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Purpose To explore the clinical significance of plasma pyruvate kinase M2 (PKM2) in assessing the incidence and prognosis of acute leukemia. Methods Plasma samples from 56 acute myeloid leukemia (AML) patients, 40 acute lymphoblastic leukemia (ALL) patients, and 66 plasma samples from healthy individuals were collected. The level of plasma PKM2 was detected by enzyme-linked immunosorbent assay. The clinical significance of PKM2 in acute leukemia was assessed by analyzing receiver operating characteristic and survival curves. Results The plasma levels of PKM2 in AML or ALL patients were significantly higher than those in healthy individuals, respectively. PKM2 can be used as a potential diagnostic index with the AUC of 0.827 for AML and 0.837 for ALL. The level of plasma PKM2 in ALL patients with a BCR/ABL-positive genotype was significantly higher than that in patients with a BCR/ABL-negative genotype (p

Cancer is one of the leading causes of death in the world. It is very important to find drugs with high efficiency, low toxicity, and low side effects for the treatment of cancer. Flavonoids and their derivatives with broad biological functions have been recognized as anti-tumor chemicals. 8-Formylophiopogonanone B (8-FOB), a naturally existed homoisoflavonoids with rarely known biological functions, needs pharmacological evaluation. In order to explore the possible anti-tumor action of 8-FOB, we used six types of tumor cells to evaluate in vitro effects of this agent on cell viability and tested the effects on clone formation ability, scratching wound-healing, and apoptosis. In an attempt to elucidate the mechanism of pharmacological action, we examined 8-FOB-induced intracellular oxidative stress and -disrupted mitochondrial function. Results suggested that 8-FOB could suppress tumor cell viability, inhibit cell migration and invasion, induce apoptosis, and elicit intracellular ROS production. Among these six types of tumor cells, the nasopharyngeal carcinoma CNE-1 cells were the most sensitive cancer cells to 8-FOB treatment. Intracellular ROS production played a pivotal role in the anti-tumor action of 8-FOB. Our present study is the first to document that 8-FOB has anti-tumor activity in vitro and increases intracellular ROS production, which might be responsible for its anti-tumor action. The anti-tumor pharmacological effect of 8-FOB is worthy of further investigation.

BACKGROUND The brain is the most complex organ in the human body. Treatment for a glioma always involves a multi-disciplinary team. Nursing care in fast-track surgery or enhanced recovery after surgery is such kind of work implemented by an interdisciplinary team to provide services to patients to improve their outcomes. AIM To explore the effects of nursing care in fast-track surgery on postoperative pain, psychological state, and patient satisfaction with nursing for glioma. METHODS From June 2018 to June 2020, 138 patients who underwent operation for glioma at Cancer Hospital Affiliated to Chongqing University were selected. They were categorized into groups according to different nursing care that they received. Of them, 69 patients receiving nursing care in fast-track surgery were included in an experimental group, and 69 patients receiving conventional postoperative nursing were included in a control group. Visual analogue scale was used to evaluate postoperative pain in the two groups immediately after the operation and at 3 d after the operation. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the psychological status of patients immediately after operation and on the 3rd postoperative day. A self-made satisfaction scale for patient satisfaction with nursing was used to evaluate and compare patient satisfaction with nursing between the two groups. RESULTS Time to excretion, time to out-of-bed activities, and length of hospital stay were significantly shorter in the observation group than in the control group (P < 0.05). There was no significant difference in duration of operative time or intraoperative bleeding between the two groups (P > 0.05). There was no significant difference in postoperative pain score between the two groups (P > 0.05). The pain score was significantly lower in the observation group than in the control group at 3 d after the operation (P < 0.05). There was no significant difference in postoperative SAS or SDS score between the two groups (P > 0.05). SAS and SDS scores were significantly lower in the observation group than in the control group at 3 d after operation (P < 0.05). The rate of patient satisfaction with nursing was 94.2% in the observation group, which was significantly higher than that (81.2%) of the control group (P < 0.05). CONCLUSION Nursing care in fast-track surgery can relieve postoperative pain, anxiety, and depression, and improve patient satisfaction with nursing in patients with glioma, which is worthy of clinical application.

This study evaluated age-associated morphology changes in the cranial base, facial development, and upper airway of patients with Treacher Collins syndrome (TCS). A total of 33 preoperative computed tomographic images (TCS, n = 14; control, n = 19) were included in the study and divided into three age-related subgroups (2-6 years, 7-18 years, and older than 18 years). Linear, angular cephalometric measurements and upper airway volumes were collected. All measurements were analyzed using ProPlan CMF software (version 3.0; Materialize, Leuven, Belgium). The association between aging and upper airway morphology was analyzed. Compared to control subjects, TCS patients had a smaller cranial base, maxilla, and nose; they also had reduced upper airway volume compared to control subjects. The observed differences were most significant in patients between the ages of 7 and 18 years. This study used computed tomography-based three-dimensional analyses to provide a detailed description of age-related changes that occur in craniofacial measurements and upper airway volumes in children, adolescents, and young adult patients with TCS in China. These data can be used to evaluate individual patients with TCS and to select treatment to improve the growth of the craniofacial region.

Background Diabetic nephropathy (DN) is a primary complication of diabetes mellitus (DM). The pathology of DN is still vague, and diagnostic accuracy is not enough. This study was performed to identify miRNAs and genes that have possibilities of being used as therapeutic targets for DN in type 2 DM. Methods Human miRNA data GSE51674 and gene data GSE111154 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) in the kidney between control and DN patients were screened out. The competing endogenous RNA (ceRNA) network was constructed, and key lncRNA-miRNA-mRNA pairs were selected accordingly. Potential drugs targeting DEGs were screened out and validated using PCR analysis. Results Totally, 83 DEmiRNAs and 293 DEGs were identified in GSE51674 and GSE111154, respectively. Thirteen of the top 20 DEmiRNAs (10 up and 10 down) targeted to 47 DEGs. In the ceRNA network, RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2 interaction pairs were identified as the key ceRNA network. Interestingly, PTGER3 and hsa-miR-1237-3p were downregulated, and MMP-2 and hsa-miR-106b-5p were upregulated in the kidney of patients with DN compared with normal controls, respectively. PTGER3 and MMP-2 were targeted by drugs including iloprost, treprostinil, or captopril, and the deregulation of the two genes was confirmed in the plasma samples from patients with DN as compared with controls. Conclusions We speculated that the RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2 networks were associated with diabetic renal injury.

In this study, we aim to provide a deep convolutional network based femoral neck fracture detection system on radiographs for emergency patients. We retrospectively collected 1,491 frontal pelvic radiographs from three institutions and assigned them to the following data sets: primary dataset (710 radiographs, to fine-tune and validate the initial model called the Digital Radiography Fracture Detection System [DR-FDS]), internal test set 1 (189 radiographs) and 2 (235 radiographs), and external test set 1 (189 radiographs) and 2 (168 radiographs). Per-bounding box recall and precision and per-image sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) were computed. We randomly extracted 300 radiographs from the above test sets and compared their effect on the diagnostic accuracy and efficiency of fine-tuned model-assisted and unassisted clinicians. The fine-tuned DR-FDS showed a better overall performance in detecting femoral neck fractures than did the initial DR-FDS. The fine-tuned DR-FDS achieved AUC values of 0.9526 (95%CI, 0.9048–0.9767) and 0.9633(95%CI, 0.9346-0.9797) in internal test sets 1 and 2. In external test sets 1 and 2, this model also achieved promising results with AUC values of 0.9231 (95%CI, 0.8779–0.9520), and 0.9937 (95%CI 0.9739–0.9985), respectively. The clinicians showed a statistically significant increase in specificity, sensitivity, and accuracy for the identification of minimal/undisplaced fracture and a decrease in the average reading time. The object detection model that is fine-tuned has high sensitivity and specificity and the universal ability to detect and locate femoral neck fractures on pelvic radiographs.

Radiation therapy is widely used to treat a variety of malignant tumors, including non-small-cell lung cancer (NSCLC). However, ionizing radiation (IR) paradoxically promotes radioresistance, metastasis and recurrence by inducing epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Here, we developed two NSCLC radioresistant (RR) cell lines (A549-RR and H1299-RR) and characterized their motility, cell cycle distribution, DNA damage, and CSC production using migration/invasion assays, flow cytometry, comet assays, and sphere formation, respectively. We also evaluated their tumorigenicity in vivo using a mouse xenograft model. We found that invasion and spheroid formation by A549-RR and H1299-RR cells were increased as compared to their parental cells. Furthermore, as compared to radiation alone, the combination of β-elemene administration with radiation increased the radiosensitivity of A549 cells and reduced expression of EMT/CSC markers while inhibiting the Prx-1/NF-kB /iNOS signaling pathway. Our findings suggest that NSCLC radioresistance is associated with EMT, enhanced CSC phenotypes, and activation of the Prx-1/NF-kB/iNOS signaling pathway. They also suggest that combining β-elemene with radiation may be an effective means of overcoming radioresistance in NSCLC.

Objective: To investigate the correlation between high-risk human papillomavirus (HR HPV)-negative cervical lesions and cervical microenvironment in Inner Mongolia, China, and to find the pathogenic factors of HR HPV-negative cervical lesions. Materials and methods: 74 cases of HR HPV-negative healthy women and 80 cases of patients with cervical lesions (28 cases of LSIL, 49 cases of HSIL and 3 cases of CSCC) were selected as the study group; 26 cases of HPV-positive women and 352 cases of patients with cervical lesions (108 cases of LSIL, 214 cases of HSIL and 30 cases of CSCC) were control group. Questionnaires were collected from the study group and the control group and specimens were collected. Gram staining, hematoxylin and eosin staining microscopy, and substrate colorimetry method were used to detect vaginal micro-ecological indicators; ELISA was used to detect the concentration of SIgA, IgG, IL-2 and IL-10 in vaginal lavage fluid. Genetic testing was used to detect HPV, mycoplasma, and chlamydia infection. The changes of vaginal micro-ecology evaluation index and local immune factor concentration in healthy women and cervical lesions of all grades in the study group and the control group were compared. Results: Patients with cervical lesions, compared with healthy women, had a decrease in dominant lactobacilli and dysbacteriosis (P

Background The aim of this study was to clarify the characteristics of gene mutation related to multidrug-resistance (MDR) of tuberculosis (TB) and diabetes in Zunyi. Methods A total 763 patients with TB were screened for TB-DNA, TB-RNA, and acid-fast staining (all were positive). They were divided into the tuberculosis (TB) group and the diabetes mellitus-tuberculosis (DM-TB) group. We compared and analyzed the MDR gene rpoB, KatG, and inhA characteristics of gene mutations in the two groups by polymerase chain reaction (PCR)-reverse dot hybridization, and collected relevant clinical data to explore its correlation with the occurrence of multidrug resistance. Results Multidrug resistance occurred in 32 of the 525 patients in the TB group, and extensive drug resistance occurred in 15 of the 207 patients in the DM-TB group. In the DM-TB group, the mutation rates of ropBS531L and ropB531 (both 53.33%) were lower than those of the TB group (both 59.38%) in rifampicin resistance mutations. Most of the mutations were at the KatG315N site, conferring isoniazid resistance. Conclusions The mutation sites of multidrug-resistant patients in Zunyi are mainly ropB531 and ropBS531L mutations, which are prone to co-occurrence; patients with MDR-TB alone are prone to mutations at the KatG315N site, while patients with diabetes and MDR-TB are more likely to have inhA15M site mutations.

We sought to determine whether high-density lipoprotein (HDL) function was altered in gout patients.The study included 95 gout patients and 68 healthy controls. The concentrations of interleukin (IL)-1β and IL-9 were measured by ELISA, and indicators such as blood uric acid, liver and kidney function, blood glucose, and blood lipids were detected. To test for the anti-inflammatory and reverse cholesterol transport (RCT) function of HDL, 11 gout patients and 11 healthy controls were randomly selected for the BioVision cholesterol efflux test, which detects the RCT activity of HDL. To assess the anti-inflammatory function of HDL, cells in co-culture with HDL were treated with inflammatory stimuli such as tumor necrosis factor-α (TNF-α), and then, the cells were assayed for the expression of intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecule-1 (VCAM-1).In total, this study enrolled 163 participants, including 95 non-hyperlipidemic gout patients and 68 healthy controls. IL-1β and IL-9 levels were significantly higher in the gout group than in the control group (85.26 ± 23.16 vs. 41.47 ± 6.48 and 33.77 ± 12.68 vs. 23.66 ± 4.53, respectively, P0.001). Additionally, plasma IL-1β and IL-9 levels were increased along with those of blood uric acid (RThe anti-inflammatory activities of HDLs are impaired in gout patients. Key Points • Gout patients show chronic inflammation. • The anti-inflammatory activity of high-density lipoprotein is impaired in gout patients.

Background This study aimed to investigate the correlation between the level of HPV16 and HPV18 in patients with cervical lesions and the local vaginal immunity after receiving treatment with different degrees of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC). Methods One hundred and thirty-six patients with LSIL (grade 1 CIN or CIN 1), 263 patients with HSIL (grade 2 and 3 CIN or CIN 2 and 3), and 33 patients with CSCC pathologically confirmed between November 2012 and September 2016 were assigned to the test group and 100 healthy women in the same period were assigned to the control group. ELISA was used to determine the levels of SIgA, IgG, IL-2, and IL-10 and the IL-2/IL-10 ratio in vaginal lavage fluid in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively. Gene chip technology was adopted to test the HPV infection in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively. Results The results showed that the levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in all patients before treatment. The levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in HPV16 and HPV18-infected patients before receiving the treatment. Conclusions The recovery after the treatment of HPV infection is time-dependent and the immune system of patients with CIN starts to recover in the 6th month after treatment, early intervention is not recommended. However, the immune system is approximately in a normal sate at 12 months after treatment, at which time the efficacy can be evaluated, and clinical intervention can be initiated if necessary. The level of local immune factors in the vagina can be monitored to determine the progression and prognosis of patients’ cervical lesions.

Major depressive disorder (MDD) is a highly prevalent debilitating psychiatric disease and a serious public health problem worldwide. Brain structural MRI and postmortem studies on patients with depression have revealed changes in the anatomy and functionality in various brain regions, including the amygdala, thalamus, hippocampus, and prefrontal cortex (PFC). The alterations in these brain regions could be a result, in part, of the dysregulation of the neurotrophic factors. Neuregulin1 (NRG1) is one of the neurotrophic factors, and our previous study showed that the NRG1-ErbB4 signaling pathway plays a critical role in epilepsy. In this study, we established a chronic social defeat stress (CSDS) model to investigate the role of the NRG1-ErbB4 signaling pathway in depression-like behaviors. In CSDS mice, we found that the NRG1 protein expression levels were significantly decreased both in the medial prefrontal cortex (mPFC) and hippocampus, while phosphorylated ErbB4 only decreased in the mPFC. In addition, lateral ventricle NRG1 administration significantly rescued depression-like behaviors in the susceptible group. The current study suggests that the NRG1-ErbB4 signaling pathway may exert a protective role in MDD.

This paper explores the diagnosis of deep invasive endometriosis through retrospective data analysis, including deep infiltration and magnetic resonance imaging. The literature retrospectively collected data from 21 patients with deep invasive endometriosis who were admitted from 2012 to 2018. The patients were confirmed to have pain and nerve growth factor (NGF) receptor expression levels after operation and underwent vaginal color ultrasound and magnetic resonance imaging before surgery. The diagnostic results of color Doppler ultrasound and magnetic resonance imaging were retrospectively analyzed and compared with the surgical results, and the cumulative site and anatomic abnormalities of the diagnosis of deep invasive endometriosis were analyzed to determine the NGF receptor table. Through research it has been found that deep invasive endometriosis mainly involves the uterine fibula ligament, vagina, uterus rectum, rectum, ureter, and so forth. Patient pain is related to the expression level of NGF receptor, and its magnetic resonance mainly manifests as signals and structural obstacles, irregular thickening of the affected area, or nodular formation and deformation of adjacent tissues and organs. Through research and demonstration of deep invasive endometriosis, transvaginal color ultrasound and magnetic resonance imaging can not only accurately locate the expression levels of pain and NGF receptors, but also show the extent of the lesions, thereby studying pain and NGF receptor expression, which is an important method for preoperative examination and postoperative follow-up.

OBJECTIVE This retrospective study aimed to evaluate the diagnostic efficiency of simultaneous positron emission tomography/magnetic resonance imaging (PET/MR) in differentiating the benign and malignant of pancreatic tumors as well as the differentiation of pancreatic cancer. METHODS A total of 62 patients with suspected pancreatic tumors, diagnosed by PET/MR examinations, were collected in this study. These patients were divided into benign group and malignant group. The characteristics of the morphological MR, apparent diffusion coefficient (ADC), the mean of standardized uptake value (SUVmean), maximum values of standardized uptake value (SUVmax), in lesions were measured, and the novel parameters SUVpeak/ADC and SUVmax/ADC were constructed. The diagnostic efficiency for differentiating the benign and malignant lesions was analyzed by receiver operating characteristic (ROC) curve, and the diagnosis efficiency for the differentiation of pancreatic cancer was analyzed by Spearman correlation analysis. RESULTS In differentiating the benign and malignant of pancreatic tumors, the diagnostic efficiency increased in the order of SUVpeak (AUROC: 0.760), SUVmax (AUROC: 0.774), T1T2 (AUROC: 0.789), ADC (AUROC: 0.817), SUVpeak/ADC (AUROC: 0.836), SUVmax/ADC (AUROC: 0.847). There was no significant correlation for SUVmax, SUVpeak, ADC, SUVpeak/ADC, and SUVmax/ADC with the differentiation of pancreatic cancer (P > 0.05). Besides, T1T2 was not significantly correlated to the differentiation of pancreatic cancer (P = 0.026, r = -0.406). CONCLUSION The integration of PET/MR imaging could be used to efficiently diagnose whether the pancreatic tumor was benign or malignant. The SUVmax/ADC was the most efficient metric, while it could not help in the differentiation of pancreatic cancer.

Mandibular angle osteotomy with outer cortex grinding has become the preferred cosmetic procedure for correcting square faces. After surgery, bone hyperplasia at the mandibular angle affects the operation result. This study evaluated the effect of the masticatory muscles on bone repair. From January 2016 to January 2019, patients who underwent mandibular angle osteotomy with outer cortex grinding were retrospectively reviewed. Computed tomography data of these patients were collected, and the bone volume of the mandibular angle changes and its correlation with masticatory muscle morphology were analyzed. Computed tomography data measurement results showed that a large amount of bone in the mandibular angle area was removed by the operation; however, the long-term follow-up results showed that there was bone hyperplasia in the mandibular angle areas. Compared with the immediate postoperative bone volume, the difference was statistically significant (P

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment.Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls.Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively.Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment.Clinical Trial Registration:ClinicalTrials.gov, identifier: ChiCTR2100046954.

The 2019 novel coronavirus (2019-nCoV) outbreak has been treated as a Public Health Emergency of International Concern by the World Health Organization. This work made an early prediction of the 2019-nCoV outbreak in China based on a simple mathematical model and limited epidemiological data. Combing characteristics of the historical epidemic, we found part of the released data is unreasonable. Through ruling out the unreasonable data, the model predictions exhibit that the number of the cumulative 2019-nCoV cases may reach 76,000 to 230,000, with a peak of the unrecovered infectives (22,000-74,000) occurring in late February to early March. After that, the infected cases will rapidly monotonically decrease until early May to late June, when the 2019-nCoV outbreak will fade out. Strong anti-epidemic measures may reduce the cumulative infected cases by 40%-49%. The improvement of medical care can also lead to about one-half transmission decrease and effectively shorten the duration of the 2019-nCoV., The flow diagram of early prediction of the 2019-nCoV. The early-stage epidemiological data is firstly analyzed to rule out unreasonable part with considering historical epidemic. The SIR model is then simplified to reduce the number of parameters and thus data requirement. The early prediction is finally obtained via integrating the simplified model with parameter estimations based on objective analysis.

BACKGROUND Sepsis is a severe medical condition. Approximately 0.75 million people are diagnosed with sepsis in the USA annually. Several of anti-inflammatory drugs are used to manage sepsis, but with a very low success rate. This study examined the possible protective effects of a naturally occurring flavanone, quercetin, in a rat model of sepsis. MATERIAL AND METHODS The study was carried out using Wistar albino rats. Sepsis was induced by cecal ligation and puncture methods. Histological analysis was performed by hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels were determined by flow cytometery. Superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) activities were determined by standard assays. Protein expression was determined by Western blot analysis. RESULTS The results showed that quercetin reduced the tissue edema, congestion, and hemorrhage, increased the alveolar volume, and helped to maintain the lung anatomy of septic rats. Admistration of quercetin at the dosage of 15 and 20 mg/kg to septic rats caused significant reduction in the ROS levels. The activities and the expression of SOD, CAT, and APX were significantly decreased upon administration of quercetin in the septic rats at the dosage of 15 and 20 mg/kg. The effects of quercetin were also examined on the expression of the High mobility group box 1 (HMGB1) protein in septic rats. The results showed that quercetin caused a significant decrease in HMGB1 protein levels. CONCLUSIONS The findings of this study suggest that quercetin has therapeutic potential in the treatment of sepsis.

BACKGROUND Sepsis is a devastating medical condition. In the USA, about 745 000 people are diagnosed with sepsis annually. Although many anti-inflammatory drugs have been used to manage sepsis, the treatment success rate is very low. This study was undertaken to examine the protective effects of naringenin on sepsis-induced kidney injury in rats. MATERIAL AND METHODS Sepsis was induced in Wistar albino rats by cecal ligation and puncture methods. Histological analysis was performed with hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels were determined by flow cytometery. TUNEL assay was used to demonstrate apoptosis. Sandwich ELISA method was used for the determination of urinary angiotensinogen, and protein expression was determined by Western blot analysis. RESULTS We found that naringenin decreased atrophy in the glomerulus and enabled maintenance of the capsule area and normal tubular cavity of the septic rats. Admistration of naringenin at the dosage of 10 and 20 mg/kg to sepsis rats caused significant reduction in the sepsis-induced apoptosis of kidney cells, accompanied by decrease in Bax and increase in Bcl-2 expression. Moreover, naringenin also decreased the ROS levels in septic rats and downregulated the expression of SOD, CAT, and APX. The effects of naringenin were also examined on the levels of urinary angiotensinogen in sepsis rats. We found that naringenin caused a significant decrease in urinary angiotensinogen levels of septic rats. CONCLUSIONS Naringenin appears to have potential in the treatment of sepsis.

Renal fibrosis is the major pathological characteristic of diabetic nephropathy (DN). Reportedly, increased SIRT1 expression played a renal protective role in animal models of DN. This study was designed to elucidate the molecular mechanisms underlying the protective effects of SRT1720, an SIRT1 activator, against diabetes-induced renal fibrosis. Type 2 diabetic mice (db/db) were treated with SRT1720 (50 mg/kg/day) by gavage for 10 weeks. Renal proximal tubular epithelial cells (HK-2 cells) were treated with high glucose (HG, 30 mM) in the presence or absence of SRT1720 (2.5 µM) for 48 h. We observed that impaired SIRT1 expression and activity were restored by SRT1720 administration in db/db mice as well as in HG-treated HK-2 cells. Moreover, SRT1720 administration improved the renal function, attenuated glomerular hypertrophy, mesangial expansion, glomerulosclerosis and interstitial fibrosis and inhibited TGFB1 and CTGF expressions and nuclear factor κB (NF-KB) activation in db/db mice. Similarly, HG-induced epithelial-to-mesenchymal transformation (EMT) and collagen IV and fibronectin expressions were inhibited in SRT1720-treated HK-2 cells. Mechanistic studies demonstrated that SRT1720 suppressed HIF1A, GLUT1 and SNAIL expressions both in vivo and in vitro. Furthermore, HIF1A or GLUT1 knockdown effectively abrogated HG-induced EMT and collagen IV and fibronectin expressions in HK-2 cells. These findings suggest that SRT1720 prevented diabetes-induced renal fibrosis via the SIRT1/HIF1A/GLUT1/SNAIL pathway.

Supplemental Digital Content is available in the text., Background: China has seen a burgeoning epidemic of obesity in recent decades, but few studies reported nationally on obesity across socio-demographic subgroups. We sought to assess the prevalence and socio-demographic associations of obesity nationwide. Methods: We assessed the prevalence of overall obesity (body mass index ≥28 kg/m2) and abdominal obesity (waist circumference ≥85/90 cm for women/men) among 2.7 million community-dwelling adults aged 35 to 75 years in the China PEACE Million Persons Project from 2014 to 2018 and quantified the socio-demographic associations of obesity using multivariable mixed models. Results: Age-standardized rates of overall and abdominal obesity were 14.4% (95% CI, 14.3%–14.4%) and 32.7% (32.6%–32.8%) in women and 16.0% (15.9%–16.1%) and 36.6% (36.5%–36.8%) in men. Obesity varied considerably across socio-demographic subgroups. Older women were at higher risk for obesity (eg, adjusted relative risk [95% CI] of women aged 65–75 versus 35–44 years: 1.29 [1.27–1.31] for overall obesity, 1.76 [1.74–1.77] for abdominal obesity) while older men were not. Higher education was associated with lower risk in women (eg, adjusted relative risk [95% CI] of those with college or university education versus below primary school: 0.47 [0.46–0.48] for overall obesity, 0.61 [0.60–0.62] for abdominal obesity) but higher risk in men (1.07 [1.05–1.10], 1.17 [1.16–1.19]). Conclusions: In China, over 1 in 7 individuals meet criteria for overall obesity, and 1 in 3 for abdominal obesity. Wide variation exists across socio-demographic subgroups. The associations of age and education with obesity are significant and differ by sex. Understanding obesity in contemporary China has broad domestic policy implications and provides a valuable international reference.

Lysosome is one of the important organelles in intracellular transport. It plays a significant role in the physiological process. The lysosomal microenvironment affects the functions of lysosome. When the original acidic environment of lysozyme is destroyed or the fluid viscosity increases gradually, various diseases are easily induced. However, most fluorescent probes can only locate in cells. The fewer probes of subcellular organelles were found and their functions are often single. So, it is of great importance to design multifunctional fluorescent probes with the capable of localizing in lysosome. In this study, a novel lysosome probe, 4-(4-Pyren-1-yl-but-3-enyl)-morpholine (PIM), was synthesized using pyrene as a fluorescent group and morpholine as a target group. The introduction of morpholine group made PIM localize in lysosome with high selectivity. The fluorescence will be enhanced with the increased viscosity because of restricting the rotation of C C bond and C N in PIM, and the detecting linear range is from 4.05 cP to 393.48 cP, which qualified the requirement of the viscosity monitoring in body. Meanwhile, the fluorescence intensity of PIM declines with the decrease of pH because the Schiff base of PIM is hydrolyzed, which was affirmed by 1H NMR, LC-MS and fluorescence spectra. Moreover, cell imaging and MTT experiments confirmed that PIM as a novel bifunctional probe can be used to detect pH and endogenous viscosity in lysosome.

To describe and advise on management protocols and infection-protection experience of the radiology department in makeshift hospitals in Wuhan during the coronavirus disease 2019 (COVID-19) outbreak. Based on the literature review and the experience in the frontline, we retrospectively reviewed the configuration of the radiology department, human resource, personal protection, examination procedures for patients confirmed with COVID-19 in Wuhan fangcang shelter hospital. From February 11, 2020 to March 10, 2020, 2730 and 510 CT examinations were performed in the Hanjiang shelter hospital and Hanyang Sports School shelter hospital, respectively, including initial examinations and re-examinations. The maximum number of daily CT examinations reached 289. The CT scanned a patient approximately once every 13 mins. Fangcang shelter radiology department could be powerful components of both global and national responses to the COVID-19 pandemic.

Objective. Driver gene mutation in lung adenocarcinoma patients in Zunyi and its relationship with clinical features were probed in this investigation. Methods. In total, with 244 patients with lung adenocarcinoma as study subjects, including 141 males and 103 females, amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) was utilized for detecting multigene mutations. Subsequently, the relationship between gene mutation and clinical characteristics was analyzed. Results. The total mutation rate of driver genes was 65.17%, including 48.36% EGFR, 6.15% KRAS, 5.74% ALK, 2.05% HER-2, 1.23% ROS1, 0.82% RET, 0.41% NRAS, and 0.41% BRAF. Among EGFR mutations, 47.46% were EGFR-19-deletion, 42.37% EGFR-21-L858R mutation, 4.24% EGFR-20-T790M mutation, 2.54% EGFR-21-L861Q mutation, 2.54% EGFR-20-insertion, and 0.85% EGFR-18-G719X mutation. Both female patients and nonsmoking patients with lung adenocarcinoma had a higher rate of EGFR mutation. Additionally, 15 patients with multiple mutations in EGFR, including 13 patients with 2 mutations in EGFR and 2 patients with 3 mutations in EGFR, were found. Conclusion. Among driver gene mutations in patients with lung adenocarcinoma in Zunyi, EGFR mutation has the highest incidence, followed by ALK fusion and KRAS mutation. Although both mutations and multisite mutations in the other driver genes account for a low proportion, they still have great clinical significance. Multigene mutation detection contributes to the rapid screening of patients with lung adenocarcinoma who respond to targeted therapy.

It is well known that hydrostatic pressure (HP) is a physical parameter that is now regarded as an important variable for life. High hydrostatic pressure (HHP) technology has influenced biological systems for more than 100 years. Food and bioscience researchers have shown great interest in HHP technology over the past few decades. The development of knowledge related to this area can better facilitate the application of HHP in the life sciences. Furthermore, new applications for HHP may come from these current studies, particularly in tumor vaccines. Currently, cancer recurrence and metastasis continue to pose a serious threat to human health. The limited efficacy of conventional treatments has led to the need for breakthroughs in immunotherapy and other related areas. Research into tumor vaccines is providing new insights for cancer treatment. The purpose of this review is to present the main findings reported thus far in the relevant scientific literature, focusing on knowledge related to HHP technology and tumor vaccines, and to demonstrate the potential of applying HHP technology to tumor vaccine development.

Accurate long-term streamflow and flood forecasting have always been an important research direction in hydrology research. Nowadays, climate change, floods, and other anomalies occurring more and more frequently and bringing great losses to society. The prediction of streamflow, especially flood prediction, is important for disaster prevention. Current hydrological models based on physical mechanisms can give accurate predictions of streamflow, but the effective prediction period is only about 1 month in advance, which is too short for decision making. The artificial neural network (ANN) has great potential for predicting runoff and is not only good at handling non-linear data but can also make long-period forecasts. However, most of ANN models are unstable in their predictions when faced with raw flow data, and have excessive errors in predicting extreme flows. Previous studies have shown a link between the El Niño–Southern Oscillation (ENSO) and the streamflow of the Yangtze River. In this paper, we use ENSO and the monthly streamflow data of the Yangtze River from 1952 to 2018 to predict the monthly streamflow of the Yangtze River in two extreme flood years and a small flood year by using deep neural networks. In this paper, three deep neural network frameworks are used: stacked long short-term memory, Conv long short-term memory encoder–decoder long short-term memory and Conv long short-term memory encoder–decoder gate recurrent unit. The results show that the use of ConvLSTM improves the stability of the model and increases the accuracy of the flood prediction. Besides, the introduction of ENSO to the experimental data resulted in a more accurate prediction of the time of the occurrence of flood peaks and flood flows. Furthermore, the best results were obtained on the convolutional long short-term memory + encoder–decoder gate recurrent unit model.

Objective. To investigate the effect of matrine on rats with collagen-induced arthritis (CIA) and its regulatory effect on receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) expression. Methods. Wistar rats ( n = 6 ) and CIA rats ( n = 30 ) were randomly divided into six groups: healthy, CIA control, low/medium/high matrine (25, 50, or 100 mg/kg, once per day for six weeks), and methotrexate (MTX) (2 mg/kg, once per week for six weeks). The degree of joint damage was evaluated by X-ray and HE staining. Bone marrow suppression was assessed by routine blood analysis. In addition, the levels of serum RANKL and OPG in the rats were measured by ELISA. Results. The level of joint swelling and degree of joint damage assessed by ankle swelling measurements, AI score, X-ray, and HE staining were alleviated in the CIA rats treated with MTX or different doses of matrine. Furthermore, no obvious inhibitory effect was observed on the bone marrow of the CIA rats, regardless of the dose of matrine or treatment with 2 mg/kg MTX ( P > 0.05 ). The levels of OPG in serum and the ratio of OPG/RANKL were higher, and RANKL expression was lower in the low/medium/high matrine group compared with that of the CIA control group. The serum levels of OPG and OPG/RANKL ratio increased with the matrine dose, while the opposite was observed for RANKL expression. Conclusion. Matrine treatment was associated with a lower degree of bone destruction, increased OPG expression and OPG/RANKL ratio, and decreased RANKL expression in CIA rats. Thus, matrine may represent a novel drug candidate for the treatment of RA.

Ovarian cancer (OC) is the fifth most common female malignant tumor and the leading cause of cancer-related death in women worldwide. Epithelial ovarian cancer (EOC) is the predominant type of OC. Investigating the mechanism underlying tumorigenesis and progression of EOC is urgent. Our previous research has shown that long non-coding RNAs (lncRNAs) CDKN2A-AS1 is upregulated in EOC tissues and cells. Furthermore, we have predicted that CDKN2A-AS1 is associated with the bone morphogenetic protein (BMP)-SMAD signaling pathway, which is negatively regulated by the sclerostin domain containing 1 (SOSTDC1). Therefore, we conjecture that the CDKN2A-AS1 regulate BMP-SMAD signaling pathway via interacting with SOSTDC1, which need more investigation. Moreover, the functions of the BMP-SMAD signaling pathway and the SOSTDC1 on EOC are still unclear. Herein, we unearthed that CDKN2A-AS1, BMP2/4/7, SMAD1/5/9 and phosphorylation of SMAD1/5/9 (p-SMAD1/5/9) were upregulated in EOC tissues and cells, whereas SOSTDC1 was downregulated in EOC tissues and cells. We firstly demonstrated that CDKN2A-AS1 bound directly with the SOSTDC1. CDKN2A-AS1 downregulated the expression of SOSTDC1, but upregulated the expression of BMP2/4/7, SMAD1/5/9, and p-SMAD1/5/9. CDKN2A-AS1 promoted the proliferation, migration, invasion of EOC cells and tumor growth in vivo, whereas SOSTDC1 inhibited the proliferation, migration, invasion of EOC cells. Knockdown SOSTDC1 rescued the inhibitory effect of si-lncRNA CDKN2A-AS1 on the EOC cells proliferation, migration and invasion. These results demonstrated that CDKN2A-AS1activated the BMP-SMAD signaling pathway by directly bind with SOSTDC1 to promote EOC tumor growth. CDKN2A-AS1/SOSTDC1 axis may provide a novel therapeutic strategy for EOC treatment.

Background With demographic and epidemiologic transitions, China has become home to the greatest number of obese individuals in the world. Effective policy intervention requires a contemporary assessment of obesity across broad socio-demographic subgroups. Purpose We aim to assess the prevalence of overall and abdominal obesity by socio-demographic characteristics and the associations of these characteristics with obesity in China. Methods Using the data of 2.7-million community-dwelling participants aged 35–75 years in the China PEACE Million Persons Project, a nationwide cross-sectional screening project from 2014 to 2018, we calculated the prevalence of overall and abdominal obesity based on national guideline definitions (body mass index ≥28 kg/m2, waist circumference ≥85/90 cm for women/men). We examined 12 available socio-demographic variables that are potentially associated with obesity, in addition to self-reported co-morbidities, and quantified the associations of these socio-demographic characteristics with obesity using multivariable mixed models. Results The prevalence of overall and abdominal obesity were 15.8% and 37.6% in women and 15.0% and 36.3% in men (Figure). Compared to individuals with normal weight, those with overall obesity had a higher prevalence of hypertension, dyslipidemia, and diabetes (in women: by 30.4, 16.1, and 6.0 percent points; in men, by 29.9, 31.2, and 5.8 percent points). A similar pattern was observed with abdominal obesity. In women, those aged 55–64 years constituted the largest age group with overall and abdominal obesity (33.7% and 35.0%), while in men, those aged 45–54 and 55–64 years constituted the largest age group with overall obesity (30.4%) and abdominal obesity (30.5%), respectively. Older women were at substantially higher risk for obesity (e.g., adjusted relative risk [95% CI] of women aged 65–75 vs. 35–44 years: 1.29 [1.27–1.31] for overall obesity and 1.76 [1.74–1.77] for abdominal obesity) while older men were not. Higher education was associated with lower risk in women (e.g., those with college or university education vs. less than primary school: 0.47 [0.46–0.48] for overall obesity and 0.61 [0.60–0.62] for abdominal obesity) but higher risk in men (1.07 [1.05–1.10] and 1.17 [1.16–1.19]). In both women and men, current smoking was associated with lower risk for obesity, and current drinking was associated with higher risk, but the magnitude of associations was smaller in women than men. Conclusions In China, over one in seven individuals meet criteria for overall obesity, and one in three for abdominal obesity. Wide variation exists across socio-demographic subgroups. The associations of age and education with obesity are significant and differ by sex. Understanding obesity in contemporary China has broad domestic policy implications and provides a valuable international reference. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): The National Key Research and Development Program from the Ministry of Science and Technology of China, the CAMS Innovation Fund for Medical Science

The aim of this study was to observe the spatial distribution and dynamic changes of matrix metalloproteinase (MMP)-2, MMP-9, and collagen in in stent restenosis (ISR) and to explore their influence on ISR.Sixty Z type stents were implanted into the common iliac arteries of minipigs, which were divided into 10 groups (six in each group) according to euthanasia time (6 hours, and 1, 3, 7, 14, 28, 56, 84, 168, and 336 days). After the samples were harvested, haematoxylin and eosin staining, immunohistochemical staining, Western blotting, and Picrosirius red staining were performed for all groups.ISR occurred in all six minipigs in the 56 day group (percentage diameter stenosis range 71.6%-79.2%, mean ± standard deviation 75.6% ± 2.5%). The percentage diameter stenosis decreased to 38.3% ± 2.7% at 336 days (p .001). Immunohistochemical staining showed that MMP-2 and MMP-9 were strongly stained near the internal elastic lamina or in the damaged parts of the intima, around the struts and neointimal lumen surface in the ISR process. The expression of MMP-2 and MMP-9 at 56 days was significantly lower compared with their peaks (seven days and one day [p .001; p = .002], respectively). At 56 days, the collagen content reached its maximum (mean integrated optical density range 0.73-0.92, mean ± standard deviation 0.82 ± 0.09). From the 14 day group to the 336 day group, mature collagen in neointima was correlated negatively with MMP-2 (γ(36) = -0.816; p .001) and MMP-9 expression (γ(36) = -0.853; p .001). During the neointimal regression period, new collagen in neointima was positively correlated with MMP-2 (γ(24) = 0.683; p .001) and MMP-9 (γ(24) = 0.873; p .001).This study has demonstrated the spatial distribution of and dynamic changes in MMP-2, MMP-9, and collagen in ISR by simulating the process of neointima from generation to regression after stent implantation. When ISR occurred, MMP-2 and MMP-9 expression decreased and collagen content reached its maximum, which might contribute to ISR.

Objective: LncRNA-KAT7 is a recently identified tumor suppressor in colorectal cancer, whereas its roles in other malignancies remain unclear. This study aimed to investigate the roles of KAT7 in n...

The objective of the study was to investigate the value of anti-α-enolase antibody (Ab) combined with RDW in evaluating the activity of systemic lupus erythematosus (SLE). Levels of serum anti-α-enolase Ab and RDW were detected in 193 SLE patients and 98 healthy controls by ELISA and automatic blood cell counter (XN9000), respectively. Furthermore, the correlation between anti-α-enolase Ab and RDW in evaluating the activity of SLE was evaluated by correlation analysis. The level of anti-α-enolase Ab (9.16 ± 0.44 ng/mL in stable group and 10.26 ± 0.36 ng/mL in activity group) was significantly higher than that in the healthy control (7.05 ± 0.27 ng/mL). The level of RDW (12.92% ± 1.23% in stable group and 13.57% ± 2.12% in activity group) was significantly higher than that in the healthy control (12.46% ± 0.61%). The levels of anti-α-enolase Ab or RDW in SLE patients were positively correlated with SLEDAI-2 K score (r= 0.75, r = 0.73), respectively. Compared with the anti-α-enolase Ab (AUC: 78.0%) or RDW (AUC:80.0%) alone, anti-α-enolase Ab combined with RDW (AUC: 81.0%) had the best of the effectiveness of evaluating activity of SLE. These data suggested that combined anti-α-enolase Ab with RDW might be good biomarker to predict the activity of SLE in clinical.

BACKGROUND The aim of this study was to compare changes in the extracellular matrix after implantation of a stent that elutes a matrix metalloproteinase (MMP) inhibitor (GM6001); and to determine the effects of the GM6001-eluting stent upon prevention of in-stent restenosis (ISR). MATERIAL AND METHODS We included 48 Guangxi Bama mini-pigs in this study. A GM6001-eluting stent was placed in one iliac artery and a stent that did not elute GM6001 was placed in the contralateral iliac artery. The iliac arteries were removed at 6 hours as well as 1, 7, 14, 56, 84, and 336 days after stent placement. Arteries were analyzed for morphometry, gelatinase content, different phenotypes of vascular smooth muscle cells (VSMCs), collagen content, apoptotic rate, and cell density. RESULTS The vascular lumen areas of the GM6001 group were significantly increased and the neointimal areas were significantly reduced compared with the control group from the 7 days to the 336 days. In the 2 groups, expression of MMP-2 and MMP-9 peaked simultaneously, but GM6001-eluting stents inhibited expression of MMP-2 and MMP-9 in the vascular media and neointima (especially around the struts) significantly. In the GM6001 group, expression of tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2, myosin heavy chain 10 (MYH-10, marker of the proliferative phenotype of VSMCs), collagen content, percentage of apoptotic cells, and cell density were also decreased significantly compared with those in the control group. CONCLUSIONS Use of GM6001-eluting stents resulted in persistent and potent inhibition of intimal hyperplasia, an increase in luminal area, and no obvious thrombosis in the arteries of the mini-pigs.

Glioblastoma (GBM) recurrence is attributed to the presence of therapy‐resistant glioblastoma stem cells. Steroid receptor coactivator‐1 (SRC‐1) acts as an oncogenic regulator in many human tumors. The relationship between SRC‐1 and GBM has not yet been studied. Herein, we investigate the role of SRC‐1 in GBM. In this study, we found that SRC‐1 expression is positively correlated with grades of glioma and inversely correlated with glioma patient’s prognosis. Steroid receptor coactivator‐1 promotes the proliferation, migration, and tumor growth of GBM cells. Notably, SRC‐1 knockdown suppresses the stemness of GBM cells. Mechanistically, long noncoding RNA X‐inactive specific transcript (XIST) is regulated by SRC‐1 at the posttranscriptional level and mediates the function of SRC‐1 in promoting stemness‐like properties of GBM. Steroid receptor coactivator‐1 can promote the expression of Kruppel‐like factor 4 (KLF4) through the XIST/microRNA (miR)‐152 axis. Additionally, arenobufagin and bufalin, SRC small molecule inhibitors, can reduce the proliferation and stemness of GBM cells. This study reveals SRC‐1 promotes the stemness of GBM by activating the long noncoding RNA XIST/miR‐152/KLF4 pathway and provides novel markers for diagnosis and therapy of GBM., Steroid receptor coactivator‐1 (SRC‐1) was positively correlated with grades of glioma and inversely correlated with glioma patient’s prognosis. SRC‐1 promoted the proliferation, migration, and tumor growth. Additionally, SRC‐1 enhanced stem‐like characteristics of GBM cells. Mechanistic studies showed that SRC‐1 enhances the stemness by activating the long noncoding RNA (lncRNA) X‐inactive specific transcript (XIST)/microRNA (miR)‐152/Kruppel‐like factor 4 (KLF4) pathway in GBM cells. Arenobufagin and bufalin, SRC small molecule inhibitors, reduced the proliferation and stemness of GBM cells.

Lipid deposition caused by the disorder of renal lipid metabolism is involved in diabetic nephropathy (DN). Carbohydrate response element-binding protein (ChREBP) is a key transcription factor in high glucose-induced cellular fat synthesis. At present, the regulation and mechanism of ChREBP on fat metabolism in diabetic kidneys are still unclear. In this study, we showed that lack of ChREBP significantly improved renal injury, inhibited oxidative stress, lipid deposition, fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC) and thioredoxin-interacting protein (TXNIP) expression, as well as the activity of mammalian target of rapamycin complex 1 (mTORC1) in diabetic kidneys. Meanwhile, ChREBP deficiency upregulated the expression of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferaser 1A (CPT1A) and acyl-coenzyme A oxidase 1 (ACOX1) in diabetic kidneys. In vitro, knockdown of ChREBP attenuated lipid deposition, mTORC1 activation, and expression of FASN and ACC, increased PPARα, CPT1A, and ACOX1 expression in HK-2 cells and podocytes under high glucose (HG) conditions. Moreover, HG-induced lipid deposition, increased expression of FASN and ACC and decreased expression of PPARα, CPT1A, and ACOX1 were reversed by rapamycin, a specific inhibitor of mTORC1, in HK-2 cells. These results indicate that ChREBP deficiency alleviates diabetes-associated renal lipid accumulation by inhibiting mTORC1 activity and suggest that reduction of ChREBP is a potential therapeutic strategy to treat DN.

[EN] Skin is an important trait for Rex rabbits and skin development is influenced by many processes, including hair follicle cycling, keratinocyte differentiation and formation of coat colour and skin morphogenesis. We identified differentially expressed microRNAs (miRNAs) between the back and belly skin in Rex rabbits. In total, 211 miRNAs (90 upregulated miRNAs and 121 downregulated miRNAs) were identified with a |log2 (fold change)|>1 and P-value, This study was supported by the Modern Agricultural Industrial System Special Funding (CARS-44-A-1), the Priority Academic Programme Development of Jiangsu Higher Education Institutions (2014-134) and the General Programme of Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (16KJB230001).

Aims In the present study, we investigated the effect of carbohydrate responsive element binding protein (ChREBP) on the TXNIP/oxidative stress and apoptosis in diabetic nephropathy. Methods ChREBP−/− mice (8-week old) were produced using the CRISPR/Cas9 gene editing approach. Diabetes was induced in C57BL/6 mice with streptozotocin. HK-2 cells was transfected with plasmid containing either ChREBP shRNA or TXNIP siRNA. Results Renal expression of ChREBP and thioredoxin-interacting protein (TXNIP) was increased in patients with type 2 diabetes mellitus (T2DM) and diabetic mice. ChREBP deficiency improved renal function, apoptosis as well as endoplasmic reticulum (ER) stress in diabetic mice. In addition, ChREBP deficiency prevented expression levels of TXNIP and NADPH oxidase 4 (Nox4), 8-hydroxydeoxyguanosine (8-OHdG) and heme oxygenase-1 (HO-1) in diabetic kidneys. The increased urinary 8-OHdG level induced by diabetes was also attenuated in ChREBP deficiency mice. Similarly, HG was shown to induce ChREBP expression and nuclear translocation in HK-2 cells. HG-induced apoptosis was inhibited by transfection of ChREBP shRNA plasmid. Moreover, we found that knockdown of ChREBP suppressed HG-induced TXNIP and Nox4 expression, reactive oxygen species (ROS) generation and ER stress in HK-2 cells. Furthermore, TXNIP knockdown effectively abrogated HG-induced apoptosis in HK-2 cells. Conclusions These results suggest that ChREBP deficiency prevents diabetes-induced apoptosis via inhibiting oxidative stress and ER stress, highlighting ChREBP as a potential therapy target for diabetic nephropathy.

Background/Aims: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear. Methods: Clone formation and MTT assays were used to examine cell proliferation. To detect the effect of Gab2 on the stemness of breast cancer cells, we used flow cytometry, a sphere formation assay, real-time PCR, and western blot. An animal model was created to validate the effect of Gab2 on tumor growth in vivo. Tissue slides were analyzed by immunohistochemistry. Results: Knockdown of Gab2 suppressed PI3K/AKT and MAPK/ERK pathway activity. Gab2 ablation also reduced the stemness of HER2-overexpressing breast cancer cells. In vivo, knockdown of Gab2 inhibited tumor growth. Conclusion: This study unveils a potential function of Gab2 in HER2-overexpressing breast cancer cells. Gab2 might be a potential target in the clinical therapy of HER2-overexpressing breast carcinoma.

Key Points Question What is the prevalence of dyslipidemia in Chinese adults and what are the treatment and control rates of elevated low-density lipoprotein cholesterol in both primary and secondary prevention populations? Findings In this cross-sectional study of 2 314 538 community residents, 33.8% had dyslipidemia, 3.2% had established atherosclerotic cardiovascular disease (ASCVD), and 10.2% had high risk of ASCVD; 26.6% of those with ASCVD and 42.9% of those at high risk of ASCVD achieved low-density lipoprotein cholesterol control targets. Statins were available in 49.7% of the primary care institutions surveyed, with the lowest availability in rural village clinics. Meaning These findings suggest that dyslipidemia has become a major public health problem in China and is often inadequately treated and uncontrolled., This cross-sectional study assesses the prevalence, treatment, and control of dyslipidemia in community residents and the availability of lipid-lowering medications in primary care institutions in China., Importance Dyslipidemia, the prevalence of which historically has been low in China, is emerging as the second leading yet often unaddressed factor associated with the risk of cardiovascular diseases. However, recent national data on the prevalence, treatment, and control of dyslipidemia are lacking. Objective To assess the prevalence, treatment, and control of dyslipidemia in community residents and the availability of lipid-lowering medications in primary care institutions in China. Design, Setting, and Participants This cross-sectional study used data from the China-PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project, which enrolled 2 660 666 community residents aged 35 to 75 years from all 31 provinces in China between December 2014 and May 2019, and the China-PEACE primary health care survey of 3041 primary care institutions. Data analysis was performed from June 2019 to March 2021. Exposures Study period. Main Outcomes and Measures The main outcome was the prevalence of dyslipidemia, which was defined as total cholesterol greater than or equal to 240 mg/dL, low-density lipoprotein cholesterol (LDL-C) greater than or equal to 160 mg/dL, high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL, triglycerides greater than or equal to 200 mg/dL, or self-reported use of lipid-lowering medications, in accordance with the 2016 Chinese Adult Dyslipidemia Prevention Guideline. Results This study included 2 314 538 participants with lipid measurements (1 389 322 women [60.0%]; mean [SD] age, 55.8 [9.8] years). Among them, 781 865 participants (33.8%) had dyslipidemia. Of 71 785 participants (3.2%) who had established atherosclerotic cardiovascular disease (ASCVD) and were recommended by guidelines for lipid-lowering medications regardless of LDL-C levels, 10 120 (14.1%) were treated. The overall control rate of LDL-C (≤70 mg/dL) among adults with established ASCVD was 26.6% (19 087 participants), with the control rate being 44.8% (4535 participants) among those who were treated and 23.6% (14 552 participants) among those not treated. Of 236 579 participants (10.2%) with high risk of ASCVD, 101 474 (42.9%) achieved LDL-C less than or equal to 100 mg/dL. Among participants with established ASCVD, advanced age (age 65-75 years, odds ratio [OR], 0.63; 95% CI, 0.56-0.70), female sex (OR, 0.56; 95% CI, 0.53-0.58), lower income (reference category), smoking (OR, 0.89; 95% CI, 0.85-0.94), alcohol consumption (OR, 0.87; 95% CI, 0.83-0.92), and not having diabetes (reference category) were associated with lower control of LDL-C. Among participants with high risk of ASCVD, younger age (reference category) and female sex (OR, 0.58; 95% CI, 0.56-0.59) were associated with lower control of LDL-C. Of 3041 primary care institutions surveyed, 1512 (49.7%) stocked statin and 584 (19.2%) stocked nonstatin lipid-lowering drugs. Village clinics in rural areas had the lowest statin availability. Conclusions and Relevance These findings suggest that dyslipidemia has become a major public health problem in China and is often inadequately treated and uncontrolled. Statins were available in less than one-half of the primary care institutions. Strategies aimed at detection, prevention, and treatment are needed.

Pancreatic carcinoma (PC) is a deadly form of cancer with poor overall survival. Currently, chemotherapy such as gemcitabine and 5-fluorouracil (5-FU) are the most popular medications that can improve survival, but rapid drug-resistance makes the search for more effective drugs urgent. Upon looking for natural components to treat PC, it was found that arenobufagin, a cardiac glycosides-like compound, showed significant effects on the gemcitabine-resistant pancreatic carcinoma cell line Panc-1 and the gemcitabine-sensitive cell line ASPC-1 at nanomolar concentrations. The present study used MTT and clonogenic survival assays to examine survival and proliferation, and western blotting to assess changes in the associated mitogen activated protein kinase and phosphoinositide 3-kinase pathways and expression of apoptosis-related proteins. The current study also detected the cell cycle by flow cytometry. Arenobufagin inhibited cell survival and proliferation, decreased the phosphorylation of key downstream proteins of K-Ras, including protein kinase B and extracellular signal related kinase, induced cell cycle G2/M phase arrest and apoptosis, and downregulated the level of phosphorylated epidermal growth factor receptor. Notably, the present data also showed that arenobufagin can enhance the sensitivity of PC cells to gemcitabine and 5-FU. In conclusion, arenobufagin could enhance the effect of gemcitabine and 5-FU on PC cells by targeting multiple key proteins. Therefore, arenobufagin has potential as anadjuvant therapy for the treatment of PC.

Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p

Objective In this study, we considered the treatment of cognitive characteristics of Parkinson's subtypes under resting magnetic resonance imaging scans, and used magnetic resonance imaging to analyze brain activity characteristics of patients with Parkinson's subtypes at rest. Methods In this study, patients with neurological Parkinson's disease subtypes were selected: 27 patients in the tremor group, 33 patients in the orthostatic gastric instability group, and 3 patients with mild cognitive impairment and neuropathic Parkinson's disease. Scientific treatment was adopted. Results Nineteen patients had mild cognitive dysfunction tremor and unstable posture, and 23 of them had mild cognitive dysfunction. Fifteen healthy controls were subjected to resting state functional magnetic resonance imaging by plane echo imaging sequence scanning. Neurological diseases-Regional consistency analysis of brain regions in patients with Parkinson's disease increased, including the right lower lobe, while regional consistency analysis of brain regions decreased, including the right frontal gyrus, right middle anterior gyrus, and lateral cerebellum. Conclusions The experimental results show that the local consistency analysis method based on resting magnetic resonance imaging scan can effectively detect the differences in early neural activity in patients with Parkinson's disease subtype cognitive impairment, and can effectively reflect the brain characteristics of Parkinson's disease.