty-two patients (64.2%) used the third-generation epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), while 17 patients (21.0%) used EGFR-TKIs in combination with other drugs, and 12 patients (14.8%) were treated with best supportive care (BSC). Sixty patients (74.1%) had a Kanofsky performance status (KPS) score of less than 60 points, and 71 patients (87.7%) had brain parenchymal metastasis and/or spinal metastasis. Twenty-two patients (27.2%) used pemetrexed through intrathecal CSF, and 17 patients (21.0%) used pemetrexed through the Ommaya sac to the CSF of the ventricle. The incidence of adverse event related to the administration of pemetrexed through CSF was 64.1% (25/39), mainly manifested as myelosuppression, including 22 patients of leukocyte reduction, 25 patients of hemoglobin reduction, and 14 patients of platelet reduction. The median post-leptomeningeal metastasis overall survival (pLM-OS) in 81 patients was 11.0 (95%CI: 7.7-14.3) months. KPS score≥60 points (HR=0.407, 95%CI: 0.170-0.973, P=0.043), CSF cytology negative after treatment (vs persistent positive, HR=0.351, 95%CI: 0.155-0.792, P=0.012), intraventricular administration of pemetrexed (vs non intraventricular administration of pemetrexed, HR=0.319, 95%CI: 0.137-0.745, P=0.008) and the treatment with third-generation EGFR-TKIs after LM (vs EGFR-TKIs in combination with other drugs, HR=0.486, 95%CI: 0.237-0.998, P=0.049) were a factor affecting pLM-OS of patients. Conclusions: Brain parenchyma, or/and spine are the most sites where the LM patients concurrently metastasize. KPS score≥60 points and CSF cytology negative after treatment, intraventricular administration of pemetrexed and the treatment with third-generation EGFR-TKIs are indictors affecting pLM-OS of the patients.

[An investigative study on the correlation between refractive status and ocular biometric parameters in 3-6-year-old children in Shunyi District, Beijing, China].

Objective: To investigate the relationship between refractive status and ocular biometric parameters in preschool children in Shunyi District, Beijing. Methods: This cross-sectional study employed a random cluster sampling method to measure the ocular axial length (AL), corneal curvature(CR), anterior chamber depth, and horizontal corneal diameter (WTW) using an optical biometer in 3-6-year-old children from 11 kindergartens in Shunyi District, Beijing. The ratio of AL to corneal curvature radius (AL/CR) was calculated. Cycloplegic refraction was performed using 1% cyclopentolate, and the equivalent spherical diopter (SE) was calculated. Ocular biometric parameters were compared among different age groups and refractive statuses. Correlation and regression analyses were conducted between SE and ocular biometric parameters. Results: A total of 1, 142 children completed the examination, with a mean age of (4.52±0.87) years, including 119 three-year-olds, 487 four-year-olds, 362 five-year-olds, and 174 six-year-olds. Among them, 554 were boys and 588 were girls. The mean SE of the examined children was (1.19±0.81) D, AL was (22.27±0.67) mm, corneal curvature radius was (7.73±0.25) mm, and the anterior chamber depth was (3.33±0.67) mm. The mean SE for three-, four-, five-, and six-year-old children was 1.18, 1.19, 1.21, and 1.13 D, respectively. SE showed correlations with AL, AL/CR, and anterior chamber depth (r=-0.350, -0.542, -0.083; all P<0.05), but no correlation with WTW or corneal curvature radius (P>0.05). Among children with different refractive statuses, SE showed stronger correlations with AL and AL/CR in myopic, hyperopic, and highly hyperopic children compared to emmetropic children, and the correlation tended to be stronger with increasing age. The linear regression equations for SE and AL, AL/CR were SE=10.64-0.42·AL and SE=21.48-7.043·AL/CR, respectively. Conclusions: The refractive status of 3-6-year-old children in Shunyi District, Beijing, showed minimal changes. Myopic children had longer AL, deeper anterior chamber, and slightly steeper cornea.

Knockout of the NONO Gene Inhibits Neointima Formation in a Mouse Model of Vascular Injury.

[Figure: see text].

Yak miR-2285o-3p attenuates hypoxia-induced apoptosis by targeting caspase-3.

miRNAs are a class of hairpin-derived RNAs, 21-24 nucleotides in length, which are involved in a range of biological processes. The bta-miR-2285 family has over 40 members spanning the entire bovine genome. We previously found that bta-miR-2285o-3p was highly expressed in yak heart and lung when compared with cattle, which prompted us to investigate its potential function in high-altitude adaptation of yaks. In this study, we detected wide-spread high expression of bta-miR-2285o-3p in yak tissues. Further experiments revealed that the protein tyrosine phosphatase receptor type M (PTPRM) gene was the host gene of bta-miR-2285o-3p and that two linked SNPs in bta-mir-2285o precursor affected the biogenesis of mature miRNA (bta-miR-2285o-3p). Functional analysis in vitro indicated that bta-miR-2285o-3p attenuated hypoxia-induced apoptosis by targeting very low-density lipoprotein receptor (VLDLR), phosphatase and tensin homolog (PTEN) and caspase-3. Expression level analysis in vivo revealed the high negative Pearson's correlation between bta-miR-2285o-3p and caspase3 in yak, highlighting the potential important roles of bta-miR-2285o-3p in yak high-altitude adaptation. Our study provides a typical model for deciphering the function of miRNAs in environmental adaptation.

Parsing the microRNA genetics basis regulating skeletal muscle fiber types and meat quality traits in pigs.

Muscle fibers are closely related to human diseases and livestock meat quality. However, the genetics basis of microRNAs (miRNAs) in regulating muscle fibers is not completely understood. In this study, we constructed the whole genome-wide miRNA expression profiles of porcine fast-twitch muscle [biceps femoris (Bf)] and slow-twitch muscle [soleus (Sol)], and identified hundreds of miRNAs, including four skeletal muscle-highly expressed miRNAs, ssc-miR-378, ssc-let-7f, ssc-miR-26a, and ssc-miR-27b-3p. Moreover, we identified 63 differentially expressed (DE) miRNAs between biceps femoris vs. soleus, which are the key candidate miRNAs regulating the skeletal muscle fiber types. In addition, we found that the expression of DE ssc-miR-499-5p was significantly correlated to the expression of Myoglobin (r = 0.6872, P < 0.0001) and Myosin heavy chain 7 (MYH7; r = 0.5408, P = 0.0020), and pH45 min (r = 0.3806, P = 0.0380) and glucose content (r = -0.4382, P = 0.0154); while the expression of DE ssc-miR-499-3p was significantly correlated to the expression of Myoglobin (r = 0.5340, P = 0.0024) and pH45 min (r = 0.4857, P = 0.0065). Taken together, our data established a sound foundation for further studies on the regulatory mechanisms of miRNAs in skeletal muscle fiber conversion and meat quality traits in livestock, and could provide a genetic explanation of the role of miRNAs in human muscular diseases.

Effect of salt concentration on microbial communities, physicochemical properties and metabolite profile during spontaneous fermentation of Chinese northeast sauerkraut.

AIM: The aim of this study was to study the effects of salt concentrations on the microbial communities, physicochemical properties, metabolome profiles and sensory characteristics during the fermentation of traditional northeast sauerkraut. METHODS AND RESULTS: Northeast sauerkraut was spontaneously fermented under four salt concentrations (0·5, 1·5, 2·5 and 3·5%, w/w). The result of microbiological analysis showed that the population of lactic acid bacteria in 2·5%-salted sauerkraut was significantly higher than that in the other samples. Correspondingly, the speed of decrease in pH and accumulation of acids were the highest in 2·5%-salted sauerkraut. The glucose (analysed by HPLC) in 2·5%-salted sauerkraut was consumed more completely to produce higher levels of organic acids compared to those in the other samples. Principle component analysis showed clear differences in the metabolites of sauerkraut according to different salt concentrations. A higher level of volatiles (detected by HS-SPME/GC-MS) was identified in 2·5%-salted sauerkraut, and sensory evaluation demonstrated that 2·5%-salted sauerkraut had the best sensory characteristics. CONCLUSION: The best quality of sauerkraut was obtained from fermented under 2·5% salt concentration. SIGNIFICANCE AND IMPACT OF THE STUDY: This study facilitated the understanding of the effects of salt on the sauerkraut fermentation and may be useful for developing the quality of sauerkraut.

ICTV Virus Taxonomy Profile: Mymonaviridae.

Members of the family Mymonaviridae produce filamentous, enveloped virions containing a single molecule of linear, negative-sense RNA of ≈10 kb. The family currently includes a single genus, Sclerotimonavirus. Mymonaviruses usually infect filamentous fungi, and one virus, Sclerotinia sclerotiorum negative-stranded RNA virus 1, induces hypovirulence in the fungal host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Mymonaviridae, which is available at ictv.global/report/mymonaviridae.

Clinical characteristics of neurogenic dysphagia in adult patients with Chiari malformation type I.

OBJECTIVE: To investigate changes of swallowing function and associated symptoms in Chiari malformation typeI (CMI) patients with and without dysphagia by the analysis of their clinical and high-resolution manometry (HRM) parameters. METHODS: A total of 42 patients diagnosed with symptomatic CMI without atlantoaxial dislocations which were confirmed by clinical manifestations and magnetic resonance imaging (MRI) findings between January 2010 and July 2015 at Peking University Third Hospital were included in this study. Twenty patients had a history of various dysphagia symptoms, or reported symptoms of choking, coughing after eating or drinking, while the other 22 patients denied symptoms of dysphagia. The data collected from the medical records of these patients included the patient's age, sex, date of diagnosis, duration of illness, symptoms, results of MRI and HRM, and date of surgery. RESULTS: (1) Dysphagia group had 14 female patients, and no-dysphagia group had 8 female patients. Dysphagia usually occurred in female patients, and in addition to dysphagia, we recorded other symptoms and signs in the CMI patients, including numbness, hypoesthesia, limb weakness, neck pain, muscle atrophy, ataxia, hoarseness, symptoms caused by posterior cranial nerve damage, pharyngeal reflex, uvula deviation, and pyramidal signs. A higher percentage of the CMI patients with dysphagia (15/20) had symptoms of posterior cranial nerve damage compared with the control group (5/22; P=0.01). (2)HRM showed a significant difference in upper esophageal sphincter (UES) relax ratio measurement (75.3% vs. 63.1%, P=0.023) and UES proximal margin (17.2 cm vs. 15.7 cm, P=0.005) between the two groups. (3) The percentage of syringomyelia affecting the bulbar or upper cervical region on MRI was significantly higher in the dysphagia group (17/20 vs. 7/22, P=0.001). CONCLUSION: CMI was usually accompanied by symptoms caused by posterior cranial nerve damage, ataxia, and positive pyramidal signs. Location of the syringomyelia affecting specifically the bulbar or upper cervical region was associated with dysphagia in CMI patients. These findings suggest that the mechanism of dysphagia in CMI may be due to a dysfunction in the neurological pathway of pharyngeal muscle movement. Dysphagia etiology work-up should include CMI in the differential diagnosis.

Developing a prenatal nursing care International Classification for Nursing Practice catalogue.

AIM: This study aimed to develop a prenatal nursing care catalogue of International Classification for Nursing Practice. BACKGROUND: As a programme of the International Council of Nurses, International Classification for Nursing Practice aims to support standardized electronic nursing documentation and facilitate collection of comparable nursing data across settings. This initiative enables the study of relationships among nursing diagnoses, nursing interventions and nursing outcomes for best practice, healthcare management decisions, and policy development. The catalogues are usually focused on target populations. Pregnant women are the nursing population addressed in this project. METHODS: According to the guidelines for catalogue development, three research steps have been adopted: (a) identifying relevant nursing diagnoses, interventions and outcomes; (b) developing a conceptual framework for the catalogue; (c) expert's validation. RESULTS: This project established a prenatal nursing care catalogue with 228 terms in total, including 69 nursing diagnosis, 92 nursing interventions and 67 nursing outcomes, among them, 57 nursing terms were newly developed. All terms in the catalogue were organized by a framework with two main categories, i.e. Expected Changes of Pregnancy and Pregnancy at Risk. Each category had four domains, representing the physical, psychological, behavioral and environmental perspectives of nursing practice. IMPLICATIONS FOR NURSING PRACTICE: This catalogue can ease the documentation workload among prenatal care nurses, and facilitate storage and retrieval of standardized data for many purposes, such as quality improvement, administration decision-support and researches. The documentations of prenatal care provided data that can be more fluently communicated, compared and evaluated across various healthcare providers and clinic settings.

Multiomic analysis of mice epilepsy models suggest that miR-21a expression modulates mRNA and protein levels related to seizure deterioration.

Epilepsy is now recognized as the second most common neurological disease in China. To determine the genetic cause of epileptic encephalopathy, we performed a multiomics study using mouse models of controls, anticonvulsant mice treated with five drugs and epileptic mice. Based on genome-wide profiling analysis, we discovered four genes in the epileptic mouse group with differentially-expressed mRNA. After isobaric tags for relative and absolute quantification (iTRAQ) validation, only one gene, SNCA, remained, which was associated with apoptotic response of neuronal cells, and regulation of dopamine release and transport. We also identified three miRNAs targeting SNCA, out of which mmu-miR-21a-3p demonstrated a seven-fold change in expression between control and epileptic mice.

Socioeconomic and lifestyle factors and melanoma: a systematic review.

Evidence of social determinants of disease and awareness of the impact of these factors on outcomes continues to increase. Social determinants include both socioeconomic and lifestyle factors. This review examines the interface between socioeconomic status (SES) and lifestyle and their effects on melanoma incidence and mortality. Lifestyle factors including occupation, occupational exposures, body mass index, marital status, smoking, recreational sun exposure and tanning were explored as they have a known relationship with melanoma. A remarkable association of SES with melanoma incidence and prognosis has been acknowledged worldwide. Melanoma incidence is increased in populations of higher SES, especially among the highly educated, while lower SES populations present with later-stage disease at time of diagnosis and display greater mortality. The aforementioned lifestyle factors are also related to SES, and have been shown internationally to affect melanoma incidence and mortality. This comprehensive systematic review suggests that lifestyle factors including occupation, occupational exposure, obesity, recreational sun exposure and tanning may explain the relationship between SES and melanoma.

Combined low dose local anesthetics and opioids versus single use of LA for transurethral urological surgery: a meta-analysis.

INTRODUCTION: The combination of reduced dose of local anesthetics (LA) and highly lipid-soluble synthetic opioids for patients undergoing transurethral surgery could reduce block duration and side-effects. However, it remains unclear what are the most appropriate levels of low dose and the extent to which the side-effects could be controlled. A meta-analysis was conducted to address this concern. MATERIALS AND METHODS: Based on twelve randomized controlled trials, this meta-analysis pooled previous results to generate integrated evidence. RESULTS: Combined low dose of LA and opioids had similar sensory block and significantly shorter motor block duration (weighted mean difference: -39.31 min, 95% confidence interval (CI): -50.58--28.05, P < 0.00001) compared with single use of LA. There was no evidence of higher risk of analgesic failure in the combination group. In addition, combined low dose LA and opioids was associated with significantly reduced rate of postoperative hypotension (risk ratios (RR): 0.60, 95% CI: 0.37-0.96, P = 0.03) and shivering (RR: 0.27, 95% CI: 0.11-0.64, P = 0.003), but with higher rate of sedation (RR: 3.14, 95% CI: 1.02-9.66, P = 0.05). CONCLUSION: Combined low dose LA and opioids is a better choice for patients received transurethral surgery compared with single use of intrathecal LA.

Higher expression of acyl-CoA dehydrogenase genes in adipose tissues of obese compared to lean pig breeds.

The balance between biosynthesis and oxidation of fatty acids determines adipose deposition in mammals. Obese and lean pigs show obvious differences in total adipose mass and therefore offer an attractive model for comparative studies. We found that obese Rongchang pigs, when compared with lean Landrace pigs, exhibited significantly higher mRNA levels for five genes encoding acyl-CoA dehydrogenases involved in mitochondrial fatty-acid ß-oxidation in eight different adipose tissues. These changes in gene expression were positively correlated with adipocyte volume in the eight adipose tissues. Based on these results, we hypothesize that acyl-CoA dehydrogenase genes participate in the regulation of fat mass in pigs.

Distribution of H-FABP and ACSL4 gene polymorphisms and their associations with intramuscular fat content and backfat thickness in different pig populations.

Here, we analyzed the distribution of H-FABP/(HinfI, MspI, and HaeIII) and ACSL4/RsaI polymorphisms, and the associations of these 4 polymorphic loci with intramuscular fat (IMF) content and backfat thickness (BFT) in Yanan, Jinhua, Duroc, Landrace, Yorkshire, and Duroc x (Landrace x Yorkshire) (DLY) pigs. H-FABP/HinfI polymorphisms were present in all the 6 populations. At the ACSL4/RsaI locus, sows had 3 genotypes, whereas boars only had haplotype A or G, in Duroc, Landrace, Yorkshire, and DLY pigs. H-FABP/(MspI and HaeIII) and ACSL4/RsaI polymorphisms were absent in Yanan and Jinhua pigs. Linkage disequilibrium analysis indicated that the 3 loci (HinfI, MspI, and HaeIII) were separated. Association analysis showed that the H-FABP/HinfI locus significantly affected IMF content in DLY (P < 0.05) and Yanan (P < 0.001) pigs. The highest IMF content was recorded in the adH haplotype of the 3 H-FABP polymorphic loci (2.59%, P < 0.05) in DLY pigs. At the ACSL4/RsaI locus, higher IMF content was recorded for sows with a GG genotype or boars with a G haplotype compared to those with an AA genotype (2.53 vs 2.10%, P < 0.05) or A haplotype (2.48 vs 1.73%, P < 0.01) in DLY pigs. Significant differences were not obtained among these 4 polymorphic loci and BFT (P > 0.05). The results indicate that H-FABP and ACSL4 genes might serve as markers to improve IMF content (but not BFT) in the pig breeding system.