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To systematically evaluate the effectiveness of mindfulness-based interventions for ruminative thinking.Cochrane Library, Web of Science, Embase, EBSCO, PubMed and Science Direct databases were searched to include randomized controlled trials of mindfulness-based interventions for rumination that met the criteria. The Rumination scale was used as the primary outcome indicator, and the secondary outcome indicator included the Mindfulness scale. An evaluation of bias risk was conducted to identify possible sources of bias based on methodological and clinical factors. Stata 16.0 software was used to perform meta-analysis, subgroup analysis, sensitivity analysis, meta-regression analysis and publication bias detection of the extracted data.A total of 61 studies with 4229 patients were included. Meta-analysis results revealed a significant intervention effect on ruminative thinking (SMD = -0.534, 95 % CI = [-0.675, -0.394], z = -7.449, P 0.001). However, there was no significant difference between mindfulness-based interventions and CBT (SMD = 0.009, 95%CI = [-0.239, 0.258], z = 0.073, P = 0.941). Meta-analysis showed that mindfulness-based interventions significantly enhanced the level of mindfulness (SMD = 0.495, 95 % CI = [0.343, 0.647], z = 6.388, P 0.001), while it was not significant compared to CBT (SMD = 0.158, 95%CI = [-0.087, 0.403], z = 1.266, P = 0.205). The two subgroups with65 % (SMD = -0.534, 95%CI = [-0.681, -0.386], z = -7.081, P 0.001) and 80 % (SMD = -0.462, 95%CI = [-0.590, -0.334], z = -7.071, P 0.001) of females showed significant improvement in ruminative thinking. There were significant intervention effects for depression, students, cancer, healthy adults, and clinical patients. Significant intervention effects were demonstrated for various participant ages and intervention periods.This study confirmed the feasibility of mindfulness-based interventions in improving ruminative thinking and enhancing the level of mindfulness. However, the effectiveness of mindfulness-based interventions was not significant compared to CBT. The two subgroups with a higher proportion of females showed a more significant improvement in ruminative thinking, whereas there were no significant differences in participant characteristics, age, and the duration of intervention.

Chenghui Zhang,* Suyuan Wang,* Yunhong Wu, Yanhong Guo, Xi Wang Endocrinology Department, Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi Wang, Email 583831270@qq.comBackground: Branched chain amino acids (BCAAs) have been revealed to be closely related to insulin resistance and obesity. This study aimed to investigate if BCAA levels at baseline are related to an improvement in insulin resistance after implementing a weight loss program intervention.Methods: Stored blood samples from participants in previous trials were used for BCAA evaluation. Linear regression was used to analyze the relationship between baseline amino acid levels and changes in the insulin resistance index (HOMA-IR) and blood glucose.Results: A total of 48 participants were enrolled. After the intervention, the body weight (78.29± 12.68 vs 72.06 ± 13.30 kg, p=0.020), fasting glucose (4.76 ± 0.43 vs 4.48 ± 0.39 mmol/L, p=0.001), fasting insulin (18.41± 13.58 vs 12.87± 10.88, p=0.028), and HOMA-IR (4.01± 3.39 vs 2.62± 2.18, p=0.018) were improved significantly. BCAA levels were related to the improvement in HOMA-IR (β=− 0.006, p=0.039), and valine was found to be the most closely related to the improvement in HOMA-IR (β=− 0.013, p=0.017).Conclusion: The baseline BCAA is related to the improvement in insulin resistance among participants after a weight loss intervention.Keywords: obesity, branched chain amino acid, weight loss, insulin resistance

Diabetic ketoacidosis (DKA) is a common, life-threatening complication of type 1 diabetes (T1D) characterized by unregulated ketogenesis caused by relative or absolute insulin deficiency. DKA management requires frequent biochemical monitoring. Plasma ß-hydroxybutyrate (BOHB) has not been included in traditional definitions of DKA resolution.The aim of this study was to determine a cut-point level of BOHB to define DKA resolution in patients with T1D treated with intravenous (IV) insulin.We identified patients with T1D receiving IV insulin for DKA treatment at a quaternary children's hospital from January 1, 2017 through December 31, 2020 who had plasma measurements of BOHB after DKA onset and whose DKA resolved by traditional laboratory criteria (venous pH (vpH) ≥ 7.3, serum bicarbonate (HCOAssociations between plasma BOHB and vpH, HCOWe analyzed 403 patients with 471 unique encounters. Plasma BOHB showed the most robust relationship with AG. The ROC curve comparing plasma BOHB to the accepted definition of DKA resolution, AG ≤14 mmol/L, had an AUC of 0.92. A BOHB value of1.5 mmol/L had a sensitivity of 83% and specificity of 87%; this cut-point correctly classified 86% of the observations.A plasma BOHB value of1.5 mmol/L can be used to define resolution of DKA.

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

Objection: To explore the brain functional impairment in patients of obsessive-compulsive disorder (OCD) with and without depressive symptoms, and then analyze the correlation between the degree of impairment and the severity of symptoms. Method: In this study, 14 patients with OCD who met the ICD-10 diagnostic criteria for "obsessive-compulsive disorder" were included; the OCD with depression (OCDd) group consisted of 15 patients; and 17 healthy controls (HC) matched for age and education were included. The Yale-Brown OCD Scale (Y-BOCS) and the 24-item Hamilton Assessment of Depression Scale (HAMD) were administered to the OCD group and the OCDd group. Resting-state functional brain magnetic resonance imaging was performed in three groups of participants. Result: The OCDd group had lower scores on the HAMD, Y-BOCS, and obsessive-compulsive thinking subscales than the OCD group (P< 0.05). Scores on the OCDd subscale were negatively correlated with HAMD scores (R = -0.568, P = 0.027). The OCDd group had higher ReHo values in the lingual gyrus than the OCD group. The OCDd group had higher ReHo values in the lingual gyrus than the HC group, while the OCDd group had higher ReHo values than the HC group. These differences were statistically significant (PP>0.05). In the OCD group, the ReHo value of the tongue was negatively correlated with the Y-BOCs total score and the compulsive behavior subscale score (R = -0.609, -0.552, P = 0.016, 0.033). Conclusion: Abnormal ReHo values in the lingual gyrus and right medial superior frontal gyrus were found in patients with OCD. No effect of OCD symptoms on the local coherence of brain function was observed, which may indicate that OCD symptoms are not responsible for the changes in local coherence of the brain, but are caused by depressive symptoms. In the OCD group, ReHo values of the lingual gyrus were negatively correlated with scores on the Y-BOCs total and obsessive-compulsive subscales, suggesting that abnormal local coherence of the lingual gyrus may be related to the severity of OCD.

There is significant uncertainty in describing prognosis and a lack of reliable entry criteria for palliative care studies in children with advanced heart disease (AHD). This study evaluates the utility of the surprise question-"Would you be surprised if this child died within the next year?"-to predict one-year mortality in children with AHD and assess its utility as entry criteria for future trials. This is a prospective cohort study of physicians and nurses caring for children (1 month-19 years) with AHD hospitalized ≥ 7 days. AHD was defined as single ventricle physiology, pulmonary vein stenosis or pulmonary hypertension, or any cardiac diagnosis with signs of advanced disease. Primary physicians were asked the surprise question and medical record review was performed. Forty-nine physicians responded to the surprise question for 152 patients. Physicians responded "No, I would not be surprised if this patient died" for 54 (36%) patients, 20 (37%) of whom died within 1 year, predicting one-year mortality with 77% sensitivity, 73% specificity, 37% positive predictive value, and 94% negative predictive value. Patients who received a "No" response had an increased 1-year risk of death (hazard ratio 7.25, p 0.001). Physician years of experience, subspecialty, and self-rated competency were not associated with the accuracy of the surprise question. The surprise question offers promise as a bedside screening tool to identify children with AHD at high risk for mortality and help physicians identify patients who may benefit from palliative care and advance care planning discussions.

Although scholars and practitioners have highlighted the significance of students’ attitudes for their future employment, few empirical examinations have attempted to determine the potential association between students’ future orientation and their perceived employability. Thus, drawing on career construction theory, we test the positive effect of students’ future orientation on their perceived employability by exploring the mediator of problem-based learning and the moderators of job market knowledge and proactive personality. Collecting our data via a time-lagged design (N = 368), we have found that the positive association between future orientation and employability is mediated by problem-based learning. Our moderation analyses further revealed that job market knowledge positively moderates the relationship between future orientation and problem-based learning and that students’ proactive personality positively moderates the relationship between problem-based learning and perceived employability.

The prevalence of iron overload in Tibetans in Tibet is higher than that in Han. DNA methylation (DNAm) is closely related to iron metabolism and iron level. Nevertheless, the epigenetic status of Tibetans with iron overload is unknown, and we therefore aimed to explore whether the phenomenon observed in the Tibetan population is regulated by epigenetics. The results showed that 2.26% of cytosine was methylated in the whole genome, and that the rate of CG cytosine methylation was higher in individuals in the iron overload (TH) group than in those in the iron normal (TL) group. We analyzed differentially methylated genes (DMGs) in whole-genome bisulfite sequencing data from the TH and TL groups of high-altitude Tibetans. Protein-protein interaction and pathway analyses of candidate DMGs related to iron uptake and transport showed that epigenetic changes in 10 candidate genes (ACO1, CYBRD1, FLVCR1, HFE, HMOX2, IREB2, NEDD8, SLC11A2, SLC40A1 and TFRC) are likely to relate to iron overload. This work reveals, for the first time, changes of DNAm in Tibetan people with iron overload, which suggest that DNAm is a mechanism underlying differences in iron content between individuals in the high-altitude Tibetan population. Our findings should contribute to the study of iron metabolism and the overall health status of Tibetans.

Purpose To identify risk factors for the recurrence of convulsions with mild gastroenteritis (CwG)1 in children. Methods Altogether, 613 children with CwG admitted to Children's Hospital of Shanxi Province from January 2010 to December 2015 were selected, their clinical data were retrospectively analyzed, and patients were followed up for 4–10 years. Risk factors for the recurrence of CwG were analyzed based on the clinical characteristics of the children. Results Relapse occurred in 35 patients (6.3 %). Recurrence occurred within 6 months after the first CwG in majority of the patients (80 %), and recurrence occurred once in most patients (91.4 %). Risk factors associated with CwG recurrence were age at first attack of ≤18 months (recurrence rates at ages ≤ and >18 months were 8.7 %, and 3.1 %, respectively; χ2 = 4.856, P = 0.028), and a history of convulsions in first-degree relatives (recurrence rates in first-degree relatives with and without a history of convulsion were 20 % and 6.2 %, respectively; χ2 = 5.501, P = 0.019). Conclusions Children with CwG have a possibility of recurrence. The risk of recurrence within 6 months of onset is high and such patients should be carefully observed. Furthermore, the age of onset of ≤18 months and history of convulsions in first-degree relatives are risks factors for CwG recurrence; therefore, these children should be closely followed up.

Aim To explore the association between the atherosclerosis and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This hospital-based cross-sectional study included 949 patients (700 males and 249 females) with T2DM. The atherosclerotic parameters were assessed using the cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), and carotid plaque. DR was assessed and graded using digital retinal photography and fundus fluorescein angiography as either nonproliferative DR (NPDR) or proliferative DR (PDR). Multiple logistic regression analysis was performed to identify the associations between the atherosclerotic parameters and DR status. Results The prevalence of DR was 23.6% in total patients, including 167 (17.6%) patients with NPDR and 57 (6.0%) patients with PDR. Patients with NPDR and PDR were more likely to have higher prevalence of increased CAVI, increased ABI, and carotid plaque than those without DR. In multivariable adjusted logistic regression analysis, patients with NPDR showed an odds ratio (OR) of 2.59 [95% confidence interval (CI), 1.61-4.19] for increased CAVI, 1.99 (0.62-6.34) for increased ABI, and 1.75 (1.13-2.71) for carotid plaque. Patients with PDR showed an OR of 7.83 (3.52-17.41) for increased CAVI, 10.65 (3.33-34.04) for increased ABI, and 11.40 (2.67-48.63) for carotid plaque. Conclusion Both NPDR and PDR were independently associated with increased CAVI and presence of carotid plaque in Chinese patients with T2DM.

Background Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that plays a major role under hypoxia conditions. Cold storage during heart transplantation causes the donor heart long-term hypoxia. There is some evidence indicating a conceivable HIF-1α/microRNA-21 (miR-21)/phosphatase and tensin homolog (PTEN)/programmed cell death 4 (PDCD4) pathway. We assessed the hypothesis that HIF-1α has a positive effect during donor heart cold storage by making the miR-21 upregulate to reduce the expression of PDCD4. Methods We established the rat heart cold storage model and stratified it into 6-hour groups from 0 to 24 hours. Western blot and quantitative reverse transcription polymerase chain reaction were performed to detect the expression of HIF-1α, miR-21, PDCD4, and PTEN. Results After cold storage the expression of HIF-1α increased from 0 to 6 hours and then gradually decreased, but the expression level was relatively higher compared with the control group. The miR-21 was upregulated from 0 to 12 hours then downregulated. The messenger RNA expression of PDCD4 was upregulated gradually, but the protein expression was significantly downregulated at 12th hour then continued to upregulate. Interestingly, the expression level of miR-21 was highest in the 12th hour, which indicated miR-21 could inhibit the PDCD4. We subsequently detected the messenger RNA of PTEN, which can inhibit HIF-1α and be inhibited by miR-21. The expression of PTEN was also significantly downregulated at the 12th hour. Conclusion In conclusion, there is possible interaction between HIF-1α and miR-21, and the conceivable HIF-1α/miR-21/PTEN/PDCD4 pathway plays a protective role in cold storage of the heart.

12019 Background: Cancer patients are more likely to use complementary and alternative medicine (CAM) than non-cancer patients for immune enhancement and symptom relief. Cancer patients with immigration background may seek out CAM use more readily due to the influence from their cultural background. Methods: We carried out a prospective questionnaire study surveying the use of 21 CAM types to cancer patients between 10/23/2015 and 10/31/2020, to evaluate the association of CAM use with patients’ age, sex, cancer types, stages, race/ethnicity, birthplace, immigration duration, first language, marital status, levels of poverty, education and anxiety. Results: 658 patients were included in this analysis. The median age was 62 years old. The prevalence of CAM use was 66.11%. CAM use was higher in females (71.98%) than the males (54.34%) (p = 1.13x10-5), and higher in patients ≥ 38 years old (67.09%) than < 38 years old (46.88%) (p = 0.0215). Patients of African American descent (both US born and foreign born) (n = 198) had statistically higher CAM use (72.73%) than the Caucasians and Others (including Middle-Eastern, Multi-Racial and Others) (n = 266) (63.53%) (p = 0.0371). There was no difference of CAM use between the US born patients (n = 301, CAM use 68.77%) and the immigrants (n = 347, CAM use 63.98%) as a whole; however, Asian born immigrants (n = 106) had statistically less CAM use (53.77%) than the US born and other non-Latin American born (n = 397, CAM use 66.50%) (p = 0.0161), while the Latin-American born had a trend towards higher CAM use (74.83%, P = 0.0608). The number of years living in the US by the immigrants did not have an association with CAM use. Among psychosocial economic factors, married patients had a lower CAM use (61.23%) than the unmarried group (defined as divorced, separated, widowed, or single status, 70.85%) (p = 0.0102). The levels of education, poverty and anxiety did not show a statistical difference in relation to CAM use. Earlier stages of disease had numerically higher CAM use than stage 4 patients, and patients with breast and GYN cancers had higher CAM use (72.30%, p = 0.00252), consistent with the data on the higher CAM use in females. Prayer and spirituality and Dietary medicine were the 2 most common CAM types used (25.91% and 16.12%, respectively). African Americans of the combined US and Non-US origin showed the highest rate of using Prayer and spirituality (84.72%), versus Hispanics (71.19%), Caucasians (53.85%), and Asians (40.32%). Chiropractic therapy was exclusively used by Caucasian CAM users (9.38%). Conclusions: Among cancer patients of multi-ethnic groups with immigration background served in a community hospital in Brooklyn, New York, CAM use appeared to be higher in the African American patients, and lower in the patients born in Eastern Asia, as compared to the US born, or to Caucasians. Cultural roots appeared to be a strong influencing factor among all the medical and socioeconomic factors.

Purpose. To explore and analyze the therapeutic effect of gamma globulins (GG) on Kawasaki disease (KD) in children and the influencing factors of short-term prognosis. Methods. First, 90 pediatric KD patients admitted between January 2019 and January 2021 were selected and divided into a control group ( n = 40 ) and a research group ( n = 50 ) according to the difference in treatment. In addition to routine treatment and nursing given to both groups, control group was given aspirin (ASA), based on which research group was supplemented with GG therapy. The treatment outcome and adverse events (AEs) of the two cohorts of patients were analyzed and compared, and the influencing factors of children’s short-term prognosis were analyzed by logistics multivariate analysis. Results. Research group had a statistical higher overall response rate than control group, with significantly fewer cases suffering from AEs such as nausea and vomiting, diarrhea, rash, dizziness and headache, and coronary artery injury. On the other hand, logistics multivariate analysis identified that gender, body mass index (BMI), onset time, platelet (PLT), and treatment mode all independently influence the short-term prognosis of children with KD. Conclusions. GG therapy is effective in treating pediatric KD patients and can effectively prevent AEs. In addition, gender, BMI, onset-to-treatment time, PLT, C-reactive protein (CRP), and treatment methods are independent risk factors for short-term prognosis of children with KD.

An expanding “gig” economy has changed the nature of employment; thus, researchers have recently focused on exploring the role of job precariousness in the workplace. However, little research attention has been given to understanding why, how and when job precariousness leads to employees’ negative behavioral outcomes in the service-oriented industry. In the current study, we examined job insecurity as a mediator and employees’ negative affect as a moderator in the relationship between job precariousness and employees’ withdrawal behavior. Using a sample of 472 employees working in Chinese hotels, we found that job precariousness is positively related to employees’ withdrawal behavior by increasing their job insecurity. Moreover, this mediating relationship is conditional on the moderator variable of employees’ negative affect for the path from job insecurity to withdrawal behavior. The importance of these findings for understanding the undesirable behavior outcomes of job precariousness is discussed.

The central molecular mechanisms of nonorganic erectile dysfunction remains unknown.This study aimed to investigate the association of dopaminergic neurons projecting to the nucleus accumbens of male rats with nonorganic erectile dysfunction.Nonorganic erectile dysfunction was induced by chronic mild stress. The sucrose consumption test, sexual behavior test, and apomorphine test were carried out to select depression-like rats with erectile dysfunction. These rats were considered as nonorganic erectile dysfunction model rats. Dopamine D1/D2 receptor agonist/antagonist was infused into the nucleus accumbens to observe the effect on sexual behavior. Dopaminergic projections to the nucleus accumbens were labeled with both the retrograde tracer FluoroGold injected into the nucleus accumbens and tyrosine hydroxylase. The expression level of tyrosine hydroxylase in dopaminergic neurons projecting to the nucleus accumbens in the ventral tegmental area was measured. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the nucleus accumbens were also measured.Nonorganic erectile dysfunction was proved by the sucrose consumption test, sexual behavior test, and apomorphine test in model rats. After central infusion of the dopamine D2 receptor agonist into the nucleus accumbens, the recovery of erectile function, sexual arousal, and motivation were indicated by increased intromission ratio and decreased mount latency. Decreased expression levels of dopamine D2 receptors and tyrosine hydroxylase in the nucleus accumbens and decreased expression level of tyrosine hydroxylase in the dopaminergic neurons projecting to the nucleus accumbens were observed in model rats.These results suggest the impairment of dopaminergic neurons projecting to the nucleus accumbens and dopamine D2 signaling in the nucleus accumbens, causing the suppression of erectile function, sexual arousal, and motivation.These results suggest that the impaired dopamine D2 receptor pathway in the nucleus accumbens may be one of the main pathway involved in the development of nonorganic erectile dysfunction in the present model.

Type 2 diabetes mellitus (T2DM) is associated with abnormal communication among large-scale brain networks, revealed by resting-state functional connectivity (rsFC), with inconsistent results between studies. We performed a meta-analysis of seed-based rsFC studies to identify consistent network connectivity alterations. Thirty-three datasets from 30 studies (1014 T2DM patients and 902 healthy controls [HC]) were included. Seed coordinates and between-group effects were extracted, and the seeds were divided into networks based on their location. Compared to HC, T2DM patients showed hyperconnectivity and hypoconnectivity within the DMN, DMN hypoconnectivity with the affective network (AN), ventral attention network (VAN) and frontal parietal network, and DMN hyperconnectivity with the VAN and visual network. T2DM patients also showed AN hypoconnectivity with the somatomotor network and hyperconnectivity with the VAN. T2DM illness durations negatively correlated with within-DMN rsFC. These DMN-centered impairments in large-scale brain networks in T2DM patients may help to explain the cognitive deficits associated with T2DM.

Background Streptococcus pneumoniae is an important cause of pediatric meningitis. Objective The aim of this study was to analyze the clinical features and outcomes of children with pneumococcal meningitis at our hospital in China, so as to provide basis for improving the clinical treatment effect. Methods This retrospective analysis included patients aged Results The analysis included 26 children aged 2 months to 13 years, with 17 (65.4%) aged Conclusion Pneumococcal meningitis is associated with a poor prognosis in many children. Poor prognosis might be related to early ineffective antibiotic therapy, a combination of systemic failure, neurological problems, and changed inflammatory response. It is important to rapid initiation of appropriate antibiotic therapy if meningitis is suspected.

Background & Aims The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8–28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. Conclusions The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Contains fulltext : 234024.pdf (Publisher’s version ) (Closed access) PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.

Zhao, Lijun, Xi Wang, Tingli Wang, Wenxin Fan, Honghong Ren, Rui Zhang, Yutong Zou, Huan Xu, Jie Zhang, Yunhong Wu, and Fang Liu. Associations between high-altitude residence and end-stage kidney disease in Chinese patients with type 2 diabetes.

Background We investigated the associations between low-density lipoprotein cholesterol (LDL-C) to high-density cholesterol (HDL-C) ratio (LDL-C/HDL-C) with structural and functional early atherosclerosis vascular changes in patients with type 2 diabetes mellitus (T2DM). Methods This hospital-based cross-sectional study included 814 patients with T2DM. Structural atherosclerotic parameters included carotid intima-media thickness (CIMT) and carotid plaque, the cardio-ankle vascular index (CAVI) was considered as the functional parameter. Multiple linear regression and logistic regression models were preformed to identify the associations between LDL-C/HDL-C with atherosclerotic parameters. Results Increased LDL-C/HDL-C corresponded with the increase levels in CIMT and percentage of carotid plaque. LDL-C/HDL-C was found to be positively associated with CIMT both in female and male patients in unadjusted model. This association persisted in male patients but not in female patients after adjusted for other related factors. No association was found between LDL-C/HDL-C with CAVI both in female and male patients. LDL-C/HDL-C was positively associated with the presence of carotid plaque in male patients. However, this association was not found in female patients. Conclusion LDL-C/HDL-C was positively associated with CIMT and presence of carotid plaque though not with CAVI in male T2DM patients. However, these associations were not observed in female patients.

Additional file 1: Table S1. The 100 most common OTUs in the five groups of samples. Abbreviation: operational taxonomic units, OTUs.

Additional file 3: Figure S1. Bacterial structure between groups of males and females and pre menstrual and post menstrual females. PCoA shows the bacterial composition clustering of the groups based on Bray–Curtis distances, with each point corresponding to a patient and coloured according to the sample type of male or female in the SKP samples (A), pre menstrual and post menstrual females in the SKP samples (B), male or female in Bladder A samples (C), and pre menstrual and post menstrual females in the Bladder A samples (D). PERMANOVA indicated that the bacterial communities between males and females were not significantly different in the SKP samples (p > 0.05).

Additional file 2: Table S2. Bacteria in bladder urine detected by EQUC and 16S rRNA sequencing Abbreviation: colony forming units, CFU. a The similarity of bacterial sequence cutoff is 97%. b If the genome sequence of a bacterium was identified as heterozygous three times or was difficult to bind, the bacterium was defined as an unidentified bacterium.

Objectives In this study, we aimed to investigate the pathologic and ultrastructural changes in transplanted mouse livers after different durations of cold storage by testing indicators of liver function and energy metabolism. We aimed to describe the effects of cold storage on liver function and the mechanisms of cold storage damage. Materials and methods We randomly placed 8-weekold male C57BL/6 mice into the following 4 groups to establish a cold-preserved mouse model of liver transplant: a normal control group and 3 cold storage groups, in which livers were stored for 4, 12, and 24 hours. Hepatic morphology, ultrastructural changes, and glycogenolysis were observed by hematoxylin and eosin staining, periodic acid-Schiff staining, and transmission electron microscopy. After different durations of cold storage, livers were reperfused with 4°C University of Wisconsin solution to obtain perfusion fluid, and alanine and aspartate aminotransferase levels were measured. Glycogen synthase, hypoxia-inducible factor-1α, Kruppel-like factor 2, and endothelial nitric oxide synthase mRNA expression levels in liver tissues were detected by real-time polymerase chain reaction, and aquaporin 8 protein expression levels in liver tissues were detected by Western blot. Results Hematoxylin and eosin staining and electron microscopy ofliver showed signs ofinjury after 12 hours of cold storage, which included mainly cytoplasmic edema characterized by loose liver cell arrangement, increased hepatic sinus fissure, mitochondrial swelling, and nuclear pyknosis. Periodic acid-Schiff staining showed that glycogen content was significantly reduced, with glycogen synthase levels also reduced. Alanine aminotransferase and aspartate aminotransferase levels gradually increasedwith cold storage. Glycogen synthase, Kruppel-like factor 2, endothelial nitric oxide synthase, and aquaporin 8 expression levels also gradually increased in liver tissue. These levels gradually decreased, but hypoxia-inducible factor-1α increased. Conclusions Mouse livers showed progressive damage to structure and function during cold storage, with mitochondrial damage perhaps showing the earliest damage.

e17566 Background: Uterine, cervical and ovarian cancers with isolated recurrences in the pelvic, para-aortic or distant lymph nodes, such as axillary, supraclavicular lymph node, or visceral organs, are uncommon conditions. The standard care is palliative systemic chemotherapy. We hypothesized that combined modality treatment (CMT) incorporating surgery or radiation for curative intent may increase local disease control and delay or mitigate further distant metastasis, thereby increase overall survival (OS). Methods: We retrospectively reviewed characteristics and outcomes of patients who had localized recurrence of gynecological malignancies and who were treated with an aggressive approach of salvage chemotherapy + radiation +/- surgery or radiofrequency ablation. Results: We identified 23 patients, including 6 cervical, 14 uterine and 3 ovarian cancer patients who were treated from 2005 to 2021. The mean age was 68. About 47.8% patients had advanced stages of disease at diagnosis (stage 3+4). Serous carcinoma (n = 7, 30.4%) was the most common uterine cancer pathology. All patients received curative intent therapy at initial diagnosis. The first recurrence sites are shown in the table, and the visceral organs involvement were liver, gluteal muscle, etc. The recurrence was within previous radiation field in 9 patients (39.1%) and outside radiation field in 12 (52.1%). 16 patients had local radiation + chemo, 6 had systemic chemo only and 1 had radiation only (see table below). Only 13 patients had a second recurrence, including 5 from the previous systemic treatment only group. Seven had local recurrence only and all received local therapy. Six patients eventually developed wide spread disease, and 2 died. After a median follow up of 56 months (range 22 to 186 months), 17 patients were alive (4 lost for follow up), and 15 had no evidence of disease (NED). The median time to first recurrence was 14.5 m [Interquartile range (IQR), Q1, Q3 to be 7, 19]. The PFS for those patients who had only 1 recurrence was 41.5 m (IQR 21, 63). The PFS for those who had the second recurrence until the next progression was 15 months (IQR 9, 37). The overall survival in all patients was 56 m (IQR 39, 71). Conclusions: A curative intent, salvage CMT protocol for advanced GYN cancer patients who develop isolated local or distant recurrence may have a therapeutic advantage. It renders a longer PFS and OS than those from systemic therapy alone reported in the historical data.[Table: see text]

Long-term treatment with certain antiepileptic drugs may lead to thyroid function disturbances or alterations in bone metabolism; the data on the effects of new antiepileptic drugs on this are limited and conflicting, especially in children with epilepsy. Therefore, the aim of this study was to investigate the effects of levetiracetam and oxcarbazepine on thyroid hormone levels and bone metabolism in children with epilepsy.A total of 51 children with new-onset partial epilepsy were selected. They were randomly treated with either levetiracetam (n = 25), or oxcarbazepine (n = 26) monotherapy. Eight of the 51 patients were excluded for failing to take the drug continuously or failing to undergo a regular review. Thus, 43 patients were finally included (levetiracetam: 23 patients, oxcarbazepine: 20 patients). A control group consisting of age- and sex-matched healthy subjects (n = 20) was included for comparison. Serum triiodothyronine, tetraiodothyronine, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, calcium, phosphorus, alkaline phosphatase, osteocalcin, parathyroid hormone, and 25-hydroxyvitamin D levels and bone mineral density values were measured before and at 6 and 12 months after therapy in all groups.At baseline, thyroid hormone levels, bone metabolism index, and bone mineral density values did not differ between the control group and the drug-treated groups. Levetiracetam-treated patients showed no significant changes in thyroid hormone levels, bone metabolism, and bone mineral density during the 12-month follow-up period compared with baseline values. In the oxcarbazepine group, compared to baseline values, serum free thyroxine levels decreased after 12 months of treatment (Z = -3.115, p = 0.002), and after 6 and 12 months of treatment, calcium levels decreased (Z = -3.705, p 0.001 and Z = -3.884, p 0.001, respectively) and parathyroid hormone levels increased (Z = -3.698, p 0.001 and Z = -3.921, p 0.001, respectively); however, all other parameters did not differ from baseline values.Our data show that levetiracetam treatment has no significant effect on thyroid function and bone metabolism in children with epilepsy. Long-term use of oxcarbazepine may reduce serum free thyroxine levels, resulting in impaired thyroid function, and may reduce serum calcium and increase parathyroid hormone levels, leading to bone metabolism disorders.

Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling has a protective effect on normal cells. A number of previous studies demonstrated that Keap1/Nrf2 signaling is associated with drug resistance in numerous tumors. The aim of the present study was to investigate the roles of Keap1 in renal cell carcinoma (RCC) and its effect on sensitivity to chemotherapy. Reverse transcription-quantitative polymerase chain reaction was used to detect the mRNA expression of Keap1 in 45 cases of RCC tumors and adjacent normal tissues. A total of five randomly selected patients with RCC, five RCC cell lines and normal renal tubular cells were examined to detect the protein and mRNA expressions of Keap1. The 5-year survival rate was analyzed by Kaplan-Meier analysis. The cell viability was assessed by a Cell Counting kit-8 assay. The cell apoptosis and reactive oxygen species (ROS) were determined by flow cytometry. The expressions of associated proteins were determined by western blot analysis. It was identified that in RCC tissues and RCC cell lines, the expression of Keap1 was downregulated, which was considered to be associated with poor prognosis. In total, 1 µM Axitinib significantly decreased cell viability, promoted ROS release and induced cell apoptosis in ACHN cells. Silencing Keap1 was able to reverse the inhibitory effect of Axitinib and enhance the protein expressions of Nrf2, NAD(P)H dehydrogenase [quinone] 1 and heme oxygenase 1. However, silencing Nrf2 increased the cell sensitivity to Axitinib. Under Axitinib condition, overexpressing Nrf2 was able to increase cell viability; however, overexpressing Keap1 resulted in an opposite effect. Keap1 serves as a tumor suppressor; its low expression was associated with poor prognosis and a decreased sensitivity of RCC cells to Axitinib. A possible mechanism underlying Axitinib resistance may involve Nrf2 overexpression.

Liver transplantation is currently a standard therapy for patients with end-stage liver diseases and hepatocellular carcinoma. Given that liver transplantation has undergone a thriving development in these decades, the survival rates after liver transplantation have markedly improved as a result of the critical advancement in surgical techniques, immunosuppressive therapies, and post-operative care. However, infection remains a fatal complication after liver transplantation surgery. In particular, enterogenic infection represents a major complication in liver transplant recipients. This article gives an overview of infection cases after liver transplantation and focuses on the discussion of enterogenic infection in terms of its pathophysiology, risk factor, outcome, and treatment.