Osteonectin bidirectionally regulates osteoblast mineralization.

OBJECTIVE: The aim of this study was to investigate whether Osteonectin/Secreted protein acidic and rich in cysteine (ON/SPARC) had a two-way dose-dependent regulatory effect on osteoblast mineralization and its molecular mechanism. METHODS: Initially, different concentrations of ON were added in osteoblasts, and the gene of bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN) and alkaline phosphatase (ALP) were detected using reverse-transcription quantitative polymerase chain reaction (RT-PCR). Secondly, based on the above results, the Optima and inhibitory concentration of ON for osteoblast mineralization were determined and regrouped, the Control group was also set up, and the gene detections of Collagen 1 (Col 1), Discoidin domain receptor 2 (DDR2) and p38 mitogen­activated protein kinase were added using RT-PCR. In the third stage of the experiment, osteoblasts were pretreated with 0.4Mm ethyl-3,4-dihydroxybenzoate (DHB) (a specific inhibitor of collagen synthesis) for 3 h before adding the optima SPARC, the gene and protein expressions of OCN, OPN, BSP, ALP, DDR2, ALP, Col 1, DDR2 and P38 were detected by RT­qPCR and western blot analysis, and the mineralized nodules were observed by alizarin red staining. RESULTS: The results showed that the expression of OCN, OPN, BSP, ALP, DDR2, ALP, Col 1, DDR2 and P38 genes and proteins in osteoblasts were significantly enhanced by 1 ug/ml ON, 100 ug/ml ON or 1 ug/ml ON added with 3,4 DHB significantly inhibited the expressions of DDR2, P38 and the above-mentioned mineralization indexes, and significantly reduced the formation of mineralized nodules. CONCLUSION: This study suggested that ON had a bidirectional dose-dependent regulatory effect on osteoblast mineralization, and the activation of P38 pathway by collagen binding to DDR2 was also an important molecular mechanism.

Stub1 ameliorates ER stress-induced neural cell apoptosis and promotes locomotor recovery through restoring autophagy flux after spinal cord injury.

Endoplasmic reticulum (ER) stress-induced apoptosis and autophagy flux blockade significantly contribute to neuronal pathology of spinal cord injury (SCI). Yet, the molecular interplay between these two distinctive pathways in mediating the pathology of SCI remains largely unexplored. Currently, we aimed at exploring the crucial role of Stub1 in maintaining ER homeostasis and regulating autophagic flux after SCI. Our results demonstrate that Stub1 reduces ER stress induced neuronal apoptosis, promotes axonal regeneration, inhibits glial scar formation and fosters functional recovery by restoring autophagic flux following SCI. Stub1 enhances autophagic flux following SCI by alleviating the permeabilization of lysosomal membrane through activating TFEB. Importantly, we showed that Stub1 promotes the activation of TFEB by targeting HDAC2 for ubiquitination and degradation. Furthermore, the neuroprotective effect of Stub1 on SCI was abrogated by chloroquine administration, underscoring the essential role of Stub1-mediated enhancement of autophagic flux in its protective effects against SCI. Collectively, our data highlights the vital role of Stub1 in regulating ER stress and autophagy flux after SCI, and propose its potential as a promising target for neuroprotective interventions in SCI.

Independent and Combined Associations of Sleep Duration, Bedtime, and Polygenic Risk Score with the Risk of Hearing Loss among Middle-Aged and Old Chinese: The Dongfeng-Tongji Cohort Study.

Evidence available on the independent and combined associations of sleep duration, bedtime, and genetic predisposition with hearing loss was lacking. The present study included 15,827 participants from the Dongfeng-Tongji cohort study. Genetic risk was characterized by polygenic risk score (PRS) based on 37 genetic loci related to hearing loss. We conducted multivariate logistic regression models to assess the odds ratio (OR) for hearing loss with sleep duration and bedtime, as well as the joint association and interaction with PRS. Results showed that hearing loss was independently associated with sleeping ≥9 h/night compared to the recommended 7 to <8 h/night, and with bedtime ≤9:00 p.m. and >9:00 p.m. to 10:00 p.m. compared to those with bedtime >10:00 p.m. to 11:00 p.m., with estimated ORs of 1.25, 1.27, and 1.16, respectively. Meanwhile, the risk of hearing loss increased by 29% for each 5-risk allele increment of PRS. More importantly, joint analyses showed that the risk of hearing loss was 2-fold in sleep duration ≥9 h/night and high PRS, and 2.18-fold in bedtime ≤9:00 p.m. and high PRS. With significant joint effects of sleep duration and bedtime on hearing loss, we found an interaction of sleep duration with PRS in those with early bedtime and an interaction of bedtime with PRS in those with long sleep duration on hearing loss (Pint <0.05), and such relationships were more evident in high PRS. Similarly, the above relationships were also observed for age-related hearing loss and noise-induced hearing loss, particularly the latter. In addition, age-modified effects of sleep patterns on hearing loss were likewise observed, with stronger estimation among those aged <65 years. Accordingly, longer sleep duration, early bedtime, and high PRS were independently and jointly related to increased risk of hearing loss, suggesting the importance of considering both genetics and sleep pattern for risk assessment of hearing loss.

Polycyclic aromatic hydrocarbons exposure and plasma lncRNA signature: A profile and functional analysis.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants that pose detrimental effects on human health, and the exploration of the associations of PAHs exposure with long non-coding RNA (lncRNA) may provide novel clues to the underlying mechanisms. In the present study, we detected 10 urinary PAHs metabolites by GC-MS and plasma lncRNAs levels by Human LncRNA Array v4 among 230 participants from two panels (160 in the Shiyan panel and 70 in the Wuhan-Zhuhai panel). We applied linear regression models to assess the associations between PAHs metabolites and lncRNAs separately in each panel and combined the results using fixed-effect meta-analysis. To explore the potential origin of PAHs-related lncRNAs in plasma, we estimated their tissue-specificity and associations between lncRNAs levels in plasma and leukocytes. Leukocytes mRNA sequencing data and RNA binding proteins were utilized to explore implicated pathways of identified lncRNAs. We found that urinary 1-hydroxyphenanthrene (1-OH-Phe) was inversely associated with 8 lncRNAs and positively associated with 1 lncRNA, as well as 9-hydroxyphenanthrene (9-OH-Phe) was inversely associated with 11 lncRNAs (FDR < 0.1). Tissue specificity analysis using Genome Tissue Expression database suggested that several identified lncRNAs might specifically express in organs targeted by PAHs exposure (lung, liver, heart, kidney, and brain). Besides, plasma levels of 1-OH-Phe related ENSG00000260616 and 9-OH-Phe related STARD4-AS1 were inversely associated with their intra-leukocytes levels (P value < 0.05). Notably, STARD4-AS1 was positively associated with the expression levels of its neighboring protein-coding gene (CAMK4 and STARD4) in leukocytes and were involved in pathways related to cellular response to DNA damage, which we further confirmed using DNA damage biomarker, 8-hydroxydeoxyguanosine. Functional analysis also revealed vital pathways related to cytokine-mediated signaling and glucose homeostasis. Our findings provided novel insights into plausible biological mechanisms underlying the adverse effects of PAHs exposure.

Identification of Diagnostic Markers in Synovial Tissue of Osteoarthritis by Weighted Gene Coexpression Network.

Osteoarthritis (OA) is a serious threat to human health. However, the etiology and pathogenesis of the disease are not fully understood. Most researchers believe that the degeneration and imbalance of articular cartilage, extracellular matrix, and subchondral bone are the fundamental causes of osteoarthritis. However, recent studies have shown that synovial lesions may precede cartilage, which may be an important precipitating factor in the early stage of OA and the whole course of the disease. This study aimed to conduct an analysis based on sequence data from the Gene Expression Omnibus (GEO) database to investigate the presence of effective biomarkers in the synovial tissue of osteoarthritis for the diagnosis and control of OA progression. In this study, the differentially expressed OA-related genes (DE-OARGs) in osteoarthritis synovial tissues were extracted in the GSE55235 and GSE55457 datasets using the Weighted Gene Co-expression Network Analysis (WGCNA) and limma. Least-Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to select the diagnostic genes based on the DE-OARGs by glmnet package. 7 genes were selected as diagnostic genes including SAT1, RLF, MAFF, SIK1, RORA, ZNF529, and EBF2. Subsequently, the diagnostic model was constructed and the results of the Area Under the Curve (AUC) demonstrated that the diagnostic model had high diagnostic performance for OA. Additionally, among the 22 immune cells of the Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and the 24 immune cells of the single sample Gene Set Enrichment Analysis (ssGSEA), 3 immune cells and 5 immune cells were different between the OA and normal samples, respectively. The expression trends of the 7 diagnostic genes were consistent in the GEO datasets and the results of the real-time reverse transcription PCR (qRT-PCR). The results of this study demonstrate that these diagnostic markers have important significance in the diagnosis and treatment of OA, and will provide further evidence for the clinical and functional studies of OA.

Laryngeal contact granuloma after radiotherapy in patients with nasopharyngeal carcinoma: a case series.

Background: Laryngeal contact granuloma (LCG) is a benign hypertrophic lesion and phonatory injury after abnormal vocal behavior is regarded as its major etiology. Patients receiving radiation for non-laryngeal head and neck tumors are troubled by persistent voice impairment. The occurrence of LCG after radiotherapy for nasopharyngeal carcinoma (NPC) in our practice has implored us to re-exam their underlying etiology. We hypothesize that a proportion of LCG results from voice change caused by non-laryngeal head and neck cancer radiotherapy and firstly describe a distinct LCG population originated after radiotherapy for NPC with respect to the clinical profile, presentation, prognosis and response to treatment of patients. Methods: We retrospectively reviewed the laryngoscopic examination and tumor study findings to elucidate the common clinical features of patients who presented with LCG after radiotherapy for NPC. All patients were regularly monitored with telescopic examination until lesions disappeared. Data on age, sex, clinical presentation, telescopic findings, management, latency time of lesion formation, remission time and clinical outcome were reviewed. Results: The medical review identified 27 cases of LCG secondary to radiotherapy for NPC. All lesions had been diagnosed during routine endoscopy following radiation. The interval between radiation onset and endoscopic diagnosis was 3.77 months (range, 0.67-11 months). 20 cases were resolved through simple observation, 4 cases were resolved with the administration of proton pump inhibitors (PPIs), and 3 cases with a poor response to PPI therapy required subsequent surgical resection. The mean remission time in the observation and PPI groups was 4.42 months (range, 0.73-18.9 months) and 5.78 months (range, 2.17-14.63 months), respectively. All patients recovered completely and none experienced recurrence during a mean follow-up of 32.44 months (range, 5.6-71.67 months). Conclusions: Iatrogenic granulomas of vocal process are presenting after radiation for non-laryngeal head and neck cancers. In contrast with spontaneous granulomas, these granulomas can be cured at high remission rates and low recurrence trend without specific intervention. Thus, simple observation may be sufficient for radiation-induced LCG.

Barrier-penetrating liposome targeted delivery of basic fibroblast growth factor for spinal cord injury repair.

Nanoparticle technologies offer a non-invasive means to deliver basic fibroblast growth factor (bFGF) for the treatment of spinal cord injury (SCI). However, the inability of bFGF to accumulate at the injury site and inefficient penetration across the blood-spinal cord barrier (BSCB) remain challenges. The present study describes a dual-targeting liposome (bFGF@Lip-Cp&Rp) with injury lesion targeting and BSCB-penetrating capability to deliver bFGF for SCI treatment. The CAQK peptide (Cp) with injury lesion targeting ability and R2KC peptide (Rp) with BSCB-penetrating capability were grafted onto the liposomes for a flexible and non-invasive drug delivery systems preparation. Results exhibit that the dual-targeted liposomes could significantly cross the BSCB and accumulate at the injury site. During the early stage of SCI, bFGF@Lip-Cp&Rp promotes repair of BSCB and facilitates M2-polarization of macrophages. Regular delivery of bFGF@Lip-Cp&Rp increase HUVECs tube formation and angiogenesis, ameliorate the microenvironment of lesion site, suppress the neuronal apoptosis and axonal atrophy in SCI rats. Importantly, continuous treatment of bFGF@Lip-Cp&Rp supports the restoration of limb motor function in SCI rats. In summary, this research implies that the injury site-targeting and BSCB-penetrating liposomes could be a promising therapeutic approach for the treatment of SCI.

Sleep Duration, Midday Napping, and Serum Homocysteine Levels: A Gene-Environment Interaction Study.

The associations of sleep duration and midday napping with homocysteine (Hcy) levels, and whether these sleep behaviors modify the association between genetic predisposition and Hcy levels, has yet to be investigated. We included 19,426 participants without severe health conditions at baseline from the Dongfeng−Tongji cohort. In a subgroup of 15,126 participants with genetic data, a genetic risk score (GRS) based on 18 Hcy-related loci was constructed to test the gene−sleep interactions in Hcy. Hcy levels were higher in subjects with a long sleep duration (≥9 h) and midday napping (>90 min), as compared to those who reported a moderate sleep duration (7 to <8 h) and midday napping (1−30 min) (all p values < 0.05). A long sleep duration and midday napping showed a joint effect in increasing Hcy (p for trend < 0.001). Significant interactions regarding Hcy levels were observed for a long sleep duration with GRS and MTHFR rs1801133, and long midday napping with DPEP1 rs12921383 (all p values for interaction < 0.05). Overall findings indicated that a long sleep duration and midday napping were associated with elevated serum Hcy levels, independently and jointly, and amplified the genetic susceptibility to higher Hcy.

Genetic susceptibility, homocysteine levels, and risk of all-cause and cause-specific mortality: A prospective cohort study.

BACKGROUND: The associations of homocysteine (Hcy) and gene-Hcy interactions with the risk of all-cause and cause-specific mortality remain unclear. METHODS: A total of 19,826 middle-aged and elderly Chinese adults were included from the Dongfeng-Tongji cohort in 2013-2014 and were followed-up to 31 December 2018. Cox regression was used to examine the association between Hcy and mortality. We selected 18 well-established Hcy-associated genetic variants to constructed the weighted genetic risk score (GRS) among 15,434 participants with genetic data, and interactions between genetic susceptibility and Hcy on mortality were assessed. RESULTS: After multivariate adjustment, elevated serum Hcy levels were associated with higher risk of mortality from all-cause, CVD, coronary heart disease (CHD), stroke, and cancer. We also observed a significant interaction between GRS and Hcy on CHD mortality. Moreover, the rs7130284 and rs957140 on NOX4 modified the association between Hcy and mortality from CVD and CHD, and rs154657 on DPEP1 modified the association between Hcy and CHD mortality. CONCLUSIONS: Elevated Hcy levels were associated with increased risk of all-cause and cause-specific mortality among middle-aged and elderly Chinese. Hcy-related genetic variants on NOX4 and DPEP1 might modify the associations of Hcy with CVD mortality or CHD mortality.

The clinical effect of trochanteric slide osteotomy combined with a cementless femoral conical stem in total hip replacement for the treatment of Crowe type IV developmental dysplasia of the hip.

BACKGROUND: Total hip replacement (THR) for Crowe type IV developmental dysplasia of the hip (DDH) is still challenging due to specific joint deformities and the high incidence of post-operative complications. OBJECTIVE: This study aimed to evaluate the clinical effect of trochanteric slide osteotomy (TSO) combined with a cementless femoral conical stem in THR for the treatment of Crowe type IV DDH. METHODS: Thirty-one total hip replacements (26 patients) with Crowe type IV DDH were performed using TSO combined with a cementless femoral conical stem. Surgical outcomes were evaluated using leg length discrepancy (LLD), Harris hip score, and post-operative complications. RESULTS: The average pre-operative LLD was 51 mm (range 46-58 mm), decreasing to an average of 10 mm (range 8-12 mm) post-operatively. As a result, the post-operative incidence of the Trendelenburg sign significantly decreased compared with the pre-operative incidence (P< 0.05). Bony union was identified in 26 hips (83.9%), fibrous union in four (12.9%), and non-union in one (3.2%). No acetabular or femoral component loosening, dislocation, or deep infection around the component was found in any of the patients during the follow-up period (27 to 39 months). The average Harris hip score improved from 63.0 ± 3.0 (range 58-69) to 93.3 ± 2.0 (range 91-96). CONCLUSION: TSO combined with a cementless conical stem in THR is an appropriate option for patients with high congenital hip dislocation.

Inhibition of autophagy impairs free fatty acid-induced excessive lipid accumulation in hepatocellular carcinoma and hepatic cells.

Autophagy is a reparative life-sustaining process. Dysfunctions of autophagy play an important role in the progression of chronic liver diseases. The role of autophagy in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is still controversial. This study aimed to analyse the roles and molecular mechanisms of autophagy in NAFLD. In hepatic L02 and liver cancer cells (HuH-7), nonalcoholic fatty liver (NAFL) cell model was induced by free fatty acids (FFA). The cytotoxic effect was measured by MTS assay. Lipid droplets were detected by immunofluorescence assay and flow cytometry. The autophagy-related genes were measured by Western blot analysis. The autophagy inhibitor 3-methyladenine (3-MA) was used to block the autophagy. FFA induced a significant increase in the intracellular content of lipid droplets, and the accumulation of fatty droplets was dose-dependent in L02 and HuH-7 cells. FFA (800 lM) had no cytotoxic effect on L02 and HuH-7 cells. The levels of LC3-II/LC3-I and BECN1 were increased, but the level of p62 was decreased in the NAFL cell models. The expression of these genes was dose-dependent in the NAFL cell models. Intracellular lipid accumulation was associated with the upregulation of LC3-II/LC3-I and BECN1 and the deregulation of p62 in the NAFL cell models. The autophagy inhibitor 3-MA suppressed the FFA-induced autophagy in the NAFL cell models. Furthermore, 3-MA treatment significantly alleviated the accumulation of lipid droplets in L02 and HuH-7 cells. Our results suggest that autophagy has a significant effect on lipid accumulation in the NAFL cell models. Inhibition of autophagy impairs FFA-induced excessive lipid accumulation in hepatocellular carcinoma and hepatic cells.

Application and the Effect of the Triple Prerehabilitation Nursing Model in the Perioperative Period of Knee Arthroplasty in Diabetic Patients.

Objective: The aim of the study was to explore the application and the effect of the triple prerehabilitation nursing model in the perioperative period of knee arthroplasty in diabetic patients. Methods: The prospectively included 60 patients with diabetes who underwent total knee replacement were admitted from August 2021 to April 2022 and were divided into 2 groups according to the (1 : 1) ratio. The control group was mainly given routine nursing care. On the basis of the control group, the observation group received triple prerehabilitation nursing. The postoperative knee flexion, hospital for the special surgery knee score (HSS), the daily living ability (Barthel) score, the modified fall efficacy scale (MFES) score, the recovery of the lower-limb muscle strength, and the incidence of complications were compared between the two groups. Results: The knee flexion degree and lower-limb muscle recovery of the observation group were better than those of the control group at 3 d, 7 d, and 14 d after operation (P < 0.05). The HSS score, Barthel score, and MFES score of the observation group were higher than those of the control group (P < 0.05). There was no significant difference in postoperative complications between the two groups (P > 0.05). Conclusion: The triple prerehabilitation nursing care for diabetic patients undergoing total knee replacement can promote the recovery of limb function.

Reliability and Validity of Common Subjective Instruments in Assessing Physical Activity and Sedentary Behaviour in Chinese College Students.

The reliability and validity of common physical activity (PA) questionnaires are not well investigated in college students. This study aims to evaluate the reliability and validity of common subjective instruments in measuring PA and sedentary behaviour (SB) among college students. A total of 142 college students were included through convenience sampling. Each participant was asked to wear Actigraph wGT3X-BT accelerometers and fill physical activity logs (PAL) for 7 consecutive days. The Global Physical Activity Questionnaire (GPAQ), the International Physical Activity Questionnaire long-form (IPAQ-LF), and short-form (IPAQ-SF) were interviewed by face-to-face at both day 0 and day 8. Reliability was evaluated by intraclass correlation coefficient (ICC), while the validity was evaluated by Spearman correlation coefficient and Bland-Altman statistics. The instruments showed moderate reliability in reporting total PA (ICC = 0.50-0.62) and SB (ICC = 0.47-0.52), while moderate validity in reporting moderate and vigorous PA (MVPA) (r = 0.37-0.42), but fair to poor validity in reporting SB (r = 0.09-0.28). Bland-Altman plots showed that all the instruments would underestimate MVPA and overestimate SB. Thus, in Chinese younger adults, the GPAQ, IPAQ-LF, IPAQ-SF, and PAL provide limited but acceptable reliability and validity in measuring MVPA and SB, among which GPAQ might be the most valid instrument.

The Relationship Between Sleep Duration and Blood Lipids Among Chinese Middle-Aged and Older Adults: Cross-Lagged Path Analysis From CHARLS.

This study used data from the China Health and Retirement Longitudinal Study to investigate the temporal relationship between blood lipids and sleep duration in Chinese middle-aged and older adults. We used medical examinations and questionnaire data of 5,016 Chinese middle-aged and older adults (age 45+) in 2011 and 2015. Cross-lagged path analysis was performed to examine the bidirectional relationships between blood lipids and sleep duration. Sleep duration and lipids data were analyzed as continuous variables. Temporal relationships between sleep duration and HDL-cholesterol, LDL-cholesterol, total cholesterol, and triglycerides were different. Sleep duration was negatively associated with HDL-cholesterol 4 year later (ß1 = -0.171, P = 0.005), and HDL-cholesterol was negatively associated with sleep duration 4 year later (ß2 = -0.006, P = 0.002). Longer sleep duration was associated lower levels of LDL-cholesterol (ß1 = -0.275, P = 0.097) and total cholesterol (ß1 = -0.329, P = 0.096) 4 year later. There was a positive correlation between triglycerides and sleep duration. The path coefficient from triglycerides to sleep duration 4 year later (ß2 = 0.001, P = 0.018) was greater than that from sleep duration to triglycerides 4 year later (ß1 = 0.109, P = 0.847), with P = 0.030 for the difference between ß1 and ß2. In stratified analysis, we found that the strength and direction of the relationships may be related to age and BMI. Effects of sleep duration on blood lipids were only observed among participants aged <60 years, while the effect in the opposite direction was observed in older adults (age 60+), and the cross-lagged path coefficients were more significant in adults with BMI > 25.

A Retrospective Study of Rare Listeria Meningoencephalitis in Immunocompetent Children in China.

Objectives: Listeria meningoencephalitis (LMM) is very rare in healthy children. We aimed to assess the clinical features, differential diagnosis, treatment options, and outcomes of LMM in immunocompetent children through a retrospective study. Methods: The clinical symptoms, laboratory findings, imaging features, antibiotic use, and metagenomic next-generation sequencing (mNGS) results of the cerebrospinal fluid (CSF) were obtained from immunocompetent children who were diagnosed with LMM and admitted to the Xi'an Children's Hospital from May 2018 to July 2020. Results: The data from 8 immunocompetent children were retrospectively analyzed in this study. The cohort included data from 5 males and 3 females who were aged from 1 year and 7 months to 16 years and 6 months. A total of 4 patients had chilled food before onset. The complications included hyponatremia (3/8), hydrocephalus (2/8), and hemophagocytic syndrome (1/8). In total, 8 patients were diagnosed with Listeria monocytogenes by positive CSF culture or mNGS results. The positive rate of CSF culture was 62.5% (5/8). A total of 5 patients conducted CSF mNGS, and the results of the mNGS were positive in 4 patients (80%, 4/5) and suspected in 1 patient. A total of 7 patients changed their therapeutic regimen to combined antibacterial therapies that included linezolid and meropenem (5/8), or ampicillin and meropenem (2/8). A total of 5 patients had favorable outcomes (Glasgow Outcome Scale, GOSE = 5) while two patients had unfavorable outcomes (GOSE = 1) and were complicated with hyponatremia and hydrocephalus. Conclusions: Listeria meningoencephalitis (LMM) can occur in children with normal immune function and is commonly mistaken for other central nervous system infections. L. monocytogenes can be quickly and accurately detected by mNGS. Hyponatremia and hydrocephalus may indicate unfavorable outcomes.

Risk Factor-Related Lifestyle Habits of Patients With Laryngopharyngeal Reflux.

OBJECTIVE: The role of lifestyle habits in patients with laryngopharyngeal reflux disease (LPRD) is comparatively underexplored. We aim to examine the specific lifestyle habits in patients with LPRD. METHODS: Systematic sampling was applied to select respondents aged 18 through 80 years in otorhinolaryngology-head and neck surgery (OHNS) clinics in Nan Fang Hospital during August 2017-July 2018, 1658 eligible participants were included by a systematic sampling method. Subjects with RSI score>13 were considered as LPRD patients. The risk of reflux symptoms was estimated and multivariate calculated as odds ratios in relation to exposure to tobacco smoking, alcohol, coffee, tea, carbonated drinks, chocolate, spicy food, night sleep time, dinner-to-bed time, subjective sleep quality, and physical exercise. RESULTS: There was a significant dose-response association between carbonated beverage and LPRD. Among people who had drinking carbonated drinks the odds ratio was 1.76 (OR 1.77, 95% CI 1.24-2.50, P = .002) compared with non-carbonated drinker. A similar positive association was found for poor subjective sleep quality and shorter night sleeping time, the odds ratio for reflux was 1.58 (95% CI 1.14 to 2.18) among those who always have poor subjective sleep quality compared with those whose have good subjective sleep quality. The odds ratio for reflux was 2.29 (95% CI 1.23-4.28, P = .015) among those who always sleep 3-5 hours every night compared with those who sleep more than 8 hours every night. Beyond that, we found high BMI may have a negative correlation with LPRD, the odds ratio for reflux was .61 (95% CI 0.39 to .95, P = .054) among those whose BMI >25 kg/m2 compared with those BMI ≤ 20 kg/m2. CONCLUSIONS: Patients with LPRD may have certain lifestyle habits, avoid carbonated beverage, poor subjective sleep quality, and lack of sleep should be advised in treatment of LPRD.

Bushen Jieyu Tiaochong Formula reduces apoptosis of granulosa cells via the PERK-ATF4-CHOP signaling pathway in a rat model of polycystic ovary syndrome with chronic stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder that is also an important cause of infertility. Adverse psychological stress can aggravate the occurrence and development of PCOS. Bushen Jieyu Tiaochong Formula (BJTF), a prescription of Traditional Chinese Medicine (TCM), has been used in the treatment of PCOS and shown to be effective in reducing negative emotion. However, the therapeutic mechanism has yet to be clearly elucidated. In the current study, we investigated the potential mechanism of action of BJTF. AIM OF THE STUDY: To investigate the role of PERK-ATF4-CHOP signaling in the molecular mechanisms that mediate the effects of BJTF in a rat model of PCOS, with chronic stress induced by letrozole and a chronic unpredictable mild stress (CUMS) paradigm. MATERIALS AND METHODS: In addition to the normal control group, the PCOS combined with CUMS model rats were randomly assigned to a model group, a Diane-35 (ethinylestradiol 35 µg/cyproterone acetate 2 mg)-treated positive control group, or one of three BJTF-treated groups receiving a low, medium, or high dose. Behavioral testing, including the sucrose preference test and open field test, was conducted, and hematoxylin and eosin (H&E) staining was used to observe changes in the pathological morphology of ovarian tissue. Free testosterone (FT), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in serum were quantified by enzyme-linked immunosorbent assays (ELISA). The hippocampal levels of norepinephrine (NE), 5-hydroxytryptamine/serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography-electrochemical detection (HPLC-ECD). Apoptotic granulosa cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to detect the expression of glucose-regulated protein 78 (GRP78) and CHOP in the ovarian tissues. The expression levels of GRP78, CHOP, PERK, and ATF4 in ovarian tissues were also measured by western blotting. RESULTS: Treatment with either BJTF or Diane-35 ameliorated the abnormal cystic dilatation of follicles in the model rats and reduced the serum levels of FT and LH, and the LH/FSH ratio. BJTF treatment also attenuated chronic psychological stress-like behavior and regulated the expression and metabolism of cerebral monoamine neurotransmitters. The efficacy of BJTF was greater than that of Diane-35, with the optimal effects observed at the medium dose. BJTF also lowered the apoptotic index of ovarian granulosa cells and downregulated the expression of GRP78, CHOP, and ATF4. Although the expression level of PERK was not significantly altered by BJTF, the mean PERK expression level was the lowest in the medium-dose BJTF group. CONCLUSIONS: Administration of BJTF has the therapeutic potential to promote the homeostasis of the reproductive endocrine environment and to restore follicular development and ovulation, possibly through the inhibition of the PERK-ATF4-CHOP signaling pathway, leading to downregulation of GRP78 expression to further delay ovarian granule cell apoptosis mediated by endoplasmic reticulum stress (ERS). Moreover, BJTF could improve behavioral performance by regulating cerebral monoamine neurotransmitters in this rat model. These findings provide a new perspective for treating PCOS related to psychological stress using TCM.

Evaluation of the seizure control and the tolerability of ketogenic diet in Chinese children with structural drug-resistant epilepsy.

OBJECTIVES: In this study, we aimed to evaluate the efficacy and tolerability of ketogenic diet (KD) in Chinese children with drug-resistant epilepsy (DRE) due to structural etiology. METHODS: We retrospectively analyzed data from 23 pediatric patients with DRE due to structural etiology who were treated with KD at Department of Neurology, between May 2014 and December 2020. Based on etiological classifications, the patients were divided into a neonatal brain injury (Group 1), an intracranial infection group (Group2) and a group that showed malformations of cortical development (MCDs) (Group 3). RESULTS: The 23 patients remained on the KD for a mean duration of 15.3 ± 9.7 months. The response rates for the control of seizures were 60.9% (14/23), 52.2 % (12/23), 47.8% (11/23) at 3, 6 and 12 months, respectively. Subjective improvements in cognition were observed in 87.0% (20/23) of the children during follow-up. Reductions in the frequency of seizures of > 50% were more commonly achieved by patients in group 1 (75.0%, 9/12) compared to the patients in groups 2 (60.0%, 3/5) and 3 (33.4%, 2/6). Further analysis of the patients in Group 1 showed that children with a history of hypoxic ischemic encephalopathy (HIE) (100.0%, 6/6) had the highest rate of > 50% seizure reduction. The main reasons for the discontinuation of the KD were due to lack of efficacy and poor compliance. Most of the side effects associated with the KD diet were minor and easily corrected by appropriately adjusting the diet. Only 1 patient discontinued the diet due to severe refusal to eat. CONCLUSIONS: KD is an effective and safe treatment for Chinese children with DRE due to structural etiology. Better efficacy of seizure control was observed in patients with a history of neonatal brain injury. Patients with DRE secondary to HIE may be particularly responsive to the KD therapy, and so KD should be considered earlier in those patients.