Effects of hypoxic compound exercise to promote HIF-1α expression on cardiac pumping function, sleep activity behavior, and exercise capacity in Drosophila.

Alteration of HIF-1α expression levels under hypoxic conditions affects the sequence of its downstream target genes thereby producing different effects. In order to investigate whether the effect of hypoxic compound exercise (HE) on HIF-1α expression alters cardiac pumping function, myocardial structure, and exercise capacity, we developed a suitable model of hypoxic exercise using Drosophila, a model organism, and additionally investigated the effect of hypoxic compound exercise on nocturnal sleep and activity behavior. The results showed that hypoxic compound exercise at 6% oxygen concentration for five consecutive days, lasting 1 h per day, significantly improved the cardiac stress resistance of Drosophila. The hypoxic complex exercise promoted the whole-body HIF-1α expression in Drosophila, and improved the jumping ability, climbing ability, moving speed, and moving distance. The expression of HIF-1α in the heart was increased after hypoxic exercise, which made a closer arrangement of myofilaments, an increase in the diameter of cardiac tubules, and an increase in the pumping function of the heart. The hypoxic compound exercise improved the sleep quality of Drosophila by increasing its nocturnal sleep time, the number of deep sleeps, and decreasing its nocturnal awakenings and activities. Therefore, we conclude that hypoxic compound exercise promoted the expression of HIF-1α to enhance the exercise capacity and heart pumping function of Drosophila, and improved the quality of sleep.

Adipose Tissue Exosome circ_sxc Mediates the Modulatory of Adiposomes on Brain Aging by Inhibiting Brain dme-miR-87-3p.

Aging of the brain usually leads to the decline of neurological processes and is a major risk factor for various neurodegenerative diseases, including sleep disturbances and cognitive decline. Adipose tissue exosomes, as adipocyte-derived vesicles, may mediate the regulatory processes of adipose tissue on other organs, including the brain; however, the regulatory mechanisms remain unclear. We analyzed the sleep-wake behavior of young (10 days) and old (40 days) Drosophila and found that older Drosophila showed increased sleep fragmentation, which is similar to mammalian aging characteristics. To investigate the cross-tissue regulatory mechanisms of adiposity on brain aging, we extracted 10-day and 40-day Drosophila adipose tissue exosomes and identified circRNAs with age-dependent expression differences by RNA-seq and differential analysis. Furthermore, by combining data from 3 datasets of the GEO database (GSE130158, GSE24992, and GSE184559), circ_sxc that was significantly downregulated with age was finally screened out. Moreover, dme-miR-87-3p, a conserved target of circ_sxc, accumulates in the brain with age and exhibits inhibitory effects in predicted binding relationships with neuroreceptor ligand genes. In summary, the current study showed that the Drosophila brain could obtain circ_sxc by uptake of adipose tissue exosomes which crossed the blood-brain barrier. And circ_sxc suppressed brain miR-87-3p expression through sponge adsorption, which in turn regulated the expression of neurological receptor ligand proteins (5-HT1B, GABA-B-R1, Rdl, Rh7, qvr, NaCP60E) and ensured brain neuronal synaptic signaling normal function of synaptic signaling. However, with aging, this regulatory mechanism is dysregulated by the downregulation of the adipose exosome circ_sxc, which contributes to the brain exhibiting sleep disturbances and other "aging" features.

Analysisof neurological disease spectrum among hospitalized patients in a tertiary hospital from 2018 to 2022 / 现代医院

Objective To analyze the changes in the disease spectrum of hospitalized patients with neurological diseases in a tertiary hospital in the past 5 years,in order to effectively develop targeted disease prevention and treatment strategies.Methods Collect case data of neurological diseases in a tertiary hospital from January 1,2018 to December 31,2022,and use ICD-10 coding for disease classification,and analyze the disease type,gender,age groups,and other factors.Results A total of 9060 patients with neurological diseases were admitted in the past five years.In 2020,the number of discharged patients affected by the COVID-19 was the smallest,accounting for 15.96% ,and in 2022,the number was the largest,accounting for 24.05% .The number of cases showed an increasing trend.There was no statistically significant difference in the composition of male and female patients;There is a statistically significant difference in the number of cases among patients of different age groups,and the incidence categories are different;The top 10 diseases in the ranking of neurological diseases are:transient ischemic attack,headache,spinal nerve disease,neurological disorders,epilepsy,Parkinson's disease,sleep disorders,paralysis,other brain diseases,hydrocephalus.The distribution of the top 10 diseases by gender has statistical significance.Conclusion The hospital can formulate the diagnosis and treatment technology for different age groups according to the distribution characteristics of disease spectrum,carry out comprehensive prevention and treatment measures for key groups,strengthen the construction of key special-ties and allocate health resources properly.

Clinical diagnosis, treatment, and genetic analysis in 4 cases of congenital hyperinsulinemia / 中国新生儿科杂志

Objective:To investigate the clinical diagnosis, treatment, and genetic variations of neonates with congenital hyperinsulinism (CHI).Methods:The clinical data of CHI newborns admitted to the Provincial Hospital Affiliated to Shandong First Medical University from September 2018 to April 2022 were retrospectively analyzed.Results:Four cases of CHI were included, three of whom were full-term infants and all were macrosomic, while one was a premature infant. One infant was born to a mother with gestational diabetes mellitus, and 1 had a family history of hypoglycemia. All the 4 patients presented with weak response, 3 with drowsiness, 1 with hypotonia and 1 with convulsions. Cranial MRI indicated abnormal signals in the occipital lobe cortex in 1 case. Gene sequencing revealed homozygous variation c.799C>G in KCNJ11 gene for 1 case, and heterozygous variations c.4477C>T, c.3540C>G, c.683G>A and c.4536C>A in ABCC8 gene for 3 cases respectively and all these variations were identified as pathogenic mutations. Notably, the c.799C>G variant in KCNJ11 gene as well as the c.3540C>G and c.4536C>A variants in ABCC8 gene were reported for the first time. Among infants with ABCC8 gene variations, two showed no response to diazoxide treatment while one patient with KCNJ11 gene variation responded effectively. The parents of the patient with hypoglycemic brain injury gave up treatment. Three other cases were discharged from hospital after improvement and followed up to 1 year old. 2 patients had stable blood glucose after ceasing medication, and 1 patient still required intermittent oral glucose to maintain normal blood glucose level.Conclusions:CHI can lead to hypoglycemic brain injury. Clinically, infants large for gestational age or with a family history of diabetes and hypoglycemia should be monitored for blood glucose early after birth, to identify CHI as early as possible and actively treat it. Different gene variants have different therapeutic responses.

Research Progress on Mechanisms of Triggeringreceptor Expressed on Myeloid Cells-2 in Cognitive Dysfunction / 中山大学学报(医学科学版)

The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.

Serum TSH levels in women aged 40 and above : association with lifespan and 10-year mortality / 中华内分泌代谢杂志

Objective:To investigate the relationship between thyroid-stimulating hormone(TSH) levels and 10-year mortality in women aged 40 years and older.Methods:Residents aged 40 and over in urban areas of Guiyang City who participated in the " Epidemiological Study of Cancer Risk in Patients with Type 2 Diabetes in China(REACTION)" were followed up in 2011. Finally, 5 614 people were enrolled, and the baseline general information, physical examination and TSH detection were carried out. The average follow-up was(9.77±1.55) years, and the treatment and death of thyroid-related diseases were recorded. The Cox proportional hazards model was used to analyze the relationship between TSH level and 10-year mortality in middle-aged and elderly women, and plotting survival time curves(Kaplan-Meier curves) to study the association between elevated TSH levels and lifespan in subjects under 65 years old. Results:The multivariate Cox proportional hazards model showed that compared with the normal group, after multivariate adjustment, the risk of death in the TSH increased group was decreased( HR=0.644, 95% CI 0.478-0.868, P<0.05); after stratifying the elevated TSH group, the risk of death was decreased in the slightly elevated TSH group( HR=0.566, 95% CI 0.405-0.791, P<0.001); the elevated TSH group was further stratified by age. In the group under 65 years old, compared to the normal group, the mildly elevated group showed a reduced risk of mortality( HR=0.429, 95% CI 0.245-0.751, P=0.003). In the group aged 65 and above, there were no statistically significant differences in mortality risk between the mildly elevated group, severely elevated group, and the normal group( P>0.05). In the group under 65 years old, the K-M curve indicated that the survival rate of the mildly elevated TSH group was significantly higher than that of the normal group( χ2=11.931, P=0.003), the difference was statistically significant. Conclusion:Mildly elevated TSH levels in women aged 40-65 years are associated with a reduced risk of all-cause death and longer lifespan.

Transcutaneous Electrical Acupoint Stimulation Promotes PGC-1α Mediated Mitochondrial Biogenesis and Antioxidant Stress to Protect Cognitive Function in Vascular Dementia Rats / 生物化学与生物物理进展

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

A Methodological Investigation of Hair Proteomics-based Differentiation of Individual Traits / 生物化学与生物物理进展

ObjectiveHair is an essential skin appendage, primarily composed of keratins and keratin-associated proteins. The protein composition and proportion of hair samples vary among different races and sexes. Currently, there is a lack of efficient methods to extract hair proteins. This study aims to explore the application of quantitative hair proteomics in distinguishing individual hair characteristics. MethodsBased on the exploration of sample processing and lysis buffer using three hair samples, we developed a stable and efficient hair protein extraction method, named PLEE (PTM lab for protein extraction from hair with high efficiency). We used the PLEE method to extract seven human hair samples and performed proteomic experiments on them using in-gel digestion method to produce data for analyzing hair protein composition and proportion among individuals. ResultsA total of 274 proteins were identified, among which 107 proteins were commonly present, and the number of non-common proteins ranged from 57-119, with some samples having unique identification proteins. Using the 107 commonly identified proteins for quantitative protein fractionation analysis, various samples were distinguished by clustering and principal component analysis, and technical repeated samples were merged, indicating the stability of the process. In addition, 10 key proteins (KRT33A, KRTAP9-6, KRT83, KRTAP7-1, KRT32, BLMH, KRT38, KRTAP11-1, NPAS1, KRTAP4-3) with large differences between individuals and stable protein identification within the same individual were screened. ConclusionThe protein composition of hair varies among different individuals, and the 10 selected proteins are expected to be key proteins for distinguishing individual hair characteristics and have significant potential applications in individual identification and criminal investigation.

Relationship Between Mindfulness and Affiliate Stigma in Parents of Children with Autism Spectrum Disorder in China: The Mediating Role of Coping Styles

Purpose@#This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China.MethodBetween February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. @*Results@#(1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = −0.38, −0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = −0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. @*Conclusions@#Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Cardiac Timeless Trans-Organically Regulated by miR-276 in Adipose Tissue Modulates Cardiac Function.

The interconnection between cardiac function and circadian rhythms is of great importance. While the role of the biological clock gene Timeless (Tim) in circadian rhythm has been extensively studied, its impact on cardiac function remains largely been unexplored. Previous research has provided experimental evidence for the regulation of the heart by adipose tissue and the targeting of miR-276a/b on Timeless. However, the extent to which adipose tissue regulates cardiac Timeless genes trans-organically through miR-276a/b, and subsequently affects cardiac function, remains uncertain. Therefore, the objective of this study was to investigate the potential trans-organ modulation of the Timeless gene in the heart by adipose tissue through miR-276a/b. We found that cardiac-specific Timeless knockdown and overexpression resulted in a significant increase in heart rate (HR) and a significant decrease in Heart period (HP), diastolic intervals (DI), systolic intervals (SI), diastolic diameter (DD), and systolic diameter (SD). miR-276b systemic knockdown resulted in a significant increase in DI, arrhythmia index (AI), and fractional shortening (FS) significantly increased and SI, DD and SD significantly decreased. Adipose tissue-specific miR-276a/b knockdown and miR-276a overexpression resulted in a significant increase in HR and a significant decrease in DI and SI, which were improved by exercise intervention. This study presents a novel finding that highlights the significance of the heart circadian clock gene Timeless in heart function. Additionally, it demonstrates that adipose tissue exerts trans-organ modulation on the expression of the heart Timeless gene via miR-276a/b.

Development of europium(III) complex functionalized silica nanoprobe for luminescence detection of tetracycline.

Increasing awareness of the health and environment impacts of the antibiotics misuse or overuse, such as tetracycline (TC) in treatment or prevention of infections and diseases, has driven the development of robust methods for their detection in biological, environmental and food systems. In this work, we report the development of a new europium(III) complex functionalized silica nanoprobe (SiNPs-Eu3+) for highly sensitive and selective detection of TC residue in aqueous solution and food samples (milk and meat). The nanoprobe is developed by immobilization of Eu3+ ion onto the surface of silica nanoparticles (SiNPs) as the emitter and TC recognition unit. The ß-diketone configuration of TC can further coordinate with Eu3+ steadily on the surface of nanoprobe, facilitating the absorption of light excitation for Eu3+ emitter activation and luminescence "off-on" response. The dose-dependent luminescence enhancement of SiNPs-Eu3+ nanoprobe exhibits good linearities, allowing the quantitative detection of TC. The SiNPs-Eu3+ nanoprobe shows high sensitivity and selectivity for TC detection in buffer solution. Time resolved luminescence analysis enables the elimination of autofluorescence and light scattering for highly sensitive detection of TC in milk and pork mince with high accuracy and precision. The successful development of SiNPs-Eu3+ nanoprobe is anticipated to provide a rapid, economic, and robust approach for TC detection in real world samples.

Multifunctional and Multicolor Perovskite-CdSe Quantum Dots Diodes for Pulse Oximetry.

A conventional pulse oximeter system is composed of two light sources with different peak emission wavelengths and a photodetector. Integrating these three independent components into one single device will absolutely simplify the system design and create a miniaturized size of the product. Here, we demonstrate a bilayer perovskite-CdSe quantum dot (hereafter perovskite-QD) diode capable of voltage-tunable green/red emission and photodetection. The proposed diode also presents an intriguing feature of simultaneous light emission and detection, which is explored as regards the diode being used as a photoconductor when the positive bias is larger than the built-in voltage. The multifunctional and multicolor diode is further employed in a reflective pulse oximeter system, as either the multicolor light sources or the sensing unit in the system provide accepted and trustful results for heart rate and arterial blood oxygenation. Our work provides a possible avenue for the simplification of the pulse oximetry with a compact and miniaturized design in the future.

Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes / 亚洲男科学杂志(英文版)

Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

Voltage Dependent Anion Channel 1 Mediated Inflammation and Obstructive Sleep Apnea Syndrome / 中山大学学报(医学科学版)

VDAC1（voltage dependent anion channel 1）is an important channel protein on the outer mitochondrial outer membrane， which regulates mitophagy， participates in the regulation of inflammatory cytokines and the activation of the inflammasome， hence being crucial to the inflammatory response. Patients with obstructive sleep apnea syndrome （OSAS） suffer neuroinflammation due to intermittent hypoxia and increased oxidative stress， leading to chronic damage and neuronal cell apoptosis， and eventually develop cognitive impairment. Since OSAS patients' cognitive impairment is significantly influenced by inflammation， and VDAC1 regulates the activation of the inflammasome， the relationship between OSAS and VDAC1， mitophagy， as well as inflammation are reviewed here. We hope that this study can provide a new breakthrough in mitophagy and inflammation in patients with cognitive dysfunction caused by OSAS.

Risk factors and complication of hemodynamically significant patent ductus arteriosus in preterm infants with gestational age <32 weeks / 国际儿科学杂志

Objective:To study the risk factors and complications of hemodynamically significant patent ductus arteriosus(hsPDA)in preterm infants <32 weeks.Methods:From January 2021 to March 2022, a total of 150 premature infants with gestational age <32 weeks admitted to the Neonatal Intensive Care Unit of Liaocheng People′s Hospital were enrolled.Nine patients who did not meet the requirements were excluded and a total of 141 infants were finally analyzed retrospectively, including PDA group with 95 cases and non-PDA group with 46 cases.According to whether hsPDA existed or not, PDA group were dirided into hsPDA group with 42 cases and non-hsPDA group with 53 cases.Univariate and regression analyses were used to determine the risk factors and complication of hsPDA.Results:Univariate analysis showed that gestational age( t=-6.861, P<0.01), birth weight( t=-4.392, P<0.01), mode of delivery( χ2=9.018, P<0.01), caffeine( χ2=4.337, P<0.05) and suffocation( χ2=7.918, P<0.01)were associated with hsPDA.Logistic regression analysis showed that gestational age( OR=2.435, P<0.01, 95% CI: 1.669~3.552)was an independent risk factor for hsPDA in gestational age <32 weeks preterm infants.The incidences of necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity in the hsPDA group were higher than those in the non-hsPDA group( P<0.05). Conclusion:Gestational age is an independent risk factor for hsPDA with gestational age <32 weeks.Necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity are related complications of hsPDA.

Status quo and influencing factors of grief in maternal spouses after perinatal loss / 中国实用护理杂志

Objective:To investigate the status of grief among maternal spouse after perinatal loss, and analyze its influencing factors, so as to provide some reference for male grief supporting strategic.Methods:Using the convenient sampling method, 180 male spouses of hospitalized women in the Department of Obstetrics from Nanjing Maternity and Child Health Care Hospital from March to October 2022 were recruited. A cross-sectional survey was conducted by the general questionnaire, the Perinatal Grief Scale, the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version, the Social Support Rating Scale, and the Simplified Coping Style Questionnaire.Results:The overall score of the Perinatal Grief Scale in male spouses of women who experienced a perinatal loss was (61.57 ± 14.14) points. The score of the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version was (121 ± 14.42) points, the score of the Social Support Rating Scale was (34.23 ± 7.21) points, and the score of the Simplified Coping Style Questionnaire was (36.08 ± 7.64) points. Multiple linear regression analysis showed that participation in fetal interaction, loss of fetal age, social support and family adaptability were the main factors affecting male grief ( P<0.05). Conclusions:The grief among male spouses of women who experienced a perinatal loss is at a low level. The clinical medical staff can refer to the influencing factors and implement effective support, such as respecting the male's father status, coordinating social support resources, and improving the family's coping ability, in order to alleviate men's grief and help them return to normal life.

A nomogram based on CT enterography signs for prediction of intestinal penetrating lesions in patients with Crohn disease / 中华放射学杂志

Objective:To explore the value of a nomogram model based on the CT enterography (CTE) signs for prediction of intestinal penetrating lesions in patients with Crohn disease (CD).Methods:The clinical and CTE data of CD patients who underwent at least two CTE examinations from January 2010 to June 2020 in the First Affiliated Hospital of Sun Yat-sen University were retrospectively collected. A total of 112 patients were enrolled, and according to whether there was intestinal wall penetration in the last CTE observation were divided into non-penetration group (84 cases) and penetration group (28 cases). First, the clinical and CTE data for the first examination was analyzed by using univariate and multivariate Cox proportional hazards regression to screen out high-risk factors that could effectively predict intestinal wall penetrating lesions in CD patients and established a nomogram model. Then the change trend of CTE data (ΔCTE) between the first and last clinical and CTE signs was analyzed by using univariate and multivariate Cox proportional hazards regression, and built a nomogram model to sort out ΔCTE that may accompany the development of penetrating lesions in CD patients. The Harrell concordance index was used to evaluate the discriminative ability of the nomogram model.Results:In the first time clinical and CTE signs, multivariate Cox proportional hazards regression results showed that numbers of diseased bowel segments (HR=0.686, 95%CI 0.475-0.991, P=0.045) and the shortest diameter of the largest lymph node (HR=0.751, 95%CI 0.593-0.949, P=0.017) were independent protection factors for penetrating lesions, and rough bowel wall surface (HR=5.626, 95%CI 2.466-12.839, P<0.001) was an independent risk factor for penetrating lesions. The specificity and sensitivity of the nomogram model to predict non-penetration lesions were 82.1% and 59.5% respectively, and the Harrell concordance index was 0.810 (95%CI 0.732-0.888). In the ΔCTE signs, multivariate Cox proportional hazards regression showed that Δrough bowel wall surface (always rough bowel wall surface HR=12.344, 95%CI 2.042-74.625, P=0.006; slide bowel wall surface becomes rough bowel wall surface HR=28.720, 95%CI 4.580-180.112, P<0.001) and Δthe shortest diameter of the largest lymph node (HR=1.534, 95%CI 1.091-2.157, P=0.014) were independent risk factors for penetrating lesions. The specificity and sensitivity of the nomogram model were 89.3% and 79.2% respectively, and the Harrell concordance index was 0.876 (95%CI 0.818-0.934). Conclusion:The nomogram based on CTE signs of numbers of diseased bowel segments, the shortest diameter of the largest lymph node and rough bowel wall surface and ΔCTE can effectively predict the intestinal wall penetrating lesions of CD patients.

Effect of Yin Yang protein 1 transcriptionally regulating acetyl-CoA carboxylase 1 on the cell migration and lipogenesis in ovarian cancer / 肿瘤研究与临床

Objective:To investigate the expression of acetyl-CoA carboxylase 1 (ACC1) in ovarian cancer tissues and cells, and the related mechanisms of the effect of ACC1 on cell migration and lipogenesis in ovarian cancer.Methods:Samples including 1 case of normal ovarian tissue, 1 case of ovarian cancer primary lesion tissue and 1 case of ovarian cancer omentum metastatic tissue diagnosed by pathology examination of patients undergoing surgery resection who admitted to Linyi Cancer Hospital between January 2019 and December 2021 were collected. Immunohistochemistry was used to detect the protein levels of ACC1 and Yin Yang protein 1 (YY1) of all tissues. The PROMO database was used to predict the possible binding sites of YY1 and ACC1 promoter region. Through the assembled viral vector, the HEY cells of human ovarian cancer with ACC1 or YY1 expression [the untreated cells were treated as the negative control (NC)], or knocked down ACC1 or YY1 (the interference sequence sh1, sh2, sh3 was transferred to the target gene, and the negative control sequence shNC was transferred to the interference sequence). Double luciferase reporter gene assay was used to verify the binding sites of YY1 and ACC1 promoter and the activity of transcriptional regulation. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of ACC1 and YY1 in the treated HEY cells, respectively. Transwell assay was used to detect the migration ability of HEY cells. Oil red O staining and Nile red staining were used to detect the lipid droplets in HEY cells.Results:The immunohistochemical scores of ACC1 and YY1 were 0, 2, 8 scores and 0, 4, 6 scores, respectively in normal ovarian tissue, primary lesion of ovarian cancer, and omentum metastatic tissue. Transwell assay showed that the number of invasive HEY cells in ACC1 overexpression group was more than that in NC group [(87.7±7.4) vs. (52.2±4.2), t = 5.19, P = 0.003]. The number of invasive HEY cells in ACC1-sh1 group, and ACC1-sh2 group with the knockdown of ACC1 was less than that in shNC group [(21.2±1.5), (29.7±2.3) vs. (56.2±5.3); t value was 6.41, 3.77; P < 0.001, P < 0.005]. The number of lipid droplets in HEY cells in the ACC1 overexpression group was more than that in the control NC group [Oil red O staining: (301±25) vs. (215±21); Nile red staining: (287±15) vs. (207±10); all P < 0.05]; the number of lipid droplets in HEY cells in ACC1-sh1 and ACC1-sh2 group with the knockdown of ACC1 was less than that in ACC1-shNC group [Oil red O staining: (113±8), (119±12) vs. (195±18); Nile red staining: (82±8), (117±11) vs. (165±17); all P < 0.05]. The result of dual luciferase reporter assay showed that overexpression of YY1 promoted the luciferase activity of the wild type ACC1 promoter region report gene ( P = 0.003), while the luciferase activity of the report gene was inhibited compared with the wild type after the mutation of binding sites of YY1 in ACCI promoter region ( P = 0.008). Western blot results showed that the expression levels of YY1 and ACC1 protein in HEY cells with YY1 overexpression group were higher than those in NC group, which indicated a synergistic increasing trend of both YY1 and ACC1; the expression levels of YY1 and ACC1 protein in YY1-sh1 group, YY1-sh2 group and YY1-sh3 group with the knockdown of YY1 were lower than those in the control YY1-shNC group, which indicated a synergistic decreasing trend of both YY1 and ACC1. Conclusions:ACC1 and YY1 are highly expressed in ovarian cancer metastatic tissues and both show a positive correlation trend. The expression level of ACC1 in vitro has an impact on cell migration and lipogenesis in ovarian cancer via YY1 transcriptionally regulating ACC1.

Stigma and Efficacy of Zhizhu Kuanzhong Capsules Versus Doxepin in the Treatment of Refractory Functional Dyspepsia: A Randomized Controlled Trial

Background/Aims@#Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy.Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD). @*Methods@#Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire). @*Results@#The MPR values for ZZKZ were significantly higher than those for doxepin (P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma (P < 0.001). The MPR values were negatively correlated with posttreatment stigma scores in both groups (P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups. @*Conclusion@#ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD.